Nevin Manimala

Brain Imaging Behav. 2025 Apr 25. doi: 10.1007/s11682-025-01007-8. Online ahead of print.

ABSTRACT

Early life adversity, defined as exposure to stressful events during childhood, is a significant risk factor for the development of psychiatric disorders. Diffusion tensor imaging studies employing tract-based spatial statistics have shown microstructural abnormalities in white matter among individuals exposed to early life adversity; however, robust conclusions are yet to be drawn. This systematic review synthesizes findings of previous tract-based spatial statistics studies to identify the white matter alterations in adult brains exposed to early life adversity, in papers with methodological consistency. The literature search (April 2024) was conducted to identify tract-based spatial statistics studies that compared diffusion metrics between adults exposed to early life adversity and adults not. Embase, Pubmed, and PsycInfo were searched, retrieving 2458 articles. Following deduplication, 1739 titles and/or abstracts were screened. 1699 articles were excluded, and 40 full texts were reviewed. Seven articles, reporting on 764 subjects, met the inclusion criteria and were included in the narrative synthesis. Compared to controls, adults exposed to early life adversity showed lower fractional anisotropy values in white matter tracts of the limbic and visual processing systems, specifically the anterior thalamic radiation, inferior longitudinal fasciculus, corona radiata, uncinate fasciculus, inferior fronto-occipital fasciculus, and cingulum bundle. This systematic review highlights that early life adversity may underlie emotional dysregulation and contribute to an increased risk of psychopathology in later life and explores the potential neurobiological mechanisms that underpin these structural changes. Understanding these associations is crucial for developing targeted interventions aimed at mitigating the long-term impact of early life adversity.

PMID:40279009 | DOI:10.1007/s11682-025-01007-8

J Clin Ultrasound. 2025 Apr 25. doi: 10.1002/jcu.24050. Online ahead of print.

ABSTRACT

PURPOSE: To create and validate a machine learning(ML) model that allows for identifying the correct capture of the midsagittal plane in a dynamic ultrasound study, as well as establishing its concordance with a senior explorer and a junior explorer.

METHODS: Observational and prospective study with 90 patients without pelvic floor pathology. Each patient was given an ultrasound video where the midsagittal plane of the pelvic floor was recorded at rest and during the Valsalva maneuver. A segmentation model was used that was trained on a previously published article, generating the segmentations of the 90 new videos to create the model. The algorithm selected to build the model in this project was XGBoost(Gradient Boosting). To obtain a tabular dataset on which to train the model, feature engineering was carried out on the raw segmentation data. The concordance of the model, of a junior examiner and a senior examiner, with the expert examiner was studied using the kappa index.

RESULTS: The first 60 videos were used to train the model and the last 30 videos were reserved for the test set. The model presented a kappa index 0.930(p < 0.001) with very good agreement for detection of the correct midsagittal plane. The junior explorer presented a very good agreement (kappa index = 0.930(p < 0.001)). The senior explorer presented a kappa index 0.789(p < 0.001) (good agreement) for detection of the correct midsagittal plane.

CONCLUSION: We have developed a model that allows determining the correct midsagittal plane captured through dynamic transperineal ultrasound with a level of agreement comparable to or greater than that of a junior or senior examiner, using expert examiner assessment as the gold standard.

PMID:40276937 | DOI:10.1002/jcu.24050

Nurs Crit Care. 2025 May;30(3):e70043. doi: 10.1111/nicc.70043.

ABSTRACT

BACKGROUND: Ventilator-associated pneumonia (VAP) is a significant healthcare-associated infection. Compliance with VAP guidelines reduces infection and leads to better patient outcomes.

AIM: The study investigated the VAP rate, nurses’ compliance with the VAP bundle and the correlation between nurses’ compliance with the VAP bundle and key patient-related outcomes.

STUDY DESIGN: This descriptive correlational prospective study was conducted at two tertiary hospitals. All intensive care unit patients on mechanical ventilators who met the inclusion criteria for 48 h or more were recruited. Data were analysed using descriptive statistics, Chi-square, independent t-test and Spearman’s rank correlation.

RESULTS: Out of the 103 patients recruited, 22.3% of patients developed VAP, with a VAP rate of 5.6 per thousand ventilator days. Nurses’ compliance with VAP guidelines in both hospitals was 69% and decreased over the admission period. Compliance with the VAP bundle was linked to less length of stay (rho = -0.260, p < .008), fewer mechanical ventilation days (rho = -0.300, p < .002) and less hospital cost (rho = -0.266, p < .007). The mean compliance with the VAP care bundle was higher in the non-VAP group (M = 72.9, SD = 23.79) than in patients who developed VAP (M = 56.6, SD = 18.96).

CONCLUSIONS: The findings underscore the critical need for healthcare organizations to prioritize strategies to enhance compliance with VAP guidelines for improved patient outcomes.

RELEVANCE TO CLINICAL PRACTICE: Ongoing quality improvement efforts through regular audits of the VAP bundle implementation are crucial for reducing infections and complications and improving patient outcomes. Future research is recommended to investigate factors that impact nurses’ adherence to VAP guidelines to develop interventions to enhance compliance.

PMID:40276934 | DOI:10.1111/nicc.70043

Clin Pharmacol Ther. 2025 Apr 25. doi: 10.1002/cpt.3688. Online ahead of print.

ABSTRACT

Improvements in the relevance and reliability of routinely collected clinical data and statistical methods to analyze the available data have enhanced the adoption of real-world data (RWD) to generate real-world evidence (RWE) for regulatory decision making of medical products. As part of the reauthorization of the Prescription Drug User Fee Act (PDUFA VII), the US Food and Drug Administration (FDA) committed to issuing annual reports describing such uses for drugs and biological products. The first report covered fiscal year (FY) 2023 and described two approvals based, at least in part, on RWE: tocilizumab (trade name Actemra) and lacosamide (trade name Vimpat). This article describes New Drug Applications and Biologics Licensing Applications approved by the Center for Drug Evaluation and Research (CDER) in FYs 2020-2022 with RWE that (1) contributed to substantial evidence of effectiveness or (2) provided safety data necessary for approval. RWE contributed to substantial evidence of effectiveness for the approval of applications for fosdenopterin (trade name Nulibry) and tacrolimus (trade name Prograf) in FY 2021 and abatacept (trade name Orencia), vosoritide (trade name Voxzogo), and alpelisib (trade name Vijoice) in FY 2022. No studies provided only safety data necessary for approval. The five approvals included six total studies that provided RWE pivotal for the applications approval. Four studies leveraged registry data, and two leveraged medical record data. In parallel with annual RWE public reporting under PDUFA VII, this report can inform interested parties regarding how RWD are used to generate RWE that can support regulatory decision making for medical products.

PMID:40276902 | DOI:10.1002/cpt.3688

Nat Prod Res. 2025 Apr 25:1-21. doi: 10.1080/14786419.2025.2494625. Online ahead of print.

ABSTRACT

Vinca alkaloids (VAs), derived from the Catharanthus roseus, are naturally occurring or semi-synthetic alkaloids primarily used in the treatment approach for diverse types of cancer. They have shown significant efficacy in treating leukaemia, Hodgkin’s lymphoma. Nevertheless, their clinical application is considerably limited owing to the severe side effects, low bioavailability, and multidrug resistance (MDR). Over the past few years, drug delivery systems such as nanoparticles, liposomes, and solid lipid nanoparticles (SLN) have been shown to improve the pharmacokinetic properties and tumour targeting of VAs. The use of multiple drugs in combination can also reduce the adverse reactions of VAs and significantly enhance their efficacy, thereby broadening their application. This review introduces the main pharmacologically active components of VAs, summarises their chemotherapeutic effects, and provides a statistical overview and analysis of recent research progress in VAs drug delivery technologies, offering a reference for further research and clinical application of VAs in cancer treatment.

PMID:40276897 | DOI:10.1080/14786419.2025.2494625

Korean J Anesthesiol. 2025 Apr 25. doi: 10.4097/kja.24934. Online ahead of print.

ABSTRACT

BACKGROUND: Predicting fatal neurological complications after clipping surgery for unruptured intracranial aneurysms (UIAs) is crucial; however, existing scoring systems are limited by narrow consideration of factors. We aimed to develop and validate a comprehensive risk stratification scoring system that incorporates patient-, aneurysm-, and operation-specific variables for predicting postoperative neurological complications in UIA surgeries.

METHODS: This multi-center retrospective cohort study was conducted from September 2018 to October 2023. Patients undergoing clipping surgery for UIAs were divided into development and validation sets based on the treating institution. A predictive score for postoperative neurological complications was developed from a multivariate logistic regression analysis. The score, named NEURO, that incorporates variables like previous neurological disease, categorized aneurysm location and size, categorized operation time, and transfusion was validated externally.

RESULTS: The study included 2847 patients, with 1547 and 1300 in the development and validation sets, based on the institution of surgery, respectively. The incidence of neurological complications was 5.7% (88 / 1547) and 5.6% (73 / 1300) in the development and validation sets, respectively. The NEURO score showed good predictive ability with C-statistics of 0.720 (95% CI, 0.667-0.776) in the development set and 0.693 (95% CI, 0.631-0.754) in the validation set, demonstrating good calibration across the predicted probability range.

CONCLUSIONS: The NEURO score, integrating multiple perioperative variables, may effectively predict the risk of neurological complications post UIA clipping surgery, aiding in identifying high-risk patients. This tool could enhance clinical decision-making and patient management in neurosurgical practice.

PMID:40276889 | DOI:10.4097/kja.24934

Aliment Pharmacol Ther. 2025 Apr 25. doi: 10.1111/apt.70169. Online ahead of print.

ABSTRACT

BACKGROUND: Individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) have a higher mortality risk, and physical activity is important to MASLD management. However, a comprehensive exploration of associations of volume and intensity of physical activity and rest-activity rhythm (RAR) based on an accelerometer with all-cause and cause-specific mortality in MASLD individuals was scarce.

METHODS: We included 10,143 individuals with MASLD from the UK Biobank. Volume and intensity of physical activity [low-intensity physical activity (LPA), moderate-to-vigorous-intensity physical activity (MVPA) and sedentary time] and RAR (amplitude, mesor, pseudo-F statistics and acrophase) were computed from accelerometer data. The Cox proportional hazards model was used to estimate the relationships of volume and intensity of physical activity and RAR with all-cause, cardiovascular disease (CVD) and cancer mortality risk in individuals with MASLD and further in common subtypes of cardiometabolic abnormalities. The population attributable risk and relative importance of physical activity were estimated.

RESULTS: Higher LPA, MVPA and normal RAR (amplitude and mesor) were associated with decreased risk of all-cause and CVD mortality among individuals with MASLD (HRs: 0.712-0.805), especially of all-cause mortality in those with common subtypes of more than two metabolic abnormalities (overweight/obesity-elevated blood pressure-hyperlipidemia and all the four abnormalities). Furthermore, we found MVPA and amplitude represented relatively important contributors to all-cause and CVD mortality risk in individuals with MASLD.

CONCLUSIONS: In individuals with MASLD, a higher volume and intensity of physical activity, as well as normal RAR supported lower all-cause and CVD mortality risk, which provided insights for management guidelines.

PMID:40276877 | DOI:10.1111/apt.70169

J Int Med Res. 2025 Apr;53(4):3000605251333654. doi: 10.1177/03000605251333654. Epub 2025 Apr 25.

ABSTRACT

ObjectiveTo evaluate the efficacy and adverse effects of phosphodiesterase 4 inhibitors in children with mild-to-moderate atopic dermatitis.MethodsElectronic searches were conducted based on PubMed, Cochrane Library, EMBASE, and Web of Science using Medical Subject Headings terms and relevant keywords. Using response rates as the primary outcome and adverse effects as the secondary outcome, statistical analysis was performed via Stata 15.1 SE, with Cochrane Q and I² statistics used for heterogeneity assessment. Publication bias and sensitivity analyses were conducted using various methods. Risk of bias was assessed using the Cochrane risk of bias tool.ResultsThe analysis included six randomized controlled trials involving 4681 children with atopic dermatitis. Phosphodiesterase 4 inhibitors were associated with significantly higher response rates than vehicle controls (odds ratio = 2.01, 95% confidence interval: 1.58 to 2.56, p < 0.001, I² = 54.8%), with no significant difference in adverse effect incidence (odds ratio = 1.07, 95% confidence interval: 0.87 to 1.30, p = 0.536, I² = 11.8%). Subgroup analysis revealed varying response rates among different phosphodiesterase 4 inhibitors, with crisaborole showing the least adverse effects.ConclusionOur meta-analysis revealed that children with atopic dermatitis treated with phosphodiesterase 4 inhibitors experienced higher remission rates and comparable adverse effect rates compared with vehicle controls. Currently, crisaborole appears to be the optimal choice for balancing safety and efficacy. As research in this area is still in its early stages, further high-quality trials are essential for establishing standards of clinical care.INPLASY registration number: INPLASY202520121.

PMID:40276862 | DOI:10.1177/03000605251333654

Gut Liver. 2025 Apr 25. doi: 10.5009/gnl240555. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: This study examined sex differences in the effect of changes in body mass index (BMI) on the development of gastric cancer (GC) in South Korea.

METHODS: Using data from the National Health Insurance Service-Health Screening Cohort, a retrospective cohort study involving 333,169 Koreans with a median follow-up of 12 years was conducted. BMI was categorized into five groups (<18.5, 18.5-22.9, 23.0-24.9 [reference], 25.0-29.9, and ≥30.0 kg/m²) and the risk of developing GC was evaluated according to changes in BMI by calculating the hazard ratio (HR) using Cox proportional hazard regression.

RESULTS: Among males, BMI ≥30.0 kg/m² was associated with a 1.27-fold higher overall risk of developing GC (95% confidence interval [CI], 1.02 to 1.57), but not in females. For non-cardia GC, a U-shaped association between BMI and risk of developing GC was observed in males, although statistical significance was observed only for BMI 18.5-22.9 kg/m². Additionally, an increase in BMI to 23.0-24.9 kg/m² was associated with a decreased non-cardia GC risk among males. In females, the largest waist circumference category was significantly associated with an increased risk of developing overall GC (HR, 1.37; 95% CI, 1.07 to 1.74).

CONCLUSIONS: This study demonstrated that maintaining a BMI in the range of 23.0-24.9 kg/m² is optimal for minimizing the risk of non-cardia GC, particularly in males. In females, visceral obesity, represented by a large waist circumference as a proxy, was associated with an increased risk of developing GC.

PMID:40276822 | DOI:10.5009/gnl240555

Indian J Orthop. 2025 Jan 13;59(4):464-471. doi: 10.1007/s43465-024-01319-9. eCollection 2025 Apr.

ABSTRACT

PURPOSE: To evaluate the incidence of knee arthritis following multiligamentous knee injuries (MLKIs) and assess other outcomes including conversion to total knee arthroplasty (TKA), return to work, return to sports, and patient satisfaction.

METHODS: A comprehensive search of PubMed, Web of Science, and Scopus databases was conducted for studies published up to April 2024. Studies focusing on patients with multiligamentous knee injuries undergoing reconstruction were included. Primary outcome was arthritis incidence; secondary outcomes included conversion to TKA, return to work, return to sports, and patient satisfaction. Data extraction and statistical analyses were performed using MedCalc statistic software, with pooled incidence rates calculated via random-effects models. Heterogeneity was assessed using Cochran’s Q test and I² statistic.

RESULTS: Seven studies met the inclusion criteria. The meta-analysis revealed a high incidence of knee arthritis after MLKIs, with a pooled incidence of 65.0% (95% CI 35.4% to 89.4%) among 158 patients, indicating substantial heterogeneity (I² = 92.9%). Conversion to TKA was reported in four studies with a pooled rate of 9.5% (95% CI: 5.4% to 14.6%) across 151 patients (I² = 0%). Return to work was reported in two studies, showing a pooled rate of 93.5% (95% CI: 71.0% to 99.7%) among 59 patients (I² = 83.4%). Return to sports was assessed in three studies, with a pooled rate of 70.8% (95% CI 48.2% to 88.9%) among 73 patients (I² = 75.0%). Patient satisfaction, reported in two studies, demonstrated a pooled rate of 82.5% (95% CI 73.0% to 90.2%) among 72 patients (I² = 0%).

CONCLUSION: MLKIs are associated with a high incidence of arthritis. However, it remains an effective intervention that facilitates a high rate of return to work, sports participation, and patient satisfaction.

PMID:40276800 | PMC:PMC12014884 | DOI:10.1007/s43465-024-01319-9