Tag: nevin manimala

JCO Precis Oncol. 2025 Apr;9:e2400459. doi: 10.1200/PO-24-00459. Epub 2025 Apr 28.

ABSTRACT

PURPOSE: Although estrogen receptor is well studied in breast cancer (BC), the role of androgen receptor (AR) in prognosis and therapy response is less understood. Here, we characterized the clinicopathologic and molecular features of AR gene expression in BC subtypes.

METHODS: Ten thousand seven hundred twenty-eight BC samples were tested by next-generation DNA sequencing, whole-transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Tumors with AR-high and AR-low RNA expression were stratified by top and bottom quartiles, respectively. Treatment-associated survival was obtained from insurance claims and calculated from treatment start to last contact using Kaplan-Meier estimates. Statistical significance was determined by chi-square and Mann-Whitney U test with P values adjusted for multiple comparisons (q < .05).

RESULTS: AR-low was associated with basal-like tumors. AR-high tumors were associated with increased mutation rates in several genes-namely PIK3CA and CDH1-across all subtypes, while other associations such as RB1 and MAP3K1 were subtype-dependent. The immune landscape was differentially affected by AR expression in each subtype, but these differences did not correspond to differential responses to immune checkpoint blockade. Patients with AR-high tumors had a longer therapy response for most subtypes, but those with AR-high tumors that were human epidermal growth factor receptor 2-enriched and luminal B trended toward worse chemotherapy or hormone therapy response, respectively.

CONCLUSION: Our data suggest a unique molecular profile of AR-high BC that is subtype-specific and generally associated with improved outcomes. Exploration of specific mutations and immune-oncology markers associated with AR-high may aid in molecularly selected clinical trial design for patients with advanced BC.

PMID:40294352 | DOI:10.1200/PO-24-00459

Pediatr Infect Dis J. 2025 Apr 28. doi: 10.1097/INF.0000000000004835. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to develop and validate a clinical score for the prediction of critical care entrance in children with dengue.

METHODS: We conducted a retrospective cohort study using admissions from January 2019 to August 2021, at Hospital Infantil Napoleón Franco Pareja, in Cartagena, Colombia. We included all children 18 years or younger, with a positive immunoglobulin M or nonstructural protein 1 laboratory test and admitted for follow-up at the emergency department. We selected variables retrospectively collected on emergency admission for feature selection. We assessed discrimination and calibration in the development dataset, using 1000 bootstrap replications for internal validation. Data from 2019 to 2020 were used for development and 2021 for temporal validation. We report the c-statistic for discrimination with 95% confidence intervals (CIs), as well as the calibration intercept and slope.

RESULTS: One thousand three hundred eighty-five patients were included for development and internal validation. In temporal validation with 519 additional patients, the c-statistic was 0.82 (95% CI: 0.77-0.87), with a calibration slope of 0.98 (95% CI: 0.77-1.18). We selected the 50th percentile of the distribution of predicted probability of critical care entrance (5%) as a threshold value for increased alert at emergency admission, missing 10% of all cases that need to enter critical care (sensitivity of 90% with 95% CI of 82-95, and specificity of 48% with 95% CI of 41-50).

CONCLUSIONS: Our validated model can be useful to predict critical care entrance in children with dengue. We recommend the validation and potential recalibration of our score in other clinical settings.

PMID:40294334 | DOI:10.1097/INF.0000000000004835

ASAIO J. 2025 Apr 28. doi: 10.1097/MAT.0000000000002450. Online ahead of print.

ABSTRACT

Extracorporeal cardiopulmonary resuscitation (ECPR) requires advanced skills for induction and management. This study evaluated whether the outcomes of ECPR differ by institutional volume. Using the Japanese Association for Acute Medicine-Out-of-Hospital Cardiac Arrest (JAAM-OHCA) registry, we analyzed adult patients (aged ≥18 years) who received ECPR between 2014 and 2020, focusing on 30 day in-hospital survival and favorable neurologic prognosis at 30 days defined as Cerebral Performance Category (CPC) 1-2. Facilities were categorized into tertiles by annual ECPR volume. Multivariable logistic regression examined outcomes across low (≤4.7 cases/year), medium (4.8-7.8 cases/year), and high (≥7.9 cases/year) volume groups. A total of 1,759 patients from 83 centers were included, with an overall 30 day survival of 21.1% and CPC 1-2 rate of 10.1%. We observed no statistically significant differences in the respective rates of 30 day survival and neurologic outcomes in the medium ECPR volume group (adjusted odds ratios 1.09 [95% confidence interval {CI}, 0.82-1.47] and 0.85 [0.56-1.26]) and higher ECPR volume group (adjusted odds ratios 1.27 [95% CI, 0.95-1.70] and 1.11 [0.75-1.63]) compared with the lower ECPR volume group. These findings suggest that ECPR outcomes for out-of-hospital cardiac arrest are not significantly affected by institutional ECPR volume.

PMID:40294333 | DOI:10.1097/MAT.0000000000002450

Pediatr Infect Dis J. 2025 Apr 29. doi: 10.1097/INF.0000000000004836. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to determine the incidence and clinical characteristics of infants evaluated and treated with a prolonged course of antibiotics for culture-negative sepsis in a quaternary Neonatal Intensive Care Unit (NICU) over a 4-year period.

STUDY DESIGN: Retrospective chart review of patients in the NICU at Children’s Hospital of Philadelphia who had negative blood cultures and received ≥5 days of antibiotics. Data collection included demographics, clinical and laboratory data, and underlying diagnoses. Statistical analysis included Mann-Whitney and chi-square tests, and multivariable logistic regression.

RESULTS: We identified 774 culture-negative sepsis evaluations where antibiotic treatment was continued ≥5 days. While the majority were attributed to a focal etiology, 146 had negative blood cultures and no focal source. Infants with no focal source were younger at the time of sepsis evaluation, of greater gestational age, and more frequently required extracorporeal membrane oxygenation (P < 0.001). In multivariable analysis, evaluations for early-onset disease and need for extracorporeal membrane oxygenation were increased among infants with no focal source (P < 0.01). Although rates of invasive ventilation, and central venous catheters were similar, length of stay and mortality were significantly higher in late-onset episodes (P < 0.001 and P = 0.029, respectively). Consultation with the infectious disease team increased during the study period (P = 0.002).

CONCLUSIONS: Although it is challenging to limit the initiation of antibiotics in infants with complex underlying disease processes with concern for sepsis, minimizing antibiotic use can be achieved by timely discontinuation when cultures are negative. A robust antimicrobial stewardship program can identify valid reasons for prolonged antibiotic administration and suggest approaches to minimize antibiotic exposure.

PMID:40294328 | DOI:10.1097/INF.0000000000004836

Cancer Control. 2025 Jan-Dec;32:10732748251339248. doi: 10.1177/10732748251339248. Epub 2025 Apr 28.

ABSTRACT

IntroductionOvarian cancer remains a leading cause of gynecologic cancer-related mortality worldwide. Identifying perioperative factors that influence survival outcomes is essential for optimizing care. This study evaluates the impact of perioperative factors such as intraoperative blood transfusions and hospital length of stay (LOS) on survival rates in ovarian cancer patients undergoing surgical debulking.MethodsThis retrospective study analyzed charts of 314 patients who underwent ovarian cancer surgery at a single institution between 2010 and 2018. Patients were grouped based on survival status: “Live” or “Death”. Variables included demographics, tumor size, comorbidity, anesthesia time, surgery time, estimated blood loss, transfusion, readmission, hospital stay length, and survival. Statistical analyses included log-rank tests and mean survival estimations: chi-square tests and Mann-Whitney U-test. Significance was set at P < .05.ResultsThe mean follow-up was 50.5 months (95% CI, 47.8-53.2). Prolonged LOS (>3 days) was significantly associated with reduced survival (47.4 vs 52.4 months, P = .015). Patients requiring intraoperative blood transfusions had poorer survival outcomes (42.0 months 95% CI, 36.3-47.7 vs 53.1 months 95% CI, 50.3-55.9, P < .001). The “Death” group experienced greater blood loss, longer surgical/anesthesia times, and higher intraoperative fluid requirements.ConclusionProlonged hospital stays and intraoperative blood transfusions are associated with worse survival outcomes in ovarian cancer patients undergoing surgery. These findings underscore the importance of perioperative optimization strategies, including minimizing transfusion requirements and reducing LOS through enhanced recovery protocols.

PMID:40294239 | DOI:10.1177/10732748251339248

J Cogn Neurosci. 2025 Apr 28:1-13. doi: 10.1162/jocn_a_02339. Online ahead of print.

ABSTRACT

In the past decade, studies have shown that attention fluctuates at ∼8 Hz, alternating between intervals of increased and decreased visual performance [Re, D., Karvat, G., & Landau, A. N. Attentional sampling between eye channels. Journal of Cognitive Neuroscience, 35, 1350-1360, 2023; Re, D., Inbar, M., Richter, C. G., & Landau, A. N. Feature-based attention samples stimuli report feature-based attention samples stimuli rhythmically. Current Biology, 1-7, 2019; Helfrich, R. F., Fiebelkorn, I. C., Szczepanski, S. M., Lin, J. J., Parvizi, J., Knight, R. T., et al. Neural mechanisms of sustained attention are rhythmic. Neuron, 99, 854-865, 2018; VanRullen, R. Perceptual cycles. Trends in Cognitive Sciences, 20, 723-735, 2016; Fiebelkorn, I. C., Saalmann, Y. B., & Kastner, S. Rhythmic sampling within and between objects despite sustained attention at a cued location. Current Biology, 23, 2553-2558, 2013; Landau, A. N., & Fries, P. Attention samples stimuli rhythmically. Current Biology, 22, 1000-1004, 2012]. This modulation of performance, which has been observed primarily in the visual modality, also manifests in behavior and has been termed “attentional sampling.” In this study, we investigate whether sampling goes beyond vision and serves as a domain general mechanism shared by other perceptual systems. Specifically, we examined the auditory modality, in which there is contradicting evidence for endogenous sampling at similar frequencies [see VanRullen, R., Zoefel, B., & Ilhan, B. On the cyclic nature of perception in vision versus audition. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences, 369, 20130214, 2014]. In addition, we sought to investigate a putative role for visual experience in sampling in audition. To this end, sighted (n = 21), sighted blindfolded (n = 26), individuals with acquired blindness (n = 13), and individuals with congenital blindness (n = 12) detected a brief target (an intensity decrement) within an ongoing white noise stimulus. We observed 8- to 10-Hz sampling in the congenitally blind group only. We discuss this finding within the context of two possible, and even compatible, accounts. The first is that brain plasticity in the congenitally blind brings about attentional sampling in audition. It is possible that the lack of early visual experience drives the recruitment of “visual” cortices for auditory inputs, resulting in the same attentional sampling dynamics typically observed in vision, for audition. The second is that auditory sampling also exists in the sighted brain but might be obscured by visual inputs and other reflexive visual processes or might unfold at an entirely different rhythm. In fact, the acquired blind and the two sighted samples exhibited a significant low-frequency fluctuation at 2 Hz in their auditory performance. Although the study was not designed to investigate sampling at delta, this finding is consistent with a role for delta-band activity in audition as well as in temporal expectation mechanisms due to the temporal statistics of the utilized target times [e.g., Herbst, S. K., & Obleser, J. Implicit temporal predictability enhances pitch discrimination sensitivity and biases the phase of delta oscillations in auditory cortex. Neuroimage, 203, 116198, 2019; Wilsch, A., Henry, M. J., Herrmann, B., Maess, B., & Obleser, J. Slow-delta phase concentration marks improved temporal expectations based on the passage of time. Psychophysiology, 52, 910-918, 2015; Stefanics, G., Hangya, B., Hernádi, I., Winkler, I., Lakatos, P., & Ulbert, I. Phase entrainment of human delta oscillations can mediate the effects of expectation on reaction speed. Journal of Neuroscience, 30, 13578-13585, 2010]. Interestingly, delta band sampling was absent in the congenitally blind group. To further substantiate a role for delta band sampling, it would be important to design paradigms better suited to study lower frequencies in behavior, both in sighted individuals and under different degrees of visual input processing.

PMID:40294234 | DOI:10.1162/jocn_a_02339

Global Spine J. 2025 Apr 28:21925682251339621. doi: 10.1177/21925682251339621. Online ahead of print.

ABSTRACT

Study DesignRetrospective cohort study.ObjectivesThis study aims to evaluate the impact of hospital volume on postoperative outcomes following single-level cervical disc arthroplasty (CDA), focusing on non-routine discharge rates, length of stay (LOS), and hospital costs.MethodsAfter applying the appropriate exclusion criteria, the National Inpatient Sample (NIS) was queried to identify 14,315 weighted cases of patients undergoing single-level CDA between 2016 and 2020. Patients were stratified by hospital volume into low, intermediate, and high categories based on annual case numbers. Multivariate logistic regression evaluated odds of non-routine discharge and complications, while linear regression analyzed LOS and hospital costs. Models were adjusted for age, sex, and comorbidities. Statistical significance was set at P < .05.ResultsPatients in high-volume hospitals had significantly lower odds of non-routine discharge compared to both intermediate-volume (OR: 0.63, 95% CI: 0.44-0.91, P = .014) and low-volume hospitals (OR: 0.66, 95% CI: 0.45-0.98, P = .040). Patients in high-volume hospitals also incurred significantly higher costs compared to low-volume hospitals (coefficient: $1,232.22, 95% CI: $189.05-$2,275.38, P = .021), while length of stay did not differ significantly across volume categories.ConclusionsHigh-volume hospitals are associated with improved discharge outcomes, but also increased costs following single-level CDA. These findings underscore the need to disseminate high-volume center practices to lower-volume hospitals while addressing cost management. Further research should explore the impact of outpatient settings and long-term outcomes to enhance care delivery for CDA patients.

PMID:40294232 | DOI:10.1177/21925682251339621

Health Psychol Rev. 2025 Apr 28:1-19. doi: 10.1080/17437199.2025.2492042. Online ahead of print.

ABSTRACT

Background: Introduction: Physical activity is essential in preventing and treating age-related chronic diseases and mortality. Retirement is a key period to promote health behaviours, as individuals restructure their routines. Thus, we aimed to identify effective components and behaviour change techniques (BCTs) in interventions promoting physical activity in retirement-age individuals. Methods: We conducted a meta-analysis. Included studies were randomised controlled trials that (p)targeted retirement-age adults (50-70 years), (i)applied BCTs, (c)had any comparator, and (o)promoted physical activity. Screening, full-text review, and data extraction were conducted independently by at least two reviewers. A multilevel random effects model with three effect sizes was fitted, and meta-regressions tested several moderators. Results: 67 studies (N = 12,147) were included. High risk of bias related to larger effects, so these studies were excluded from the main analyses. While individual effects were often non-significant, the overall pooled effect was small but statistically significant. Predictors varied across effect sizes and included action planning, motivational interviewing, and prompts/cues. Email and website delivery were associated with smaller effect sizes. Conclusions: The effectiveness of lifestyle interventions is heterogeneous and presented small effects; implementing action planning, motivational interviewing, and prompts could improve the effectiveness. However, many BCTs that are not frequently used remain unexplored.

PMID:40294226 | DOI:10.1080/17437199.2025.2492042

Eur J Prev Cardiol. 2025 Apr 28:zwaf270. doi: 10.1093/eurjpc/zwaf270. Online ahead of print.

ABSTRACT

BACKGROUND: The elucidation of the contributory role of multimorbidity to heart failure (HF) including the gut-heart axis has added a new dimension to our understanding of HF pathophysiology which is not reflected in currently available risk scores. The present investigation aimed to develop and validate a novel risk score model of multimorbidity for HF risk stratification.

METHODS: A risk model was developed based on the contribution of markers associated with HF multimorbidities on outcomes of mortality and/or rehospitalization due to HF (death/HF) at one year. Two independent HF cohorts were combined and randomly split 70:30 using a split-sample validation approach for training and validation cohorts which were not significantly different for investigated variables. Backward logistic regression was used to develop the risk model with a further scoring system to create a simple risk calculator.

RESULTS: A final 11-variable risk model (age, previous HF hospitalization, NYHA group III/IV, NT-proBNP, diastolic blood pressure, loop diuretic use, beta-blocker non-use, creatinine, COPD, diabetes, and combined gut metabolites) showed a diagnostic performance of 0.71 in the training cohort (C-statistic validation cohort, 0.70, p<0.001). A risk score/calculator was further developed based on this model with categorization into three (low-, mid- and high-) and two (low- and high-) risk groups, with both approaches demonstrating increased incidence of death/HF in patients at the highest risk (p<0.001).

CONCLUSION: A novel risk model and score were derived which showed the contribution of comorbidities including the added value of the gut-heart axis on risk stratification of HF patients on rehospitalization and death.

PMID:40294213 | DOI:10.1093/eurjpc/zwaf270

Eur J Prev Cardiol. 2025 Apr 28:zwaf269. doi: 10.1093/eurjpc/zwaf269. Online ahead of print.

ABSTRACT

AIMS: Chronotropic incompetence (ChI) in heart failure with preserved ejection fraction (HFpEF) is associated with a reduced exercise capacity. The role of exercise training in improving chronotropic response (ChR) and functional capacity in these patients remains uncertain. This study assessed the effects of four different exercise programs on peak oxygen consumption (peakVO₂), Kansas City Cardiomyopathy Questionnaire (KCCQ) score and ChR in patients with the ChI HFpEF phenotype.

METHODS: In this randomized clinical trial, 80 symptomatic (NYHA class II-III/IV) patients with the ChI HFpEF phenotype were randomized (1:1:1:1) to one of four interventions: (a) a 12-week supervised aerobic training (AT) program, (b) AT with low-intensity strength training (AT/LRT), (c) AT with moderate- to high-intensity strength training (AT/HRT), or (d) non-supervised exercise recommendations (ER). The primary endpoint was the change in peakVO2 at 12 weeks. Secondary endpoints included changes in ChR and KCCQ. A linear regression model was used.

RESULTS: The mean age of 80 participants was 75.1±7.2 years, and 59.6% were women. Baseline values for peakVO2, chronotropic index, and KCCQ were 11.8±2.6 mL/kg/min, 0.4±0.2, and 63.5±17.9, respectively, with no significant differences across arms. All supervised training programs led to significant improvements in peakVO2 compared to ER: AT/HRT: Δ+4.0, (95% CI: 2.9 to 5.1, p< 0.001), AT/LRT: Δ+3.6, (95% CI: 2.5-4.6, p<0.001), and AT: Δ+2.9, (95% CI: 1.9-4.0, p<0.001). AT/HRT was superior over AT alone: Δ+1.1, (95% CI, 0.1 to 2.2, p=0.046). Likewise, supervised exercise improved ChR and KCCQ without statistical differences between groups.

CONCLUSIONS: Different supervised exercise training improved peakVO2, ChR and KCCQ in patients with ChI HFpEF phenotype.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT05649787).

PMID:40294211 | DOI:10.1093/eurjpc/zwaf269