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Background: Type 2 diabetes mellitus (T2DM) increases the risk of biliary diseases (BD). This study aimed to evaluate the association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) use andBD risk in T2DM patients, compared with sulfonylureas.

Methods: We conducted a multi-center retrospective cohort study using electronic health records from Nanjing Medical University (January 2017-September 2022). Adults aged 18-75 years with T2DM newly prescribed SGLT2i or sulfonylureas were included. Propensity score with inverse probability of treatment weighting (IPTW) was applied to balance baseline covariates. Follow-up continued until BD onset, last visit, death, or study end. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) complemented by sensitivity analyses, time-stratified analyses and subgroup analyses. Metabolic and biliary biomarkers were also compared.

Results: A total of 1,901 T2DM patients were included (453 SGLT2i users and 1,448 sulfonylurea users). BD occurred in 24 SGLT2i users and in 188 sulfonylurea users. After IPTW adjustment, SGLT2i use was associated with a lower BD risk (HR 0.595, 95% CI 0.410-0.863, p = 0.020), remaining significant beyond 24 months and was stronger in patients aged over 60 years, without diabetic complications, or with high comorbidity burdens, consistent regardless of prior biguanides use. Glycemic control and body weight remained comparable, whereas SGLT2i users showed higher high-density lipoprotein cholesterol and lower total bile acid, and bilirubin levels.

Conclusion: SGLT2i use was associated with a lower BD risk in T2DM patients, particularly with long-term treatment and among high-risk subgroups. Improved biliary biomarkers paralleled this reduction, suggesting a potential link that warrants further study.

Background: Acute myeloid leukaemia (AML) is a highly heterogeneous haematologic malignancy. Current therapeutic strategies include chemotherapy, targeted therapy and haematopoietic cell transplantation (allo-HSCT) and autologous haematopoietic cell transplantation (auto-HSCT). The graft-versus-leukaemia (GVL) effect and graft-versus-host disease (GVHD) in allo-HSCT remain major research foci, with emerging evidence highlighting the synergistic roles of T cells and natural killer (NK) cells in allo-HSCT immunity. This review systematically integrates the cooperative immunological interactions between T cells and NK cells and elucidates their critical significance in post-transplant immunotherapy.

Methods: This review systematically summarizes the cytotoxic mechanisms, immune reconstitution processes and related immunotherapeutic approaches involving T cells and NK cells in AML in the context of allo-HSCT and further elucidates their unique role in post-transplant immune regulation from the perspective of coordinated T-cell and NK-cell interactions.

Results: T cells and NK cells exert synergistic effects in post-transplant immune reconstitution, GVL responses, GVHD regulation and subsequent immunotherapeutic interventions. Early NK-cell reconstitution provides a critical window for the restoration of T-cell function, whereas cytokines derived from T cells, such as IL-2 and IL-15, further enhance NK-cell activity. This dynamic immunological interplay not only shapes the balance between GVL and GVHD, but also informs the development of post-transplant immunotherapeutic strategies.

Conclusion: The dynamic interplay between T cells and NK cells plays a pivotal role in allo-HSCT for AML. This review systematically integrates the cooperative functions of T cells and NK cells within the allo-HSCT immune landscape, offering new perspectives for advancing post-transplant immunotherapy. A deeper understanding of these mechanisms is expected to provide a theoretical foundation for optimizing post-transplant immune interventions in AML patients and for developing more precise therapeutic strategies.

Background and purpose: The benefit of adding anti-PD-1 antibodies to definitive chemoradiotherapy (dCRT) in elderly patients with esophageal squamous cell carcinoma (ESCC) remains uncertain. This study evaluated its efficacy and safety versus dCRT alone.

Materials and methods: We retrospectively analyzed the patients aged ≥ 70 years with ESCC treated at three academic centers from 2009 to 2023. All patients received first-line dCRT and the study group additionally received anti-PD-1 antibodies (IO group). Propensity score matching (PSM) was applied to balance baseline factors.

Results: A total of 241 patients were enrolled, including 130 in the IO group and 111 in the dCRT group. After 1:1 PSM (110 patients per group), no significant differences in overall survival (OS) or progression-free survival (PFS) were observed. The median OS was 34.5 vs 33.7 months (HR = 0.86, 95%CI: 0.58-1.28, p = 0.467) and median PFS was 29.8 vs 17.8 months (HR = 0.79, 95%CI: 0.55-1.13, p = 0.194). Multivariate Cox analysis identified high nutritional risk as an independent predictor of worse OS (p = 0.014), while both advanced TNM stage (p = 0.030) and high nutritional risk (p = 0.016) were independently associated with shorter PFS. Subgroup analyses suggested that patients with good performance, better nutritional status or lower comorbidity burden may benefit from combination therapy. Grade 3-4 adverse events were comparable between two groups.

Conclusion: Adding anti-PD-1 antibodies to dCRT did not result in a significant improvement in OS or PFS in the ESCC patients aged ≥ 70 years; however exploratory findings indicate a potential PFS signal in selected patients with favorable baseline conditions, which requires confirmation in prospective studies.

This case report characterizes the molecular pathology of two synchronous IDH mutant gliomas in a 28-year-old female patient. The patient exhibited symptoms of dizziness, retro-orbital pain, headache, and numbness with paresthesia in her right arm. MRI imaging revealed two distinct non-enhancing T2/FLAIR hyperintense lesions in the left frontal and parietal lobes. Histopathologic and molecular analyses, including whole exome sequencing, were performed on the resected specimens from each location. The left parietal tumor was diagnosed as a grade 4 astrocytoma with an IDH1 R132H mutation, while the left frontal tumor was classified as a grade 2 oligodendroglioma with an IDH1 R132S mutation. Given the distinct molecular profiles of both synchronous tumors, treatment consideration was given to each individual primary tumor.

Background: Postural Orthostatic Tachycardia Syndrome (POTS) and Neurally-Mediated Hypotension (NMH) are heterogeneous syndromes characterized by dysautonomia and multisystem symptoms. Mast cell activation, often manifesting as hives, has been proposed as a contributing mechanism, but its prevalence and clinical relevance in POTS and NMH are poorly defined.

Method: Patients from the Johns Hopkins POTS Clinic completed surveys assessing hives frequency and symptom burden using the Malmö POTS, the Composite Autonomic Symptom Score (COMPASS)-31, and a pain questionnaire. Associations between hives and clinical features were evaluated among patients with confirmed POTS, NMH, or clinically diagnosed orthostatic intolerance.

Result: Among 188 respondents, 80 (42.6%) reported hives sometimes and 33 (17.6%) reported hives often or always. Increasing hives frequency was associated with higher Malmö POTS scores and greater autonomic symptom burden across multiple COMPASS-31 subdomains, including gastrointestinal, bladder, and vasomotor symptoms (all p < 0.05). Hives was also associated with pain (OR 3.47, 95% CI 1.54-7.77, p = 0.002) and tingling (OR 5.73, CI 2.15-15.26, p < 0.001), but not orthostatic symptoms. These associations persisted after multivariable adjustment.

Conclusion: Hives are common in orthostatic intolerance syndromes and are associated with increased symptom burden. Future studies are needed to clarify the role of mast cell activation and evaluate mast cell-targeted therapies.

Background: The Beirut pager explosions on September 17, 2024 resulted in mass casualties with severe upper limb trauma admitted to Rafik Hariri University Hospital (RHUH), Lebanon's national war trauma referral center. Initial opioid-based anesthesia was associated with postoperative respiratory complications and high opioid requirements. Ketamine became available the following day through the International Committee of the Red Cross (ICRC). This study evaluates the transition to ketamine as a primary anesthetic and its effects on pain control, hemodynamics, respiration, and opioid use.

Methods: We retrospectively reviewed 100 hand and finger amputation surgeries. Patients initially received fentanyl intraoperatively and opioids postoperatively. Ketamine was subsequently introduced as the primary anesthetic. Pain was assessed using the Visual Analog Scale (VAS), while respiratory and hemodynamic parameters were monitored perioperatively.

Results: Ketamine was associated with significantly lower VAS scores (3.2 vs 7.8; p < 0.001), no respiratory complications (0 vs 18 cases), stable mean arterial pressure in 94% of patients, and reduced postoperative opioid use (5% vs 65%).

Conclusion: Ketamine is a safe, effective, opioid-sparing anesthetic and should be prioritized in conflict and resource-limited trauma settings.

Background: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with a poor prognosis, and its molecular mechanisms remain unclear. Our previous research identified the signal sequence receptor subunit delta (SSR4) of the TRAP complex as a potential ESCC biomarker. The TRAP complex, composed of SSR1, SSR2, SSR3, and SSR4, is essential for protein translocation, folding, and quality control, crucial for cellular balance. While individual TRAP subunits have been studied, a comprehensive understanding of their roles in human diseases is lacking.

Aim: This review synthesizes current evidence on the TRAP complex and its subunits (SSR1-SSR4) to clarify their roles in tumor progression and other diseases, identify knowledge gaps, and evaluate their potential as therapeutic targets.

Results: The study shows that TRAP subunit genes are significantly upregulated in various cancers, influencing tumor progression and immune infiltration, with some subunits showing different responses to chemotherapy. A pan-cancer analysis highlights their roles, while SSR3 and SSR4 mutations are linked to congenital glycosylation disorders. SSR1 and SSR3 are essential for glucose metabolism and are associated with diabetes risk. The interaction between TRAP and endoplasmic reticulum stress suggests potential therapeutic applications.

Conclusion: This review emphasizes the crucial roles of the TRAP complex and its subunits (SSR1-SSR4) in various diseases, highlighting their potential as therapeutic targets and biomarkers. Future research should focus on understanding the mechanisms through integrated experimental and multi-omics approaches, defining subunit interactions, and exploring structure-based drug design for clinical applications.