Citations

This cross-sectional study examines the lawsuits that followed national and international policies for pembrolizumab approval.

Background: Intracardiac thrombosis (ICT) during liver transplantation (LT) is a rare but life-threatening complication with limited data regarding its risk factors, management, and outcomes. This study aimed to identify factors associated with ICT development, define predictors of intraoperative outcomes, and propose a novel classification and management algorithm for ICT. Methods: A multicenter, international retrospective case-control study was conducted on liver transplant recipients from seven centers between January 2005 and December 2023. ICT cases were identified through transesophageal echocardiography (TEE) or autopsy and matched 1:1 with controls. Results: Among 11 077 liver transplant recipients screened, 133 patients (1.2%) developed ICT. ICT occurred predominantly after reperfusion (58%). Compared to controls, ICT cases exhibited higher preoperative international normalized ratio ( P = 0.001) and fibrinogen levels ( P = 0.014). Post-reperfusion syndrome ( P < 0.001), disseminated intravascular coagulation ( P < 0.001), and primary graft failure ( P = 0.002) were also more common in the ICT group. Continuous veno-venous hemofiltration during surgery (odds ratio [OR] 8.20, 95% confidence interval [CI]: 2.09–38.1; P = 0.004) was associated with ICT development. ICT was associated with markedly higher rates of cardiac arrest ( P < 0.001) and intraoperative mortality ( P < 0.001), with thrombus location in the left heart chambers representing a significant predictor of mortality (OR 20.7, 95% CI: 6.25–81.3; P < 0.001). ICT grades 2 and 3 were associated with a markedly increased risk of intraoperative cardiac arrest ( P < 0.05). Importantly, delayed use of TEE was strongly associated with intraoperative death (OR 6.27, 95% CI: 1.45–27.1; P = 0.014). The 90-day mortality was 43% in ICT cases compared to 4.5% in controls, while 1-year mortality was 46% versus 10.5%, respectively. Conclusions: ICT during LT is a rare but severe complication associated with intraoperative mortality and poor short-term survival. Coagulation profile and intraoperative management play critical roles in ICT development. The early use of TEE enables timely diagnosis and intervention, improving patient outcomes. We propose a novel ICT classification offering a systematic framework for risk stratification and management to mitigate progression and mortality.

Background/Objectives: Human endogenous retroviruses (ERVs) are genomic sequences integrated into the human genome from ancestral exogenous retroviruses and are epigenetically silenced under normal conditions. Growing evidence has shown that they can be reactivated in human diseases such as cancers and autoimmune diseases. However, their clinical implications in colon cancer are yet to be explored. Methods: RNA-seq data were downloaded from RNA Atlas and TCGA for cell lines and tissue samples, respectively. After alignment, ERV expression was quantified against comprehensively compiled ERVs (3220). ERV expression profiles were compared between sequencing protocols, cancer and normal cells, and matched tumor and normal tissue pairs. Unsupervised clustering was used to identify ERV-defined tumor subtypes and their associations with clinical and other molecular features. ERV association with disease-specific survival (DSS) was performed using the Cox regression model. Results: PolyA and total RNA protocols were comparable in ERV expression detection. Cancer cells had significantly increased ERV expression and reactivation. Upregulated ERVs were significantly enriched in viral protein interactions with cytokine and cytokine receptors. ERV expression-defined tumor classes were significantly associated with tumor mutation burden and immuno-phenotypes such as antigen processing and presenting machinery and tumor immune infiltration score. Survival analysis identified 152 ERVs to be independently associated with DSS. Conclusions: ERV abnormal expression is common in colon cancer. The ERV-defined subtypes are associated with tumor immunity, and some ERVs are independently associated with patient outcomes.

Background/Objectives: Coronavirus disease 2019 (COVID-19) is associated with gastrointestinal (GI) symptoms. Small intestinal bacterial overgrowth (SIBO) is emerging as a significant GI sequela post-COVID-19 infection. This study aimed to evaluate the prevalence and incidence of SIBO post-COVID-19 infection across different age groups and to identify associated risk factors in a global cohort. Methods: A retrospective study utilized the TriNetX database and included adult patients (≥18 years) diagnosed with SIBO following COVID-19 infection (1 January 2022–30 May 2024). A propensity score matching (1:1) was used to adjust for demographics and SIBO risk factors. Kaplan–Meier survival analysis assessed the SIBO incidence within 12 months. Results: Among 1,660,092 COVID-19 patients and 42,322,017 controls, SIBO was diagnosed in 353 COVID-19 patients without hydrogen breath tests (BT) and 78 with BT, compared to 3368 controls without BT and 871 with BT. Age-specific analysis demonstrated a clear, progressive increase in the SIBO incidence, becoming distinctly significant by 6 months and highest at 12 months post-infection. The highest risks were noted in ages 60–69 (0.011% vs. 0.004%, OR 2.6, p = 0.0003) and 70–79 (0.011% vs. 0.005%, OR 2.0, p = 0.0004), with younger age groups (30–49 years) also showing significantly increased risks. The medication analysis revealed strong associations with chronic opioid, proton pump inhibitor, and antidiarrheal medication. Conclusions: COVID-19 significantly increased the risk of SIBO, particularly within the first 12 months post-infection, across various age groups and, notably, in association with certain chronic medications. Clinical vigilance and targeted management strategies are recommended to mitigate long-term GI consequences.

Retrieval-Augmented Generation (RAG) offers a promising strategy to harness large language models (LLMs) for delivering up-to-date, accurate clinical guidance while reducing physicians’ cognitive burden, yet its effectiveness hinges on query clarity and structure. We propose an adaptive Self-Query Retrieval (SQR) framework that integrates three refinement modules—PICOT (Population, Intervention, Comparison, Outcome, Time), SPICE (Setting, Population, Intervention, Comparison, Evaluation), and Iterative Query Refinement (IQR)—to automatically restructure and iteratively enhance clinical questions until they meet predefined retrieval-quality thresholds. Implemented on Gemini-1.0 Pro, we benchmarked SQR using thirty postoperative rhinoplasty queries, evaluating responses for accuracy and relevance on a three-point Likert scale and for retrieval quality via precision, recall, and F1 score; statistical significance was assessed by one-way ANOVA with Tukey post-hoc testing. The full SQR pipeline achieved 87% accuracy (Likert 2.4 ± 0.7) and 100% relevance (Likert 3.0 ± 0.0), significantly outperforming a non-refined RAG baseline (50% accuracy, 80% relevance; p < 0.01 and p = 0.03). Precision, recall, and F1 rose from 0.17, 0.39 and 0.24 to 0.53, 1.00, and 0.70, respectively, while PICOT-only and SPICE-only variants yielded intermediate improvements. These findings demonstrate that automated structuring and iterative enhancement of queries via SQR substantially elevate LLM-based clinical decision support, and its model-agnostic architecture enables rapid adaptation across specialties, data sources, and LLM platforms.

Rationale Immunoglobulin A (IgA) deficiency, a rare, highly heritable trait, is associated with frequent pulmonary infections, emphysema, airway changes and low lung function; however, it is unclear if reduced IgA levels may affect lung structure and function. Methods Serum IgA, IgA1 and galactose-deficient IgA1 (Gd-IgA1) levels were measured in the population-based Multi-Ethnic Study on Atherosclerosis (MESA). The MESA Lung Study measured percent emphysema on cardiac CT and airway dimensions on chest CT, and performed spirometry. Regression models were evaluated after adjustment for demographic and CT factors. Mendelian randomisation (MR) analyses were conducted using genetic variants from the Trans-Omics for Precision Medicine (TOPMed) programme. A replication analysis was performed in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS). Measurements and main results Among 5497 participants, lower log-normalised serum IgA levels were associated with greater percent emphysema (β=−0.084; 95% CI −0.14 to –0.026; p=0.005), which was confirmed on MR (β=−0.79; 95% CI −1.4 to –0.18; p=0.011). Greater log-normalised serum Gd-IgA1 levels were associated with airway wall thickness (β=0.0079; 95% CI 0.0017 to 0.014; p=0.012; n=2580) and decline in the forced expiratory volume in one second (FEV1) (β=−0.012; 95% CI −0.021 to –0.0036; p=0.0055; n=2778) and FEV1/forced vital capacity (FVC) ratio (β=−0.0028; 95% CI −0.0048 to –0.00084; p=0.0054; n=2778). Conclusion Lower serum IgA levels were associated with greater percent emphysema. Additionally, higher Gd-IgA1 levels were associated with airway wall thickness and lung function decline. These findings support a protective role of IgA in emphysema pathogenesis and possible deleterious role of Gd-IgA1 in airway diseases.

Inflammatory bowel disease (IBD) is associated with significant impacts on patients’ health and quality of life. Chronic inflammation is linked to an increased risk of malignancies, venous thromboembolisms and infections. Chronic diseases are also associated with an increased risk for psychiatric comorbidities, such as anxiety and depression. Consequently, IBD can greatly impact health-related quality of life. While endoscopic healing is a target of therapeutic efficacy in the management of IBD, patients prioritise achieving clinical remission, with symptom control being a primary motivator for IBD management. With the ever-evolving therapeutic landscape in IBD, the need for effective communication and shared decision-making (SDM) is crucial when relaying risks and benefits of treatment options: no treatment, complementary and alternative medicine, surgical resection and medical management. Various visual decision aids, patient-specific activities and predictive tools enhance patients’ understanding of the risks and benefits associated with certain treatments and enable patients to make informed decisions aligned with their personal values. Through SDM, the patient–provider relationship is strengthened, patient satisfaction is enhanced, patient quality of life is improved and better outcomes are achieved.

Background and objectives Arteriovenous malformations (AVMs) with perinidal aneurysms and single draining vein are associated with an elevated risk of rupture and increased procedural complexity. The role of preoperative embolization in this high-risk anatomical subset remains unclear. This study aimed to evaluate the safety and efficacy of microsurgery with preoperative embolization, compared with microsurgery alone in patients with such AVMs. Methods We conducted a multicenter retrospective analysis of an AVM registry from the MISTA (Multicenter International Study for Treatment of Brain AVMs) consortium and included AVMs with perinidal aneurysms and a single draining vein. Baseline characteristics, angiographic outcomes, functional outcomes, and complication rates were compared. Propensity score weighting (PSW) using the covariate balancing method was applied to adjust for baseline differences. Results Out of a total of 1919 patients, 65 met the inclusion criteria; 45 patients underwent preoperative embolization followed by microsurgery, and 20 underwent microsurgery alone. After adjustment, complete obliteration rates were similar between groups (OR 0.87, 95% CI 0.04 to 16.33, P=0.92), as were rates of functional independence at discharge and follow-up. Overall complication, symptomatic complication, and mortality rates did not differ significantly between groups. However, permanent complications were significantly lower in patients with preoperative embolization (OR 0.06, 95% CI 0.004 to 0.84, P=0.03). Discussion In patients with AVMs featuring perinidal aneurysms and single draining vein, preoperative embolization followed by microsurgery was associated with fewer permanent complications and no increase in adverse outcomes compared with microsurgery alone. However, given the small number of events, this finding should be interpreted cautiously.