To evaluate menstrual recovery, reproductive outcomes, and survival following fertility-sparing surgery and platinum-based chemotherapy in women with malignant ovarian germ cell tumors (MOGCTs).

We retrospectively reviewed women aged 15-40 years with MOGCT treated at a university hospital (2001-2012). All underwent fertility-sparing surgery and platinum-based chemotherapy. Menstrual and reproductive outcomes were assessed through structured interviews and compared with age-matched controls. Survival outcomes were analyzed by Kaplan-Meier method.

Among 1934 ovarian cancer cases, 209 (10.8%) were MOGCT; 44 patients met inclusion criteria and were matched to 44 controls. Median age was 21 years; dysgerminoma was the most common histology (40.9%), and 70.4% had Stage I disease. All received bleomycin, etoposide, and cisplatin (median 4 cycles). After a median follow-up of 55 months, 97.7% resumed menstruation. Compared with baseline and controls, cycles were shorter (4 vs. 5 days, p = 0.026), lighter (2 vs. 3 pads/day, p = 0.004-0.047), and longer in interval (29.2 vs. 26.4 days, p < 0.001). Of 17 patients attempting conception, 9 achieved 10 pregnancies, with a pregnancy rate of 52.9% and live-birth rate of 90.9%, without congenital anomalies. Only one recurrence occurred, with 10-year progression-free and overall survival of 95.3% and 97.9%, respectively.

Fertility-sparing surgery followed by platinum-based chemotherapy was associated with excellent long-term survival, high rates of menstrual recovery, and favorable reproductive outcomes in young women with MOGCT. These findings support current international recommendations for fertility-preserving treatment in selected patients and provide long-term evidence from a Southeast Asian cohort.

Leptomeningeal metastasis (LM) is a rare complication of cervical cancer associated with a poor prognosis. We report a 61-year-old woman with stage IVB cervical squamous cell carcinoma who developed acute headache and diplopia during systemic chemotherapy. Brain magnetic resonance imaging suggested LM, which was confirmed by cerebrospinal fluid (CSF) cytology. An Ommaya reservoir was inserted, and intrathecal methotrexate therapy was initiated. The patient showed rapid neurological improvement, normalization of CSF opening pressure, and sustained clearance of malignant cells on serial CSF cytology. Although systemic disease subsequently progressed, LM-related neurological symptoms remained well controlled. The patient survived for 8 months after LM diagnosis. This case highlights the importance of considering LM in cervical cancer patients with new neurological symptoms and suggests that intrathecal chemotherapy via an Ommaya reservoir may provide effective neurological control and symptomatic relief.

Diabetic foot ulcers (DFUs) can lead to amputation, especially when complicated by osteomyelitis (OM) or soft tissue infection. Although MRI is the standard imaging method, ultrasonography (US) is increasingly used because it is more accessible. This study compared the diagnostic performance of US and MRI in DFU-related infections.

In this descriptive cross-sectional study, consecutive adults with diabetes and suspected diabetic foot infection underwent both US and MRI. One ulcer per patient wasanalysed. US was compared with expert clinical assessment for cellulitis and with MRI for abscess and OM, following IWGDF recommendations. Diagnostic measures were calculated overall and by ulcer severity.

Among 127 patients, most had advanced Wagner grades (3-5) and forefoot ulcers. Cellulitis was clinically present in all cases; MRI and US concordance with the clinical diagnosis was 100.0% and 99.2%, respectively. For abscesses, US showed 100% sensitivity but low specificity, resulting in moderate accuracy. For OM, US had very poor sensitivity (17.9%) despite high specificity, especially in severe ulcers. MRI detected no OM in moderate-grade ulcers.

US showed near-complete concordance with MRI for cellulitis, though this was assessed in a study in which cellulitis was universally present, and US performs poorly for OM and cannot reliably exclude bone infection. It is best used as an initial triage tool, while MRI remains essential when OM is suspected. Because MRI is not a perfect reference standard, the findings reflect diagnostic concordance rather than absolute accuracy and support a tiered imaging approach.

Interleukin (IL)-12 and IL-35 are heterodimeric cytokines that share the p35 subunit and have opposing inflammatory roles. Dysregulated IL-12/IL-35 p35 may reflect an imbalance between pro- and anti-inflammatory pathways linking metabolic dysfunction to cardiovascular risk in type 2 diabetes (T2D). However, the clinical significance of circulating IL-12/IL-35 p35 levels remains unclear. This study investigated the association between IL-12/IL-35 p35 levels and metabolic and atherogenic risk markers in T2D.

This cross-sectional study stratified 80 patients with T2D into Low and High IL-12/IL-35 p35 groups (n = 40/group) using a median split of plasma IL-12/IL-35 p35 (18.48 pg/mL). Laboratory parameters were measured using standard methods, and IL-12/IL-35 p35 concentrations were quantified by Enzyme Linked Immunosorbent Assay.

Patients with High IL-12/IL-35 p35 had significantly elevated fasting glucose (p = 0.0318), triglycerides (p < 0.0001), triglyceride/HDL ratio (p < 0.0001), Triglyceride-Glucose (TyG) (p < 0.0001), and atherogenic index of plasma (AIP) (p < 0.0001). Circulating IL-12/IL-35 p35 levels positively correlated with triglycerides, AIP, Trig/HDL ratio and TyG index (all p < 0.0001), and negatively correlated with HDL (p = 0.0466). In the multiple linear regression analysis, IL-12/IL-35 p35 levels and TyG index (all p < 0.05) independently predicted atherogenicity after adjusting for glycaemic control. Receiver operating characteristic analysis demonstrated that IL-12/IL-35 p35 discriminated participants with high-risk AIP (AUC = 0.79, 95% CI: 0.68-0.89, p < 0.0001) and elevated TyG index (AUC = 0.78, 95% CI: 0.63-0.93, p = 0.0147).

Elevated circulating IL-12/IL-35 p35 in T2D is associated with suboptimal glucose control and pronounced atherogenicity, suggesting altered activity within this immunoregulatory axis. These findings highlight the shared p35 subunit as a marker of immune imbalance and support its potential utility in identifying heightened atherogenic risk in T2D beyond the traditional markers. Future studies should directly quantify intact IL-12 and IL-35 to elucidate their individual contributions to the alteration of this immunoregulatory axis.

Although international guidelines primarily position the sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) combination as a salvage therapy for treatment-experienced patients, specific national reimbursement policies in Türkiye have uniquely positioned this regimen as a first-line treatment for treatment-naive individuals. Because international protocols largely restrict this combination to salvage settings, there remains limited real-world evidence regarding its efficacy and safety as a first-line therapy. This study aims to evaluate the real-world clinical performance of the SOF/VEL/VOX regimen in both treatment-naive and treatment-experienced patients with chronic hepatitis C (CHC), thereby providing additional real-world evidence for this underexplored clinical setting.

This retrospective, single-center observational longitudinal cohort study included 124 non-cirrhotic patients with CHC treated with the SOF/VEL/VOX regimen. The cohort comprised 86 (69.3%) treatment-naive and 38 (30.6%) treatment-experienced patients. Treatment-naive patients received the regimen for 8 weeks, whereas treatment-experienced patients received it for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12). Liver fibrosis was evaluated using the aspartate aminotransferase-to-platelet ratio index (APRI).

The mean age was 42 years, with a male predominance (81.4%) and a substantial proportion of individuals from the incarcerated population (44.3%). The most prevalent clinical comorbidities within the cohort were hypertension (8.1%) and diabetes mellitus (8.1%). Genotype 1 (58.1%) and genotype 3 (40.3%) were the most common variants. Regarding baseline differences, treatment-experienced patients were younger (mean age: 37.4 vs. 44.1 years) and exhibited a higher prevalence of genotype 1a infection compared to the treatment-naive group. At SVR12, hepatitis C virus ribonucleic acid (HCV RNA) clearance was achieved in 100% of both treatment-naive and treatment-experienced patients, with no significant difference between the groups (p = 1.000). Concomitant with virological clearance, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) significantly decreased (p < 0.001), reflecting the resolution of hepatic necroinflammation. Furthermore, the median APRI score decreased from 0.28 at baseline to 0.14 at SVR12 (p < 0.001), reflecting the rapid resolution of hepatic necroinflammation following viral clearance rather than definitive structural fibrosis regression in this predominantly non-cirrhotic cohort. The regimen was well tolerated, with no serious adverse events or treatment discontinuations. Minor transient adverse events (3.2%) resolved completely during follow-up.

This real-world study demonstrate that the SOF/VEL/VOX combination achieved a 100% SVR12 rate with excellent tolerability in both treatment-naive and treatment-experienced CHC patients. These findings support the use of SOF/VEL/VOX as a first-line option for treatment-naive patients, particularly in settings where alternative pangenotypic regimens are unavailable, while providing high virological efficacy and promoting rapid resolution of hepatic necroinflammation.

MELD-based scores do not fully account for systemic and metabolic risk in liver transplant candidates, with notable gaps for those with metabolic dysfunction-associated steatotic liver disease (MASLD). In this retrospective, outcome-anchored, single-center proof-of-concept study, we analyzed adult patients listed for liver transplantation at our institute from 2004 to 2025. We analyzed clinical and laboratory data collected 3-12 months prior to death, transplantation, or censoring, focusing on advanced disease stages. Exclusion criteria included hepatocellular carcinoma and incomplete MELD 3.0 data. We developed a competing-risk random survival forest (RSF) model using nine metabolic and systemic variables, and compared its performance to MELD-Na and MELD 3.0 via time-dependent discrimination and calibration metrics. Among 434 candidates (median age 56.8 years, 60.4% male), 43.3% died on the waitlist, 45.6% underwent transplantation, and 11.1% were alive at study end. The RSF model showed numerically higher discrimination for 180-day waitlist mortality (AUC = 0.81) versus MELD 3.0 and MELD-Na (AUC = 0.75 each), but this exploratory improvement did not demonstrate statistically significant superiority in pairwise AUC comparison. Albumin, diabetes mellitus, and hemoglobin were the strongest predictors. Exploratory reclassification analyses demonstrated a positive Net Reclassification Index (NRI = 0.30), driven primarily by improved identification of patients who died on the waiting list, with minimal misclassification among survivors. Exploratory subgroup analyses showed numerically higher discrimination among candidates with MASLD. These findings support further evaluation of the RSF model as a research framework for outcome-anchored 180-day waitlist mortality assessment. Prospective, multicenter, and external validation will be required before any consideration of clinical use.

Reducing postprandial blood glucose (PBG) constitutes a core objective in the clinical management of diabetes mellitus. Urtica cannabina L., a traditional medicinal and edible homologous plant, is widely distributed in China; however, research on its pharmacological activity and chemical composition remains relatively scarce. In the present study, the PBG-lowering potential of U. cannabina L. was confirmed both in vitro and in vivo, and its chemical constituents were preliminarily identified by UPLC-triple-TOF-MS/MS for the first time. Notably, acarbose (8 mg/kg), a clinically approved first-line α-glucosidase inhibitor, and UCE20 (20% ethanol extract of U. cannabina L.) at 10 mg/kg both significantly reduced PBG levels. Furthermore, UPLC-triple-TOF MS/MS analysis combined with correlation analysis has preliminarily indicated that hydroxycinnamoyl quinates and flavonoid C-glycosides may serve as the primary bioactive components responsible for the PBG-lowering effect. These findings suggested U. cannabina L. holds potential as a medicinal ingredient or health food to assist in the regulation of PBG levels.

Insulin resistance (IR) is the key driver of type 2 diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and cardiometabolic disorders. Mesenchymal stem cell-derived exosomes (MSC-Exos) as a potent cell-free alternative can deliver miRNAs, proteins, and mitochondrial regulators to reactivate the IRS1/PI3K/Akt/GLUT4 axis. Beyond restoring insulin signalling, these vesicles can protect β-cells, alleviate endoplasmic reticulum stress, rescue mitochondrial mitophagy and respiration. The genetic engineering strategies including improving the expression of miR-21, miR-3075, or Sirtuin-3, and silencing miR-29b-3p amplify the therapeutic efficacy. However, scalable good manufacturing practice production, long-term safety of modified products, and advanced therapy medicinal product regulation are still needed to overcome. This review will introduce the potential of gene-modified MSC-Exos and miRNAs targeting insulin signalling and mitochondrial rescue, which have shown a shift from symptomatic relief to precision disease-modifying therapy for IR.

The ability to generate stem cell-derived pancreatic β (SCβ) cells and stem cell-derived islets has opened new opportunities for type 1 diabetes mellitus therapies and disease modelling. Carefully assessing how closely SCβ cells resemble their primary counterparts is crucial to the support of ongoing clinical trials and human-centric studies on diabetes pathophysiology. Observed differences between SCβ cells and primary human β cells are generally attributed to the incomplete maturation of SCβ cells in vitro. However, even cells further matured in vivo can differ considerably from mature primary islet cells. In this Review, we examine key features of human β cells and islets, and summarize our current knowledge of these features in stem cell-derived products. We highlight knowledge gaps and discuss the requirements for comparative studies, emphasizing the importance of tissue quality, harmonizing approaches, integrating datasets and data sharing.

The differentiation between benign and malignant biliary strictures remains a significant clinical challenge. Recent studies have suggested that next generation sequencing (NGS) can improve the diagnostic accuracy. However, evidence on its performance in routine clinical practice is limited. Therefore, validation of the diagnostic value of NGS using real-world clinical data is warranted. We compared the performance of NGS analysis of cholangiocellular carcinoma (CCC)-associated mutations in endoscopic biopsies with that of histopathology, CA19-9 and cross-sectional imaging. NGS showed higher sensitivity for malignancy (65%) compared to histopathology (52%) at similar specificity (96% vs. 100%). The combination of NGS and histopathology further increased sensitivity for malignancy to 78% (p = 0.03) at similar specificity (96%). Our data provide support for the use of NGS in the diagnostic workup of biliary strictures.