Biomedicines最新文献

{"title":"Temporal Trends and Differences in Inpatient Palliative Care Use in Metastatic Penile Cancer Patients.","authors":"Carolin Siech, Lukas Scheipner, Andrea Baudo, Mario de Angelis, Letizia Maria Ippolita Jannello, Francesco Di Bello, Fred Saad, Shahrokh F Shariat, Nicola Longo, Luca Carmignani, Ottavio de Cobelli, Sascha Ahyai, Alberto Briganti, Séverine Banek, Luis A Kluth, Felix K H Chun, Pierre I Karakiewicz","doi":"10.3390/biomedicines13071756","DOIUrl":"10.3390/biomedicines13071756","url":null,"abstract":"<p><p><b>Objectives</b>: To quantify inpatient palliative care use over time and to test whether patient or hospital characteristics represent determinants of inpatient palliative care use in patients with metastatic penile cancer. <b>Methods</b>: Relying on the National Inpatient Sample database (2006-2019), we identified 1017 metastatic penile cancer patients. Estimated annual percentage change analyses and multivariable logistic regression models addressing inpatient palliative care use were fitted. <b>Results</b>: Of 1017 metastatic penile cancer patients, 139 (13.7%) received inpatient palliative care. Over time, the proportion of inpatient palliative care use per year increased from 6.5% in 2006 to 17.8% in 2019 (estimated annual percentage change +6.7%; <i>p</i> = 0.001). In the multivariable logistic regression models, contemporary study years (odds ratio [OR] 1.80; <i>p</i> = 0.003), the presence of bone metastases (OR 1.90; <i>p</i> = 0.002) and the presence of brain metastases (OR 2.60; <i>p</i> = 0.013) independently predicted higher inpatient palliative care use. Conversely, distant lymph node metastases independently predicted lower inpatient palliative care use (OR 0.58; <i>p</i> = 0.022). Finally, hospital admission in the South (OR 2.42; <i>p</i> = 0.007) and in the Northeast (OR 2.34; <i>p</i> = 0.015) was associated with higher inpatient palliative care use than hospital admission in the Midwest. <b>Conclusions</b>: In metastatic penile cancer patients, the proportions of inpatient palliative care use were low but have increased over time. Unfortunately, some geographical regions are more refractory to inpatient palliative care use than others. Finally, specific patient characteristics such as bone metastases and brain metastases represent independent predictors of higher inpatient palliative care use.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727471","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":"Improvement of Blood Flow and Epidermal Temperature in Cold Feet Using Far-Infrared Rays Emitted from Loess Balls Manufactured by Low-Temperature Wet Drying Method: A Randomized Trial.","authors":"Yong Il Shin, Min Seok Kim, Yeong Ae Yang, Yun Jeong Lee, Gye Rok Jeon, Jae Ho Kim, Yeon Jin Choi, Woo Cheol Choi, Jae Hyung Kim","doi":"10.3390/biomedicines13071759","DOIUrl":"10.3390/biomedicines13071759","url":null,"abstract":"<p><p><b>Background:</b> Cold feet syndrome is characterized by hypersensitivity of sympathetic nerves to cold stimuli, resulting in vasoconstriction and reduced peripheral blood flow. This condition causes an intense cold sensation, particularly in the extremities. Although hormonal changes (e.g., during childbirth or menopause) and psychological stress have been implicated, the mechanisms and effective treatments remain unclear. <b>Methods:</b> Ninety adult volunteers were randomized into three groups based on the type of heating mat applied to the feet, with surface temperatures gradually increased from 20 °C to 50 °C. Group A (control) used non-FIR electric mats, Group B used carbon FIR mats, and Group C used loess bio-ball FIR mats. Blood flow (mL/min/100 g) and epidermal temperature (°C) in the left big toe (LBT) and right big toe (RBT) were measured before and after heating or FIR exposure using laser Doppler flowmetry and infrared thermometers. <b>Results:</b> No significant changes in blood flow or skin temperature were observed in Group A. In Group B, blood flow increased by 15.07 mL/min/100 g in the LBT (from 4.12 ± 2.22 to 19.19 ± 5.44) and by 14.55 mL/min/100 g in the RBT (from 4.26 ± 2.29 to 18.81 ± 4.29). In Group C, blood flow increased by 32.86 mL/min/100 g in the LBT (from 4.23 ± 1.64 to 37.09 ± 6.04) and by 32.63 mL/min/100 g in the RBT (from 4.20 ± 1.61 to 36.83 ± 6.48). Epidermal temperature also increased significantly in Group C. All changes in Groups B and C were statistically significant (<i>p</i> < 0.05), with Group C showing the most prominent enhancement. <b>Conclusions:</b> The loess bio-ball mat significantly increased both peripheral blood flow and epidermal temperature compared to the electric and carbon mats. These findings suggest that FIR emitted from loess bio-balls may enhance peripheral circulation through hypothalamus thermogenic response and nitric oxide (NO)-dependent pathways and could serve as a complementary and non-invasive intervention for individuals with poor blood flow.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727424","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":"Revolutionizing Allogeneic Graft Tolerance Through Chimeric Antigen Receptor-T Regulatory Cells.","authors":"Alvin Man Lung Chan, Rajalingham Sakthiswary, Yogeswaran Lokanathan","doi":"10.3390/biomedicines13071757","DOIUrl":"10.3390/biomedicines13071757","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Organ transplantation is a life-saving intervention for patients with terminal organ failure, but long-term success is hindered by graft rejection and dependence on lifelong immunosuppressants. These drugs pose risks such as opportunistic infections and malignancies. Chimeric antigen receptor (CAR) technology, originally developed for cancer immunotherapy, has been adapted to regulatory T cells (Tregs) to enhance their antigen-specific immunosuppressive function. This systematic review evaluates the preclinical development of CAR-Tregs in promoting graft tolerance and suppressing graft-versus-host disease (GvHD). <b>Methods:</b> A systematic review following PROSPERO guidelines (CRD420251073207) was conducted across PubMed, Scopus, and Web of Science for studies published from 2015 to 2024. After screening 105 articles, 17 studies involving CAR-Tregs in preclinical or in vivo transplant or GvHD models were included. <b>Results:</b> CAR-Tregs exhibited superior graft-protective properties compared to unmodified or polyclonal Tregs. HLA-A2-specific CAR-Tregs consistently improved graft survival, reduced inflammatory cytokines, and suppressed immune cell infiltration across skin, heart, and pancreatic islet transplant models. The inclusion of CD28 as a co-stimulatory domain enhanced Treg function and FOXP3 expression. However, challenges such as Treg exhaustion, tonic signaling, and reduced in vivo persistence were noted. Some studies reported synergistic effects when CAR-Tregs were combined with immunosuppressants like rapamycin or tacrolimus. <b>Conclusions:</b> CAR-Tregs offer a promising strategy for inducing targeted immunosuppression in allogeneic transplantation. While preclinical findings are encouraging, further work is needed to optimize CAR design, ensure in vivo stability, and establish clinical-scale manufacturing before translation to human trials.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727516","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":"On the Merits of Targeted and Individualized Physical Exercise in Persons with Diabetic Foot Disease-From Controversies to Consensus.","authors":"Edyta Sutkowska, Anna Korzon-Burakowska, Karolina Biernat","doi":"10.3390/biomedicines13071752","DOIUrl":"10.3390/biomedicines13071752","url":null,"abstract":"<p><p>Exercise is a cornerstone of diabetes management, but the onset of diabetic foot disease (DFD) can significantly limit its implementation. Meanwhile, physical activity (PA) has been shown to reduce the risk of developing DFD through various mechanisms, and emerging evidence also supports the role of exercise in managing the active phase of the condition. Appropriately tailored PA offers both local and systemic benefits-even in clinical contexts where foot offloading is recommended. The research indicates that selected exercises can be safely incorporated into care plans, providing therapeutic effects without compromising wound healing. Drawing from current knowledge based on basic science, clinical research, and relatively general recommendations, this article summarizes the local and systemic effects of properly selected exercises in patients with DFD. It explains the underlying mechanisms and briefly discusses practical examples, integrating the most recently published findings.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12293001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727457","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":"Treatment of Chronic Neck Pain with Transcranial Direct Current Stimulation: A Single-Blinded Randomized Clinical Trial.","authors":"Manuel Rodríguez-Huguet, Miguel Ángel Rosety-Rodríguez, Daniel Rodríguez-Almagro, Rocío Martín-Valero, Maria Jesus Vinolo-Gil, Jorge Bastos-Garcia, Jorge Góngora-Rodríguez","doi":"10.3390/biomedicines13071746","DOIUrl":"10.3390/biomedicines13071746","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Neck pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, affecting the cervical region. It represents one of the leading causes of disability, with a prevalence of 30%. Transcranial direct current stimulation (tDCS) is a non-invasive electrotherapy technique that enables direct modulation of cortical excitability. It involves the application of a low-intensity electrical current to the scalp, targeting the central nervous system. The aim of this study was to analyze the effects of tDCS on functionality, pain, mobility, and pressure pain threshold in patients with chronic nonspecific neck pain. <b>Methods</b>: Thirty participants (18-60 years) were selected to receive ten treatment sessions over a four-week period using tDCS (CG = 15) or transcutaneous electrical nerve stimulation (TENS) (CG = 15), with the following various related variables evaluated: functionality (Neck Disability Index), pain intensity (NPRS), cervical range of motion (ROM), and pressure pain threshold (PPT). Assessments were conducted at baseline, post-treatment, one month, and three months after the intervention. <b>Results</b>: The within-group analysis revealed statistically significant improvements for both groups at post-treatment, one-month follow-up, and three-month follow-up. <b>Conclusions</b>: The comparison between groups shows favorable changes in the tDCS group for PPT measurements.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727556","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":"Comparative Diagnostic Efficacy of Four Breast Imaging Modalities in Dense Breasts: A Single-Center Retrospective Study.","authors":"Danka Petrović, Bojana Šćepanović, Milena Spirovski, Zoran Nikin, Nataša Prvulović Bunović","doi":"10.3390/biomedicines13071750","DOIUrl":"10.3390/biomedicines13071750","url":null,"abstract":"<p><p><b>Background and Objectives</b>: The aim of our study was to assess the diagnostic accuracy of four imaging modalities-digital mammography (DM), digital breast tomosynthesis (DBT), ultrasound (US), and breast magnetic resonance imaging (MRI)-applied individually and in combination in early cancer detection in women with dense breasts. <b>Methods</b>: This single-center retrospective study was conducted from January 2021 to September 2024 at the Oncology Institute of Vojvodina in Serbia and included 168 asymptomatic and symptomatic women with dense breasts. Based on the exclusion criteria, the final number of women who were screened with all four imaging methods was 156. The reference standard for checking the diagnostic accuracy of these methods is the result of a histopathological examination, if a biopsy is performed, or a stable radiological finding in the next 12-24 months. <b>Results</b>: The findings underscore the superior diagnostic performance of breast MRI with the highest sensitivity (95.1%), specificity (78.7%), and overall accuracy (87.2%). In contrast, DM showed the lowest sensitivity (87.7%) and low specificity (49.3%). While the combination of DM + DBT + US demonstrated improved sensitivity to 96.3%, its specificity drastically decreased to 32%, illustrating as ensitivity-specificity trade-off. Notably, the integration of all four modalities increased sensitivity to 97.5% but decreased specificity to 29.3%, suggesting an overdiagnosis risk. DBT significantly improved performance over DM alone, likely due to enhanced tissue differentiation. US proved valuable in dense breast tissue but was associated with a high false-positive rate. Breast MRI, even when used alone, confirmed its status as the gold standard for dense breast imaging. However, its widespread use is constrained by economic and logistical barriers. ROC curve analysis further emphasized MRI's diagnostic superiority (AUC = 0.958) compared with US (0.863), DBT (0.828), and DM (0.820). <b>Conclusions</b>: This study provides a unique, comprehensive comparison of all four imaging modalities within the same patient cohort, offering a rare model for optimizing diagnostic pathways in women with dense breasts. The findings support the strategic integration of complementary imaging approaches to improve early cancer detection while highlighting the risk of increased false-positive rates. In settings where MRI is not readily accessible, a combined DM + DBT + US protocol may serve as a pragmatic alternative, though its limitations in specificity must be carefully considered.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727350","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":"Tazarotene-Induced Gene 3 (TIG3) Induces Apoptosis in Melanoma Cells Through the Modulation of Inhibitors of Apoptosis Proteins.","authors":"Chun-Hua Wang, Lu-Kai Wang, Fu-Ming Tsai","doi":"10.3390/biomedicines13071749","DOIUrl":"10.3390/biomedicines13071749","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Retinoic acid has been shown to inhibit melanoma progression; however, its underlying mechanisms remain unclear. In this study, we investigated the role of the retinoic acid-inducible gene TIG3 in regulating melanoma cell growth, as well as elucidating its involvement in apoptosis. <b>Methods:</b> The expression of TIG3 in melanoma tissues was analyzed using a cDNA microarray. Cell viability and cell death were measured using the WST-1 and LDH assay kits, respectively. The gene expression changes that were induced by TIG3 were identified through RNA sequencing, while apoptosis-related pathways were examined using a human apoptosis protein array. The protein expression levels were further validated using Western blot analysis. <b>Results:</b> TIG3 expression was significantly downregulated in melanoma tissues. The overexpression of TIG3 in melanoma cells led to reduced cell viability and increased cell death. TIG3 suppressed the expression of several apoptosis-regulating proteins, including PON2, Fas, cIAP-1, Claspin, Clusterin, HTRA2, and Livin, while promoting the expression of cleaved Caspase-3. Supplementation with cIAP-1, HTRA2, or Livin partially reversed TIG3-induced Caspase-3 expression and cell death. <b>Conclusions:</b> Our findings suggest that TIG3 may contribute to the anti-melanoma effects of retinoic acid, with IAP family proteins playing a key role in the TIG3-mediated regulation of melanoma cell survival.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727469","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":"The Molecular Landscape of Nitric Oxide in Ovarian Function and IVF Success: Bridging Redox Biology and Reproductive Outcomes.","authors":"Diamandis Athanasiou, Charalampos Voros, Ntilay Soyhan, Georgia Panagou, Maria Sakellariou, Despoina Mavrogianni, Eleni Sivylla Bikouvaraki, George Daskalakis, Kalliopi Pappa","doi":"10.3390/biomedicines13071748","DOIUrl":"10.3390/biomedicines13071748","url":null,"abstract":"<p><p><b>Background</b>: Nitric oxide (NO) is an important modulator of ovarian physiology, which contributes to angiogenesis, steroidogenesis, and redox control. The stable metabolites nitrate (NO₃^-) and nitrite (NO₂^-) may indicate real-time follicular function during IVF. <b>Methods</b>: In this prospective study, we included 89 women who underwent controlled ovarian stimulation. The Griess test was used to measure NO₂-NO₃ concentrations in follicular fluid collected on the day of oocyte retrieval. Non-parametric and correlation tests were used to investigate the associations between oocyte yield, maturity (MII), fertilization (2PN), embryo development, and hormone levels. <b>Results</b>: Higher NO₂-NO₃ levels were substantially associated with increased total oocyte count, MII oocytes (<i>p</i> = 0.014), and 2PN embryos (<i>p</i> = 0.029). This suggests a strong relationship between NO bioavailability and oocyte competence. NO₂-NO₃ levels showed a positive correlation with estradiol (<i>p</i> < 0.001) and progesterone (<i>p</i> < 0.001), suggesting a possible function in granulosa cell steroidogenesis. <b>Conclusions</b>: Follicular NO metabolites are candidate functional indicators for oocyte quality evaluation and intrafollicular steroidogenic activity. Their predictive value may improve customized IVF treatment, especially in individuals with complicated ovarian phenotypes such as PCOS or decreased ovarian reserve.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727498","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":"A Mid-Term Follow-Up in Patients with Symptomatic Moderate to Severe and Severe Degenerative Mitral Valve Regurgitation After Transapical NeoChord Implantation.","authors":"Argyro Kalompatsou, Dimitris Tousoulis, Yannis Dimitroglou, Eirini Beneki, Panagiotis Theofilis, Konstantinos Tsioufis, Constantina Aggeli, Vasilis Lozos","doi":"10.3390/biomedicines13071751","DOIUrl":"10.3390/biomedicines13071751","url":null,"abstract":"<p><p><b>Background:</b> The transapical off-pump NeoChord procedure is a recognized minimally invasive surgical approach for the treatment of severe degenerative mitral regurgitation. This study aims to report the initial Greek experience with the NeoChord procedure, presenting mid-term clinical and echocardiographic outcomes from a single cardiothoracic surgical center, with a median follow-up duration of 20 months. <b>Methods:</b> In this study, 42 symptomatic patients with moderate to severe and severe primary mitral regurgitation underwent mitral valve repair with the Neochord procedure between March 2018 and December 2024. All patients were evaluated clinically and echocardiographically by the Heart team preoperatively, after 1 month, and at the last follow-up (end of 2024). The primary endpoint was established as the presence of a major clinical event (all-cause mortality, reintervention due to deterioration of MR, and cardiac-related rehospitalization). <b>Results:</b> The median age of patients was 69 [61.75-79.25] years, and 69% of patients were men. The median EuroScore II was 1.79 [1.32-2.48], and the STS-PROM MV repair score was 3.18 [2.28-4.66]. Regarding the preprocedural mitral valve anatomical evaluation, 35 patients had type A (83.3%),4 had type B(9.5%), whereas only two patients had type C and 1 with type D anatomy. The median of LAI was 1.2 [1.15-1.25], whereas the CI was 4 [2.15-5]. More than two neochordae were implanted in 34 patients (81%). MR severity improved at 1-month (<moderate:92.85%) and at the last follow-up (<moderate:92.1%). NYHA class decreased within 1 month (I + II: 95.23%) after the procedure and was maintained at the last follow-up (I + II: 94.73%). The median left ventricular ejection fraction (LVEF) before the procedure was 63 [58-67]%, which significantly decreased to 57 [53-61]% at the 1-month follow-up (2-sided <i>p</i> < 0.001). At the final follow-up, LVEF increased to 65 [60-68]%, however, this change was not statistically significant compared to the preprocedural value. During the follow-up period, four deaths were documented-three due to non-cardiac and one attributable to a cardiac cause. Two cases proceeded to reoperation for surgical valve implantation due to recurrent mitral valve regurgitation 6 months and 8 months after the NeoChord procedure. <b>Conclusions:</b> Transapical off-pump NeoChord implantation offers a minimally invasive alternative to conventional surgery for symptomatic patients with moderate-to-severe or severe primary mitral regurgitation. Among patients with suitable mitral valve anatomy, the procedure has demonstrated a favorable safety profile and promising mid-term outcomes, in terms of cardiac mortality, as well as freedom from reoperation and rehospitalization.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727301","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":"Necroptotic and Apoptotic Pathways in Sepsis: A Comparative Analysis of Pediatric and Adult ICU Patients.","authors":"George Briassoulis, Konstantina Tzermia, Kalliopi Bastaki, Marianna Miliaraki, Panagiotis Briassoulis, Athina Damianaki, Eumorfia Kondili, Stavroula Ilia","doi":"10.3390/biomedicines13071747","DOIUrl":"10.3390/biomedicines13071747","url":null,"abstract":"<p><p><b>Background:</b> Necroptosis, a regulated form of inflammatory cell death, is increasingly recognized as a key driver of sepsis and critical illness. The balance between necroptosis and apoptosis may influence immune responses and outcomes in ICU patients. <b>Objective:</b> To evaluate necroptosis- and apoptosis-related protein expression in critically ill pediatric and adult patients with sepsis/septic shock, trauma/SIRS, or cardiac conditions, and assess their association with clinical outcomes. <b>Methods:</b> In this prospective, observational study, 88 patients admitted to a tertiary ICU were categorized into four groups: sepsis/septic shock, trauma/SIRS, cardiac disease, and healthy controls. Serum levels of RIPK1, RIPK3, MLKL, A20, caspase-8, IL-1β, and IL-18 were measured within 24 h of admission using ELISA. Biomarkers were analyzed by disease group, age, and severity indices. <b>Results:</b> Patients with sepsis-both adults and children-exhibited significantly elevated levels of RIPK1, IL-1β, and IL-18 (<i>p</i> < 0.001) and reduced levels of caspase-8 (<i>p</i> = 0.015), indicating activation of the necroptosis pathway. A20 was significantly upregulated (<i>p</i> < 0.001) and independently associated with lactate levels. RIPK1, IL-1β, and IL-18 were positively correlated with ICU length of stay and illness severity, whereas caspase-8 showed an inverse correlation. ROC analysis demonstrated strong predictive performance for sepsis/septic shock using RIPK1 (AUC = 0.81), IL-18 (AUC = 0.71), and A20 (AUC = 0.71); conversely, caspase-8 was inversely associated with sepsis (AUC = 0.32). <b>Conclusions:</b> Necroptosis appears to play a central role in the pathophysiology of sepsis across age groups. Elevated levels of RIPK1, IL-1β, IL-18, and A20 may serve as biomarkers of disease severity, while reduced caspase-8 supports a shift away from apoptosis toward necroptotic cell death. These findings highlight the potential of necroptosis-related pathways as targets for risk stratification and therapeutic intervention in critically ill patients of all ages.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727403","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}