BackgroundNeonatal jaundice is a leading cause of newborn hospitalization in low- and middle-income countries (LMICs), yet factors influencing length of hospital stay (LOS) in non-infectious cases remain poorly characterized.MethodsWe retrospectively analyzed 1262 neonates with confirmed non-infectious jaundice admitted to a tertiary referral hospital in southern Vietnam between January 2024 and June 2025. Demographic characteristics, admission bilirubin levels, complete blood count (CBC) parameters, and derived inflammatory indices were evaluated. LOS was analyzed primarily as a continuous outcome, with prolonged hospitalization (≥3 days) assessed as a secondary outcome. Robust OLS, Poisson, and logistic regression models identified independent predictors after adjustment for age, sex, and ethnicity.ResultsHigher total and indirect bilirubin levels were associated with longer LOS in univariable analyses. Across all multivariable models, total bilirubin independently predicted longer hospitalization and increased odds of prolonged stay. Higher monocyte count showed a modest inverse association with LOS, although this finding should be considered exploratory. Other CBC-derived inflammatory indices (NLR, MLR, PLR, SII, and SIRI) and demographic factors, including ethnicity, were not independently associated with LOS.ConclusionsBilirubin burden was the dominant determinant of hospitalization duration in neonates with non-infectious jaundice. Routine CBC-derived inflammatory indices provided little incremental prognostic value beyond bilirubin concentration. The modest association between monocyte count and shorter LOS warrants prospective validation, while additional clinical and health-system factors not captured in this study are also likely to influence hospitalization duration.
Reproductive hormones may influence immune responses to tumors. Tumor-infiltrating lymphocytes (TILs), CD4 +, and CD8 + T cell densities are markers of immune activity and breast cancer prognosis. We examined associations between lifetime reproductive hormone exposure, tumor immune infiltration, and survival among women with breast cancer. The study included invasive breast cancer cases in the Women's Circle of Health Study and the Women's Circle of Health Follow-up Study. Lifetime endogenous hormone exposure (LHEendo) was defined as reproductive years plus pregnancy duration minus breastfeeding duration; lifetime exogenous hormone exposure (LHEexo) was defined as the combined cumulative duration of oral contraceptive and hormone replacement therapy use. TILs were scored as ordered percentage values from 0 to 100% stromal area; CD4 + /CD8 + T cell densities were quantified by immunohistochemistry. TILs were modeled using ordinal logistic regression, and CD4 + /CD8 + T cell densities were modeled using gamma generalized linear models among participants with positive density values, with covariates selected by directed acyclic graphs. Overall survival was assessed using Cox proportional hazards models, and breast cancer-specific survival was assessed using Fine-Gray competing-risk models. Among 1195 women with valid TILs measurements, 553 and 610 had CD4 + and CD8 + T cell density data, respectively. Across all tumor molecular subtypes, a 1-year increment of LHEendo was associated with a 2.85% decrease in CD8 + T cell density (95% CI - 5.14%, - 0.61%). LHEendo was associated with lower odds of being in a higher TIL level among women with hormone receptor (HR) + /HER2- tumors (OR = 0.977, 95% CI 0.957, 0.997), although the interaction by molecular subtype was not statistically significant. LHEexo was associated with lower risk of all-cause mortality (HR = 0.979, 95% CI 0.960, 0.998). TIL-stratified analyses suggested that this association may be more apparent among women with TILs ≥ 50% (HR = 0.90, 95% CI = 0.82, 0.99; P-interaction = 0.10). Lifetime endogenous hormone exposure was associated with lower CD8 + T cell density overall, with exploratory findings of lower TIL levels among women with HR + /HER2- tumors. Lifetime exogenous hormone exposure was associated with a lower risk of all-cause mortality, with possible variation by TIL levels.
The objective of this study was to assess whether interhospital transfer delays completion of the Surviving Sepsis Campaign (SSC) 3-hour bundle among rural sepsis patients. We conducted a multicenter (n = 23) cohort study among adult rural sepsis patients in an ED-based telemedicine network between August 2016 and June 2019. The primary exposure was interhospital transfer and the primary outcome was completion of the SSC 3-hour bundle. Secondary outcomes included SSC component adherence, ED length-of-stay, and in-hospital mortality. We used a Cox proportional hazards model to evaluate time to bundle completion by transfer status, generalized linear models for dichotomous outcomes, and linear and quantile regression for ED length-of-stay. A total of 1,191 patients were treated in participating hospitals, with 359 (30%) undergoing interhospital transfer. SSC bundle adherence was similar in both groups (difference 2.2%; 95% confidence interval [CI]: - 2.2, 6.5%). Among eligible patients, transfer was associated with a longer ED length-of-stay (3.1 hours vs 2.6 hours; difference 0.6 hours; 95%CI: 0.4, 0.7).
Early hospital readmission after heart failure (HF) hospitalization is a major determinant of morbidity, mortality, and healthcare utilization. Most evidence informing readmission risk prediction originates from high-income countries, with limited data from low- and middle-income countries (LMICs), where healthcare delivery and post-discharge care differ substantially. We aimed to determine the rate and clinical predictors of 30-day readmission following HF hospitalization in an LMIC setting. We conducted a retrospective cohort study of adult patients hospitalized with a primary diagnosis of HF between January 2020 and December 2022 at a tertiary care center in Pakistan. The primary outcome was unplanned all-cause readmission within 30 days of discharge. Baseline demographic, clinical, and laboratory variables were extracted from electronic health records. Multivariable logistic regression was performed using clinically informed, parsimonious modeling with continuous variables retained. Model discrimination and calibration were assessed using the C-statistic and Hosmer-Lemeshow test, respectively. Among 557 patients hospitalized with HF, 172 (30.9%) experienced 30-day readmission. In multivariable analysis, a prior history of HF hospitalization was independently associated with increased readmission risk (adjusted odds ratio 1.9, 95% confidence interval 1.0-3.8; p = 0.04). Age, sex, HF phenotype, diabetes mellitus, renal function, and natriuretic peptide levels were not independently associated with readmission after adjustment. The model demonstrated acceptable calibration (Hosmer-Lemeshow p = 0.25) and modest discrimination (C-statistic 0.62). Nearly one-third of patients hospitalized with heart failure in this LMIC cohort experienced 30-day readmission. Prior heart failure hospitalization was the only variable independently associated with early readmission, while inpatient clinical markers alone demonstrated limited predictive utility. These findings support the need for transitional care strategies and incorporation of socioeconomic and outpatient care factors into future readmission models in resource-limited settings.
In border regions where small ruminants are lifelines, peste des petits ruminants (PPR) remains a silent killer for the small ruminants, undermining food security and rural economies. A cross-sectional survey was conducted between June 2023 and February 2025 in Comilla, Kushtia, Meherpur and Panchagarh districts of Bangladesh. A total of 389 goat blood samples were collected and performed competitive ELISA for peste des petits ruminants virus (PPRV) antibody detection. Among the unvaccinated goats 39.34% (120/305) were found to be seropositive, whereas 48.8% (41/84) was observed in the vaccinated group. Multivariable logistic regression identified several significant risk factors. Goats in Meherpur were significantly more likely to be seropositive (OR = 6.3; 95% CI: 2.74-15.44; p < 0.001) compared to Comilla. Female goats had increased odds of seropositivity (OR = 2.9; 95% CI: 1.67-5.42; p < 0.001) compared to males. Jamunapari goats showed higher odds of infection compared to crossbred goats (OR = 6.6; 95% CI: 1.94-27.64; p = 0.004). Additionally, the extensive rearing system was associated with greater risk (OR = 3.7; 95% CI: 1.89-7.46; p < 0.001). These findings underscore the need for region-specific vaccination strategies, along with strengthened surveillance in high-risk border districts, to support national PPR eradication roadmap.
The combination of radiotherapy (RT) and immunotherapy has emerged as a central strategy in modern oncology, yet clinical outcomes remain highly variable. This variability is critically influenced by timing, including sequencing, interval, and temporal alignment with immune dynamics. We performed a systematic review to evaluate how mechanism-guided timing of RT relative to different immunotherapy classes shapes antitumor efficacy. A systematic literature search was conducted in PubMed, Embase, and Web of Science for studies published between 2009 and January 2026 evaluating RT-immunotherapy combinations with explicit timing or sequencing analysis. Preclinical and clinical studies reporting immune mechanisms, systemic immune responses, or efficacy outcomes were included. Data were extracted on immunotherapy class, RT regimen, sequencing strategy, and outcomes. Risk of bias was assessed using design-appropriate tools. A total of 84 studies met inclusion criteria: 56 preclinical and 28 clinical, including four randomized controlled trials. Timing emerged as a critical biological determinant of synergy. Radiotherapy induced a temporally dynamic immune response encompassing immunogenic cell death, innate immune activation, T‑cell priming, and adaptive immune resistance. Optimal sequencing was mechanism-dependent: Cytotoxic T‑lymphocyte-associated protein 4 (CTLA-4) blockade was most effective before or concomitantly with RT; programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors performed best after RT, during peak T‑cell infiltration and checkpoint upregulation; co-stimulatory agonists showed optimal activity shortly after RT; and innate immune activators required immediate post-RT administration. Emerging evidence suggests circadian timing may further modulate efficacy. Timing is not a logistical variable but a central biological component of RT-immunotherapy combinations. A mechanism-guided temporal framework substantially influences immune responses and therapeutic outcomes, representing a low-cost, high-impact optimization strategy. Circadian considerations remain compelling but require validation in prospective trials.
Severe neonatal hyperbilirubinaemia represents a considerable cause of mortality and long term-morbidity in neonates born in low resource settings. Early identification of risk factors, such as glucose-6-phosphate dehydrogenase (G6PD) status, has the potential to prevent severe hyperbilirubinaemia and improve the clinical outcomes. The primary aim of the study was to assess equivalency of cord blood and neonatal capillary blood for diagnosis of G6PD deficiency using the quantitative point-of-care "STANDARD G6PDTM" test (SD Biosensor, Korea). The secondary aim was to analyse changes in G6PD activity in the first 4 months of life. A total of 75 neonates born in Shoklo Malaria Research Unit (SMRU) clinics were selected based on their G6PD status assessed through routine cord blood screening using the "STANDARD G6PDTM" test. Using activity thresholds established before in this setting, 25 G6PD deficient, 25 G6PD intermediate and 25 G6PD normal neonates were identified and re-tested using capillary blood collected within 24 hours of life and at day 7 by both "STANDARD G6PDTM" test and gold standard spectrophotometric assay. They were also followed-up at 1 and 4 months of age to study haematologic and G6PD activity changes over time. The results showed that the "STANDARD G6PDTM" can be used reliably up to one week of life for testing neonates using the same thresholds established in cord blood. Agreement of G6PD activity measured by the point-of-care test as compared to the gold standard spectrophotometry remained excellent at all sampling time-points. Nevertheless, G6PD activity assessed longitudinally in the same participants decreased over time, both at 1 month of age and at 4 months of age, and interpretation of results in female infants with intermediate activity might require different thresholds. The study demonstrated that the "STANDARD G6PDTM" can effectively support clinical care in neonates and infants in populations with prevalent G6PD deficiency at the primary care level and especially in low-resource settings.
The Geisinger Inherited Risk Gastrointestinal clinic (IRGI) offers annual multidisciplinary care to patients with Lynch syndrome (LS). Adherence to recommended colonoscopy and esophago-gastro-duodenoscopy (EGD) surveillance among IRGI patients with LS were compared with patients with LS not followed by IRGI (non-IRGI). A validated query of electronic health record data was performed. Gene-specific guidelines were used to determine adherence to recommended surveillance following result disclosure until March 2025. For those who received results before 2016, adherence was assessed from April 2016 to March 2025. Pearson's chi-square, Fisher's exact, Wilcoxon rank-sum tests, and logistic regressions were performed to compare adherence to recommended surveillance between IRGI and non-IRGI patients. A total of 548 patients with LS were included, of which 167 (30.5%) attended IRGI and 381 (69.5%) did not. Patients who were younger (odds ratio [OR], 1.03 [95% CI, 1.01 to 1.04]; P = .0002) or were identified via indication-based testing (OR, 9.69 [95% CI, 5.63 to 17.1], P < .0001) were more likely to be IRGI patients. For colonoscopy adherence among patients eligible for surveillance, 74.0% (94/127) of IRGI patients and 31.0% (97/313) of non-IRGI patients were adherent to all recommended postresult surveillance (P < .0001). For EGD adherence, 89.3% (50/56) of IRGI patients and 40.9% (61/149) of non-IRGI patients were adherent (P < .0001). Across the cohort, IRGI patients were more likely to be adherent to colonoscopy (OR, 7.40 [95% CI, 4.07 to 14.0], P < .0001) and EGD (OR, 7.32 [95% CI, 2.92 to 21.2], P < .0001). Attending IRGI was associated with higher adherence to surveillance guidelines among individuals with LS. Additional efforts are required to increase clinic attendance or otherwise improve adherence among patients with LS.
Digital technologies increasingly shape postgraduate medical education, yet orthopedic and trauma training face unique challenges because of the tactile, procedurally focused skills involved. Digital tools partially address these needs, but gaps remain, particularly across diverse European contexts. Our primary aim was to quantitatively assess predictors of digital learning technology acceptance (e-learning, distance education, and virtual reality [VR] and augmented reality [AR]) among European orthopedic and trauma trainees, drawing on the technology acceptance model (TAM) and the unified theory of acceptance and use of technology (UTAUT) as conceptual guides. Specifically, we examined how perceived usefulness and perceived ease of use (TAM), alongside performance expectancy, effort expectancy, social influence, and facilitating conditions (UTAUT), related to trainees' acceptance of digital technologies. These constructs guided variable selection and grouping, attitudinal scale design, and interpretation of how individual and contextual factors shape acceptance of digital learning tools in orthopedic training. Secondary aims were to describe adoption and attitude patterns, identify attitudinal trainee profiles, and examine contextual associations (eg, workplace type and national gross domestic product [GDP]). We distributed a multinational survey via European trainee federations and used validated scales to assess digital competence and attitudes and gathered demographic data (n=217 across 29 European countries). We administered the questionnaire in English; however, respondents who self-reported English proficiency below the intermediate level were excluded from the analyses to minimize potential comprehension-related bias. The survey assessed digital experience, self-reported digital competence, and attitudes toward e-learning, distance education, and VR/AR, and collected detailed demographic and workplace data. Expert review, cognitive pretesting, and pilot testing ensured validity and clarity. Analytical methods included Wilcoxon tests, ANOVA, clustering, multinomial logistic regression, and factor analysis to ensure the reliability and validity of attitudinal measures. e-Learning technologies were the most widely adopted, whereas VR/AR tools were less frequently used despite high average attitude ratings (mean 4.07, SD 0.88). Cluster analysis identified 3 distinctive groups-enthusiastic, supportive, and hesitant-that differed significantly in digital competence and acceptance profiles. Digital competence and national GDP emerged as significant predictors of group membership, consistent with TAM/UTAUT expectations that perceived capability and contextual facilitating conditions shape acceptance. Variation in attitudes was further associated with workplace type and regional resource disparities, underscoring the influence of contextual factors on technology adoption. European orthopedic trainees show broad support for digital innovations, preferring VR/AR despite low use. Preliminary evidence supports digital competence as a key mediator of acceptance, with GDP and workplace disparities predicting profiles (hesitant vs enthusiastic). Competence-first strategies and targeted resource equity (eg, low-GDP subsidies), together with policy adjustments, may address regional disparities. Future longitudinal and multimethod studies are needed to test causal pathways implied by TAM and UTAUT and to evaluate the generalizability of these findings across specialties and educational contexts.
Harassment, including sexual harassment, in the workplace poses a significant threat to workers' wellbeing and contributes to social inequities. Organizations play a pivotal role in both enabling and preventing workplace harassment. We use a grounded theory approach to understand how workers experience workplace sexual harassment. Drawing on semi-structured interviews with thirty U.S. workers, most from the service industry in the San Francisco Bay Area, who have experienced sexual harassment at work, we describe organizational practices that workers believe effectively prevent and respond to harassment. Findings demonstrate that workplaces may better support workers by (1) setting clear expectations that harassment will not be tolerated and (2) responding effectively to incidents of harassment by establishing an independent entity to whom victims can report incidents, providing verbal support, and taking appropriate actions to support and protect victims.
To evaluate longitudinal trends in gender and regional equity in membership and governance representation within the European Society of Gynaecological Oncology and the European Network of Young Gynaecological Oncologists. We analyzed European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists membership and governance data from 2013 to 2024. Descriptive analyses were supplemented with multi-variable logistic regression models to identify predictors of female membership and European Society of Gynaecological Oncology Council representation, including European Network of Young Gynaecological Oncologists status, calendar year or Council term, and United Nations geographic region. European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists membership increased from 1588 members in 2013 to 3385 in 2024, and female members reached parity by 2024. Female membership was associated with European Network of Young Gynaecological Oncologists participation (odds ratio 1.82, 95% confidence interval 1.73 to 1.91, p <.001) and calendar year (odds ratio 1.04 per year, 95% confidence interval 1.03 to 1.05, p <.001). Compared with Western Europe, female membership was higher in Northern Europe (odds ratio 1.69, 95% confidence interval 1.55 to 1.84, p <.001) and lower in Eastern Europe (odds ratio 0.78, 95% confidence interval 0.71 to 0.85, p <.001) and non-European regions (odds ratio 0.80, 95% confidence interval 0.74 to 0.86, p <.001). Gender was not associated with Council membership (odds ratio 0.95, 95% confidence interval 0.63 to 1.42, p =.79), and no independent temporal trend was observed (odds ratio 0.91 per term, 95% confidence interval 0.81 to 1.03, p =.13). Geographic variation was evident, with lower odds of Council representation in Eastern Europe (odds ratio 0.54, 95% confidence interval 0.28 to 0.98, p =.05), while estimates for non-European regions were unstable because of sparse representation. European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists have made substantial progress toward gender equity at the membership level, largely through early-career engagement. Governance representation appears to be influenced more by geographic and structural factors than by gender, highlighting the need for equity-focused strategies that sustain gender-balanced leadership development while addressing regional disparities.
To assess the incidence and determinants of early first-line systemic anticancer therapeutic attrition after metastatic recurrence in triple-negative breast cancer (TNBC) treated with neoadjuvant chemo-immunotherapy. We conducted a retrospective multicenter analysis of 209 consecutive patients with early-stage TNBC treated with neoadjuvant chemo-immunotherapy. After a median follow-up of 24 months, 54 developed metastatic recurrence. Early first-line systemic anticancer therapeutic attrition was defined as failure to initiate systemic anticancer therapy within 90 days of documented recurrence. Associations were evaluated using univariate and multivariable logistic regression. Among patients who developed metastatic recurrence, 17 of 54 evaluable patients (32.7%) experienced early first-line systemic anticancer therapeutic attrition. Patients who did not initiate treatment had a significantly shorter disease-free interval compared with those who received first-line therapy (median 7.4 vs. 14.3 months; p = 0.011). PD-L1 positivity was more frequent in the attrition group (64.7% vs. 28.6%; p = 0.021), and central nervous system metastases were more commonly observed (41.2% vs. 20.0%). Median overall survival from metastatic recurrence was 3.4 months in the attrition group compared with 12.4 months in the no-attrition group. In multivariable analysis, shorter disease-free interval (OR 0.87 per month; 95% CI 0.78-0.97), PD-L1 positivity (OR 8.73; 95% CI 1.81-42.04), and presence of central nervous system metastases (OR 7.09; 95% CI 1.41-35.57) were independently associated with early first-line therapeutic attrition. In this real-world multicenter cohort, nearly one-third of patients with TNBC experiencing metastatic recurrence after neoadjuvant chemo-immunotherapy did not initiate first-line systemic therapy within a clinically relevant timeframe. Early first-line systemic anticancer therapeutic attrition represents a meaningful gap in the care continuum and warrants improved surveillance and multidisciplinary management strategies. Not applicable.
To investigate the incidence, anatomical distribution, severity and concordance of congenital malformations (CMs) in twin pregnancies according to both zygosity and chorionicity in a cohort selected to minimize non-embryological confounding factors. This was a retrospective single-center cohort study including twin pregnancies evaluated at a fetal medicine referral center (Fetal Medicine Unit, Di Venere Hospital, Bari, Italy) between 1 January 2016 and 31 December 2025. Pregnancies conceived via assisted reproductive technology and those complicated by major maternal metabolic or systemic conditions or abnormalities attributable to secondary hemodynamic complications of monochorionic pregnancy were excluded. Chorionicity was determined on first-trimester ultrasound. Zygosity was established by invasive prenatal molecular testing when available or by standard clinical criteria; molecular confirmation was obtained for almost all pregnancies with structural CMs. CMs were classified according to anatomical district, severity (major vs minor) and concordance. Analyses were performed at pregnancy level. Based on descriptive evidence of anatomical clustering, logistic regression analysis was performed using monozygosity as the exposure variable and cardiac and/or central nervous system (CNS) malformations as the outcome. Among 936 twin pregnancies evaluated, 564 met the inclusion criteria. Overall, CMs were identified in 102 (18.1%) pregnancies, including 57 (55.9%) major and 45 (44.1%) minor anomalies. The overall prevalence of CMs was broadly comparable between twin types. CMs were predominantly discordant between cotwins across all groups. Monozygotic pregnancies demonstrated a distinct non-random anatomical distribution pattern characterized by enrichment of cardiac anomalies, particularly conotruncal defects, and CNS anomalies, particularly neural tube defects. When pregnancies were analyzed according to zygosity alone, cardiac and CNS anomalies accounted for over half of major CMs in monozygotic twins compared with approximately one-quarter in dizygotic twins. Logistic regression analysis confirmed an association between monozygosity and cardiac and/or CNS malformations (odds ratio, 4.13 (95% CI, 1.02-16.68); P = 0.047). Monozygosity was not associated with an increased overall prevalence of CMs but with selective anatomical clustering and a predominance of discordant phenotypes. These findings support the concept that monozygotic twinning may influence early developmental patterning rather than simply increasing the overall risk of malformation. © 2026 International Society of Ultrasound in Obstetrics and Gynecology.
Neurodegenerative diseases (NDDs) are progressive disorders in which mitochondrial dysfunction, oxidative stress, proteostasis failure, neuroinflammation, and synaptic damage progressively interact to drive neuronal vulnerability. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) links metabolic adaptation to stress-response pathways that are repeatedly disrupted in Alzheimer's disease, Parkinson's disease, Huntington's disease, polyglutamine (PolyQ) disorders, and amyotrophic lateral sclerosis. Rather than providing only an updated catalogue of studies, this review organizes the evidence into a cross-disease rheostat framework that explains why PGC-1α modulation is protective in some settings but incomplete or maladaptive in others. Current findings indicate that PGC-1α supports mitochondrial biogenesis, oxidative phosphorylation, antioxidant defense, mitophagy, autophagy, protein quality control, and inflammatory balance. However, its effects are highly context dependent. In several models, restoration of PGC-1α-related signaling improves mitochondrial function and reduces neuronal injury, whereas broad, sustained, or cell-inappropriate activation may produce limited benefit or undesirable outcomes. These observations suggest that PGC-1α is not a simple neuroprotective switch, but a flexible regulatory hub whose therapeutic value depends on cell type, isoform profile, disease stage, and activation level. Emerging strategies, including small-molecule modulators, gene delivery, antisense-based approaches, nanoparticle systems, and exercise-related interventions, remain largely preclinical and face major barriers related to CNS delivery, pathway selectivity, dose and cell-type control, peripheral safety, and validated target-engagement biomarkers. Nevertheless, clinical translation requires stronger causal validation, reliable target-engagement biomarkers, selective delivery methods, and long-term safety assessment. Future research should focus on precision-based modulation of PGC-1α to determine when and how this pathway can be safely used for disease modification. Such a careful approach may help transform PGC-1α from a broad experimental target into a clinically relevant strategy for well-defined neurodegenerative phenotypes.
To determine whether a structured early nephrology consultation triggered by a machine-learning acute kidney injury (AKI) risk score (electronic signal to prevent AKI [ESTOP-AKI]) in patients at high risk for stage 2 AKI improves patient outcomes. This randomized clinical trial was conducted at the University of Chicago, Illinois, from March 13, 2019, to August 21, 2024, in hospitalized patients with no serum creatinine (SCr)-based AKI and an ESTOP-AKI score more than 0.01. Patients were randomized to receive a structured early nephrology consultation (ENC) from an attending nephrologist or usual care (UC). The ENC included an in-person assessment and recommendations regarding volume status, kidney perfusion, medication dosing and selection, electrolytes, nutritional needs, and further testing. Patients in the UC arm only received a nephrology consultation when clinically requested by the primary team. The primary outcome was the peak change in SCr from enrollment (ΔSCr) during the 7-day follow-up. Secondary outcomes included development of AKI, need for kidney replacement therapy, and inpatient and 90-day mortality. Of the 180 patients randomized (median [IQR] age, 62.5 [50.0-71.0] years; 102 males [56.7%]), 89 (49.4%) received ENC, and 91 (50.6%) received UC. There was no significant adjusted mean (SE) difference in the 7-day ΔSCr between the ENC and UC groups, adjusted for the ESTOP risk group (0.04 [0.07] mg/dL vs -0.03 [0.07] mg/dL; P = .30), among the 70 patients (38.9%) in the development of stage 1 or higher AKI (37 [42%] vs 33 [36%]; P = .47) or among the 29 patients (16.1%) with stage 2 or higher AKI (17 [19%] vs 12 [13%]; P = .28). During the study period, there were 121 ENC consultations containing 270 recommendations compared with 19 UC consultations and 36 recommendations. Medication dosage and discontinuation, diuretics or fluids, and vasopressor recommendations were more likely to be completely followed in the UC arm (15 of 22 [68%]) compared with in the ENC arm (48 of 116 [41%]). Over the 90-day follow-up, there was no significant difference in readmission rates (ENC: 30 [34.1%] vs UC: 40 [44.4%]; P = .21) or 90-day mortality (ENC: 13 [14.8%] vs UC: 17 [18.7%]; P = .62) between the ENC and UC arms. In this randomized clinical trial of structured ENC triggered by a machine-learning AKI risk score, there was no difference in ΔSCr. AKI consultation recommendations were not followed the majority of time; whether increasing adherence to recommendations could improve outcomes deserves further study. ClinicalTrials.gov Identifier: NCT03590028.
Preoperative risk-stratification tools, including frailty, nutritional, and surgical risk metrics, are used to predict complications after spine surgery. The relative performance of these tools across complication types and surgical subgroups is not well characterized. This study aimed to compare the predictive performance of 5 risk metrics, American College of Surgeons Surgical Risk Calculator (ACS SRC), serum albumin, Risk Analysis Index (RAI), modified 5-item frailty index (mFI-5), and Geriatric Nutritional Risk Index (GNRI), for perioperative complications. The authors analyzed 362,145 adult spine surgery patients from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2017 to 2022. Adjusted odds ratios were estimated via multivariable logistic regression, controlling for age, sex, urgency, and procedure type (defined by Current Procedural Terminology [CPT] codes). Subgroup analyses were stratified by ICD-10 diagnosis category, including degenerative disease, tumor, trauma, infection, and spinal deformity. Discrimination for predicting complications was assessed using C-statistics and DeLong's test. Across all endpoints, ACS SRC had the best predictive accuracy: mortality C-statistic (95% CI) 0.908 (0.900-0.916), Clavien-Dindo grade IV (CD-IV) 0.823 (0.816-0.830), and major complications 0.749 (0.745-0.752). Serum albumin, despite being a single laboratory value, ranked second with mortality C-statistic (95% CI) 0.820 (0.807-0.833), CD-IV 0.734, and major complications 0.682 and showed strong discrimination for infectious complications (e.g., sepsis, septic shock, surgical site infection, and urinary tract infection), as well as for hospital length of stay and nonhome discharge. Compared to frailty-based metrics, albumin showed significantly better predictive value (p < 0.001 for pairwise comparisons) and maintained its advantages across all subgroups, including high-risk groups such as infection, trauma, and tumor cases. RAI provided moderate mortality prediction (C-statistic 0.807) and was most effective for predicting cardiovascular events, while both GNRI (0.753) and mFI-5 (0.647) were less consistent and demonstrated weaker associations with adverse outcomes. Multivariable regression confirmed that lower preoperative albumin and higher ACS SRC predictions were robust, independent predictors of increased risk for major complications, CD-IV events, and mortality. These performance patterns remained stable across surgical indications and in subgroup analyses. ACS SRC remains among the comprehensive tools for risk stratification in spine surgery. Serum albumin offers strong, consistent predictive value, especially for infectious, respiratory, and life-threatening complications, and may be a valuable alternative when calculator inputs are incomplete.
Dexmedetomidine has been used to treat toxicologic conditions, but high-quality data on its use for this indication in the emergency department setting are lacking. We sought to characterize the use of dexmedetomidine in this context. We conducted a dual-center retrospective cohort study of patients treated with dexmedetomidine in two academic emergency departments. We included patients who received dexmedetomidine in the emergency department and had a toxicologic condition, as adjudicated by a medical toxicologist on chart review. We abstracted data from the electronic medical record. We conducted multilevel logistic regression to explore factors associated with intubation after the initiation of dexmedetomidine. We screened 1,081 patients and included 320. The most common toxicologic conditions were ethanol withdrawal (20%) and acute poisoning by sympathomimetics (19.7%). Culprit xenobiotics were primarily ethanol and substances of misuse. Median nadir heart rate and mean arterial pressure after dexmedetomidine initiation were normal, and there was no substantial change in nadir hemodynamic parameters after dexmedetomidine administration, although there was an increase in vasopressor administration (6.6% to 11.9%). Among patients who were not intubated when dexmedetomidine was initiated (n = 200), the frequency of intubation was 21.5% (95% CI 16-28). On multilevel logistic regression, antipsychotic administration was associated with increased odds of intubation (adjusted odds ratio 2.52, 95% CI 1.15-5.51). Dexmedetomidine was primarily used to treat emergency department patients with intoxication or withdrawal from ethanol and substances of misuse. The frequency of intubation in spontaneously breathing patients after the initiation of dexmedetomidine was 21.5%. Further prospective research is needed to evaluate dexmedetomidine in the treatment of toxicologic conditions.
Although HOMA-IR is widely used to assess insulin resistance, reported cut-off values vary substantially across population, particularly during adolescence. The aim of this study was to determine the distribution of HOMA-IR values. identify a HOMA-IR cut-off associated with metabolic syndrome (MS), and assess modifiable risk factors of IR in a longitudinal cohort of Peruvian adolescents. We performed a secondary data analysis from a longitudinal adolescent's study. A sample of 371 adolescents (14.5 ± 0.1 years old) from low- medium socioeconomic status. ROC curve analysis was used to identify the specific cut-off point to classify IR using the sensitivity and specificity values in comparison with the MS. Multiple logistic regression analysis including diet, physical activity and body composition from adolescence, excess weight during infancy and family history of non-chronic disease was included to identify risk factors (FHCD) associated with IR. The HOMA-IR was 3.29 (SD 1.71) with no differences by sex. We identified 3.9 for HOMA-IR as the cut-off point with sensitivity (72.4%) and specificity (75.4%) for predicting MS. IR was present in 28.6% (95% CI 24.2;33.4%); 84% had at least one cardiometabolic risk factor and low HDL and abdominal obesity were the most prevalent (62 and 35%, respectively). Adolescents with higher fat mass index (OR 16.03, 95% CI 6.79 to 37.86), and those physically inactive (OR 2.08 95% CI 1.06 to 4.07) were more likely to have IR. No association was found with diet, excess weight at infancy and FHCD. A cut-offs point of 3.9 for HOMA-IR allows to identify adolescents with high metabolic risk. Strategies to promote lower FMI and improve the physical activity levels could reduce the risk of IR in adolescents.
The global impact of sexually transmitted infections (STIs) significantly affects low- and middle-income countries (LMIC). Iin Kenya, where access to STI diagnostics is limited, effective diagnostic solutions are critically needed. Nucleic acid amplification tests are considered the laboratory gold standard for detecting pathogens such as Chlamydia trachomatis and Neisseria gonorrhoeae due to their high sensitivity and specificity. However, these methods typically require centralized laboratories, trained personnel, and longer turnaround times. FlashDx is a near-point-of-care molecular diagnostic platform designed to address these challenges by integrating automated sample processing and multiplex pathogen detection within a compact system suitable for decentralized use. The primary aim of this study is to validate the performance of the FlashDx STI multiplex assay for detecting STIs including Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, Mycoplasma hominis, and Ureaplasma species compared with the reference Conformité Européenne In-Vitro Diagnostic (CE-IVD)-D dual real-time polymerase chain reaction (rtPCR) from Mikrogen. We propose a comparative cross-sectional study conducted with up to 400 young pre-exposure prophylaxis (PrEP) users aged between 15 years and 55 years at the Kenya Medical Research Institute Center for Microbiology Research Care and Training Program research site in Kisumu, Kenya. Urine samples were collected and analyzed using the FlashDx STI multiplex chip-based assay to detect 6 STIs, with results confirmed by the CE-IVD-D certified Mikrogen assay in the Netherlands. Participants were recruited in Kisumu, Kenya, from existing HIV prevention programs and sexual health services. Diagnostic performance will be assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value with 95% CIs. Descriptive and epidemiological analyses will summarize participant characteristics, behavioral risk factors, and the prevalence of STI infections within the cohort. Epidemiological data generated will include prevalence rates for all 6 STIs, providing an overview of STI prevalence with external validation to ensure accuracy and reliability. The study was funded by Microbe & Lab, with in-kind contributions from the Kenya Medical Research Institute (KEMRI) Centre for Microbiology Research (CMR) Research Care and Training Program (RCTP). Data collection was conducted between April 2025 and June 2025 at the KEMRI research site in Kisumu, Kenya. A total of 400 participants were recruited for the study. The study is currently in the data analysis phase. Statistical evaluation of the diagnostic performance of the FlashDx STI multiplex assay is being carried out. In parallel, epidemiological analyses are being conducted. Final results and associated epidemiological findings are expected to be completed and prepared for publication in the summer of 2026. The findings from this study are expected to show the FlashDx STI multiplex assay as an effective point-of-care system for diagnosing 6 common STIs in settings such as Kenya. By demonstrating its usability, accuracy, and reliability, the FlashDx assay could be considered for broader implementation in clinical settings across Kenya and other LMIC.
Post-marketing safety surveillance is essential for ensuring vaccine safety and maintaining public trust, particularly in African settings where evidence on the safety of COVID-19 vaccines remains limited. This study aimed to determine the overall incidence and types of AEFIs, as well as the factors associated with their occurrence, during COVI-19 mass vaccination campaigns in Democratic Republic of Congo. From December 1-29, 2023, a prospective safety surveillance study was conducted in Kinshasa Province. Participants were surveyed through phone calls from day 1-28 following COVID-19 vaccine administration. AEFI incidence rates were calculated by type of vaccine, sex, number of dose and age group. Factors associated with AEFIs were identified using multivariable logistic regression models, expressed by adjusted odds ratio and its 95% confidence interval. The study included 4766 participants. Their median [IQR] age was 36 [27-48] years and 2503 (53%) were males, 94.63% received the J&J vaccine while 256 (5.37%) received the BNT162b2 vaccine. Incidence of AEFIs was 23.75% (95%CI: 22.54%-24.99%). AEFIs mostly reported were fever (9.61%, 95%CI: 8.88%-10.48%), injection site pain (9.00%, 95%CI: 8.20%-9.85%), headache (4.11%, 95%CI: 3.57%-4.72%), stiffness (1.51%, 95%CI: 1.18%-1.89%) and myalgia (1.15%, 95%CI: 0.87%-1.49%). The incidence of AEFIs was higher for the BNT162b2 vaccine at 34.48% (95% CI: 28.57%-40.54%) vs. 23.15% (95% CI: 21.92%-24.41%) for the J&J vaccine. Compared to participants aged 18-59 years, those under 18 years old were associated with decreased odds of reporting any AEFI (aOR= 0.26, 95%CI: 0.13-0.88) and injection site pain (aOR=0.18, 95%CI: 0.05-0.75). Those aged 60 years and older were associated with decreased odds of reporting any AEFI (aOR= 0.78, 95%CI: 0.62-0.99) and fever (aOR=0. 63, 95%CI: 0.43-0.92). Approximately one-quarter of participants reported AEFI. The observed association with vaccine type and age underscores the need for systematic vaccine safety monitoring in the population. This is critical for guiding future vaccination strategies tailored to individuals who may be more susceptible to AEFIs.