Annals of Translational Medicine

Rapid prediction of the severity of acute coronary syndrome (ACS) is crucial for appropriate intervention in emergency department. Neutrophils (Neu), lymphocytes (Lym) and monocytes (Mon) and their ratios (Neu/Lym, NLR; Mon/Lym, MLR NeuxMon/Lym, SIRI) are acknowledged to be associated with the prediction of the severity and adverse outcome of ACS patients. Here, we analysed retrospectively eosinophils (Eos) and Eos-derived novel ratios (Neu/Eos, NER; Mon/Eos, MER; Neu x Mon/Eos, SIII; Neu/Eos x Lym, NEL; Mon/Eos x Lym, MEL; Neu x Mon/Eos x Lym, SV) of first admitted 1053 ACS patients within 24 hours of symptom onset to predict ST-segment elevation of myocardial infarction (STEMI), high Gensini score (H) and cardiac dysfunction (Killip Classification l to III grades). Results showed that Eos was significantly decreased in ST (n=227), Gensini (H) (n=311) and Killip I group (n=237) (P<0.05). All Eos-derived ratios (NER, MER, SIII, NEL, MEL, SV) were significantly higher with diagnostic severity (ST, Gensini (H), and Killip I group (P<0.05). ROC analysis revealed that SIII and SV predicted ST and Gensini (H) with high specificity and sensitivity, which were similar to that of NLR, MLR and SIRI. Conclusion: Eos and Eos-derived ratios, SIII and SV in particular, are strongly linked to the prediction of the severity of ACS, along with those of well-established leukocyte ratios. The new ratios of Eos hold significant importance in emergency department for quick evaluation of ACS patients.

ObjectiveTo compare the efficacy and safety of etomidate versus ketamine as induction agents for rapid sequence intubation in critically ill adults, focusing on 28-day mortality and post-intubation hypotension. Data SourcesPubMed, Embase, and the Cochrane Library were systematically searched from inception to January 2026. Reference lists of included studies were also manually screened. Study SelectionWe included randomized controlled trials (RCTs) comparing single-dose intravenous ketamine versus etomidate for emergency rapid sequence intubation in critically ill adults ([&ge;] 18 years) in non-operating room settings (e.g., intensive care unit or emergency department). Data ExtractionTwo investigators independently screened records, extracted data using a standardized form and assessed the risk of bias using the RoB 2 tool. The certainty of evidence was evaluated using the GRADE framework. Data SynthesisSix RCTs comprising 4,108 patients (2,046 assigned to ketamine and 2,062 to etomidate) were included. The pooled analysis showed no statistically significant difference in 28-day mortality between the ketamine and etomidate groups (39.0% vs. 40.3%; relative risk [RR] 0.96; 95% CI, 0.89-1.03; p=0.29; I{superscript 2}=11%). In a prespecified subgroup analysis of patients with sepsis (n=1,546), mortality also did not differ significantly (RR 0.94; 95% CI, 0.86-1.03). However, ketamine was associated with a statistically significant increase in the incidence of post-intubation hypotension (14.2% vs. 11.3%; RR 1.25; 95% CI, 1.01-1.53; p=0.04; I{superscript 2}=0%). No significant differences were observed regarding peri-intubation cardiac arrest, first-attempt intubation success, or ventilator- and intensive care unit-free days. ConclusionsThere is no statistical difference in 28-day mortality between etomidate and ketamine for emergency intubation in critically ill adults, including those with sepsis. The higher incidence of post-intubation hypotension with ketamine suggests etomidate presents a more favorable hemodynamic safety profile in this setting. Key pointsO_ST_ABSQuestionC_ST_ABSDoes the choice between etomidate and ketamine for emergency intubation in critically ill patients impact 28-day mortality? FindingsIn this systematic review and meta-analysis of randomized controlled trials, there was no statistically significant difference in 28-day mortality between patients induced with ketamine (39.0%) and those induced with etomidate (40.3%). MeaningThe use of etomidate versus ketamine for rapid sequence intubation does not alter 28-day mortality, indicating that the choice of induction agent should be individualized.

BackgroundSevere Fever with Thrombocytopenia Syndrome (SFTS) is an acute infectious disease with high mortality. This study aimed to develop a quantitative scoring system for grading SFTS severity using dynamic clinical data. MethodsA retrospective study included 547 confirmed SFTS patients from two hospitals. Clinical data were collected over a 14-day course (divided into four phases). Patients were grouped into survivors (n=451) and non-survivors (n=96). Statistical analyses, including Kaplan-Meier curves and log-rank tests, were performed. An external validation cohort of 44 new patients was used to validate the scoring system via C-statistic, calibration curves, and decision curve analysis (DCA). ResultsOf 547 patients, 96 (17.55%) were non-survivors. Multivariate logistic regression identified six independent prognostic factors across phases: age, platelet (PLT), aspartate aminotransferase (AST), and creatinine (Cr) (days 5-7); age, red blood cell distribution width (RDW), Cr, and lactate dehydrogenase (LDH) (days 8-10); Cr and LDH (days 11-14). A scoring system (0-11 points) was developed, stratifying patients into low (0-3), intermediate (4-7), and high (8-11) risk groups, with adverse outcome rates of 1.04%, 22.92%, and 76.04%, respectively. Kaplan-Meier curves showed significant prognostic differences (log-rank P<0.001). External validation (44 cases) confirmed excellent performance: AUC 0.810-0.952, good calibration (Hosmer-Lemeshow P>0.05), and net clinical benefit (DCA Eavg 0.068-0.098, Emax 0.422-0.559). ConclusionA dynamic SFTS severity scoring system was developed and validated. Internal and external validation confirmed its reliability and clinical utility, providing a simple, practical tool for timely assessment and early intervention.

Background and ObjectivesDecision-making about resuscitating a critically ill child is complex yet common. We aimed to study the survival thresholds at which physicians, compared to parents, decide to treat or withhold resuscitating a child. Moreover, we aimed to compare physicians survival estimates with those from a nationwide registry. MethodsWe conducted a cross-sectional survey-based study in the United States. Clinical vignettes based on hypothetical survival probabilities were used to study and compare the decision thresholds for parents and physicians. Vignettes developed using the Get-With-The-Guidelines-Resuscitation registry were used to explore physicians decision thresholds and compare their survival estimates with those from the data. Thresholds were determined using mixed-effect logistic regression models. ResultsWe had decisions for 501 and 257 vignettes from 167 parents and 43 physicians, respectively. The decision threshold for survival to discharge was 5.3% (95% CI: 3.7 to 7.0) for physicians and 1.2% (95% CI: -0.8 to 3.0) for parents. Whereas the decision threshold for survival to discharge with PCPC 1 or 2 was 3.5% (95% CI: 1.1 to 7.1) for physicians and 0.6% (95% CI: -1.2 to 1.8) for parents. About 58% of the physicians overestimated the likelihood of survival. ConclusionsThe study found that the decision threshold for the physicians was higher than that for the parents (5.3% vs. 1.2%). This illustrates that parents still want to attempt resuscitation at a survival probability where physicians would recommend withholding resuscitation. These findings have implications for clinical practice and counseling the parents of critically ill hospitalized children.

The red cell distribution width (RDW) is a recognized prognostic marker in sepsis, yet its dynamic changes over time and their relationship with outcomes remain unexplored. This study aimed to identify distinct RDW trajectories during the early phase of sepsis and evaluate their association with mortality. We conducted a retrospective cohort study using data from the MIMIC-IV database (n=3,813) as the derivation cohort and from the First Affiliated Hospital of Kunming Medical University (n=467) for external validation. Sepsis patients with at least seven RDW measurements within the first ten days of hospitalization were included. Group-based trajectory modeling (GBTM) was employed to identify RDW trajectories. A three-trajectory model was selected based on model fit indices and clinical interpretability: Trajectory 1 (Slow-Decrease, 32.97%), Trajectory 2 (Slow-Increase, 43.30%), and Trajectory 3 (Fluctuating-Rapid Decrease, 23.73%). In the our study, Cox models adjusted for confounders revealed that, compared to Trajectory 1, Trajectory 3 was independently associated with significantly increased 30-day (HR 1.47, 95% CI 1.17-1.84) and 90-day mortality (HR 1.54, 95% CI 1.25-1.88). Conversely, Trajectory 2 was associated with the most favorable survival rates. Kaplan-Meier analysis consistently showed the highest mortality in the Trajectory 3 group. External validation confirmed the models robustness and the consistent prognostic value of the identified trajectories. We conclude that dynamic RDW trajectories, readily identifiable from routine clinical data, provide significant prognostic information beyond single-time-point measurements and can aid in the risk stratification of sepsis patients.

Background and AimsThe prognosis of interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) has not been studied as extensively as IPF. This study aimed to evaluate baseline factors associated with mortality in non-IPF ILD, including demographic characteristics, respiratory function test (RFT), comorbidities, and ILD subtypes. MethodsThis retrospective cohort study analysed prospectively collected data of patients with non-IPF ILD at a single tertiary centre in Malaysia (2010-2023). Patients without baseline RFT or HRCT were excluded. Survival was assessed using Kaplan-Meier analysis, and mortality predictors were identified using Cox regression. ResultsThe mean age was 60 {+/-} 15 years, with a male-to-female ratio of 1:3. Indian ethnicity constituted the largest group (n = 109, 47.6%). The mean baseline forced vital capacity (FVC) was 53.3 {+/-} 21% predicted. An FVC <50% predicted, age [&ge;]50 years at diagnosis, specific ILD subtypes, and ethnicity were independently associated with mortality. Compared with Malays, both Chinese (hazard ratio [HR] 9.86, 95% confidence interval [CI] 1.27-76.89, p = 0.037) and Indians (HR 8.59, 95% CI 1.14-64.69, p = 0.001) were associated with a higher risk of death. Kaplan-Meier analysis demonstrated significant differences in survival across non-IPF ILD subtypes (log-rank p = 0.048), with hypersensitivity pneumonitis showing the poorest prognosis (mean survival 6.1 years). ConclusionEthnicity emerged as an independent prognostic factor for mortality in non-IPF ILD. The underlying mechanisms remain unclear and may reflect differences in genetic variation, cultural factors, or environmental exposures. Larger prospective studies are required to validate these findings.

BackgroundDiabetes mellitus (DM) remains a major global health challenge and is associated with vision-threatening complications, including diabetic macular edema (DME), a leading cause of visual impairment. Dyslipidemia has been implicated in the development of macular edema through mechanisms involving vascular permeability, endothelial dysfunction, and chronic inflammation. However, evidence regarding the relationship between lipid abnormalities and macular edema remains inconsistent across studies. AimThis study aimed to evaluate the association between abnormal lipid profiles and diabetic macular edema among patients with type 2 diabetes mellitus attending Kilimanjaro Christian Medical Centre (KCMC). MethodsA hospital-based analytical cross-sectional study was conducted among 296 diabetic outpatients at KCMC. Participants underwent comprehensive ophthalmic evaluation including fundoscopy and imaging with optical coherence tomography (OCT) for assessment of macular edema. Blood samples were collected for biochemical lipid analysis. Data were cleaned and analyzed using STATA version 17. ResultsDiabetic macular edema was identified in 56.4% (167/296) of participants. Abnormal lipid parameters were common, with elevated total cholesterol observed in 48.6%, triglycerides in 43.6%, low-density lipoprotein (LDL) in 36.1%, and reduced high-density lipoprotein (HDL) in 38.9% of patients. Elevated total cholesterol, triglycerides, and LDL levels showed significant associations with macular edema (p < 0.05). After multivariable adjustment, serum triglycerides remained independently associated with macular edema (p = 0.002). ConclusionDyslipidemia demonstrated a significant association with diabetic macular edema, with serum triglycerides emerging as an independent predictor. These findings highlight the importance of lipid monitoring, lifestyle modification, and strengthened screening strategies in reducing the burden of vision-threatening diabetic complications.

ObjectiveWe aimed to prospectively validate and compare published prediction models and clinician-assigned triage categories for early trauma care. DesignProspective multicentre cohort study. SettingThree public hospitals in urban India: one secondary care hospital in Mumbai and one tertiary care teaching hospitals in Delhi and Kolkata each. ParticipantsAdult patients aged over 18 years presenting to the emergency department with a history of trauma between 2016 and 2022. A total of 13,041 patients were included in the final analysis. MethodsWe externally validated five published trauma prediction models (GAP, Gerdin, KTS, MGAP, and RTS) and clinician-assigned triage categories based on initial assessment. The primary outcome was 30-day all-cause mortality. Models were recalibrated using a separate updating sample prior to evaluation, and model performance was assessed in terms of discrimination (AUC), calibration (calibration slope and plots), and decision curve analysis. ResultsAll models and clinician gestalt-based triage demonstrated excellent discrimination (AUC range: 0.90-0.96) and good calibration after updating. The GAP model achieved the highest AUC (0.96, 95% 0.94-0.97), and RTS demonstrated the highest sensitivity (0.70). ConclusionSimple, physiology-based prediction models and clinician gestalt both demonstrated excellent performance in predicting 30-day mortality among adult trauma patients in Indian emergency departments. These findings provide a practical foundation for further development of trauma triage systems.

BackgroundBoth hemorrhagic fever with renal syndrome (HFRS) and scrub typhus (ST) are acute zoonotic infectious diseases. There is an overlap in their epidemiological characteristics and clinical manifestations, posing challenges for early differential diagnosis. This study aims to identify predictive factors for these two diseases to provide a basis for early diagnosis. Method/FindingsA retrospective analysis was conducted on the clinical data of patients diagnosed with HFRS and ST at the First Affiliated Hospital of Dali University. Logistic regression analysis was employed to explore independent risk factors for the early differential diagnosis of these two diseases, and a nomogram model was constructed based on these risk factors. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC). The nomogram was utilized to visually present the predictive variables. Decision curve analysis (DCA) was performed to assess the clinical utility of the model. ResultsA total of 235 patients each with HFRS and ST were included in this study. After adjusting for confounding factors, the results of multivariate logistic regression analysis revealed that sex (male) (adjusted odds ratio [ajOR]: 2.093, 95% confidence interval [CI]: 1.107 - 3.957, P = 0.018), positive proteinuria (ajOR: 4.937, 95% CI: 2.427 - 10.042, P < 0.001), creatinine (CREA) (ajOR: 1.009, 95% CI: 1.003 - 1.015, P = 0.005), heart rate (ajOR: 0.981, 95% CI: 0.966 - 0.997, P = 0.018), and conjunctival congestion (ajOR: 16.167, 95% CI: 5.326 - 49.072, P < 0.001) were independent risk factors for differentiating HFRS from ST. The AUC of the model constructed based on these five independent risk factors was 0.856. ConclusionSex (male), positive proteinuria, elevated CREA, decreased heart rate, and conjunctival congestion are effective predictive factors.

BackgroundAI-based radiomics has demonstrated promising diagnostic performance for pancreatic cystic neoplasms, yet clinical translation remains limited. Whether this reflects insufficient model performance or structural limitations of the evidence base remains unclear. MethodsWe performed a systematic review and diagnostic test accuracy meta-analysis of AI-based radiomics in pancreatic cyst (2015-2025), addressing two clinically relevant tasks (Q1: cyst type differentiation/Q2: malignancy or high-grade dysplasia prediction). Training and validation datasets were synthesized independently using hierarchical models. Study evaluation extended beyond diagnostic performance to a four-dimensional framework integrating RQS 2.0, METRICS, TRIPOD+AI and PROBAST+AI explicitly contrasting pooled diagnostic performance with reporting quality, methodological rigor, and risk of bias. The review was pre-registered (PROSPERO) and conducted according to PRISMA 2020. ResultsTwenty-nine studies were included (Q1: n = 15; Q2: n = 14), predominantly retrospective and single center. Training-based analyses showed high apparent diagnostic performance for Q1 (pooled sensitivity/specificity: 0.89 [95% CI, 0.85-0.92]/ 0.90 [0.85-0.93]), but there was substantial heterogeneity ({tau}{superscript 2} = 0.56/0.78; {rho} = 0.38). Validation-based performance remained high (0.86 [0.82-0.89]/ 0.88 [0.81-0.93]), while heterogeneity persisted and prediction regions exceeded confidence regions. Training-based analyses demonstrated similarly high apparent performance (0.88 [0.79-0.95]/0.89 [0.81-0.94]) for Q2, with pronounced heterogeneity ({tau}{superscript 2} = 1.98/1.61; {rho} = 0.63). Validation-based performance was slightly lower, yet still clinically comparable (0.82 [0.75-0.89]/0.86 [0.80-0.91]), and heterogeneity persisted ({tau}{superscript 2} = 0.71/0.43; {rho} = 0.15). Across both tasks, high diagnostic accuracy occurred alongside incomplete reporting, limited validation and an elevated risk of bias. ConclusionAI-based radiomics for pancreatic cysts has reached a structural performance plateau. Further improvements in diagnostic accuracy alone are insufficient to achieve clinical translation and must be accompanied by a paradigm shift from performance-driven model development toward decision-anchored study designs, robust validation strategies, transparent reporting standard, and clinically integrated evaluation frameworks. SummaryAlthough pancreatic cystic lesions are increasingly being detected, imaging-based decision-making remains limited, particularly regarding differentiating between cyst types and stratifying malignancy risk. In this PRISMA-compliant and PROSPERO-registered systematic review and meta-analysis of diagnostic tests, we evaluated the use of AI-based radiomics for these two tasks, as well as its contextualized performance. In addition, a four-dimensional framework was employed to conduct the evaluation, incorporating diagnostic accuracy, reporting quality, risk of bias, and radiomics maturity. Across studies published between 2015 and 2025, the pooled diagnostic performance was consistently high, with only modest declines observed from the training to the validation stage. Nevertheless, considerable heterogeneity between studies and limited transportability remained evident. Multidimensional evaluation indicated a systematic dissociation between reported performance and methodological robustness, characterized by incomplete reporting, restricted validation, and an elevated risk of bias. These limitations were consistent across both clinical questions and were not resolved by increasing model complexity. The findings of this meta-analysis suggest that the structural performance of AI-based radiomics for pancreatic cysts has plateaued. To progress towards clinical translation, it is necessary to employ study designs anchored in decision-making processes, robust multi-center validation, and transparent, reproducible evaluation frameworks. This is preferred to further optimization of model architecture alone.

Sepsis is a complex condition with a time-dependent evolution. Longitudinal biomarker dynamics could help us to better characterise sepsis. We hypothesised that the kinetics of biomarkers are associated with sepsis and with the intensity of organ dysfunction, and may have predictive capacity for patient survival. This single-centre, prospective, observational study included adult patients presenting to the Emergency Department (ED) with suspected infection. Patients were included in the study if they had a National Early Warning Score 2 (NEWS 2) of 3 or higher. Blood samples were obtained at baseline, 4hs and 24 hs. Linear mixed models were constructed to analyse the association between biomarker concentrations over time, sepsis diagnosis and organ dysfunction severity. Joint models were used to evaluate the predictive ability of individual biomarker kinetics during the first 24 hours for in-hospital mortality Of 214 screened patients, 173 patients were analysed, and 137 (79%) developed sepsis. Linear mixed models revealed time-dependent decreases in IL10 ({beta} -0.016, 95%CI -0.028 to -0.004), IL1RN ({beta} -0.014, 95%CI -0.024 to -0.004), and IL6 ({beta} -0.012, 95%CI -0.024 to 0.00). Sepsis was associated with higher IL1RN ({beta} 0.378, 95%CI 0.153-0.603), and TNFRSF1A ({beta} 0.40, 95%CI 0.21-0.58); only models evaluating IL6 showed significant interaction between sepsis and time ({beta} -0.14, 95%CI -0.028 to 0.00). SOFA correlated with elevated IL10 ({beta} 0.048, 95%CI 0.021-0.075), IL1RN ({beta} 0.044, 95%CI 0.017-0.071), CCL2 ({beta} 0.046, 95%CI 0.021-0.071), TNFRSF1A ({beta} 0.050, 95%CI 0.030-0.070), and PCT ({beta} 2.63, 95%CI 1.32-3.93); the interaction between SOFA score and time was significant only for IL6 ({beta} -0.003, 95%CI -0.005 to -0.001). Joint survival models (adjusted for age and highest SOFA) identified IL8 (HR 0.655, 95% CrI 0.582-0.728), TNFRSF1A (HR 0.505, 95% CrI 0.419-0.682), and PCT (HR 1.004, 95% CrI 1.001-1.008) as predictors. ConclusionSepsis diagnosis and severity of organ dysfunction may be associated with higher levels and kinetic values of inflammatory biomarkers such as IL1RN and TNFRSF1A. IL6 levels showed a significant association for the interaction of time with both sepsis diagnosis and SOFA score. TNFRSF1A, IL8 and PCT dynamics were found to be associated with survival and could be useful in developing prognosis tools.

IntroductionRecent evidence has shown that vitamin C has analgesic properties in immediate postoperative context. However, while a clinical trial is currently underway to evaluate vitamin C for reducing opioid consumption in acute musculoskeletal (MSK) injuries emergency department (ED) patients, its direct analgesic effect in this population has not yet been established. This pilot study evaluated the feasibility of conducting a randomized placebo-controlled trial to determine the analgesic effect of vitamin C alone compared with placebo in acute MSK injured ED patients. MethodsWe conducted a double-blind, randomized controlled pilot trial stratified by fracture status in a tertiary care center. Adults ([&ge;]18 years) presenting to the ED with MSK injuries of [&le;] 48 hours duration and pain intensity >3/10 were randomized to receive vitamin C 900 mg twice daily for three days or placebo. Participants completed a six-day diary (electronic or paper) and were contacted on day six to document analgesic use, treatment adherence, and pain intensity. ResultsOverall, 147 patients were screened; 63 (42.9%) were excluded, 24 (16.4%) refused, leaving 60 (41.1%) participants, with a consent rate of 13.0/month. Mean age (SD) was 41.8 years (14.23) and 50% were female. Lost to follow-up rate differed between participants with electronic diary (n=7; 16.7%) and participants with paper diary (n=10; 55.6%). Patients compliance with treatment was 97.6%. The least-squares mean difference between group A and group B in the time-weighted sum of pain intensity differences over 72 hours (SPID72) was 348.7 (95% confidence interval [CI]:-698.9 to 1396.4) for the intention-to-treat analysis and 357.6 (95%CI:-709.67 to 1424.82) for the per-protocol analysis. ConclusionThis pilot study supports the feasibility of a larger randomized controlled trial on the analgesic properties of vitamin C for acute MSK injured ED patients. Strategies to reduce the missed patients and lost to follow-up rates are proposed. Trial registration numberNCT06306183, ClinicalTrials.gov

The terms personalized, individualized and precision medicine are increasingly used to describe health interventions, yet their operational meaning in clinical research remains unclear. Despite extensive conceptual discussion, there is limited empirical evidence on how these labels are applied in randomized controlled trials (RCTs) and whether such trials meet standards of transparency and methodological rigor. We systematically examined 262 RCTs published between 2020 and 2022 that used the terms "personalized", "individualized", or "precision" in the title to describe an intervention. The term "personalized" was used most frequently (49.2%), followed by "individualized" (45.8%) and "precision" (5.0%). In most trials, personalization involved behavioral, digital, or pharmacological interventions, with few studies employing -omics approaches. Personalization was most often based on individual lifestyle factors, psychological characteristics, or disease classification. We also found that in most trials, personalization consisted of tailoring a single intervention to individuals (82.8%), often through individualized dosage (73.2%). Most included RCTs were judged to be at high risk of bias and showed limited transparency with respect to data and code sharing. Our study suggests that, in contemporary RCTs, the labels "personalized", "individualized", and "precision" are applied interchangeably to a wide range of heterogeneous interventions that are predominantly non-genomic. Greater conceptual clarity and stronger methodological standards are needed to ensure that claims of personalization in clinical research are empirically meaningful and reliable.

BackgroundStandardized training and competency testing is needed for appropriate point-of-care ultrasound (POCUS) clinical use. Our study objective assesses a low-fidelity simulation pig model workshop and tests the knowledge and technical skills of emergency medicine (EM) clinicians when performing simulated ultrasound-guided serratus anterior nerve block (UG-SANB). MethodsEM residents, attendings, and advanced practice providers (APP) participated in a prospective cohort study, completing a one-time simulation-based UG-NB training session at a single academic medical center between November 2024 to February 2025. Training model acceptability, appropriateness, and feasibility was assessed using the validated AIM-IAM-FIM tool (pre/post-surveys). Effectiveness outcomes were participant knowledge score, technical skill score, and self-rated confidence in performing NBs pre-, post-, and 3-months post-intervention. Clinical ED-performed ultrasound-guided nerve blocks were reported pre-/post-intervention. Scores were summarized using mean (S.D.) and total question percent correct. Paired individual assessments were compared pre/post-intervention using paired t-tests and group assessments using t-tests for normal data distribution. Results63/104 ED providers (60.6%) responded to surveys pre-intervention and 57 post-intervention (54.8%). 63 providers (16 EM attendings, 33 residents, and 14 APPs) underwent SANB training and testing. Participant survey responses reported the training model was acceptable, appropriate, and feasible (at least 54/57 agreed or strongly agreed for all three). Mean knowledge scores were 85% (SD 14.8%) post- and 70% (SD 18.2%) 3-months post-workshop. Mean technical skills exam scores were 98% (SD 4.5%) post- and 95% (5.8%) 3-months post-intervention. Perceived confidence in teaching clinical NBs increased pre-/post-intervention (from 11.3% to 58.2%) and for SANB (3.2% to 70.2%). Clinically performed NBs at pre and post were 21 and 15 respectively. ConclusionEmergency clinicians knowledge, technical skills, and confidence scores increased after an UG-NB training intervention. This standardized, reproducible simulation model could improve clinical skills and patient care outcomes but needs additional steps to increase clinical UG-NB performance.

BackgroundThe epidemiology of suspected pediatric meningoencephalitis has shifted in the era of conjugate vaccines and multiplex PCR diagnostics, with viral pathogens now predominating over bacterial causes. Updated epidemiologic data are essential to adapt diagnostic and therapeutic algorithms to current clinical practice. MethodsThis retrospective single-center study included children and adolescents <18 years who underwent lumbar puncture with cerebrospinal fluid multiplex PCR for suspected central nervous system infection at a tertiary-care pediatric hospital in Germany between 2016 and 2024. Clinical, laboratory, and outcome data were extracted from electronic medical records. Cerebrospinal fluid was analyzed using the BioFire(R) FilmArray(R) Meningitis/Encephalitis Panel. Statistical analyses included descriptive statistics, nonparametric group comparisons, receiver operating characteristic analyses. ResultsAmong 1,198 included children, definite bacterial meningitis was diagnosed in 13 (1.1%), definite viral meningitis in 80 (6.7%), aseptic meningitis of unknown etiology in 131 (11.0%), confirmed/probable encephalitis in 53 (4.4%), and possible encephalitis in 34 (2.8%). Bacterial meningitis accounted for 5.8% of all meningitis cases. A causative pathogen was identified in all bacterial meningitis cases, most commonly Streptococcus pneumoniae (n = 7). Enterovirus (n = 52) and parechovirus (n = 9) predominated in viral meningitis, whereas an infectious etiology was identified in only 13 of 53 confirmed/probable encephalitis cases. The Bacterial Meningitis Score showed a sensitivity of 80.0% and a specificity of 57.6%. The recently published UK-ChiMES-pre- and post-lumbar puncture scores demonstrated sensitivities of 84.6% and 76.9% and specificities of 86.3% and 92.7%, respectively. DiscussionBacterial meningitis was rare in this contemporary cohort, while viral and etiologically unresolved infections predominated despite routine multiplex PCR diagnostics. Clinical prediction scores supported risk stratification, with the UK-ChiMES-pre-lumbar puncture score showing the most favorable balance between sensitivity and specificity and potential to guide diagnostic decisions and antiinfective therapy.

BackgroundHospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP), particularly those caused by multi-drug resistant organisms (MDROs), often require newer antibiotic treatment. The efficacy and safety of newer antibiotics compared to generic antibiotics in randomized controlled trials (RCTs) have not been evaluated before. MethodsIn this systematic review, we searched RCTs in the United States National Library of Medicine (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Ovid MEDLINE, Clinical Trials.gov and Google Scholar databases published between 2013 and 2025. The primary efficacy endpoint was 28-day all-cause mortality. Secondary efficacy endpoints were clinical and microbiological response. Safety endpoint was nephrotoxicity. ResultsWe identified eight eligible RCTs involving 2,881 patients (1,450 patients treated with newer antibiotics and 1,431 patients treated with generic antibiotics) with HABP/VABP. The meta-analysis did not reveal any significant differences between newer and generic antibiotics for all-cause mortality at day 28 (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.72-1.30), clinical response (RR 1.04, 95%CI 0.93-1.17), and microbiological response (RR 1.05, 95%CI 0.89-1.24). However, newer antibiotics showed significant lower occurrences of nephrotoxicity compared to colistin component (RR 0.30, 95%CI 0.11-0.79). In subgroup analysis, newer antibiotic regimens demonstrated significant improvement in microbiological eradication of carbapenem-resistant Gram-negative bacilli (RR 1.50, 95%CI 1.18-1.90). ConclusionsNewer antibiotics showed similar efficacy and safety in treating HABP/VABP compared to generic drugs. The superiority in microbiological eradication of carbapenem-resistant Gram-negative bacilli of newer antibiotics could suggest that future trials should be targeted for those patients to improve understanding of their therapeutic use and pathophysiology of these conditions. Key pointsNewer antibiotics, despite broader antimicrobial coverage, have not significantly outperformed generic comparators in terms of 28-day all-cause mortality, clinical, or microbiological response in patients with Gram-negative HABP/VABP. This may reflect limitations in current trial designs focused primarily on regulatory approval.

ImportanceCurrent guidelines from the World Health Organization, Centers for Disease Control and Prevention, and Academy of Breastfeeding Medicine recommend discarding all milk remaining in bottles immediately after infant feeding. However, these recommendations lack supporting microbiological evidence from studies of actual infant feeding, imposing substantial financial and emotional burden on the 78 million families worldwide who bottle-feed their infants. ObjectiveTo determine (1) the financial, emotional, and time burden associated with bottle feeding and parental milk disposal practices, and (2) bacterial growth in leftover human milk and formula under different storage conditions. Design(1) Cross-sectional online survey (January 2023-February 2024) and (2) prospective microbiological cohort study. Setting(1) Online survey, (2) infants recruited in Hannover, Germany Participants(1) Survey respondents (n=1056; 99% mothers) and (2) healthy, full-term, bottle-fed infants (n=44; 17 humanmilk, 27 formula) aged 0-12 months. Main Outcomes and MeasuresParental burden scores, milk disposal frequency, and bacterial colony-forming units (CFU)/ml in milk samples before feeding, immediately after feeding, and at 4, 8, and 24 hours post-feeding at 4{degrees}C and 20{degrees}C. ResultsAmong surveyed parents, 46% discarded leftover milk daily, yet 84% reported they would keep milk longer if deemed safe. In microbiological testing, median bacterial burden in humanmilk increased from 4200 CFU/ml (range 300-350,000) pre-feeding to 24,600 CFU/ml (range 1900-29,004,400) post-feeding, but showed no significant further increase at 4 hours (p=0.82) or 8 hours (p=0.64) when stored at either 4{degrees}C or 20{degrees}C. Formula showed similar stability: median CFU/ml increased from 0 (range 0-10,700) to 11,700 (range 1900-630,000) post-feeding, with no significant change at 4 hours (p=0.91) or 8 hours (p=0.73) at either temperature. Significant bacterial growth occurred only after 24 hours at 20{degrees}C (p<0.001). Conclusions and RelevanceBacterial burden in leftover infant milk remained stable below concerning thresholds for 8 hours when refrigerated and 4-8 hours at room temperature, challenging current guidelines that mandate immediate disposal. Evidence-based guideline revision could reduce financial burden and milk waste for families around the globe without compromising infant safety. Key PointsO_ST_ABSQuestionC_ST_ABSHow long is it safe to offer leftover milk in a bottle to an infant that has previously drunk from it? FindingsThe number of bacteria in leftover human milk or formula did not significantly increase from 0 to 8h post-feeding in milk bottles sampled from 44 infants, regardless of whether the milk was kept at room temperature or refrigerated. MeaningLeftover milk may be safely reoffered beyond the limits of the current guidelines.

BackgroundIn the United States, emergency clinicians are often the first to care for injured patients in the hospital setting. To better understand end-user needs, we evaluated emergency clinician priorities and preferences in accessing, interpreting, and applying trauma clinical guidance. MethodsEmergency clinicians were recruited via email for semi-structured video conference interviews. Rapid directed qualitative analysis of interview notes and audio recordings yielded initial insights about guidance barriers and facilitators. A subsequent quantitative survey was developed and distributed via email to members of relevant professional associations. Survey results were analyzed using descriptive and inferential statistics. ResultsTwelve emergency clinicians participated in interviews. 154 eligible participants responded to the survey. Clinicians expressed support for trauma clinical guidance overall but often find resources lacking. Barriers to guidance usage include lack of awareness, difficulty locating guidance, and cumbersome design. Clinical guidance should be objective, concise, updated, and easy-to-use at bedside. The strongest determinant of guidance usability was being quickly understood in a time-pressured situation. Clinicians prefer to access guidance through mobile applications or multi-modal channels. Rural clinicians reported additional difficulties in staffing and having resources needed to follow guidance. ConclusionWhen developing trauma clinical guidance, the trauma community should continue to consider the variety of end users and clinical settings, including emergency clinicians. Developing mobile device-friendly, quickly understandable guidance should be a priority for authors of trauma clinical guidance.

PurposeTo systematically evaluate ocular biometric and systemic laboratory factors associated with cataract in highly myopic eyes and to characterize potential nonlinear associations using an interpretable machine learning approach, thereby providing deeper mechanistic insights into the pathogenesis of highly myopic cataract. DesignA cross-sectional study encompassed 770 eyes of 594 patients with high myopia from Eye & ENT Hospital of Fudan University. SubjectsThe non-cataract control group included 458 eyes while the cataract group contained 312 eyes. MethodsDemographic traits, ocular biometric and systemic laboratory factors were gathered while features with over 30% of missing data were excluded. Composite indices were obtained through calculation. Multiple machine learning models were compared to investigate the association between features and highly myopic cataract, and the random forest (RF) model was chosen and fine-tuned. Feature selection was carried out by means of Shapley additive explanations (SHAP) and non-linear relationships were probed using SHAP dependence diagrams and confirmed with partial dependence plots. Main Outcome Measures(1) The Area Under the Curve (AUC) and other metrics of multiple machine learning models; (2) Top feature importance of the final simplified RF model; (3) Overall trends between features and highly myopic cataract; (4) Potential inflection points of top continuous features. ResultsA simplified fine-tuned RF model with 17 features reached stable discriminative performance, with a mean AUC of 0.762 (95%CI: [0.731, 0.794]) among 10 independent testing sets. Age and axial length (AL) turned out to be the most influential features which had non-linear relationships highly myopic cataract, with an inflection point seen around 65.75 (95%CI: [63.72, 67.79]) years for age and 30.55 (95% CI: [29.22, 31.88]) mm for axial length respectively, while the ratio of anterior chamber depth to axial length (ACD/AL) was associated with highly-myopic cataract in a U-shape. Ocular biometric factors were more strongly related to highly myopic cataract than systemic laboratory factors. ConclusionsOcular biometric factors, especially age, AL, and composite indices like ACD/AL, have strong and non-linear connections with highly myopic cataract. These results emphasize the significance of ocular structural arrangement in cataract within highly myopic eyes and indicate that interpretable data-driven methods could offer clinically relevant understandings regarding its phenotypic description.

The rapid diagnosis of Campylobacter infections is important for the management of infectious gastroenteritis. Although stool culture is considered the gold standard, its sensitivity is limited and it requires prolonged incubation times. We performed a prospective multicenter study at nine healthcare facilities in Japan to evaluate a Campylobacter rapid antigen test using stool specimens between March 2024 and August 2025. Patients with suspected infectious gastroenteritis were consecutively enrolled and tested using QuickNavi-Campylobacter and compared with the FilmArray Gastrointestinal Panel as the reference method. Discordant results were further evaluated by culturing and additional PCR assays. In total, 410 patients were included in the final analysis. The positive, negative, and total concordance rates between QuickNavi-Campylobacter and FilmArray Gastrointestinal Panel were 79%, 99%, and 93%, respectively. The positive concordance rate decreased in specimens collected [&ge;] 6 days after the onset of symptoms (50%). QuickNavi-Campylobacter demonstrated relatively good concordance with the FilmArray Gastrointestinal Panel in a real-world multicenter setting. These results suggest that this rapid antigen test may be particularly useful for the early diagnosis of suspected campylobacteriosis.