Search Results (5,308)

Aim: Neurological manifestations are common in patients with chronic liver diseases. This study aimed to depict the association between liver cirrhosis and Parkinson’s disease (PD) and propose a clinically relevant diagnostic scheme. Methods: We examined patients’ medical records with PD and chronic liver impairment secondary to cirrhosis or liver metastases for temporal correlations between liver insult and Parkinsonian signs. Results: Thirty-five individuals with PD and chronic liver impairment were included due to either cirrhosis or liver metastases. In all 22 patients with PD and liver metastases, the diagnosis of PD preceded the diagnosis of cancer. Conversely, patients with cirrhosis were often diagnosed with liver impairment before diagnosing PD. Age at diagnosis did not account for this difference. Conclusions: This study reinforces the potential clinical association between cirrhosis and PD. We also provide a diagnostic scheme that may guide therapeutic interventions and prognostic assessments. Full article

Sex chromosome aneuploidies (SCAs) collectively occur in 1 in 500 livebirths, and diagnoses in the neonatal period are increasing with advancements in prenatal and early genetic testing. Inevitably, SCA will be identified on either routine prenatal or newborn screening in the near future. Tetrasomy SCAs are rare, manifesting more significant phenotypes compared to trisomies. Prenatal cell-free DNA (cfDNA) screening has been demonstrated to have relatively poor positive predictive values (PPV) in SCAs, directing genetic counseling discussions towards false-positive likelihood rather than thoroughly addressing all possible outcomes and phenotypes, respectively. The eXtraordinarY Babies study is a natural history study of children prenatally identified with SCAs, and it developed a longitudinal data resource and common data elements with the Newborn Screening Translational Research Network (NBSTRN). A review of cfDNA and diagnostic reports from participants identified a higher than anticipated rate of discordance. The aims of this project are to (1) compare our findings to outcomes from a regional clinical cytogenetic laboratory and (2) describe discordant outcomes from both samples. Twenty-one (10%), and seven (8.3%) cases were found to be discordant between cfDNA (result or indication reported to lab) and diagnosis for the Babies Study and regional laboratory, respectively. Discordant results represented six distinct discordance categories when comparing cfDNA to diagnostic results, with the largest groups being Trisomy cfDNA vs. Tetrasomy diagnosis (66.7% of discordance in eXtraordinarY Babies study) and Mosaicism (57.1% in regional laboratory). Traditional genetic counseling for SCA-related cfDNA results is inadequate given a high degree of discordance that jeopardizes the accuracy of the information discussed and informed decision making following prenatal genetic counseling. Full article

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder potentially linked to gut dysbiosis. This comparative cross-sectional study profiled the gut microbiota in 24 treatment-naïve Thai children diagnosed with ADHD and 24 healthy ones matched by age and gender (median age: 7 years). Fecal microbial compositions were genetically analyzed using 16s rRNA gene amplicon sequencing. The study findings indicated no statistically significant differences in microbial diversity between groups, although Firmicutes and Actinobacteria appeared dominant in both groups. Moreover, ADHD patients exhibited enrichment in Alloprevotella, CAG-352, Succinivibrio, and Acidaminococcus genera, while healthy controls had higher levels of Megamonas, Enterobacter, Eubacterium hallii, and Negativibacillus genera. Spearman correlation analysis demonstrated a significant positive association between CAG-352 and inattention and hyperactivity/impulsivity scores, whereas the Eubacterium hallii group and Megamonas exhibited negative correlations with these symptomatology domains. Beta-carotene intake was associated with the Eubacterium hallii group and Succinivibrio: likewise, vitamin B2 intake was associated with Alloprevotella. Additional research should aim to elucidate the underlying mechanisms influencing clinical biomarkers that signify alterations in specific gut microbiome profiles linked to ADHD. Full article

Thrombotic microangiopathy (TMA) is an anatomopathological lesion mediated by endothelial dysfunction and characterized by the creation of microthrombi in small vessels. In patients with cancer, it may be due to toxicity secondary to chemotherapy, tumor embolization, or hematopoietic progenitor transplantation. Cancer-associated TMA is an underestimated entity that generally appears in the final stages of the disease, although it may also be the initial manifestation of an underlying cancer. Support treatment is necessary in all cases and, depending on the cause, different targeted therapies may be used. The prognosis is very poor. In this article we present a comprehensive review of the existing literature on the physiological mechanisms of cancer-associated TMA. Afterwards, five clinical cases will be presented of patients who developed TMA and were diagnosed in our Department in 2023. We present a discussion of the different causes that triggered the condition, the possible reasons behind the underestimation of this pathology, and the measures that may be adopted. Full article

Background: Duplications on the short arm of chromosome X, including the gene NR0B1, have been associated with gonadal dysgenesis and with male to female sex reversal. Additional clinical manifestations can be observed in the affected patients, depending on the duplicated genomic region. Here we report one of the largest duplications on chromosome X, in a Lebanese patient, and we provide the first comprehensive review of duplications in this genomic region. Case Presentation: A 2-year-old female patient born to non-consanguineous Lebanese parents, with a family history of one miscarriage, is included in this study. The patient presents with sex reversal, dysmorphic features, optic atrophy, epilepsy, psychomotor and neurodevelopmental delay. Single nucleotide variants and copy number variants analysis were carried out on the patient through exome sequencing (ES). This showed an increased coverage of a genomic region of around 23.6 Mb on chromosome Xp22.31-p21.2 (g.7137718-30739112) in the patient, suggestive of a large duplication encompassing more than 60 genes, including the NR0B1 gene involved in sex reversal. A karyotype analysis confirmed sex reversal in the proband presenting with the duplication, and revealed a balanced translocation between the short arms of chromosomes X and 14:46, X, t(X;14) (p11;p11) in her/his mother. Conclusions: This case highlights the added value of CNV analysis from ES data in the genetic diagnosis of patients. It also underscores the challenges encountered in announcing unsolicited incidental findings to the family. Full article

Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy and is a major cause of cancer-related mortality in the world. This study aimed to characterize glutamine amino acid transporter expression profiles in HCC compared to those of normal liver cells. In vitro and in vivo models of HCC were studied using qPCR, whereas the prognostic significance of glutamine transporter expression levels within patient tumors was analyzed through RNAseq. Solute carrier (SLC) 1A5 and SLC38A2 were targeted through siRNA or gamma-p-nitroanilide (GPNA). HCC cells depended on exogenous glutamine for optimal survival and growth. Murine HCC cells showed superior glutamine uptake rate than normal hepatocytes (p < 0.0001). HCC manifested a global reprogramming of glutamine transporters compared to normal liver: SLC38A3 levels decreased, whereas SLC38A1, SLC7A6, and SLC1A5 levels increased. Also, decreased SLC6A14 and SLC38A3 levels or increased SLC38A1, SLC7A6, and SLC1A5 levels predicted worse survival outcomes (all p < 0.05). Knockdown of SLC1A5 and/or SLC38A2 expression in human Huh7 and Hep3B HCC cells, as well as GPNA-mediated inhibition, significantly decreased the uptake of glutamine; combined SLC1A5 and SLC38A2 targeting had the most considerable impact (all p < 0.05). This study revealed glutamine transporter reprogramming as a novel hallmark of HCC and that such expression profiles are clinically significant. Full article

Aims: Pathogenic variants in the CYP21A2 gene are related to the classic and non-classic forms of congenital adrenal hyperplasia (CAH). However, the role of CAH carrier status in the clinical presentation of polycystic ovarian syndrome (PCOS) is still unclear. Moreover, the possible associations of different CYP21A2 gene polymorphisms with metabolic and reproductive abnormalities in PCOS have not been investigated. Therefore, the present study aims to examine the prevalence of the most common CYP21A2 pathogenic variant IVS2-13A/C>G (c.293-13A/C>G) in Eastern European women with PCOS and to evaluate the associations between common intron 2 genetic polymorphisms and the clinical symptoms of the patients. Methods: Sixty consecutively recruited women with PCOS were genotyped for the CYP21A2 intron 2 IVS2-13A/C>G genetic variant. Additionally, CYP21A2 intron 2 polymorphic variants rs6453 (c.293-44G>T), rs6451 (c.293-67C>A/G), rs369651496 (c.293-104del), and rs6474 (c.308G>A/p.R103L) were tested and described. The clinical and hormonal characteristics were compared in women with PCOS and with polymorphic and wild-type genotypes. Results: The heterozygous CYP21A2 pathogenic variant IVS2-13A/C>G was found in one of the investigated PCOS patients (1.67%) with a non-hyperandrogenic type of PCOS. The presence of the rs6453 (c.293-44G>T) T-allele was associated with increased levels of DHEAS (15.18 vs. 9.14 µmol/L, p = 0.003) compared to the wild-type genotype in the investigated group. The rs6451 (c.293-67C>A/G) minor alleles were associated with an earlier age of menarche in the patients (12.0 vs. 13.0 years, p = 0.007). The polymorphic rs369651496 minor 6G allele was related to a better lipid profile in the women with PCOS, while the rs6474 variant modulated the blood pressure of the patients. Conclusions: The presence of CYP21A2 genetic minor alleles of rs6467 (IVS2-13A/C, c.293-13A/C), rs6453 (c.293-44G>T), rs6451 (c.293-67C>A/G), rs369651496 (c.293-104del), and rs6474 (c.308G>A/p.R103L) might modulate the adrenal androgens, age of menarche, and metabolic features in women with PCOS. Further studies on 21-hydroxylase genetic variants (pathogenic and polymorphisms) in different ethnic groups might help reveal the influence of adrenal steroidogenesis on PCOS development, clinical manifestations, and lifelong cardiovascular risks. Full article

We conducted a prospective cohort study at the IRCCS Sacro Cuore Don Calabria Hospital in Negrar di Valpolicella from 2019 to 2021 to investigate the duration of T. whipplei colonization. In addition, the correlation between persistent colonization and the continent of origin, current treatment regimen, clinical manifestations, and parasite coinfection was evaluated. The cohort included subjects who were tested in a previous study (years 2014–2016) and found to be positive for T. whipplei DNA in fecal samples. Thirty-three subjects were enrolled in a prospective study between 2019 and 2021. Feces, saliva, urine, and blood were collected at baseline and after 12 months. Medical history, current treatment, and symptoms were recorded. Among them, 25% showed persistent intestinal or oral colonization, 50% had no colonization at both visits, and 25% had intermittent colonization. No association was found between persistent T. whipplei colonization and subjects’ continent of origin, current treatment regimen, initial clinical manifestations, and parasite coinfection. The longest duration of persistent T. whipplei intestinal colonization exceeded six years, with 11 subjects presenting persistent positivity for more than three years, including 1 minor. Our research was limited by the lack of a strain-specific identification of T. whipplei that made it impossible to distinguish between persistence of the same T. whipplei strain, reinfection from household exposure, or infection by a new strain. Larger prospective studies are needed to further explore the implications of this persistence and determine the key factors influencing the duration of colonization and its potential health impacts. Full article

Objective: To clarify the therapy response in orbital inflammatory diseases (OID), we analyzed the treatment effects of steroid therapy, the use of disease-modifying antirheumatic drugs (DMARDS), and biologicals in our tertiary referral center cohort. Methods: We collected the clinical and demographic data of all patients treated for non-specific orbital inflammation (NSOI) (n = 111) and IgG4-ROD (n = 13), respectively at our center from 2008 to 2020 and analyzed them with descriptive statistics. NSOI were sub-grouped according to the location into either idiopathic dacryoadenitis (DAs) (n = 78) or typical idiopathic orbital myositis (n = 32). Results: Mean age at first clinical manifestation was significantly different between subgroups (IOI: 49.5 ± 18, IgG4-ROD: 63.2 ± 14, p = 0.0171). Among all examined OID, 63 patients (50%) achieved full remission (FR) with corticosteroids (NSOI 53%/IgG4-ROD 31%). In contrast, classic myositis showed a significantly higher response (76%). Disease-modifying drugs (DMARDS) for myositis accomplished only 33% FR (NSOI 57%) and 66% did not respond sufficiently (NSOI 43%). The biologic agent (Rituximab) was significantly more efficient: 19 of 23 patients (82%) achieved full remission and only 4 (17%) did not respond fully and needed orbital irradiation or orbital decompressive surgery. Full article

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a), and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses the diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk. Full article

Endometriosis and adenomyosis are complex gynecological conditions characterized by diverse clinical presentations, including superficial peritoneal endometriosis (SPE), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). The hallmark features of these pathologies involve the manifestation of pain symptoms and infertility, and approximately 30% of patients are asymptomatic. Despite ongoing research, definitive treatments for these conditions remain elusive, and clinical management primarily revolves around medical or surgical interventions. Recent advancements in our understanding of the efficacy of various treatment modalities, including medical therapy and surgical interventions, have provided clinicians with valuable insights into pain relief and fertility preservation. This review aims to provide an updated overview of the latest literature on clinical outcomes, treatment options, and management strategies for different types of endometriosis. By synthesizing the newest available data, this review seeks to inform clinicians and guide decision making based on factors such as patients’ symptom severity, childbearing desire, and overall health. Full article

Rheumatoid arthritis (RA) is a chronic, autoimmune rheumatic disease characterized by synovial joint inflammation with subsequent destruction as well as systemic manifestation, leading to impaired mobility and impaired quality of life. The etiopathogenesis of RA is still unknown, with genetic, epigenetic and environmental factors (incl. tobacco smoking) contributing to disease susceptibility. The link between genetic factors like “shared epitope alleles” and the development of RA is well known. However, why only some carriers have a break in self-tolerance and develop autoimmunity still needs to be clarified. The presence of autoantibodies in patients’ serum months to years prior to the onset of clinical manifestations of RA has moved the focus to possible epigenetic factors, including environmental triggers that could contribute to the initiation and perpetuation of the inflammatory reaction in RA. Over the past several years, the role of microorganisms at mucosal sites (i.e., microbiome) has emerged as an essential mediator of inflammation in RA. An increasing number of studies have revealed the microbial role in the immunopathogenesis of autoimmune rheumatic diseases. Interaction between the host immune system and microbiota initiates loss of immunological tolerance and autoimmunity. The alteration in microbiome composition, the so-called dysbiosis, is associated with an increasing number of diseases. Immune dysfunction caused by dysbiosis triggers and sustains chronic inflammation. This review aims to provide a critical summary of the literature findings related to the hypothesis of a reciprocal relation between the microbiome and the immune system. Available data from studies reveal the pivotal role of the microbiome in RA pathogenesis. Full article

This study aims to analyze the changes in dermal thickness in patients with systemic scleroderma (SSc) in comparison with normal skin and also compare clinical forms with diffuse and limited cutaneous involvement. The study group consisted of female patients diagnosed with SSc with a disease history not exceeding 5 years. The areas of interest for ultrasound examination included the proximal phalanx of the third finger, the second intermetacarpal space, and the extension surface of the lower third of the forearm. The study included 20 patients diagnosed with SSc and 14 controls. SSc patients were subdivided into two subgroups based on the clinical form. Compared to the control group, patients with SSc had higher mean measurements in all three skin areas, with statistically significant differences in the hand and forearm areas. Patients with diffuse SSc displayed, on average, higher skin thickness compared to limited SSc in all skin areas examined, with a statistically significant difference only in the forearm area. Based on disease manifestations, significant differences were observed only with regard to the presence of pulmonary hypertension in the diffuse SSc group. In conclusion, skin ultrasound is a useful and accessible imaging method for diagnosing and quantifying dermal fibrosis in systemic scleroderma. Full article

Immunocompromised patients with hematologic diseases may experience life-threatening infections with rather uncommon manifestations. Laryngitis has been described as a potential infection in such vulnerable patients and may result in major complications, ranging from impending airway obstruction to total laryngeal necrosis. Immediate laryngoscopy is of paramount importance, as it provides quantification of laryngeal edema and evidence of necrosis. Documentation of the causative pathogen is usually feasible through tissue culture. In the literature, 14 cases of necrotizing laryngitis have already been published. Here, we present the case of a 38-year-old male with a recent diagnosis of multiple myeloma, who received the first cycle of therapy a few days before admission. The patient presented with neutropenic fever, diarrhea, and multiple organ dysfunction. His course was complicated with hemophagocytic lymphohistiocytosis and stridor. A diagnosis of necrotizing laryngitis attributed to Acinetobacter baumannii invasion of the larynx was established. This manuscript highlights that the management of patients with hematologic disease and necrotizing laryngitis should be coordinated in highly specialized centers and clinicians should have a high level of clinical suspicion and act promptly. Full article

Sarcoidosis and Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) are two rare entities primarily characterised by the development of Interstitial Lung Disease (ILD) in the context of systemic immune dysregulation. These two conditions partially share the immunological background and pathologic findings, with granuloma as the main common feature. In this narrative review, we performed a careful comparison between sarcoidosis and GLILD, with an overview of their main similarities and differences, starting from a clinical perspective and ending with a deeper look at the immunopathogenesis and possible target therapies. Sarcoidosis occurs in immunocompetent individuals, whereas GLILD occurs in patients affected by common variable immunodeficiency (CVID). Moreover, peculiar extrapulmonary manifestations and radiological and histological features may help distinguish the two diseases. Despite that, common pathogenetic pathways have been suggested and both these disorders can cause progressive impairment of lung function and variable systemic granulomatous and non-granulomatous complications, leading to significant morbidity, reduced quality of life, and survival. Due to the rarity of these conditions and the extreme clinical variability, there are still many open questions concerning their pathogenesis, natural history, and optimal management. However, if studied in parallel, these two entities might benefit from each other, leading to a better understanding of their pathogenesis and to more tailored treatment approaches. Full article