Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P < 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the “gateway microbiomes.” Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18–48. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness.

The study aimed to identify clinical pharmacology patterns of prescribed and taken medications in older cardiovascular patients using electronic health records (EHRs) (n = 704) (2019–2022). Medscape Drug Interaction Checker was used to identify pairwise drug-drug interactions (DDIs). Prevalence rates of DDIs were 73.5% and 68.5% among taken and prescribed drugs, respectively. However, total number of DDIs was significantly higher among prescribed medications compared with the list of taken drugs (p < 0.05). Serious DDIs comprised 16% and 7% of all DDIs among prescribed and taken medications, correspondingly (p < 0.05). Median DDI numbers between prescribed versus taken medications were Me = 2, IQR 0-7 and Me = 3, IQR 0-7 per record, respectively. Prevalence of polypharmacy was significantly higher among prescribed medications compared with taken medications (p < 0.05). Women were taking significantly more drugs and had higher rates of polypharmacy and DDIs (p < 0.05). No sex-related differences were observed in the list of prescribed medications. ICD code U07.1 (COVID-19, virus identified) was associated with the highest median DDI number per record. Further research is warranted to improve EHR structure, patient engagement in reporting adverse drug reactions, and genetic profiling of patients to avoid potentially serious DDIs.

Background: The hypothesis is that a hypoxic-hyperoxic preconditioning (HHP) is associated with a protective effect on myocardial function by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: Patients (n=120) were randomly assigned to an HHP and a control group. A safe inhaled oxygen fraction for the hypoxic preconditioning phase (10-14% oxygen for 10 minutes) was determined by measuring the anaerobic threshold. At hyperoxic phase, 75-80% oxygen fraction was used during 30 minutes. Results: The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs 23 (41.1%), p=0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low more than 24 h in control group. The endothelial damage markers appeared to be predictors of postoperative complications. Conclusion: The HHP with individual parameters based on the anaerobic threshold is a safe procedure, it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications.

Wall Shear Stress (WSS) abnormalities in carotid artery blood flow are key hemodynamic factors leading to arterial endothelial damage, atherosclerotic plaque formation, and carotid artery stenosis. Precise simulation of carotid artery blood flow WSS in vitro play an important role in understanding the underlying hemodynamic mechanism of carotid artery stenosis. This study presents a design for a microfluidic cell culture chamber with a variable cross-section and a step structure, leveraging microfluidic technology and principles of fluid dynamics. We propose an optimization strategy for microchannel dimensions based on Computational Fluid Dynamics (CFD) simulations. This strategy aims to replicate the distinct WSS waveform features found at various locations within the carotid bifurcation as observed in vivo. Our simulations indicate that with a step height of 0.09 mm, a width of 4 mm for the initial segment, and 5 mm for the subsequent wider channel, the device can effectively model the characteristics of low oscillatory WSS seen at sites of carotid sinus stenosis. Furthermore, it accurately represents the high-magnitude pulsatile WSS waveforms in the more uniform arterial sections downstream of the carotid sinus. The study also reveals that vortex formation and variations in low oscillatory WSS within the stepped section of the microchannel correlate with the step's height and width, as well as with the dimensions of the wider channel section. An increase in step width leads to a decrease in both the vortex area and the magnitude of negative WSS oscillations. When the step height is less than 0.03 mm, vortex formation is inhibited, challenging the simulation of low oscillatory WSS patterns. The variable cross-section microfluidic channel developed in this study provides a platform for simulating carotid artery WSS waveforms and facilitates research into the interplay between low oscillatory WSS at sites of carotid sinus stenosis and arterial endothelial dysfunction.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

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.

The aim of study was to investigate epidemiology aspects of magnetic resonance imaging (MRI) during COVID-19 pandemic. The study comprised depersonalized residents of Tomsk and Tomsk Region (n = 1714). Invitations to take online survey were sent to 50,000 residents by target SMS with response rate of 1.2% (n = 727, Cohort 1). Cohort 2 comprised retrospective patients (n = 987) who underwent contrast-enhanced cardiac MRI (CMR) in 2019-2022. Referrals, clinical characteristics, diagnosis, gender, age, past COVID-19, MRI study protocols, and MRI data were analyzed. 29% of respondents in cohort 1 received MRI examination within past two years; 26% of respondents considered MRI the most informative imaging modality for detecting COVID-19 pneumonia; 12% of respondents reported MRI unavailable. Proportion of CMR among MRI studies increased during COVID-19 pandemic, and maximum incidence of cardiac diseases detected by MRI was in 2021. Incidence of myocardial fibrosis increased from ~67% in 2019 to ~84% in 2022. The rate of outpatient MRI studies significantly increased in 2020, but returned to pre-pandemic level in 2021. COVID-19 pandemic increased the need for MRI and CMR. Patients with history of COVID-19 had persistent and newly occurring symptoms of myocardial damage suggesting chronic cardiac involvement requiring continuous follow-up.

Chronic Kidney Disease (CKD) and Cardiovascular Disease (CVD) are two devastating diseases that may occur in non-diabetics or individuals with diabetes and when combined is referred to as cardiorenal disease. The impact of cardiorenal disease on society, the economy and the healthcare system is enormous. Although there are numerous therapies for cardiorenal disease, one therapy showing a great deal of promise is sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The SGLT family member, SGLT2, is often implicated in the pathogenesis of a range of diseases and dysregulation of the activity of SGLT2 markedly effects the transport of glucose and sodium across the luminal membrane of renal cells. Inhibitors of SGLT2 were developed based on the anti-diabetic action initiated by inhibiting renal glucose reabsorption, thereby increasing glucosuria. Of great medical significance, large-scale clinical trials utilising a range of SGLT2 inhibitors have demonstrated both metabolic and biochemical benefits via numerous novel mechanisms such as sympathoinhibition which will be discussed in this review. In summary, SGLT2 inhibitors clearly exert cardio-renal protection in diabetic and non-diabetic subjects in both pre-clinical and clinical settings by improving hyperglycemia, high blood pressure, hyperlipidemia and diabetic retinopathy. (188 Words)

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Background: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. Patients and methods: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. Results: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1&gt;49% in combination with a negative KRAS result had a median survival of 40 months compared to patients with a positive KRAS result (9 months, p&lt;0.05). In addition, patients diagnosed with adenocarcinoma, PDL1&lt;49% and negative KRAS result had a median survival of 39 months compared to patients with a positive result (28 months, p&lt;0.05). Conclusions: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Background: Oscillation and pulmonary expansion (OPE) therapy can decrease postoperative pulmonary complications in a general surgical population, but its effect after cardiac surgery has not been reported, to our knowledge. We hypothesized that using an OPE device after cardiac surgery before extubation would decrease pulmonary complications. Methods: This retrospective cohort study included adults undergoing elective open cardiac surgery at our institution from January 2018 through January 2019, who had an American Society of Anesthesiologists score of 3 or greater. For mechanically ventilated patients after cardiac surgery, a new OPE protocol was adopted July 1, 2019, comprising an initial 10-minute OPE treatment administered in-line with the ventilator circuit, then continued treatments for 48 hours after extubation. Severe postoperative respiratory complications (primary outcome measure) included need for antibiotics, increased supplemental oxygen use, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcomes data were compared for patients before (usual care with postextubation hyperinflation) and after protocol implementation (OPE). Results: Of 104 patients, 54 patients received usual care, and 50 received OPE. Usual-care recipients had more men (74% vs 62%; P=.19) and were older (median, 70 vs 67 years; P=.009) than OPE recipients. The OPE group had a significantly shorter hospital LOS than the usual-care group (mean, 6.2 vs 7.4 days; P=.04). Other measures improved with OPE but did not reach significance: shorter ventilator duration (mean, 0.6 vs 1.1 days with usual care; P=.06) and shorter LOS in the intensive care unit (mean, 2.7 vs 3.4 days; P=.06). On multivariate analysis, intensive care unit LOS was significantly shorter for the OPE group (mean difference, 0.85 days; 95% CI, 1.65 to 0.06; P=.04). The OPE group had a lower percentage of postoperative complications (10% vs 20%). Conclusion: OPE therapy after cardiac surgery is associated with decreased ICU and hospital LOS.

Background and Objectives. Prevalence of GERD is increased among individuals with obesity and RYGB is considered as the most effective procedure to control GERD and obesity. However, some patients continue to have GERD after RYGB. The aim of the study was to investigate the prevalence and the risk factors of GERD after RYGB. Material and Methods. This prospective study included 180 patients operated with RYGB and followed for on average of 12.2 (0.6) years. 126 (70%) patients agreed to participate in online consultations and provided data on weight, GERD symptoms, filled GERD-HRQL, TFEQ-18 and GSRS questionnaires. Results. The average age before surgery was 42.7 (10.5) years and BMI was 45.2 (6.4) kg/m2. 128 (71.1%) were females and preoperative GERD was diagnosed in 74 (41.1%) patients. At 12 years follow-up the mean %EBMIL and %TWL were 60.37 and 25.73, respectively. The median %WR was 18.0 (39.0). The GERD was present in 30 (23.8%) patients, of whom 12 (40%) continued to have GERD symptoms and 18 (60%) developed de novo GERD. The GERD-HRQL score significantly decreased from 3.0 (8.0) at baseline to 2.0 (5.0) (p=0.028) at 12 years. GSRS Diarrhea and Indigestion median scores increased significantly, from 1.33 (0.67) to 1.5 (2.42) (p 3.2.

Duct-dependent lesions are classically divided into duct dependent pulmonary circulation which involves severe right sided obstructive lesions such as pulmonary atresia or critical stenosis, and duct dependent systemic circulation which is characterized by malformation of the left side of the heart, and whose severest spectrum is hypoplastic left heart syndrome. Dextro-transposition of the great arteries remains in gray zone between being included in some old classifications as a duct dependent pulmonary circulation lesion or a new category of duct-dependent or independent mixing lesion. We hypothesize that re-classifying duct dependent congenital defects into duct dependent perfusion and oxygenation offers a model to fit D-TGA into the same category of right sided obstructive lesions and reflects the clinical spectrum in a more comprehensive way.

Decades of research identified numerous gene biomarkers of cardiac diseases whose restored sequence or/and expression level was hoped to recover the normal cardiac function. However, each human has unique and dynamic pathophysiological characteristics resulting from the unrepeatable combination of favoring factors such are: race, sex, age, medical history, diet, stress, exposure to toxins, habits etc. As such, no treatment fits everybody and finding personalized solutions is a top priority for medicine of 21st century. The Genomic Fabric Paradigm (GFP) provides the most theoretically possible comprehensive characterization of the transcriptome, its alterations in disease and recovery following a treatment. By attaching to each gene the independent average expression level, expression variation and expression coordination with each other gene, GFP delivers thousands times more information than the traditional analysis. This report presents the theoretical bases of the GFP and some applications to our microarray data from mouse models of post ischemic, and constant and intermittent hypoxia-induced heart failure. The GFP analyses revealed novel transcriptomic aspects of the gene expression control and networking under ischemic conditions. Through all-inclusive characterization of the transcriptome and the unrepeatable gene hierarchy in each condition, GFP is an essential avenue towards development of a truly personalized cardiogenomic therapy.

Hypoxia can induce pulmonary edema (PE) and inflammation. Furthermore, hypoxia depresses left ventricular (LV) inotropy despite sympathetic activation. Here, we investigated the role of nitrosative stress and cardiovascular dysfunction in hypoxic lung injury. Additionally, we studied effects of adrenergic blockade (AB) on hypoxia-induced pulmonary injury. Eighty-six female rats were exposed for 72 h to normoxia or normobaric hypoxia and received infusions with NaCl, prazosin, propranolol or prazosin-propranolol combination. We evaluated hemodynamic function and performed histological and immunohistochemical analyses of the lung. Hypoxia significantly depressed LV but not right ventricular (RV) inotropic and lusitropic functions. AB significantly decreased LV function both in normoxia and hypoxia. AB effects on RV were weaker. Hypoxic rats showed signs of moderate PE and inflammation. This was accompanied by elevated levels of tumor necrosis factor (TNF)  and nitrotyrosine, a marker of nitrosative stress in the lungs. In hypoxia, all types of AB significantly reduced both TNF and nitrotyrosine to normoxic levels. However, AB did not attenuate PE. Results suggest that hypoxia-induced sympathetic activation contributes to inflammation and nitrosative stress in the lungs but not to PE. We suggest that AB in hypoxia aggravates hypoxia-induced inotropic LV dysfunction and backlog into pulmonary circulation, thus promoting PE.

Background: COPD is characterized by dyspnea, chronic cough, sputum production and extra pulmonary multimorbidity including depression, anxiety and cognitive problems. Methods: Cognitive and psychological clinical alterations/disorders; QoL/Health-related QoL; and Coping strategies were evaluated in 71 COPD patients characterized for FKBP5 gene (rs4713916). Instruments: MMSE, MoCA, ROCF, BDI-II, CES-D, SAS, SF-36, ADL, IADL, SGRQ, MRF 26, CIRS, Brief COPE. Results: Carriers of the rs4713916 polymorphisms (G:A) show better cognitive performances, higher degree of independence in the ADL and IADL, better QoL before and after rehabilitation, no presence of depressive mood and anxiety symptoms, no family history of psychiatric disorder, more ability to cope with stressors by avoiding emotions but demanding emotional support, and lesser use of anti-anxiety, anti-depressant anti-psychotic, hypnotic-sedative drugs. On the other hand, no difference was found as regards the number of comorbidities. Conclusions: Our study shows that rs4713916 is positively associated with better outcome for COPD. These results offer valuable insights into the role of FKBP5 in the complex network of mechanisms associated to clinical and behavioral features of COPD patients.. Our data may be used as initial benchmark for future clinical studies.

Immune checkpoint inhibitors (ICI’s) are in the forefront of advanced Non Small Cell Lung Cancer (NSCLC) treatment. Still, only 27- 46% of patients respond to initial therapy with ICI’s and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6-3.1 months and a Disease Control Rate (DCR) of 21.4%-41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75-81%, according to post-hoc analyses of several clinical trials. Future research of ICI rechallenge for NSCLC should focus on better patient stratification, to reflect the underlying biology of immunotherapy resistance more accurately.

Non-tuberculous mycobacteria (NTM) are opportunistic pathogens that cause illness primarily in the elderly, in the immunocompromised or in patients with underlying lung disease. Mycobacterium chimaera is a NTM species belonging to the M. avium Complex (MAC) group of species. Since 2013, a global outbreak of M. chimaera infection related to heater-cooler units (HCU) used in cardio-thoracic surgery has been identified. This outbreak was caused by a single strain of M. chimaera. In order to estimate the prevalence of this outbreak strain in Israel, we sampled M. chimaera from several HCU machines in Israel, as well as from patients, sequenced their genomes and compared them to the outbreak strain. The presence of mixed mycobacteria species in the samples complicated the analysis of obtained sequences. By applying a metagenomic binning strategy, we were able to obtain genomes of single strains from the mixed samples, and characterized them. M. chimaera strains were compared to each other and to previously reported genomes from other countries. The strain causing the outbreak related to the HCU machines was identified in several such machines in Israel but not in any of the clinical samples.

Background: The annual mortality of patients with untreated chronic thromboembolism pulmonary hypertension (CTEPH) is approximately 50% unless a timely diagnosis is followed by adequate treatment. In pulmonary embolism (PE) survivors with functional limitation the diagnostic work-up starts with echocardiography. It is followed by lung scintigraphy and right heart catheterization. However, noninvasive test providing diagnostic clues to CTEPH, or ascertain this diagnosis as very unlikely, would be extremely useful since the majority of post PE functional limitations is caused by deconditioning. Methods: Patients after acute PE underwent a structured clinical evaluation with electrocardiogram, routine laboratory tests including NT-proBNP and echocardiography. The aim of study was to verify whether the parameters from echocardiographic or perhaps electrocardiographic examination and NT-proBNP concentration best determine the risk of CTEPH. Results: A total (n = 261, male n = 123) patients after PE were included into the study, in group of 155 patients (59.4%) with reported functional impairment 13 patients (8.4%) had CTEPH and 7 PE survivors had chronic thromboembolic pulmonary disease (CTEPD) (4,5%). Echo parameters differed significantly between CTEPH/CTEPD cases and other symptomatic PE survivors. Patients with CTEPH/CTEPD had also higher level of NT-proBNP (p = 0.022) but concentration of NT-proBNP above 125 pg/ml did not differentiate patients with CTEPH/CTEPD (p>0.05). Additionally, proportion of patients with right bundle brunch block registered in ECG was higher in group with CTEPH/CTED (23.5% vs. 5.8%, p = 0.034) but there were no differences between other ECG characteristics of right ventricle overload. Conclusion: Screening for CTEPH/CTEPD should be performed in patients with reduced exercise tolerance compared to pre PE period, It is not effective in asymptomatic PE survivors. Patients with CTEPH/CTED had predominantly abnormalities indicatingchronic thromboembolism in the echocardiographic assessment. NT-proBNP and electrocardiographic characteristics of right ventricle overload proved to be insufficient in predicting CTEPH/CTEPD development.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including but not limited to imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neu-rostimulation including acupuncture. Lastly, we also touch upon the disease’s different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

This review brings together the current knowledge regarding the risk factors, and the clinical, radiologic and histological features of both post-COVID-19 interstitial pul-monary fibrosis (PCPF) and Idiopathic Pulmonary Fibrosis (IPF) with a particular fo-cus on describing the similarities and the disparities between the fibrotic changes in these two diseases. It is important to highlight the common points of PCPF and IPF to observe if they are some targetable changes to improve patient outcomes. The litera-ture review was performed using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists and researchers to make an accurate diagnosis, which can be useful in identifying the group of patients who can be selected for antifibrotic therapies, and future therapeutic perspectives.

Background/Goals: The gut hormone PYY secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, HOMA-IR, and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as GLP-1 remain to be investigated.

Purpose: To create a highly balanced comparison of ab interno trabeculectomy (Trabectome, AIT) and trabecular bypass stenting (iStent, TBS).Setting: Eye and Ear Institute, Pittsburgh, Ross Eye Institute, Buffalo, and Glaucoma Associates of Texas, Dallas, USA.Design: Retrospective Exact Matching analysis.Methods: AIT and TBS patients were included from three large glaucoma practices. The primary outcome measure was the unmedicated IOP ≤ 21 mmHg at 2-year follow-up visit. A secondary measure was unmedicated IOP reduction ≥ 20% at 2 years. Patients were matched by baseline IOP, the number of glaucoma medications and glaucoma type using Exact Matching and by age using Nearest Neighbor matching. Patients without a close match were excluded. All surgeries were combined with phacoemulsification. Results: 154 AIT and 110 TBS eyes were analyzed. 48 AIT patients were exactly matched to 48 TBS patients. Both groups had a baseline IOP of 15.3±3.1 mmHg. At 24 months, the mean IOP was 13.9±3.3 for AIT versus 16.8±2.8 mmHg for TBS (p=0.04), while the number of medications was 0.7±1.0 for AIT versus 1.7±1.2 for TBS (p=0.04). The proportion of subjects achieving IOP ≤ 21 mmHg without medications at 24 months was 53% in AIT versus 16.6% in TBS (P < 0.05). At 24-month follow up 17.6% of patients in AIT had ≥ 20% IOP reduction without medication versus no patient in TBS. Conclusions: An Exact Matching comparison of AIT and TBS demonstrated greater IOP reduction with fewer medications in AIT.

INTRODUCTION: Achalasia is a pathology with an incidence of 1 in 100,000 inhabitants per year. There are very limited data on achalasia in the obese population, especially in those undergoing bariatric surgery. The approach of choice for cases of achalasia is fundoplication to correct the reflux; however, lacking a fundus due to a previous gastrectomy, an alternative that offers optimal results should be chosen. Here we present the surgical approach in a case of esophageal achalasia and a history of vertical sleeve gastrectomy, where we performed simultaneous Heller's cardiomyotomy and laparoscopic Roux-en-Y gastric bypass, as well as the results obtained. CASE PRESENTATION: 44-year-old woman with no chronic degenerative diseases, with a previous record of vertical sleeve gastrectomy 5 years ago, who started 1 year and 5 months earlier with dysphagia to liquids, then to solids, in addition to weight loss of 10 kilograms in 4 months. The BMI before vertical sleeve gastrectomy was 32 kg/m2, her BMI at the time of admission was 20 kg/m2; she also presented regurgitation and generalized weakness. After analyzing the surgical options, it was decided to perform a Heller cardiomyotomy and a Roux-en-Y gastric bypass. DISCUSSION AND CONCLUSIONS: The procedure turned out to be safe and successful in treating achalasia symptomatology, in addition to complete resolution of the reflux symptom.

Background and Aims Insulin resistance is pivotal in the pathogenesis of Metabolic Syndrome (MetS), which predisposes to both type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). The triglyceride-glucose index (Ty-G index), a validated measure of insulin resistance also predicts MetS, T2DM, severity of albuminuria and ASCVD. There is scantly data providing mechanistic insights into these sequalae. Accordingly, we investigated the relationship between the TyG index and biomarkers of inflammation, oxidative stress, free fatty acids (FFA) levels and adipokine dysregulation in a cohort comprising both controls and patients with nascent MetS. Patients and Methods Participants included 47 patients with MetS and 41 controls. Persons with diabetes, ASCVD, smoking and macro-inflammation were excluded. Fasting blood was obtained for both plasma and monocyte isolation. Results: Receiver operating Characteristic (ROC) curve analysis revealed that TyG index was an excellent predictor of MetS with an area under the curve of 0.87 and it correlated with both hepatic and adipose tissue insulin ressitance .Both serum FFA levels and non-HDL-cholesterol increased significantly over tertiles of TyG index. Based on TyG index tertiles and or correlations, C reactive protein, endotoxin, chemerin , interleukin-6 levels and monocyte toll-like receptor (TLR)- 4 and TLR-2 and their cellular signaling were significantly associated with TyG index . Conclusion: Increased non-HDL-C and most importantly a pro-inflammatory state evidenced by both circulating and cellular biomarkers could be advanced as potential mechanisms explaining the increased risk for T2DM and ASCVD.

Acute kidney injury (AKI) is a highly prevalent and a critical complication of cardiac surgery (CS). Serum lactate levels (sLac) have consistently shown an association with morbimortality after CS. We performed a cross-sectional study including 264 adult patients that had a cardiac surgery between January and December 2020. Logistic regression analysis was performed to determine factors associated with AKI development. We measured the postoperative levels of sLac to all participants immediately after CS (T0) and after 4 hours (T4) of the surgical intervention. Linear regression model was carried out to identify the factors influencing both levels of sLac. We identified four risk predictors of AKI; one was preoperative (atrial fibrillation), one intraoperative (cardiopulmonary bypass time), and two were postoperative (length of hospital stay and postoperative sLac). T0 and T4 sLac levels were higher among CS-AKI patients than in Non-CS-AKI. Postoperative sLac levels were significant independent predictors of CSA-AKI and the sLac levels are influenced by length of hospital stay, the number of packed red blood cells transfused and the use of furosemide in CS-AKI patients. These findings may facilitate the earlier identification of patients susceptible to AKI after CS.

Polyelectrolyte-drug complexes are interesting alternatives to improve unfavourable drugs properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use as inhalable formulations. Particulate-solid HA-VAN25 complex by spray drying from an aqueous dispersion was obtained. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern by X-ray was observed. The powder density, geometric size and morphology showed a suitable aerosolization and aerodynamic performance of the powder, indicating the capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 hours. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus, showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

Colorectal cancer is the third most diagnosed cancer in males and in females, representing 8% of estimated new cases and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9 – 12% are eligible for local treatments with radical intent, including surgical resection, SBRT and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy.

Individual susceptibility to pulmonary oxygen toxicity (PO2tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (FENO) levels can provide an indication of PO2tox susceptibility in humans. Eight U.S. Navy trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and FENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO2tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. FENO decreased by 55% immediately following the six-hour oxygen exposure (n=8, p<0.0001) and by 63% following the eight-hour exposure (n=4, p<0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline FENO and the lowest post-dive FENO and had clinical symptoms of PO2tox. Individuals with low FENO were the first to develop PO2tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lung may protect against the development of PO2tox.

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.

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassemia and 14,3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization, were included in the study. The patients were divided into three groups according to haemodynamics and overall diagnostic approach: 42,9% had precapillary PH (Pulmonary Arterial Hypertension -PAH group), 25% post-capillary PH and 32.1% Chronic Thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics was recorded. PAH-specific drug therapy received 82.1% of patients and Balloon Pulmonary Angioplasty (BPA) was performed in 6 patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for PAH-group. Patients who underwent BPA improved Pulmonary Haemodynamics. Median survival time was 162 months and the survival rate was 1yr-100%, 2,3,4,5,6 years 96%, 9yrs 90% and 13yrs 78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlights the importance of a correct diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies, however the management should be offered in expert PH centers under patients’ individualized approach.

The high morbidity and mortality rate of the pulmonary arterial hypertension (PAH) is partially explained by the metabolic deregulation associated with the disease. The present study identified statistically significant increase of the glucose transporter solute carrier family 2 (Slc2a1), beta nerve growth factor (Ngf), and nuclear factor erythroid derived 2, like 2 (Nfe2l2) on three standard PAH rat models and their healthy counterpart. PAH was induced by subjecting the animals to hypoxia (HO group) or by injecting them with monocrotaline in either normal (CM) or hypoxic (HM) atmospheric conditions. The Western blot and double immunofluorescent experiments were complemented with the gene expression profiling of the animal lungs analyzed from the perspective of the Genomic Fabric Paradigm. We found substantial remodeling of the genomic fabrics of the citrate cycle, pyruvate metabolism, glycolysis/gluconeogenesis and fructose and manose pathways. According to the novel transcriptomic distance criterion, the most comprehensive measure of the transcriptomic alteration, glycolysis/gluconeogenesis was the most affected functional pathway in all three PAH models. PAH decoupled the coordinated expression of many metabolic genes and replaced Pmm2 with Pmm1 in the center of the fructose and mannose metabolism. Our data show that metabolic dysregulation is a major pathogenic factor of the PAH.

There are evidences of shared biological mechanisms between obesity and hypertension during childhood in the adulthood, and loads of research literatures have proven that, it will cost the economies and health of nations profoundly if neglected. The Prevention and early diagnosis of cardiovascular risk factors such as overweight and hypertension is an essential strategy for control, effective treatment and prevention of its’ complications. The aim of the study is to assess the effect of school based Exercise and Life style Motivation Intervention (SEAL-MI) on adolescent's cardiovascular risk factors and academic performance. An experimental study was conducted among 1005 adolescents - 520 and 485 adolescents were randomly selected for control and study group, respectively. Demographic details and the data related to dietary habits, physical activity and sleep quality were collected by a structured interview questionnaire. The study group adolescents were given the SEAL-MI for six months which includes a school based rope exercise for 45 minutes per day for 5 days a week and a motivation intervention related to dietary habits, physical activity and sleep. Post-test 1 and 2 were done after 3 and 6 months of intervention. The prevalence of overweight among adolescents was 28.73% and prehypertension was 9.26%. Among overweight adolescents, the prevalence of prehypertension was found to be very high (32.25%). In post intervention, there was a significant reduction in weight, BP (p=0.000) and improvement in dietary habits, physical activity, sleep (p=0.000) and academic performance. A significant positive correlation was found between BMI and SBP (p=0.000) and BMI and academic performance (p=0.003). The linear regression analyses revealed that the gender (ß: 0.47, 95% CI: 0.39, 0.81), age (ß: 0.39, 95% CI: 0.17, 0.46), family income (ß: 0.2, 95% CI: 0.41, 0.5), residence (ß: 0.19, 95% CI: 0.01, 0.27) and type of family (ß: 0.25, 95% CI: 0.39, 0.02) had the strongest correlate with the BMI of the adolescents. Also, Mother’s education Mother’s education (ß: 0.35, 95% CI: 0.18, 0.59) had the strongest correlate with the SBP of the adolescents. In contrast, the DBP was negatively persuaded by age (ß: -0.36, 95% CI: 1.54, 0.29) and gender (ß: -0.26, 95% CI: 1.34, 0.12) of the adolescents. Regular practice of rope exercise and lifestyle modification such as diet, physical activity and sleep quality among adolescents prevent and control childhood CVD risk factors like overweight, hypertension. The SEAL-MI may lead to age appropriate development of adolescents and improves their academic performance and quality of life. Giving importance to the adolescents from urban habitat, from affluent nuclear family and catching them young will bring significant change in the disease burden.

The standard treatment for early-stage lung cancer is complete tumor excision by limited resection of the lung. Pre-operative localization is used before video-assisted thoracoscopic surgery (VATS) to improve the accuracy of pulmonary nodule excision. However, lung atelectasis and hypoxia resulting from controlling apnea during the localization procedure may affect the localization accuracy. Pre-procedural pulmonary recruitment may improve respiratory mechanics and oxygenation during localization. In this study, we investigated the potential benefits of pre-localization pulmonary recruitment prior to pulmonary ground-glass nodule localization in a hybrid operating room. We hypothesized that pre-localization pulmonary recruitment would increase localization accuracy, improve oxygenation, and prevent the need for re-inflation during the localization procedure. We retrospectively enrolled patients with multiple pulmonary nodule localizations before surgical intervention in our hybrid operating room. We compared localization accuracies between patients who had undergone pre-procedure pulmonary recruitment and patients who had not. Saturation, re-inflation rate, apnea time, procedure-related pneumothorax, and procedure time were also recorded as secondary outcomes. Patients who had undergone pre-procedure recruitment had better saturation, shorter procedure time, and higher localization accuracy. The pre-procedure pulmonary recruitment maneuver was effective in increasing regional lung ventilation, leading to improved oxygenation and localization accuracy.

Objectives: Minimally invasive direct coronary artery bypass (MIDCAB) is an alternative for revascularisation of isolated left anterior descending (LAD) or as multi-vessel (MV) procedure for diagonal branch (RD) or circumflex artery (RCX) region. Methods: From 2021 to 2022 91 patients underwent MIDCAB procedure in our heartcenter. 80% were male. Eighty percent of the patients had two or three vessel coronary artery disease. Mean age was 65±10 years. The left internal mammary artery (LIMA) was anastomosed to the left anterior descending via left minithoracotomy approach in all patients. Fourteen patients received multi-vessel MIDCAB (15%) with two or three anastomoses a saphenous vein graft (as T-graft to LIMA) was anastomosed to RD or RCX. Results: Mean operation time was 2.6±0.8 hours. The 30-day mortality was 0. Mean required packed red blood cells (pRBC) was 0.4±1.2 unit. The intensive care unit stay (ICU) was 1.5±1.6 days mean. We observed two patients (2%) with wound infections postoperatively. Four patients underwent rethoracotomy because of bleeding. Mean follow-up time was 1.5±0.5 years. Seventy-eight patients (86%) were in New York Heart Association (NYHA) class 1, 11 patients (12%) were in NYHA class 2. One patient received percutaneous coronary intervention due to de novo stenosis of the RCA. Late mortality was 2%. The Kaplan-Meier survival rate was 98.8% at 1 and 2 years. Conclusion: MIDCAB is technically demanding. Our postoperative and short-term clinical results demonstrate that this procedure is safe and feasible. Optimal patient selection and an experienced surgical team are mandatory.

Background and Objectives: To evaluate the effectiveness and safety of balloon pulmonary angio-plasty in patients with inoperable chronic thromboembolic pulmonary hypertension in Vilnius Pulmonary Hypertension Referral centre and provide comparative analysis with other centres. Materials and Methods. This study included all balloon pulmonary angioplasty procedures per-formed between 2019 and 2024 in a single tertiary centre. Invasive haemodynamic parameters and clinical variables were assessed at baseline, at the end of invasive treatment, and at the con-clusion of follow-up (average 8.6 months) following the last balloon pulmonary angioplasty. Ad-ditionally, respective literature review was performed. Results. Twenty-six patients with inoper-able chronic thromboembolic pulmonary hypertension were enrolled. The mean age of the pa-tients was 61.6 (40-80) years. Each patient underwent an average of 4.2 (1-9) procedures. Fol-low-up data were available for 12 patients. Mean pulmonary arterial pressure decreased by 38.8% (p

Background: At altitudes beyond 2500 m the risk of developing high altitude pulmonary edema (HAPE) grows with the increases in pulmonary arterial pressure. HAPE is characterized by severe pulmonary hypertension, though the incidence and relevance of individual risk factors are not yet predictable. However, the systolic pulmonary pressure (SPAP) and peak in tricuspid regurgitation velocity (TVR) are crucial factors when diagnosing pulmonary hypertension by echocardiography. Methods: The SPAP and TVR of 27 trekkers aged 20-65 years en route in the Solu Khumbu region of Nepal was assessed. Echocardiograph measurements were performed at Lukla (2,860 m), Gorak Shep (5170 m), and the summit of Kala Patthar (5,675 m). The altitude profile and the participant’s characteristics were also compiled for correlation with the measured data. Results: The results showed a highly significant increase of SPAP and TVR after ascending Kala Patthar. The study revealed a lower increase of SPAP and TVR in the group of older participants, although the initial respective measurements in Gorak Shep were significantly higher for this group. A similar finding occurred in those using Diamox® as prophylaxis. There was an inverse relationship between TVR and SPAP, the peripheral capillary oxygen saturation and heart rate. Conclusions: The echocardiograph results indicate that older people are a risk group for developing a HAPE. The prophylactic use of acetazolamid led to higher initial SPAP values in Gorak Shep, and a lower increase of SPAP as well as TRV after ascending Kala Patthar. Arterial oxygen saturation measurements can provide an indicator for the self-assessment for the risk of developing HAPE and provide a rule of thumb for the altitude profile but does not replace a HAPE diagnosis. The collected data variables concerning backpack weight, sex, workload (actual ascent speed), and pre-existing diseases were not statistically significant factors related to SPAP and TVR (p=<0.05).

The objective of this study was to analyze the effects of a pulmonary telerehabilitation (TR) program in young adults with post-COVID-19 syndrome. The information of sixteen students' medical files were analyzed and allocated to one of two groups (control=CG/experimental=EG). Twelve TR sessions were performed distantly and asynchronously at the EG patients' homes during 4-weeks. The program included diaphragmatic pattern breathing and aerobic exercises. The parameters: i) vital signs (oxygen saturation "SpO2", heart rate "HR", respiratory rate "RR" and blood pressure "BP"; ii) physical capacity “Sit-to-stand test”; iii) cardiorespiratory capacity “6-Minute Walk Test”; and iv) perceived effort "Borg scale" were assessed in both groups. The statistical analyses showed a significant decrease of RR and HR (p < 0.012) accompanied by a significant increase in SpO2 (p < 0.042), physical (p < 0.012) and respiratory (p < 0.028) capacity. The perceived effort decreased significantly in both groups (CG: p < 0.006; EG p < 0.001) only for physical but not for cardiorespiratory capacity (p < 0.106). There were no statistical changes registered in BP (p > 0.05). The current study suggests that a TR program that involves breathing and aerobics exercises is feasible and effective in treating post-COVID-19 syndrome in young patients.

Differentiation of induced pluripotent stem cells to a range of useful, mature target cell types is ubiquitous in monolayer culture. To further improve the phenotype of the cells produced, 3D organoid culture is becoming increasingly prevalent. Mature organoids typically require the involvement of cells from multiple germ layers. The aim of this study was to produce pulmonary organoids from defined endodermal and mesodermal progenitors. Endodermal and mesodermal progenitors were differentiated from iPSCs then combined in 3D Matrigel hydrogels and differentiated for a further 14 days to produce pulmonary organoids. The organoids expressed a range of pulmonary cell markers such as SPA, SPB, SPC, AQP5 and T1α. Furthermore, organoids expressed ACE2 capable of binding SARS-Cov2 spike protein demonstrating the physiological relevance of the organoids produced. This study demonstrates the rapid production of pulmonary organoids using a multi-germ layer approach that could be used for studying novel respiratory disease interactions.

A warning sign for impending cardio-vascular events is not fully established. In the process to plaque rupture, formation of vulnerable plaque is important, and oxidized cholesterols play important role in its progression. Furthermore, the significance of vasa vasorum penetrating medial smooth muscle layer and rich in atheromatous lesion should be paid attention. Cardio-ankle vascular index (CAVI) is new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle. CAVI reflects functional stiffness in addition to structural stiffness. Rapid rise of CAVI means medial smooth muscle cell contraction, and strangling vasa vasorum. We reported rapid rise of CAVI in peoples after big earthquake, following high frequency of cardiovascular events. And we met several cases who showed rapid rise of CAVI a few weeks or months before suffering cardiovascular events. To explain these sequences of events, we proposed a hypothesis; A rapid rise of CAVI means medial smooth muscle contraction, strangling vasa vasorum, leading ischemia, necrosis of vulnerable plaque, then, the plaque ruptures. In individuals having high CAVI, further rapid rise of CAVI might be a warning sign for impending cardiovascular events. In such case, treatments to decrease CAVI had better to be taken soon.

Coccidioides spp are thermally dimorphic fungi found in geographically defined areas of the Western Hemisphere. The primary portal of entry is respiratory, with a symptomatic pneumonic disease as the most common presentation. Subsequent pulmonary complications as well as extrapulmonary metastatic infection may occur, either of which may be the presenting disease manifestation. Cavitary lung disease may be found incidentally or when investigating symptoms such as cough or hemoptysis. This study aims to explore the spectrum of coccidioidal cavities and the evaluation and management in a cohort of patients seen at Kern Medical over the last 12 years.

Idiopathic Pulmonary Fibrosis (IPF) is most common idiopathic interstitial pneumonia. IPF is often seen in elderly men who smoke. Diagnosis of IPF requires integration of a detailed clinical history, specific physical examination, laboratory findings, pulmonary function tests, high-resolution computed tomography (HRCT) of the chest, and histopathology. IPF has a heterogeneous clinical course, from an asymptomatic stable state to progressive respiratory failure or acute exacerbation (AE). AE of IPF has several important differential diagnoses, such as heart failure and volume overload. The International working project proposed new criteria of AE of IPF in 2016 dividing it into triggered and idiopathic AE. On the basis of these criteria, physicians can detect AE of IPF more easily. The recent international IPF guideline emphasized the utility of chest HRCT. In addition, two anti-fibrotic agents have become available. We should attend not only to management of AE, but also to its prevention. The diagnostic process, laboratory findings, typical chest imaging, management and prognosis of AE are comprehensively reviewed.

In order to balance the conflicts among mass flow rate, total pressure ratio, adiabatic efficiency and stall margin in a low-bypass transonic fan, the optimization of the rotor blade is implemented in this study. An advanced 3D optimization design system is adopted, and flow diagnostic methods based on vorticity dynamics are employed to discuss the flow field. Results indicate that by controlling the blade camber line curvature, significant improvements in the aerodynamic performance for the fan stage are achieved, the total pressure ratio is increased by 1.90%, while the adiabatic efficiency and mass flow rate are increased by 4.45% and 5.82%, respectively. Vorticity diagnosis suggest that there exists a close link between performance parameters and vorticity parameters in the axial fan/compressor, both azimuthal vorticity and boundary vortex flux have significant influences on the stage performance. Moreover, the boundary layer separation is accompanied by the spike of entropy and static pressure, while the derivation/gradient of these flow parameters would also suffer drastic changes under the effect of shock wave. The vorticity parameters could provide detailed flow information about the on-wall flow with high accuracy, which provides the researchers with a novel method for the turbomachinery aerodynamic design and analysis.

Purpose: Cardiovascular disease (CVD) is a major risk factor for mortality in patients with osteoarthritis, and comorbidities increase postoperative complications after total knee arthroplasty (TKA). Arteriosclerosis plays a major role in hemodynamic dysfunction and CVD; however, arteriosclerosis has not been preoperatively evaluated before TKA using the cardio–ankle vascular index (CAVI). In this study, we evaluated the degree of preoperative arteriosclerosis using the CAVI in patients undergoing TKA, as well as its correlations with several preoperative patient factors. Methods: Arteriosclerosis was evaluated in 209 consecutive patients (251 knees) with osteoarthritis who underwent TKA at our institution between May 2011 and June 2022. The CAVI was measured in the supine position 1 day before TKA, and the correlations between the CAVI and several clinical factors were analyzed. A p value of <0.05 was considered statistically significant. Results: The CAVI was normal in 62 knees (25%), borderline in 71 knees (28%), and abnormal in 118 knees (47%). Univariate analysis revealed a moderate positive correlation between preoperative CAVI and age (r = 0.451, p < 0.001) and a weak negative correlation between preoperative CAVI and body weight (r = −0.306, p < 0.001) and body mass index (BMI) (r = −0.319, p < 0.001). Multivariate analysis showed that age (β = 0.349, p < 0.001) and BMI (β = −0.235, p < 0.001) were significantly correlated with preoperative CAVI. Conclusion: Arteriosclerosis should be carefully managed intraoperatively and postoperatively in patients with osteoarthritis undergoing TKA, particularly in older patients and patients with a low BMI.

Studies have shown increased nontuberculous mycobacterial pulmonary disease (NTM) incidence with inhaled corticosteroid (ICS) use in patients with chronic respiratory diseases; however, this association in chronic obstructive pulmonary disease (COPD) remains insufficiently studied. Using a nationwide population-based database of the Korean National Health Insurance Service, newly diagnosed COPD patients (20052018) treated with inhaled bronchodilators were selected. An NTM case was defined by the presence of the first diagnostic code following inhaled bronchodilator use. Results indicated that ICS users did not have an increased risk of NTM disease compared to non-ICS users (hazard ratio [HR], 1.121; 95% confidence interval [CI], 0.9501.323; p = 0.1755). The highest quartile of the cumulative ICS dose was associated with the development of NTM (1.200, 0.9501.323, p = 0.0497). Medium (1.229, 1.0081.499, p = 0.0410) and high daily doses of ICS (1.637, 1.2412.160, p = 0.0005) were associated with an increased risk of NTM disease. There was no difference in the risk of NTM according to ICS type. ICS use may not increase the risk of developing NTM disease in patients with COPD. However, physicians should weigh the potential benefits and risks of ICS, especially when using high doses and prolonged durations.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

In the diagnosis of olfactory neuroblastoma (ONB), the presence of S-100–positive sustentacular cells surrounding the tumor is important; however, these are also present in normal nasal sinus epithelium. Although ONB often has a different final diagnosis, complete resection of the tumor has a good prognosis and minimally affects the patient's treatment plan. When the tumor extends around the internal carotid artery (ICA), complete resection is difficult due to the high risk of vascular injury; revascularization using a high-flow bypass can avoid this complication. In the present case, the tumor was located in the left sphenoid sinus and extended around the ICA. Preoperative biopsy tissue was positive for neuroendocrine markers and slightly positive for S-100 protein, leading to a diagnosis of ectopic ONB. High-flow bypass revascularization with trapping of the ICA allowed complete tumor resection. The postoperative histopathological diagnosis was neuroendocrine carcinoma, showing no S-100 protein–positive cells. There was no sign of recurrence two and a half years after surgery without additional treatment. This case demonstrates that the presence of S-100 protein–positive cells in ONB may be misleading. Although misdiagnosis of ectopic ONB should be anticipated, a complete resection of the tumor is an effective treatment strategy.

This study aims to evaluate the patient’s dose exposure from Computed Tomography Pulmonary Angiography (CTPA) examination and to estimates the cancer risk induced from the examinations based on the patient’s size. One hundred patients were recruited, and data information was collected retrospectively. A multi-detector (MDCT) (Philips Brilliance 128, USA) scanner were utilized for the CTPA examination, and dose data were obtained from the system. The effective diameter of each subjects’ image was measured for the Size-specific dose estimates (SSDEs). All subjects divided into Group 1 (19 – 25 cm), Group 2 (25-28 cm) and Group 3 (28-38 cm), where the association between gender were analysed. Effective dose (E), SSDE, organ dose and cancer risk of each group were evaluated and compared statistically using independent t-test and one-way ANOVA. The range of mean CTDI_vol, DLP and E values were (6.44 – 17.42 mGy), (239 – 631 mGy), (5.19 – 13.90 mSv), respectively. In respective with the patient’s effective diameter, the mean SSDE value for Group 1, Group 2 and Group 3 were 9.93 ± 3.89 mGy, 13.70 ± 9.04 mGy and 22.29 ± 7.35 mGy. The organ dose and cancer risk attained for breast, lung and liver were 17.05 ± 10.40 mGy (194 per one million procedure), 17.55 ± 10.86 mGy (192 per one million procedure) and 15.04 ± 9.75 mGy (53 per one million procedure), respectively. Lung and breast with more massive patient’s effective diameter received the highest dose exposure which increases the probability of the cancer risk. CTDI_vol was found to be underestimated, and SSDE provides more accurate in describing the radiation dose and cancer risk. Body effective diameter found to be significant on the estimation except for gender. Therefore, it is essential to apply optimised protocols in order to reduce patient’s exposure during CTPA examination.

Background: Pulmonary sequestration (PS), generally diagnosed using computed tomography pulmonary angiography (CTPA), is a rare congenital developmental malformation of the lung that is characterized by nonfunctional lung tissue independent of the normal lung tissue. This study summarizes the imaging features of the supplying arteries and draining vessels in patients with PS with an aim to assist with timely clinical diagnosis and operation guidance. Materials and Methods: A total of 55 patients with PS diagnosed on CTPA from multiple clinical centers were retrospectively analyzed. Data included demographic characteristics, imaging features, disease location, isolation type, and the features of supplying and draining vessels, as shown on CTPA images. Results: Of the 55 patients reviewed, 3 (5.45%) were children, 3 (5.45%) were adolescents, and 49 (89.09%) were adults, with a mean age of 44 years. Fifty-four (98.18%) patients had intralobar sequestration and one (1.82%) had extralobar sequestration. PS was noted 3.5 times more frequently in the left lower lobe than in the right lower lobe. For the supplying arteries, 47 (85.45%) were derived from the descending thoracic aorta, 1 (1.82%) from the abdominal aorta, 7 (12.73%) from the celiac axis, and 1 (1.82%) from the bronchial artery. The draining vessels were the pulmonary veins in 49 patients (89.09%), the umbilical vein in 1 (1.82%), the venae intercostal in 1 (1.82%), the pulmonary arteries in 11 (20.00%), and not shown on the images in 2 (3.64%). Conclusion: Clinical presentations of PS are non-specific and can be easily missed or misdiagnosed. However, CTPA can help improve the diagnostic accuracy and identify the supplying arteries and draining vessels, which significantly contribute to surgical planning.

The quarantine imposed as the response to the COVID 19 pandemic has been related to an increase in cases of thromboembolism in Non-COVID19 patients .We report the case of a patient with pulmonary thromboembolism without usual triggering causes during the quarantine period, related to a previously undiagnosed hypercoagulable condition.

Objective: The aim of this study was to evaluate the clinical outcome of patients suffering from chronic limb threatening ischemia (CLTI) and tissue loss treated with primary isolated femoral bifurcation endarterectomy (FBE) or with FBE combined with bypass surgery. Methods: This retrospective study was performed in a tertiary university based care center. Between January 2008 and December 2019 a prospectively collected database of patients suffering from CLTI and tissue loss and undergoing either primary FBE (group A) or FBE in combination with bypass surgery (group B) was analysed. Study endpoints were ulcer healing, primary and secondary patency rate, limb salvage and survival. Results: In total, FBE was performed in 73 and FBE with bypass in 60 patients. Between both groups there were no significant differences regarding demographic data or the Global Limb Anatomic Staging System (GLASS) grade III and IV of femoropopliteal lesions. After 3 years, ulcer healing could be achieved in 72% of FBE and in 75% of FBE with bypass patients. The primary patency rate was 95% and 91% for FBE and 83% and 80% for FBE with bypass after one and three years, respectively. The 3-year limb salvage rate was 78% for FBE and 84% for FBE with bypass. The secondary patency rate after one and three years was 99% and 97% for FBE and 93% and 88% for FBE with bypass. Conclusion: FBE and FBE with bypass are equally effective for ulcer healing in cases of combined CFA and superficial femoral artery lesions. There was no significant difference between both groups regarding primary and secondary patency

Pulmonary Embolism (PE) is the obstruction of blood arteries in the lungs by a blood clot. The mortality risk for PE is approximately 30%. Detecting pulmonary embolism in the segmental arteries of the lung is more challenging than in the main arteries and is very prone to being missed. A computer-based approach was created in this work to automatically identify pulmonary embolism in the segmental arteries using computed tomography images. The system's infrastructure includes an enhanced Mask R-CNN deep neural network that has been trained with images containing PE. The network accurately identifies the location of the pulmonary embolism on the computed tomography picture and successfully extracts its borders. The investigation was conducted by generating a local dataset. The study's performance was evaluated using pulmonary embolisms identified manually by the expert radiologist. The sensitivity, specificity, accuracy, dice coefficient, and Jaccard index values for 2130 pictures were 96.4%, 93.5%, 96.1%, 0.96, and 0.90, respectively. The improved Mask R-CNN model has demonstrated superior performance when compared to the traditional Mask R-CNN and U-Net models. This high-performance technology is designed to identify pulmonary embolism and will aid professionals in assessing the size of the embolism.

Background – Endobronchial squamous cell carcinoma is one of the most common types of tumors with such a location. Patients often present in advanced stages of the disease, which leads to a targeted therapeutic attitude of pneumonectomy, most of the time. Practicing a lung parenchyma-preserving surgery led us to do this review. Material and Methods - We used three search platforms SCIENCE, MEDLINE and PubMed, in order to identify studies presenting case reports, studies and reviews on endobronchial squamous cell carcinoma. We identified clinical and paraclinical features of endobronchial squamous cell carcinoma. All selected articles were in English and contained clinical criteria of endobronchial squamous cell carcinoma, autofluorescence bronchoscopy in endobronchial squamous cell carcinoma, imaging features of endobronchial squamous cell carcinoma, blood tumor markers specific for lung squamous cell carcinoma, histopathological features of endobronchial squamous cell carcinoma. Results - 73 articles were analyzed, from which 47 articles were selected as bibliographic references. We have presented the criteria found for endobronchial squamous cell carcinoma in order to highlight the main characteristics and high reliability technologies for the detection of this type of cancer. Conclusions – The current literature review highlights the clinical and paraclinical characteristics of endobronchial squamous cell carcinoma. It aims to open new horizons for research and early detection, frequent practice of lung parenchymal preservation surgery.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.

The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. 2 years follow-up of the study population after initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF), and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was done. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes) – blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity, and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression.

Metabolic and bariatric surgery (MBS) is the most effective long-term treatment for Class III obesity. Reduced dietary intake is considered a behavioral driver of post-surgical weight loss, but limited data have examined this association. Therefore, this study examined prospective, longitudinal relationships between dietary intake and weight loss over 24 months following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy. Relationships between weight loss and dietary intake were examined using a validated 24-hour dietary recall method. Associations between total energy/macronutrient intake and weight loss outcomes were assessed at 12-, 18-, and 24-months following MBS, defining patients as “responders” and “suboptimal responders” according to the Reinhold criteria of 50% excess weight loss. Consistent with previous literature, 12-month responders and suboptimal responders showed significant associations between weight loss and dietary intake. Unlike previous work, this study revealed that many of these associations are no longer significant 24 months post-MBS, despite consistent weight loss trends. This study suggests a short-term signal between these dietary factors and weight loss outcomes 12 months post-MBS, consistent with previous observations. However, this signal does not persist beyond 12 months. These results are essential for interpreting and designing clinical studies measuring long-term post-surgical weight loss outcomes.

Selected glasses with 10 Na₂O + (90-x) P₂O₅ + x BCD where bypass cement dust (BCD) x value =10, 20, 30 in mol% were synthesized by recognizable melting annealing technique. Cooperative characterization of the prepared glasses were carried out through FTIR and SEM analysis before and after immersed in simulated body fluid (SBF) solution for 13 and 23 days at 37 ^oC. After immersion in SBF, apatite layer is produced on the glass surface after 13 day and increase after 23 day, showing good bioactivity after immersion in the SBF especially for bioglass sample with 30% BCD. A porous hydroxy apatite layer produced on the surface of SBF-glass composite and this layer became denser after more soaking time, periods were extended from 13 to 23 days. Atomic absorption spectroscopy explained the early period of soaking that cause release of both Si and Ca ions through the glass beside decreasing of phosphrous ions. Bioglass (BCD-30) is studied as shielding for gamma, protons and alphas by using Phy-X software, SRIM Monte Carlo simulation code and its subroutine TRIM. The gamma shielding parameters, mass stopping power (MSP), range for both proton (H- ions) and alpha (He- ions) in bioglass- BCD-30 and human bone tissue have estimated. Also, comparison between them is calculated in predicting the radiation damage and atomic displacements per atom (dpa).

A single coronary artery is a very rare condition, commonly associated with other congenital anomalies. It could be generally classified as neither benign nor malignant form of congenital coronary artery anomalies since its pathophysiological and clinical implications grossly depend on different anatomical patterns defined by the site of origin and distribution of the branches. By presenting the patient with an isolated single coronary artery, who underwent successful combined aortic valve replacement and coronary artery bypass grafting surgery, we intend to distinguish casual from causal in this extremely rare clinical and surgical scenario. This is the first-ever case published, combining such underlying pathology, clinical presentation, and surgical treatment.

The right heart catheterisation constitutes the gold standard for pulmonary hypertension (PH) diagnosis. However, echocardiography remains a reliable, non-invasive, inexpensive, convenient, and easily reproducible modality not only for the preliminary screening of PH but also for PH prognosis. The aim of this review is to describe a cluster of echocardiographic parameters for the detection and prognosis of PH and analyse the challenges of echocardiography implementation in patients with suspected or established PH. The most important echocardiographic index is the calculation of pulmonary arterial systolic pressure (PASP) through the tricuspid regurgitation (TR). It has shown high correlation with invasive measurement of pulmonary pressure, but several drawbacks have questioned its accuracy. Besides this, the right ventricular outflow track acceleration time (RVOT-AT) has been proposed for PH diagnosis. A plethora of echocardiographic indices: right atrial area, pericardial effusion, the tricuspid annular plane systolic excursion (TAPSE), the TAPSE/PASP ratio, tricuspid annular systolic velocity (s′) and recently, can reflect the severity and prognosis of PH. Recent advances in echocardiography with 3-dimensional right ventricular (RV) ejection fraction, RV free wall strain and right atrial strain may further assist the prognostication of PH.

Pulmonary fibrosis causes scar tissue formation that disrupts the functioning of the lungs. Uncaria gambir (Hunter) Roxb (hereafter gambir)—a plant native to West Sumatra in Indonesia—contains flavonoid (+)-catechin and has strong antioxidant activity, and it can be used to combat pulmonary fibrosis. This random in vivo experimental study analyzed the antifibrotic effect of gambir on the lungs of rats with bleomycin-induced fibrosis. The subjects were 10 groups of 10-week-old male rats weighing around 200–250 g. All groups were terminated at the end of the seventh week or on day 50. The lungs were cleaned, and tissues were taken to analyze inflammatory cell counts and TGF-β1 levels using bronchoalveolar lavage (BAL) with ELISA; type I collagen and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels using immunohistochemistry (IHC); and activation of NF-κB using ELISA and Western blot assays. The most severe histopathological characteristic based on the modified Ashcroft score was in the bleomycin group (BG), whereas the mildest was in the 262 mg/kg of bodyweight antifibrotic gambir-dosed group (AF G262). The results showed a significant difference in the BAL inflammatory cell count (p = 0.017; p &lt; 0.05). AF G262 differed most from the other antifibrotic groups in terms of the number of inflammatory cells (0.63), TGF-β1 levels (3.80), and NF-κB levels (0.48), followed by the 131 mg/kg of bodyweight antifibrotic gambir-dosed group (AF G131), which also differed most from other antifibrotic groups in terms of NF-κB (0.48), TIMP-1 (11.74), and collagen I (14.50) levels. Western blot analysis showed that the fibropreventive and antifibrotic groups had a specific band size of p65, whereas no specific band binding existed in the control group. This study concluded that the administration of AF G262 could improve fibrosis by lysing the extracellular matrix (ECM) in rat lungs.

Hantavirus cardiopulmonary syndrome (HCPS) is characterized by capillary leak, pulmonary edema (PE) and shock that leads to death in up to 40% of patients. Treatment is supportive, including mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO). Hemodynamic monitoring is critical to titrate therapy and to decide ECMO support. Transpulmonary thermodilution (TPTD) provides hemodynamic and PE data that has not been systematically used to understand HCPS pathophysiology. We identified 11 HCPS patients monitored with TPTD; 5 on MV, 3 on ECMO. We analyzed 133 measurements to describe the hemodynamic pattern and its association to PE. The main findings were reduced stroke volume, global ejection fraction (GEF) and preload parameters associated to increased extravascular lung water and pulmonary vascular permeability compatible with hypovolemia, myocardial dysfunction and increased permeability PE. Lung water correlated positively with heart rate (HR, r=0.20) and negatively with mean arterial pressure (r=-0.27) and GEF (r=-0.36), suggesting that PE is linked to hemodynamic impairment. Pulmonary vascular permeability correlated positively with HR (r=0.31) and negatively with cardiac index (r=-0.49), end-diastolic volume (r=-0.48) and GEF (r=-0.40), suggesting that capillary leak contributes to hypovolemia and systolic dysfunction. In conclusion, TPTD data suggests that in HCPS patients, increased permeability leads to PE, hypovolemia and circulatory impairment.

Many lifestyle and occupational habits negatively impact on physical and mental health, increasing the risk of cardiovascular and other diseases. While larger institutions fulfill occupational health requirements to ensure their employees’ wellbeing at work, smaller business workers and entrepreneurs may neglect initial signs of stress or physical decline, putting themselves at increased risk. Early detection of compromised cardiopulmonary health or fitness has the potential to flag up indications for early interventions and reduce the risk of disease onset and progression. This case study highlights the usefulness of respiratory muscle training (RMT) in improving pulmonary and cardiovascular parameters as an early countermeasure to cardiopulmonary decline. We suggest RMT as an easily accessible, cost- and time effective opportunity to support a healthy lifestyle.

Recurrent respiratory papillomatosis (RRP) is a non- malignant disease, characterized by the production of wart-like growths in respiratory tract, affecting both young and adults (Juvenile-Onset Recurrent Respiratory Papillomatosis, JORRP and Adult-Onset Recurrent Respiratory Papillomatosis, AORRP, respectively). Infection caused by Human Papillomavirus (HPV) is known as the main factors involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review was aimed to evaluate the prevalence of severe complications, as lung involvement and lung tumor in JORRP and AORRP patients, following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). Among the 378 studies were found on PubMed and Scopus using the following MESH terms “recurrent respiratory papillomatosis and lung tumor” and “pulmonary tumor and recurrent respiratory papillomatosis”. Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI:4%-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7%-18%; I2 :85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1%- 7%; I2: 67.1%), and a pooled prevalence mortality for this group of 4% (95% CI:2%-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV 11 was 21% (95% CI: 5%-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11 positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

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.

There have been significant collaborative efforts over the past three years to develop therapies against COVID-19. During this journey, there has also been a lot of focus on understanding at-risk groups of patients who either have pre-existing conditions or have developed concomitant health conditions due to the impact of COVID-19 on immune system. There was a high incidence of COVID-19 induced pulmonary fibrosis (PF) observed in patients. PF can cause significant morbidity, long-term disability, and lead to death in the long run. Additionally, being a progressive disease, PF can also impact the patient for a long time after COVID infection and affect the overall quality of life. Although current therapies are being used as the mainstay for treating PF, there is no therapy specifically for COVID-induced PF. As observed in the treatment of other diseases, nanomedicine can show a significant promise in overcoming the limitations of current anti-PF therapies. In this review, we summarize the efforts reported by various groups to develop nanomedicine therapeutics to treat COVID-induced PF.

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents may be beneficial in patients with CPFE, but further studies are needed.

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.

There is currently a lack of pathologic data on the novel coronavirus (SARS-CoV-2) pneumonia, or COVID-19, from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of surgery. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that, apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Since both patients did not exhibit symptoms of pneumonia at the time of surgery, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.

Neutrophil elastase (NE) is taken up by macrophages, retains intracellular protease activity and induces a pro-inflammatory phenotype. However, the mechanism of NE-induced pro-inflammatory polarization of macrophages is not well understood. We hypothesized that intracellular NE degrades histone deacetylases (HDAC) and Sirtuins, disrupting the balance of lysine acetylation and deacetylation, and resulting in nuclear to cytoplasmic translocation of a major alarmin, High Mobility Group Box 1 (HMGB1), a pro-inflammatory response in macrophages. Human blood monocytes were obtained from healthy donors, or from subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Monocytes were differentiated into blood monocyte derived macrophages (BMDM) in vitro. Human BMDM were exposed to NE or control vehicle and the abundance of HDACs and Sirtuins was determined by western blotting of total cell lysates or nuclear extracts, or determined by ELISA. HDAC, Sirtuin, and Histone acetyltransferase (HAT) activities were measured. NE degraded most HDACs and Sirtuin (Sirt)1, resulting in decreased HDAC and sirtuin activities, with minimal change in HAT activity. We then evaluated whether the NE-induced loss of Sirt activity or loss of HDAC activities would alter the cellular localization of HMGB1. NE-treatment or treatment with Trichostatin A (TSA), a global HDAC inhibitor, both increased HMGB1 translocation from the nucleus to the cytoplasm, consistent with HMGB1 activation. NE significantly degraded Class I and II HDAC family members and Sirt 1 which shifted BMDM to a pro-inflammatory phenotype.

Despite needs for new therapies and improvements in existing approaches in cardiovascular, pulmonary, endocrine, and renal disease, investment in these areas is lagging relative to other specialties. This article summarizes a meeting of key stakeholders of U.S. Food and Drug Administration (FDA) officials, representatives from academia, national organizations, and patients and caregivers. The purpose was to identify and discuss high-priority issues, establish areas of common interest, and explore opportunities for collaboration. During the meeting (September 2016), the construct of a “multimorbidity continuum” emerged, in which chronic diseases are understood as their effects on the whole rather than individual organ systems. Cross-disciplinary priorities included: 1) the need to generate greater high-quality evidence at lower cost; 2) the imperative to develop and implement patient-centered approaches to clinical investigations; 3) the importance of trial participation in under-represented populations, particularly with comorbid conditions, and 4) the need for progress in tobacco regulation. Representatives from each therapeutic area reported on their consensus priorities, and FDA representatives discussed the agency’s role in facilitating broader approaches to therapeutic development and evaluation of disease as linked across organ systems rather than in isolation, and emphasized the importance of patient engagement, collaboration and communication across stakeholders.

Background: Coronary artery bypass grafting (CABG) can be performed using on-pump or off-pump techniques. The optimal approach remains debated. Objectives: The COMPARE CABG (Comparative Outcomes of Mortality, Perioperative complications, cARdiac function, and Hospital stay in On-Pump versus Off-Pump Coronary Artery Bypass Grafting) study aims to systematically compare the outcomes of these surgical approaches. Methods: A comprehensive search was conducted in Pubmed, Cochrane Library, and other databases. Studies with a sample size > 4000 were included. Outcomes analyzed included mortality, complications, cardiac function, and hospital stay. Results: Meta-analysis of 5 studies with 58,232 patients showed that off-pump CABG was associated with a slightly lower complication rate: 15% for on-pump CABG and 13.5% for off-pump CABG with a pooled effect size of 0.90 (95% CI: 0.85-0.95). In terms of cardiac function and hospital stay, results were also favorable to off-pump CABG with an effect size of 1.12 (95% CI: 1.05-1.19) and 1.15 (95% CI: 1.10-1.20), respectively. The pooled mortality rate was 2.5% for on-pump and 2.4% for off-pump CABG, with an effect size of 1.05 (95% CI: 0.98-1.12), indicating no significant difference between the groups. Conclusion: These findings suggest that off-pump CABG may be a preferable option for reducing surgical complications, though both techniques yield comparable mortality outcomes. Further research is needed to explore long-term cardiac function and patient-specific factors influencing the choice of surgical method.

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.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

Pulmonary Hypertension (PH) is a terminal disease characterized by severe pulmonary vascular remodeling. Unfortunately, targeted therapy to prevent disease progression is limited. Here, the vascular cell populations that contribute to the molecular and morphological changes of PH in conjunction with current animal models for studying vascular remodeling in PH will be examined. The status quo of epigenetic targeting for treating vascular remodeling in different PH subtypes will be dissected, while parallel epigenetic threads between pulmonary hypertension and pathogenic cancer provide insight into future therapeutic PH opportunities.

This study aimed to assess the prognostic significance of total leukocyte count (TLC) and hemoglobin (Hb) levels upon admission for patients with acute pulmonary embolism (PE), considering the European Society of Cardiology (ESC) model for mortality risk. 1622 patients from a regional PE registry were included. Decision tree statistics were employed to evaluate TLC and Hb's prognostic value, both independently and in conjunction with the ESC model. Results indicated all-cause and PE-related in-hospital mortality rates of 10.7% and 6.5% respectively. Subgrouping patients based on TLC cutoff values (≤11.2, 11.2-16.84, &gt;16.84 x10^9/L) revealed increasing all-cause mortality risks (7.0%, 11.8%, 30.2%). Incorporating Hb levels (≤126 g/L or above) further stratified the lowest risk group into two strata with all-cause mortality rates of 10.1% and 4.7%. Similar trends were observed for PE-related mortality. Notably, TLC improved risk assessment for intermediate-high risk patients within the ESC model, while Hb levels enhanced mortality risk stratification for lower risk PE patients in the ESC model for all-cause mortality. In conclusion, TLC and Hb levels upon admission can refine the ESC model's mortality risk classification for patients with acute PE, providing valuable insights for improved patient management.

COVID-19 generated a scenario for global health with multiple systemic impairments. This retrospective study evaluated the clinical, radiological, and pulmonary functional evolution in 302 post-COVID-19 patients. Regarding post-COVID-19 pulmonary symptoms, dry cough, dyspnea, and chest pain were the most frequent. Of the associated comorbidities, asthma was more frequent (23.5%). Chest Tomography (CT) initially showed a mean pulmonary involvement of 69.7%, and the evaluation in the subsequent months showed an improvement in the evolutionary image, and with less than six months post-pathology, there was a commitment of 37 .7%, from six to twelve months, 20% and after 12 months, 9.9%. And as for most of the sample, 50.3% of the patients presented CT normalization in less than six months after infection, 23% normalized between six and twelve months, and 5.2% normalized the images after twelve months, with one remaining. Percentage of 17.3% who maintained post-COVID-19 pulmonary residual sequelae. Regarding spirometry, in less than six months after the pathology, 59.3% of the patients already showed a regular exam; 12.3% normalized their function within six to twelve months, and 6.3% concluded a normal exam after twelve months of post-pathology evaluation. Only 3.6% of the patients still showed some alteration in this period.

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaza (bovhyaluronidase azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaza was administered at different doses by intranasal and intramuscular routes. Histology, hematology and enzyme-linked immunosorbent assay were used in the study. The use of Longidaza reduced pulmonary fibrosis as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaza inhibited the inflammatory response in pulmonary fibrosis, decreased the levels of IL-6, TNF-α, hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaza at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaza is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [ nuclear factor-κB (NF-кB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.

Background: The Corona Virus Disease 2019 (COVID-19) is spreading globally now. However, the clinical presentation that predict prognosis of the patients are still largely unknow. Methods: We enrolled 393 patients infected with COVID-19 and 30 patients with common pulmonary bulla and reviewed their clinical features to evaluate the potential prognostic value of pulmonary vesicles, especially in the patients with severe symptoms. One COVID-19 patient with vesicles was treated by bullectomy for last resort, and its characteristics of the patient’s perioperative laboratory tests was analyzed. The pathological findings of bullectomy were described and compared with those of common bulla cases. Results: Patients infected with COVID-19 showed more dependence on ventilator, occurrence of super resistant bacteria, and prone to vesicle formation than common bulla (p<0.05). Disease severity is associated with age, sex, and usage of ventilator, ECMO and antibiotics, super resistance bacteria and vesicle formation (p<0.05). The average mortality rate of COVID-19 patients was 4.10% (25.4% in severe patients, 0.00% in mild patients). Interestingly, the mortality rate further increased in severe patients with pulmonary vesicles than those without pulmonary vesicles (35.7% vs 22.4%, p=0.0442). One COVID-19 patient with vesicles underwent bullectomy and had a poor prognosis, who showed diffuse alveolar damage and extensive necrosis in bullectomy specimen. Conclusions: Patients infected with COVID-19 are more prone to form pulmonary vesicles showed on chest CT scans, as an important poor prognosis factor, especially in the severe patients.

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.

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.

Numerous genes expression lead to inflammation in the individuals’ lungs that have chronic obstructive pulmonary disease (COPD) may be affected by epigenetic alteration. Important epigenetic processes include methylation of DNA and different histones post-translational changes, including ubiquitination, phosphorylation, methylation, SUMOylation and acetylation. Smoking can trigger the enzymes that control these epigenetic changes. According to the majority of publications, both environmental and genetic variables have a substantial role in the development of COPD. Although, the information about COPD epigenetic is not much but, a better perception of the disease pathophysiology and identifying new markers to create novel therapeutics for patients can be achieved via a better understanding of the epigenetic processes involved.

Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), lung histology and transcriptomes of six weeks old male rats with PH induced by: 1) hypoxia (HO), 2) administration of monocrotaline (CM) or 3) administration of monocrotaline and exposure to hypoxia (HM). The results in PH rats were compared to those in control rats (CO). After four weeks exposure, increased RVSP and RVH, pulmonary arterial wall thickening, and alteration of the lung transcriptome were observed in all PH groups. The HM group exhibited the largest alterations and also neointimal lesions and obliteration of lumen in small arteries. We found that the PH increased the expression of caveolin1, matrix metallopeptidase 2 and numerous inflammatory and cell proliferation genes. The cell-cycle, vascular smooth muscle contraction and the oxidative phosphorylation pathways, as well as their interplay were largely perturbed. Our results also suggest that the up-regulated Rhoa (ras homolog family member A) mediates its action through expression coordination with several ATPases. The upregulation of antioxidant genes and the extensive mitochondrial damage observed especially in HM group, indicate metabolic shift towards aerobic glycolysis.

Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of leptin receptor signalling. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

Hemodynamics is the eternal theme of the circulatory system. Abnormal hemodynamics and cardiac and pulmonary development intertwine to form the most important features of children with congenital heart diseases (CHDs), thus determining these children’s long-term quality of life. However, due to the lack of neonatal rodent models of CHDs, it is unclear how CHD-associated hemodynamics shape postnatal cardiac and pulmonary development. Here, we review the varieties of hemodynamic abnormalities that exist in children with CHDs, the recently developed neonatal rodent models of CHDs, and the inspirations these models have brought us in the areas of cardiomyocyte proliferation and maturation, and in alveolar development. Furthermore, current limitations, future directions, and clinical decision-making based on these inspirations are highlighted. Understanding how CHD-associated hemodynamic scenarios shape postnatal heart and lung development may provide a novel path to improving the long-term quality of life of children with CHDs, transplantation of stem cell–derived cardiomyocytes, and cardiac regeneration.

Pulmonary fibrosis is a chronic, progressive and fatal disease of the interstitial lung， there still lack of efficient therapy to reverse the prognosis of patients currently. In this study, a fucoidan from Costaria costata was isolated and its anti-idiopathic fibrosis activity was investigated both in vitro and in vivo. The chemical composition analysis results show that Costaria costata polysaccharide (CCP) is consisting of galactose and fucose as the main monosaccharides with a sulfate group content of 18.54%. The results found that CCP could resist TGF-β1-induced epithelial-mesenchymal transition (EMT) in A549 cells by inhibiting the TGF-β/Smad and PI3K/AKT/mTOR signaling pathways. In vivo data found that CCP treatment alleviated bleomycin (BLM)-stimulated fibrosis and inflammation in mice lung tissue. This study suggests that CCP could protect the lung from fibrosis by relieving the EMT process and inflammation in lung cells.

Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, IL1RA, IL8 and TNFB) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (IFNG, IL12, IL4, TNFB and IL1RA and TLR2,4 associated with PTB susceptibility and cytokine levels but not LNTB (p &lt; 0.05). Similarly, genetic variants in LTA4H, P2RX7, DCSIGN and SP110 showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future susceptibility and functional studies.

Aim: In individuals with COVID-19, the study assessed the relationship between cytokine expression and pulmonary dysfunction. These correlations may help to suggest strategies for prevention and therapies of coronavirus disease outbreak. Patients and methods: 50 healthy participants and 100 COVID-19 patients participated in this study. COVID-19 participants were subdivided into moderate and severe groups based on the severity of their symptoms. In both patients and controls, measurements of white blood cells (WBCs), lymphocytes, C-reactive protein (CRP), interleukin (IL)-1, IL-4, IL-6, IL-18, and IL-35 were estimated. All the patients performed chest CT and CO-RADS score was assessed. Results: All patients had increased WBCs count and CRP, IL-1, IL-4, IL-6, IL-18, and IL-35 levels than healthy controls. While WBCs, CRP, and cytokines like IL-1β and IL-6 showed significantly higher levels in the severe group as compared to moderate patients, IL-4, IL-35, and IL-18 showed comparable levels in both disease groups. Furthermore, CO-RADS score was positively connected with WBCs, CRP, and cytokine levels (IL-35, IL-18, IL-6, IL-4 and IL-1β) in both groups, and lymphocyte levels in all patient groups considerably decreased as compared to the controls. CO-RADS score, also demonstrated a positive correlation with lymphocytes in the moderate COVID-19 patients, whereas in the severe patients, it demonstrated a negative correlation with lymphocytes. Conclusion: Severe COVID-19 patients, compared to individuals with moderate illness and healthy controls, patients had lower lymphocyte counts and increased CRP with greater WBCs counts. In contrast to moderate COVID-19 patients, severe COVID-19 patients had higher levels of IL-1β and IL-6, but IL-4, IL-18, and IL-35 between both illness categories at close levels. CO-RADS 5 was the most frequent category in both moderate and severe cases. Patients with a typical CO-RADS involvement had a higher CRP and white blood cell count with a lower lymphocyte count than the others. Cytokine levels were considered a surrogate markers of severe lung affection in COVID 19 patients.

Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a systemic disease rather than a mere disorder of the lungs. Central (respiratory) and peripheral (limb) muscle weakness are among the main pronounced systemic effects of COPD. While the disease primarily affects the lower limb muscles and contributes to gait impairment, COPD is also associated with an increasing risk of falls in patients (COPDp). Previous studies have reported higher rates of falls among COPDp (1.17 to 1.20 falls/person-year), amounting to four times higher than an age-matched healthy group. Potential fall risk factors include muscle weakness, impaired daily activities, cognitive dysfunction, and gait and balance impairment. Although COPDp often manifest many of these risk factors, there remains a gap in literature regarding falls during walking in this population. This study aimed to 1. analyze the literature to identify the risk factors of falling in COPDp, and 2. investigate the underlying mechanisms by which these risk factors can lead to increased prevalence of falling. The results suggest that in addition to the known risk factors of falling, low back pain and mental fatigue should also be considered as relevant risk factors in the treatment process of these patients. Moreover, respiratory problems, which are common in this population, have demonstrated pronounced effects on energy expenditure, gait, and other types of activities of daily living (ADLs), leading to reduced intensity, disrupted coordination of the trunk-pelvic structure with the lower limbs during gait, and altered motor control performance due to activation of muscles in an inefficient synergic manner. These problems potentially lead to the increased vulnerability of these patients to external disturbances and higher incidence risk of falls and injuries. Cognitive problems, which are typically due to reduced oxygen received by the brain, as well as general inflammation caused by COPD, also play a significant role in gait disruption and balance. Future research is warranted to determine the prevalence of falls in COPDp by examining the response of these patients to Medio-Lateral (ML) and Anterior-Posterior (AP) disturbances during gait in association with traditional and recommended fall risk factors.

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.

Introduction: The rising trend in allergic diseases has occurred in parallel with an increasing prevalence in obesity, and suggesting a possible association. The increased body mass has numerous health consequences, including an impairment function of the respiratory system. The associations between eating habits and hypersensitivity to allergens have not been clarified sufficiently. Aim: to evaluate pulmonary function, nutritional status, eating habits and risk factors of obesity in children and adolescents with allergic rhinitis. Material and Methods: The study was performed in 106 children with allergic rhinitis (mean age 12.1+/-3.4; M/F 60/46) from the Department of Allergology. 43 (40.6%) of children presented only allergic rhinitis and in 63 (59.4%) additionally diagnosed with asthma bronchiale. Clinical data, detailed interview about allergies, assessment of pulmonary function and nutritional status, allergy skin test (Allergopharma) and spirometry (Jaeger) were evaluated. Nutritional habits were assessed by a food frequency questionnaire. The statistical analysis was done using the program Statistica v 10.0. Results: In the study group the mean centile of BMI was 49.4; underweight presented 25.4% of children, 55.6 % normal BMI and 18.8 % presented overweight or obesity. Multiple regression analysis showed a significant (adjusted R-squared: 0.97; p<0.05) association between high BMI and snacking between meals and low physical activity. No statistical association between the severity of diseases and BMI or body composition was observed. Conclusions: 1. The prevalence of excess body mass in the study group reached 13.5%. Eating habits were incorrect, especially obese children significantly more frequently ate snacks between meals than children with normal body weight. 2. Among the studied group of children and adolescents with allergic rhinitis and asthma bronchiale, the significant risk factors of obesity were snacking and low physical activity.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

Up to 56% of patients develop chronic postsurgical pain (CPSP) after coronary artery bypass grafting (CABG). CPSP can affect patients’ moods and decrease daily activities. The primary aim of this study was to investigate CPSP severity in patients following off-pump (OP)-CABG using the Neuropathic Pain Symptom Inventory (NPSI). This was a prospective cohort study conducted in a cardiac surgery department of a teaching hospital. Patients undergoing OP-CABG were enrolled in an erector spinae plane block (ESPB) group (n = 27) or a control (CON) group (n = 24). Before the induction of general anesthesia, ESPB was performed on both sides under ultrasound guidance using 0.375% ropivacaine. The secondary outcomes included cumulative oxycodone consumption, acute pain intensity, mechanical ventilation time, hospital length of stay, and postoperative complications. CPSP intensity was lower in the ESPB group than in the CON group 1, 3, and 6 months postsurgery (p < 0.001). Significant between-group differences were also observed in other outcomes, including postoperative pain severity, opioid consumption, mechanical ventilation time, and hospital length of stay in favor of the ESPB group. Preemptive ESPB appears to decrease the risk of CPSP development in patients undergoing OP-CABG. Reduced acute pain severity and shorter mechanical ventilation times and hospital stays should improve patients’ satisfaction and reduce perioperative complications.

Background: Transit-time flow measurement (TTFM) is frequently used to evaluate intraoperative quality control during coronary artery bypass grafting (CABG). Although TTFM has the ability to assess graft failure intraoperatively, the perioperative factors affecting TTFM during CABG surgery remain poorly understood. Methods: Patients who underwent CABG surgery at a single institution between July 2016 and May 2018 were prospectively evaluated. Patients’ demographic characteristics, previous medical history, Euroscore, the results of preoperative blood tests, and intraoperative data were recorded. TTFM and blood viscosity were measured hemodynamically, and mean flow (mL/min) and pulsatility index (PI) were recorded. Arterial blood gas was analyzed immediately after anastomosis of the left internal mammary artery (LIMA) to the left descending artery (LAD) and before sternal closure. Factors associated with TTFM were assessed by multiple linear regression analysis. Results: Of the 62 patients who underwent CABG surgery during the study period, 57 were evaluated, including 49 who underwent off-pump and eight who underwent on-pump surgery. Blood viscosity was not significantly associated with TTFM (p > 0.05). However, TTFM was significantly associated with body mass index (BMI), systolic blood pressure, and cardiac index (p < 0.05 each). Conclusions: Blood viscosity was not significantly associated with intraoperative graft flow. Blood flow of graft vessels, however, was significantly associated with BMI, systolic blood pressure, and cardiac index.

This is a single center retrospective study to assess safety and tolerability of continuous inhaled iloprost use as rescue therapy for refractory pulmonary hypertension (PH) in critically ill neonates and infants. Retrospective chart review was performed on 58 infants and data was collected at baseline, 1, 6, 12, 24, 48, and 72 hours of iloprost initiation. Primary outcomes were change in heart rate (HR), fraction of inspired oxygen (FiO2), mean airway pressures (MAP), blood pressure (BP) and oxygenation index (OI). Secondary outcomes were need for extracorporeal membrane oxygenation (ECMO) and death. 51 patients treated for > 6 hours were analyzed in 2 age groups, neonate (≤28 days: n=32) and infant (29-365 days: n=19). FiO2 (p

Background: Influenza vaccine is a tool for preventing infection and reducing exacerbations in patients with asthma and chronic obstructive pulmonary disease (COPD). Purpose of this study is to investigate dynamics of CRP and serum cytokines (IL-2, IL-6, IL-10, IL-17) in patients with asthma and COPD, as well as to perform a correlation analysis with the clinical parameters of the disease manifestation. Methods: The study included 34 patients with asthma, 20 patients with COPD vaccinated against influenza during a period of remission from 2 to 4 weeks, both groups being under a basic maintenance therapy, and 26 healthy individuals vaccinated with the trivalent polymer-subunit vaccine Grippol® Plus, containing 5 µg of influenza virus strains and 500 µg of azoximer bromide. Results: Observing patients with asthma and COPD, during a year after the vaccination, has revealed a significant reduction in exacerbations frequency (p < 0.05) and duration (p < 0.05) of the bronchial obstructive syndrome (BF). Before the vaccination the IL-6 level in patients with asthma had a direct moderate correlation with duration of exacerbations of the underlying disease (p < 0.05), along with the number of systemic corticosteroids courses during exacerbations (p < 0.05). In 12 months after the vaccination, while assessing cytokine profile of all study groups, a significant reduction in the level of IL-6 was observed, compared to the baseline values (p< 0.05). Conclusion: Conducted analysis of immunological, clinical, and functional parameters of patients with asthma and COPD has proven for influenza vaccine to be effective in BF patients.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in early predicting CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on November 12th, 2023, using the MeSH terms “Children”, “CPB”, “L-FABP”, and “Acute Kidney Injury”. Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p

Obesity is a troubling public health problem worldwide as it increases risks of respiratory complications, systemic arterial hypertension, type 2 diabetes mellitus, sleep disorders, cardiovascular diseases, and metabolic syndrome (MetS). As a measure to counteract comorbidities associated with severe obesity, bariatric surgery stands out. This study aimed to investigate the adiponectin/leptin ratio in women with severe obesity with and without MetS undergone Roux-en-Y Gastric Bypass (RYGB) and to characterize the biochemical, glucose, and inflammatory parameters of blood in women with severe obesity before and after RYGB. Were enrolled female with severe obesity undergoing RYGP with MetS (n=11) and without (n=39). Anthropometric data and blood samples were obtained before and 6 months after RYGB to analyze total cholesterol, low-density lipoprotein (LDL), high- density lipoprotein (HDL), non-HDL total cholesterol, and glucose; and circulating levels of adiponectin and leptin. Significant reductions in weight, body mass index, and glucose, total cholesterol, LDL, and leptin were observed after surgery, with higher levels of HDL, adiponectin, and adiponectin/leptin ratio observed after surgery compared to preoperative values. This study demonstrated that weight loss induced by RYGB in patients with severe obesity with or without MetS improved biochemical and systemic inflammatory parameters, particularly the adiponectin/leptin ratio.

Fungal-bacterial co-colonization and co-infections are emerging among TB-suspected patients, yet the underlying mechanisms that enable and arise from their interactions are poorly understood. Understanding how environmental microbes such as fungi and bacteria co-evolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic co-infections. Our previous work has demonstrated that fungal-bacterial interactions can have dramatic impacts on fungal pathogenesis and drug resistance. Here, we, therefore, hypothesize that cross-kingdom synergistic interactions between environmental fungi and bacteria may influence both fungal and bacterial virulence, antimicrobial resistance patterns and aetiology. Through this, we aimed to establish the prevalence of fungal–bacterial microbial communities associated with chronic primary or opportunistic pulmonary infections. Concordantly, through surveilling 302 clinical samples from 151 patients, we established the prevalence of TB (0.7%) to be lower than that of fungi (1.3%) and non-TB bacterial (4.6%) mono-aetiologies Figure 2. However, our main observation was the unexpected taxonomic diversity with a striking twist of fungal-bacterial di-kingdom aetiological conformities. Interestingly, the majority of the patients presented with at least a di or mono-kingdom aetiological pairings. Importantly, fungi and non-TB bacteria formerly regarded as atypical opportunists are now frequently isolated as possible aetiology for chronic pulmonary infection. Hence, we revealed many di-kingdom aetiological pairings here but their significance remains a question of further examination. Among which Acremonium spp + K. pneumoniae (n=5), Acremonium spp +Streptococcus pneumoniae (n=4), Acremonium spp + C. albicans + K. pneumoniae (n=3) were among the most dominant aetiological pairings observed. Interestingly, Acremonium spp + K. pneumoniae pairings were also seen to be the most commonly associated with pulmonary TB both during and after treatment. Isolation from the same infection niche as seen here calls for further investigations into any interaction signatures that may exist between these organisms. Taken together, our data suggest that fungal-bacterial co-existence may influence their virulence attributes and antimicrobial resistance patterns, with relevance to patient outcomes. Therefore, our data reveals an array of fungal-bacterial pairings that may influence the prognosis of chronic pulmonary disease. Importantly, suggesting that the diversity of pulmonary infective fungi and bacteria, and their complex population structures may pose challenges to the analysis and interpretation of conventional data. Thus, there is a need to redirect our diagnostic approaches to encompass polymicrobial aetiology in order to enhance our suspicion index for better management of opportunistic fungal-bacterial co-infections.