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13 pages, 353 KiB  
Systematic Review
Radiofrequency Ablation of Painful Spinal Metastasis: A Systematic Review
by Jacopo Scaggiante, Salvatore Marsico, Andrea Alexandre, Simona Gaudino, Monica Ferrante, Riccardo Caronna, Ettore Squillaci, Iacopo Valente, Giuseppe Garignano, Francesco D’Argento, Reade De Leacy and Alessandro Pedicelli
Curr. Oncol. 2025, 32(6), 301; https://doi.org/10.3390/curroncol32060301 - 23 May 2025
Viewed by 183
Abstract
Objective: To systematically evaluate the effectiveness and safety of radiofrequency ablation (RFA) for managing pain caused by spinal metastases. This review aimed to consolidate evidence on RFA’s analgesic efficacy and associated risks to inform clinical practice in palliative cancer care. Methods: A systematic [...] Read more.
Objective: To systematically evaluate the effectiveness and safety of radiofrequency ablation (RFA) for managing pain caused by spinal metastases. This review aimed to consolidate evidence on RFA’s analgesic efficacy and associated risks to inform clinical practice in palliative cancer care. Methods: A systematic review adhering to PRISMA guidelines was conducted. Databases were searched for studies evaluating RFA for spinal metastases pain. Inclusion criteria specified: randomized or non-randomized studies (prospective/retrospective); ≥3 adult patients; RFA used alone or combined with other treatments; reported pre- and post-RFA pain assessments; English language publication. Data extracted included patient demographics, primary tumor type, lesion location, pain scores (e.g., NRS/VAS), and complications. Pain response was assessed using definitions including the International Consensus Pain Response Endpoints (ICPRE) and definitions for moderate (≥2-point reduction) and high (≥4-point reduction) effectiveness. Results: This review included 33 studies, totaling 1336 patients (53.7% female) and 1787 treated lesions. The majority (85%) of studies reported highly effective pain management (≥4-point pain score reduction). The remaining 15% showed moderate effectiveness (≥2-point reduction). All studies reported achieving at least a partial pain response per ICPRE criteria. Mean pain scores decreased significantly from baseline (7.56/10) within 24–72 h (3.65) and remained low at 4 weeks (2.99), 12 weeks, and 24 weeks (both 2.70). Common primary cancers were lung (27.6%), breast (26.2%), and genitourinary (11.3%). Lesions were primarily in the thoracic (47.9%) and lumbar spine (47.3%). Crucially, no life-threatening (grade IV–V) complications occurred. The overall rate of grade I–III complications was low at 2.11%. Limitations: This systematic review is limited by its study-level nature, preventing detailed subgroup analyses regarding specific metastasis characteristics or the impact of complementary therapies. Conclusions: This systematic review suggests that RFA is a safe and effective treatment for pain control in patients with spinal metastases. It provides both rapid (within 24 h) and durable mid-term (up to 24 weeks) analgesia. The favorable safety profile, with a low complication rate, supports RFA as a valuable complimentary option within the multidisciplinary palliative management of painful spinal secondary tumors. Future randomized-controlled studies may help to further define its role when associated with other treatments. Full article
(This article belongs to the Special Issue 2nd Edition: Treatment of Bone Metastasis)
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18 pages, 893 KiB  
Article
RUNX3 Methylation: An Epigenetic Biomarker for Early Liver Damage Induced by Co-Exposure to Aflatoxin B1 and Hepatitis B Virus
by Yunying Mo, Xiaodan Lu, Shixiong Zheng, Junfeng Deng, Shihan Huang, Ye Hong, Xiaoyu Xian, Aliya Yijiati, Xingyu Yu, Xunwu Luo, Miner Xiao, Xingfen Yang, Michael N. Routledge, Yunyun Gong and Zhini He
Toxics 2025, 13(6), 425; https://doi.org/10.3390/toxics13060425 - 23 May 2025
Viewed by 190
Abstract
Aflatoxin B1 (AFB1), a well-established hepatic carcinogen, has limited research on early-stage epigenetic biomarkers for aflatoxin-induced liver damage. In this study, we investigated 168 unpackaged peanut oil (UPP) consumers to evaluate associations among AFB1 exposure, HBV infection, RUNX3 methylation, and liver function. Our [...] Read more.
Aflatoxin B1 (AFB1), a well-established hepatic carcinogen, has limited research on early-stage epigenetic biomarkers for aflatoxin-induced liver damage. In this study, we investigated 168 unpackaged peanut oil (UPP) consumers to evaluate associations among AFB1 exposure, HBV infection, RUNX3 methylation, and liver function. Our findings indicated an average daily AFB1 intake of 3.14 ng/kg·bw/day from UPP oil consumption. The high AFB1 exposure group exhibited significantly elevated gamma-glutamyl transferase (GGT) levels compared with the low AFB1 exposure group (p = 0.030). AFB1 exposure was negatively correlated with methylation status at the 2nd, 8th, and 9th CpG sites of RUNX3 (rs = −0.196, −0.192, −0.181, p = 0.021, 0.024, 0.036). Furthermore, methylation at the 8th and 9th CpG sites positively correlated with GGT (rs = 0.206, 0.203, p = 0.019, 0.024). HBV infection significantly influenced RUNX3 methylation, with the HBsAg+ group exhibiting 16.25% lower methylation (p < 0.05). Stratified analysis by HBV and AFB1 revealed that in the low AFB1 exposure subgroup, RUNX3 methylation in the HBsAg+ group exhibited a significant 26.38% reduction compared with the HBsAg group. These results indicated that AFB1 and HBV independently and synergistically promote site-specific RUNX3 hypomethylation. Our results implicated RUNX3 methylation as a critical mediator in HBV-AFB1 co-exposure hepatotoxicity, potentially serving as a novel epigenetic biomarker for early liver damage detection. Full article
(This article belongs to the Section Exposome Analysis and Risk Assessment)
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14 pages, 1355 KiB  
Article
Apigenin Attenuates Hepatic Ischemia–Reperfusion-Induced Lung Injury via Downregulation of MMP-3 and MCP-1: An Experimental Study in Rats
by Chrysovalantis Mariorakis, Maria Lambropoulou, Panagoula Oikonomou, Christos Tsalikidis, Michail Pitiakoudis, Elissavet Anestiadou, Orestis Ioannidis and Alexandra K. Tsaroucha
J. Clin. Med. 2025, 14(10), 3530; https://doi.org/10.3390/jcm14103530 - 18 May 2025
Viewed by 253
Abstract
Background/Objectives: In liver transplant surgery, ischemia–reperfusion (I-R) maneuvers are frequently employed to control bleeding; however, such interventions can result in injury not only to the liver but also to remote organs. The lungs, in particular, are highly susceptible due to their extensive [...] Read more.
Background/Objectives: In liver transplant surgery, ischemia–reperfusion (I-R) maneuvers are frequently employed to control bleeding; however, such interventions can result in injury not only to the liver but also to remote organs. The lungs, in particular, are highly susceptible due to their extensive vascularization and inflammatory response. While pulmonary injury secondary to hepatic I-R is recognized, and despite the fact that various antioxidant compounds have been investigated for their potential to mitigate I-R-induced damage to hepatic tissue, few studies have focused on evaluating therapeutic agents aimed at mitigating lung damage in this setting. This study aimed to evaluate the protective effect of apigenin on pulmonary tissue following liver I-R injury using an experimental rat model. Methods: Sixty-three male albino Wistar rats (approximately 15 weeks old, weighing 220–350 g) were randomly allocated into three groups: a sham group (open–close surgery; n = 7), a control (C) group subjected to liver I-R injury only (n = 28), and an apigenin (Ap) group receiving intraperitoneal apigenin administration immediately after liver ischemia and prior to reperfusion (n = 28). Both the C and Ap groups were subdivided into four equal subgroups corresponding to euthanasia at 60-, 120-, 180-, and 240 min post-reperfusion. Lung tissues were harvested for immunohistochemical analysis targeting the expression of matrix metalloproteinase-3 (MMP-3) and monocyte chemoattractant protein-1 (MCP-1). Results: The apigenin-treated groups exhibited significantly reduced expression levels of MMP-3 and MCP-1 across all time points when compared to the control groups. In contrast, no expression of MMP-3 or MCP-1 was observed in the sham group. Conclusions: The findings support the protective role of the antioxidant apigenin in reducing pulmonary injury following liver I-R. The diminished expression of MMP-3 and MCP-1 in the apigenin-treated rats provides compelling evidence for its protective effects on remote organs. Full article
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19 pages, 4638 KiB  
Article
Genome-Wide Identification, Evolution and Expression Analysis of the G-Protein Gene Family in Poplar (Populus alba × Populus glandulosa)
by Bobo Song, Qian Liu, Zitong Zeng, Yiyang Gu, Wenxin Ye, Fangfang Fu and Meiling Ming
Forests 2025, 16(5), 805; https://doi.org/10.3390/f16050805 - 12 May 2025
Viewed by 227
Abstract
Heterotrimeric G-proteins are key signal transduction mediators involved in regulating plant growth and development, and responses to various stress in plants. G-proteins are extensively investigated in model plants, such as Arabidopsis thaliana and Oryza sativa. However, the identification and function of G-proteins in [...] Read more.
Heterotrimeric G-proteins are key signal transduction mediators involved in regulating plant growth and development, and responses to various stress in plants. G-proteins are extensively investigated in model plants, such as Arabidopsis thaliana and Oryza sativa. However, the identification and function of G-proteins in woody species, particularly Populus, remain largely unexplored. In this study, we performed a genome-wide identification and comprehensive analysis of the G-protein gene family in poplar, aiming to reveal their evolutionary history, structural diversity and potential function roles. As a result, a total of 27 G-protein genes were identified in the poplar genome, including 18 Gα, 4 Gβ and 5 Gγ subunits. Phylogenetic analysis indicated that 27 G-protein genes were divided into three subgroups. Gene structure, conserved domain and motifs indicated the conserved nature of G-protein at sequence and structure. In addition, synteny analysis revealed that whole-genome duplication events contributing to the expansion of the G-protein gene family in poplar. Cis-regulatory element analysis indicated that many G-protein genes in poplar contain hormone and stress related motifs, suggesting that G-protein genes are involved in environmental adaptation. Expression profiling analysis demonstrated that G-protein genes exhibited tissue-specific expression and stress-responsive expression patterns, highlighting their potential regulatory roles in growth and development and responses to biotic and abiotic stresses. This study provides valuable insights into the poplar G-protein gene family and lays the foundation for further functional analyses, contributing to improving stress tolerance in forestry species. Full article
(This article belongs to the Section Genetics and Molecular Biology)
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27 pages, 5331 KiB  
Systematic Review
Comparative Efficacy and Precision of Robot-Assisted vs. Conventional Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Ümit Mert, Moh’d Yazan Khasawneh, Maher Ghandour, Ahmad Al Zuabi, Klemens Horst, Frank Hildebrand, Bertil Bouillon, Mohamad Agha Mahmoud and Koroush Kabir
J. Clin. Med. 2025, 14(9), 3249; https://doi.org/10.3390/jcm14093249 - 7 May 2025
Viewed by 306
Abstract
Background/Objectives: Total knee arthroplasty (TKA) is a common procedure for knee osteoarthritis. While conventional TKA (C-TKA) remains standard, robot-assisted TKA (RA-TKA) has been introduced to enhance implant positioning and clinical outcomes. However, its comparative benefits remain unclear. This systematic review and meta-analysis [...] Read more.
Background/Objectives: Total knee arthroplasty (TKA) is a common procedure for knee osteoarthritis. While conventional TKA (C-TKA) remains standard, robot-assisted TKA (RA-TKA) has been introduced to enhance implant positioning and clinical outcomes. However, its comparative benefits remain unclear. This systematic review and meta-analysis compared RA-TKA with C-TKA, examining the influence of robotic system, surgeon experience, and follow-up duration. Methods: A systematic search was conducted across the PubMed, Scopus, Web of Science, and Cochrane Library databases. Randomized controlled trials (RCTs) comparing RA-TKA with C-TKA were included. Outcomes were categorized into clinical, radiographic, and safety endpoints. Subgroup and meta-regression analyses explored factors influencing outcome variability, including robotic system, number of surgeons, and follow-up duration. Results: Twenty-five RCTs (5614 patients) were analyzed. RA-TKA showed modest improvements in clinical outcomes, such as KSS and VAS pain scores, but results varied across subgroups. RA-TKA demonstrated a significantly better flexion range of motion (ROM) in certain countries (e.g., Russia, MD = 10; 95%CI: 5.44, 14.56) and with specific robotic systems (e.g., NAVIO). No significant differences were found in OKS and HSS scores. Radiographic outcomes, including the HKA Angle, varied by robotic system, with NAVIO and YUANHUA showing better alignment than C-TKA. Complication rates were comparable, though RA-TKA had a higher risk of conversion to open surgery (10% vs. 2%). Meta-regression identified robotic system and surgeon experience as key predictors of outcome variability. Conclusions: RA-TKA offers advantages in implant alignment and postoperative pain reduction. However, benefits are inconsistent across settings, and some robotic systems may not provide improvements over C-TKA. Full article
(This article belongs to the Section Orthopedics)
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15 pages, 1045 KiB  
Article
Association Between Healthy Dietary Patterns and Chronic Kidney Disease in Patients with Diabetes: Findings from Korean National Health and Nutrition Examination Survey 2019–2021
by Minsang Kim, Jung Hun Koh, Jeong Min Cho, Semin Cho, Soojin Lee, Hyuk Huh, Seong Geun Kim, Sehyun Jung, Eunjeong Kang, Sehoon Park, Jin Hyuk Paek, Woo Yeong Park, Kyubok Jin, Seungyeup Han, Kwon Wook Joo, Kyungdo Han, Dong Ki Kim and Yaerim Kim
Nutrients 2025, 17(9), 1600; https://doi.org/10.3390/nu17091600 - 7 May 2025
Viewed by 316
Abstract
Background/Objectives: Although a healthy dietary pattern is a modifiable lifestyle factor in the prevention of chronic kidney disease (CKD), studies that investigate the association between a healthy diet and prevalent CKD in patients with diabetes, using the Korean Healthy Eating Index (KHEI), [...] Read more.
Background/Objectives: Although a healthy dietary pattern is a modifiable lifestyle factor in the prevention of chronic kidney disease (CKD), studies that investigate the association between a healthy diet and prevalent CKD in patients with diabetes, using the Korean Healthy Eating Index (KHEI), are lacking. Methods: This cross-sectional study included 1991 patients with diabetes from the eighth Korean National Health and Nutrition Examination Survey 2019–2021. A higher KHEI indicated healthier eating habits. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin–creatinine ratio ≥ 30 mg/g. The risk of prevalent CKD was evaluated according to the median KHEI value using logistic regression analysis adjusted for various clinicodemographic characteristics. Each KHEI component score was compared between those with and those without CKD, using the Student’s t-test. Results: Participants with a higher KHEI were older, with higher proportions of women, non-smokers, and non-alcoholics. A higher KHEI was significantly associated with a lower risk of prevalent CKD (adjusted odds ratio [aOR], 0.73 [0.58–0.93]). Subgroup analysis revealed stronger associations in those without hypertension status (aOR, 0.57 [0.37–0.87]) with at least high school education (aOR, 0.56 [0.38–0.81]). Moreover, patients with diabetes and CKD had significantly lower KHEI, particularly in the adequacy category components, including breakfast consumption, total fruit intake, and dairy product intake. Conclusions: A healthier dietary pattern was associated with a lower risk of prevalent CKD in patients with diabetes. Dietary intervention, which recommends the intake of breakfast, fruits, and dairy products, may be an effective strategy for CKD prevention. Full article
(This article belongs to the Section Nutrition Methodology & Assessment)
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11 pages, 274 KiB  
Article
Multilevel Factors Influencing Perceived Barriers to Adjuvant Endocrine Therapy Among Breast Cancer Patients at Medication Onset
by Timothy Cocozza, Rita Smith, Ana Maria Lopez, Shari Rudoler, Rachel Slamon, Tingting Zhan, Jazmarie L. Vega, Minal Dhamankar, Aruna Padmanabhan, Suzanne M. Miller and Kuang-Yi Wen
Int. J. Environ. Res. Public Health 2025, 22(5), 734; https://doi.org/10.3390/ijerph22050734 - 6 May 2025
Viewed by 235
Abstract
Purpose: Adjuvant endocrine therapy (AET) significantly diminishes recurrence and mortality risks in hormone receptor-positive breast cancer (BCa) patients. Nonetheless, suboptimal adherence and premature discontinuation during the initial year of treatment undermine these positive outcomes. This study aims to understand the potential diverse factors [...] Read more.
Purpose: Adjuvant endocrine therapy (AET) significantly diminishes recurrence and mortality risks in hormone receptor-positive breast cancer (BCa) patients. Nonetheless, suboptimal adherence and premature discontinuation during the initial year of treatment undermine these positive outcomes. This study aims to understand the potential diverse factors associated with perceived barriers to AET compliance at the onset of medication. Methods: We assessed perceived barriers to AET using the ASK-20 instrument for BCa patients initiating AET within 3 months. Our survey also included demographic variables (e.g., musculoskeletal symptoms) and clinical traits (e.g., medication type). Stepwise regression analyses were employed to elucidate the links between multilevel factors and perceived barriers to AET adherence. Results: In our cohort of 272 women, the mean ASK-12 score was 38.2 +/− 9.2 (range 20–100). In the multivariable regression model, greater perceived barriers to adhering to AET were found to be associated with African American ethnicity (Β  =  2.47; 0.53–4.21; p  <  0.05), lower self-efficacy in medication management (Β  =  −0.80; −1.03–−0.58; p  <  0.001), higher psychological distress (Β  =  2.79; 0.61–4.97; p  <  0.05), increased reported distress related to musculoskeletal side effects (Β  =  0.64; 0.31–0.97; p  <  0.001), weight gain symptoms (Β  =  0.61; 0.18–1.03; p  <  0.05), less family support (Β  =  −0.38; −0.53–−0.13; p  <  0.05), and higher levels of concern pertaining to AET (Β  =  0.64; 0.41–0.87; p  <  0.001). Conclusions: Modifiable factors are associated with women’s perceived barriers to AET at the onset of treatment. Proactively addressing patient concerns about AET, improving self-regulatory skills for medication management and family support, and enhancing symptom management strategies, along with addressing distress at the onset of treatment, hold promise for mitigating barriers to AET. Furthermore, recognizing the distinctive challenges faced by African American subgroups is crucial, necessitating culturally tailored interventions to reduce potential disparities and ensure equitable access and adherence to AET. Continued research and tailored interventions are important for optimizing outcomes and reducing the impact of modifiable barriers on AET adherence. Full article
31 pages, 6396 KiB  
Systematic Review
Pharmacological and Non-Pharmacological Interventions for Polycystic Ovary Syndrome (PCOS) in Indian Women: A Systematic Review and Meta-Analysis
by Pratibha Maan, Rohit Gautam, Sudharsan Vasudevan, Geetha R. Menon, Amit Arora, Abilash Nair, Puthiyaveettil Khadar Jabbar and Taruna Arora
Pharmaceuticals 2025, 18(5), 680; https://doi.org/10.3390/ph18050680 - 2 May 2025
Viewed by 818
Abstract
Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age. Treatment or management of this syndrome includes several pharmacological and non-pharmacological treatment approaches for different manifestations of the disease that vary with the patient’s age, symptoms, requirements, and [...] Read more.
Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age. Treatment or management of this syndrome includes several pharmacological and non-pharmacological treatment approaches for different manifestations of the disease that vary with the patient’s age, symptoms, requirements, and geographical location. Objective: This systematic review aims to conduct a comprehensive and evidence-based analysis of the various available treatment options and identify knowledge gaps in PCOS management in India. Methods: A comprehensive search was conducted in PubMed, Scopus, and Embase databases from January 2010 till February 2024. We included randomized control trials (RCTs) using any pharmacological drugs (e.g., insulin sensitizers, anti-androgens, anti-obesity drugs, oral contraceptive pills, ovulation induction drugs, etc.) or non-pharmacological intervention (e.g., yoga, diet, herbal supplements, etc.) with Indian PCOS patients for improving common manifestations of PCOS and written in the English language. Studies were screened by two authors independently in a two-level process. Data extraction was also performed by two authors. Risk of bias was performed using the RoB 2 Tool. Subgroup analysis and meta-analysis were performed using the RevMan tool. Results: Thirty RCTs on pharmacological and eight on non-pharmacological interventions were included in the study. However, all the RCTs were so heterogeneous in terms of intervention used, subject recruited, and outcomes measured that meta-analysis was possible for only three subgroups (metformin vs. inositol, metformin vs. metformin+ inositol, and letrozole vs. clomiphene citrate), with only two or three studies per analysis. Most studies were single-centric and small-sized and had a high risk of bias, limiting their generalizability. Conclusions: This systematic review synthesized existing research and evaluated the effectiveness and safety of existing treatments. Limitations and gaps in the current research were identified, which may inform future research for better understanding and management of PCOS in the Indian context. Full article
(This article belongs to the Special Issue NeuroImmunoEndocrinology)
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23 pages, 1093 KiB  
Article
Spillover Effects of Physicians’ Prosocial Behavior: The Role of Knowledge Sharing in Enhancing Paid Consultations Across Healthcare Networks
by Yuting Zhang and Jiantong Zhang
J. Theor. Appl. Electron. Commer. Res. 2025, 20(2), 87; https://doi.org/10.3390/jtaer20020087 - 1 May 2025
Viewed by 280
Abstract
This study investigates the spillover effects of physicians’ prosocial behavior, specifically knowledge sharing, on the paid consultations of other physicians within the same specialty and offline hospital. Using data from an online healthcare platform, we apply propensity score matching to explore how the [...] Read more.
This study investigates the spillover effects of physicians’ prosocial behavior, specifically knowledge sharing, on the paid consultations of other physicians within the same specialty and offline hospital. Using data from an online healthcare platform, we apply propensity score matching to explore how the sharing of medical knowledge by physicians influences the consultation outcomes of their colleagues. The results reveal significant positive spillover effects, indicating that prosocial behavior benefits other physicians within the same specialty and healthcare institution, thereby enhancing collaboration within the healthcare ecosystem. The spillover effect is stronger within the same offline hospital’s physicians on the online healthcare platform, suggesting that knowledge sharing has a more localized impact within the same healthcare institution. Furthermore, the study examines heterogeneity across both physician-level characteristics (e.g., popularity, title, price, gender) and contextual factors (e.g., specialty type, hospital level, wait time, regional GDP). The findings show that the magnitude and direction of spillover effects differ by subgroup, shaped by professional visibility, authority, and organizational structure. These insights contribute to the understanding of how prosocial behavior can foster collaboration and benefit healthcare networks beyond individual physicians, offering practical implications for healthcare platforms, administrators, and policymakers. Full article
(This article belongs to the Topic Data Science and Intelligent Management)
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12 pages, 1057 KiB  
Article
Analysis of the DYNC1H1 Gene Polymorphic Variants’ Association with ASD Occurrence and Clinical Phenotype of Affected Children
by Anna Balcerzyk-Matić, Tomasz Iwanicki, Alicja Jarosz, Tomasz Nowak, Ewa Emich-Widera, Beata Kazek, Agnieszka Kapinos-Gorczyca, Maciej Kapinos, Joanna Iwanicka, Katarzyna Gawron, Wirginia Likus and Paweł Niemiec
Genes 2025, 16(5), 510; https://doi.org/10.3390/genes16050510 - 28 Apr 2025
Viewed by 257
Abstract
Objectives: To analyze potential associations between three polymorphisms (rs3818188, rs941793, rs2403015) of the DYNC1H1 gene and the occurrence of autism spectrum disorder as well as the clinical phenotype of affected individuals. Methods: This family-based study included 206 children diagnosed with ASD and 364 [...] Read more.
Objectives: To analyze potential associations between three polymorphisms (rs3818188, rs941793, rs2403015) of the DYNC1H1 gene and the occurrence of autism spectrum disorder as well as the clinical phenotype of affected individuals. Methods: This family-based study included 206 children diagnosed with ASD and 364 of their biological parents. To examine the potential association between three polymorphisms of the DYNC1H1 gene and ASD occurrence, a transmission disequilibrium test was performed. Additionally, associations between the studied polymorphisms and the clinical phenotype of affected individuals were analyzed using the χ2 test. Results: None of the polymorphisms studied showed an association with ASD in the overall patient group. However, an association between the rs3818188 polymorphic variant and ASD was observed in a subgroup of girls, with the G allele being transmitted more than 2.5 times as frequently as the A allele. Moreover, several associations between the tested variants and features related to neuromotor development, communication, and social skills were observed in univariate analysis. However, after correction for multiple comparisons, only the association between the rs2403015 polymorphism and transient increase in muscle tone during infancy remained statistically significant. Conclusions: This study demonstrated an association between the rs3818188 polymorphism and ASD in a subgroup of girls. Additionally, the rs2403015 polymorphism was found to be associated with transient increase in muscle tone during infancy. Full article
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15 pages, 822 KiB  
Article
Contemporary Trends and Predictors Associated with Adverse Pathological Upstaging Among Non-Metastatic Localized Clinical T2 Muscle-Invasive Bladder Cancers Undergoing Radical Cystectomy: Outcomes from a Single Tertiary Centre in the United Kingdom
by Francesco Del Giudice, Yasmin Abu-Ghanem, Rajesh Nair, Elsie Mensah, Jonathan Kam, Youssef Ibrahim, Mohamed Gad, Kathryn Chatterton, Suzanne Amery, Romerr Alao, Ben Challacombe, Mohammed Hegazy, Felice Crocetto, Valerio Santarelli, Jan Łaszkiewicz, Bernardo Rocco, Alessandro Sciarra, Benjamin I. Chung, Ramesh Thurairaja and Muhammad Shamim Khan
Cancers 2025, 17(9), 1477; https://doi.org/10.3390/cancers17091477 - 27 Apr 2025
Viewed by 273
Abstract
Introduction: Radical cystectomy (RC) is the gold standard for urothelial cT2-4a, N0, M0 muscle-invasive bladder cancer (MIBC). However, bladder-sparing strategies (BSS) such as Trimodality Therapy (TMT) have emerged as alternative treatments for a select group of localized muscle-confined (cT2) urothelial bladder cancers. [...] Read more.
Introduction: Radical cystectomy (RC) is the gold standard for urothelial cT2-4a, N0, M0 muscle-invasive bladder cancer (MIBC). However, bladder-sparing strategies (BSS) such as Trimodality Therapy (TMT) have emerged as alternative treatments for a select group of localized muscle-confined (cT2) urothelial bladder cancers. Accordingly, reliable preoperative staging and a reliable risk factor assessment linked to pathological upstaging play a key role in adequate counselling and patient selection for BSS. Patients and Methods: cT2 MIBC patients undergoing RC at our institution from 2014 to 2024 were reviewed. Preoperative staging modalities, demographics, and tumour and patient characteristics were assessed. Multivariable logistic regression was applied to explore the relative effect of confounders on any pathological upstaging from robot-assisted or open RC specimens. Subgroup analysis according to the local upstaging (>pT2) or nodal dissemination (pN+) was also performed. Results: N = 275 RCs were included (73.5% males, 26.5% females). Upstaging was documented in n = 141 (51%) cases. Of these, n = 125 (45.5%) were upstaged locally (>pT2) and n = 35 (23%) yielded pN+ disease. Preoperative parameters like gender, the number of TURBTs, previous BCG exposure, and concomitant CIS did not significantly influence the risk of any kind of upstaging (p > 0.05). At multivariable analysis, neoadjuvant chemotherapy (NAC) and multi-disciplinary team (MDT) discussion were found protective (odds ratio [OR]: 0.4, 95%CI 0.2–0.7, p = 0.001 and OR: 0.51, 95%CI 0.2–0.9, p = 0.01). Preoperative FDG-PET assessment yielded higher risk for later pN upstaging (OR: 1.8, 95%CI 1–3, p = 0.05). HG/G3 features at TURBT along with mixed/pure histology variants in RC specimens were the most relevant independent predictors for both any and pT upstaging (OR: 4.3, 95%CI 1–34, p = 0.04 and OR: 2.3, 95%CI 1.1–4.6, p = 0.02 for any upstaging and OR: 5.6, 95%CI 1.3–36, p = 0.02 and OR: 2.5, 95%CI 1.3–5, p = 0.01 for pT upstaging, respectively). Conclusions: In this study, over half of the patients undergoing RC for cT2 were upstaged at the final pathology. Therefore, adequate counselling and examining the non-conventional criteria for prognosis is mandatory in the contemporary era of bladder-preservation strategies. Full article
(This article belongs to the Special Issue Advancements in Bladder Cancer Therapy)
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24 pages, 3312 KiB  
Review
Liquid Biopsy in Peritoneal Carcinomatosis from Colorectal Cancer: Current Evidence and Future Perspectives
by Valentino Martelli, Joana Vidal, Sílvia Salvans, Concepción Fernández, Jordi Badia-Ramentol, Jenniffer Linares, Marta Jiménez, Annarita Sibilio, Joan Gibert, Marina Pérez, Beatriz Bellosillo, Alexandre Calon, Filippo Pietrantonio, Mar Iglesias, Marta Pascual and Clara Montagut
Cancers 2025, 17(9), 1461; https://doi.org/10.3390/cancers17091461 - 26 Apr 2025
Viewed by 441
Abstract
Peritoneal carcinomatosis (PC) represents a challenge in the management of metastatic colorectal cancer (mCRC) because of the difficulties in diagnosis, tumor burden assessment, and in selecting the optimal treatments. A critical limitation is the lack of robust prognostic and predictive biomarkers, largely relying [...] Read more.
Peritoneal carcinomatosis (PC) represents a challenge in the management of metastatic colorectal cancer (mCRC) because of the difficulties in diagnosis, tumor burden assessment, and in selecting the optimal treatments. A critical limitation is the lack of robust prognostic and predictive biomarkers, largely relying on serum markers (e.g., carcinoembryonic antigen) or the peritoneal carcinomatosis index (PCI) for disease extent. Circulating tumor DNA (ctDNA)—genomic fragments shed by tumor cells into the bloodstream—is now recommended by international guidelines for mCRC management. Its potential extends to PC, where it may enhance diagnostic, therapeutic, and follow-up strategies. However, PC from CRC (PC-CRC) is associated with lower ctDNA levels and detection rates compared to other metastatic sites, posing a challenge for its clinical utility. To address these limitations, peritoneal fluid analysis has emerged as a promising alternative, with peritoneal tumor DNA (ptDNA) detected at higher concentrations in this anatomical space. Integrating ctDNA and ptDNA may offer a deeper understanding of PC-CRC biology and provide more precise tools for managing this complex disease. This approach has the potential to revolutionize the treatment paradigm for PC-CRC, bringing precision medicine even to this subgroup of patients traditionally associated with poor outcomes. This review aims to evaluate the diagnostic, prognostic, and therapeutic implications of ctDNA and ptDNA in PC-CRC, highlighting current limitations and future directions. Full article
(This article belongs to the Special Issue Chemotherapy and Treatment: Metastasis of Colorectal Cancer)
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13 pages, 761 KiB  
Article
Fragility Fractures of the Pelvic Ring: Analysis of Epidemiology, Treatment Concepts, and Surgical Strategies from the Registry of the German Pelvic Multicenter Study Group
by David B. Osche, Emmanouil Liodakis, Stefan Huber, Tim Pohlemann, Christian Kleber, Steven C. Herath and Andreas Höch
J. Clin. Med. 2025, 14(9), 2935; https://doi.org/10.3390/jcm14092935 - 24 Apr 2025
Viewed by 282
Abstract
Background: Fragility fractures of the pelvic ring (FFPs) represent a fast-growing entity in geriatric traumatology with increasing incidence worldwide. This study aimed to analyze the epidemiology, treatment concepts, and surgical strategies for FFPs based on data collected by the German Pelvic Multicenter Study [...] Read more.
Background: Fragility fractures of the pelvic ring (FFPs) represent a fast-growing entity in geriatric traumatology with increasing incidence worldwide. This study aimed to analyze the epidemiology, treatment concepts, and surgical strategies for FFPs based on data collected by the German Pelvic Multicenter Study Group documented in the German Pelvic Fracture Registry. It is the largest cohort study of its kind. Methods: This retrospective cohort study included patients aged 65 years or older after FFPs, as classified according to the Rommens and Hofmann classification. Data were collected from July 2018 onward and analyzed for demographics; fracture classifications; treatment modalities (operative vs. non-operative); and details of surgery, including timing and choice of implants. Patients after high-energy trauma were excluded. Statistical analyses included descriptive metrics and subgroup comparisons. Results: Among 1242 patients (84% female; median age 83.4 years), FFP Type II was the most common fracture type (50.8%), followed by Type IV (21.1%). Non-operative management was employed in 68.8% of cases, while 30.9% underwent surgery. Surgical intervention was more frequent in higher-grade FFPs (e.g., 72.1% in Type IV). The most common surgical technique for the posterior pelvic ring was percutaneous screw fixation (61.3%), with navigation used in 47.4% of cases. Conclusions: This study highlights the variability in treatment strategies for FFPs, with conservative management predominating in lower-grade fractures and surgical approaches increasingly utilized for more complex cases. The findings underscore the need for standardized, evidence-based guidelines and further research to optimize treatment and long-term outcomes for geriatric patients with FFPs. Full article
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21 pages, 2588 KiB  
Systematic Review
The Role of Salivary Diagnostic Techniques in Screening for Active Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis
by Radwan Darwish, Maya Tama, Sidra Sharief, Osama Zeidan, Sara Mohammed Ahmed Rady, Kareeza Selby Chacko, Bindhu Nair, Vijayalakshmi S. Bhojaraja and Jeevan K. Shetty
Microorganisms 2025, 13(5), 973; https://doi.org/10.3390/microorganisms13050973 - 24 Apr 2025
Viewed by 464
Abstract
Since the World Health Organization (WHO) issued guidelines for developing a non-sputum test for active tuberculosis (TB) diagnosis that exhibits similar performance characteristics to sputum-based diagnosis, salivary diagnostic techniques have gained prominence as potential screening tools or adjuncts to existing diagnostics. We searched [...] Read more.
Since the World Health Organization (WHO) issued guidelines for developing a non-sputum test for active tuberculosis (TB) diagnosis that exhibits similar performance characteristics to sputum-based diagnosis, salivary diagnostic techniques have gained prominence as potential screening tools or adjuncts to existing diagnostics. We searched online databases for studies that looked at salivary diagnostic techniques. Afterwards, duplicates were removed, titles and abstracts were screened, and full-text studies were assessed for eligibility based on inclusion and exclusion criteria. The studies chosen for final analysis underwent a rigorous quality assessment following a QUADAS-2 template, and data were extracted. The primary outcome assessed the difference in mean levels of interleukins between TB+ patients and TB-controls (Hedges’ g). We then conducted two subgroup analyses: the first segregated the control group into healthy patients, and those with other respiratory diseases (ORD), and the second addressed three different interleukins separately (IL-6, IL-5, IL-17). The secondary outcome involved comparing salivary molecular diagnostic assays to WHO guidelines. This study is registered with PROSPERO, CRD42024536884. A total of 17 studies, out of an initial 1010, were chosen for the final analysis, but one was then excluded for being of poor quality. Our meta-analyses for the primary outcome revealed minimal diagnostic potential for interleukins. Our first subgroup analysis showed that interleukins were incapable of differentiating active TB patients from both healthy controls and ORD patients. Our second subgroup analysis showed that IL-17 was reduced in active TB patients. Assessment of the secondary outcome revealed that most studies relied on a GeneXpert MTB/RIF assay on saliva, but none fulfilled WHO guidelines for a non-sputum test. Individual biomarkers currently lack sufficient discriminatory power to definitively distinguish active tuberculosis from healthy individuals or those with other respiratory diseases (ORD), reinforcing the need for multi-biomarker panels. Interleukins may be alternatively used as markers for prognosis, severity, or treatment response. Our findings also suggest that assays are unable to meet WHO guidelines. Full article
(This article belongs to the Special Issue Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition)
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16 pages, 1976 KiB  
Article
High-Voltage Injuries and Train Surfing: A 30-Year Review of Epidemiology, Treatment, and Outcomes
by Viktoria Koenig, David Lumenta, Julian Joestl, Gerald Ihra, Marita Windpassinger, Maximilian Monai and Alexandra Fochtmann
J. Clin. Med. 2025, 14(9), 2918; https://doi.org/10.3390/jcm14092918 - 23 Apr 2025
Viewed by 345
Abstract
Background: High-voltage injuries associated with train surfing are a distinct subset of electrical injuries, yet detailed analyses remain limited. This study retrospectively reviewed train-surfing injuries admitted between 1994 and 2024, comparing their characteristics and outcomes to work-related high-voltage injuries. Methods: Medical records of [...] Read more.
Background: High-voltage injuries associated with train surfing are a distinct subset of electrical injuries, yet detailed analyses remain limited. This study retrospectively reviewed train-surfing injuries admitted between 1994 and 2024, comparing their characteristics and outcomes to work-related high-voltage injuries. Methods: Medical records of 102 patients admitted for high-voltage injuries were analyzed, including 32 train-surfing and 70 work-related cases. Demographics, injury patterns, and clinical outcomes were assessed. Results: Train surfers were predominantly young males (median age 19 years), while work-related injuries involved slightly older males (median age 34 years). Train surfers sustained more severe burns (%TBSA: 47.6% vs. 25.4%, p < 0.0001) and higher ABSI scores (6.7 vs. 5.3, p < 0.01). Vertical electrical flow was predominant in train surfing (65.6%), reflecting contact with overhead lines, while work-related injuries showed varied flow patterns, with diagonal flow being most frequent (58.6%). Train surfers had longer ICU stays (38.7 vs. 17.9 days, p < 0.001) and underwent more surgeries per patient (5.3 vs. 2.8, p < 0.01). Fasciotomy rates were significantly higher among train surfers (84.4% vs. 55.7%, p < 0.01), as were amputations (53.1% vs. 25.7%, p < 0.001). Mortality rates were similar in both groups (25%). Conclusions: Train-surfing injuries represent a distinct and highly severe subgroup of high-voltage trauma, marked by greater burn extent, predominantly vertical electrical flow due to contact with overhead lines, and significantly higher surgical complexity—including increased rates of fasciotomies and amputations. Despite comparable mortality, the clinical burden for train-surfing victims is substantially higher, reflected in longer ICU stays and more operations per patient. These findings underscore the urgent need for targeted prevention strategies addressing youth engagement in train surfing. Public health campaigns, railway infrastructure modifications (e.g., deterrent systems or physical barriers), and early educational interventions could play a critical role in reducing these preventable injuries. Furthermore, trauma centers should be prepared for the specific reconstructive and critical care demands posed by this high-risk group, emphasizing the importance of specialized multidisciplinary management protocols. Full article
(This article belongs to the Special Issue Burn Wounds Management: Challenges and New Perspectives)
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