The Interplay of Heart Failure and Pulmonary Embolism: A Comprehensive Review.

Frailty Reversal and Mortality in Lung Transplant Recipients: Prognostic and Predictive Implications

The role of germline mutations in non-small cell lung cancer: A systematic review of emerging genetic drivers and clinical implications.

Homologous recombination deficiency (HRD), a genomic instability phenotype resulting from impaired DNA repair, has been associated with increased tumor immunogenicity in several solid tumors. However, its clinical relevance in metastatic gastric cancer (mGC), particularly in the context of immunotherapy-containing regimens, remains unclear. This study included 139 GC patients with nivolumab plus chemotherapy as first line between May 2022 and May 2024 and underwent tissue-based NGS (n = 116); a smaller subset additionally underwent ctDNA-based NGS (n = 24). HRD was defined by the presence of pathogenic or likely pathogenic variants in predefined homologous recombination repair (HRR) genes. Treatment outcomes, and molecular characteristics were compared according to HRD status based on tissue- and/or circulating tumor DNA (ctDNA) NGS results. Among 116 patients who underwent tissue-based NGS, HRD-positive tumors (14.7%) were significantly associated with longer progression-free survival (PFS; median 23.1 vs. 9.6months; p = 0.032) to immune checkpoint inhibitor (ICI) plus chemotherapy and overall survival (OS; median not reached vs. 17.9months; p = 0.027). HRD positivity remained an independent favorable prognostic factor for OS in multivariate analysis (HR: 0.247; 95% CI 0.071-0.859; p = 0.028). HRD-positive tumors showed higher frequencies of high tumor mutational burden (TMB) and microsatellite instability (MSI)-high tumors. However, exploratory analysis of ctDNA-based HRD in a small subset did not demonstrate a statistically significant association with survival outcomes. Tissue-based HRD positivity was associated with favorable survival outcomes and may provide complementary prognostic information in mGC patients with nivolumab plus chemotherapy as first line.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent and increasingly recognized as a multisystem cardiometabolic disorder. The global burden, incidence and prognostic implications of coexisting chronic kidney disease (CKD) in MASLD remain uncertain. In this meta-analysis, we searched MEDLINE and EMBASE from inception through September 25, 2025, for observational studies reporting CKD prevalence and/or incidence among adults (≥ 18 years) with MASLD. The primary outcomes were pooled CKD prevalence, estimated using random-effects models on the logit scale with the Hartung-Knapp adjustment, and pooled CKD incidence (per 1000 person-years), estimated using random-effects models with exact Poisson confidence intervals. Secondary outcomes included all-cause mortality and cardiovascular, renal and cancer outcomes. From 2811 records, 36 observational studies met the inclusion criteria. Twenty-three studies contributed prevalence estimates (575 615 participants; 56 248 CKD cases) and thirteen studies contributed incidence estimates (27 996 new events). The pooled global CKD prevalence among individuals with MASLD was 15.22% (95% CI 9.69-23.12). The pooled CKD incidence was 22.17 per 1000 person-years (95% CI 11.44-32.89) in the MASLD population. Hypertension (OR 1.49, 95% CI 1.29-1.72), dyslipidaemia (OR 1.22, 95% CI 1.20-1.24) and diabetes (OR 1.94, 95% CI 1.69-2.22) were associated with higher odds of CKD in the MASLD population. All-cause mortality rates were 18.28 per 1000 person-years (95% CI 3.45-33.11) in coexistent MASLD and CKD, more than double those in the MASLD-only population (7.26 per 1000 person-years (95% CI 2.97-11.56)). Coexistent CKD affects one in seven individuals with MASLD worldwide, conferring a more than two-fold increased risk of all-cause mortality compared with individuals with MASLD alone.

Risk Factors and Prognostic Implications of Unplanned Reintubation Following Lung Transplantation

Targeting PERK signaling: mechanisms and roles in myocardial protection.

Less Biopsy, Less Blowback: Prevalence and Prognostic Implications of Tricuspid Regurgitation in the dd-cfDNA Era

Extramedullary hematopoiesis (EMH) in myelofibrosis manifests beyond classical splenomegaly, causing life-threatening complications, yet lacks systematic characterization in the JAK inhibitor era. We systematically reviewed 36 publications (2011-2025), available on PubMed database, reporting 47 unique myelofibrosis-associated EMH cases, analyzing demographics, anatomic distribution, presentations, diagnostics, treatments, and outcomes.Median age was 68 years (range 43-82; M: F 26:21); primary myelofibrosis predominated (64%). EMH favored atypical sites: abdominopelvic (28%), thoracic (26%; pulmonary/pleural), serosal (17%), cutaneous (13%). Symptomatic onset occurred in 75% (dyspnea 28%, abdominal pain 21%). CT/MRI revealed characteristic lobulated masses with T2 hypointensity; biopsy confirmed trilineage hematopoiesis with atypical megakaryocytes (CD61+). Ruxolitinib-based regimens, administered in 19 patients (40%) as EMH-directed therapy, yielded rapid palliation (dyspnea/ascites resolution), complemented by radiotherapy (11%) and splenectomy; HSCT achieved complete remission in one case. Mortality reached 38% (median follow-up 5 months), driven by EMH-related organ failure or AML transformation. Atypical EMH signals advanced myelofibrosis with dismal prognosis, responsive to JAK inhibitors/locoregional therapies but highlighting sanctuary biology. Systematic surveillance and transplant referral are imperative; prospective registries are needed to refine risk models and test novel antifibrotics.

Osteosarcoma (OSA) is the most common primary bone tumor in dogs and cats, and accurate diagnosis of OSA has therapeutic and prognostic implications. Immunohistochemistry targeting osterix (Osx), a transcription factor expressed in osteoblasts, was applied to 80 canine samples (40 OSAs and 40 controls (8 chondrosarcomas, 8 fibrosarcomas, 8 hemangiosarcomas, 8 histiocytic sarcomas, and 8 malignant melanomas)) and 40 feline samples (20 OSAs and 20 controls (5 fibrosarcomas, 5 hemangiosarcomas, 5 chondrosarcomas, 3 malignant melanomas, and 2 histiocytic sarcomas)), diagnosed histologically. All 120 samples were assessed blinded using a previously established semiquantitative scoring and classification system. In dogs, 37/40 OSAs (true positives, sensitivity 92.5%) and 2/40 controls (false positives, specificity 95.0%) were classified as OSA. In cats, 14/20 OSAs (true positives, sensitivity 70.0%) and 5/20 controls (false positives, specificity 75.0%) were classified as OSA. Tumors most often "misclassified" as OSAs were chondrosarcomas in both dogs (2/8) and cats (4/5). In 4 cases for which paired decalcified and nondecalcified samples of the same OSA were available, decalcification of OSAs did not affect classification. Quiescent canine, feline, and murine osteoblasts and canine reactive, metaplastic, and non-OSA neoplastic osseous conditions were also tested and demonstrated Osx immunoreactivity; avian and piscine osteoblasts did not. In conclusion, Osx is a highly sensitive and specific marker of canine OSA and a moderately sensitive and specific marker of feline OSA. The diagnostic algorithm applied in this study is a useful adjunctive tool in the diagnosis of canine OSA.

Prognostic Implications of Personalized Circulating Tumor DNA Testing in Patients with Advanced Urothelial Carcinoma Treated with Enfortumab Vedotin±Pembrolizumab.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by extracellular deposition of misfolded transthyretin protein in the myocardium, leading to progressive dysfunction of both the left ventricle (LV) and left atrium (LA). While LV impairment has traditionally been emphasized in risk stratification, emerging evidence suggests that LA dysfunction may also contribute significantly to clinical outcomes. However, the prognostic implications of combining both LV and LA functional assessments in ATTR-CM remain unknown. We retrospectively evaluated 139 patients with ATTR-CM treated with disease-modifying therapies. LV and LA function were assessed using global longitudinal strain (GLS) and LA reservoir strain via speckle-tracking echocardiography. Patients were categorized into three groups based on median GLS (10.9%) and LA strain (9.5%): (1) preserved both LV and LA function, (2) impaired both, and (3) preserved only one. The primary endpoint was a composite of cardiovascular death or hospitalization for heart failure, with a median follow-up of 1.50years after treatment initiation. Patients with preserved function in both chambers experienced significantly fewer cardiovascular events, while those with impairment in both had the highest event rate. Patients with preserved function in only one chamber showed intermediate outcomes. In multivariable Cox regression analysis, combined LV and LA dysfunction was independently associated with adverse events (HR 8.89, 95% CI 2.38-44.20, P = 0.001). In conclusion, simultaneous evaluation of LV and LA function provides enhanced prognostic stratification in patients with ATTR-CM. This combined approach may support more accurate risk assessment and guide individualized therapeutic strategies in clinical practice.

Primary and secondary mesenteric panniculitis: A descriptive cohort study with clinical and prognostic implications.

Brain metastases have traditionally been considered well-demarcated lesions; however, increasing evidence demonstrates frequent microscopic infiltration of the surrounding brain parenchyma, with relevant prognostic implications, despite current intraoperative tools. The aim of this study was to evaluate the feasibility and diagnostic performance of a label-free nanoplasmonic biosensor for intraoperative discrimination between tumor tissue and peritumoral brain in brain metastases surgery. A prospective multicenter study was conducted in patients undergoing surgical resection of brain metastases. Paired tumor and adjacent peritumoral tissue samples were collected intraoperatively following a standardized protocol across participating centers. Samples were analyzed ex vivo using a plasmonic nanostructured biosensor, which detects tissue-specific refractive index differences. Histopathological examination served as the reference standard. Paired comparisons were performed using the Wilcoxon signed-rank test, and diagnostic performance was assessed using receiver operating characteristic analysis. Twenty paired tumor and peritumoral samples from a consecutive series of 20 patients were analyzed. Refractive index values were significantly higher in tumor tissue compared with peritumoral brain (p = 0.0008). In 85% of cases, tumor samples showed higher refractive index values than their paired peritumoral counterparts. Using the optimal cut-off value, sensitivity was 76% and specificity was 68%. Tumor and peritumoral brain tissue can be discriminated through the measurement of intrinsic biophysical properties with a label-free nanoplasmonic biosensor, supporting its potential role as an objective intraoperative tool for margin assessment without the need of exogenous agents.

The association between uveitis and spondyloarthritis is well established. However, its characterization across the different types of spondyloarthritis remains limited in the literature. Therefore, this study aimed to perform a comparative characterization of uveitis in the various types of spondyloarthritis. Retrospective observational study that included patients with non-infectious uveitis and spondyloarthritis from a multidisciplinary uveitis clinic. A descriptive analysis was performed across the different subtypes of spondyloarthritis, followed by a comparative analysis regrouping patients into axial and peripheral SpA categories. 163 patients with spondyloarthritis-associated uveitis were included, comprising radiographic axial spondyloarthritis (49%), non-radiographic axial spondyloarthritis (21%), spondyloarthritis associated with inflammatory bowel disease (13%), psoriatic arthritis (12%), and peripheral spondyloarthritis (4%). Anterior uveitis (97%), acute relapsing course (79%), and alternating laterality (47.4%) were predominant in the overall sample. When comparing axial versus peripheral forms, significant differences were observed: intermediate, posterior, and panuveitis locations occurred exclusively in the peripheral forms, which also showed higher frequencies of chronic courses (p < 0.001), bilateralism (p < 0.05), and greater use of systemic therapy (p = 0.05). Regarding this treatment to control uveitis, 28.2% of patients required immunomodulatory therapy (more sulfasalazine in axial forms, and methotrexate in peripheral) and 17.8% required biologic therapy. Biologic discontinuation was higher in peripheral forms (p = 0.059). Variables predicting greater need for systemic therapy included chronic course, bilateralism, higher number of annual episodes, younger age of onset, peripheral joint involvement, and presence of vitritis (all p < 0.05). Acute anterior uveitis constitutes the most frequent pattern in all spondyloarthritis types. However, peripheral forms exhibit a higher prevalence of non-anterior, chronic, and bilateral uveitis, and, additionally, appeared to require greater use of immunomodulatory therapy. Key Points • Understanding and distinguishing the ocular inflammatory processes associated with SpA may have important therapeutic and prognostic implications. • Although acute recurrent anterior uveitis was the most frequent patternacross all SpA subtypes, in the peripheral SpA group (pSpA, IBD-SpA, and PsA) a higher prevalence of intermediate, posterior, panuveitis, chronic course, and bilateral uveitis was observed. • The peripheral SpA group (pSpA, IBD-SpA, and PsA) appeared to require greater use of immunomodulatory drugs (csDMARDs or biologics) for control of the ocular condition, suggesting the need for closer monitoring and tailored therapeutic strategies.

Apolipoprotein C1 (APOC1) has been implicated in several malignancies, yet its expression patterns, clinical significance, and immunomodulatory roles across cancer types remain poorly characterized. We performed a comprehensive multi-omic analysis of APOC1 across 33 cancer types integrating transcriptomic, proteomic, genomic, epigenomic, and pharmacogenomic data from TCGA, GTEx, CPTAC, and multiple independent external cohorts. Immune infiltration was assessed using seven complementary algorithms. Spatial transcriptomics and single-cell RNA sequencing were employed to determine the cellular source of APOC1 expression. APOC1 upregulation in most cancers was associated with cancer type-specific prognosis. After adjustment for clinical covariates and macrophage infiltration, high APOC1 remained an independent adverse factor in KIRC, LGG, and STAD. APOC1 expression positively correlated with genomic instability hallmarks, including homologous recombination deficiency and aneuploidy, with these associations largely independent of immune infiltration; in contrast, associations with tumor mutational burden were substantially confounded by macrophage abundance. Immune infiltration analysis revealed a pattern consistent with adaptive immune resistance: APOC1 correlated positively with immune-activating signatures (STAT1, MHC-II, TCR signaling) and immunosuppressive M2 macrophages and Tregs, yet negatively with anti-tumor effectors (activated NK cells, dendritic cells). Spatial transcriptomics and single-cell RNA sequencing identified tumor-associated macrophages (TAMs) as the primary cellular source of APOC1, with transcripts co-localizing with CD68 in tissue sections. APOC1 expression correlated with multiple immune checkpoint molecules and was elevated in responders to immune checkpoint blockade, consistent with an inflamed yet regulated tumor microenvironment. Pharmacogenomic analyses revealed that APOC1-high tumors display distinct drug response profiles, characterized by resistance to MAPK pathway inhibitors and potential sensitivity to the HDAC inhibitor Entinostat. This pan-cancer analysis establishes APOC1 as a context-dependent biomarker and a TAM-derived modulator of adaptive immune resistance, with prognostic and therapeutic implications across malignancies. APOC1-expressing TAMs represent a potential target for combination immunotherapy strategies.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in developed countries, with prevalence expected to reach nearly 288million by 2040. Accurate classification of AMD is critical for patient care and clinical research, guiding prognosis, therapeutic strategies, and the design of clinical trials. A widely adopted framework, the Beckman classification, stratifies AMD based primarily on color fundus photography (CFP) findings, defining stages from early to late disease. While simple and clinically applicable, such systems do not account for several key phenotypes revealed by advances in multimodal imaging. Such novel phenotypes include reticular pseudodrusen (RPD), acquired vitelliform lesions (AVL), non-exudative macular neovascularization (MNV), incomplete retinal pigment epithelium and outer retina atrophy (iRORA), and non-neovascular exudative fluid. Recent imaging modalities-including optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography (OCTA)-have uncovered features with important prognostic implications that are currently misclassified with respect to AMD. For example, eyes with RPD or AVL in the absence of drusen are currently misclassified as "early AMD" or excluded altogether, despite their high risk of progression. Similarly, the ambiguous status of non-exudative MNV, which carries both protective and harmful potential, highlights the need for greater granularity. The Classification of Atrophy Meetings (CAM) group has also introduced refined OCT-based definitions such as iRORA and cRORA, underscoring early degenerative changes that precede geographic atrophy. Moreover, novel entities like non-neovascular intraretinal or subretinal fluid challenge the assumption that exudation is synonymous with neovascular AMD. This review synthesizes recent evidence highlighting the limitations of current classification systems in light of these advances. Furthermore, we emphasize that intermediate AMD, currently treated as a uniform category, actually encompasses highly heterogeneous phenotypes with distinct risks and trajectories. A more nuanced, imaging-integrated classification system is urgently needed to improve disease staging, identify high-risk eyes, and ensure appropriate patient selection for emerging therapies. Such a framework would not only better reflect the complex natural history of AMD but also facilitate the regulatory shift toward continuous, quantitative endpoints in clinical trials.

Right ventricular-pulmonary arterial coupling is a known prognostic marker in patients with tricuspid regurgitation (TR). However, its assessment by cardiac magnetic resonance and its clinical implications have not been evaluated. We aimed to assess the prognostic role of a cardiac magnetic resonance surrogate of right ventricular-pulmonary arterial coupling in a large cohort of patients with a spectrum of TR severity. Comprehensive data were collected from patients referred for cardiac magnetic resonance from 2019 to 2024 who had TR quantification. Right ventricular-pulmonary arterial coupling was calculated by dividing the forward right ventricular stroke volume (f-RVSV) by the right ventricular end-systolic volume (ESV). The outcome of interest was the composite of all-cause death and heart failure hospitalization, under medical management. In the 631 patients included, median age was 66 (interquartile range [IQR], 54-75) years, median tricuspid regurgitant volume was 18 (IQR, 12-30 mL), median left ventricular ejection fraction was 53 (IQR, 41-61)%, median RV ejection fraction was 53 (IQR, 45-58)%, and median f-RVSV/ESV ratio was 0.82 (IQR, 0.58-1.11). In restricted spline curve analysis, the f-RVSV/ESV ratio cutoff associated with a hazard >1 for the composite outcome was ≤0.57. At baseline, a low f-RVSV/ESV ratio was strongly associated with subjective and objective signs of right heart failure, higher TRI-SCORE, and worse right-sided chamber remodeling (all P<0.001). After a median follow-up of 1.8 years (IQR, 1.5-2.0), patients with a low f-RVSV/ESV ratio showed worse survival (P<0.001). After comprehensive adjustment for clinical and imaging confounders, f-RVSV/ESV ≤0.57 remained a powerful predictor of outcome (adjusted hazard ratio, 2.36 [95% CI, 1.27-4.37]; P=0.004). Finally, patients with low f-RVSV/ESV displayed a worse long-term prognosis across mild, moderate, and severe TR groups (P<0.001, P<0.001, and P=0.018, respectively). In this large cohort of patients with a wide spectrum of TR severity, right ventricular-pulmonary arterial coupling assessed by cardiac magnetic resonance was strongly associated with right-sided heart failure and worse long-term prognosis, even after comprehensive adjustment.

Exploring the prognostic implications of programmed death-ligand 1 expression in canine nodal lymphoma: Insights from surface membrane expression, transcript amount and plasmatic levels.

While glycemic variability (GV) affects outcomes in critically ill patients, its temporal patterns and prognostic implications in severe pneumonia remain unclear. This study aimed to identify distinct GV trajectory patterns and their associations with clinical outcomes. This prospective cohort study enrolled 315 patients with severe pneumonia admitted to our intensive care unit (ICU) at Taicang Hospital of Nanjing University of Chinese Medicine, from January 2021 to December 2024. Using group-based trajectory modeling (GBTM), we analyzed the coefficient of variation (CV) trajectories during the first 5 ICU days. We compared clinical characteristics between trajectory groups, conducted exploratory landmark survival analysis, and assessed the performance of clinical parameters for identifying trajectory classification. GBTM identified two distinct GV trajectories: Dynamic Variant (DV, 12.1%) characterized by initially high variability that gradually decreased but remained persistently elevated, and Stable Control (SC, 87.9%) with consistently low variability. While early outcomes were comparable, after day 14, the DV group demonstrated significantly higher mortality (70.3% vs. 60.0%, p = 0.034). DV patients had higher procalcitonin (PCT, 2.35 vs. 0.76 ng/ml, p = 0.030) and glycated hemoglobin A1c (HbA1c, 7.1% vs. 6.3%, p = 0.002) levels on ICU admission, despite similar disease severity scores and other clinical parameters. Combined prediction using PCT and HbA1c showed good performance in identifying trajectories (Area Under the Receiver Operating Characteristic curve: 0.87, 95% Confidence Interval: 0.80-0.94). Distinct GV trajectories in severe pneumonia patients are associated with differential subsequent mortality risks, with admission PCT and HbA1c levels serving as predictors of trajectory group classification. Not applicable.