Pediatric myocarditis is an inflammatory disease of the heart with heterogeneous clinical presentations and poorly understood immune mechanisms. T cell receptor (TCR) repertoire profiling provides insights into disease-associated adaptive immune responses.

We performed high-throughput sequencing of TCR β chain CDR3 repertoires from 28 peripheral blood samples of pediatric myocarditis patients (Myo) and nine age-matched healthy controls (NC). Clonal diversity, V and J gene usage, CDR3 length distribution, clonotype sharing, and antigen-specific annotations were systematically analyzed.

The Myo group exhibited significantly reduced clonal diversity as measured by D50 and Chao1 indices, accompanied by expansion of large clones and reduced representation of small clones. Distinct biases in V and J gene usage were observed, with increased TRBV14, TRBV28, TRBJ1-1, TRBJ1-2, TRBJ1-5, TRBJ1-6, and TRBJ2-2, and decreased TRBV9, TRBJ2-4, TRBJ2-5, and TRBJ2-7. CDR3 length distribution showed an enrichment of longer sequences in myocarditis patients, alongside altered nucleotide insertions/deletions and amino acid usage. Clonotype sharing was markedly higher in the Myo group, and 16,460 public clonotypes were detected in ≥10 patients. Database annotation revealed an enrichment of matches to pathogen-associated TCR records, predominantly associated to Mycobacterium tuberculosis, influenza, cytomegalovirus, and Epstein-Barr virus. Seventeen high-frequency clonotypes were highlighted as candidate myocarditis-related TCR signatures based on database matches.

Our study demonstrates distinct repertoire remodeling in pediatric myocarditis, characterized by reduced diversity, skewed V/J gene usage, biased CDR3 composition, and enriched public clonotypes. These findings provide novel insights into disease-related adaptive immune responses and may inform biomarker discovery for diagnosis and therapeutic strategies.

Post-transplant anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) recurrence on the allograft is rare and, to our knowledge, has never been described in the situation of a previous double-positive vasculitis with both ANCA and anti-glomerular basement membrane (GBM) antibodies. We report an unusual case of anti-myeloperoxydase (MPO) antibody-associated vasculitis recurrence occurring 14 years after kidney transplantation following a double-positive anti-GBM and anti-MPO glomerulonephritis. The transplant induction regimen consisted of anti-thymocyte globulin, and initial maintenance therapy associated tacrolimus, mycophenolate mofetil, and corticosteroids. Mycophenolate mofetil was discontinued 4 months after transplantation due to persistent leukopenia, and tacrolimus was maintained along with corticosteroids. At 14 years post-transplantation, the patient presented with diffuse alveolar hemorrhage, acute kidney injury stage 1 of Kidney Disease Improving Global Outcomes, proteinuria, microhematuria, serous otitis media and anti-MPO antibodies resurgence, without detectable anti-GBM antibodies. A kidney allograft biopsy was performed and showed rare active crescents with severe chronic injuries. This pulmonary and renal involvement was attributed to an anti-MPO antibody-associated vasculitis recurrence. The induction treatment of the relapse consisted of methylprednisolone at 5 mg/kg and rituximab at 375 mg/m² per week for 4 weeks. Renal function remained stable, urinary protein to creatinine ratio decreased from 0.9 g/g to 0.3 and 0.2 g/g at 6 and 12 months, respectively. Microhematuria resolved at 6 months and remained absent subsequently. Maintenance treatment was continued with rituximab every 6 months. According to the literature, post-transplant isolated AAV recurrence on the allograft remains exceptional, ranging between 0.003 and 0.076 per patient per year. To our knowledge, there are no reported cases of post-transplant anti-MPO-associated vasculitis recurrence in a patient with former anti-MPO and anti-GBM antibody-associated vasculitis. This case underlines the fact that AAV can recur late after transplantation in previously double-positive vasculitis patients. Thus, close monitoring of clinical and biological signs of recurrence is necessary in these patients. Because the pathophysiology of this atypical entity remains unclear, further trials are still necessary to highlight the underlying mechanisms of this particular auto-immune association and, more specifically, of isolated post-transplant AAV recurrence in double-positive patients to improve prevention and to elaborate more efficient immunosuppressive strategies.

Acute and chronic inflammation are known to contribute to the pathogenesis of various diseases, including cardiovascular disorders, Parkinson's, Alzheimer's, diabetes, and cancer. Classical nonsteroidal anti-inflammatory drugs reduce inflammation primarily by suppressing the cyclooxygenase (COX) pathway. COX enzymes facilitate the conversion of membrane phospholipids into prostaglandins and play functional roles in several metabolic processes, including analgesia, anti-inflammation, apoptosis, angiogenesis, and drug resistance. Moreover, they are also implicated in cancer development, invasion, metastasis, and the differentiation. In this study, eight pyrazolone derivative compounds with potential anti-inflammatory properties were synthesized. Their structures were successfully characterized using ¹H nuclear magnetic resonance (NMR), ¹³C NMR, infrared spectroscopy (IR), and high-resolution mass spectrometry (HRMS) spectroscopy. Their inhibitory activities againt COX-1, COX-2, and 5-lipoxygenase were evaluated to determine their anti-inflammatory potential. Epidermal growth factor receptor inhibition assays were performed for the active compounds 7 and 8, while compound 7, the most potent molecule, was further assessed for p38 mitogen-activated protein kinase inhibition. Several compounds exhibited selective cytotoxicity toward cancer cell lines. Notably, compounds 7 and 8 showed no inhibitory activity against COX-1 yet demonstrated considerable selectivity toward COX-2. Interestingly, some derivatives displaying selective cytotoxic effects were not among the most potent COX-2 inhibitors. Overall, the findings indicate that the synthesized pyrazolone derivatives represent promising lead candidates for the development of anti-inflammatory and anticancer agents.

Intracerebral hemorrhage (ICH), a life‑threatening subtype of stroke accounting for 10‑15% of global stroke cases, is characterized by high disability and mortality rates, imposing a heavy socioeconomic burden worldwide. Despite its clinical importance, no effective therapeutic interventions exist for this condition. As the resident immune cells of the central nervous system, microglia play a pivotal role in the pathophysiology of ICH. These cells can be activated to adopt either anti‑inflammatory or pro‑inflammatory phenotypes. Following ICH, pro‑inflammatory mediators derived from microglia act as key drivers of neuroinflammation, thereby exacerbating secondary brain injury. By contrast, promoting the phenotypic shift of microglia toward an anti‑inflammatory state has been shown to mitigate an inflammatory response and facilitate neurological recovery. In the present study, existing evidence was reviewed to propose that post‑ICH brain injury and repair are orchestrated not by isolated cells, but by a highly dynamic neuroimmune network centered on microglia. Elucidating the spatiotemporal dynamics and key communicative nodes within this network represents a critical frontier. Moving beyond the classical M1/M2 dichotomy to target this network contextually offers a promising and precise therapeutic aim for future investigations.

This study aimed to investigate the prevalence of dysphagia in cardiac patients admitted to intensive rehabilitation following cardiac surgery or interventional procedures and to identify associated clinical and demographic risk factors.

A retrospective observational study was conducted on 93 patients consecutively admitted to a cardiac intensive rehabilitation unit between March and April 2023. Swallowing function was assessed using the Gugging Swallowing Screen (GUSS), Mealtime Assessment Scale (MAS), and the Italian Dysphagia Handicap Index (I-DHI). The impact of these scales on the American Speech-Language-Hearing Association National Outcome Measurement System (ASHA-NOMS) scale was assessed. Logistic regression identified predictors of dysphagia.

Dysphagia (ASHA-NOMS ≤6) was identified in 33.3% of patients. Dysphagic patients were older (median 73 vs. 67.5 years, p = 0.001) and had a higher prevalence of prior intubation (93.6% vs. 75.8%, p = 0.037). Intubation (OR = 6.33, p = 0.033) and age (OR = 1.08, p = 0.012) were independent predictors of dysphagia. The MAS safety subscale showed the highest correlation with dysphagia severity (r=-0.93).

Dysphagia is common in patients with cardiovascular disease admitted to the intensive cardiac rehabilitation, regardless of surgical history. Early identification of dysphagia and timely intervention within a multidisciplinary rehabilitation framework are essential to prevent complications and optimize functional recovery in cardiac patients.

More than one million women in Russia enter menopause each year. The severe estrogen deficiency associated with this transition causes symptoms that significantly impair quality of life and contribute to an increased risk of cardiovascular and metabolic diseases. Menopausal hormone therapy (MHT) is the established standard of care for menopausal symptoms. On the initiative of several professional societies (the Russian Society of Obstetricians and Gynecologists, the Russian Society of Cardiology, the Russian Association of Endocrinologists, the Eurasian Association of Therapists, the Russian Society of Gynecological Endocrinology and Menopause, the Russian Association of Gerontologists and Geriatricians, the Association of Phlebologists of Russia), a Delphi panel was convened to develop a multidisciplinary expert consensus on MHT for patients with cardiovascular and metabolic diseases. The goal was to enhance research and clinical approaches to managing menopausal women. A consensus was reached at the end of the first Delphi round. The experts agreed that initiating MHT requires a thorough assessment of individual risks, including cardiovascular health and comorbidities. MHT can offset metabolic and cardiovascular risk factors in peri- and postmenopausal women by normalizing the lipid profile, improving carbohydrate metabolism, and reducing insulin resistance. An interdisciplinary approach allows for personalized MHT, minimizes potential complications, improves the quality of life for peri- and postmenopausal women, and promotes active longevity.

Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-producing neuroendocrine tumors with significant systemic effects. While catecholamine-related cardiovascular manifestations are well-characterized as a prominent component of the clinical presentation, other systemic effects, particularly those on bone and mineral metabolism, remain much less characterized. Bone physiology and health in patients with PPGLs can be affected through catecholamine-mediated changes, skeletal metastases, or specific skeletal abnormalities associated with syndromic PPGL forms. The catecholamine effect on bone density was first noticed in experimental murine models, where β-adrenoceptor signaling was shown to increase bone resorption. These findings were further supported by epidemiological and translational studies indicating a protective role of β-adrenoceptor blockers in maintaining bone density. Both preclinical and clinical studies draw attention to the potential alterations of bone physiology in patients with PPGLs. To date, a few retrospective studies have evaluated bone turnover markers and bone mineral density (BMD) in these patients, consistently showing lower BMD and trabecular bone score, as well as elevated serum C-terminal telopeptides levels, compared to healthy controls with partial reversibility following surgical resection of the tumor. In this review, we summarize the available mechanistic and clinical literature on bone health in PPGLs, to raise awareness among clinicians, identify opportunities for primary prevention, and ensure a better quality of life.

Secondhand smoke (SHS) remains a major global health concern, exposing individuals to toxic compounds that significantly increase the risk of cardiovascular diseases, metabolic disorders, and respiratory illnesses. This study aims to assess the global burden of disease attributable to SHS by analyzing Disability-Adjusted Life Years (DALYs) across Socio-Demographic Index (SDI) regions. This study utilized secondary data from the Global Burden of Disease (GBD 2021) database, analyzing epidemiological metrics across 204 countries. The SDI was applied to assess disparities, and SHS exposure was defined based on household and workplace factors. Statistical analyses estimated the burden of SHS-associated diseases, stratified by demographic and socioeconomic categories, with results mapped globally using ArcGIS. Globally, ischemic heart disease posed a greater burden on males (131.31 DALY) compared to females (96.42 DALY), while diabetes mellitus and stroke affected females more (46.99 and 84.05 DALY, respectively). COPD exhibited the highest DALY rates in low-middle SDI regions (males: 129.85; females: 124.42), whereas high-income regions had the lowest burden. Diabetes mellitus showed a rising trend across SDI regions, with females in middle and high-middle SDI regions experiencing the highest YLDs. The analysis reveals significant disparities in disease burden from secondhand smoke exposure across regions and sexes. The findings highlight the sex-specific and regional variations in disease burden, underscoring the need for targeted health interventions and tobacco control strategies.

An expert commission (The Lancet Diabetes & Endocrinology Commission on Clinical Obesity) proposed novel diagnostic criteria distinguishing between preclinical and clinical obesity and suggesting treatment indications for the latter. However, the proportional assignment to preclinical and clinical obesity in adults with BMI-defined obesity, the associated disease risks, as well as the response to lifestyle interventions are not well known. Here we show that among those with BMI-based obesity, 100% are confirmed to have obesity by at least one other anthropometric measure in NHANES 2017-2018 and the prospective EPIC-Potsdam cohort. More than 80% of adults with confirmed obesity meet the criteria for clinical obesity and have 2.8-fold increased risk of incident cardiovascular disease and 7.9-fold increased risk for type 2 diabetes compared to adults without obesity and not fulfilling clinical criteria. Adults with preclinical obesity have no elevated cardiovascular disease risk, but type 2 diabetes risk is markedly increased. A 9-months lifestyle intervention (Tübingen Lifestyle Intervention Programme) decreases the proportion of clinical obesity from 71% to 57%, and that of prediabetes from 52% to 29%.

Psychiatric comorbidities are increasingly prevalent among patients undergoing total hip arthroplasty (THA), yet their impact on clinically meaningful outcomes remains underexplored. This study evaluates the association between preoperative psychiatric diagnoses and patient-reported outcomes (PROMs), satisfaction, and healthcare utilization following THA.

A retrospective cohort of 11,766 patients undergoing primary elective unilateral THA between 2016 and 2022 across a multisite academic center was analyzed. Psychiatric diagnoses were identified via ICD-9/10 codes within 2 years preoperatively. PROMs were collected at baseline and 1 year postoperatively, including HOOS Pain, HOOS Physical Function Shortform (PS), HOOS Joint Replacement (JR), and VR-12 Mental Component Score (MCS). Outcomes included failure to achieve minimal clinically important difference (MCID), failure to reach patient acceptable symptom state (PASS), dissatisfaction, non-home discharge, prolonged length of stay (LOS ≥ 2 days), and 90-day readmission. Multivariable logistic regression adjusted for demographic and clinical covariates.

Psychiatric diagnoses were present in 26.1% of patients. Psychiatric illness was associated with failure to achieve MCID in HOOS Pain (OR 1.43), HOOS PS (OR 1.31), and HOOS JR (OR 1.54), as well as failure to reach PASS thresholds (all p < 0.001). Patients with psychiatric diagnoses had increased odds of dissatisfaction (OR 1.34), non-home discharge (OR 1.36), prolonged LOS (OR 1.24), and readmission (OR 1.54). Subgroup analysis demonstrated a dose-dependent relationship, with multiple psychiatric diagnoses conferring the highest risk of poor outcomes.

Preoperative psychiatric illness is an independent predictor of suboptimal functional outcomes, lower satisfaction, and increased healthcare utilization after THA. These findings highlight the need for psychiatric screening and optimization during the preoperative period to improve outcomes in this high-risk population.