The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines, however, has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease alongside the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out with the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms from thrombosis following vaccination was also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.

Introduction: Hemostatic dysfunction during extracorporeal membrane oxygenation (ECMO) due to blood-circuit interaction and the consequences of shear stress by flow rates lead to rapid activation of the coagulation cascade and thrombus formation in the ECMO system and blood vessels. In this study, we aimed to identify the incidence and risk factors for cannula-associated arterial thrombosis (CaAT) post-decannulation. Methods: A retrospective study of patients undergoing arterial cannula removal following ECMO. We evaluated the incidence of CaAT and compared clinical characteristics, pre-ECMO severity, and daily hemostasis parameters in patients with and without CaAT. Multivariate analysis revealed the risk factors for CaAT. Results: Forty-seven patients requiring venoarterial ECMO or hybrid methods were recruited to be screened for thrombosis. The median SOFA score was 11 (8-13). CaAT occurred in 29 patients (61.7%), with thrombosis in the superficial femoral artery accounting for 51.7%. Limb ischemia complications in the group with CaAT was 17.2%. In multivariate analysis, an ECMO flow rate of 100 mL/min was determined to be the independent factor for CaAT with an OR of 0.84 (95% CI, 0.73–0.95, p=0.008). Conclusion: In patients successfully weaned from ECMO, the incidence of CaAT was 61.7%. Our study found that a low-flow rate of ECMO was an independent risk factor for CaAT.

Traumatic vascular injuries consist in direct or indirect damage to arteries and/or veins and accounts for 3% of all traumatic injuries. Typical consequences are hemorrhage and ischemia. Extremities vascular injuries can occur isolated or in association in major trauma with other organ injuries. They account for 1-2% of patients admitted to Emergency Department, for approximately 50% of all arterial injuries. Lower extremities are more frequently injured than the upper ones in adult population. The outcome of vascular injuries is strictly correlated to the environment and the time background. Treatment can be challenging notably in polytrauma because of the dilemma of which injury should be prioritized and treatment delay can cause disability or even death especially for limb vascular injury. Our purposes are to discuss the role of Computed Tomography Angiography (CTA) in the diagnosis of vascular trauma and its optimized protocol to achieve the definitive diagnosis, and to assess the radiological signs of vascular injuries and the possible pitfalls.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.

Once considered relatively benign, superficial vein thrombosis (SVT) of the lower limbs is often linked to deep vein thrombosis (DVT) or pulmonary embolism (PE). Treatment goals include alleviating local symptoms and preventing SVT from recurring or extending into DVT or PE. Fondaparinux 2.5 mg once daily for 45 days is the treatment of choice for most patients with SVT. Potential alternatives include intermediate-dose low-molecular-weight heparin or the direct oral factor Xa inhibitor rivaroxaban. Despite these treatment options, significant gaps remain, including the role of systemic or topical anti-inflammatory agents alone or combined with anticoagulants, and the optimal duration of anticoagulation for patients at varying risk levels. Additionally, the efficacy and safety of factor Xa inhibitors other than rivaroxaban, management of upper extremity SVT, and optimal treatment for SVT near the sapheno-femoral or sapheno-popliteal junctions are not well understood. This narrative review aims to summarize current evidence on anticoagulant treatment for SVT, highlight key unmet needs in current approaches, and discuss how ongoing studies may address these gaps.

Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s^-1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s-1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modelling informed by biology can provide new pathphysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.

Since its inception in December 2019, Covid-19 has challenged the global scientific community. Some treatments were used in this infection, but doubts still persist regarding the use of medications ¹. More severe cases complicate with endothelial dysfunction, excess thrombin synthesis and decreased fibrinolysis which, associated with hypoxemia, lead to a hypercoagulability state ² and some authors indicate the use of anticoagulants for these ³. For mild cases, doubts remain regarding this indication. We will report the case of a patient with mild symptoms of covid-19, complicated by inferior mesenteric vein thrombosis.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an increased risk of cardiovascular diseases (CVD), leading to elevated mortality rates among patients. We aimed to evaluate the levels of cardio-ankle vascular index (CAVI), global longitudinal strain (GLS), ventricular-arterial coupling (VAC) and high-sensitivity cardiac troponin (hsTn), in SLE patients and to explore their relationship with clinical parameters. Methods: This cross-sectional study enrolled 82 SLE patients without evident cardiac or kidney impairment and 41 age- and sex matched healthy controls. We comparatively evaluated CAVI, GLS, VAC, and hsTn between SLE patients and controls, and we assessed their association among SLE patients with disease activity based on the SELENA-SLEDAI Activity Index. Multivariate regression analysis was performed to identify independent predictors of CAVI and hsTn within the SLE cohort. Results: In comparison to healthy controls, SLE patients presented with significantly higher CAVI, GLS and hsTn levels, while VAC was significantly reduced (p&lt;0.001). Further, SLE patients with active disease (SELENA-SLEDAI≥4) exhibited higher levels of CAVI and troponin than those with inactive disease (p&lt;0.001). SLEDAI was an independent predictor of CAVI, while VAC and SLEDAI were independent determinants of hsTn in SLE cohort. Conclusion: SLE patients displayed abnormal levels of CAVI, VAC, GLS, and troponin compared to healthy individuals. Our findings implicate the potential of those CV novel CVD risk factors to refine screening and therapeutic strategies for this specific population.

Background: Cytomegalovirus (CMV) infection has been associated with venous thromboembolism (VTE) and acute coronary syndromes (ACS). Methods: A retrospective study was conducted within the OSF HealthCare System in Peoria, Illinois. The objectives were to determine the incidence of acute VTE and ACS within one year of CMV testing. The “study group” included patients with positive CMV IgM or positive CMV Polymerase Chain Reaction (PCR). The “seropositive control” group included patients with positive CMV IgG and negative IgM. The “seronegative control” group included patients with negative CMV IgG and IgM, or negative PCR. Results: Within one year of CMV infection, 38 of 379 patients (10.0%) developed VTE in the study group compared to 41 of 1334 patients (3.1%) in the seropositive control and 37 of 1249 (3.0%) in the seronegative control. Adjusting for age and gender, both control groups were less likely to have VTE than the study group within one year (Seropositive Control: OR = 0.3, 95% CI 0.2-0.5, p <0.0001; Seronegative Control: OR = 0.4, 95% CI 0.2-0.6, p <0.0001). ACS was more likely to occur in the study group, with incidence of 7.7% compared to 4.7% (p <0.0001) in the seropositive control and 1.9% (p <0.0001) in the seronegative control. Adjusting for age and gender, the seronegative control was less likely to develop ACS than the study group within one year (OR = 0.4, 95% CI 0.2-0.7, p = 0.003). Conclusions: This retrospective study demonstrates that CMV infection may be a significant risk factor for VTE and ACS.

Globally, road traffic collisions cause over a million deaths annually, with pedestrians accounting for nearly one-quarter (23%) of these fatalities. This casualty proportion highlights the critical importance of adhering to traffic regulations. This study analyzes the factors influencing driver yielding behavior at midblock crosswalk improvements, comparing (1) a typical zebra crossing (C1) and (2) an intelligent signalized crosswalk (C2). The study used video-based observational data to investigate driver behaviors and factors influencing driver behaviors. The study applied multinomial logistic regression to formulate yielding behavior models. The results indicate that the number of traffic lanes, width of the traffic lanes, width and length of the crosswalk, vulnerable group, the number of pedestrian crossings, pedestrian crossing time, the number of vehicles approaching a crosswalk, speed of vehicle, headway, the post-encroachment time (PET) between vehicles and pedestrian, and roadside parking are the significant factors influence yielding behavior. These findings provide a better understanding of the factors influencing driver yielding behavior and propose measures to set proper physical improvements (e.g., curb extensions, raised pedestrian platforms, and pedestrian fencing), enforcement (e.g., parking restriction, speed violation detection), public awareness campaigns, and education initiatives.

Pulmonary arterial hypertension is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors, and likely gene x environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 36% of pediatric-onset idiopathic PAH (IPAH) compared to ~11% of adult-onset IPAH. De novo variants are frequently associated with PAH in children, and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, the increased etiologic heterogeneity, poorer prognosis and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

This case report presents a 63-year-old male patient who developed deep vein thrombosis (DVT) shortly after undergoing retroperitoneal laparoscopic nephroureterectomy for ureteral and renal pelvis tumors. Despite early postoperative mobilization and administration of low molecular weight heparin, the patient developed DVT, highlighting the limitations of current postoperative management strategies. The patient was promptly treated with the placement of an inferior vena cava filter and continued anticoagulation therapy, preventing the progression to pulmonary embolism and leading to a successful discharge.The report emphasizes the importance of vigilant postoperative monitoring and timely intervention in preventing complications such as DVT. It suggests that current strategies, including early mobilization and standard anticoagulation therapy, may not be sufficient to fully prevent DVT, necessitating further optimization of postoperative care. Regular monitoring of D-Dimer levels and ultrasound examinations, as well as appropriate limb protection measures during surgery, are recommended to detect and manage potential DVT early.This case contributes valuable insights into the early detection and management of postoperative DVT, providing useful references for similar cases and stressing the need for enhanced postoperative monitoring and timely intervention.

Background: To investigate the safety and efficacy of palliative arterial embolization for metastases of the scapula. Materials and Methods: We studied the files of the patients who underwent palliatrive arterial embolization for metastases of the scapula from January 2016 to January 2023, 15 patients (8 M, and 7 F) with a mean age of 62 years (SD 10.2) with two patients receiving a second procedure, for a total of 17 embolizations. Data on technical and clinical success, as well as changes in tumor size, were collected. All embolization-related complications were evaluated according to the CIRSE classification system for complications. Results: The average follow-up was 18 months (Range 6-36 months). The main primary tumor were renal, lung and breast cancer. The primary arteries embolized were the circumflex scapular artery, the dorsal scapular artery, and the thoracoacromial trunk. A mixture of Glubran and Lipiodol in a 1:2 ratio was used for embolization, with an average of 1.1 mL (Range 0.5-1.5 mL) used per procedure. The efficacy of embolization was measured using the Visual Analogue Scale (VAS), with values recorded at baseline, at 1, 3, 6, and 12 months post-embolization, and at 6-month intervals after. Baseline VAS scores averaged 7.2 (SD 1.5), decreasing to 2.8 (SD 0.9) at one month. Progressive reduction was observed at 3, 6, and 12 months with scores of 2.3 (SD 0.8), 1.9 (SD 0.7), and 1.6 (SD 0.6) respectively. Metastatic tumor size was reduced from a mean of 192.2 cm3 (range 38.7 to 480.1 cm3) pre-embolization to a mean of 177.3 cm3 (range 37.2 to 455.5 cm3) at the 12-month follow-up (p

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalised patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed by white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells and platelets. Immune cells, cytokines, chemokines and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate pro-inflammatory and pro-coagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2 associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism, chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalised patients with severe disease, that would target the crossroads of inflammatory and coagulation pathways.

Background: Antiphospholipid antibodies (aPL) are a laboratory criterion for the classification of antiphospholipid syndrome (APS), and are known to cause clinical symptoms: vascular thrombosis or obstetric complications. It is suggested that aPL may be associated with thromboembolism in severe COVID-19 cases. Aim: to combine clinical data with aPL findings at 4 time points (admission, worsening, discharge, 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. Methods: current and past history of thrombosis and obstetric complications; aPL determined at 4 time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG or IgA isotypes. Results: 111 patients with COVID-19 pneumonia were enrolled. During hospitalization, 7 patients died, 3 of them due to pulmonary artery thromboembolism (none was aPL positive). Only one of the five who developed pulmonary artery thrombosis was aPL positive. Of 9/101 patients with a history of thrombosis, 5 had arterial thrombosis and none was aPL positive at admission and follow-up; 4 had venous thrombosis and one was aPL positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPL positive at discharge only, compared to 26.1% without history of thrombosis (p=0.05). Conclusions: aPL were not associated with fatal outcomes and vascular thrombosis; aPL were transiently positive in more than half of patients with a history of thrombosis.

The coexistence of SAH with T2DM is a common comorbidity. In this present study, we investigated the link between altered plasma antioxidant trace elements (ATE: Manganese, Selenium, Zinc and Copper) and fatty acids ratio (FAR: polyunsaturated/saturated) imbalance as transition biomarkers between vascular pathology (SAH) to metabolic pathology (T2DM). Our data revealed strong correlation between plasma ATE and FAR profile which is modified during SAH-T2DM association compared to healthy group. This relationship is mediated by lipotoxicity (simultaneously prominent visceral adipose tissue lipolysis, significant flow of non-esterified free fatty acids release, TG-Chol-dyslipidemia, high association of Total SFA, Palmitic acid, Arachidonic acid and PUFA 6/ PUFA 3; drop in tandem of PUFA / SFA and EPA+DHA); oxidative stress (lipid peroxidation confirmed by TAS depletion and MDA raise, concurrently drop of Zn/Cu-SOD, GPx, GSH, Se, Zn, Se/Mn, Zn/Cu; concomitantly enhance Cu, Mn and Fe); endothelial dysfunction (endotheline-1 increase); athero-thrombogenesis risk (concomitantly raise of ApoB100/ApoA1, Ox-LDL, tHcy and Lp(a)) and inflammation (higher of Hs-CRP, Fibrinogen and Ferritin). Our study open to new therapeutic targets and to better dietary management, such as to establish dietary ATE and PUFA 6 / PUFA 3 or PUFA / SFA reference values for atherosclerotic risk prevention in hypertensive-diabetics patients.

This analytical cross-sectional study was designed to evaluate the association between glycemic control and peripheral arterial disease in patients with diabetic foot with more than ten years of evolution of diabetes mellitus who attended the diabetic foot outpatient clinic of the Guillermo Almenara National Hospital between June 2015 and February 2017. Glycosylated hemoglobin (HbA1C) and ankle-brachial index (ABI) were used to diagnose glycemic control and peripheral arterial disease, respectively. A generalized Poisson log-linear regression model was used to calculate the crude (cPR) and adjusted (aPR) prevalence ratios, with 95% confidence intervals, and a significance level of p < 0.05. 226 patients were included in the study, finding 23% (n=52) with good glycemic control, and 44.7% (n=101) with peripheral arterial disease. The adjusted model found statistically significant associations for glycemic control, age, and sedentary lifestyle with peripheral arterial disease. Compared with patients with good glycemic control, those with poor glycemic control had a 34% higher probability of presenting peripheral arterial disease (aPR: 1.34, 95%CI: 1.01-1.79, p=0.045). The prevalence of good glycemic control in the population with diabetic foot is low. Poor glycemic control was found to be independently associated with the presence of peripheral arterial disease.

Pneumatosis intestinalis is the presence of air within the two layers of the wall of the gastrointestinal tract, specifically in the small and large intestines. This accumulation of gas can cause thicker walls of the intestines in X-ray or CT scans. Superior Mesenteric Artery (SMA) Thrombosis occurs due to the formation of blood clots within the SMA. As it supplies from the ampulla in the second part of the duodenum to the splenic flexure of the large intestine its thrombosis can cause ischemia in any part depending upon its branch. A 67-year-old male patient presented to the hospital with the complaint of generalized abdominal pain for 5 days along with fever, nausea, vomiting, obstipation, and postprandial fullness. On further investigation with the help of an MDCT scan and X-ray, proximal jejunal loops showed circumferential air within the walls giving the diagnosis of Pneumatosis Intestinalis along with Superior Mesenteric Artery Thrombosis causing jejunal infarct.

Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a respiratory disease, it is clear that COVID-19 is systemic illness impacting multiple organ systems. One defining clinical feature of COVID-19 has been the high incidence of thrombotic events. The underlying processes and risk factors for the occurrence of thrombotic events in COVID-19 remain inadequately understood. While severe bacterial, viral or fungal infections are well recognized to activate the coagulation system, COVID-19 associated coagulopathy is likely to have unique mechanistic features. Inflammatory-driven processes are likely primary drivers of coagulopathy in COVID-19, but the exact mechanisms linking inflammation to dysregulated hemostasis and thrombosis are yet to be delineated. Cumulative findings of microvascular thrombosis has raised question if the endothelium and microvasculature should be a point of investigative focus. Von Willebrand Factor (VWF) and its protease, ADAMTS13 play important role in the maintenance of microvascular hemostasis. In inflammatory conditions, imbalanced VWF-ADAMTS13 characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS13 has been reported. Also, an imbalance between ADAMTS13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. A thorough understanding of VWF-ADAMTS13 interactions during early and advanced phases of COVID-19 could help better define the pathophysiology, guide thromboprophylaxis and treatment and improve clinical prognosis.

Although COVID-19 primarily affects the respiratory system, it can have various effects on other organs, including the cardiovascular system. COVID-19 can lead to a prothrombotic status, promoting bloodclotting, which can potentially affect native vessels and implanted de-vices. The exact mechanisms by which it leads to increased clotting are not yet fully understood but may involve inflammation, endothelial dysfunction, and a hyperactive immune response. In the present report, we describe a case of an acute aortic stent-graft thrombosis four days after resolution of Sars-Cov2 infection. The patient required emergent explantation of the stent-graft, after the failure of endovascular bailout procedures.

Ongoing concerns regarding the morbidity and mortality from cancer-associated thrombosis led the European Cancer Patient Coalition (ECPC), the voice of cancer patients across Europe, to create a pan-European cancer-associated awareness patient survey to assess CAT knowledge among a large population of patients with cancer. The ECPC survey represents the largest of its kind amongst patients/caregivers with CAT and identified significant gaps in patient awareness and knowledge of CAT. It also identified a need for educational CAT-related discussions and interventions between healthcare professionals and patients with cancer and their caregivers. The aim of this paper is to highlight these gaps and to provide healthcare professionals with awareness of what information should be shared with patients/caregivers as well as how and when that information should be provided. Notably, the importance of providing information on CAT risk and risk factors, how to reduce their risk of CAT, the role of anticoagulant prophylaxis and treatment (short- and long-term) including possible side-effects, and finally how to early identify CAT symptoms. Here we outline what type of information should be provided, as well as when and how to best discuss CAT with our oncology patients and their caregivers along the cancer care continuum, to reduce the risk of CAT and associated complications with a goal of improving patient outcomes.

Background: Annual influenza epidemics are a serious public health problem, causing particularly severe morbidity and mortality in high-risk groups. The study aimed to understand Poles' attitudes and beliefs towards influenza vaccinations in the flu season of 2022–2023, analyze preferences and unmet needs regarding influenza vaccinations, and examine the perception and acceptance of the influenza vaccine among individuals at risk of flu complications. Methods: A cross-sectional survey-based study was carried out on a sample of 1446 respondents. The Google Forms questionnaire was created and disseminated electronically using social media and e-mail. The pre-test was performed at the beginning of the project. Results: The majority of respondents (71%) could identify "high-risk groups" recommended for influenza vaccination. Furthermore, it was observed that individuals aged 21 to 59 demonstrated a higher level of knowledge in this regard compared to those below 20 and above 65 years old, and individuals with higher and medium education levels were much better at identifying risk groups for influenza virus infection. The majority of respondents (52.01%) reported receiving influenza vaccination at some point in the past, with 32.12% receiving it in the 2022–2023 flu season and 41.09% in the 2021–2022 season. The majority of respondents declaring acceptance of the vaccine for the 2022-2023 season were in the high-risk group. Only 17.28% of respondents declared receiving both influenza and SARS-CoV-2 vaccines in the 2022-2023 season, with the vast majority being respondents from the "high-risk group" (p

Renal artery thrombosis is a sporadic serious clinical condition which potentially cause renal infarction. Diagnosis of renal infarction can be delayed or missed due to non specific clinical presentation and overlapping appearance of medical and surgical phenomena. Early diagnosis supported by biochemical and radiological findings while appropriate management potentially improve morbidity and mortality. Persistent abdominal or flank pain with raised LDH and proteinuria on background of thromboembolism risk factors supports the diagnosis. Despite the rarity of the disease rapid identification with prompt medical or endovascular intervention could prevent irreversible renal parenchymal damage.

Pulmonary arterial hypertension (PAH) is a pathophysiological condition characterized by pulmonary vascular remodeling and elevated vascular resistance, which may ultimately result in cardiovascular failure and sudden cardiac death. In recent years, the occurrence of pregnancy complicated by pulmonary arterial hypertension has witnessed a notable increase, whereas the incidence of postpartum pulmonary arterial hypertension is comparatively rare. This study presents a case involving a 39-year-old female who exhibited severe pulmonary arterial hypertension, finally diagnosed as idiopathic pulmonary arterial hypertension, within 2 days postpartum. The diagnosis was made following a thorough clinical examination. This case report emphasizes the significance of promptly initiating targeted therapy as an initial step in effectively managing patients and the criticality of conducting a thorough assessment of multidisciplinary collaboration in postpartum management. Furthermore, the report has the potential to enhance awareness and education regarding the future management of similarly intricate conditions.

Endothelial autocrine signaling is essential to maintain vascular hemostasis. There is limited in-formation about the role of endothelial autocrine signaling in regulating severe pulmonary vas-cular remodeling during the onset of pulmonary arterial hypertension (PAH). In this study, we employed the first severe PAH mouse model, Egln1Tie2Cre (Tie2Cre-mediated disruption of Egln1) mice, to identify the novel autocrine signaling mediating the pulmonary vascular endothelial cells (PVECs) hyperproliferation and the pathogenesis of PAH. PVECs isolated from Egln1Tie2Cre lung expressed upregulation of many growth factors or angiocrine factors such as CXCL12, and exhib-ited hyperproliferative phenotype in coincident with upregulation of proliferation specific tran-scriptional factor FoxM1. Treatment of CXCL12 on PVECs increased FoxM1 expression, which was blocked by CXCL12 receptor CXCR4 antagonist AMD3100 in culture human PVECs. Endo-thelial specific deletion of Cxcl12 (Egln1/Cxcl12Tie2 Cre) or AMD3100 treatment in Egln1Tie2Cre mice downregulated FoxM1 expression in vivo. We then generated and characterized a novel mouse model with endothelial specific FoxM1 deletion in Egln1Tie2Cre mice (Egln1/Foxm1Tie2Cre), and found that endothelial FoxM1 deletion reduced pulmonary vascular remodeling and right ventricular systolic pressure. Together, our study identified a novel mechanism of endothelial autocrine sig-naling in regulating PVECs hyperproliferation and pulmonary vascular remodeling in PAH.

UEDVT still remains an underdiagnosed entity due to a significant percentage of patients who remain asymptomatic. The etiology of UEDVT is overwhelmingly attributed to secondary causes including but not limited to central venous access devices and malignancy. Treatment modalities include anticoagulation, catheter directed thrombolysis, percutaneous mechanical thrombectomy or a multimodality approach along with the management of underlying etiology. We describe a case of a female with breast cancer, who came with left UEDVT and CVC malfunction and was successfully treated using the ClotTriever system to maintain continuous intravenous access.

The main manifestation of new coronavirus disease 2019 (COVID-19) is respiratory disease. The new coronavirus (SARS-CoV-2) attacks the lungs and may result in severe acute respiratory syndrome. In such cases, the infected person has difficulty breathing, which impairs oxygen uptake in the body. If pneumonia or another respiratory illness develops, and the host immune system is unable to combat SARS-CoV-2, the infected person may eventually die. Meanwhile, reports on unexpected symptoms in organs other than the nasal cavity, throat, and lungs are emerging. To elucidate the causes of such symptoms, we analyzed the expression status of angiotensin-converting enzyme 2 (ACE2), the host receptor used by SARS-CoV-2, in various tissues. This study confirmed that alveolar macrophages appear to be involved in pneumonitis and thrombus formation. In this report, we introduce some new symptoms.

Abstract: Arterial hypertension is the main preventable risk factor for premature death and stroke worldwide and anxiety is a real public health problem. Stress is the common denominator for both cases. In the last 3 years, the aggressive exposure of the population to negative emotions (fear of disease in a pandemic, fear of war, financial instability) was the trigger factor. The psycho-neuro-endocrine mechanisms include the hypothalamic-pituitary-adrenal axis and induce sympathetic-parasympathetic imbalance, hypercortisolemia, endothelial dysfunction, oxidative stress, inflammation, cytokine growth, and atherosclerosis. The individual’s vulnerability to stress depends on many factors, but the key role in the perception of stress belongs to immunogenic personality traits. Among them, self-efficacy is a protective factor against stress. Our research aimed to evaluate the connections between psycho-emotional factors and hypertension, using psychometric tests, to identify vulnerability to stress, perceived stress level, anxiety, self-efficacy, and psychobehavioral type, for 215 patients, 104 hypertensive and 111 non-hypertensive patients. The results of the study confirmed that there is a statistically significant difference, which requires psychological screening measures to identify patients vulnerable to stress, as well as medical education courses for doctors in the field of psychology.

Genetic variability in rice breeding program plays the very crucial role. It provides outstanding pool of superior alleles governing better agronomic and quality characters through association mapping. For the understanding of population structure and genetic relationship among the different rice lines is indispensable prior to setting of correlation among dynamic alleles and traits. In the present investigation, genetic diversity and population structure of 116 rice accessions by using 64 polymorphic SSR markers was targeted for the evaluation of the genetic relatedness and diversity. Genotyping assessment based on SSR markers revealed a total of 225 alleles, with an average PIC value of 0.755. The germplasm lines were classified into three distinct subgroups through population structure analysis, utilizing both model and distance-based approaches. AMOVA analysis showed that 11% of the total variation could be attributed to differences between groups, while the remaining 89% of the variation was likely due to differences within groups. The study suggests that the population structure and genetic relatedness should be considered when working with the core collection of 116 rice germplasm lines for association mapping, aiming to establish marker-trait associations.

Stormwater runoff from large roads is a major source of pollutants to receiving waters. Porous pavements have been shown to substantially reduce many of these pollutants, but studies are lacking on arterial roads. We sampled typical stormwater pollutants in runoff from sections of an arterial road 9-16 years after installation of three pavement types: control with conventional asphalt, porous asphalt overly, and full-depth porous asphalt. Both types of porous pavements substantially reduced most of the stormwater pollutants measured. Total suspended solids, turbidity, total lead, total copper, and 6PPD-quinone were all reduced by &gt;75%. Total nitrogen, ammonia, total phosphorus, biochemical oxygen demand, total and dissolved copper, total mercury, total zinc, total polycyclic aromatic hydrocarbons, and di-2-ethylhexyl phthalate were all reduced by &gt;50%. Reductions were lower or absent for nitrate, orthophosphate, E. coli, dissolved lead, and dissolved zinc. Most reductions were statistically significant. Many pollutants exceeded applicable water quality standards in the control samples but met them with both types of porous pavement. This study demonstrates that porous overlays and full-depth porous asphalt can provide substantial reductions of several priority stormwater pollutants on arterial roads for many years after installation.

The basilar arterial endothelium mediates blood-vessel relaxation, partly through release of nitric oxide (NO). Apoptosis of cerebrovascular endothelial cells is linked to high mortality rate in chickens infected with highly pathogenic avian influenza virus, but interestingly ducks exhibit greater resistance to this virus. In this study, we examined the responsiveness of duck basilar arteries (BAs) to various vasoactive substances, including 5-hydroxytryptamine (5-HT), histamine (His), angiotensin (Ang) II, noradrenaline (NA), acetylcholine (ACh), and avian bradykinin ornithokinin (OK), aiming to characterize the receptor subtypes involved and the role of endothelial NO in vitro. Our findings suggest that arterial contraction is mediated by 5-HT1 and H1 receptors, while relaxation is induced by β3-adrenergic and M3 receptors. Additionally, OK elicited a biphasic response in duck BAs, and Ang II had no effect. Endothelial NO appears to be crucial in relaxation mediated by M3 and OK receptors, but not β3-adrenergic receptors, in the duck BA. The reduced endothelial NO involvement in the receptor-mediated relaxation response in duck BAs represents a clear difference from the corresponding response reported in chicken BAs. This physiological difference may explain differences in lethality between ducks and chickens when vascular endothelial cells are infected by the virus.

Abstract: Background: Aging is an important risk factor for cardiovascular diseases and con-vincing data has shown that chronic low-grade inflammation, which develops with advanced age, contributes significantly to cardiovascular risk. Objectives: The present study aimed to use ¹⁸F-FDG/¹⁸F-NaF-PET/CT imaging to respectively gauge arterial inflammation and microcalcifi-cation in healthy elderly and to assess the potential benefits of a tyrosol- and hydroxytyrosol-rich diet on these two markers of atherosclerotic plaque fragility. Methods: Eleven healthy partici-pants (mean age 75 ± 5.67 years) were supplemented for 6 months with high polyphenol-rich extra virgin olive oil (HP-EVOO), extra virgin olive oil (EVOO), or refined olive oil (ROO). The partic-ipants underwent PET/CT imaging with ¹⁸F-FDG and ¹⁸F-NaF radiotracers at baseline and after 6 months. ¹⁸F-FDG and ¹⁸F-NaF uptakes were quantified using standardized uptake values (SUV) and were categorized based on artery calcification and olive oil type. Results: A total of 324 slices of the aortas of the imaged participants were analyzed for arterial inflammation and 327 slices were analyzed for microcalcification. 18F-FDG uptake was significantly higher in the non-calcified segments than in the calcified segments (SUVmax = 2.70  0.62 and SUVmax = 2.54  0.44, respectively, p<0.042). Conversely, the non-calcified segments displayed significantly lower 18F-NaF uptake than the calcified segments (SUVmax = 1.90 0.37 and 2.09  0.24, respec-tively, p<0.0001). The 6-month supplementation with HP-EVOO induced a significant reduction in 18F-FDG uptake in both the non-calcified (2.93  0.23 to 2.75  0.38, p<0.004) and calcified seg-ments of the aortas (2.25  0.29 to 2.15  0.19, p<0.02). 18F-NaF uptake was also significantly low-er in patients supplemented with HP-EVOO (SUVmax = 1.98  0.33 at baseline compared to 1.85  0.28, after the 6-month supplementation, p<0.004), whereas no significant effect was observed with EVOO. Conversely, participants supplemented with ROO displayed a significant increase in 18F-NaF uptake (SUVmax = 1.78  0.34 to 1.95  0.34, p<0.0001). Conclusion: The present study confirmed that ¹⁸F-FDG/¹⁸F-NaF-PET/CT imaging is a valuable approach for assessing age-related arterial damage and demonstrated that a phenolic compound-rich diet reduces both arterial inflammation and atherosclerotic lesion microcalcification.

We report the case of a 44-year-old woman who suffered gastric perforation after receiving bag-valve-mask (BVM) ventilation in the setting of alcohol intoxication. She had a markedly distended abdomen and cold, dusky lower extremities upon arrival to the emergency department. Imaging revealed a large volume intraabdominal accumulation of air with compression of the aorta. Needle decompression relieved symptoms of lower extremity arterial insufficiency. However, the patient quickly decompensated and subsequent exploratory laparotomy confirmed gastric rupture. A subtotal gastrectomy was performed but the patient ultimately passed on post-operative day two due to multi-organ dysfunction. Although BVM ventilation is commonplace in both the hospital and field, there is a lack of awareness of the serious complications of abdominal air accumulation due to their rareness in the adult population. Checking for abdominal distention during resuscitation ought to be routine in all patients. Signs of arterial insufficiency accompanying abdominal distention, once confirmed by diagnostic imaging that shows extensive pneumoperitoneum, are indicators of having reached a life-threatening level of air accumulation, calling for immediate needle decompression and exploratory laparotomy.

Reliable quantification of pulmonary arterial pressure is essential in the diagnostic and prognostic assessment of a range of cardiovascular pathologies including rheumatic heart disease, yet an accurate and routinely available method for its quantification remains elusive. This work proposes an approach to infer pulmonary arterial pressure based on scientific machine learning techniques and non-invasive, clinically available measurements. A 0-D multicompartment model of the cardiovascular system was optimized using several optimization algorithms, subject to forward-mode automatic differentiation. Measurement data were synthesized from known parameters to represent the healthy, mitral regurgitant, aortic stenosed and combined valvular disease situations with and without pulmonary hypertension. Eleven model parameters were selected for optimization based on 95 % explained variation in mean pulmonary arterial pressure. A hybrid Adam and limited-memory Broyden-Fletcher-Goldfarb-Shanno optimizer yielded the best results with input data including valvular flow rates, heart chamber volume changes and systematic arterial pressure. Mean absolute percentage errors ranged from 1.8 % to 3.78 % over the simulated test cases. The model was able to capture pressure dynamics under hypertensive conditions with pulmonary arterial systole, diastole, and mean pressure average percentage errors of 1.12 %, 2.49 % and 2.14 %, respectively. The relatively low errors highlight the potential of the proposed model to recover pulmonary pressures for diseased heart valve and pulmonary hypertensive conditions.

Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cells killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit of the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacting liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate reducing by 4 the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible.

The current echocardiography reference values are derived primarily from populations in North America and Europe. It becomes necessary to study ethnically different groups of the population, which often have different living conditions, food habits and lifestyle. The aim of the study was to compare echocardiography indicators in urbanized patients with arterial hypertension of the Shor and non-indigenous ethnic groups living in the Gornaya Shoria region. The study included patients with arterial hypertension: 58 Shors (20 men and 38 women) and 50 non-indigenous residents (15 men and 35 women) of Gornaya Shoria. All underwent an echocardiographic study with an assessment of the left heart parameters. We assessed the left ventricular hypertrophy (LVH) severity, LV geometry and diastolic function in the ethnic and sex groups. Shor with hypertension no showed a significant difference in left ventricular dimensions compared to Caucasian. Severe abnormal LVH was associated in the Shors with glucose levels (OR 3.24, 95%CI 1.56-6.7, p=0,001), and in Caucasians with systolic (p=0.021) and diastolic (p=0.011) blood pressure, and heart rate (p=0.033). The Shor men were more likely to have normal LV diastolic function (p=0.029) and LV concentric remodeling (p=0.023), and less often to have normal LV geometry (p=0.015) compared to non-indigenous men. Thus, this study can be useful in assessing the impact of the development of arterial hypertension, as well as the impact of changing the lifestyle of the Shors when moving to the city from rural areas on ethnic differences in echocardiography.

Despite the advances in stent design, coating drugs, polymers, the use of intravascular imaging, special devices (such as intravascular lithotripsy, ultra-high-pressure non-compliant balloons, and drug-coated balloons), and improved operator skills and techniques, the problem of in-stent restenosis (ISR) and stent thrombosis (ST) remains a challenge for interventional cardiologists. Atherosclerotic lesions, ISR, and ST, are systemic metabolic chronic inflammatory illnesses with a local manifestation in the coronary vessels. Therefore, we propose managing these systemic illnesses systemically through plant-based diet (PBD) intervention. We explain how PBD intervention can help mitigate atherosclerosis, ISR, and ST. Thus, PBD intervention can overcome biological and epigenetic problems in managing ISR and ST similarly to reversing atherosclerosis. Our team is pioneering the implementation of PBD for cardiology patients who have undergone coronary intervention. So far, the results have been very promising. We hope that in the future, many research studies will be performed to investigate further the role of PBD in decreasing the incidence of ISR and ST.

Colorectal cancer is third most common malignancy. For metastasis of rectal cancer, metastasis to skeletal muscle tissue is rare. In this case report, we describe a 51-year-old male patient with rectal cancer with neoadjuvant concurrent radiotherapy and chemotherapy followed by transanal total mesorectal excision with ileostomy. However, he had deep venous thrombosis of left leg after operation and skeletal muscle metastasis was diagnosed via tissue proof. Therefore, less possibility of metastasis increased included brain, duodenum, bone, and nervous system. The prognosis of metastasis to skeletal muscle is poor in contrast to liver or lung metastasis.

Introduction: Adverse events related to vaccines are reactions that can lead to serious complications, in the present that we live at the publication of this article with the need to generate high rates of vaccination have been presented in the case of vaccine agents against COVID-19 adverse events, with thrombotic events being the most important. Case Presentation: This is a 37-year-old female patient who presents 11 days after ChAdOx1-S vaccination against COVID-19 presents with intense headache associated with symptoms of intracranial hypertension, she was initially taken to simple cranial tomography showing presence of cerebral edema and indirect signs of cerebral venous thrombosis, it is proposed to carry out cerebral angiography which showed the presence of thrombosis of both transverse venous sinuses, no hypercoagulability states were found in the laboratories, the immunological tests carried out for antiphospholipid syndrome were negative, the thrombotic event was associated with the ChAdOx1-S vaccine, later the patient was taken to thrombectomy by Neuroradiology, achieving complete channeling of both transverse venous sinuses. Conclusions: Adverse events associated with vaccination have been described with multiple vaccine agents, this component against COVID-19 is also an event to consider, knowing the pathophysiology of these events is essential to be able to reduce these risks and select the least risky agent. Despite this risk, vaccination remains the only cost-effective measure to reduce the morbidity and mortality associated with COVID-19.

Individuals diagnosed with systemic arterial hypertension (SAH) are considered risk groups for COVID-19 severity. This study assessed differences in cardiac autonomic function (CAF) and functional capacity (CF) in SAH individuals without COVID-19 infection compared to SAH individuals post-COVID-19. Participants comprised 40 SAH individuals aged 31 to 80 years old, grouped as SAH with COVID-19 (G1; n=21) and SAH without COVID-19 (G2; n=19). CAF was assessed via heart rate variability (HRV), measuring R-R intervals during a 10-minute supine period. Four HRV indices were analyzed through symbolic analysis: 0V%, 1V%, 2LV%, and 2UV%. FC assessment was performed by a 6-minute walk test (6MWT). G1 and G2 showed no difference between significant age, anthropometric, clinical and medication. G2 exhibited superior 6MWT performance, covering more distance (522±78 vs. 465±59 meters, p&lt;0.05). Specifically, G2 demonstrated a moderate, positive correlation between 6MWT and the 2LV% index (r=0.58; p&lt;0.05). Shorter walking distances were observed during 6MWT in SAH individuals post-COVID-19. However, the study did not find impaired cardiac autonomic function in SAH individuals post-COVID-19 compared to those without. This suggests that while COVID-19 impacted FC, CAF remained relatively stable in this population.

Background: We studied the outcomes of SARS-CoV-2 (COVID) hospitalizations and their association with myocardial injury and thrombosis. Methods: Retrospective analysis of the National Inpatient Sample 2020 database. Results: We identified 335,799 hospitalizations with COVID. Of these, 1.6% (5,355) were diagnosed with non-ST-segment myocardial infarction (COVNSTEMI). The mean age of COVID hospitalizations was 71.7, with 60.50% being males. The population prevalence included 53.10% Whites, 17.80% Blacks, 19.20% Hispanics, and 4.10% Asians. The average length of stay (LOS) was 10 days, and 37.60% of patients died during their hospitalization. The average cost of hospitalization (TOTCHG) was $156,633. The COVSTEMI group comprised 1,364 cases, with a mean age of 67.4, in-hospital mortality of 47.4%, and the mean TOTCHG was $177,600. The DVTCOV group comprised 2,869 cases, while the PECOV group had 4,828 cases. Male predominance was observed in both groups, with mean ages of 66 years in the DVTCOV group and 64 years in the PECOV group. The DVTCOV group had a LOS of 16 days, with 24.71% mortality, while the PECOV group had a LOS of 11 days, with 19.20% mortality. The average TOTCHG in the DVTCOV group was $248,900, whereas it was $145,378 in the PECOV group. Conclusion: Our study revealed significant mortality rates across different groups, including 38% in COVNSTEMI, 47% in COVSTEMI, 25% in DVTCOV, and 19% in PECOV. These findings highlight the severity of COVID-related complications and the substantial financial burden of hospitalization.

Objectives: To analyze the clinical characteristics and factors associated with adverse drug reactions (ADR) in liver cancer patients receiving oxaliplatin‐based hepatic arterial infusion chemotherapy (HAIC). Methods: A retrospective analysis was performed on the clinical data of 137 patients with liver cancer who received oxaliplatin‐based HAIC. Changes in baseline characteristics, inflammatory factors, and other laboratory indicators in the no‐ADR and ADR groups were analyzed. Results: The incidence of serious ADR (CTCAE ≥ 3) was 21.9% (30/137). There was no significant difference in the cumulative dose of oxaliplatin between the two groups [157.3 (80.3, 322.4) vs. 206.6 (139.1, 324.2), P=0.161]. The increase in NEUT and IL‐6 was greater in the group treated with ADR than in the group not treated with ADR. Changes in NEUT [4.1 (1.5, 6.2) vs. 2.5 (0.5, 4.9), P=0.045] and changes in NEUTIL‐6 [4.2 (‐0.2, 22.9) vs. 0.8 (‐3.9, 7.7), P=0.026]. TBIL, ALT, AST, ALP, WBC, NEUT, PCT, CRP, TNF, IL‐2R, IL‐6, and IL‐10 were significantly higher after treatment than before in the ADR group (P < 0.05). In contrast, ALB and AFP were decreased. Conclusions: The severe ADR (CTCAE ≥ 3) associated with oxaliplatin‐based HAIC may be closely related to increased inflammatory factors such as NEUT and IL‐6. We should be vigilant for allergic reactions to oxaliplatin and increase monitoring during treatment

Antioxidants reduce arterial stiffness but the effects previously reported are weak. The present study evaluated the effects of 2 weeks of therapy with a combination of antioxidants (l-cysteine, thiamine, pyridoxine and ascorbic acid) compared to placebo on stiffness index (SI) a measure of arterial stiffness that is strongly correlated with central pulse wave velocity (PWV), using a Pulse Trace recorder in a diverse group of 78 volunteers. SI fell by 1.7 m/sec relative to placebo (95% confidence intervals 0.6 to 2.7 m/sec), a reduction of 19% (95% confidence intervals 9% to 31%). The Glass effect size was 1.4, indicating a very strong treatment effect which was substantially greater than found in previous studies of the effects of antioxidant therapy on arterial stiffness. The magnitude of reduction in SI was positively correlated with increasing age (r = 0.362 P = 0.02). The change in RI, a measure of compliance of small to medium size arteries, did not differ between the antioxidant and placebo groups The combination of antioxidants studied reduced PWV to a much greater extent than reported for other antioxidants. This combination may be of value in the treatment of cardiovascular disease.

Contrast-enhanced ultrasonography (CEUS) is useful for evaluation of the hemodynamics of hepatic tumors and surrounding he-patic parenchyma in real time. CEUS with intravenous contrast administration is well established for evaluation of hepatocellular carcinoma (HCC). On the other hand, intra-arterial (transcatheter) CEUS (IAUS) is an emerging technique that allows more selective evaluation of the arterial supply to the tumor. IAUS was performed by administration of Sonazoid® through the microcatheter and imaging of the area of the target lesion with a dedicated, contrast-specific technique. Sonazoid® (0.5 ml diluted with 49.5 ml of distilled water) was used as the contrast medium in IAUS. The diluted Sonazoid® was introduced into the feeding artery by in-termittent injection of 0.3-1.0 ml through a microcatheter placed in the artery and flushing with saline at the same flow rate. We report the three cases in which IAUS was useful in transarterial chemoembolization (TACE) for HCC. Two cases were performed TACE for hepatic metastasis. In any cases, plain computed tomography (CT) after TACE showed accumulation of Lipiodol® only in the metastases. One case was suspected having HCC rupture and urgent abdominal angiography was performed. IAUS was performed frequently to reduce the amount of iodinated contrast agent as much as possible because of renal failure. Concomitant use of IAUS enabled reduction of the amount of contrast agent.

Peripheral arterial diseases (PAD) are complex cardiovascular conditions influenced by environmental factors and somatic mutations in multiple genes involved in hematopoiesis and inflammation. While traditional risk factors such as smoking, hypercholesterolemia, and hypertension have been extensively studied, the role of somatic mutations in PAD progression remains underexplored. This article aims to provide a comprehensive review of the molecular mechanisms, genetic landscape, prognostic significance, and clinical implications of somatic mutations in PAD. The expansion of clonal hematopoiesis of indeterminate potential (CHIP) clones in the circulating blood, named clonal hematopoiesis (CH), leads to the infiltration of these clones into atherosclerotic plaques and the production of inflammatory cytokines, increasing the risk of cardiovascular diseases including PAD. Furthermore, recent experimental evidence has demonstrated the involvement of somatically mutated TP53 genes with a high variant allele frequency (VAF) in PAD development and prognosis. The review delves into the relationship between CH and PAD, elucidating the prevalence, impact, and underlying mechanisms of this association. This understanding paves the way for novel therapeutic approaches targeting CHIP to promote tissue regeneration and improve outcomes in PAD patients. It emphasizes the need for further re-search to fully unravel the genetic footprint of the disease and highlights potential clinical implications. The findings presented in this article lay the foundation for personalized medicine approaches and open avenues for the development of targeted therapies based on somatic mutation profiling.

Human arteries show structural and functional peculiarities according to the nutrient and oxygen needs of a specific vascular district. This architectural heterogeneity is reflected in the pathological setting of cardiovascular diseases (CVDs). Indeed, the responsiveness to cardiovascular risk factors, the morphological and molecular patterns are discriminating factors among CVDs affecting different vascular beds. Micro-RNAs (miRNAs) are endogenous regulators of gene expression and fine tuners of vascular cell differentiation, thus these non-coding RNAs can modulate the arterial heterogeneity. The identification of a miRNA signature artery-specific would be promising in the therapy of CVDs, especially in frail elderly patients. In the present review we will provide a concise description of the arterial tree heterogeneity on structural and cellular basis, mainly in the pathological context. Secondly, we will address the miRNA potential as crucial mediators of arterial heterogeneity focusing on abdominal aorta and femoral artery, with the final goal of strengthening the search of more targeted therapies in CVDs and stratification approaches in frail elderly patients.

Background: In recent years, the assessment and guidance of cardiopulmonary resuscitation (CPR) quality using noninvasive and invasive monitoring techniques have been increasingly recommended. In this study, we introduce a new physiological monitoring system that simultaneously measures arterial pressure (AP), venous pressure (VP), and cerebral tissue oxygen saturation (SctO2) during CPR. Methods: This prospective observational study was conducted at a single center (Kagoshima City Hospital). Adult out-of-hospital patients aged ≥18 years with an intravenous femoral arterial line, venous line, and SctO2 monitor were included. We measured femoral arterial pressure (FAP) and femoral venous pressure (FVP) invasively if catheters were immediately inserted into the femoral artery and vein for potential candidates who require interventions such as extracorporeal cardiopulmonary resuscitation but did not receive such interventions as a result. Results: We observed several representative cases that provided the following insights: We presented several cases, including two patients with significant increases in FVP and low SctO2 values, and in both cases, return of spontaneous circulation (ROSC) was not achieved. In contrast, we also presented two cases in which CPR resulted in higher FAP compared to FVP and an upward trend in SctO2 values was observed, and both instances achieved ROSC. Conclusion: We presented a simultaneous physiological monitoring system that can monitor AP, VP, and SctO2 during CPR. Further case accumulations will be necessary to assess the variations in hemodynamic status during CPR and the association between each hemodynamic status and outcomes after cardiac arrest.

Thoracic aortic and arterial aneurysms are cardiovascular conditions associated with life-threatening endpoints including dissection and rupture. The genetic basis underlying the development these disease states is an evolving field, and the reporting of variants associated with aneurysms in patients are essential for advancing screening and diagnostic tools. Among all patients in our program who underwent clinical genetic screening (N=145) for arterial aneurysm and dissection disorders, we identified three patients with single nucleotide variants in the TNXB gene. This gene has known roles in collagen fibrillogenesis and classic Ehlers Danlos Syndrome. This is one of the first reports to associate this gene with aortopathy/arteriopathy and advances the literature relating extracellular matrix genes to arterial aneurysm development.

In response to injury, vascular smooth muscle cells (VSMCs) of the arterial wall dedifferentiate into a proliferative and migratory phenotype, leading to intimal hyperplasia. The ERK1/2 pathway participates in cellular proliferation and migration while dual-specificity phosphatase 6 (DUSP6, also named MKP3) can dephosphorylate activated ERK1/2. We showed that DUSP6 was expressed in low baseline levels in normal arteries; however, arterial injury significantly increased DUSP6 levels in the vessel wall. Compared with wild-type mice, Dusp6-deficient mice had smaller neointima. In vitro, IL-1β induced DUSP6 expression and increased VSMC proliferation and migration. Lack of DUSP6 diminished IL-1β-induced VSMC proliferation and migration. DUSP6 deficiency did not affect IL-1β-stimulated ERK1/2 activation. Instead, ERK1/2 inhibitor U0126 prevented DUSP6 induction by IL-1beta, indicating that ERK1/2 functions upstream of DUSP6 to regulate DUSP6 expression in VSMCs rather than downstream as a DUSP6 substrate. IL-1β decreased levels of cell cycle inhibitor p27 and cell-cell adhesion molecule N-cadherin in VSMCs whereas lack of DUSP6 prevented their downregulation, revealing novel functions of DUSP6 in regulating these two molecules. Taken together, our results indicate that lack of DUSP6 attenuated neointima formation following arterial injury by reducing VSMC proliferation and migration, which were likely mediated via maintaining p27 and N-cadherin levels.

Hypertension is one of the most common and significant cardiovascular risk factor. With the emergence of COVID-19, concerns have arisen about its potential to exacerbate cardiovascular morbidity and mortality. Several theories have emerged linking hypertension with COVID-19. However, the relationship between SARS-CoV-2 infection and long-term risk of hypertension remains insufficiently explored. Therefore, our study aimed to investigate the impact of COVID-19 infection on blood pressure and long-term risk of hypertension developing. A comprehensive search was conducted in the PubMed and SCOPUS databases up to 10th August 2023 for relevant papers. The analysis included 35 eligible articles. The majority of the latest studies pointed to increase BP after COVID-19 infection. However, several observations contradicted the influence of SARS-CoV-2 on the hypertension development or suggesting a transient effect. The possible role of the loss of angiotensin-converting enzyme 2, cytokine storm, increased sympathetic activity, and endothelial dysfunction were considered. On the other hand, BP changes following COVID-19 could be a consequence of lifestyle changes, which often accompanied COVID-19 infection. Our findings highlight the urgent need for comprehensive research on the COVID-19 and hypertension link. These insights are crucial for implementing effective prevention and management strategies for individuals with the history of COVID-19 infection.

Background High Mobility Group Box-1 (HMGB-1) is implicated in the pathogenesis of thrombosis and cancer. In the present study, we aimed to evaluate its potential role as a diagnostic biomarker of portal vein thrombosis (PVT) among patients with hepatocellular carcinoma (HCC). Methods The study population included N=100 prospectively recruited patients with a novel diagnosis of HCC. We compared circulating HMGB-1 levels between 34 healthy controls, HCC patients with PVT (N=22), and HCC patients without PVT (N=78). Results HCC patients without PVT showed significantly higher median HMGB-1 serum levels (8.2 [5.5-13.1] ng/ml) than those observed in the case of HCC with PVT (5.5 [4.4-8.5] ng/ml; p=0.012) and in healthy controls (4.1 [3.1-8.2] ng/ml; p&lt;0.001). Among HCC patients, at univariate analysis, the presence of PVT was associated with higher median age (p=0.036), larger major cancer node diameter (p&lt;0.001), and lower HMGB-1 serum level (p=0.012). At multivariate analysis, the presence of PVT maintained a positive association with major node diameter p=0.001) and an inverse association with serum HMGB-1 levels (p=0.003). Conclusions These findings indicate that serum HMGB-1 bears an inverse association with PVT complicating HCC at the time of diagnosis and suggest that serum HMGB-1 depletion may mark PVT development in cirrhotic patients with HCC.

Conducting computational stress-strain analysis using finite element methods (FEM) is a common approach when dealing with the complex geometries of atherosclerosis, which is a leading cause of global mortality and complex cardiovascular disease. The considerable expense linked to FEM analysis encourages the substitution of FEM with a considerably faster data-driven machine learning (ML) approach. This study investigated the potential of end-to-end deep learning tools as a more effective substitute for FEM in predicting stress-strain fields within 2D cross sections of arterial wall. We first proposed a U-Net based fully convolutional neural network (CNN) to predict the von Mises stress and strain distribution based on the spatial arrangement of calcification within arterial wall cross-sections. Further, we developed a conditional generative adversarial network (cGAN) to enhance, particularly from the perceptual perspective, the prediction accuracy of stress and strain field maps for arterial walls with various calcification quantities and spatial configurations. On top of U-Net and cGAN, we also proposed their ensemble approaches to further improve the prediction accuracy of field maps. Our dataset, consisting of input and output images, was generated by implementing boundary conditions and extracting stress-strain field maps. The trained U-Net models can accurately predict von Mises stress and strain fields, with structural similarity index scores (SSIM) of 0.854 and 0.830 and mean squared errors of 0.017 and 0.018 for stress and strain, respectively, on a reserved test set. Meanwhile, the cGAN models in a combination of ensemble and transfer learning techniques demonstrate high accuracy in predicting von Mises stress and strain fields, as evidenced by SSIM scores of 0.890 for stress and 0.803 for strain. Additionally, mean squared errors of 0.008 for stress and 0.017 for strain further support the model's performance on a designated test set. Overall, this study developed a surrogate model for finite element analysis, which can accurately and efficiently predict stress-strain fields of arterial walls regardless of complex geometries and boundary conditions.

Background: Myocardial infarction is increasing at a young age. New tools are needed to evaluate the risk population of young patients. GDF-15 has been implicated in several key mechanisms of atherogenesis and also is associated with increased mortality and cardiovascular events in patients with coronary artery disease. Arterial stiffness parameters, including pulse wave velocity, can also be measured using peripheral arterial tonometry and can indicate the presence or progression of atherosclerotic changes. The aim of this study is to evaluate the GDF-15 level and arterial stiffness parameters in patients with premature myocardial infarction Method: Thirty patients who recovered from a myocardial infarction were consecutively included. Fifteen age-sex-matched subjects were included as controls. The patients’ serum GDF-15 concentration levels were measured using relevant kits. Measurements of arterial stiffness [pulse-wave velocity (PWV) and augmentation index (AIx)] were performed using a Mobil-O-Graph arteriography system. Results: GDF-15 concentration levels were significantly higher in the patients with premature myocardial infarction when compared to controls. PWV and AIx were similar between the groups. GDF-15 level was negatively correlated with high-density cholesterol (HDL) and positively correlated with uric acid levels in all study populations. Conclusions: GDF-15 levels may be a risk factor for patients with premature myocardial infarction. This pilot study may trigger further studies to elucidate the central role of GDF-15 in the pathophysiology of early atherosclerosis in the young population.

Blood flow-restricted training (BFR) is constantly growing in popularity. Despite growing evidence of the significant influence of BFR training on different body functions, its impact on the vascular system, especially the arteries, is controversial. Therefore, the objective of our study was to analyze how BFR exercise, compared to other types of exercise without restriction of blood flow or other active intervention, influences arterial functions and angiogenesis in adults. Studies comparing the effect of BFR versus non-BFR training on arterial parameters are divided into three categories. Endothelial function, angiogenesis, and other vasculature functions. The search was based on three databases (Cochrane Library, PubMed®, Embase). In this systematic review, 38 studies were included. Meta-analysis revealed a more significant improvement in flow-mediated dilatation (FMD) (p=0.002) and the production of the primary angiogenesis biomarker Vascular Endothelial Growth Factor (VEGF) (p=0.009) after training in BFR compared to nonBFR (p=0.002). Analysis of pulse wave velocity, ankle-brachial index, systolic blood pressure, or heart rate did not show a significant difference in changes between BFR and non-BFR training. Other parameters examined were not sufficiently provided to be included in the meta-analysis. The results obtained, present trends suggesting the significant impact of BFR training on endothelial functions and angiogenesis. Unfortunately, there is still a lack of multicenter randomized clinical trials, including many participants, that are necessary to confirm the advantage of BFR over non-BFR activity.

Photoplethysmography (PPG) is a simple-to-perform vascular optics measurement technique that can detect changes in blood volume in the microvascular tissue bed. Beat-to-beat analysis of the PPG waveform enables the study of the variability of pulse features such as amplitude and pulse arrival time (PAT), and when quantified in the time and frequency domains, has considerable potential to shed light on perfusion changes associated with peripheral arterial disease (PAD). In this pilot study innovative multi-site bilateral finger and toe PPG recordings from 43 healthy control subjects and 31 PAD subjects were compared (recordings each at least 5 minutes, collected in a warm temperature-controlled room). Beat-to-beat normalized amplitude and PAT variability was then quantified in the time-domain using SD and IQR measures and in the frequency-domain bilaterally using Magnitude Squared Coherence (MSC). Significantly reduced normalized amplitude variability (healthy control 0.0384 (IQR 0.0217-0.0744) vs PAD 0.0160 (0.0080-0.0338) (p<0.001) and significantly increased PAT variability (healthy control 0.0063 (0.0052-0.0086) vs PAD 0.0093 (0.0078-0.0144) (p<0.001) was demonstrated in PAD using the time-domain analysis. Frequency-domain analysis demonstrated significantly lower MSC values across a range of frequency bands for PAD patients. These changes suggest a loss of right-to-left body side coherence and cardiovascular control in PAD. This study has also demonstrated the feasibility of using these measurement and analysis methods in studies investigating multi-site PPG variability for a wide range of cardiac and vascular patient groups.

Pulmonary hypertension (PH) is a severe vascular complication of connective tissue diseases (CTD). Patients with CTD may develop PH belonging to different groups: 1) pulmonary arterial hypertension (PAH), 2) PH secondary to lung disease and/or hypoxia, 3) PH due to left heart disease, and 4) chronic thromboembolic pulmonary hypertension (CTEPH). PAH most often develops in systemic scleroderma (SSc), mostly in its limited variant. PAH-CTD is a progressive disease characterized by poor prognosis, therefore the early diagnosis should be established A specific treatment for PAH-CTD is currently available and recommended: prostacyclin derivative (treprostinil, epoprostenol, iloprost, selexipag), nitric oxide and natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase 5 inhibitors (PDE5i: sildenafil, tadalafil), endothelin receptor antagonists (ERA: bosentan, macitentan, ambrisentan). Moreover, novel drugs e.g. sotatercept are intensively investigated in the clinical trials. The aim of this paper is to review the literature on the recent advances in treatment strategy and prognosis of patients with PAH-CTD.

Purpose: A number of imaging readout schemes have been proposed for renal arterial spin labelling (ASL) to quantify kidney cortex perfusion, including gradient echo based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo based schemes of spin-echo echo planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T. Methods: Ten healthy volunteers with normal renal function were scanned using each 2D multislice imaging scheme, in combination with a respiratory triggered FAIR (flow-sensitive alternating inversion recovery) ASL scheme on a 3 T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability. Results: For each imaging scheme, renal cortex perfusion was calculated (bFFE: 276 ± 29 mL/100 g/min, GE-EPI: 222 ± 18 mL/100 g/min, SE-EPI: 201 ± 36 mL/100 g/min, TSE: 200 ± 20 mL/100 g/min). Perfusion was found to be higher for GE based readouts compared to SE based readouts, with significantly higher measured perfusion for the bFFE readout compared to all other schemes (P < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI compared to all other schemes (P < 0.05), the SE-EPI readout gave the highest tSNR and was found to be the most reproducible scheme for the assessment of kidney cortex, with a CoV of 17.2%, whilst minimizing variability of the perfusion weighted signal across slices for whole kidney perfusion assessment. Conclusion: For the assessment of kidney cortex perfusion, SE-EPI provides optimal tSNR, minimal variability across slices and repeatable data acquired in a short scan time with low specific absorption rate.

The arterial network in healthy young adults is thought to be structured to minimise wave reflection in conduit arteries, producing an ascending aortic pressure waveform with three key features: early systolic peak, negative systolic augmentation, and diastolic hump. One-dimensional computer models have provided significant insights into arterial haemodynamics, but no previous models of the young adult have exhibited these three features. Since the latter was likely to be related to unrepresentative or non-optimised impedance properties of the model arterial networks, we developed a new ‘YoungAdult’ model that incorporated 1) a novel and more accurate empirical equation for approximating wave speeds, based on area and relative distance to elastic-muscular arterial transition points, 2) optimally-matched arterial junctions, and 3) an improved arterial network geometry that eliminated ‘within-segment’ taper (which causes wave reflection in conduit arteries) whilst establishing ‘impedance-preserving’ taper. These model properties led to wave reflection occurring predominantly at distal vascular beds, rather than in conduit arteries. The model predicted all three typical characteristics of an ascending aortic pressure waveform observed in young adults. When compared with non-invasively acquired pressure and velocity measurements (obtained via tonometry and Doppler ultrasound in 7 young adults), the model was also shown to reproduce the typical waveform morphology observed in the radial, brachial, carotid, temporal, femoral, and tibial arteries. The YoungAdult model provides support for the concept that the arterial tree impedance in healthy young adults is exquisitely optimised, and it provides an important baseline model for investigating cardiovascular changes in ageing and disease states.

Hypertension and arterial stiffness are the main factors contributing to cardiovascular disease. L-citrulline, a nitric oxide precursor, has been proposed as a blood pressure-lowering intervention. This study aimed to investigate the impact of L-citrulline on central and peripheral blood pressure, arterial stiffness, and muscle oxygenation at rest and during an isometric knee extension exercise protocol. Twelve older males received 6 g of L-citrulline or a placebo for six days using a double-blind crossover design. Blood hemodynamics parameters (i.e., arterial and brachial systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, heart rate), arterial stiffness (i.e., augmented pressure, augmentation index, forward, backward wave pressure and carotid-femoral pulse wave velocity) and muscle oxygenation [i.e., oxyhemoglobin (Δ[O2Hb]) and deoxyhemoglobin (Δ[HHb]), total hemoglobin concentration (Δ[tHb]) and tissue saturation index (TSI%)], were measured at baseline, post-supplementation and during isometric exercise. No significant effects of L-citrulline supplementation were observed at rest or during exercise on blood pressure, arterial stiffness, and muscle blood flow. Both central and peripheral blood pressure were increased during the exercise, which is consistent with isometric contractions. The results of the present study question the efficacy of short-term L-citrulline in decreasing blood pressure at rest or attenuating blood pressure increases during isometric exercise.

Leukotrienes are proinflammatory mediators that participate in the process of atherogenesis and contribute to the development of symptomatic peripheral arterial disease. The aim was to evaluate the relationship between leukotriene E4 (LTE4) and B4 (LTB4) with parameters reflecting endothelial vascular function in patients with chronic lower limb ischemia. This prospective observational study enrolled 50 consecutive patients undergoing endovascular treatment due to chronic lower limb ischemia (Rutherford 3). All participants were followed-up for one year (after 1, 3, 6 and 12 months), with a sequential assessment of urinary LTE4 and LTB4, as well as measures of endothelial and vascular function: Flow-Mediated Dilatation (FMD), Intima-Media Thickness (IMT), corrected Augmentation Index (AI75), Shear Rate (SR), Ankle-Brachial Index (ABI), Toe-Brachial Index (TBI). There was a significant relationship between LTE4 and measures of vascular function: FMD (R2 = 0.69, P&lt;0.001), IMT (R2=0.12, P&lt;0.01), AI75 (R2=0.43, P&lt;0.001), SR (R2=0.48, P&lt;0.001). Similar findings were noted for LTB4: FMD (R2=0.47, p&lt;0.001), IMT (R2=0.23, P&lt;0.001), AI75 (R2=0.61, P&lt;0.001) and SR (R2=0.33, P&lt;0.001). Alterations in parameters were significantly related: ΔLTE4 vs ΔFMD(R2=0.63, P&lt;0.001), ΔSR (R2=0.42, P&lt;0.001) and ΔLTB4 vs AI75(R2=0.40, P&lt;0.001), SR(R2=0. 29, P&lt;0.001). We conclude, that increasing concentrations of LTE4 and LTB4 are associated with impairment of vascular and endothelial function, which may lead to worse endovascular treatment clinical outcomes.

Pulmonary hypertension (PH) is a progressive condition that affects pulmonary vessels, but its main prognostic factor is right ventricle (RV) function. Many mice/rat models are used for research in PAH, but results fail to translate in clinical trials. This study reviews studies that test interventions on pulmonary artery banding (PAB), a model of isolated RV disfunction, and PH models. Multiple tested drugs both improved pulmonary vascular hemodynamics in PH models and RV structure and function in PAB animals. PH models and PAB frequently exhibited similar results (73.1% concordance) with drugs other than endothelin receptor antagonists and phosphodiesterase inhibitors. RV systolic pressure accounted for most differences between PH models and PAB. On the other side, all results on RV fibrosis agreed (12 drugs). Macitentan, sildenafil and tadalafil improved most tested pathophysiological parameters in PH models, but almost none in PAB animals. Dapagliflozin was the only drug that improved no parameters. This review shows that many drugs currently under research for PAH have a cardioprotective effect on animals that may translate to humans. To improve the translational potential of drugs in this field, researchers should test them in multiple models, including PAB, while optimizing induction methods for human disease translation.

Background: Hypertrophic Cardiomyopathy (HCM) is the most common inherited Cardiomyopathy. The hallmark of HCM is myocardial fibrosis which contributes to heart failure, arrhythmias, and sudden cardiac death (SCD). Objective: To identify the factors implicated in heart failure symptoms and functional capacity of patients with HCM. Methods: In this cohort study, 43 patients with HCM were recruited. According to functional capacity and symptoms presentation, patients were categorized according to NYHA classification, and echocardiographic measurements of left ventricle systolic and diastolic function have been conducted. The echocardiographic assessment of right vetriculo-arterial coupling (RVAC) has been made by calculating the tricuspid annular peak systolic tissue Doppler velocity (TASV)/estimated RV systolic pressure (RVSP) ratio. Results: Almost half, 22 (51%) of our study population present symptoms of heart failure and were categorized as the symptomatic group - NYHA 2 or higher. Maximum LVOT gradient, RVSP, and the ratio of E/e’ were higher in the “symptomatic” compared to the “asymptomatic” group. TASV was lower in the “symptomatic” compared to the asymptomatic group (11±1cm/sex vs. 13±2cm/sec, p=0.04). However, there was no difference in other potentially influential factors, such as heart rate or systemic blood pressure. The SCD risk score does not differ between the two studied groups. The RVAC (estimated with the TASV/RVSP ratio) was lower in the “symptomatic” compared with the “asymptomatic” group (0.32±0.09 vs. 0.46±0.11, p<0.001). Conclusion: A low RVAC (as TASV/RVSP ratio) value could represent an echocardiographic marker of right ventricular-arterial uncoupling in patients with HCM and may impaired functional status.

Background The operator's ability in performing carotid stenting (CAS) has improved clinical outcomes. However, more than 3% of patients need to be treated again after CAS. Most of the cases requiring further intervention are affected by hyperplasia. The recommended procedure is the DEBalloon. On the other hand, the literature reports a small number of carotid neoatherosclerosis cases and is recommended to be treated using elective Micronet-covered stent. Discriminating between the two types of in-stent-restenosis ISR (hyperplasia or neoatherosclerosis) is critical for a positive outcome.Case summary We describe a case in which a patient treated with carotid stenting 8 years before, was diagnosed with ISR. Due to the development of neurological symptoms and progressive increases in Peak Systolic Velocity (PSV) eight years following carotid stenting, a DEBalloon was used in a carotid in-stent-restenosis (ISR) standard procedure. About ten minutes after the procedure, the patient developed hemiplegia consistent with the treated carotid territory. The implantation of a MicroNet-covered stent excluded the thrombus and reverted symptoms with a normal MR control at 24 h. Conclusion This case illustrates that when in-stent stenosis evolves years after the stent implantation, neoatherosclerosis should be assessed, and a MicroNet-covered stent should be considered.

The comparative efficacy and safety between lenvatinib and hepatic artery infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC) are still unclear. This multicenter historical cohort study enrolled 244 patients who were treated with HAIC (n = 173) or lenvatinib (n = 71) between 2012 and 2020. Propensity score matching (PSM) was performed, and 52 patients were selected per group. Clinical outcomes and safety were compared. Objective response rate (ORR) was not different between the two groups (26.0% vs. 23.1%, P = 0.736). Before PSM, HAIC group had a higher proportion of Child-Pugh B and portal vein tumor, whereas lenvatinib group had more patients with extrahepatic metastases, which was adjusted after PSM. There were no differences in progression-free survival (PFS) and overall survival (OS) after PSM (HAIC vs. lenvatinib, median PFS, 3.6 vs. 4.0 months, P = 0.706; median OS 10.8 vs. 7.9 months, P = 0.106). Multivariate Cox-regression showed that alpha-fetoprotein ≤ 1000 ng/mL was only associated factor for OS after PSM in all patients (hazard ratio = 0.421, P = 0.011). Subgroup analysis for patients with high tumor burden beyond the REFLECT eligibility criteria revealed that HAIC group (n = 29) had a significantly longer OS than did lenvatinib group (n = 30) (10.0 vs. 5.4 months, P=0.004). More patients in HAIC group achieved better liver function than those in lenvatinib group at the time of best responses. There was no difference in the incidence of grade 3 and 4 adverse events between the two groups. Therefore, lenvatinib is comparable to HAIC in terms of ORR and OS in unresectable HCC meeting REFLECT eligibility criteria.

A key feature of pulmonary arterial hypertension (PAH) is the hyperplastic proliferation exhibited by the vascular smooth muscle cells from patients (HPASMC). The growth inducers FOXM1 and PLK1 are highly upregulated in these cells. The mechanism by which these two proteins direct aberrant growth in these cells is not clear. Herein we identify cyclin dependent kinase 1 (CDK1) also termed cell division cycle protein 2 (CDC2), as having a primary role in promoting progress of the cell cycle leading to proliferation in HPASMC. HPASMC obtained from PAH patients and pulmonary arteries from Sugen/hypoxia rats were investigated for their expression of CDC2. Protein levels of CDC2 were much higher in PAH than in cells from normal donors. Knocking down FOXM1 or PLK1 protein expression with siRNA or pharmacological inhibitors lowered the cellular expression of CDC2 considerably. However, knockdown of CDC2 with siRNA or inhibiting its activity with RO-3306 did not reduce the protein expression of FOXM1 or PLK1. Expression of CDC2 and FOXM1 reached its maximum at G1/S, while PLK1 reached its maximum at G2/M phase of the cell cycle. The expression of other CDKs such as CDK2, CDK4, CDK6, CDK7 and CDK9 did not change in PAH HPASMC. Moreover, inhibition via Wee1 inhibitor adavosertib or siRNAs targeting Wee1, Myt1, CDC25A, CDC25B, or CDC25C led to dramatic decreases in CDC2 protein expression. Lastly, we found CDC2 expression at the RNA and protein level to be upregulated in pulmonary arteries during disease progression Sugen/hypoxia rats. In sum, our present results illustrate that the increased expression of FOXM1 and PLK1 in PAH leads directly to increased expression of CDC2 resulting in a potentiated growth hyperactivity of PASMC from patients with pulmonary hypertension. Our results further suggest that the regulation of CDC2, or associated regulatory proteins, will prove beneficial in the treatment of this disease.

Pulmonary arterial hypertension (PAH) is a complex and devastating disease that the underlying cellular and molecular mechanisms are largely remains unknown. This study aimed to elucidate the key hub genes and pathways in PAH by bioinformatics analysis. In the current study, we performed WGCNA analysis to systematically identify the hub genes for PAH using transcriptome microarray data. From the Gene Expression Omnibus (GEO) database, one microarray dataset (GSE113439) was downloaded for this study. There were 26 samples in this data set, including 15 PHA samples and 11 normal controls. Based on weighted correlation network analysis, 11 modules were identified and the MEgreenyellow module showed a significantly positive correlation with PAH (r = 0.93, P = 1e−06). The genes in greenyellow module were mainly significantly enriched in mitophagy related pathways by KEGG analyses. Combined with the protein–protein interaction (PPI) and co-expression networks, ten hub genes were identified as candidate biomarkers for PAH in the greenyellow module, including CTNNB1, NIPBL, ROCK2, ROCK1, SCAF11, JAK1, BIRC6, KIF5B, PPP1R12A and XRN1. These hub genes might be potential targets for clinical therapy against PAH. The molecular mechanisms involved in these genes that affected the prognosis of PAH should be further validated through biological and basic studies.

Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analy-sis was performed by using univariate (Spearman, t-Student, X2) and multivariate (multiple lo-gistic regression) tests. Results: 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age:71.4±12.4 (79.4% male); TNF-α:10.7±4.9; hs-CRP:1.6±2.2; Neutrophil-to-lymphocyte ratio (NLR):3.5±2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hs-CRP (≥0.5) in 60.5%. Diabetic patients with high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p=0.0346). Plasma TNF-α had a negative correlation with eNOS expression (-0.5, p=0.015) and hs-CRP with VEGF-A (-0.63, p=0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p=0.037), especial-ly in DM. Cumulative mortality at 12-month was related to NLR ≥3 (p=0.019) and TNF-α ≥8.1 (p=0.048). The best cut-off point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hs-CRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suita-ble markers of mortality in CLTI. These results are novel because they connect muscle gene expres-sion and plasma information in patients with advanced PAD, deepening the search of new and ac-curate targets for this condition.

Background: Elevated fasting plasma glucose and visceral fat area (VFA) is highly prevalent in obese adults. This study investigated the associations between systemic arterial hypertension (SAH) and laboratory, anthropometric, heart rate variability (HRV), and obstructive sleep apnea markers. Methods: Cross-sectional study with 95 obese patients treated at Obesity Treatment and Surgery Center, located in Salvador, BA, Brazil. SAH data were obtained from electronic medical records of patients. To evaluate the association of SAH with the predictor variables, the sample was stratified in Normotense Group (NG) and Hypertensive Group (HG), and laboratory markers, body composition, polysomnography data, and HRV were measured. Results: The average age of the NG was 36.3 ± 10.1 and HG 40.4 ± 10.6 years, 73.7% were women in the NG and 57.9% in HG; 82.4% in HG had insulin resistance. In the multivarious logistics regression model with adjustments age, sex, height, and oxyhemoglobin saturation, SAH was inversely associated with fasting plasma glucose mg/dL (odds ratio [OR] = 0.96; 95% interval confidence [CI] = 0.92 - 0.99) and VFA cm² (OR = 0.98; 95% CI = 0.97 - 0.99). The area under curve the VFA was 0.728; CI 95% (0.620 - 0.836) and fasting plasma glucose 0.693; CI 95% (0.582 - 0.804). Conclusions: Lower VFA and fasting plasma glucose concentrations were inversely associated with SAH. These results indicate opportunities to improve the outcome in obese patients through counseling and clinical interventions.

Purpose: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in present study. In DIACRT group, 25 patients had T2, 20 patients had T3. A total of 9 patients had T2 and 2 had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months respectively. The 5-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for DIACRT group, 60.6% and 63.6% for WIACRT group respectively. The LC rate and OS of DIACRT group were significantly higher than that of WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods both in two groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

While fibrinolytic enzymes and thrombolytic agents offer assistance in treating cardiovascular diseases, the existing options are associated with a range of adverse effects. In our previous research, we successfully identified ficin, a naturally occurring cysteine protease that possesses unique fibrin and fibrinogenolytic enzymes, making it suitable for both preventing and treating cardiovascular disorders linked to thrombosis. Papain is a prominent natural cysteine protease derived from the latex of Carica papaya. The potential role of papain in preventing fibrin(ogen)lytic, anticoagulant, and antithrombotic activities has not yet been investigated. Therefore, we examine how papain influences fibrinogen and the process of blood coagulation. Papain is highly stable at pH 4-11 and 37-60°C by azocasein assay. In addition, SDS gel separation electrophoresis, zymography, and fibrin plate assays were used to determine fibrinogen and fibrinolysis activity. Papain appears to have a molecular weight of around 37 kDa, and is highly effective in degrading fibrin, with a molecular weight of over 75 kDa. Furthermore, papain-based hemostatic performance was confirmed in blood coagulation tests, a blood clot lysis assay, and a κ-carrageenan rat tail thrombosis model, highlighting its strong efficacy in blood coagulation. Papain shows dose-dependent blood clot lysis activity, cleaves fibrinogen chains of Aα, Bβ, and γ-bands and significantly extends prothrombin time (PT) and activated partial thromboplastin time (aPTT). Moreover, the mean length of the infarcted regions in the tails of Sprague-Dawley rats with κ-carrageenan was shorter in rats administered 10 U/kg of papain than in streptokinase-treated rats. Thus, papain, a natural cysteine protease, has distinct fibrin and fibrinogenolytic properties, suggesting its potential for preventing or treating cardiovascular issues and thrombosis-related diseases.

1) Background: Spirulina (Arthrospira) maxima has shown beneficial effects such anti-dyslipidemic, antiviral, antioxidant and antihypertensive. However, there are few and limited clinical studies. 2) Methods: a prospective, randomized, parallel pilot study of 4.5 g administration of Spirulina maxima or placebo for 12 weeks in 16 patients with systemic arterial hypertension undergoing treatment with ACE inhibitors was performed to assess the effects on endothelial damage and oxidative stress indicators. The blood levels of sICAM-1, sVCAM-1, endothelin-1, and sE-selectin were quantified; the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and concentrations of reduced glutathione, oxidized glutathione, and thiobarbituric acid reactive susbtances, were also quantified before and after the treatment period. 3) Results: There were statistically significant (p < 0.05) decreases in systolic blood pressure, sVCAM-1, sE-selectin and endothelin-1 levels, and increases in glutathione peroxidase activity and oxidized glutathione levels. 4) Conclusion: The effects found in the present study agree with antihypertensive and antioxidant effects previously reported for Spirulina maxima. However, this is the first report about the effects on indicators of endothelial damage. More research in this field is necessary to gain an insight into the effects of Spirulina on these indicators.

Arterial ageing is thought to cause a diastolic-to-systolic shift in the return time (RT) of backward waves to central arteries. However, current methods of estimating RT—inflection point, zero crossing, and foot methods—depend on a single waveform feature and produce systolic RT throughout life. We propose a novel centroid method that accounts for the entire backward pressure waveform and develop a ground truth RT (GTRT), which can be used in computational models to test the accuracy of RT estimation methods. Linear wave tracking was implemented in a one-dimensional systemic arterial tree model and GTRT was calculated as the amplitude-weighted mean RT of backward waves at the ascending aorta. Using a virtual cohort of 1200 patients, the centroid RT was closest to GTRT compared to the zero crossing, inflection point, and foot methods; mean differences (limits of agreement) were -8 (-47,30), vs -42 (-136,52), -78 (-305,149), and -197 (-379,-15) ms, respectively. The sensitivity of the methods to changes in RT was also assessed in ten sheep. A balloon catheter in the descending thoracic aorta was used to generate a backward-running pulse that arrived at the ascending aorta at different times during diastole or systole, allowing the “bulk” RT of the backward-running wave ensemble to be manipulated. Only the centroid method was sensitive to both diastolic and systolic changes in RT. We conclude that the accuracy and robustness of the centroid method make it most suitable for evaluating the diastolic-to-systolic shift in RT of backward waves with ageing.

Objectives The most severe type of peripheral arterial disease (PAD) is critical limb ischaemia (CLI). In CLI, calcification of the vessel wall plays an important role in symptoms, amputation rate and mortality. However, calcified arteries are also found in asymptomatic persons (non-PAD patients). We investigated whether the calcification pattern in CLI patients and non- PAD patients are different and could possibly explain the symptoms in CLI patients. Materials and Methods 130 CLI and 204 non-PAD patients underwent a CT of the lower extremities. This resulted in 118 CLI patients (mean age 72±12, 70.3% male) that were age-matched with 118 non-PAD patients (mean age 71±11, 51.7% male). The characteristics severity, annularity, thickness and continuity were assessed in the femoral and crural arteries and analysed by binary multiple logistic regression. Results Nearly all CLI patients have calcifications and these are equally frequent in the femoropopliteal (98.3%) and crural arteries (97.5%), while the non-PAD patients had in just 67% any calcifications with more calcifications in the femoropopliteal (70.3%) than in the crural arteries (55.9%, p<0.005). The crural arteries of the CLI patients had significantly more complete annular calcifications (OR 2.92, p=0.001.) while in the non-PAD patients dot-like calcifications dominated. In CLI patients, the femoropopliteal arteries had more severe, irregular / patchy and thick calcifications (OR 2.40, 3.27, 1.81, p≤0.05, respectively) while in non-PAD patients, thin continuous calcifications prevailed. Conclusions Compared with non-PAD patients CLI patients are more frequently and extensively calcified. Annular calcifications were found in the crural arteries of CLI patients while dot-like calcifications were mostly present in the non-PAD patients. These different patterns of calcifications in CLI point at different etiology and can have prognostic and eventually therapeutic consequences.

Background: Chronic exposure to severe hypoxia causes an increase in hematocrit (Hct) and hemoglobin concentration ([Hb]), which can lead to Excessive Erythrocytosis (EE), which could impact physical performance. This work aims to determine the differences in the six-minute walking test (6MWT) outputs between EE and healthy subjects residing at more than 5000 meters. Methods: A prospective, cross-sectional study was performed on 71 men (36 healthy and 25 suffering EE) living in La Rinconada, Peru (5100 m). Basal levels of [Hb] and Hct were obtained. All the subjects per-formed the 6MWT, and distance reached, vital signs, dyspnea, and fatigue (Borg scale) at the end of the test were recorded. Results: The average [Hb] and Hct levels in the control group were 18.7 ± 1.2 g/dL and 60.4 ± 7.1%, respectively, contrasting with EE subjects who showed 23.4 ± 1.6 g/dL and 73.6 ± 5.9% (p < 0.001). However, no statistically significant differences were observed in BMI or other anthropometric parameters. At the end of the 6MWT, the distance traveled, and vital constants were similar between both groups, except for arterial oxygen saturation which was consistently lower in subjects with EE along the test. Conclusion: EE does not significantly affect 6MWT performance at high altitudes nor the hemodynamic control during moderate aerobic exercise of subjects who live permanently in a severe hypoxic environment.

Accidental arterial embolization of hyaluronic acid (HA) fillers can lead to severe complications, including skin ischemia, blindness, and stroke. Currently, the intra-arterial dispersal and fragmentation behavior of HA gels is unknown but is critical to our understanding of the pathomechanism of these injuries. This work introduces the Pulsatile Unit for the Laboratory Simulation of Arterioembolic Restrictions (PULSAR) and evaluates the intravascular behavior of different HA gels. The fragmentation and dispersal behaviors of four HA gels with distinct rheological properties were evaluated via high-resolution videography and ImageJ particle size and morphology analysis. The gels' elastic modulus (G'), loss modulus (G''), tan(δ), and HA concentration were subsequently correlated with their intra-arterial behaviors. This study effectively confirms the extensive fragmentation of HA gels upon arterial inoculation, with particle sizes ranging from &lt;50 µm to &gt;1 mm. Gel particle size and morphology correlate most significantly with tan(δ). Conversely, arterial flow rates do not significantly influence gel fragmentation behavior, though the probability of proximal, macrovascular obstruction is affected. Overall, this study validates the PULSAR model for simulation of arterial dynamics and the testing of intravascular filler kinematics. The findings highlight the importance of gel viscoelasticity and flow parameters in determining particle size, dispersibility, and occlusive potential.

Background: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. There is a growing recognition of the causal interplay between arterial stiffness and HFpEF. We recently reported that phosphate retention is a trigger for arterial stiffness. This study focuses on whether arterial stiffness due to phosphate retention could be a predictor for HFpEF. Methods: The study subjects were 158 patients (68 males and 90 females, mean age 74.8±11.2). HFpEF was defined according to the guidelines of the ESC 2019. Pulse wave velocity (PWV) and central systolic blood pressure (CSBP) were used as markers for arterial stiffness and afterload, respectively. We measured serum levels of fibroblast growth factor 23 (FGF23) as a marker of phosphate retention. Results: The serum levels of FGF23 had significant relationship with PWV. PWV had significant relationships with LV mass index, plasma BNP levels, and relative wall thickness, e’ and E/e’ (p<0.001, respectively). Multivariate logistic regression analysis revealed that PWV higher values and hypertension were significant predictors for the dependent factor (HFpEF). Conclusions: Arterial stiffness amplified LV afterload, leading to LV concentric hypertrophy and LV diastolic dysfunction. This study presents that arterial stiffness due to phosphate retention, and hypertension are important predictors of HFpEF.

Previous studies have revealed the microbial metabolism of dietary choline in the gut, leading to its conversion into trimethylamine (TMA), a precursor of the cardiovascular inflammatory marker trimethylamine N-oxide (TMAO). Polymethoxyflavones (PMFs), exemplified by tangeretin, demonstrate efficacy in mitigating TMAO-induced cardiovascular inflammation. However, the specific mechanism by which these compounds exert their effects, particularly in modulating the gut microbiota, remains uncertain. This investigation focused on tangeretin, a representative PMFs, exploring its influence on the gut microbiota and the choline-TMA conversion process. Experimental results showed that tangeretin treatment attenuated the population of CutC-active bacteria, specifically Clostridiaceae and Lactobacillus, induced by choline chloride in rat models. This inhibition resulted in reduced efficiency in choline conversion to TMA, thereby ameliorating cardiovascular inflammation resulting from prolonged choline consumption. In conclusion, tangeretin's preventive action against cardiovascular inflammation is intricately linked to its targeted modulation of TMA-producing bacterial activity.

Aim. Atherosclerotic complex femoropopliteal lesions have traditionally been treated with bypass surgery. A prosthetic graft is used to save the vein graft for more distal revascularization or when unavailable. However, the endovascular approach has gained popularity and is offered as first-line strategy for complex lesions. This study aimed to evaluate whether endovascular procedures for complex femoropopliteal native lesions can be a first-line treatment strategy over open surgery with prosthetic bypass in patients with peripheral arterial disease (PAD). Methods. A retrospective study was conducted between 2013 and 2021 to identify patients with symptomatic PAD who required limb revascularization at the femoropopliteal segment and complex lesions (TASC II C and D). Primary endpoints were technical success, primary patency, freedom from clinically driven target lesion revascularization (cdTLR), freedom from major adverse limb and cardiovascular events (MALE and MACE), freedom from limb loss, and survival. Secondary endpoints were length of in-hospital stay, duration of the procedure, and costs. Results. We identified 185 limbs among 174 suitable candidates for comparison, wherein 105 were treated with endovascular procedure and 80 with femoral popliteal prosthetic bypass. Most patients in both groups presented with chronic limb-threatening limb ischemia, and all were ASA >3. There were more octogenarians (p = 0.02) and patients with coronary disease (p = 0.004) in the endovascular group. Median follow-up was 30 months. Technical failure rate for endovascular procedures was 4.8% vs 0% in the open group (p 0.003). Freedom from MACE was similar in both groups. The endovascular group showed superior primary patency (p<0.0001), cdTLR (p<0.0001), MALE (p<0.0001), and freedom from limb loss (p = 0.0018) at 24 months. Further analysis performed for the open above-the-knee subgroup showed that the aforementioned endpoints were similar at 12 months, and favoured the endovascular group at 24 months. Procedural time and in-hospital stay were longer in the open group (p<0.0001 and p<0.001). Finally, procedural cost was 10-fold lower in the endovascular bypass group than in the prosthetic bypass group. Conclusion. Endovascular procedures for complex femoropopliteal lesions are safe in patients at high risk for surgery and show better outcomes at 24 months than prosthetic bypasses. The latter may be considered as an alternative in cases of endovascular failure.

Medium-Long term impacts of Antiretroviral drugs on arterial blood pressure in people living with HIV in Malawi.SAGNO Jean Bpatiste², Loenardo Palombi¹ , Giuseppe Liotta¹, Victor T Tolno², Sangare H Mamary², Jere Haswel ².1= University of Tor vergata Roma, 2= Dream Health center MalawiKey Words: HIV, hypertension ABSTRACTIntroduction: We aimed to explore the medium-long term impacts of Anti-Retroviral Treatment (ART) on Hypertension in a sample of HIV-positive in Malawi. Methodology: This was a retrospective case control study carried out at DREAM health Centre in Blantyre/Malawi on patients who were enrolled from 2005 to 2019, Information about age, gender, blood pressure, ART regimen, BMI, CD4 count, Viral load, Biochemistry, hemoglobin, marital status, education level, survival and period on ARVs were retrieved from data base from 01/01/2006 to 31/12/2015.. In total, we enrolled (alive and on HAART)1350 patients > 18 years (mean age: 43.4 and the SD was ±10.7 with 1031 (65.9%) females and 534 (34.1%) males who were taking (or have taken) ARVs for more than 6 months at the date of enrollment and who were not affected by hypertension or potentially related diseases like Renal failure at the enrollment. The mean observation time, from the HAART initiation was 77 months per person (SD±40). Results: The sample was made up by two groups of patients, 675 who developed hypertension and 675 who did not, with similar age and gender composition. Among patients with hypertension, 30/675 (4.4%) developed a stage 3 hypertension, 154 a stage 2 (22.8%) and 491 a stage 1 (72.8%). Hypertension stages were not associated to statistic significant differences of age and/or gender ( p=0.422, p=0.281 respectively). At baseline, patients who developed hypertension showed higher hemoglobin, higher CD4 count and lower VL ( P<0.001). Patients on AZT-based regimen and TDF based regimen were at high risk to develop hypertension while PI-based regimen was protective to hypertension (P<0.001). In a multivariate analysis, factors independently associated to Hypertension were higher CD4 count and Body Mass Index at the visit date, while Baseline Viral Load and PI-Including regimes were protective factors. Education level was inversely associated with risk of hypertension, while being married was associated of risk of hypertension (p<0.001). Mortality rate among hypertensive patients was 1.6% for those treated for hypertension against the 3.6% for those not treated. Conclusion: this study shows a protective action of PI-including regimens compared with AZT based regimen that is associated to an increased risk of hypertension. Factors related to a better general health status are associated to an higher risk of hypertension as well as lower education, older age and male gender. Treatment should be started as soon as Hypertension stages 2-3 are reached and control by behavioral factors is no longer effective.

Given that the outcome of hepatic arterial infusion chemotherapy (HAIC) with cisplatin for intrahepatic advanced hepatocellular carcinoma (HCC) is unclear, we aimed to compare prognostic factors for overall survival (OS) following HAIC with cisplatin versus sorafenib for intrahepatic advanced HCC using propensity score-matched analysis. We enrolled 348 patients with intrahepatic advanced HCC who received HAIC with cisplatin (n = 97) or sorafenib (n = 251) between June 2006 and March 2020. No significant difference was observed in OS between HAIC with cisplatin and sorafenib cohorts (median survival time [MST]: 13.9 vs. 12.7 months; p = 0.0989). To reduce confounding effects, 176 patients were selected using propensity score-matched analysis (n = 88 for each treatment). HAIC with cisplatin significantly prolonged OS compared with sorafenib (MST: 16.2 vs. 12.2 months; p = 0.0060). Following stratification according to the Child–Pugh classification, for both patients with class A (MST: 24.0 vs. 15.6 months; p = 0.0097) and class B (MST: 8.5 vs. 6.9 months; p = 0.0391), HAIC with cisplatin rather than sorafenib significantly prolonged OS. Our findings suggest that HAIC with cisplatin demonstrates longer prognostic effects than sorafenib in intrahepatic advanced HCC, regardless of the hepatic reserve.

Exercise training influences the risk of vascular thrombosis in patients with peripheral arterial disease (PAD). Mitochondrial functionalities in platelets involve the cellular bioenergetics and thrombogenesis. This study aimed to elucidate the effect of cycling exercise training (CET) on platelet mitochondrial bioenergetics in PAD patients. Forty randomly selected patients with PAD engaged in general rehabilitation (GR) with CET (i.e., cycling exercise at ventilation threshold for 30 min/day, 3 days/week) (GR+CET, n=20) or to a control group that only received GR course (n=20) for 12 weeks. Systemic aerobic capacity and platelet mitochondrial bioenergetics that included oxidative phosphorylation (OXPHOS) and electron transport system (ETS) were measured using automatic gas analysis and high-resolution respirometry, respectively. The experimental results demonstrated that GR+CET for 12 weeks significantly (i) elevated VO2peak and lowered VE-VCO2 slope, (ii) raised resting ankle-brachial index and enhanced cardiac output response to exercise, (iii) increased the distance in 6-minute walk test and raised the Short Form-36 physical/mental component scores, and (iv) enhanced capacities of mitochondrial OXPHOS and ETS in platelets by activating FADH2 (Complex II)-dependent pathway. Moreover, changes in VO2peak levels were positively associated with changes in platelet OXPHOS and ETS capacities. However, no significant changes in systemic aerobic capacity, platelet mitochondrial bioenergetics, and health-related quality of life (HRQoL) occurred following GR alone. Hence, we conclude that CET effectively increases the capacities of platelet mitochondrial bioenergetics by enhancing Complex II activity in patients with PAD. Moreover, the exercise regimen also enhanced functional exercise capacity, consequently improving HRQoL in PAD patients.

Stem/progenitor cell transplantation is a potential novel therapeutic strategy to induce angiogenesis in ischemic tissue, which can prevent major amputation in patients with advanced peripheral artery disease (PAD). Thus, clinicians can use cell therapies worldwide to treat PAD. However, some cell therapy studies did not report beneficial outcomes. Clinical researchers suggested that classical risk factors and comorbidities may adversely affect the efficacy of cell therapy. Some studies have indicated that the response to stem cell therapy varies among patients even in those harboring limited risk factors. This suggested the role of undetermined risk factors, including genetic alterations, somatic mutations, and clonal hematopoiesis. Personalized stem cell-based therapy can be developed by analyzing individual risk factors. These approaches must consider several clinical biomarkers and perform studies (such as genome-wide association studies (GWAS)) on disease-related genetic traits and integrate the findings with those of transcriptome-wide association studies (TWAS) and whole-genome sequencing in PAD. Additional unbiased analyses with state-of-the-art computational methods, such as machine learning-based patient stratification, are suited for predictions in clinical investigations. The integration of these complex approaches into a unified analysis procedure for the identification of responders and non-responders before stem cell therapy, which can decrease treatment expenditure, is a major challenge to increase the efficacy of therapies.

Gut dysbiosis, alongside with high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiome of 15 CAD patients and age-matched 15 healthy controls was analyzed by metagenome sequencing. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients sera on endothelial cells was investigated. A metagenome sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated levels of LPS and indoxyl sulfate in patients sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate in meager concentrations demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production and promoting thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression.

Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal and postnatal period. Alveolar oxygen tension (PAO2) and pulmonary arterial PO2 are the main factors that influence hypoxic pulmonary vasoconstriction (HPV). Inability to achieve adequate pulmonary vasodilation at birth leads to persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen is the mainstay of PPHN management. However, optimal monitoring of oxygenation to achieve low pulmonary vascular resistance (PVR) and optimize oxygen delivery to vital organs is not known. Noninvasive pulse oximetry measures peripheral saturations (SpO2) and ranges 91-95% are recommended during acute PPHN management. However, for a given SpO2, there is wide variability in arterial oxygen tension, especially with variations in hemoglobin type (transfusions), pH and body temperature. This review evaluates the role of alveolar, preductal, postductal, and mixed venous oxygen tension and SpO2 in the management of PPHN. Translation and clinical studies suggest maintaining an arterial oxygen tension of 50-80 mmHg to help decrease PVR and optimize pulmonary vasodilator management. Nevertheless, there are no randomized clinical trials evaluating outcomes in PPHN based on targeting SpO2 or PO2. However, most critically ill patients have umbilical arterial catheters and postductal arterial oxygenation may not be an accurate assessment of oxygen delivery to vital organs or factors influencing HPV. The mixed venous oxygen tension from umbilical venous catheter blood gas may assess pulmonary arterial PO2 and potentially predict HPV. It is crucial to conduct randomized controlled studies with different PO2/SpO2 ranges and compare outcomes in PPHN.

Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90 loaded microspheres. This was a multicenter retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm2) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT) and 126 (36.3%) were classified as sarcopenic. The median overall survival (OS) was 28.1 months (95% CI, 24.8-35.7) and median progression-free survival was 8.0 months (95% CI, 6.4-9.4). Multivariate Cox regression analysis revealed that sarcopenia (hazard ratio [HR], 1.36; 95% CI, 1.00-1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33-2.49, p &lt; 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04-1.92, p = 0.03), and albumin-bilirubin grade (2-3) (HR 1.74; 95% CI, 1.24-2.43, p &lt; 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment sarcopenia independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates.

Coronary artery disease (CAD) represents a modern pandemic associated with significant morbidity and mortality. The multi-faceted pathogenesis of this entity has long been investigated, highlighting the contribution of systemic factors such as hyperlipidemia and hypertension. Nevertheless, recent research has drawn light to the importance of geometrical features of coronary vasculature on the complexity and vulnerability of coronary atherosclerosis. Various parameters have been investigated so far, including vessel-length, cross-sectional area, curvature, and tortuosity, using primarily invasive angiography and recently non-invasive cardiac computed tomography angiography (CCTA). It is clear that there is correlation between geometrical parameters and both the haemodynamic alterations augmenting the atherosclerosis-prone environment and the extent of plaque burden. The purpose of this review is to discuss the currently available literature regarding this issue and propose a potential non-invasive imaging biomarker, the geometric risk score, which could be of importance to allow early detection of individuals at increased risk of developing CAD.

We sought to evaluate the effects of non-surgical periodontal treatment (NSPT) on periodontal clinical parameters, systemic blood pressure (BP) and plasma levels of systemic inflammation markers in patients with combined refractory arterial hypertension (RAH) and stage III grade B periodontitis. Twenty-seven participants with RAH and periodontitis received NSPT. The analyzed clinical parameters were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI). An assessment was performed for systemic BP, complete blood count, coagulogram, creatinine measurement, C-reactive protein (CRP), glycated hemoglobin, cholesterol, glutamic oxaloacetic transaminase, glutamate pyruvic transaminase, waist-hip ratio, and body mass index. In the follow-up period, twenty-two patients were evaluated at baseline and after 90 and 180 days. The data were submitted to statistical analysis (α=0.05%). As expected, the clinical results showed a significant improvement in the percentages of PI, BOP, PD and CAL, which were statistically significant at 90 and 180 days (p&lt;0.0001). Importantly, NSPT significantly reduced the blood level of CRP (p&lt;0.02). However, no significant reduction in BP parameters was noted in the evaluated follow-up periods. NSPT, despite the benefits in periodontal clinical parameters, reduced the plasma level of CRP but not the BP in patients with combined RAH and periodontitis.

Blood gas analysis is a diagnostic tool to evaluate the partial pressures of gas in blood and acid-base content. The use of blood gas analysis enables to clear understanding the respiratory, circulatory, and metabolic disorders. The arterial blood gas (ABG) explicitly analyzes blood taken from an artery, assessing the patient's partial pressure of oxygen (PaO2), carbon dioxide (PaCO2) pH (acid/base). PaO2 indicates the oxygenation status, and PaCO2 indicates the ventilation status (chronic or acute respiratory failure). PaCO2 is affected by hyperventilation characterized by rapid or deep breathing, and hypoventilation characterized by slow or shallow breathing. The acid-base balance tested by the ABG procedure measures the pH and PaCO2 directly while the use of the Hasselbach equation gives the serum bicarbonate (HCO3) and base deficit or excess. The measured HCO3is based on strong alkali that frees all CO2 in serum, including dissolved CO2, carbamino compounds, and carbonic acid the calculation uses a standard chemistry analysis giving the amount of "total CO2", the difference will amount to around 1.2 mmol/L. Though ABG is frequently ordered in emergency medicine contests for acute conditions it may also be needed in other clinical settings. The ABG analysis shows to be an exceptional diagnostic tool including the group of those diseases known as acid-base diseases (ABDs) which include a great variety of conditions as such severe sepsis, septic shock, hypovolemic shock, diabetic ketoacidosis, renal tubular acidosis, chronic respiratory failure, chronic heart failure, and diverse metabolic diseases.

Access to health services compromises therapeutic adherence in patients with HTN, which is a risk factor for cardiovascular disease and premature death. The aim of the research is to determine the influence of access to health services on adherence to antihypertensive treatment during the COVID-19 pandemic. We included a cross-sectional analytical study. A survey was applied to 241 hypertensive patients at the Daniel Alcides Carrión Hospital, Callao-Peru. Data were analyzed using SPSS software. Absolute and relative frequencies were reported and the chi-square test was applied with a statistical significance level of p&lt;0.05. In addition, multiple logistic regression analysis was performed using the Stepwise method. An association was found between non-adherence to treatment and health expenses (ORa: 1.9 CI 95% 1.7-2.2), not receiving care due to lack of a doctor (ORa: 2.8 CI 95% 1.5-3.2), having difficulty with schedules (ORa: 3.7 CI 95% 2. 3-5.5), fear of receiving care at the hospital (ORa: 4.5 CI 95 % 2.7-6.8), trust in health personnel (ORa: 7.5 CI 95% 2.3-10.5) and considering that the physician does not have enough knowledge (ORa: 3.1 CI 95% 2.4-7.8). Therapeutic adherence was associated with physician availability for care, difficulty with schedules, fear of being seen in the hospital, trust in health personnel, and waiting time.

It has been reported that prostaglandin I2, such as epoprostenol, develops Grave's disease. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she started complaining of neck swelling and was diagnosed with Grave’s disease. Thyroid function was controlled by thiamazole and levothyroxine. Nevertheless, her thyroid gland enlargement worsened as epoprostenol dose was titrated. After 23 years of treatment with epoprostenol, she suddenly experienced respiratory failure with a giant goiter leading to airway stenosis and passed away. The autopsy confirmed a giant goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

This study aimed to identify the utility of diffusion-weighted magnetic resonance (MR) imaging with an apparent diffusion coefficient (ADC) map as a predictor of the intrahepatic response of hepatocellular carcinoma (HCC) to cisplatin-based hepatic arterial infusion chemotherapy (HAIC). We retrospectively evaluated 113 consecutive patients with HCC who underwent gadoxetic acid-enhanced and diffusion-weighted MR imaging. The appropriate cutoff for the tumor-to-liver ADC ratio was determined to be 0.741. Of the 113 patients, 51 (45%) presented with a tumor-to-liver ADC ratio < 0.741. Evaluation of the intrahepatic treatment response after 2-3 cycles of HAIC in these 51 patients revealed that 20 patients (39%) experienced an objective response to HAIC. On the other hand, only 10 of the 62 patients with a tumor-to-liver ADC ratio ≥ 0.741 (16%) experienced an objective response. Thus, the objective response rate was significantly higher in patients with a tumor-to-liver ADC ratio < 0.741 than in those with a tumor-to-liver ADC ratio ≥ 0.741 (P = 0.006). Multivariate logistic regression analysis using parameters including perfusion alteration, percentage of a non-enhancing portion, and tumor-to-liver ADC ratio revealed that a tumor-to-liver ADC ratio < 0.741 (odds ratio 3.03; P = 0.015) is the sole predictor of an objective response to HAIC. Overall survival rates were significantly higher in patients with objective responses to HAIC than in those without objective responses (P = 0.001 by log-rank test). In conclusion, patients with unresectable HCC with a tumor-to-liver ADC ratio < 0.741 showed a favorable intrahepatic response to HAIC. Therefore, diffusion-weighted MR imaging can play a critical role as a predictor of response to cisplatin-based HAIC in unresectable HCC.

Background: Although lower extremity revascularization is commonly performed in hemodialysis patients, poor prognosis remains a major problem. Protein-energy wasting is reportedly associated with chronic inflammation and advanced atherosclerosis in hemodialysis patients. We investigated the association between the geriatric nutritional risk index (GNRI) as a surrogate marker of protein-energy wasting, C-reactive protein (CRP), and their joint roles in the prediction of amputation and/or mortality. Methods: We enrolled 800 patients successfully underwent lower extremity revascularization. Patients were divided into low, middle and high tertile (T1, T2 and T3) according to GNRI and CRP levels, respectively. Results: Amputation-free survival rates for 8 years were 47.0%, 56.9%, and 69.5% in T1, T2, and T3 of the GNRI, and 65.8%, 58.7%, and 33.2% for T1, T2, and T3 of CRP, respectively (p<0.0001 for both). Declined GNRI [adjusted hazard ratio (aHR) 1.78, 95% confidence interval (CI) 1.24-2.59, p=0.0016 for T1 vs. T3] and elevated CRP (aHR 1.86, 95%CI 1.30-2.70, p=0.0007 for T3 vs. T1) were independent predictors of amputation and/or mortality. In the combined setting of both variables, the risk was 3.77-fold higher (95% CI 1.97-7.69, p<0.0001) in the T1 of GNRI with T3 of CRP than in the T3 of GNRI with T1 of CRP. Conclusions: Patients with pre-procedural decreased GNRI and elevated CRP levels frequently experienced amputation and/or mortality, and a combination of both variables could more accurately stratify the risk.

The relationship between arterial stiffness and oxygen uptake (VO2) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to investigate this relationship and factors contributing to VO2 in patients with AMI. The role of arterial stiffness in cardiac-skeletal muscle coupling during exercise was then elucidated. The exercise capacity via cardiopulmonary exercise testing (CPX), cardio-ankle vascular index (CAVI), and body composition of 101 patients with AMI were measured at discharge. Patients were categorized based on their CAVI into three groups: (i) normal (CAVI: ≤7.9), (ii) borderline (CAVI: 8.0–8.9), and (iii) abnormal (CAVI: ≥9.0). Subsequently, VO2 was compared among these groups. The relationship between the CAVI and peak VO2 (VO2 Peak) during CPX and factors contributing to VO2 Peak were investigated. The abnormal CAVI group had a significantly lower VO2 Peak than the normal and borderline groups. The CAVI was associated with VO2 Peak in patients with AMI. Furthermore, the CAVI was found to be a factor contributing to VO2 Peak. These findings suggest that arterial stiffness in tissue blood distribution and blood supply defines systemic exercise limits in patients with AMI. This suggested that arterial stiffness plays a significant role in cardio-vascular-skeletal muscle coupling.

Background. There are scant data about the effectiveness of high flow nasal cannula (HFNC) oxygen therapy in patients hospitalized with severe acute respiratory failure (ARF) in non-intensive medical wards, particularly regarding the effect on arterial oxygenation compared to conventional oxygen therapy (COT) and non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP). Methods. In a retrospective observational study, oxygenation parameters were measured before and immediately after HFNC initiation in 37 consecutive patients hospitalized in a geriatric ward in 2017. Results. HFNC was used as escalation therapy for untreatable hypoxia after failure of NIV/CPAP (n=18) or COT (n=19). Twenty-two patients died, 2 were transferred to the intensive care unit, while 13 were discharged alive. A “do not intubate” status was identified in 17 of the 22 deceased patients. Partial pressure of oxygen (pO2, p< 0.0001), oxygen saturation (SO2, p< 0.0001), pO2/fraction of inspired oxygen ratio (p=0.004) and peripheral SO2 measured by pulse oximetry (p< 0.0001) significantly increased soon after HFNC application. Oxygenation improvements were greater after escalation from NIV/CPAP and in patients discharged alive. Conclusion. HFNC significantly improved oxygenation in severe ARF after failure of COT or NIV/CPAP and may be particularly suitable for older patients hospitalized in non-intensive medical wards.

The aim of the study was to examine the long-term prognostic value of changes in cardio-ankle vascular index (CAVI) within a year after coronary artery bypass grafting (CABG). Methods. Patients with coronary artery disease (n = 251) in whom cardio-ankle vascular index (CAVI) was assessed using the VaSera VS-1000 device before and in a year after CABG. Groups with improved CAVI (CAVI decreased from pathological value to normal or the index remained within normal values) or worsened CAVI (persistent pathological index value or an increase in CAVI to pathological values or an increase of 1 unit or more) were identified. The groups were compared for the following events at 10-year follow-up: death from all causes, myocardial infarction, stroke/transient ischemic attack, and the combined endpoint. Results. A year after CABG surgery, 45% of patients showed positive dynamics or stable normal CAVI values. Death from all causes was significantly more common in the group with CAVI progression - 32 (27.6%) than in the group with CAVI improvement - 14 (14.8%; p = 0.029). Patients with CAVI progression were more likely to have MACE (death, MI, stroke/TIA) in 49 (42.2%) cases, compared with patients with CAVI improvement - in 23 (24.5%; p=0.008). Negative dynamics of CAVI (p = 0.024), number of shunts (p = 0.006), and the presence of carotid stenosis more than 30% (p = 0.051) were independent predictors of death from all causes at 10-year follow-up after CABG. The presence of carotid stenosis more than 30% (p = 0.002) and the group with negative dynamics of CAVI after a year (p = 0.008) were independent predictors of the development of the combined endpoint during long-term follow-up. Conclusions. Patients with negative dynamics of CAVI one year after CABG were more likely to experience death from all causes and combined endpoint in the long-term follow-up than patients with normal CAVI. In further studies, it is advisable to evaluate the dynamics of CAVI and, based on this, identify the most effective interventions to improve the prognosis of patients after CABG.

Abstract: This paper outlines the methodology and results for a two species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA) ) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two species (free-drug and bound-drug) mass transport setup including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of drug between the free and bound-drug states. The model is solved by a 2-D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over our previously developed model using the finite-difference method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 hours (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.