The aim of this retrospective study is to analyze the outcome and survival of patients with well-differentiated metastatic neuroendocrine neoplasm (NEN) treated with peptide receptor radionuclide therapy (PRRT).

The treatment was applied to 32 subjects, 18 men and 14 women, aged 39-79 years (median 65 years). The dominant grade of the tumor according to the Ki-67 index was G2 (75%) compared to G1 (25%). The average number of three-day protocol PRRT cycles was 4 (1.00-9.00). Lutetium-177- DOTA⁰,Tyr³,Thr⁸-octreotide (¹⁷⁷Lu-DOTA-TATE) was used in 22 (69%), both ¹⁷⁷Lu-DOTA-TATE and yttrium-90-DOTA⁰,Tyr³-octreotide (⁹⁰Y-DOTA-TOC) in 8 (25%), and ⁹⁰Y-DOTA-TOC in 2 (6%) patients. No adverse effects of PRRT were recorded excerpt one patient who has died soon after the first therapy due to ileus after surgery.

Response to PRRT according to response evaluation criteria in solid tumors (RECIST) 1.1. criteria showed that 9 (28%) patients had disease progression, 16 (50%) had stable disease, and 7 (22%) had partial remission. Significantly shorter time until progression or death of 18 months was detected for patients with disease progression than for other groups with stable disease (34.5 months, P<0.02) and partial remission (35 months, P<0.05). However, the values obtained for overall survival were not significantly different between the studied groups being 33 months in subjects with disease progression, and 34.5 and 35 months in groups with stable disease and partial remission, respectively. In 6 subjects, an asymptomatic low hemoglobin level was detected that did not require intervention (Grade1). In 2 subjects, nephrotoxicity occurred with glomerular filtration rate (GFR) values below 30mL/min/1.73m² (Grade3).

It can be concluded that PRRT according to a three-day nephroprotection protocol is a reliable and safe method of treatment for advanced NEN. Longer time to disease progression and overall survival in most patients underline the great potential of this treatment method in patients with advanced NEN.

SCF (Skp1-Cullin1-Fbox protein) is a multi-subunit RING-type E3 ligase and plays critical roles in various pivotal physiological and pathological processes by mediating the ubiquitination and degradation of key proteins. F-box proteins directly bind substrates, thereby determining their specificity, stability, and function. However, the regulatory mechanisms of FBXO21 degradation in human cancers remain largely elusive. In this study, we demonstrated that Neddylation-ROC1 E3 ligase regulates the protein level of FBXO21. Mechanistic studies revealed that Neddylation-ROC1 targeted FBXO21 for ubiquitination and degradation. Moreover, we found that FBXO21 depletion increased p53 protein stability by delaying its degradation, followed by increasing the transcriptional level of p21. Taken together, our findings reveal a previously unrecognized mechanism by which FBXO21 is regulated by Neddylation modification and regulates the p53-p21 signaling pathway.

This case report and literature review of previously published cases describe the rare complication of cerebral aspergillosis in paediatric neuro-oncology patients. A boy in early childhood with high-risk medulloblastoma developed recurrent episodes of febrile neutropenia, persistent headache and cerebrospinal fluid (CSF) pleocytosis following surgical resection and two courses of intensive chemotherapy. Despite broad-spectrum antibiotic therapy, the fever remained unresolved. He subsequently developed worsening headache along with ongoing CSF pleocytosis, raising suspicion of meningitis. Blood and cerebrospinal cultures were negative, and later, cerebral MRI revealed multiple ischaemic lesions and raised suspicion of large-vessel vasculitis with arterial occlusions. Regardless of adding methylprednisolone and amphotericin to the broad-spectrum antibiotic treatment, the boy developed hemiparesis, coma and seizures preceding death. Autopsy findings revealed cerebral aspergillosis and infiltration of inflammatory cells along the blood vessels.

Obstructive Sleep Apnoea (OSA) is a common, yet underdiagnosed disorder, with significant health implications. Continuous positive airway pressure (CPAP) remains the reference standard and first-line therapy. However, successful CPAP usage is influenced by factors such as access, cost, tolerance, patient education, early troubleshooting, and long-term adherence, all of which can be challenging and resource-demanding. Adding therapeutic options to the armamentarium is therefore welcome. There is a need for clinicians to be abreast of all the available therapeutic options for treatment of OSA.

We conducted an extensive literature review of the published studies that were conducted using non-CPAP pharmacotherapeutic modalities for OSA.

This narrative review summarises the current landscape of OSA pharmacotherapy, focusing on mechanisms of action, clinical trial evidence, and endotype-based selection strategies. Emerging therapies such as the atomoxetine-oxybutynin combination and topiramate show promise in reducing severity of OSA, and improving sleep quality. GLP-1 receptor agonists like liraglutide and tirzepatide offer benefits beyond reducing the severity of OSA. Other agents such as sulthiame, solriamfetol, and pitolisant have also demonstrated efficacy. Wake-promoting agents like modafinil and armodafinil target the commonest symptom of OSA, sleepiness.

This review provides a practical, endotype-aligned summary of pharmacologic options for the management of OSA.

Objective: To explore the clinical characteristics, efficacy and safety of different therapeutic regimens in patients with anti-MDA5 antibody positive dermatomyositis (anti-MDA5⁺DM) stratified by disease risk, and to analyze the influencing factors for prognosis. Methods: This was a retrospective cross-sectional study. Clinical data of 82 patients with anti-MDA5⁺DM admitted to the First Affiliated Hospital of Guangxi Medical University from January 2018 to June 2024 were retrospectively analyzed. All patients were stratified into low-risk group and intermediate-high-risk group based on the FLAIR model, a predictive model for mortality risk in amyopathic dermatomyositis combined with interstitial lung disease. Meanwhile, patients were divided into four groups according to treatment regimens: Regimen A: glucocorticoids combined with calcineurin inhibitors and cyclophosphamide; Regimen B: glucocorticoids combined with Janus kinase inhibitors with or without calcineurin inhibitors; Regimen C: glucocorticoids combined with calcineurin inhibitors; Regimen D: glucocorticoids combined with cyclophosphamide. The clinical manifestations, laboratory parameters, infection events and survival outcomes were compared among groups with different risk stratification and different treatment regimens. Multivariate logistic regression analysis was performed to identify clinical indicators independently associated with all-cause mortality. Results: Among the 82 patients with anti-MDA5⁺DM, 19 (23.2%) were males and 63 (76.8%) were females, with a median age of 50 years (range, 37-63 years). The incidence of cough was higher in the intermediate-high risk group [44 cases (74.6%)] than that in the low-risk group [10 cases (43.5%)] (χ²=7.12, P=0.008). The intermediate-high risk group also exhibited higher frequencies of expectoration [35 cases (59.3%) vs. 7 cases (30.4%), χ²=5.53, P=0.019], dyspnea [37 cases (62.7%) vs. 8 cases (34.8%), χ²=5.21, P=0.022] and fever [36 cases (61.0%) vs. 6 cases (26.1%), χ²=8.08, P=0.004]. Median serum ferritin level was 1 545.3 (936.8, 2 376.9) μg/L in the intermediate-high risk group versus 442.8 (138.9, 759.0) μg/L in the low-risk group (Z=-4.89, P<0.001). The intermediate-high risk group had significantly elevated median levels of lactate dehydrogenase [371.0 (302.0, 473.0) vs. 242.0 (208.0, 318.0) U/L, Z=-4.95, P<0.001], creatine kinase [87.0 (60.0, 254.0) vs. 45.0 (34.0, 113.0) U/L, Z=-2.83, P=0.005], carcinoembryonic antigen [6.8 (3.2, 12.5) vs. 3.8 (2.4, 6.0) μg/L, Z=-2.32, P=0.021], aspartate aminotransferase [74.0 (47.0, 133.0) vs. 45.0 (31.0, 55.0) U/L, Z=-3.44, P=0.001], C-reactive protein [7.6 (2.6, 16.3) vs. 2.4 (0.7, 5.0) mg/L, Z=-3.24, P=0.001] and erythrocyte sedimentation rate [42.0 (23.8, 63.5) vs. 23.0 (13.0, 34.0) mm/1 h, Z=-3.36, P=0.001].The prevalence of periorbital edematous erythema was significantly lower in the intermediate-high risk group [29 cases (49.2%)] compared with the low-risk group [17 cases (73.9%)] (χ²=4.12, P=0.042). The median immunoglobulin M level was markedly decreased in the intermediate-high risk group [1.2 (0.9, 1.6) g/L] relative to the low-risk group [1.7 (1.2, 2.8) g/L] (Z=-2.66, P=0.008).Complete follow-up data were obtained from 78 patients. The all-cause mortality rate (13.0% vs. 38.2%) and infection rate (6.7% vs. 57.1%) of the low-risk group were obviously lower than those of the intermediate-high-risk group. Within each risk stratum, there was no statistically significant difference in the incidence of severe infections among the four treatment regimens. Regimen A was associated with the highest survival rate among patients in the intermediate-high-risk group. Taking Regimen A as the reference, Regimens B, C and D were correlated with higher mortality risk, with corresponding OR values as follows: Regimen B OR=0.07 (95%CI 0.01-0.43, P=0.002), Regimen D OR=0.07 (95%CI 0.01-0.62, P=0.008), Regimen C OR=0.06 (95%CI 0.01-0.41, P=0.001).Multivariate logistic regression analysis revealed that rapidly progressive interstitial lung disease (RP-ILD) and dysphagia were independently correlated with mortality outcomes: RP-ILD (OR=24.95, 95%CI 1.47-422.55, P=0.026), dysphagia (OR=11.62, 95%CI 1.23-110.15, P=0.033). Positive anti-Ro52 antibody (OR=6.40, 95%CI 0.90-45.47, P=0.063) and elevated C-reactive protein (OR=1.04, 95%CI 0.99-1.10, P=0.091) showed a trend toward higher mortality risk. Conclusions: In patients with intermediate-high-risk anti-MDA5⁺DM, inflammatory biomarkers and clinical symptoms were positively associated with adverse mortality outcomes. RP-ILD and dysphagia were independently correlated with all-cause mortality. Among intermediate-high-risk patients, the regimen combining glucocorticoids, calcineurin inhibitors and cyclophosphamide was associated with higher survival probability, without an increased incidence of severe infections.

A retrospective analysis was conducted of 29 patients with postoperative bronchopleural fistula. All patients had fistulas ≤5 mm in diameter and underwent bronchoscopic submucosal polidocanol injection. The overall treatment efficacy rate was 86.2%. After treatment, Karnofsky Performance Status and dyspnea scores improved significantly compared with pretreatment values (both P<0.05). Post-procedural complications included fever in 3 patients (10.3%), mild hemoptysis in 4 (13.8%), and worsening pneumothorax in 1 (3.4%); no procedure-related infections or deaths occurred. These findings suggest that bronchoscopic submucosal polidocanol injection is an effective and safe treatment for postoperative bronchopleural fistulas ≤5 mm in diameter.

Objective: To summarize the clinical features, imaging findings, and diagnostic and therapeutic experience of adult patients with congenital pulmonary vein atresia (CPVA), in order to improve clinicians' awareness of this rare disease. Methods: The clinical data of 2 adult patients initially diagnosed with CPVA in our hospital were retrospectively analyzed. In combination with literature retrieved from PubMed and Web of Science up to June 2025, we performed a pooled analysis of CPVA cases diagnosed at age ≥18 years. A total of 30 cases from 27 articles were included; together with 2 cases, a total of 32 cases were analyzed. Their clinical manifestations, imaging characteristics, treatment, and prognosis were summarized. Results: Both of our 2 patients were female, aged 24 and 68 years. Case 1 presented with cough and blood-streaked sputum during pregnancy, with symptom relief after delivery; imaging revealed absence of the right pulmonary veins and a right aortic arch. Case 2 presented with chronic cough and was found to have right upper pulmonary vein atresia with collateral circulation. Among the 32 pooled patients, the median age at diagnosis was 25 years. The main symptoms were hemoptysis (13 cases), dyspnea (11 cases), and cough with sputum (6 cases); 5 cases were asymptomatic. Unilateral involvement occurred in 24 cases (right 16, left 8). Conservative treatment was given in 16 cases, and pneumonectomy in 8 cases. Most patients improved after conservative or surgical treatment, with only 1 death due to postoperative complications. On imaging, CPVA often manifested as non-visualization of the affected pulmonary veins, interstitial lung changes, and systemic-to-pulmonary collaterals, and was easily misdiagnosed as interstitial lung disease or infectious lesions. Conclusion: Although CPVA is rare in adults, some cases can be well compensated and remain undiagnosed until adulthood or even old age. The clinical manifestations are nonspecific, and imaging examinations often provide the first clue to diagnosis; therefore, vascular malformations should be considered in the differential diagnosis of unilateral pulmonary lesions. Treatment should be individualized: conservative follow-up is suitable for asymptomatic or mild cases, whereas surgery or interventional therapy may be considered for those with massive hemoptysis or severe symptoms.

Objective: To investigate the high-resolution CT (HRCT) imaging phenotypes, clinical characteristics and prognostic differences between emphysema-dominant (CPFE-E) and fibrosis-dominant (CPFE-F) subtypes of combined pulmonary fibrosis and emphysema (CPFE). Methods: A retrospective study of 383 CPFE patients was retrospectively enrolled. Based on quantitative HRCT analysis of emphysema and fibrosis proportions, patients were classified into CPFE-E group (emphysema proportion>fibrosis proportion, n=96; 90 men; median age 65 years) and CPFE-F group (fibrosis proportion>emphysema proportion, n=287; 230 men; median age 65 years). Clinical features, treatment regimens, and survival rates (Kaplan-Meier method) were compared, with Cox regression estimating Hazard ratio (HR) and 95%CI of emphysema/fibrosis subtypes on all-cause mortality. Results: The CPFE-E group had higher median emphysema proportion (12% vs. 1%, W=24 101.00, P<0.001), male predominance (93.8% vs. 80.1%, χ²=9.70, P=0.002), smoking index (650 vs. 400 pack-years, W=16 049.50, P=0.014), and bronchodilator use (39.6% vs. 22.0%, χ²=11.52, all P<0.001), but lower diabetes prevalence (6.3% vs. 18.5%, χ²=8.24, P=0.004). Survival analysis revealed lower 2-year survival in CPFE-E (18/96 vs. 51/287); however, the long-term survival trend over the entire follow-up period (median, 390 days) showed no significant difference between the two groups (21/96 vs. 58/287, log-rank P=0.594). Multivariate Cox regression showed that each 1% increase in emphysema proportion was associated with a 6% increase in mortality risk in the CPFE-E group (adjusted HR=1.06, 95%CI: 1.04-1.08, P<0.001), whereas fibrosis proportion significantly increased mortality risk only in CPFE-E (HR=1.24, 95%CI:1.15-1.33, P<0.001). Conclusion: CPFE imaging phenotypes can be classified into CPFE-E and CPFE-F, which show marked heterogeneity. Emphysema proportion is an independent risk factor for prognosis in CPFE-E group. Subtype-oriented individualized management may improve clinical outcomes.

Objective: To preliminarily evaluate the efficacy and safety of sotatercept in patients with pulmonary arterial hypertension (PAH) in China. Methods: This single-center, retrospective case series analysis included seven consecutive PAH patients treated at Ruijin Hainan Hospital, Shanghai Jiao Tong University School of Medicine, who received sotatercept in addition to stable background therapy from May to December 2025. Key efficacy indicators included 6-minute walk distance (6MWD), World Health Organization functional class (WHO FC), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and systolic pulmonary artery pressure (PASP). The core safety indicators were the dynamic changes in hemoglobin (Hgb) and platelet count (PLT). Results: Of the seven patients treated with sotatercept, one received only a single dose and discontinued for personal reasons, and was therefore excluded from subsequent analysis. The remaining six patients completed one-month follow-up, with three completing both one-and three-month follow-ups. At one month, 6MWD significantly improved in five of six patients (5/6), with further improvement in two of three patients (2/3) at three months. At the one-month follow-up, NT-proBNP significantly decreased in five of six patients (5/6) compared to baseline, with further reduction in one of three patients (1/3) at the three-month follow-up. At the three-month follow-up, echocardiographic estimates of pulmonary artery pressure decreased in two of three patients (2/3), and WHO FC improved in two of three patients (2/3). Among the six patients, one (1/6) had a delayed sotatercept dose due to an excessive increase in hemoglobin, and one developed a decrease in platelet count; no other adverse reactions occurred. Conclusions: Sotatercept demonstrated significant short-term improvements in cardiac function and exercise capacity in Chinese PAH patients, with a manageable safety profile. However, due to the small sample size and short follow-up period, these findings require further validation through large-scale, long-term prospective studies.

To compare the risk of moderate or severe exacerbations of chronic obstructive pulmonary disease (COPD) among new users of azithromycin versus roflumilast in a population of patients with active COPD treated in routine clinical practice.

Target trial emulation.

Optum Clinformatics Data Mart Database from 1 March 2011 to 31 August 2024.

Patients aged >40 years with active COPD and at least 183 days of continuous insurance enrolment who initiated a new oral prescription for maintenance azithromycin or roflumilast. Those with evidence of other pulmonary conditions or alternative indications for azithromycin were excluded. Propensity score matching was used between treatment groups.

The primary outcome was time to first moderate or severe COPD exacerbation. Cox proportional hazards models estimated hazard ratios.

A total of 7550 matched pairs of patients initiating azithromycin versus roflumilast were included in the cohort. The mean age of patients was 70 years, and 56% were women. The unadjusted incidence of a first moderate or severe COPD exacerbation among patients in the cohort receiving azithromycin or roflumilast was 1.2 per person year. Compared with roflumilast, azithromycin was associated with a 17% reduction in the hazard of first moderate or severe COPD exacerbation (hazard ratio 0.83, 95% confidence interval (CI) 0.79 to 0.87; number needed to treat 15, 95% CI 12 to 21). These results were robust across a range of prespecified sensitivity and subgroup analyses.

Among patients with active COPD, azithromycin use was associated with a reduced likelihood of moderate or severe COPD exacerbations compared with roflumilast use. Although this study did not assess the comparative safety of these agents, it provides evidence on treatment outcomes that may complement forthcoming data from a large randomised controlled trial.

Centre for Open Science Real-World Evidence Registry https://osf.io/95d2v.