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PURPOSE Chronic myelomonocytic leukemia (CMML) is a rare myeloid neoplasm characterized by clinical heterogeneity and is associated with poor outcomes. To date, limited molecular information has been incorporated into disease classification and risk stratification. We aimed to integrate genomic features into the clinical decision-making process for CMML. PATIENTS AND METHODS We analyzed a retrospective cohort of 3013 patients with CMML (training set) and a prospective population of 516 patients (validation set). Using an innovative framework for multimodal data analysis, we developed molecular-based disease taxonomy and prognostication. RESULTS Unsupervised clustering identified nine entities with distinct genomic features and outcomes ( P < .001), including splicing machinery, transcription factors, signal transduction and tyrosine kinase pathways aberrations, and high-risk molecular signatures. Notably, 15% of patients showed molecular/clinical overlap with other myeloid neoplasms. We integrated molecular and clinical information to build the international CMML Prognostic Scoring System (iCPSS), incorporating mutations in nine genes together with hematologic parameters and cytogenetic abnormalities. The iCPSS identified five groups with distinct probability of overall and leukemia-free survival in both training and validation cohorts ( P < .001), outperforming existing prognostic models. Importantly, 55% of patients were reassigned to higher or lower risk groups by the iCPSS. Decision analysis demonstrated that iCPSS could refine the optimal timing of allogeneic transplantation at the individual level; compared with conventional prognostic tools, iCPSS-based decision modeling changed transplantation strategy in 31% of cases, resulting in a significant gain-in-life expectancy for eligible patient population ( P < .001). A federated learning platform was implemented to enable continuous, privacy-preserving model update across multiple centers. CONCLUSION Molecular information improves CMML classification and prognostication, supports more effective clinical decision making, and potentially refines the design of clinical trials.

Abstract Left atrial enlargement is a well-recognized marker of adverse cardiovascular outcomes, but its impact on early morbidity and mortality after valve replacement remains uncertain. We retrospectively reviewed 422 patients who underwent aortic and/or mitral valve replacement (MVR) for rheumatic heart disease at X between 2004 and 2022. Preoperative left atrial diameter index (LADI) was measured, and patients were classified as normal (<2.3 cm/m2) or abnormal (≥2.3 cm/m2). Clinical, operative, and postoperative outcomes were compared. The primary endpoint was 30-day all-cause mortality; secondary endpoints included postoperative atrial fibrillation (POAF), neurological events, renal impairment, re-exploration for bleeding, and intraoperative pacing wire requirement. Nearly half of patients (48.8%) had abnormal LADI. Patients with enlarged atria were more often female, had smaller body size, and were significantly more likely to undergo MVR (42.7% versus 18.1%, p < 0.001). Abnormal LADI was strongly associated with POAF (16.0% versus 7.4%, p = 0.006) and intraoperative pacing wire insertion (38.3% versus 23.5%, p = 0.001). Multivariate analysis confirmed severe LADI as an independent predictor of POAF (OR 3.91, p = 0.001) and pacing requirements (OR 2.31, p = 0.004). No significant differences were observed in 30-day mortality, stroke/transient ischemic attack, renal dysfunction, or bleeding complications. Preoperative LADI is an independent predictor of postoperative arrhythmic complications and pacing needs after valve replacement, but not early mortality. Incorporating LADI into preoperative risk assessment may improve rhythm surveillance and perioperative planning. Future prospective studies should evaluate its long-term prognostic value and role in reverse remodeling after surgery.

Post-COVID syndrome comprises persistent neuropsychiatric manifestations for more than 12 weeks after recovery from acute SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. Ferroptosis, an iron-dependent form of cell death with three hallmarks, iron dysregulation, antioxidant failure, and lipid peroxidation, seems to be involved in COVID-19/post-COVID-19 pathophysiology. Here, we administered the SARS-CoV-2 spike protein S1 subunit intranasally to K18-hACE2 transgenic mice and quantified ferroptotic marker protein expression in four brain regions (hippocampus, prefrontal cortex, cerebellum, and olfactory bulb) at 2, 6, and 12 weeks post-administration, alongside ultrastructural assessment by transmission electron microscopy (TEM) that was limited to the hippocampus and prefrontal cortex. Two-way ANOVA revealed region- and time-dependent modulation of iron-handling, antioxidant, and lipid peroxidation markers. In the hippocampus, FPN1 was significantly increased at 2 weeks, while TFR1 showed a time-dependent pattern without significant week-specific differences. In the prefrontal cortex, DMT1 significantly increased at 2 weeks, and GPx4 showed an overall treatment effect with a trend of increase at 6 weeks. The cerebellum exhibited early increases in FPN1 and GPx4 and a delayed increase in MDA-conjugated proteins. In the olfactory bulb, FPN1 increased at 12 weeks, with GPx4 showing an overall treatment effect and an early trend of decrease. TEM identified ferroptosis-consistent features in the hippocampus and prefrontal cortex at all time points. These findings suggest that spike protein exposure may be associated with time-dependent and brain-region-specific alterations of ferroptosis-related markers. These preliminary findings are based on a limited sample size, which needs further research to elucidate the clinical implication and to study the mechanism in more depth as well as future validation with pharmacological inhibitors.

Background/Objectives: Despite immune checkpoint inhibitors (ICPIs)’s transformation of lung cancer treatment, pneumonitis remains a potentially serious immune-related adverse event. However, reliable data on the comparative risks of individual ICPIs remain unknown. We conducted this network meta-analysis (NMA) to, therefore, quantify and compare the exact pooled burden of pneumonitis risk across multiple ICPI analogs. Methods: We searched the following databases, PubMed, Embase, Scopus MEDLINE and Cochrane Database of Systematic Reviews, as well as gray literature on Google Scholar for eligible studies reporting on the prevalence of pneumonitis following immune check point inhibitor exposures. Pairwise and network meta-analyses were performed to estimate pooled odds ratios (ORs) for pneumonitis, using placebo as the common comparator. Sensitivity analyses assessed the impact of study quality and combination therapies. Results: A total of 29 studies enrolling 15,271 patients with non-small cell lung cancer (NSCLC) or small-cell lung cancer (SCLC) satisfied the inclusion criteria and are included in the meta-analysis. Pembrolizumab was associated with a significantly increased risk of pneumonitis compared to placebo (odds ratio [OR] = 2.67, 95% confidence interval [CI]: 1.70–4.17), with similar elevated risk observed for sugemalimab (odds ratio [OR] = 2.45, 95% confidence interval [CI]: 1.52–3.95). Nivolumab was associated with increased odds of pneumonitis, although with unstable point estimate (odds Ratio [OR] = 2.69, 95% confidence interval [CI]: 0.64–11.35). Statistical heterogeneity was low (H statistics = 1.34). Atezolizumab and ipilimumab demonstrated modest or uncertain risk. Heterogeneity was low (I2 = 12%), and results were robust to sensitivity analyses. Higher pneumonitis rates were observed in combination regimens. Conclusions: Our analysis demonstrates that pneumonitis risk varies among ICPIs, with pembrolizumab and sugemalimab showing the highest odds. Although the absolute incidence is low, the potential severity of pneumonitis warrants vigilant monitoring. These results should guide clinicians in risk stratification and treatment planning, and they should support the development of standardized reporting criteria and further comparative research.

Background: Rotator cuff tears are a common orthopaedic injury often resulting in shoulder pain and functional impairment. Despite the prevalence of rotator cuff tears, the incidence of retear after rotator cuff repair (RCR) remains high. There is growing interest in the use of structural augmentation in RCR to decrease retear rates and improve patient outcomes. Purpose: The purpose of this systematic review and meta-analysis was to compare the clinical and imaging outcomes of structural augmentation versus standard RCR in patients with full-thickness rotator cuff tears. The effectiveness of different augment subtypes was also assessed. Study Design: Meta-analysis; Level of evidence, 3. Methods: A comprehensive literature search was conducted in CENTRAL, Embase, and Medline from inception to November 13, 2024. Eligible studies included comparative trials evaluating structural augmentation in RCR for repairable full-thickness tears. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomized controlled trials and the MINORS (Methodological Index for Non-randomized Studies) score for observational studies. Meta-analyses were performed via a random effects model, with subgroup analyses performed by study design and augment type. Results: Twenty-four studies (12 randomized controlled trials and 12 cohort studies) were included in this review, all of which evaluated biologic augments (xenograft, allograft, autograft). Structural augmentation significantly reduced the risk of retear by 35% as compared with standard RCR (risk ratio, 0.65; 95% CI, 0.48-0.89; P = .01). Retears were confirmed radiographically by magnetic resonance imaging or ultrasound. Subgroup analysis revealed the greatest reduction in retear rates with allograft augmentation (risk ratio, 0.34; 95% CI, 0.21-0.56). No significant differences were observed in patient-reported outcomes, including pain scores, American Shoulder and Elbow Surgeons scores, or Constant scores. Conclusion: Structural augmentation in RCR significantly reduces retear rates, particularly with allografts, but does not improve short-term patient-reported outcomes. Further research is needed to identify which patient and tear characteristics may influence the effectiveness of augmentation.

Sharing research code in an open access version-controlled repository offers significant benefits for both science as a whole and for individual researchers. In this article, we focus on this practice, which is fully aligned with the NIH’s Gold Standard Science (GSS) program as well as FAIR (findable, accessible, interoperable, reusable) and TRUST (transparency, responsibility, user focus, sustainability, technology) principles. Gold Standard Science supports open science by emphasizing transparency, reproducibility, and the use of best practices that enable others to verify and extend research. Pairing a research article’s cited data snapshot with a versioned, environment-specific code release, deposited in a companion code repository, ensures that, upon submission to a medical journal, readers and reviewers can directly verify results. An executable and updatable companion code repository complements, rather than replaces, established research data repositories. When code underlying medical research results is made openly available, then other scientists can inspect, run, and validate analyses. These activities enhance reproducibility, which is a core aim of GSS. Shared code also facilitates collaborative innovation by allowing researchers to extend the utility of the code to new datasets and applications. For researchers, code sharing can increase visibility, credibility, and citation impact. Demonstrating transparency through shared executable and updatable code builds trust with journal readers, peer reviewers, funders, and peers. Shared code in an open access repository signals adherence to high standards of scientific integrity and attracts opportunities for collaboration. A researcher who shares code receives recognition as a leader in reproducible, trustworthy research consistent with NIH’s GSS principles.

741 Background: IP strategies directly target the peritoneal compartment in PDAC, where systemic chemotherapy alone demonstrates poor efficacy. Approaches include HIPEC, normothermic intraperitoneal paclitaxel (NIPEC/IP-PTX) given with systemic therapy, and PIPAC. This systematic review synthesizes evidence on feasibility, perioperative safety, and clinical outcomes of IP therapy in PDAC. Methods: We conducted a systematic search in PubMed, Embase, Scopus, and Cochrane databases for studies published through August 2025. Eligible studies included prospective or retrospective studies evaluating HIPEC, NIPEC/IP-PTX, or PIPAC with extractable safety or oncologic outcomes. Outcomes included feasibility, 30-day mortality, perioperative complications, locoregional recurrence (LRR) in the adjuvant setting, overall survival (OS) from peritoneal metastasis (PM) diagnosis or first IP therapy, conversion-to-resection, and histologic/radiologic response. Results: Sixteen studies met criteria, including 7 on HIPEC, 5 on NIPEC/IP-PTX, and 4 on PIPAC. In the adjuvant setting, 2 HIPEC studies demonstrated high feasibility (>85%), 0–5% 30-day mortality, and complication rates comparable to pancreatectomy. A randomized trial reported significantly lower LRR with adjuvant gemcitabine HIPEC. Median OS in treated arms was ~17–18 months, with 1-year OS ~63%. In the cytoreductive surgery (CRS) plus HIPEC setting for isolated peritoneal metastases, patients achieved CC-0/1 cytoreduction in most cases, with median OS ~24–41 months and 1-, 2-, and 3-year OS ranging 60–91%, 33–66%, and 39–59%, respectively. Thirty-day mortality was 0–4.3%, and major morbidity 20–43%. For NIPEC/IP-PTX, multicenter and single-institution cohorts consistently reported median OS ~14–16 months, 1-year OS ~60%, and conversion-to-resection rates of 17–24%. Ascites control and feasibility were reproducible, and device-related adverse events were generally manageable. PIPAC programs established oxaliplatin at 120 mg/m² as the recommended dose, with ~50–60% histologic regression by PRGS and disease stabilization in 50–60% after 1–2 cycles. Median OS in PDAC subsets was ~9–13 months, with low major toxicity, though early discontinuation was frequent in progressive disease. Conclusions: Intraperitoneal therapies for PDAC are feasible and show promising biologic and clinical signals. Adjuvant HIPEC reduces locoregional recurrence without excess mortality; CRS plus HIPEC can achieve multi-year survival in selected patients with isolated PM metastases; NIPEC/IP-PTX offers reproducible survival and conversion-to-resection; and PIPAC provides histologic regression with acceptable safety.

117 Background: Oxaliplatin remains a cornerstone of colorectal cancer (CRC) chemotherapy but is frequently complicated by chemotherapy-associated liver injury (CALI). This manifests as sinusoidal obstruction syndrome (SOS), nodular regenerative hyperplasia (NRH), or porto-sinusoidal vascular disorder (PSVD). These microvascular changes lead to portal hypertension (PH), splenomegaly, and thrombocytopenia, interrupting chemotherapy delivery and compromising survivorship. Despite increasing recognition, the incidence, spectrum, and management of oxaliplatin-induced portal hypertension (OIPH) remain undefined. Methods: We systematically reviewed PubMed, Embase, and Cochrane through August 2025 for prospective and retrospective cohorts of oxaliplatin-treated CRC patients reporting OIPH incidence, pathology, radiology, or interventional management. Case reports were excluded. Outcomes included incidence, latency, complications, misdiagnosis, and interventions such as bevacizumab and partial splenic embolization (PSE). Results: Eight studies including 730 patients were analyzed. OIPH developed in ~20–30% of patients, with 2–5% progressing to clinically overt disease requiring variceal banding, Transjugular Intrahepatic Portosystemic Shunt (TIPS), PSE, or management of liver failure. Latency to presentation was typically 4–10 years after oxaliplatin exposure. Common features included splenomegaly, thrombocytopenia, varices, and ascites. Histopathology consistently showed sinusoidal dilatation, congestion, perisinusoidal fibrosis, NRH, and microthrombi, confirming endothelial-mediated injury. Up to half of chronic cases were misclassified as metabolic dysfunction–associated steatotic liver disease (MASLD/NAFLD) or cryptogenic cirrhosis. Bevacizumab demonstrated consistent hepatoprotection, delaying splenic enlargement and reducing thrombocytopenia, likely via preservation of sinusoidal endothelial integrity and reduction of von Willebrand factor–mediated platelet microthrombi. Interventional radiology provided therapeutic options: in a prospective phase II study, PSE restored platelet counts >130×10⁹/L in 94% and enabled chemotherapy resumption within a median of 14 days, with no grade ≥3 adverse events. Conclusions: OIPH is an under-recognized complication of CRC chemotherapy, with latency spanning years after treatment. Splenomegaly and thrombocytopenia serve as early clinical signals, while misdiagnosis as MASLD or cirrhosis is common. Bevacizumab provides hepatoprotection, and PSE offers a safe and effective option for chemotherapy-limiting thrombocytopenia. Routine monitoring of spleen volume and platelet trends should be integrated into follow-up, and prospective validation of prophylactic and interventional strategies is urgently needed.

Objectives: To identify factors associated with short-term mortality among patients receiving microaxial flow pump (mAFP) therapy for acute myocardial infarction-related cardiogenic shock (AMI-CS). Data Sources: We searched four databases (MEDLINE, Embase, CENTRAL, and Scopus) from January 1, 2004, to January 1, 2025. Study Selection: We selected English-language studies that included adults with AMI-CS receiving mAFP and evaluated factors associated with short-term mortality. We excluded patients receiving concurrent venoarterial extracorporeal membrane oxygenation, as well as studies that solely included patients presenting with out-of-hospital cardiac arrest. Data Extraction: Two authors performed citation screening and data extraction. For each factor evaluated in at least two studies, we performed meta-analyses of adjusted odds ratios (aORs) using a random-effects model. Risk of bias was evaluated using the Quality in Prognosis Studies tool, and the certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. Data Synthesis: Our primary analysis included 18 studies, encompassing 20,617 patients. Median short-term mortality across studies was 50.7% (interquartile range 38.4–55.3%). Factors associated with short-term mortality based on high-certainty evidence included: increased age (aOR, 1.04 per year [95% CI, 1.03–1.05 per year] or ≥ 65 yr (aOR, 2.42 yr [95% CI, 0.77–7.64 yr]), female sex (aOR, 1.26 [95% CI, 1.09–1.45]), higher body mass index (aOR, 1.05 per point [95% CI, 1.04–1.07 per point]), higher heart rate (aOR, 1.02 per beats/min [95% CI, 1.01–1.02 per beats/min]), higher serum creatinine (aOR, 1.35 per mg/dL [95% CI, 1.08–1.70 per mg/dL]), mechanical ventilation (aOR, 2.53 [95% CI, 1.82–3.53]), vasopressors (aOR, 1.52 [95% CI, 1.11–2.08] for any vasopressors and aOR, 1.37 [95% CI, 1.18–1.58] per each vasopressor), presentation with ST-elevation myocardial infarction (aOR, 1.59 [95% CI, 1.11–2.26]), cardiac arrest (aOR, 2.85 [95% CI, 2.22–3.64]), and hypoxic-ischemic brain injury (aOR, 5.36 [95% CI, 3.03–9.47]). Conclusions: We identified several prognostic factors associated with short-term mortality in AMI-CS patients receiving mAFP support. This work may help inform clinicians, patients, and families regarding utilization of mAFP in AMI-CS.