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PubMed2026

Diagnostic and Predictive Value of Circulating and Exosomal microRNAs in Ferroptosis-Associated Neurological Conditions: A Systematic Review and Meta-analysis.

Circulating microRNAs (miRNAs) have emerged as potential non-invasive markers for intracranial pathology, yet their diagnostic accuracy and relationship with ferroptosis-mediated neuronal damage remain poorly defined. The primary objective of this study was to evaluate the diagnostic and predictive potential of circulating and exosomal miRNAs across ferroptosis-associated neurological conditions and to explore their associations with ferroptosis-related pathways. Following PRISMA-DTA guidelines, a systematic literature search was conducted across PubMed, Scopus, Cochrane, and ScienceDirect, identifying 205 records. After screening for human clinical cohort validation, 7 studies were included in the qualitative synthesis and 5 in the quantitative meta-analysis. Pooled Area-under-the-Curve (AUC) was calculated using a random-effects inverse-variance model, while prognostic correlation coefficients (r) were synthesized using Fisher's Z-transformation. Methodological quality was assessed via QUADAS-2. Analysis of 7 clinical cohorts provided heterogeneous evidence on the diagnostic and prognostic potential of miRNAs. Random-effects pooling of the two eligible diagnostic AUC estimates yielded an exploratory pooled AUC of 0.87 (95% CI, 0.79-0.94; I2 .90%). Prognostic synthesis of Group 2 identified an exploratory association between miRNA levels and clinical severity scales (exploratory pooled correlation coefficient of 0.67 (95% CI: 0.56-0.76; I2 .714.4%). Selected miRNAs were mapped to ferroptosis-associated regulators, including SLC7A11, ABCB8, and SLC40A1. Exosomal miRNAs hold potential to indicate disease-associated molecular information, although comparative clinical evidence remains yet to be explored. Circulating and exosomal miRNAs show promising diagnostic and prognostic potential across selected neurological conditions. These findings highlight a potential mechanistic association between miRNA expression and ferroptosis-mediated neuronal injury.

Humans↗

PubMed2026

Ruling out pediatric bacterial epididymo-orchitis with urinalysis - The case for minimizing unnecessary antibiotic prescription.

INTRODUCTION: Epididymo-orchitis in pediatric patients is predominantly non-bacterial, often stemming from viral or reactive etiologies. Despite guidelines recommending conservative management for non-bacterial cases, antibiotic overtreatment remains prevalent in the outpatient setting. We evaluated the diagnostic accuracy of urinalysis in ruling out bacterial infection to support antibiotic stewardship in this population. METHODS: We conducted a cross-sectional diagnostic accuracy study using electronic health records from a large health maintenance organization in Israel. The cohort included patients younger than 18 years with a diagnosis of epididymo-orchitis or clinically overlapping entities (acute scrotum, appendage torsion) who had paired urinalysis and urine culture results within one week of diagnosis. Logistic regression and ROC curve analysis were performed to assess the ability of urinalysis parameters to predict positive urine cultures. RESULTS: Of 682 eligible cases, confirmed bacterial infection was rare, occurring in only 17 patients (2.5%). Nitrite positivity was the strongest independent predictor of infection (OR 43.98; p < 0.001). A prediction model incorporating all urinalysis parameters yielded an area under the curve (AUC) of 0.825 and achieved a 97.7% classification accuracy for correctly predicting negative cultures. Despite the low prevalence of infection, antibiotics were prescribed in 237 cases (34.7%). Urinary anatomic abnormalities were significantly associated with culture positivity. CONCLUSIONS: Bacterial coinfection in pediatric epididymo-orchitis is uncommon. Urinalysis serves as a highly accurate screening tool to rule out bacterial etiology. A negative urinalysis supports withholding antibiotics in this setting, reserving treatment for children with positive markers or known anatomic abnormalities. This evidence-based approach This evidence-based approach has the potential to reduce unnecessary antibiotic exposure, however prospective studies are needed to validate these findings before broad implementation.

Humans↗

PubMed2026

Cefoxitin versus cefotaxime as empirical treatment of spontaneous bacterial peritonitis in liver cirrhotic patients: randomized controlled clinical trial.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhosis requiring immediate empirical antibiotic therapy. Third-generation cephalosporins are the traditional agents of choice; however, increasing clinical failure rates necessitate the evaluation of alternative antibiotics to ensure optimal therapeutic outcomes. The aim was to investigate the efficacy of cefoxitin versus cefotaxime for SBP treatment. METHODS: A randomized clinical trial was conducted on 140 cirrhotic patients with community-acquired SBP at Al-Rajhy Liver University Hospital, Assiut, Egypt. Patients were randomized to receive either cefotaxime (n = 70) or cefoxitin (n = 70), 2 g every 8 h for 5 days. Polymorphonuclear neutrophil (PMN) counts were measured upon admission, on Day 2 and on Day 5. Clinical response rates at Days 2 and 5, development of hepatorenal syndrome, length of stay and mortality were assessed. RESULTS: According to intention-to-treat analysis, clinical response rates at Day 2 were 74.2% in the cefotaxime group and 80% in the cefoxitin group, while at Day 5, they were 71.4% and 74.3%, respectively (P = 0.704). The PMN counts at Days 0, 2 and 5 showed no significant differences between the cefotaxime and cefoxitin groups (P = 0.889, 0.909 and 0.360, respectively). The incidence of hepatorenal syndrome was 7.1% in the cefotaxime group compared with 8.6% in the cefoxitin group (P = 0.753), and mortality was 15.7% and 12.9%, respectively (P = 0.629). CONCLUSIONS: Cefoxitin showed comparable effectiveness to cefotaxime but may be utilized in selected clinically stable SBP patients.

Humans↗

PubMed2026

Cognitive Behavioral Therapy vs Media Literacy for Prevention of Gaming Disorder and Unspecified Internet Use Disorder: A Randomized Clinical Trial.

IMPORTANCE: Mitigating the harmful effects of digitalization on youth mental health is essential. OBJECTIVES: To evaluate the effectiveness of cognitive behavioral therapy (CBT) compared with a media literacy-based intervention for gaming disorder and unspecified internet use disorder and to determine whether universal or indicated prevention yields stronger benefits. DESIGN, SETTING, AND PARTICIPANTS: PROTECTconfirm was a randomized clinical trial conducted from July 1, 2020, to August 31, 2024, across 44 secondary schools in Baden-Württemberg, Germany, with 1-, 4-, and 12-month follow-up. All students were included in universal prevention analyses, whereas indicated prevention analyses included a subgroup of adolescents at high risk meeting 2 or more Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for gaming disorder or unspecified internet use disorder at baseline. INTERVENTIONS: Students were individually randomized within 90 classes to PROTECTtraining, a CBT-based program; or PROTECTinfo, a structurally parallel media literacy program. Both consisted of four 90-minute sessions delivered weekly during school hours by trained local prevention professionals under live supervision and adherence protocols. MAIN OUTCOMES AND MEASURES: The primary outcome was gaming disorder symptom severity and unspecified internet use disorder symptom severity, assessed at 12 months with a modified version of the Video Game Dependency Scale. Secondary outcomes included internalizing, externalizing, and transdiagnostic symptoms. Primary and secondary outcomes were analyzed according to the intention-to-treat principle. RESULTS: A total of 1793 students were randomized to PROTECTtraining (n = 896; mean [SD] age, 13.1 [1.5] years; 498 male students [56.1%]) or PROTECTinfo (n = 897; mean [SD] age, 13.1 [1.5] years; 484 male students [54.8%]). Participants in the subsample of 205 adolescents at high risk showed significantly lower 12-month severity of gaming disorder and unspecified internet use disorder symptoms with PROTECTtraining than with PROTECTinfo (mean [SD] Modified Video Game Dependency Scale score: 14.7 [9.7] vs 17.7 [10.3]; within-group Cohen d = -0.91 [95% CI, -1.10 to -0.72] vs Cohen d = -0.61 [95% CI, -0.80 to -0.42]; between-group Cohen d = -0.30 [95% CI, -0.55 to -0.05]), but not in the total sample (mean [SD] Modified Video Game Dependency Scale score: PROTECTtraining, 8.8 [8.3] vs PROTECTinfo, 9.4 [8.4]; within-group Cohen d = -0.11 [95% CI, -0.18 to -0.05] vs Cohen d = -0.04 [95% CI, -0.11 to 0.02]; between-group Cohen d = -0.07 [95% CI, -0.16 to 0.01]). Secondary outcomes did not differ significantly between groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of 1793 adolescents, the CBT-based intervention reduced gaming disorder symptoms and unspecified internet use disorder symptoms more effectively than the media literacy-based intervention among adolescents at high risk. These findings support the use of CBT-based approaches primarily within indicated, rather than universal, prevention. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) trial registration: DRKS00033989.

Humans↗

PubMed2026

Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.

Suicide is one of the leading causes of death among adolescents, yet little is understood about the biopsychosocial factors related to suicidality. The demographic, clinical, and biological characteristics of adolescents with and without psychiatric histories may help inform mechanistic approaches to treatment of mood disorders and suicidality. The 'characterizing the inflammatory profile and suicidal behavior in adolescents' and 'RAD arm of the Texas Resilience Against Depression' studies aimed to characterize the clinical and biological profiles of youth with suicidal behavior and youth at risk for mood disorders, compared to healthy adolescents (n = 75 in each group). Here, we report the descriptive baseline clinical and psychological characteristics of adolescents at risk of mood disorders and those with suicidal behavior. The adolescents with suicidal behavior reported 3.53 lifetime suicidal events on average, predominantly reported moderate to very severe depression (34.7%, 24%, to 9.3%), moderate to severe anxiety (58.6%), low optimism (91.9%), and mild (39.2%) to moderate (28.4%) degree of hopelessness. The at-risk adolescents predominantly reported no depression (60%) or anxiety (68.9%), moderate optimism (50%), and a positive outlook (85.7%). Healthy adolescents predominantly reported no depression (88.3%) or anxiety (93.2%), moderate optimism (59%), and a positive outlook (87%). The adolescents with suicidal behavior and those at risk of mood disorders exhibited significantly higher irritability and borderline personality disorder features (uncorrected p = 0.02 to p < 0.001) and lower resilience compared to healthy adolescents. Ongoing investigations using the longitudinal clinical and biological data will help identify the immune biosignatures of suicidality in youth.

Humans↗

PubMed2026

Matched targeted therapy use after broad genomic profiling in advanced Non-Small cell lung cancer.

INTRODUCTION: While broad genomic profiling is increasingly used in advanced NSCLC (aNSCLC), the impact of test results on subsequent guideline-concordant targeted therapy selection remains incompletely understood. METHODS: Using a merged dataset of two large, nationwide, patient-level databases, we identified patients who were diagnosed with aNSCLC 2017-2023, had potentially actionable genomic profiling findings, and initiated systemic therapy. Patients were categorized into actionability subgroups based on contemporaneous regulatory approvals and NCCN guideline recommendations. Within each subgroup, we assessed receipt of guideline-concordant targeted therapy within 24 months, including potential underuse (non-receipt of recommended treatment) and overuse (receipt of non-recommended treatment). RESULTS: Among 6620 patients (67.4% ≥65 years, 54.6% female, 68.9% White), guideline-concordant targeted therapy use varied substantially by actionability category: 2313 (89.6%) of 2582 patients with available 1st-line on-label options received them (10.4% underuse), while 212 (67.3%) of 315 patients with available later-line on-label options received them after 1st-line (32.7% underuse). Among 441 patients with available guideline-concordant off-label options, only 122 (27.7%) received them (72.3% underuse). Conversely, 238 (8.6%) of 3282 patients received matched but guideline-discordant off-label options, representing overuse of ineffective or unestablished therapies. Smoking history, squamous histology, and high PD-L1 expression were associated with lower targeted therapy receipt. CONCLUSIONS: In this cohort study of aNSCLC care, the guideline concordance of targeted therapy use varied by clinical actionability of molecular testing results. Underuse was more common in patients with later-line and off-label targeted therapy options. Patients with classical smoking-related risk profiles were substantially less likely to receive targeted therapy even when actionable alterations were identified.

Journal Article↗

PubMed2026

Reported exposure to news portrayals about mental health problems and their impact: Findings from the 2025 National Survey of Stigma and Discrimination.

OBJECTIVE: Media portrayals of people with mental illness have the power to mitigate or perpetuate stigma related to mental health. This study aimed to investigate reported real-world exposure to news media portrayals about people with mental health problems in the past 12 months and the impact of these. METHODS: Data were from a nationally representative survey of 6032 Australians exploring attitudes towards people with mental health problems. Participants were asked about their exposure to positive news stories about a person with a mental health problem, as well as negative portrayals, in which someone was harmed by a person with a mental health problem. Further questions covered the sources (traditional or social media) and impact of these exposures. RESULTS: Regression models were used to explore sociodemographic predictors of impact. Most participants reported exposure to negative news portrayals (68.4%, 95% confidence interval = [66.9, 69.8]), while fewer reported exposure to positive news stories (33.7%, 95% confidence interval = [32.3, 35.2]). Most people exposed to the negative news stories reported a negative impact (69.0%, 95% confidence interval = [67.2, 70.7]), and most exposed to positive news stories reported a positive impact (80.2%, 95% confidence interval = [77.6, 82.5]). Age and gender were associated with reported impact but not lived experience of mental illness. CONCLUSIONS: Exposure to negative news stories about mental health problems was prevalent. Given their impact on news audiences broadly, negative news stories need to be accurate and responsible to mitigate negative impacts. A renewed focus on generating and promoting positive and stigma-challenging news stories is needed to increase subsequent positive impacts.

Humans↗

PubMed2026

COMBI-I: Long-Term Overall Survival With Spartalizumab Plus Dabrafenib and Trametinib in BRAF V600-Mutant Advanced Melanoma.

The COMBI-I trial (ClinicalTrials.gov identifier: NCT02967692) evaluating spartalizumab plus dabrafenib and trametinib (sparta-DabTram, n = 267) versus placebo plus dabrafenib and trametinib (placebo-DabTram, n = 265) for BRAF V600-mutant unresectable or metastatic melanoma failed to reach its primary end point of progression-free survival at 24 months. This final analysis reports overall survival (OS) during at least 5 years of extended follow-up. At the end of the trial (August 21, 2024), the median duration of follow-up was 76.9 months (range, 73.7-83.3 months). The median OS was 61.5 months (95% CI, 41.6 to not evaluable) for the sparta-DabTram arm and 41.6 months (95% CI, 30.6 to 56.9) for the placebo-DabTram arm (hazard ratio, 0.760 [95% CI, 0.598 to 0.966]). The safety findings were consistent with the known safety profile for sparta-DabTram. The most common treatment-related adverse event (TRAE) was pyrexia (65.9% v 46.2%, respectively, in the two study arms). Grade ≥3 TRAEs were reported in 57.3% and 36.7% of patients in the two arms, respectively. The combination of sparta-DabTram appears to improve OS compared with dabrafenib and trametinib alone in patients with BRAF V600-mutant metastatic melanoma.

Adult↗

PubMed2026

Effect of brewers' yeast or beta-glucan derived from Saccharomyces cerevisiae on breast milk supply following preterm birth: the BLOOM randomised controlled trial.

OBJECTIVE: Breast milk is the optimal source of nutrition for preterm infants; however, low breast milk production is common following a preterm birth. This study aimed to determine if taking brewers' yeast or beta-glucan improves daily expressed breast milk volume. DESIGN: Randomised, blinded, parallel, placebo-controlled trial. SETTING: Three Australian tertiary-level neonatal units. PATIENTS: Mothers with a singleton or twin pregnancy who gave birth at <34 weeks' gestation. INTERVENTIONS: Mothers were randomised within 72 hours of birth into three parallel groups in a 1:1:1 ratio to receive either brewers' yeast, beta-glucan or placebo capsules for 7 days. MAIN OUTCOME MEASURE: Total expressed breast milk volume over a 24-hour period on day 7 of intervention. RESULTS: A total of 105 mothers underwent randomisation between August 2022 and April 2024 (36 brewers' yeast, 35 beta-glucan and 34 placebo). The adjusted mean difference in daily expressed breast milk volume was 94 mL/day (95% CI -51 mL/day to 239 mL/day) between the brewers' yeast and placebo groups and -25 mL/day (95% CI -173 mL/day to 123 mL/day) between the beta-glucan and placebo groups. Maternal side effects were similar across groups. CONCLUSION: We found no clear effect of short-term administration of brewers' yeast or beta-glucan on breast-milk production following preterm birth; both interventions were well tolerated. Given the small sample size, these findings do not rule out the possibility of a clinically meaningful benefit of brewers' yeast and suggest further research with a larger sample size may be warranted to clarify the potential clinical impact. TRIAL REGISTRATION NUMBER: ACTRN12622000968774.

Intensive Care Units, Neonatal↗

PubMed2026

Study of prescription-indication of antivirals for herpesviruses in a Colombian population: a cross-sectional study.

BACKGROUND: To describe the utilization patterns and therapeutic indications of antivirals used for herpesvirus infections in Colombian patients. RESEARCH DESIGN/METHODS: A cross-sectional study on the use of antivirals for treating outpatients with herpesviruses between November 2023 and January 2024 in a Colombian population database. The Micromedex® database was used to identify Food and Drug Administration (FDA)-approved indications, off-label uses, and potentially inappropriate indications. RESULTS: A total of 14,816 individuals were included (median age:53.0 years [IQR:35.0-65.0]; 60.5% women). Acyclovir was the most frequently prescribed antiviral (oral:77.3%; topical:43.4%). Overall, 56.1% received oral therapy only, 25.2% combined oral and topical therapy, and 18.7% topical therapy only. FDA-approved indications accounted for 29.1% of use (herpes zoster), off-label use for 26.9% (mainly prophylaxis in immunocompromised patients), and potentially inappropriate use for 25.3% (primarily topical treatment of herpes zoster). Acyclovir use (OR:5.93; 95%CI:4.60-7.64) and specialist care (OR:2.17; 95%CI:1.73-2.71) were associated with off-label use. CONCLUSIONS: Antiviral prescribing for herpesvirus infections in a group of patients in Colombia is largely driven by acyclovir, with a substantial proportion of off-label and potentially inappropriate use, particularly involving topical therapies for herpes zoster. These findings highlight significant gaps in adherence to evidence-based recommendations and underscore the need for targeted interventions to optimize prescribing practices.

Humans↗

PubMed2026

Venetoclax added to dose-adjusted EPOCH-R for newly diagnosed double-hit lymphomas: phase 2 results from ALLIANCE A051701, an open-label, randomised, controlled, phase 2-3 trial.

BACKGROUND: High-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6, known as double-hit lymphoma, is a highly aggressive malignancy with poor outcomes after standard chemoimmunotherapy. We aimed to study whether the addition of the BCL2-inhibitor venetoclax to chemoimmunotherapy in patients with double-hit lymphoma resulted in superior efficacy compared with chemotherapy alone. METHODS: ALLIANCE A051701 is an open-label, randomised, controlled, phase 2-3 trial in separate cohorts of patients with double-hit lymphoma and patients with double-expressor lymphoma. In this analysis, we report phase 2 results from the double-hit lymphoma cohort. Patients aged 18-80 years with newly diagnosed double-hit lymphoma and Eastern Cooperative Oncology Group (ECOG) performance status 0-2 were recruited from 41 hospitals and outpatient clinics in the USA. Patients were randomly assigned (1:1) to receive DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) either alone (DA-EPOCH-R group) or with venetoclax (DA-EPOCH-R plus venetoclax group) using permuted block randomisation schedule. All patients and investigators were aware of group assignment. DA-EPOCH-R was administered on a 21-day schedule for up to six total cycles. Venetoclax was given as 600 mg by mouth daily on days 4-8 of cycle 1 and on days 1-5 of cycles 2-6. The primary endpoint was progression-free survival in the modified intent-to-treat population inclusive of all eligible patients with centrally confirmed double-hit lymphoma. The safety analysis population consisted of all evaluable patients who received at least one dose of protocol treatment. This trial is registered with ClinicalTrials.gov (NCT03984448) and is closed to enrolment. FINDINGS: 36 patients were randomly assigned to the DA-EPOCH-R group and 37 to the DA-EPOCH-R plus venetoclax group between Oct 22, 2019, and Sept 18, 2020. Median age was 65 years (IQR 56-73) and baseline demographic factors were well balanced between groups, with 30 (45%) female and 36 (55%) male patients. Most patients (59 [89%]) were white, two (3%) were Asian, one (2%) was Black or African American, and four (6%) had unknown or unreported ethnicity. The majority of patients had MYC-BCL2 double-hit lymphoma (59 [89%] patients), advanced stage disease (57 [86%] patients), and high-intermediate/high-risk IPI score (42 [64%] patients). Median follow-up was 34·7 months (IQR 30·1-36·8). Median progression-free survival was 28·4 months (95% CI 5·2-not estimable) in the DA-EPOCH-R group (n=30) and 7·7 months (95% CI 4·7-NE) in the DA-EPOCH-R plus venetoclax group (n=36; hazard ratio [HR] 1·13, 95% CI 0·53-2·37; p=0·75). Deaths on treatment occurred in one (3%) patient in the DA-EPOCH-R group (due to dyspnoea; possibly related to treatment) and six (17%) patients in the DA-EPOCH-R plus venetoclax group (four due to sepsis [three at least possible related and one unrelated], two due to cardiac arrest [at least possibly related]), prompting early closure of the double-hit lymphoma cohort. The most common grade 3-4 non-haematological adverse event was febrile neutropenia, occurring in 15 (43%) of 35 patients in the DA-EPOCH-R plus venetoclax group and 11 (37%) of 30 patients in the DA-EPOCH-R group. The median overall survival has not been reached in either group. The 24-month overall survival estimates were 72% (95% CI 52-85) in the DA-EPOCH-R group compared with 52% (95% CI 33-68) in the DA-EPOCH-R plus venetoclax group (HR 2·49, 95% CI 1·03-6·04; p=0·038). INTERPRETATION: The addition of venetoclax to DA-EPOCH-R resulted in excess mortality, prompting early study closure. Robust accrual shows that prospective multicentre trials are feasible in double-hit lymphoma, and the outcomes in the DA-EPOCH-R group serve as a benchmark for future studies. FUNDING: National Cancer Institute of the National Institutes of Health.

Humans↗

PubMed2026

Adjuvant apatinib therapy following concurrent chemoradiotherapy in patients with high-risk nasopharyngeal carcinoma: A multicenter, prospective phase 2 study.

PURPOSE: To assess the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with apatinib in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: This multicenter, prospective, phase II study enrolled patients with newly histologically confirmed LA-NPC, who were randomly assigned to receive CCRT followed by adjuvant apatinib (investigational arm) or CCRT alone (control arm). The investigational arm received 250 mg/day of oral apatinib administered every 28 days for up to six cycles after CCRT. The primary endpoint was 3-year progression-free survival (PFS) and secondary endpoints of overall survival (OS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS) of 3-year, and safety. RESULTS: From July 2018 to September 2020, 44 and 44 patients were randomized into the CCRT-alone and CCRT and apatinib groups, respectively. The median follow-up duration 56 (range: 40.0-58.6) months. The survival outcomes were the 3-year PFS, OS, and DMFS rates in the adjuvant apatinib following CCRT group were significantly higher than those observed in the CCRT-alone group((PFS, 78.6%vs. 54.5%, p = 0.027; OS, 88.1% vs. 75.0%, p = 0.029; DMFS, 85.4%vs. 59.1%, p = 0.009). The 3-year LRFS was similar between the groups. The grade 3-4 treatment-related adverse events(TRAEs) were higher in the former group than in the latter. The most common grade 3-4 non-hematology-related adverse events were hypertension (14.3%), hand-foot syndrome (9.5%), increased transaminase levels (7.1%), and headache (7.1%). CONCLUSION: Apatinib significantly improved the treatment effects of CCRT for high-risk LA-NPC patients. Therefore, CCRT and adjuvant apatinib may represent a promising option for this patient population.

Adjuvant therapy↗

PubMed2026

Migration intentions among nigerian neurosurgeons: a national survey of workforce retention.

Physician emigration from low- and middle-income countries creates critical workforce shortages. This study explored factors influencing migration intentions among Nigerian neurosurgeons and trainees. We conducted an anonymized survey of consultant neurosurgeons, fellows, and residents practicing in Nigeria. Invitations were sent by email and professional messaging platforms, and snowball sampling was used to increase participation. The survey included quantitative and open-ended questions on demographics, income, migration plans, and retention factors. Seventy-nine respondents participated (61.5 % consultants; 93.7 % male; median age: 44 years). Nearly all practiced general neurosurgery (97.3 %), and many also performed trauma (65.3 %) and spine (61.3 %) neurosurgery. Most (85.7 %) reported that their earnings were insufficient to support their families. Nearly 40 % were considering emigration, most often citing financial pressures (88.5 %) and poor working conditions (63.5 %) as push factors. By contrast, personal or family ties (63.0 %) and relocation costs (45.2 %) were cited as reasons to stay. Respondents identified higher salaries (58.1 %) and greater investment in the health sector (51.4 %) as key measures to improve retention. In univariable analyses, younger age, income insufficiency, income dissatisfaction, and feeling undervalued at work were associated with migration intention. Financial insecurity emerged as the dominant driver of migration intentions among Nigerian neurosurgeons. In addition to salary increases, sustained investment in healthcare infrastructure and workforce support is essential to improve retention. International partnerships may complement these efforts by building neurosurgical capacity and mitigating brain drain.

Humans↗

PubMed2026

Splenic hilum nodal involvement in resected left-sided pancreatic cancer: meta-analysis.

BACKGROUND: Splenectomy is standard of care during left pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) to obtain adequate lymphadenectomy. However, evidence supporting this approach is lacking. Splenic preservation would reduce short-term morbidity and is essential for emerging oncological adjunctive therapies, including immunotherapy and personalized cancer vaccines. This study reviewed the incidence of splenic hilum nodal involvement (SHNI) in left-sided PDAC. METHODS: A systematic review of the PubMed, Embase, and Cochrane databases was performed, identifying studies published from inception to July 2026. Outcomes of interest were the rate of SHNI (station 10), overall survival, and the rate of splenic artery nodal involvement (SANI; station 11). Meta-analyses were conducted using random-effects models. Subgroup analyses for SHNI were performed per tumour localization (pancreatic neck, body, tail). RESULTS: Among 2776 screened studies, 22 with 2260 patients undergoing left pancreatectomy for PDAC were included. The pooled prevalence of SHNI was 3.7% (95% confidence interval (c.i.) 2.2% to 6.2%); 1.1% for pancreatic body PDAC (95% c.i. 0.3% to 4.3%) and 9.7% for pancreatic tail PDAC (95% c.i. 3.5% to 24.0%). SHNI was not significantly associated with survival (pooled hazard ratio 2.05; 95% c.i. 0.89% to 4.72; P = 0.072). The pooled prevalence of SANI was 39.1% (95% c.i. 25.1% to 55.1%). CONCLUSION: In patients undergoing left pancreatectomy for PDAC, the presence of SHNI is rare, particularly in pancreatic body cancer (1.1%). These findings suggest that the relevance of routine splenectomy remains unclear, especially for pancreatic body PDAC. However, because the quality of current evidence is low, further investigation in prospective studies is required.

Humans↗

PubMed2026

Prion disease mimicking rapidly progressive Alzheimer disease: case series and systematic review.

BACKGROUND: Prion disease and Alzheimer disease (AD) are common causes of rapidly progressive dementia (RPD). Although most patients with prion disease are distinguished by MRI and CSF findings, selected cases mimic rapidly progressive AD. We characterized AD-prion disease mimics within a prospective cohort and the extant literature to identify the clinical features and tests that support accurate diagnoses in these patients. METHODS: Patients with prion disease initially diagnosed as rapidly progressive AD were identified from a prospective cohort study at Mayo Clinic (February 2020-June 2026) and through systematic review of MEDLINE and Embase. RESULTS: Of 204 patients with RPD, five (2.5%) were initially diagnosed with clinically probable AD but ultimately determined to have prion disease. Systematic review identified 10 additional cases (n=15, median age-at-onset, 59 years; 67% male). Presentations reproduced amnestic (53%), dysexecutive (27%), primary progressive aphasia (13%), and posterior cortical atrophy (7%) AD phenotypes; median time from AD diagnosis to consideration of prion disease was 2 months. Diffusion-weighted MRI abnormalities were absent in Mayo Clinic cases and absent/equivocal (n=2) or overlooked (n=8) in published cases. CSF biomarkers were consistent with AD in 6/9 tested patients, with elevated total tau levels in 11/13 patients and total-tau/p hosphorylated-tau181 ratios in 5/9 patients. Real-time quaking-induced conversion assays for prions were positive in the CSF of 9/12 patients. Prion disease was confirmed by neuropathology (n=7), genetics (n=2), or real-time quaking-induced conversion (n=6) assays. CONCLUSIONS: Prion disease may rarely mimic rapidly progressive AD. Disproportionate elevations in CSF total-tau levels or total-tau/p hosphorylated-tau181 ratios should prompt consideration of prion disease.

Humans↗

PubMed2026

Immunogenicity and safety of prophylactic HPV vaccines in people living with HIV: A systematic review and meta-analysis.

Human papillomavirus (HPV) is a major global public health concern, causing genital warts and cancers of the cervix, anus, oropharynx, vulva, and penis. People living with HIV (PLWH) face a disproportionately elevated burden of HPV infection and HPV-related malignancies due to chronic immunosuppression. We conducted a systematic review and meta-analysis searching six databases from January 2006 to June 2026 without language restrictions. Twenty-five studies were included in the systematic review; 12 independent studies (N = 1,493 for HPV16) were included in the quantitative meta-analysis. Using a DerSimonian-Laird random-effects model with logit transformation, pooled seroconversion rates were: HPV16 97.8% (95% CI: 94.9-99.1%; I2 = 89.6%; 15 datasets), HPV18 94.2% (95% CI: 86.1-97.7%; I2 = 95.8%; 13 datasets), HPV6 97.0% (95% CI: 93.7-98.6%; I2 = 66.1%; 10 studies), and HPV11 97.1% (95% CI: 90.5-99.1%; I2 = 95.5%; 10 studies). CD4 count was the most consistently reported modifier of immunogenic response: HPV16 seroconversion was 98.5% in PLWH with CD4 > 350 cells/μL vs. 71.1% in those with CD4 ≤ 200 cells/μL (ACTG A5240). All three vaccine generations demonstrated high immunogenicity. Two doses of the nonavalent vaccine were non-inferior to three doses in virologically suppressed women (Papillon RCT). No vaccine-related serious adverse events were reported. GRADE certainty of evidence was moderate for HPV16, HPV6, and HPV11, and low for HPV18. Prophylactic HPV vaccination achieves high seroconversion rates across all vaccine generations in PLWH. CD4 count significantly modifies vaccine response, underscoring the importance of vaccination before severe immunosuppression develops. These findings support current international recommendations advocating HPV vaccination for all PLWH.

Humans↗

PubMed2026

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200 mg) or two subcutaneous doses (300 and 600 mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24 h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans↗

PubMed2026

Genomic epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli across humans, poultry and wastewater sectors in Douala, Cameroon.

BACKGROUND: The global health threat of antimicrobial resistance involves the human, animal and environmental sectors. Data from Cameroon are scarce. OBJECTIVES: This study aimed to define extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) rates and associated risk factors across the three sectors in Douala, Cameroon, and to define molecular characteristics of isolates. METHODS: From June 2022 to May 2023, we collected blood cultures from hospitalized patients, rectal swabs from healthy pregnant women, caeca from broiler chickens and environmental wastewater. Samples were screened for ESBL-Ec using CHROMAgar™ ESBL and cefotaxime-supplemented Tryptone Bile X-glucuronide agar. Antimicrobial susceptibility testing was performed by disk diffusion following EUCAST guidelines. Whole-genome sequencing was carried out using Illumina technology. RESULTS: Of 628 samples, 374 yielded ESBL-Ec. Prevalence was 54.6% (131/240) in pregnant women, 70.4% (169/240) in chickens and 93.1% (67/72) in wastewater. The proportion of ESBL-Ec among E. coli-positive-blood cultures was 9.2% (7/76). Multi-family household living was independently associated with ESBL-Ec carriage among pregnant women (adjusted odds ratio = 1.7, 95% CI 1.0-3.1, P = 0.03). High co-resistance (>70%) was observed for tetracycline, ciprofloxacin and trimethoprim/sulfamethoxazole. Sequencing of 32 isolates revealed 45 distinct resistance genes, including blaCTX-M-15 (n = 13, 40.6%), blaCTX-M-55 (n = 11, 34.4%) and last-resort antibiotic resistance genes mcr-1 and bla OXA-181. High-risk sequence types included ST131 (pregnant women) and ST10 (chickens). Notably, ST48 was shared between pregnant women and chickens, and ST155 between pregnant women and wastewater. CONCLUSION: Cross-sectoral ESBL-Ec in Douala exhibits high genomic diversity and alarming resistance. The occurrence of last-resort genes requires immediate One Health surveillance and coordinated interventions.

Journal Article↗