Medical sciences (Basel, Switzerland)最新文献

{"title":"Time-Zero Kidney Biopsy and Deceased-Donor Transplant Outcomes: A Systematic Review and Meta-Analysis of Prognostic Value, Prediction, and Clinical Utility.","authors":"Livier Sainz-Bravo, Benjamín Gómez-Navarro, Diana Laura Figueroa-Gamiño, Jenniffer Topacio Tapia-Báez, José David González-Barajas, Manuel Luis Prieto-Magallanes, José Ángel Solís-Rojas, Edgar Bautista-Reyes, Juan Alberto Gómez-Fregoso, Judith Carolina De Arcos-Jiménez, Ramón Medina-González, Violeta Aidee Camarena-Arteaga, Manuel Arizaga-Napoles, Jaime Briseno-Ramirez","doi":"10.3390/medsci14050566","DOIUrl":"10.3390/medsci14050566","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Time-zero biopsy informs deceased-donor kidney implantation or discard, but its prognostic value is contested. We systematically reviewed pre-reperfusion morphological biopsy evidence in adult deceased-donor kidney transplantation, keeping four questions separate: prognostic association, incremental prediction, clinical utility and measurement reproducibility. <b>Methods:</b> We searched PubMed/MEDLINE, Embase, Scopus, Web of Science, CENTRAL and three trial registries through 25 July 2026 without date or language restriction. One estimate per non-overlapping cohort was selected under a prespecified hierarchy; random-effects models used restricted maximum likelihood with Hartung-Knapp inference; GRADE assessed certainty. <b>Results:</b> Of 45,676 records, 25,746 were screened; 203 eligible reports (159 study investigations and 154 cohort families) and 22 contextual reports were included. Vascular injury was associated with delayed graft function (odds ratio: 1.85, 95% CI 1.11-3.06), glomerulosclerosis with graft failure (hazard ratio: 2.03, 1.22-3.39) and vascular injury with graft failure (hazard ratio: 1.48, 1.07-2.04); glomerulosclerosis with delayed graft function was inconclusive (odds ratio: 1.13, 0.59-2.17). All 12 pooled bodies were of very low certainty. <b>Conclusions:</b> Current evidence does not support time-zero histology as a stand-alone rule for accepting or discarding a deceased-donor kidney. Whether standardized histology adds predictive information beyond established clinical variables remains open and should be addressed in linked registry analyses before biopsy findings guide management.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of Rebamipide, Pantoprazole, and Their Combination for Gastroprotection in Patients with Atrial Fibrillation Receiving Direct Oral Anticoagulants: The Randomized REGATA Study.","authors":"Natalya M Vorobyeva, Irina P Malaya, Vadim D Zakiev, Antonina A Masharova, Tatiana P Pinchuk, Irina V Kostomarova, Valentina S Ostapenko, Yulia V Kotovskaya, Olga N Tkacheva","doi":"10.3390/medsci14050565","DOIUrl":"10.3390/medsci14050565","url":null,"abstract":"<p><p><b>Background:</b> Patients with atrial fibrillation (AF) receiving direct oral anticoagulants (DOAC) are at an elevated risk of gastrointestinal (GI) mucosal damage and bleeding. Proton pump inhibitors (PPI) are conventional gastroprotectors, but their efficacy in the lower GI tract is limited. This study evaluated the efficacy and safety of rebamipide monotherapy and combination pantoprazole-rebamipide (P + R) therapy compared to pantoprazole monotherapy in this vulnerable population. <b>Methods:</b> In the randomized, parallel-group, open-label, single-center REGATA trial, 210 AF patients receiving DOAC were randomized (1:1:1) to three gastroprotective regimens (<i>n</i> = 70 each) for 24 weeks: pantoprazole monotherapy, rebamipide monotherapy, or their combination. Efficacy analyses were performed in the per-protocol population (<i>n</i> = 118: pantoprazole, <i>n</i> = 36; rebamipide, <i>n</i> = 39; P + R, <i>n</i> = 43). The primary and secondary outcomes included composite clinical GI events (bleeding classified by ISTH/BARC, ulcers/erosions, and severe dyspepsia) and biomarkers of mucosal barrier function (fecal zonulin and calprotectin). <b>Results:</b> The incidence of primary efficacy endpoint events was 13.9% (<i>n</i> = 5; 95% CI: 3.1-25.7) in the pantoprazole group, 10.3% (<i>n</i> = 4; 95% CI: 2.3-21.1) in the rebamipide group, and 9.3% (<i>n</i> = 4; 95% CI: 2.1-18.6) in the P + R group, successfully confirming the non-inferiority hypothesis for both experimental arms within the pre-specified margin of 10% (<i>p</i> < 0.05). Multivariable regression analysis showed that compared with pantoprazole monotherapy, rebamipide monotherapy demonstrated an odds ratio OR of 0.71 (95% CI: 0.18-2.88, <i>p</i> = 0.630), while the P + R therapy was associated with an OR of 0.64 (95% CI: 0.16-2.57, <i>p</i> = 0.525). No major GI bleeding events or fatalities occurred; a single episode of GI bleeding (ISTH minor/BARC Type 2) was recorded in the pantoprazole arm (2.8%). Fecal calprotectin levels significantly decreased in the rebamipide group (by 37.6%, from 139 to 78 µg/g; <i>p</i> < 0.001) and the P + R group (by 50.0%, from 135 to 61 µg/g; <i>p</i> < 0.001), while no significant changes were observed in the pantoprazole group (<i>p</i> = 0.530). Concurrently, fecal zonulin levels, reflecting intestinal epithelial permeability, fell by 45.1% in the rebamipide arm (from 434 to 225 ng/mL; <i>p</i> < 0.001) and by 47.1% in the P + R arm (from 347 to 182 ng/mL; <i>p</i> < 0.001) compared to a minimal 3.0% fluctuation in the pantoprazole group. <b>Conclusions:</b> While demonstrating non-inferiority regarding primary clinical endpoints, both rebamipide monotherapy and combination (P + R) therapy achieved some advantages over pantoprazole monotherapy in decreasing subclinical GI inflammation and restoring intestinal epithelial barrier integrity.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multivalvular Involvement in Acute Heart Failure: Associations with One-Year Outcomes and the Right-Heart Phenotype.","authors":"Georgios Aletras, Stylianos Fiflis, Theodora Georgopoulou, Georgia Halkiadaki, Yannis Pantazis, Konstantinos Stylianou, Michalis Hamilos, Emmanuel Foukarakis","doi":"10.3390/medsci14050564","DOIUrl":"10.3390/medsci14050564","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Valvular heart disease frequently accompanies acute heart failure (AHF), yet most studies address single valve lesions, and the prognostic weight of concurrent multivalvular involvement is less well defined. We examined the prevalence of single- and multi-valve disease and its relationship with one-year mortality. &lt;b&gt;Methods:&lt;/b&gt; We analyzed 530 consecutive patients enrolled in a prospective single-center AHF registry between February 2023 and June 2025 and followed for 12 months. Aortic, mitral and tricuspid disease was graded according to European Society of Cardiology/European Association of Cardiovascular Imaging (ESC/EACVI) criteria, a valve being considered involved when it carried at least moderate stenosis and/or regurgitation; multivalvular disease was defined as involvement of two or more valves. The primary endpoint was one-year all-cause mortality. Cox regression was adjusted for admission log N-terminal pro-B-type natriuretic peptide (NT-proBNP), frailty (Clinical Frailty Scale ≥ 5) and age. In-hospital acute kidney injury was examined descriptively but was not entered into the models, because it is ascertained after admission. &lt;b&gt;Results:&lt;/b&gt; Overall, 71.3% of patients had at least one significantly diseased valve-mitral in 44.3%, tricuspid in 43.8% and aortic in 27.5%-and 34.9% had multivalvular involvement. One-year mortality rose stepwise with the number of valves involved: 19.7%, 24.9%, 36.3% and 54.0% for zero, one, two and three valves, respectively (log-rank &lt;i&gt;p&lt;/i&gt; &lt; 0.001), corresponding to a crude hazard ratio (HR) of 1.51 (95% confidence interval [CI] 1.28-1.78) per additional valve. Multivalvular versus single or no valve involvement carried a crude HR of 2.07 (1.51-2.84) and remained associated with mortality after adjustment (HR 1.48, 95% CI 1.06-2.07, &lt;i&gt;p&lt;/i&gt; = 0.020), as did each additional valve (HR 1.22, 1.03-1.45, &lt;i&gt;p&lt;/i&gt; = 0.023). Adjustment for clinically manifest right heart failure (HF) attenuated the association with mortality (HR 1.15, 95% CI 0.96-1.37), whereas the association with the triple composite remained significant (HR 1.19, 95% CI 1.03-1.36). Propensity-score adjustment excluding right HF retained the association with mortality (HR 1.43, 95% CI 1.02-2.00), whereas inclusion of right HF attenuated it (HR 1.33, 0.94-1.87). The association was not detectable in the 304 patients without clinically manifest right HF (HR 1.06, 0.80-1.41, &lt;i&gt;p&lt;/i&gt; = 0.69). In a post-discharge sensitivity analysis, the adjusted associations were directionally similar but did not reach statistical significance. &lt;b&gt;Conclusions:&lt;/b&gt; In hospitalized AHF, multivalvular involvement was common, followed a predominantly mitral-tricuspid pattern, and identified an older, frailer, more congested phenotype with substantial right-sided and chronic renal involvement. Valve burden showed a graded association with one-year mortality that persisted after adjustment for baseline prognostic characteristics, but w","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-Treatment High-Risk HPV Testing as a \"Test of Cure\": A Systematic Review.","authors":"Gavrila Timis, Romeo Micu, Adriana Oana Oltean, Iulian Goidescu, Renata Nicula, Lucian Constantin Mocan","doi":"10.3390/medsci14050561","DOIUrl":"10.3390/medsci14050561","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Excisional treatment is effective for cervical intraepithelial neoplasia grade 2 or 3 (CIN2-3), but residual or recurrent high-grade disease remains clinically important. This focused systematic review evaluated post-treatment high-risk human papillomavirus (hrHPV) testing as a test of cure and compared it with cytology and resection-margin status. <b>Methods:</b> PubMed/MEDLINE was searched and supplemented by structured citation checking and targeted verification, with supplementary Embase and CENTRAL searches conducted during peer review; the review was not prospectively registered. Mixed-grade cohorts were retained only when a high-grade subgroup was extractable or for supportive qualitative evidence. <b>Results:</b> Fifteen primary studies enrolled 21,932 treated women, of whom 18,992 contributed to endpoint-specific analyses. Explicit CIN2+/CIN3+/HSIL+ event rates were 1.9-6.8% in most studies, with 11.8% in one earlier intensively verified cohort; higher rates in other reports reflected any-grade CIN or composite outcomes and were not treated as CIN2+. In the subset reporting directly comparable accuracy measures, hrHPV testing was generally more sensitive than cytology and negative predictive values were 98.0-100%. These values require caution because recurrence prevalence was low and histological verification was incomplete in several cohorts. Five studies were judged at low, eight at unclear, and two at high overall risk of bias for their diagnostic-accuracy contributions. <b>Conclusions:</b> The evidence supports hrHPV-based risk stratification and reduced-intensity surveillance after a negative test, but not unqualified return to routine population screening. Standardised prospective studies with uniform CIN2+ endpoints and complete verification remain needed.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D and Gastric Cancer: A Systematic Review and Meta-Analysis.","authors":"Roxana Pântea, Lorena Elena Meliț","doi":"10.3390/medsci14050562","DOIUrl":"10.3390/medsci14050562","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Gastric cancer is a major global health challenge with multifactorial aetiology. Vitamin D has been investigated for a potential role in gastric carcinogenesis, but evidence remains heterogeneous. This systematic review aimed to synthesise evidence on serum 25(OH)D, dietary vitamin D intake and VDR polymorphisms in relation to gastric cancer in adults and children. <b>Methods:</b> A systematic search following PRISMA 2020 standards was conducted in PubMed, Web of Science, Scopus and Lens.org for studies published from January 2007 to January 2026. Observational studies evaluating vitamin D exposure or VDR polymorphisms in relation to gastric cancer were eligible. Risk of bias was assessed using established instruments. Where comparable data were available, random-effects meta-analyses were performed, with REML estimation and Knapp-Hartung adjustment. <b>Results:</b> Twenty-four studies met the inclusion criteria, and no eligible paediatric studies were identified. Four studies evaluating serum 25(OH)D showed a non-significant tendency towards lower concentrations in gastric cancer patients (MD = -8.82 ng/mL, 95% CI -18.15 to 0.51). Five studies evaluating dietary vitamin D showed no significant association with gastric cancer risk (OR = 0.87, 95% CI 0.47-1.60). Five studies evaluating the VDR FokI polymorphism under the dominant model demonstrated increased gastric cancer susceptibility among variant carriers (OR = 1.44, 95% CI 1.03-2.01). <b>Conclusions:</b> Associations between vitamin D and gastric cancer varied by exposure type. Serum 25(OH)D and dietary intake showed no significant pooled associations, whereas VDR FokI was associated with increased gastric cancer susceptibility. The absence of paediatric evidence highlights an important knowledge gap.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive Spastic Paraparesis Caused by Thoracic Spinal Epidural Lipomatosis: A Case Report and Systematic Review.","authors":"Wojciech S Gaweł, Justyna M Fercho, Olga Kałużna, Zuzanna Krasula, Mateusz Tyburski, Julia Nakoneczna, Remigiusz Kopeć, Jacek Szypenbejl, Jakub Soboń, Marcin Birski, Jacek Furtak, Mariusz Siemiński","doi":"10.3390/medsci14050559","DOIUrl":"10.3390/medsci14050559","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Spinal epidural lipomatosis (SEL) is a rare disorder characterized by excessive epidural fat accumulation. Diagnosis may be challenging because imaging findings are frequently overlooked, and evidence-based management guidelines, particularly thoracic disease, remain limited. &lt;b&gt;Case report:&lt;/b&gt; We present a case report of a 54-year-old male patient, who suffered from lower limb spastic paresis and associated muscle spasms (Nurick grade V). After a difficult diagnostic process, MRI of the thoracic spine confirmed dorsal/posterior spinal epidural lipomatosis (SEL; Manjila grade IIb-α) extending from Th2 to Th9, with moderate thecal sac compression. A small Th6-Th7 intervertebral disc prolapse was also present, without evidence of scoliosis, syrinx, spinal cord edema, or myelomalacia. Following bilateral thoracic decompression and complete resection of the SEL tissue, the patient's neurological function improved markedly, from Nurick grade V preoperatively to Nurick grade II at 11 months of follow-up. Consequently, bilateral laminectomy of the thoracic region was performed with total resection of the SEL tissue. Following surgery, the patient's neurological symptoms improved markedly (Nurick grade II; 11 months postoperatively), and histopathological examination confirmed the diagnosis of spinal epidural lipomatosis. &lt;b&gt;Methods:&lt;/b&gt; We performed a systematic review of case reports of SEL occurring, or co-occurring in the thoracic region based on the literature identified on PubMed, Scopus and Web of Science databases, after using search terms: \"(thoracic) AND (\"spinal\" OR \"epidural\") AND (lipomatosis)\" and filters: [English], [humans] and [year 2020-2026], with the accordance to the PRISMA guidelines. &lt;b&gt;Results:&lt;/b&gt; We identified 21 cases of thoracic SEL from 19 articles. In 12 cases the patients were male, in 9 female. Reported etiological associations included type 1 diabetes mellitus, exogenous corticosteroid exposure, obesity/metabolic syndrome, Cushing syndrome, and CLOVES syndrome. Given the small, case-report-based sample, these findings should be considered reported associations rather than estimates of prevalence or independent risk factors. Surgical treatment of thoracic SEL can be accomplished by various techniques such as laminectomy (continuous or skip), laminoplasty, or minimally invasive procedures-including endoscopic spine surgery. &lt;b&gt;Conclusions:&lt;/b&gt; Large-volume, multicenter studies with long-term clinico-radiological follow-up would be necessary to understand the natural history and treatment outcomes, and to form evidence-based guidelines for interventions. Our case report and findings highlight that thoracic SEL should be included in the differential diagnosis of unexplained compressive myelopathy, even when imaging studies are inconclusive. Rapid identification or possibly reversible causes of myelopathy and initiation of treatment can significantly relieve symptoms, so it is important to remember th","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of Aortic Valve Replacement Across Two Eras: Institutional Changes in Transcatheter and Surgical Practice and Outcomes.","authors":"Jack T Nickles, Marco Tagliafierro, Ezra Moos, Kenji Kaproth, Sarab Anand, Shirley Ge, Ali Fatehi Hassanabad, Luigi Pirelli","doi":"10.3390/medsci14050558","DOIUrl":"10.3390/medsci14050558","url":null,"abstract":"<p><p><b>Objectives:</b> Conventionally, the gold standard for aortic valve disease has been surgical aortic valve replacement (SAVR). Advances in transcatheter aortic valve replacement (TAVR) have since produced marked improvements in both outcomes and procedural volume. We sought to characterize this evolution by comparing the earliest and most recent 100 procedures of each modality at a single high-volume institution. <b>Methods:</b> We retrospectively compared four cohorts of 100 consecutive isolated procedures: 100 TAVRs from 2012 (the earliest period of complete and verifiable registry capture) and 100 first-time SAVRs from a contemporaneous period (2011), each versus the 100 most recent procedures of the same modality (TAVR 2024; SAVR 2024-2025). The SAVR cohorts were limited to first-time, isolated replacement; the TAVR cohorts to native-valve procedures. The primary endpoint was the 30-day composite of death or stroke. Secondary endpoints included new permanent pacemaker implantation, paravalvular leak, vascular access route, anesthetic technique, and length of stay. <b>Results:</b> For TAVR, the 30-day composite of death or stroke fell from 10% to 1% (<i>p</i> = 0.010), with fewer in-hospital deaths (6% to 0%; <i>p</i> = 0.029) and less new dialysis (4% to 0%; <i>p</i> = 0.059). A paravalvular leak of at least mild severity fell from 27% to 3% (<i>p</i> < 0.001), with none as moderate or greater in either era. New pacemaker implantation decreased from 15% to 6% (<i>p</i> = 0.056). Within the same comparison, general anesthesia decreased from 100% to 23%, non-transfemoral access from 29% to 2%, median ICU stay from 43 to 0 h, and hospital stay from 6 to 1 day (all <i>p</i> < 0.001). SAVR outcomes remained similar (composite 2% to 0%, <i>p</i> = 0.497; pacemaker 1% to 0%; and paravalvular leak 0% to 4%), while prolonged ventilation (11% to 1%; <i>p</i> = 0.007) and hospital stay (8 to 5 days; <i>p</i> < 0.001) improved. The SAVR population became younger (74 to 64 years; <i>p</i> < 0.001), and isolated first-time surgery was markedly less frequent, requiring 18.9 versus 5.7 months to accrue 100 consecutive cases. <b>Conclusions:</b> In this two-era institutional comparison, recent-era TAVR outcomes were markedly better, while SAVR outcomes remained excellent in both eras within a recent population that was younger and in whom eligible isolated first-time surgery was less frequent. Because the eras differed substantially in patient risk profile, these unadjusted within-modality comparisons describe a real-world redistribution of aortic stenosis care between two increasingly complementary treatments rather than isolating the effect of any single procedural or technological factor.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabigerol at the Interface of the Gut Microbiota and EndoCannabinoidome: Mechanistic Insights into Inflammation and Pain Modulation.","authors":"Gloria Marisol Castañeda-Ruelas, Lucía Elhy Grijalva-Contreras, Geovanna Nallely Quiñonez-Bastidas","doi":"10.3390/medsci14050560","DOIUrl":"10.3390/medsci14050560","url":null,"abstract":"<p><p>Recent years have seen growing medical interest in the influence of crosstalk between the gut microbiota and the endocannabinoidome (eCBome) on inflammation and pain modulation. Growing evidence indicates that gut microbiota can modify the effects of several marketed drugs, including analgesics. Cannabigerol (CBG) is an overlooked phytocannabinoid with a broad pharmacological spectrum and no psychotropic effects, which has anti-inflammatory and antinociceptive properties. This review aims to provide a comprehensive exploration of CBG and its role at the intersection of gut microbiota and eCBome, detailing the pharmacological mechanisms by which it acts as a promising therapeutic agent to modulate chronic inflammation and pain. Our data review suggests that CBG could act on the eCBome by activating CB2, PPARs, TRPV1, TRPA1, and α2-adrenergic receptors, while suppressing cellular and molecular mechanisms of inflammation, such as TNFα, COX-2, iNOS, IL-1β, and IL-6, and increasing antioxidant factors. These receptors and enzymes are distributed across neurons, glial, immune, and epithelial cells, which can also positively modulate gut microbiota and its metabolites, producing neurotransmitters, cytokines, and enzymes that regulate eCBome tone, and generating cannabinoid-mimetic compounds as part of pleiotropic functions. Nevertheless, CBG may exert direct effects on gut microbiota, promoting eubiosis and symbiotic bacteria. Moreover, there are no specific preclinical assays that demonstrate how CBG modulates the bidirectional communication between the gut microbiota and eCBome, addressing the specific mechanism involved in eCBome activation, and determining whether its anti-inflammatory and analgesic effects are dependent on gut microbiota type. Therefore, studies are required to evaluate this hypothesis to achieve translational medicine impact.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adiposity-Metabolic Discordance Identifies Cardiometabolically Heterogeneous Profiles in Normal-Weight Adults: A Cross-Sectional Study.","authors":"Diego González Carrasco, Pedro Juan Tárraga López, Mónica Silu Piña Dabreu, Lluis Rodas Cañellas, Ángel Arturo López-González, José Ignacio Ramírez-Manent","doi":"10.3390/medsci14050557","DOIUrl":"10.3390/medsci14050557","url":null,"abstract":"<p><strong>Background: </strong>Body mass index (BMI) is widely used to classify obesity and cardiometabolic risk, although it may fail to detect hidden metabolic impairment in individuals with normal body weight. Increasing evidence suggests that adiposity and metabolic dysfunction may not always coexist, giving rise to biologically discordant phenotypes associated with different cardiometabolic profiles.</p><p><strong>Methods: </strong>This cross-sectional study was a secondary analysis of a subset of normal-weight adults selected from a larger database of Spanish workers undergoing routine occupational health examinations between 2019 and 2024. The final analytical sample included 166,008 workers aged 18-69 years with BMI values between 18.5 and 24.9 kg/m². Participants were classified into four adiposity-metabolic phenotypes according to the presence or absence of increased adiposity, operationally defined as a waist-to-height ratio (WtHR) ≥ 0.50, and metabolic dysfunction, defined as the presence of ≥2 of five adverse cardiometabolic criteria. METS-VF was additionally evaluated as a marker of visceral adiposity. Anthropometric, metabolic, vascular, and lifestyle-related variables were analyzed. Multivariable logistic regression models were used to evaluate factors associated with discordant phenotypes.</p><p><strong>Results: </strong>The concordant healthy phenotype was the most prevalent subgroup (78.9%), followed by adiposity-only (9.8%), metabolic-only (9.2%), and concordant high-risk phenotypes (2.0%). Despite normal BMI, approximately 21% of participants exhibited adiposity-metabolic discordance or combined high-risk status. The metabolic-only phenotype showed markedly adverse triglyceride, TG/HDL-c ratio, fasting glucose, and blood pressure values despite relatively preserved anthropometric parameters. Conversely, the adiposity-only phenotype exhibited increased central and visceral adiposity with comparatively preserved metabolic status. Sedentary lifestyle, unfavorable dietary adherence, smoking, older age, male sex, and higher BMI within the normal-weight range were independently associated with metabolically adverse phenotypes. The concordant high-risk phenotype demonstrated the greatest overall cardiometabolic burden.</p><p><strong>Conclusions: </strong>Adults with normal BMI are metabolically heterogeneous and may present clinically relevant hidden-risk phenotypes despite conventional normal-weight classification. Adiposity-metabolic discordance highlights the limitations of BMI-based screening alone and supports the incorporation of multidimensional anthropometric, metabolic, and lifestyle-related assessment strategies for earlier identification of cardiometabolic risk.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning-Predicted Length of Hospital Stay in Pediatric Appendicitis: An Exploratory Comparative Study of Clinical and Ultrasound-Based Models with Explainable Artificial Intelligence and Bayesian Analysis.","authors":"Kannan Sridharan, Gowri Sivaramakrishnan","doi":"10.3390/medsci14050556","DOIUrl":"10.3390/medsci14050556","url":null,"abstract":"<p><p><b>Background:</b> Accurate prediction of hospital length of stay (LOS) in pediatric appendicitis is essential for optimizing resource allocation, guiding discharge planning, and improving patient outcomes. This study aimed to explore the potential of machine learning (ML) models for predicting LOS using clinical and ultrasound features, compare the added value of ultrasound findings, and provide interpretable insights using explainable artificial intelligence (XAI) and Bayesian analysis. <b>Methods:</b> A retrospective cohort of 323 pediatric patients with uncomplicated appendicitis was analyzed from publicly available open-access data from the UCI Machine Learning Repository. Clinical-only and clinical-plus-ultrasound feature sets were used to train Random Forest, XGBoost, and Bayesian Additive Regression Trees (BART) models. Performance was evaluated using mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE), and P20 (percentage of predictions within 20% of actual values) with 95% confidence intervals (CIs) from bootstrap resampling. XAI analysis was employed for model interpretability, with exploratory, hypothesis-generating subgroup analyses and sensitivity analyses conducted across patient demographics and imputation strategies. <b>Results:</b> The Random Forest clinical model achieved the best performance (RMSE: 1.66 days, 95% CI: 1.20-2.15; MAE: 1.08 days, 95% CI: 0.80-1.42; P20: 58.7%, 95% CI: 46.0-69.8), significantly outperforming XGBoost (<i>p</i> = 0.03 for RMSE). BART demonstrated comparable accuracy (RMSE: 1.57 days, 95% CI: 1.21-2.12). SHAP analysis identified absence of peritonitis and appendix diameter as the most influential predictors. Subgroup analysis revealed a potentially better performance in female patients (RMSE: 1.21 days, P20: 75.8%) but poor accuracy for prolonged LOS ≥6 days (RMSE: 4.13 days, P20: 0%). Sensitivity analysis confirmed robustness of imputation (Spearman's rho: 0.782-0.927). <b>Conclusions:</b> ML models, particularly Random Forest, predict LOS in pediatric appendicitis using clinical features. XAI provides clinically interpretable insights.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}