Biomedicines最新文献

{"title":"Unraveling the Functional Impact of Splicing Variants in Inherited Hearing Disorders Through Minigene Splicing Assays.","authors":"Lara Emily Rosso, Giulia Pianigiani, Anna Morgan, Elisa Rubinato, Elisa Paccagnella, Stefania Lenarduzzi, Anita Wischmeijer, Beatrice Spedicati, Giorgia Girotto","doi":"10.3390/biomedicines13092245","DOIUrl":"10.3390/biomedicines13092245","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Hereditary hearing loss (HHL) is a genetically heterogeneous condition, involving more than 150 genes in non-syndromic cases and associated with over 400 distinct disorders in syndromic forms. Although whole-exome sequencing (WES) has markedly increased diagnostic yield, a substantial number of cases remain unsolved, often due to intronic variants that affect splicing and are difficult to interpret. This study aimed to characterize the potential impact of intronic variants predicted to alter splicing in families affected by HHL. <b>Methods</b>: The effect of seven intronic variants, previously identified in a diagnostic setting by WES within <i>ADGRV1</i>, <i>ATP11A</i>, <i>GSDME</i>, <i>OTOF</i>, <i>OTOGL</i>, and <i>USH2A</i> genes, was evaluated. To functionally validate these predictions, in vitro minigene splicing assays were subsequently performed. <b>Results</b>: All the identified variants were predicted to disrupt normal RNA splicing. The functional studies with minigene assays confirmed this observation and showed that the tested variants induced both exon skipping and activation of cryptic splice sites. In five out of seven cases, these splicing alterations caused a frameshift and introduced a premature termination codon, ultimately resulting in nonsense-mediated mRNA decay and protein degradation. <b>Conclusions</b>: This study expands the mutational spectrum of HL-related genes and highlights the importance of integrating in silico predictions with minigene assays. Such a combined approach is crucial for accurate interpretation of splicing variants, particularly when patient-derived RNA samples are unavailable.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymorphisms in <i>VEGF</i> Signaling Pathway Genes and Their Potential Impact on Type 2 Diabetes Mellitus and Associated Complications: A Scoping Review.","authors":"Christiane Mayrhofer Grocoske de Lima, Rafaela Cirillo de Melo, Nathalia Marçallo Peixoto Souza, Paula Rothbarth Silva, Dayane Ferreira Aguiar, Luana Mota Ferreira, Waldemar Volanski, Geraldo Picheth, Fabiane Gomes de Moraes Rego, Marcel Henrique Marcondes Sari","doi":"10.3390/biomedicines13092242","DOIUrl":"10.3390/biomedicines13092242","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Type 2 diabetes mellitus (T2DM) is a chronic and multifactorial metabolic disorder associated with genetic and environmental factors. Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and vascular homeostasis, and genetic polymorphisms in the <i>VEGF</i> signaling pathway have been linked to the T2DM development, progression, and complications. This scoping review investigated the association between <i>VEGF</i> gene and <i>VEGF</i> receptors single-nucleotide polymorphisms (SNPs) and susceptibility to T2DM and vascular complications. <b>Methods</b>: A thorough systematic review was performed utilizing scientific databases (PubMed, Web of Science, and Scopus) in March 2025. From an initial pool of 796 records, 59 relevant articles were selected for inclusion in the analysis. <b>Results:</b> The most frequently studied SNPs were rs2010963 (31/59), rs699947 (16/59), rs3025039 (15/59), rs833061 (11/59), rs1570360 (7/59) in the <i>VEGFA</i> gene and rs2071559(6/59) in <i>VEGFR2</i>. The studies include a diverse range of ethnic groups, including Asian, European and Middle Eastern populations. The main complications associated with these SNPs were microvascular conditions such as diabetic retinopathy (DR) (49/59), diabetic neuropathy (DPN) (6/59), diabetic nephropathy (DNP) (2/59), and as well as macrovascular complications including diabetic foot ulcers (DFU) (10/59). The results revealed that these polymorphisms, particularly rs3025039 and rs2010963, were more consistently associated with microvascular complications such as DR rather than with T2DM itself. The C allele of rs2010963 was associated with increased risk of DR in Indian populations, while no such association was observed in European. Similarly, the T allele of rs3025039 conferred protection against DPN in a Chinese population but was associated with higher DR risk in an Indian study, suggesting that the same allele may play distinct roles depending on ethnic background and clinical phenotype. <b>Conclusions</b>: <i>VEGF</i> signaling pathway genetic polymorphisms demonstrate potential as biomarkers for diabetic complications, especially microvascular outcomes. The findings suggest a genetic basis for differences in complications of T2DM. Future studies should investigate relevant SNPs across diverse ethnic groups to better understand genetic risks associated with the disease and its vascular complications.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TCF Plus Radiochemotherapy Versus Neoadjuvant Radiochemotherapy Versus Flot Perioperative Chemotherapy in Esophageal Adenocarcinoma: The Results of a Three-Cohort, Multi-Centric Comparison: The A4 Study.","authors":"Marco Lorenzo Bonù, Giulia Volpi, Gloria Zanni, Jacopo Balduzzi, Fabrizia Terraneo, Giusto Pignata, Giuseppina Arcangeli, Francesco Frassine, Paola Vitali, Eliana La Rocca, Simone Giacopuzzi, Jacopo Weindelmayer, Carlo Alberto De Pasqual, Martina Milazzo, Michele Pavarana, Valentina Zen, Stefano De Pascale, Uberto Fumagalli Romario, Michela Buglione, Giovanni De Manzoni","doi":"10.3390/biomedicines13092236","DOIUrl":"10.3390/biomedicines13092236","url":null,"abstract":"<p><p><b>Introduction:</b> Recent randomized evidence suggests that stage II-IV non metastatic esophageal adenocarcinoma is best managed with perioperative chemotherapy (CHT) and surgery. Intensification of neoadjuvant chemotherapy and radiochemotherapy are proposed before surgery in high-volume centers with the aim of increasing both systemic and locoregional control. However, few data comparing intensified RTCHT, CHT plus RTCHT and perioperative CHT with FLOT in real-life scenarios are available. <b>Methods:</b> This is a multicenter, retrospective series, including three cohorts of patients treated for esophageal adenocarcinoma: Cohort A: nRTCHT; Cohort B: TCF plus RTCHT, defined as triplet chemotherapy followed by dose-reduced triplet therapy + RT; Cohort C: perioperative chemotherapy with FLOT regimen. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were pathologic complete response (pCR), pathologic lymph-node complete response (ypN0), overall survival (OS), and perioperative acute toxicity. <b>Results:</b> From January 2013 to December 2023, 142 patients were identified. All patients received multimodal therapy with radical esophagectomy. A total of 95% of patients were male; the majority of patients presented with stage cT3cN1. A total of 63 patients were treated in Cohort A (31 cases with doublet 5FU-CDDP concurrent to 50.4 Gy and 32 cases with CROSS regimen), 36 in Cohort B, and 43 in Cohort C. After a median FU of 36 months, the 3-year DFS resulted 58.6%. pCR occurred in 26 cases (18.6%). Three-year OS had a value of 72%. At univariate analysis, ypN0 was related to better DFS; cN+ disease was related with worse OS. The treatment cohort did not impact survival outcomes; however, an effect on CR was shown, with pCR in 15% (A), 36.3% (B), 11% (C) of cases, respectively (χ: 0.008). A total of 67% of patients in Cohort B experienced a ypN0. Two treatment-related deaths occurred (one in Cohort A and one in C) with a slight increase in G3 toxicity in cohort C. <b>Conclusions:</b> In this real-life multicenter series, oncological results were adequate for all three neoadjuvant strategies. TCF plus RTCHT guaranteed a higher pCR and ypN0 rate without increasing toxicity. An intensified neoadjuvant schedule, such as TCF plus RTCHT, may be useful in cases where higher tumor and nodal responses are needed. Taken together, our data highlight that further investigation is warranted before abandoning radiotherapy-based neoadjuvant approaches in esophageal and GEJ adenocarcinoma.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk for COVID-19 Vulnerability in Patients with Inflammatory Bowel Disease: Assessing Alterations in ACE2 and TMPRSS2.","authors":"Jorge Sáez-Leyva, Matthew P Lennol, Carlos Avilés-Granados, María-Salud García-Ayllón, Javier Sáez-Valero","doi":"10.3390/biomedicines13092240","DOIUrl":"10.3390/biomedicines13092240","url":null,"abstract":"<p><p>Chronic inflammatory conditions often involve the dysregulation of key enzymes, including serine proteases such as transmembrane serine protease 2 (TMPRSS2) and the angiotensin converting enzyme 2 (ACE2), which are key proteins implicated in the cellular entry mechanism of SARS-CoV-2. It remains uncertain whether the gastrointestinal symptoms observed in COVID-19 patients result from direct viral infection of the gastrointestinal tract, a process that may be exacerbated by altered expression of ACE2 or TMPRSS2. In this review, we explore the interplay among ACE2 and TMPRSS2 in the context of inflammatory bowel disease (IBD), including their roles in disease pathology and response to therapy. We also examine methodological approaches for assessing whether protease alterations contribute to increased susceptibility to infection, considering that TMPRSS2 exists in inactive (zymogen) and active forms. Furthermore, while membrane-bound ACE2 facilitates viral entry, soluble ACE2 fragments may act as decoys, preventing virus-receptor interaction. Therefore, the interpretation of changes in full-length versus cleaved forms of ACE2 and related enzymes is critical for understanding vulnerability to SARS-CoV-2 infection.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optical and Scanning Electron Microscopy Thrombus Findings in Patients with STEMI Undergoing Primary Versus Rescue PCI.","authors":"Stella Marinelli Pedrini, Thiago P A Aloia, André H Aguillera, Paula M P S Gomes, Jamil R Cade, Francisco Sandro Menezes-Rodrigues, Bárbara P Freitas, Marco T Souza, Francisco A H Fonseca, Marcos Danillo Oliveira, Breno O Almeida, Andrey J Serra, Renato D Lopes, Rita Sinigaglia-Coimbra, Adriano Caixeta","doi":"10.3390/biomedicines13092235","DOIUrl":"10.3390/biomedicines13092235","url":null,"abstract":"<p><p><b>Background</b>: The mechanisms underlying fibrinolysis failure in patients with STEMI who are undergoing a pharmacoinvasive strategy appear to be multifactorial and may be associated with the thrombus's architecture and composition. <b>Objective</b>: We aimed to compare the thrombus composition in patients with STEMI who were undergoing rescue percutaneous coronary intervention (rPCI) versus primary PCI (pPCI) using optical microscopy (OM) and scanning electron microscopy (SEM). Methods: Fifty-three patients were prospectively enrolled, with twenty-five undergoing rPCI and twenty-eight undergoing pPCI. After thrombus aspiration, each harvested fragment was divided into two pieces: one was analyzed using OM with a 60× magnifying lens on hematoxylin-eosin-stained samples, and the other with SEM at 5000× magnification. <b>Results</b>: Patients who underwent rPCI had significantly higher C-reactive protein levels and a longer ischemic interval at admission compared to those treated with pPCI (9.92 h [range: 1.58-106.17] vs. 2.14 h [range: 0-48]; <i>p</i> < 0.001). Optical microscopy analysis revealed that thrombi from rPCI patients exhibited a significantly higher erythrocyte area percentage (18.36% [range: 0.3-50.08] vs. 0.91% [range: 0-70.1]; <i>p</i> = 0.001), a lower fibrin content as assessed by optical microscopy (79.49% [range: 49.2-98.25] vs. 94.43% [range: 29.19-99.92]; <i>p</i> = 0.006), and a greater amount of cholesterol crystals as measured by SEM (1.73 μm² [range: 0-18.51] vs. 0.08 μm² [range: 0-0.71]; <i>p</i> < 0.001). <b>Conclusions</b>: The thrombus composition of patients with STEMI who are undergoing rPCI had higher amounts of erythrocytes and cholesterol crystals and a lesser area occupied by fibrin compared to those undergoing pPCI. The composition of thrombi in rPCI could potentially contribute to the failure of fibrinolytic therapy within a pharmacoinvasive strategy.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-Citrulline Improves Recovery of Enterocytes While Not Affecting Gut Microbiota in an In Vitro Model of Chemotherapy-Induced Gastrointestinal Mucositis.","authors":"Wally van der Laan, Pablo A Gallardo Molina, Debby P Y Koonen, Hermie J M Harmsen, Wim J E Tissing","doi":"10.3390/biomedicines13092244","DOIUrl":"10.3390/biomedicines13092244","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Despite significant advancements in cancer treatment outcomes, side effects, such as gastrointestinal mucositis (GIM), continue to impair patients' quality of life. The recent literature suggests L-citrulline as a novel treatment for GIM. However, no in vitro model to study the potential for L-citrulline as a treatment for GIM is currently available, and the effect of L-citrulline on the gut microbiota remains unclear. This study aims to propose a suitable in vitro model to study the effect of L-citrulline on the gut microbiota and to determine whether it can mitigate GIM. <b>Methods:</b> The CaCo-2 and T84 cell lines were cultured using cell impedance assays and treated with different doses of methotrexate and melphalan to select an appropriate model for L-citrulline research. The selected model was further used to investigate the impact of L-citrulline on gut microbiota cultured using microbial culture assays containing YCFAG. <b>Results:</b> Neither CaCo-2 nor T84 cells treated with methotrexate were suitable models for our study due to varying responses to treatment. T84 cells treated with 100 μg/mL melphalan demonstrated a consistent response, making them a suitable model for in vitro research on treatments for GIM. The use of L-citrulline demonstrated potential protective effects, as melphalan-treated enterocytes showed less cellular damage in its presence and slightly reduced enteroaggregative <i>E. coli</i> growth. <b>Conclusions:</b> L-Citrulline supplementation reduced epithelial cell injury due to melphalan, suggesting therapeutic potential. Further testing is required to determine its efficacy in vivo and clarify the mechanisms underlying this potential benefit.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Biomarkers to Behavior: Mapping the Neuroimmune Web of Pain, Mood, and Memory.","authors":"Masaru Tanaka, Simone Battaglia","doi":"10.3390/biomedicines13092226","DOIUrl":"10.3390/biomedicines13092226","url":null,"abstract":"<p><p>Mounting evidence situates mood disturbance, memory decline, and chronic pain within a single neuro-immune conversation [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the Polyphenolic Profile and Beneficial Effects of Red and Green Propolis in Skin Inflammatory Conditions and Oxidative Stress.","authors":"Andrea Magnavacca, Giulia Martinelli, Nicole Maranta, Carola Pozzoli, Marco Fumagalli, Giangiacomo Beretta, Stefano Piazza, Mario Dell'Agli, Enrico Sangiovanni","doi":"10.3390/biomedicines13092229","DOIUrl":"10.3390/biomedicines13092229","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Propolis is a complex natural product with long-standing traditional use as an antimicrobial remedy. Several studies suggest that Brazilian varieties of propolis may promote wound healing and protect the skin from UV damage, most likely due to antioxidant and anti-inflammatory mechanisms. However, the literature provides limited support for this topic. The present work aimed at characterizing the polyphenolic profile of two Brazilian propolis samples, investigating their biological activity. <b>Methods:</b> Biological experiments were conducted in human keratinocytes (HaCaT) and fibroblasts (HDF) stimulated by cytokines involved in skin inflammation and remodeling (TNF-α and IL-1β), while phytochemical analyses were conducted by LC-MS techniques. <b>Results:</b> Our findings indicate that artepillin C and drupanin were the principal phytochemicals of green propolis, while vestitol, medicarpin, and neovestitol were the most abundant in red propolis. The presence of phenolic compounds was correlated with the antioxidant activity demonstrated by ORAC and intracellular ROS assays. Accordingly, both Brazilian propolis samples impaired NF-κB activity, while only red propolis hindered IL-8 release in both cell lines with an IC₅₀ lower than 25 μg/mL. Surprisingly, both propolis samples at the same concentrations enhanced the production of IL-6 and VEGF, thus suggesting the coexistence of anti-inflammatory, antioxidant, and trophic mechanisms contributing to skin repair. In line with this hypothesis, propolis also induced the stabilization of HIF-1α, paralleling the biological effect of a well-known synthetic HIF stabilizer (DMOG). <b>Conclusions:</b> This work supports the investigation of Brazilian red and green propolis as potential modulators of the inflammatory phase in wound healing.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemodynamic and Clinical Predictors of Thrombolysis in Post-COVID Venous Thromboembolism: A Retrospective Cohort Study.","authors":"Giulia-Mihaela Cojocaru, Antoniu Octavian Petriş, Alin-Constantin Pînzariu, Tudor Cojocaru, Andreea Coca, Ruxandra Cojocaru, Catherine-Teodora Costan, Victorița Șorodoc, Elena Cojocaru","doi":"10.3390/biomedicines13092232","DOIUrl":"10.3390/biomedicines13092232","url":null,"abstract":"<p><p><b>Objectives:</b> Post-acute venous thromboembolism (VTE) is a well-recognized complication of COVID-19, driven by persistent endothelial dysfunction and thromboinflammation. Identifying simple clinical predictors of VTE may optimize therapy and limit adverse outcomes. We propose a pragmatic risk-stratification approach, based on clinical and echocardiographic parameters. <b>Methods:</b> We conducted a retrospective cohort study in a Romanian tertiary hospital (March 2020-April 2022) in 54 adults with laboratory-confirmed COVID-19 and imaging-confirmed VTE. Demographics, comorbidities, laboratory markers, and echocardiographic variables-particularly tricuspid annular plane systolic excursion (TAPSE), peripheral oxygen saturation (SpO₂), and left-ventricular end-diastolic diameter (LVEDD)-were collected. The primary outcome was the percentage of patients receiving systemic thrombolysis. Statistical analyses included Mann-Whitney U tests, chi-square, Spearman correlations, and multivariable logistic regression. <b>Results:</b> The mean age was 61.2 ± 14.7 years, and 63% were men. Eleven patients (20.4%) underwent thrombolysis. Compared with conservatively managed patients, those receiving thrombolysis had lower TAPSE (13.0 vs. 20.8 mm), lower SpO₂ (90.1 vs. 97.0%), and smaller LVEDD (24.4 vs. 46.1 mm); all differences were statistically significant. Each 1 mm decrease in TAPSE and 1% decrease in SpO₂ increased the likelihood of thrombolysis (adjusted odds ratios 1.58 and 1.34, respectively). Inflammatory markers and right-ventricular diameter were not associated with treatment. <b>Conclusions:</b> Reduced TAPSE, lower SpO₂, and decreased LVEDD identify post-COVID VTE patients at elevated risk of hemodynamic compromise requiring thrombolysis. A point-of-care assessment incorporating these variables may improve early risk stratification and guide therapeutic decisions.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension (CTEPH): A Systematic Review of Prevalence, Clinical Phenotype, and Surgical Outcomes.","authors":"Ema Borsi, Cristina Potre, Ioana Ionita, Miruna Samfireag, Cristina Secosan, Ovidiu Potre","doi":"10.3390/biomedicines13092215","DOIUrl":"10.3390/biomedicines13092215","url":null,"abstract":"<p><p><b>Background and Objectives:</b> Congenital thrombophilias are biologically plausible contributors to chronic thromboembolic pulmonary hypertension (CTEPH), yet their frequency and clinical impact remain uncertain. We undertook a systematic review to (i) estimate the pooled prevalence of specific hereditary defects among adults with CTEPH, (ii) characterise associated demographic and haemodynamic phenotypes, and (iii) summarise peri-operative and survival outcomes after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in genetically defined subgroups. <b>Methods:</b> A protocol compliant with PRISMA-2020 was registered prospectively on the Open Science Framework (OSF). PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to 1 June 2025 using validated, PRESS-reviewed strings combining CTEPH and thrombophilia terms. Observational cohorts, case-control studies and trials reporting laboratory-confirmed congenital thrombophilias in adults with right-heart-catheter-defined CTEPH were eligible. <b>Results:</b> Eight studies encompassing 677 unique CTEPH patients met the inclusion criteria. Among the 400 individuals screened for deficiencies of the natural anticoagulant pathways, 56 possessed a defect: protein S deficiency 5.3% (21/400; 95% CI 3.3-8.0), protein C deficiency 4.3% (17/400; 2.5-6.8), and antithrombin deficiency 1.5% (6/400; 0.6-3.3). In 520 genotyped patients, factor V Leiden and prothrombin G20210A were infrequent (1.3% and 1.0%, respectively) and confined to European/North American cohorts. Baseline haemodynamics were uniformly severe (mean mPAP 46.7 mm Hg; pulmonary vascular resistance ≈ 9 WU). Definitive reperfusion therapy was common (PEA 63%; BPA 18%), reducing mPAP to 20.5 mm Hg and yielding a weighted one-year survival of 96.2%. No study demonstrated a thrombophilia-specific effect on surgical candidacy or early survival. <b>Conclusions:</b> Approximately one in seven patients with CTEPH harbours a congenital thrombophilia, most often protein S or protein C deficiency, whereas classic venous-thrombo-embolism mutations are rare and ethnically restricted. Current evidence indicates that genetic status does not materially influence haemodynamic severity, uptake of PEA/BPA, or short-term survival, supporting guideline recommendations for universal referral to specialist reperfusion centres. Future multicentre registries integrating systematic genotyping and long-term outcome capture are needed to clarify genotype-specific prognostic and therapeutic implications.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}