Nevin Manimala

Nutr Metab (Lond). 2025 Aug 27;22(1):101. doi: 10.1186/s12986-025-01000-4.

ABSTRACT

BACKGROUND: The coexistence of sarcopenia and obesity has been established as a pivotal factor driving the pathological progression of metabolic dysfunction-associated steatotic liver disease (MASLD). This study systematically evaluates the prevalence and risk of MASLD in patients with sarcopenic obesity (SO).

METHOD: A comprehensive literature search was conducted in PubMed, Cochrane Library, EMBASE, Web of Science and SCOPUS up to March 2025. All studies investigating the association between SO and MASLD were included in this meta-analysis. Two independent reviewers performed screening and data extraction. ORs and 95% CIs were calculated using random effect models. Subgroup analysis was used to identify the sources of heterogeneity. Heterogeneity was assessed using Cochran’s Q test and quantified via the I² statistic. Quality assessment and publication bias (by Funnel plots and Egger’s test) evaluation were also performed.

RESULTS: Thirteen studies involving 35,373 SO patients (from six countries) were included after screening. Odds ratios (ORs) of the included studies were combined by random effect model. The pooled results revealed that 63.4% of SO patients had MASLD. Compared to non-SO individuals, SO was significantly associated with an increased risk of MASLD (OR = 4.45, 95% confidence interval (CI): 2.57-7.72, P < 0.001). Females exhibited a higher MASLD risk than males (OR = 4.22, 95% CI: 2.10-8.50 vs. OR = 7.56, 95% CI: 2.39-23.92). Substantial heterogeneity was observed across pooled results and subgroups. Additionally, SO patients had a 2.34-fold higher risk of MASLD-related fibrosis than non-SO individuals (OR = 2.34, 95% CI: 1.78-3.08, P < 0.001).

CONCLUSION: SO may be closely associated with a high prevalence of MASLD and accelerated fibrosis progression. These findings highlight SO as a potential high-risk population for MASLD, underscoring the need for targeted screening and intervention strategies. However, more high-quality research with unified definitions and different races is needed.

PMID:40866987 | DOI:10.1186/s12986-025-01000-4

Eur J Med Res. 2025 Aug 27;30(1):814. doi: 10.1186/s40001-025-03097-y.

ABSTRACT

PURPOSE: This meta-analysis aimed to evaluate the incidence and risk factors of intraoperative acquired pressure injuries (IAPIs) in open heart surgical patients, focusing exclusively on prospective studies to address gaps in the existing literature.

METHODS: A systematic search was conducted across PubMed, Embase, and Web of Science up to January 2025. Data on incidence and risk factors were extracted, and statistical analyses were performed using random-effects models. Heterogeneity was assessed using I² statistics; publication bias was assessed by funnel plot and Egger’s test.

RESULTS: Ten prospective studies involving 1311 patients were included. The pooled incidence of IAPIs was 25% (95% CI 16%-35%), with high heterogeneity (I² = 94%). Sensitivity analysis confirmed stable results. Significant risk factors included prolonged surgical duration (SMD: 1.76, 95% CI 0.10-3.42, I² = 98%), advanced age (SMD: 0.30, 95% CI 0.14-0.46, I² = 0%), female sex (RR: 1.36, 95% CI 1.03-1.80, I² = 53%), and perioperative corticosteroid use (RR: 3.63, 95% CI 1.64-8.06, I² = 0%).

CONCLUSION: This study assessed the incidence of IAPIs in open heart surgical patients and identifies key risk factors, including prolonged surgical duration, advanced age, female sex, and perioperative corticosteroid use. However, the results should be interpreted with caution due to the high heterogeneity observed across studies. Future research should focus on larger, multicenter prospective studies to provide more robust evidence.

PMID:40866984 | DOI:10.1186/s40001-025-03097-y

Stem Cell Res Ther. 2025 Aug 27;16(1):463. doi: 10.1186/s13287-025-04601-1.

ABSTRACT

Recent evidence suggests that EpCAM and CD44 could serve as diagnosis or prognosis markers in pancreatic cancer (PC). In this meta-analysis, we evaluated their associations with clinicopathologic features. Specifically, we compared immunohistochemical-positive and -negative PC patients for T stage (T3-T4 vs. T1-T2), N stage (N1 vs. N0), M stage (M1 vs. M0), tumor grade (well/moderately vs. poorly differentiated), UICC Stage (III, IV vs. I, II), and overall survival (OS). The diagnostic meta-analysis was performed analysing the pooled sensitivity and specificity and evaluating overall accuracy to indicate the diagnostic efficacy of the markers. The protocol of this systematic review and meta-analysis was registered on the PROSPERO website under the registration number of CRD42024568390. A systematic search of PubMed, Scopus, and ISI Web of Science was conducted on January 30th, 2025. The statistical analysis was performed using the Review Manager 5.4 software and R language (R package Mada and Metafor). The quality of the studies included was assessed using the Newcastle-Ottawa scale and the QUADAS-2 tool. Data from relevant studies were independently screened and extracted using Rayyan, by at least two authors. A total of 19 studies were eligible (9 studies for EpCAM, 9 studies for CD44, and 2 studies for both EpCAM and CD44), comprising a total of 1370 patients. The diagnostic meta-analysis demonstrated moderate accuracy for EpCAM (AUC, 95% CI of 0.802, 0.69-0.96). A statistically significant association was found for CD44 expression and T-status (OR = 2.04, 95%CI = 1.18-3.51), or N-stage (OR = 2.68, 95%CI = 1.86-3.85), or TNM stage (OR = 3.79, 95%CI = 2.14-6.71). CD44v6 overexpression predicted worse OS (HR = 2.33, p < 0.00001), while EpCAM + CD44 + co-expression was prognostic (HR = 2.02, p = 0.02). Heterogeneity was not observed among the studies included, but further research is warranted to better understand the clinical implications of these markers’ positivity in PC diagnosis and prognosis.

PMID:40866982 | DOI:10.1186/s13287-025-04601-1

Orphanet J Rare Dis. 2025 Aug 27;20(1):458. doi: 10.1186/s13023-025-03993-w.

ABSTRACT

BACKGROUND: Human umbilical cord mesenchymal stem cells (HUMSCs) are effective therapies for inflammatory bowel disease. However, the mechanisms remain unresolved. We found HUMSCs express CD126 (IL-6 receptor), which indicated CD126 sub-populations might show a distinct response to inflammation. In the present study, we explored whether CD126 is a critical molecule for HUMSCs in regulating inflammation.

METHODS: We assessed the regulatory effects of CD126 high (CD126^hi) on the T lymphocyte subpopulations and related cytokines in the dextran sulfate sodium (DSS)-induced colitis model. The effect of CD126^hi was evaluated by Hematoxylin and Eosin (H&E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Statistical significance was typically determined using Student’s t-test or one-way analysis of variance (ANOVA) with Tukey test.

RESULTS: The disease symptoms were markedly ameliorated and the interleukin-6 (IL-6), interleukin-17 (IL-17), interferon-γ (IFN-γ), Tumor necrosis factor-α (TNF-α), and interleukin-4 (IL-4) levels were significantly reduced in DSS-treated mice administered with CD126^hi HUMSCs but not in DSS-treated mice administered with CD126 low (CD126^lo) HUMSCs. Intriguingly, CD126^hi HUMSCs significantly increased the levels of transforming growth factor-β (TGF-β1) and interleukin-10 (IL-10) in DSS-treated mice, accompanied by an increase in regulatory T cells (Treg cells). In vitro experiments showed that CD126^hi HUMSCs secreted TGF-β1 in response to IL-6 stimulation, while CD126^lo HUMSCs were latent in the inflammatory environment. We considered that TGF-β1 secreted by CD126^hi HUMSCs regulated the balance of Treg cells and thus promoted the recovery of murine colitis.

CONCLUSION: Our results revealed a mechanism wherein CD126^hi HUMSCs function as inflammatory sensors and secrete anti-inflammatory cytokines to rebalance the population of T cells. This study shed light on the potential therapeutic application of CD126^hi HUMSCs for inflammatory diseases such as inflammatory bowel disease.

PMID:40866981 | DOI:10.1186/s13023-025-03993-w

Diabetol Metab Syndr. 2025 Aug 27;17(1):360. doi: 10.1186/s13098-025-01928-w.

ABSTRACT

BACKGROUND: Type 1 diabetes (T1D) and autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), are characterized by immune-mediated damage. Prior observational studies have reported associations between these conditions, but definitive causal relationships remain elusive. This study leverages genetic data to clarify the nature of these associations.

METHODS: We conducted a bidirectional Mendelian randomization (MR) analysis using summary-level data from large-scale genome-wide association studies. The inverse variance weighted was the primary method, supplemented by diverse sensitivity analyses (MR-Egger, weighted median, weighted mode, cML-MA, BWMR, MR-PRESSO, and CAUSE) to rigorously assess causality and address potential pleiotropy. We assessed genetic correlation using linkage disequilibrium score regression and performed colocalization to evaluate shared causal variants.

RESULTS: Our findings revealed a causal effect of genetically predicted T1D on an increased risk of AIH (OR = 1.32, 95% CI: 1.16-1.50, P = 2.72 × 10⁻⁵), robustly supported by sensitivity analyses and replicated in an independent cohort. Evidence for a potential bidirectional causal relationship emerged between T1D and PBC, where genetically predicted T1D increased PBC risk (OR = 1.10; 95% CI: 1.02-1.20; P = 0.014), and genetically predicted PBC also increased T1D risk (OR = 1.13; 95% CI: 1.09-1.17; P = 3.45 × 10⁻¹¹), albeit with potential pleiotropy. No evidence for a genetic causal relationship was observed between T1D and PSC (IVW, P = 0.695). Significant genetic correlations were present between T1D and all AILDs, but colocalization did not support shared causal variants.

CONCLUSIONS: This study provides genetic evidence for a causal effect of T1D on AIH and a likely bidirectional relationship between T1D and PBC. These findings refine our understanding of their comorbidity, suggesting the need for heightened clinical surveillance and warranting further mechanistic investigation to elucidate the biological pathways.

PMID:40866980 | DOI:10.1186/s13098-025-01928-w

Trials. 2025 Aug 27;26(1):314. doi: 10.1186/s13063-025-09041-z.

ABSTRACT

BACKGROUND: Patients with persistent pain and comorbid insomnia often experience a dual burden with significant day- and nighttime impairments. This comorbidity is associated with health problems like depression and a self-perpetuating vicious circle in which pain and insomnia symptoms mutually reinforce each other. Cognitive behavioural therapy for insomnia (CBT-i) has demonstrated efficacy in facilitating the behavioural and psychological changes necessary to improve sleep. However, its applicability to patients with the insomnia-pain comorbidity condition is underexplored. We will expand the knowledge base of CBT-i to this patient group by examining the effects on core insomnia symptoms, including sleep onset, the frequency and duration of nightly and early morning awakenings, sleep efficiency and daytime impairments at post-test and follow-up. Secondary outcomes include reductions in pain intensity and interference, depression and fatigue; improved pain acceptance and quality of life; and more adaptive sleep-related beliefs. This study also explores mediators of the expected effects, patient experiences of the feasibility and acceptability of the intervention and how these experiences relate to individual differences in treatment benefits.

METHODS: The study includes hospital patients with a chronic pain condition according to the criteria from the International Association for the Study of Pain and a DSM-5 diagnosis of insomnia. The study will recruit 106 patients based on a power analysis that accounts for 20% dropout, and block-randomise them to a group-based CBT-i intervention or treatment as usual (TAU). The latter consists of consultations and potential pain- and sleep medication. The participant timeline includes a baseline registration, seven sessions of the CBT-i within a 10-week period, a post-test and two follow-up measurements at 4 and 12 months, respectively. The statistical analyses will be intention-to-treat and include random factors to adjust for data dependencies. Patients’ experiences of feasibility and acceptability will be analysed using a reflexive thematic approach.

DISCUSSION: This study addresses a knowledge gap by evaluating the effectiveness of CBT-i adapted for patients with insomnia and non-malignant, persistent pain. Given positive findings, the study may support clinical recommendations by providing empirical evidence for implementing psychological sleep interventions for somatic hospital patients having comorbid sleep issues.

TRIAL REGISTRATION: Clinical Trials.gov ID NCT06351839. Registered 08 April 2024.

PMID:40866978 | DOI:10.1186/s13063-025-09041-z

Trials. 2025 Aug 27;26(1):317. doi: 10.1186/s13063-025-09035-x.

ABSTRACT

BACKGROUND: Opioid use and misuse during pregnancy rose from 1.5 to 6.5 per 1000 deliveries between 1999 and 2014 and continues as a significant public health concern. A fivefold increase in neonatal opioid withdrawal syndrome (NOWS) has accompanied the increase in opioid use. The Eating, Sleeping, Consoling care approach (ESC) has been shown to improve outcomes for infants with NOWS and is quickly becoming the standard of care for infants affected by opioid use disorder. Quality improvement initiatives following the implementation of ESC provide some evidence to suggest that symptom-based (i.e., as needed, PRN, just in time) dosing of opioid medications for infants with significant withdrawal may be an effective alternative to using a traditional scheduled opioid taper approach. These initiatives have shown reduced length of hospital stay and decreased postnatal opioid exposure when compared to scheduled opioid dosing for infants with NOWS who receive pharmacologic treatment. It is unknown if the findings from these quality improvement initiatives are generalizable, and little is known about the safety of this approach in a diverse population. The purpose of this manuscript is to describe the design and rationale for an ongoing study to evaluate the effect of symptom-based opioid dosing compared to traditional scheduled opioid taper on short-term outcomes for infants with NOWS.

METHODS/DESIGN: In this ongoing multi-center two-period cluster crossover randomized controlled trial, 24 sites within the USA were randomized at the site level into one of two sequences. Prior to randomization, sites were stratified by care approach used (ESC vs. usual care) and these strata were independently randomized. All study sites will provide care based on their random allocation. Data will be collected under waiver of consent for in-hospital and short-term outcomes for eligible infants. A minimum of 480 infants will be enrolled. We hypothesize that use of symptom-based dosing will safely reduce the length of time until infants with NOWS and at risk for pharmacological treatment are medically ready for discharge when compared to infants treated with a scheduled opioid taper.

DISCUSSION: This trial is uniquely and efficiently designed to establish the efficacy, safety, and generalizability of the symptom-based dosing approach to opioid treatment for NOWS.

TRIAL REGISTRATION: NCT05980260 ; registered July 27, 2023.

PMID:40866977 | DOI:10.1186/s13063-025-09035-x

Int J Health Geogr. 2025 Aug 27;24(1):23. doi: 10.1186/s12942-025-00400-2.

ABSTRACT

BACKGROUND: The optimal placement of ambulances is critical for ensuring timely emergency medical responses, especially in regions with high accident frequencies. In Rwanda, where road accidents are a leading cause of injury and death, the strategic positioning of ambulances can significantly reduce response times and improve survival rates. The national records of Rwanda reveal a rising trend in the number of road accidents and deaths. In 2020, there were 4203 road traffic crashes throughout Rwanda with 687 deaths, data from 2021 demonstrated 8639 road traffic crashes with 655 deaths. Then in 2022 national statistics indicated 10,334 crushes with 729 deaths. The study used emergency response and road accident data collected by Rwanda Biomedical Centre in two fiscal years 2021-2022 and 2022-2023 consolidated with the administrative boundary of Rwandan sectors (shapefiles).

METHODS: The main objective was to optimize ambulance locations based on road accident data using machine learning algorithms. The methodology of this study used the random forest model to predict emergency response time and k-means clustering combined with linear programming to identify optimal hotspots for ambulance locations in Rwanda.

RESULTS: Random forest yields an accuracy of 94.3%, and positively classified emergency response time as 926 fast and 908 slow. K-means clustering combined with an optimization technique has grouped accident locations into two clusters and identified 58 optimal hotspots (stations) for ambulance locations in different regions of Rwanda with an average distance of 1092.773 m of ambulance station to the nearest accident location.

CONCLUSION: Machine learning may identify hidden information that standard statistical approaches cannot, the developed model for random forest and k-means clustering combined with linear programming reveals a strong performance for optimizing ambulance location using road accident data.

PMID:40866972 | DOI:10.1186/s12942-025-00400-2

Infect Agent Cancer. 2025 Aug 27;20(1):59. doi: 10.1186/s13027-025-00690-y.

ABSTRACT

BACKGROUND: Women treated with cervical loop electrosurgical excision procedure require follow-up to detect residual or recurrent HSIL+, defined as high-grade squamous intraepithelial lesions, adenocarcinoma in situ or cervical cancer. Currently, co-testing with cytology and human papillomavirus (HPV) analysis is usually recommended. This study investigates whether HPV testing alone is comparable to co-testing in detecting HSIL + up to three years after treatment. Recurrence rates of HSIL + are also presented, with follow-up extending up to 18 years.

METHODS: This retrospective cohort study included all 3,540 women treated with a cervical excision in Uppsala County between 1 January 2005 and 31 December 2019. Women with cancer identified in the cone biopsy were excluded. The main outcome was HSIL + detected within three years of follow-up. Sensitivity, specificity and negative predictive value were calculated for the 1,938 women who had a co-testing result as part of their test of cure. Thus, the analysis for the main outcome could finally be performed on 1,938 out of the total number of 3,540 women. Additionally, long-term data on recurrence and time to HSIL+, along with a separate analysis of results prior to cervical cancer diagnosis, were collected for the whole cohort of 3,399 women.

RESULTS: The sensitivity and negative predictive value for detecting HSIL + were 69% and 97% for HPV alone, and 74% and 98% for co-testing, respectively. These differences were not statistically significant. Specificity was higher for HPV alone than for co-testing. The negative predictive value of HPV testing for excluding cervical cancer (n = 5) within three years was 100%. Recurrence rate of HSIL + in the three-year follow up was 8%, and the total recurrence rate of HSIL + with a mean follow-up of nine years was 10%. Mean time to recurrence was 28 months. None of 19 cervical cancer cases identified in the long-term follow-up had a co-testing result showing negative HPV but positive cytology.

CONCLUSIONS: HPV testing alone, as a single test, is comparable to co-testing in detecting HSIL + up to three years after treatment independently of margin status, and demonstrates a higher specificity. Cytology plays a very limited role in the test of cure analysis and could therefore be omitted.

PMID:40866961 | DOI:10.1186/s13027-025-00690-y

Radiat Oncol. 2025 Aug 27;20(1):134. doi: 10.1186/s13014-025-02713-9.

ABSTRACT

BACKGROUND: Radiotherapy (RT) is a standard curative treatment for prostate cancer (PCa) and there is growing evidence of the high efficacy of moderate and ultra-hypofractionated RT. Reducing treatment duration to one week or less is a major advance, but very few studies have explored single-fraction therapy. This study evaluates the feasibility, safety, and efficacy of single-fraction stereotactic body RT (SBRT) while delivering the entire procedure in one day, with a potentially high benefit in terms of patient comfort and therapy cost and logistics.

METHODS: This prospective, non-randomized monocentric trial uses Robotic Radiosurgery (CyberKnife v.7 system) to deliver a single 24 Gy fraction to the prostate (± seminal vesicles) with a “urethral sparing HDR-like” technique, and target tracking. The first phase will enroll 13 PCa patients following Simon’s optimal design. Treatment is to be stopped if ≥ 2 patients develop ≥ G3 toxicity (CTCAE v5.0) within a month from RT end; otherwise, 52 more patients will be added, totaling 65. To account for minimal drop-out, 5 extra patients will be enrolled, reaching 70. All procedures are performed in a single day, including fiducial implantation, imaging acquisition, contouring, planning, dosimetry quality control, and treatment. Apart from treatment feasibility in terms of one-month acute toxicity, secondary endpoints include late toxicity, biochemical and clinical control.

DISCUSSION: Few others have investigated the 24 Gy single-fraction schedule using different delivery modalities (not including tracking), which has proved to be non-inferior to 5 fraction SBRT. Our approach aims to maintain (and possibly improve) the previously reported acute, subacute and late toxicity as well as disease control, adding evidence in favor of single-fraction delivery. Another significant goal of the study is the demonstration that all the complex treatment procedures can be safely delivered in a single day. This would be especially appealing for patients far from radiotherapy centers and those with work commitments not allowing daily hospital visits. The study of response to RT can also provide useful information about PCa radiobiology. Planned additional analyses may help in better assessing the clinical value of PSMA PET/CT in the selection of high-risk patients with true limited disease, and in identifying radiomic features associated to outcome.

TRIAL REGISTRATION: The study was prospectively registered at clinicaltrials.gov (NCT05936736).

PMID:40866948 | DOI:10.1186/s13014-025-02713-9