Background: Lymph node biopsy is an important means of etiologic diagnosis for patients with fever of unknown origin (FUO) and lymphadenopathy. However, it is an invasive procedure and may yield negative results. It is worth exploring which kinds of patients could benefit most from lymph node biopsy. Methods: FUO patients (n = 242) who had lymphadenopathy and underwent lymph node biopsy were enrolled into this retrospective single-center study. Clinical manifestations were documented and risk factors suggestive of an underlying positive lymph node biopsy (providing diagnostic clues) and lymphoma were analyzed. Results: The etiologies were as follows: infectious disease in 10 (4.1%) cases, connective tissue diseases in 51 (21.1%) cases, neoplastic diseases in 57 (23.6%) cases, other diseases in 28 (11.6%) cases, and unknown diagnosis in 96 (39.7%) cases. A total of 88 patients (36.4%) were diagnosed through lymph node biopsy. The following four independent risk factors were found to be related to positive lymph node biopsy: male gender (OR 2.471; 95% CI 1.158–5.270; p = 0.019), no rash (OR 3.531; 95% CI 1.595–7.816; p = 0.002), shape index of the lymph node (OR 8.566; 95% CI 1.035–70.915; p = 0.046), and hypoalbuminemia (OR 3.370; 95% CI 1.470–7.728; p = 0.004). Later, 146 patients with a confirmed diagnosis (including 57 cases of lymphoma and 89 cases of non-lymphoma) were included in the analysis of lymphoma-related factors. Age older than 45 years (OR 8.663; 95% CI 3.045–24.647; p < 0.001), no rash (OR 4.946; 95% CI 1.646–14.859; p = 0.004), serositis (OR 3.588; 95% CI 1.137–11.318; p = 0.029), abnormal blood flow of the lymph node (OR 3.025; 95% CI 1.034–8.848; p = 0.043), abnormal central lymph nodes (OR 6.546; 95% CI 1.721–24.898; p = 0.006), focal lesions in the spleen (OR 13.386; 95% CI 2.067–86.706; p = 0.006), and serum lactate dehydrogenase (LDH) > 250 U/L (OR 3.885; 95% CI 1.111–13.584; p = 0.034) were independent risk factors for lymphoma. Conclusions: Lymph node biopsy is a valuable diagnostic procedure for patients with FUO and lymphadenopathy. For male patients without rash, more rounded lymph nodes, and hypoalbuminemia, we strongly recommend lymph node biopsy. Age older than 45 years, no rash, serositis, abnormal blood flow of the lymph node, abnormal central lymph nodes, focal lesions in the spleen, and serum LDH > 250 U/L are risk factors suggesting an underlying lymphoma, and multi-site biopsy should be considered if necessary.

Background: This study aimed to investigate the attitudes of infectious disease specialists toward shared decision-making (SDM) and identify the perceived barriers to its implementation in the management of fever of unknown origin (FUO) in China. Methods: A nationwide, cross-sectional, online survey was conducted in July 2025 among infectious disease specialists at Chinese general hospitals. Eligible participants were infectious disease specialists registered and working in Chinese general hospitals. Exclusion criteria were: (1) individuals without prior experience treating patients with FUO; (2) individuals practicing in other specialties; (3) individuals unable to complete the survey on digital devices; and (4) questionnaires completed in under 120 s. The 27-item questionnaire assessed: (1) attitudes and implementation tendencies regarding the six steps of SDM; (2) perceived barriers to SDM; and (3) perceived effectiveness using the 9-item Shared Decision-Making Questionnaire-Doctor version (SDM-Q-Doc). Data were analyzed using descriptive statistics, univariate tests, Random Forest model, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and multivariate linear regression. Results: Of the 429 responses received, 386 were eligible (67.4% females and 32.6% males). The mean age of participants was 41.42 years. Only 107 participants (27.7%) reported prior knowledge of SDM, and 33 (8.5%) had received formal training. Mean scores were 4.46/6 for attitudes, 3.52/9 for barriers, and 40.77/45 for perceived effectiveness. Higher perceived effectiveness scores were significantly associated with gender, managing≥10 FUO cases annually, frequent participation in multidisciplinary discussions, prior knowledge of SDM, and positive attitudes toward SDM. Primary barriers included unequal information between physicians and patients ( n = 256, 66.3%), patients’ limited knowledge ( n = 243, 63.0%), and insufficient technical support and training ( n = 242, 62.7%). Multivariate analysis identified “presenting options clearly,” “inviting patients to participate in SDM,” “facilitating deliberation and decision-making” and “gender” as independent predictors of perceived effectiveness. Conclusion: Infectious disease specialists in China demonstrated positive attitudes toward SDM in FUO management, which correlate with higher perceived effectiveness. To promote consistent and high-quality SDM in complex diagnostic scenarios, interventions should focus on structured training programs and the integration of decision-support tools into continuing medical education.

Background: Fever of unknown origin (FUO) remains a major diagnostic challenge due to its heterogeneous etiologies and nonspecific clinical manifestations. Although metagenomic next-generation sequencing (mNGS) represents a promising diagnostic tool, its clinical utility in adult patients with FUO remains incompletely characterized. Methods: In this study, we retrospectively analyzed adult FUO patients who underwent mNGS testing at Peking Union Medical College Hospital between March 2022 and April 2024. Clinically meaningful diagnostic contribution was determined according to the final clinical diagnosis following multidisciplinary adjudication. Diagnostic performance, pathogen spectrum, therapeutic impact, specimen type, and predictors of clinically meaningful mNGS results were evaluated. Results: A total of 127 FUO patients were included in the study. Infectious diseases accounted for 53.5% of final diagnoses, followed by noninfectious inflammatory diseases (11.0%), malignancies (10.2%), and undiagnosed conditions (19.7%). mNGS made a clinically meaningful diagnostic contribution in 31.5% (40/127) of patients, despite an overall positivity rate of 56.7% (72/127), and showed a higher sensitivity than conventional culture for infectious etiologies (69.1% vs. 16.9%), though with a lower specificity (57.6% vs. 96.0%). Diagnostic contribution varied significantly by specimen type, with drainage fluid/abscess samples showing the highest diagnostic yield (90.9%). Lower white blood cell count was independently associated with clinically meaningful mNGS results (OR 0.87, 95% CI 0.77–0.98). Conclusions: mNGS provides clinically meaningful diagnostic value in adult patients with FUO, particularly for identifying occult infectious etiologies. Lesion-directed sampling, whenever feasible, and careful interpretation of sequencing results in the clinical context are essential to maximize the diagnostic utility of this approach. A lower white blood cell count was independently associated with clinically meaningful mNGS results, although this finding requires validation in larger prospective studies.