Mechanical valve replacement is a primary treatment for rheumatic heart disease, yet prosthesis-related adverse outcomes remain underreported in India. This study aimed to examine the in-hospital mortality rate among patients who underwent prosthetic heart valve replacement surgeries in the past five years.

A retrospective analysis of 221 rheumatic heart disease patients (2019–2023) who underwent aortic valve replacement (AVR), mitral valve replacement (MVR), or double valve replacement (DVR) was conducted. Comorbidities (hypertension, type-2 diabetes mellitus) and valve origin (Indian vs. foreign-made) were also evaluated. Data were analyzed using SPSS (v25.0), with p < 0.05 considered statistically significant.

Among 221 patients, 262 valves were implanted (54 AVR, 126 MVR, 41 DVR). Overall in-hospital mortality was 7.24% (16/221), with rates of 5.55% (AVR), 7.14% (MVR), and 9.75% (DVR). No sex-based differences were observed (p > 0.05). The five-year actuarial survival rate was 92.8±4.8%, with no intergroup disparities (p > 0.05). Mortality was higher in patients >50 years (13/16 deaths) and in females (10/16 deaths), though these differences were not statistically significant. Hypertension was more prevalent in females and type-2 diabetes mellitus in males, but neither condition showed a significant association with outcomes (p > 0.05). Most fatalities were associated with thromboembolism, acute kidney injury, and congestive heart failure, and valve origin did not significantly impact mortality.

Over the past five years, we observed a 7.24% mortality rate at our tertiary care facility following prosthetic heart valve implantation across all age groups. The data suggest that mortality may be more common among females and older individuals; however, these differences did not reach statistical significance.

Metabolic dysfunction-associated steatohepatitis (MASH) represents a critical step in the progression from simple fatty liver disease to more severe conditions such as cirrhosis and hepatocellular carcinoma, and it remains difficult to treat. Arctigenin (ATG), a monomer of Fructus Arctii, exhibits anti-inflammatory activity. Therefore, we aimed to examine its potential protective role against MASH and explore the underlying mechanisms.

Male C57BL/6 mice were divided into four groups: control, MASH, low-dose ATG (30 mg/kg/day), and high-dose ATG (120 mg/kg/day). MASH was induced through a choline-deficient, L-amino acid-defined high-fat diet for eight weeks, with concurrent preventive ATG administration. Liver injury, lipid metabolism, inflammation, oxidative stress, and fibrosis were assessed. Network pharmacology was employed to identify the potential protective mechanisms of ATG. Key factors were evaluated in vitro to verify the ATG targets.

ATG administration prevented the progression of MASH in a dose-dependent manner. High-dose ATG significantly reduced hepatic macrophage and neutrophil infiltration, serum enzyme levels, and lipid peroxidation, while enhancing antioxidant enzyme activity. Mechanistic network pharmacology identified modulation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome as the central pathway underlying ATG’s bioactivity. Functional analyses in lipopolysaccharide-stimulated RAW264.7 cells confirmed that ATG inhibited NLRP3 expression, pyroptosis-related protein cleavage (hereinafter referred to as GSDMD-N), and pro-inflammatory chemokine production in a concentration-dependent manner. Notably, ATG disrupted NLRP3/GSDMD-N axis activity in macrophages without causing cellular toxicity.

ATG may inhibit the inflammatory cascade primarily by targeting macrophage NLRP3 inflammasomes, thereby preventing the progression of MASH.

Primary biliary cholangitis (PBC) is a chronic progressive autoimmune disorder characterized by small non-purulent intrahepatic bile duct destruction (ductopenia) and cholestasis. While the etiology of PBC remains unclear, it is believed to involve genetic-environmental interactions. Emerging evidence highlights gut microbiota dysbiosis in PBC patients, with increased symbiotic bacteria and decreased pathogenic bacteria. Microbial alterations potentially influence disease pathogenesis through multiple mechanisms, including immune dysregulation, intestinal barrier damage, BA metabolic dysregulation, and cholestasis. These findings suggest that the gut microbiota can serve not only as a non-invasive biomarker for diagnosis and prognosis evaluation but also as a therapeutic target for the disease. In this review, we summarize changes in PBC patients’ gut microbiota, explain how these changes affect disease occurrence and development, and discuss treatment methods with potential clinical value that intervene in gut microbiota.

Regular exercise is fundamental for people with metabolic dysfunction-associated steatotic liver disease (MASLD), yet exercise maintenance is generally poor. This generative co-design process aimed to embed the voices and opinions of people with lived experience of MASLD and their care stakeholders to (i) frame barriers and enablers to exercise maintenance and (ii) highlight priorities for exercise-focused research agendas in MASLD.

A generative co-design framework was applied. Two virtual co-design sessions were undertaken: Session 1 – Framing the issue, where initial discovery was conducted with people with lived experience of MASLD; and Session 2 – Generative design and sharing ideas with lived experience partners and healthcare stakeholders. Sessions were audio-recorded and transcribed, and key determinants and considerations were discerned by two independent researchers.

Lived experience partners (n = 5, 53 ± 16 years, 40% male) ranked five equally important barriers to exercise maintenance: musculoskeletal and pain issues, lack of access to exercise equipment/facilities, cost, competing priorities, and low energy levels, which influenced core positive and negative determinants. Alongside lived experience partners, healthcare stakeholders (hepatologists [n = 3], exercise professionals [n = 3], 67% male) identified three core needs with eight considerations. Some disconnects in priorities were observed. Lived experience partners emphasized affordability, accessibility, and considerations for comorbidities, while healthcare partners advocated for research on natural history, prevention, behavior change, cost-effectiveness, and health system change.

This co-design methodology highlights unique consumer-informed research questions. Exercise interventions and their associated implementation trials will benefit from being co-designed with both people with MASLD and care stakeholders.

High-grade serous carcinoma is a rare diagnosis in cervical biopsies. Cervical serous carcinoma is no longer recognized as a primary cervical tumor in the 2020 World Health Organization classification. This study aimed to characterize the clinicopathologic, immunohistochemical, and molecular features of high-grade serous carcinoma identified in cervical or endocervical biopsies, to assess tumor origin and ensure accurate classification.

Fifty-nine cases originally diagnosed as “serous carcinoma” or “high-grade serous carcinoma” in cervical or endocervical biopsies from 2013 to 2023 were retrospectively reviewed. Clinical data, radiologic findings, and follow-up information were analyzed. Histologic features and immunohistochemical profiles were re-evaluated. Targeted next-generation sequencing was performed on a subset of cases.

The majority of tumors (96%) were determined to originate from the endometrium (n = 47) or the tubo-ovarian region (n = 4), with only one case confirmed as a primary cervical carcinoma. Morphologic patterns varied and could mimic human papillomavirus-associated adenocarcinoma. All tumors showed aberrant p53 expression and diffuse p16 positivity. WT-1 was expressed in all tubo-ovarian tumors but in only 12% of endometrial cases. Estrogen receptor and progesterone receptor were frequently positive in endometrial tumors; human epidermal growth factor receptor 2 was positive in 31% of cases. Molecular analysis confirmed tumor protein p53 mutations and other alterations typical of uterine serous carcinoma.

High-grade serous carcinoma identified in cervical biopsies is overwhelmingly secondary to upper genital tract tumors, most commonly of endometrial origin. A small subset of endocervical adenocarcinomas may mimic serous carcinoma. These findings support the exclusion of primary cervical serous carcinoma from the current World Health Organization classification and emphasize the importance of accurate diagnosis for appropriate management.

Khat (Catha edulis) is a plant native to East Africa and the Arabian Peninsula, chewed for its stimulant effects by millions worldwide. Its sympathomimetic properties, primarily due to cathinone and other pyrrolizidine alkaloids, resemble those of amphetamine. Emerging reports have linked khat use to the development of autoimmune hepatitis, supported by elevated autoimmune markers, characteristic liver biopsy findings, and clinical resolution following khat cessation or a prompt response to corticosteroid therapy without recurrence. In this review, we aimed to update knowledge on both acute and chronic forms of khat-associated AIH. We discuss cathinone metabolism, pharmacokinetics, and proposed mechanisms of khat hepatotoxicity. We also provide an updated synthesis of published cases of khat-associated autoimmune hepatitis, including our calculated Roussel-Uclaf Causality Assessment Method analysis and the simplified Hennes AIH score where data were available. Case presentations, diagnostic criteria, histopathological findings, and treatment approaches are summarized to help guide management.