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PubMed2026

Potential of plasma metagenomic next-generation sequencing to guide antibiotic therapy in acute necrotizing pancreatitis with early fever: a prospective multicenter cohort study.

BACKGROUND: Indiscriminate antibiotic use remains common in febrile patients with acute necrotizing pancreatitis (ANP), particularly during the early phase. Metagenomic next‑generation sequencing (mNGS) has shown diagnostic utility for infected pancreatic necrosis (IPN) and may offer a means to guide antimicrobial therapy. We aimed to explore whether mNGS could potentially improve the appropriateness of antibiotic use in ANP patients presenting with early fever. METHODS: This prospective multicenter cohort study was conducted at five hospitals in China, enrolling ANP patients who developed fever within two weeks of symptom onset. Antibiotic susceptibility was defined per local microbiology laboratory reports. The hypothetical impact of mNGS on reducing inappropriate antibiotic use was evaluated through a retrospective simulation using predefined criteria from the BGI China antimicrobial drug usage card, as mNGS results were not disclosed to the treating teams during the actual clinical course. RESULTS: Between May 2023 and December 2024, 125 ANP patients with early fever were enrolled. Antibiotics were administered to 91.2% (114/125) of patients, whereas only 23.2% (29/125)were eventually confirmed to have IPN, and the rate of appropriate antibiotic use was 14.5% (17/117) based on conventional culture. In our simulated model, if therapy had been guided by plasma mNGS results, the estimated rate of appropriate antibiotic use could have increased to 71.8%. CONCLUSIONS: Plasma mNGS facilitates rapid pathogen identification and shows potential for improving antibiotic appropriateness in ANP patients with early fever.

Adult↗

PubMed2026

Clinical relevance of HRD score in pheochromocytomas and paragangliomas: molecular cluster distribution and prognostic implications.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with variable metastatic potential across molecular clusters. While the homologous recombination deficiency (HRD) score has been established as a surrogate for HRD-related genomic instability to guide prognostic evaluation and therapeutic options in multiple solid tumors, its relevance in PPGLs remains unexplored. Here, data from 133 PPGL patients in the TCGA database were extracted to assess relationships between the HRD score and molecular clusters, metastasis, metastasis-free survival (MFS), and other clinical characteristics. Subsequently, a real-world cohort of 54 matched blood-tumor pairs was subjected to whole-exome sequencing, with HRD scores calculated to confirm the prior observations. The median HRD score was 7.0 and 9.0 in the TCGA-PPGL dataset and the clinical cohort, respectively. In the TCGA dataset, an elevated HRD score significantly correlated with metanephrine secretion, C2 cluster, and metastasis. Multivariate analysis identified a higher HRD score as an independent risk factor for shorter MFS (HR = 1.33, P = 0.008). Patients with HRD scores ≥ 7 exhibited significantly shorter MFS (P = 0.037), which was observed exclusively within the C1A cluster (P = 0.007). Analyses of our clinical validation cohort corroborated this cluster-specific distribution and further revealed higher HRD scores in three temozolomide-treated PPGLs compared with those treatment-naive C1A tumors (P = 0.043). In conclusion, despite exhibiting lower levels in C1A clusters, an elevated HRD score emerges as a promising indicator for refined metastatic risk stratification in PPGLs. Futhermore, the substantial increase in HRD score following temozolomide treatment provides a rationale for PARP inhibitor sequential or combination therapy in metastatic PPGLs.

Humans↗