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Search Results (1,983)

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Keywords = Cox proportional hazard model

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11 pages, 608 KiB  
Article
Both Alcoholic and Non-Alcoholic Liver Cirrhosis Are Associated with an Increased Risk of HF—A Cohort Study Including 75,558 Patients
by Karel Kostev, Jamschid Sedighi, Samuel Sossalla, Marcel Konrad and Mark Luedde
J. Cardiovasc. Dev. Dis. 2025, 12(8), 295; https://doi.org/10.3390/jcdd12080295 (registering DOI) - 31 Jul 2025
Abstract
The objective of the present study was to evaluate the association between liver cirrhosis (LC) and subsequent Heart failure (HF). This retrospective cohort study utilized data from the Disease Analyzer database (IQVIA) and included adults with a first-time diagnosis of LC in 1293 [...] Read more.
The objective of the present study was to evaluate the association between liver cirrhosis (LC) and subsequent Heart failure (HF). This retrospective cohort study utilized data from the Disease Analyzer database (IQVIA) and included adults with a first-time diagnosis of LC in 1293 general practices in Germany between January 2005 and December 2023. A comparison cohort without liver diseases was matched to the cirrhosis group using 5:1 propensity score matching. Univariable Cox proportional hazards models were used to assess the association between alcoholic vs. non-alcoholic LC and HF. The final study cohort included 5530 patients with alcoholic LC and 27,650 matched patients without liver disease, as well as 7063 patients with non-alcoholic LC and 35,315 matched patients without liver disease. After up to 10 years of follow-up, HF was diagnosed in 20.9% of patients with alcoholic LC compared to 10.3% of matched cohort, and in 23.0% of patients with non-alcoholic LC, compared to 14.2% in matched cohort. Alcoholic LC (Hazard Ratio (HR): 2.07 (95% CI: 1.85–2.31) and non-alcoholic LC (HR: 1.70; 95% CI: 1.56–1.82) were associated with an increased risk of HF. The association was also stronger in men than in women. LC, both alcoholic and non-alcoholic, is significantly associated with an increased long-term risk of HF. The association is particularly pronounced in patients with alcoholic cirrhosis and in men. To the best of the authors’ knowledge, this is the first real-world evidence for the positive association between LC and subsequent HF from Europe. Full article
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22 pages, 716 KiB  
Article
Survival in Patients with Colorectal Cancer and Isolated Brain Metastases: Temporal Trends and Prognostic Factors from the National Cancer Database (2010–2020)
by Zouina Sarfraz, Diya Jayram, Ahmad Ozair, Lydia Hodgson, Shreyas Bellur, Arun Maharaj, Vyshak A. Venur, Sarbajit Mukherjee and Manmeet S. Ahluwalia
Cancers 2025, 17(15), 2531; https://doi.org/10.3390/cancers17152531 - 31 Jul 2025
Abstract
Background: The development of brain metastases (BM) is a relatively uncommon but significantly adverse event in the spread of colorectal cancer (CRC). Although management of CRC BM has improved with advances in imaging and systemic therapies, clinical outcomes remain poor. Methods: This retrospective [...] Read more.
Background: The development of brain metastases (BM) is a relatively uncommon but significantly adverse event in the spread of colorectal cancer (CRC). Although management of CRC BM has improved with advances in imaging and systemic therapies, clinical outcomes remain poor. Methods: This retrospective cohort study used the U.S. National Cancer Database to evaluate survival outcomes, treatment patterns, and prognostic factors in CRC patients diagnosed with BM between 2010 and 2020. Patients with isolated brain-only metastases formed the primary analytic cohort, while those with additional extracranial metastases were included for descriptive comparison. Multivariable Cox proportional hazards and logistic regression models were used to assess factors associated with of survival. Proportional hazards assumptions were tested using Schoenfeld residuals. Accelerated failure time models were also employed. Results: From a cohort of 1,040,877 individuals with CRC, 795 had metastatic disease present along with relevant data, of which 296 had isolated BM. Median overall survival (mOS) in BM-only metastatic disease group was 7.82 months (95% CI: 5.82–9.66). The longest survival was observed among patients treated with stereotactic radiosurgery combined with systemic therapy (SRS+Sys), with a median OS of 23.26 months (95% CI: 17.51–41.95) and a 3-year survival rate of 35.8%. In adjusted Cox models, SRS, systemic therapy, and definitive surgery of the primary site were each independently associated with reduced hazard of death. Rectal cancer patients had longer survival than those with colon primaries (mOS: 10.35 vs. 6.08 months). Age, comorbidity burden, and insurance status were not associated with survival in adjusted analyses. Conclusions: SRS+Sys was associated with longer survival compared to other treatment strategies. However, treatment selection is highly dependent on individual clinical factors such as performance status, comorbidities, and disease extent; therefore, these findings must be interpreted with caution Future prospective studies incorporating molecular and biomarker data are warranted to better guide care in this rare and high-risk group. Full article
(This article belongs to the Section Cancer Metastasis)
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14 pages, 958 KiB  
Article
Adverse Childhood Experiences, Genetic Susceptibility, and the Risk of Osteoporosis: A Cohort Study
by Yanling Shu, Chao Tu, Yunyun Liu, Lulu Song, Youjie Wang and Mingyang Wu
Medicina 2025, 61(8), 1387; https://doi.org/10.3390/medicina61081387 - 30 Jul 2025
Abstract
Background and Objectives: Emerging evidence indicates that individuals exposed to adverse childhood experiences (ACEs) face elevated risks for various chronic illnesses. However, the association between ACEs and osteoporosis risk remains underexplored, particularly regarding potential modifications by genetic susceptibility. This prospective cohort study aims [...] Read more.
Background and Objectives: Emerging evidence indicates that individuals exposed to adverse childhood experiences (ACEs) face elevated risks for various chronic illnesses. However, the association between ACEs and osteoporosis risk remains underexplored, particularly regarding potential modifications by genetic susceptibility. This prospective cohort study aims to examine the relationship of ACEs with incident osteoporosis and investigate interactions with polygenic risk score (PRS). Materials and Methods: This study analyzed 124,789 UK Biobank participants initially free of osteoporosis. Cumulative ACE burden (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) was ascertained through validated questionnaires. Multivariable-adjusted Cox proportional hazards models assessed osteoporosis risk during a median follow-up of 12.8 years. Moderation analysis examined genetic susceptibility interactions using a standardized PRS incorporating osteoporosis-related SNPs. Results: Among 2474 incident osteoporosis cases, cumulative ACEs showed dose–response associations with osteoporosis risk (adjusted hazard ratio [HR]per one-unit increase = 1.07, 95% confidence interval [CI] 1.04–1.11; high ACEs [≥3 types] vs. none: HR = 1.26, 1.10–1.43). Specifically, emotional neglect (HR = 1.14, 1.04–1.25), emotional abuse (HR = 1.14, 1.03–1.27), physical abuse (HR = 1.17, 1.05–1.30), and sexual abuse (HR = 1.15, 1.01–1.31) demonstrated comparable effect sizes. Sex-stratified analysis revealed stronger associations in women. Joint exposure to high ACEs/high PRS tripled osteoporosis risk (HR = 3.04, 2.46–3.76 vs. low ACEs/low PRS) although G × E interaction was nonsignificant (P-interaction = 0.10). Conclusions: These results suggest that ACEs conferred incremental osteoporosis risk independent of genetic predisposition. These findings support the inclusion of ACE screening in osteoporosis prevention strategies and highlight the need for targeted bone health interventions for youth exposed to ACEs. Full article
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19 pages, 1086 KiB  
Article
The Value of the Naples Prognostic Score at Diagnosis as a Predictor of Cervical Cancer Progression
by Seon-Mi Lee, Hyunkyoung Seo, Seongmin Kim, Hyun-Woong Cho, Kyung-Jin Min, Sanghoon Lee, Jin-Hwa Hong, Jae-Yun Song, Jae-Kwan Lee and Nak-Woo Lee
Medicina 2025, 61(8), 1381; https://doi.org/10.3390/medicina61081381 - 30 Jul 2025
Abstract
Background and Objectives: The Naples prognostic score (NPS), which incorporates inflammatory and nutritional indicators, is increasingly used as a prognostic score for various malignancies. Nonetheless, few studies have specifically evaluated the NPS as a prognostic factor for cervical cancer. This study aimed [...] Read more.
Background and Objectives: The Naples prognostic score (NPS), which incorporates inflammatory and nutritional indicators, is increasingly used as a prognostic score for various malignancies. Nonetheless, few studies have specifically evaluated the NPS as a prognostic factor for cervical cancer. This study aimed to assess the value of NPS at diagnosis as a predictor of cancer progression. Materials and Methods: This study included patients diagnosed with cervical cancer at Korea University Anam Hospital from January 2019 to December 2023. Patients with incomplete data or those who were lost to follow-up were excluded. The NPS was calculated based on laboratory results at the time of diagnosis, categorizing patients into the low-NPS group (NPS 0–1) and high-NPS group (NPS ≥ 2). Survival analysis was performed using the Kaplan–Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Results: Out of 178 patients, 98 and 80 were categorized into the low-NPS and high-NPS groups, respectively. Kaplan–Meier survival analysis showed that the high-NPS group had significantly lower disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p = 0.02) rates than the low-NPS group. Multivariate Cox regression analysis identified the NPS as an independent prognostic factor for DFS (adjusted hazard ratio, 1.98; p = 0.017), but not for OS. Conclusions: This study demonstrated that the NPS measured at diagnosis may serve as a useful independent prognostic factor for cancer progression in patients with cervical cancer. Full article
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12 pages, 729 KiB  
Article
Association of Prognostic Nutritional Index and Mortality in Older Adults Undergoing Hip Fracture Surgery: A Retrospective Observational Study at a Single Large Center
by Yeon Ju Kim, Ji-In Park, Hyungtae Kim, Won Uk Koh, Young-Jin Ro and Ha-Jung Kim
Medicina 2025, 61(8), 1376; https://doi.org/10.3390/medicina61081376 - 30 Jul 2025
Viewed by 54
Abstract
Background and Objectives: Patients with hip fractures have a high mortality rate, highlighting the need for a reliable prognostic tool. Although the prognostic nutritional index (PNI) is a well-established predictor in patients with cancer, its utility has not been thoroughly investigated in [...] Read more.
Background and Objectives: Patients with hip fractures have a high mortality rate, highlighting the need for a reliable prognostic tool. Although the prognostic nutritional index (PNI) is a well-established predictor in patients with cancer, its utility has not been thoroughly investigated in patients with hip fractures. Therefore, this study aims to evaluate the association between PNI and mortality in patients undergoing hip fracture surgery. Materials and Methods: A retrospective review was conducted on all patients aged ≥65 years who underwent surgery for hip fracture between January 2014 and February 2018. Quartile stratification was chosen because no universally accepted clinical cut-off exists for PNI; this approach enables comparison of equally sized groups and exploration of potential non-linear risk patterns. The primary endpoints were 1-year and overall mortality in older adults undergoing hip fracture surgery. Multivariable Cox proportional-hazards models adjusted for age, sex, ASA class and comorbidities. Results: A total of 815 patients were analyzed. One-year and overall mortality rates were highest in the Q1 group (26.6%, 14.2%, 6.9%, 6.4% [p < 0.001] and 56.7%, 36.3%, 27.0%, 15.2% [p < 0.001], respectively). In Cox regression analysis, a lower preoperative PNI was significantly associated with an increased risk of overall mortality (Q1: HR 3.25, 95% confidence interval [CI] 2.11–5.01, p < 0.001; Q2: HR 1.85, 95% CI 1.19–2.86, p = 0.006; Q3: HR 1.52, 95% CI 0.97–2.38, p = 0.065; Q4 as reference), indicating a stepwise, dose–response increase in mortality risk as PNI decreases. Conclusions: The findings demonstrate that a lower preoperative PNI is significantly associated with higher 1-year and overall mortality in older adults undergoing hip fracture surgery. Although further prospective validation is needed, preoperative PNI may help predict mortality in frail patients undergoing hip fracture surgery and identify those who could benefit from nutritional assessment and optimization before surgery. Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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14 pages, 1025 KiB  
Article
Prognostic Significance of AI-Enhanced ECG for Emergency Department Patients
by Yu-Te Su, Sy-Jou Chen, Chin Lin, Chin-Sheng Lin and Hsiao-Feng Hu
Diagnostics 2025, 15(15), 1874; https://doi.org/10.3390/diagnostics15151874 - 25 Jul 2025
Viewed by 215
Abstract
Background/Objectives: Artificial intelligence (AI)-enabled electrocardiogram (ECG) analysis may assist in objective and reproducible risk stratification. However, the prognostic utility of serial ECGs, particularly the follow-up ECG prior to discharge, has not been extensively studied. This study aimed to evaluate whether dynamic changes [...] Read more.
Background/Objectives: Artificial intelligence (AI)-enabled electrocardiogram (ECG) analysis may assist in objective and reproducible risk stratification. However, the prognostic utility of serial ECGs, particularly the follow-up ECG prior to discharge, has not been extensively studied. This study aimed to evaluate whether dynamic changes in AI-predicted ECG risk scores could enhance prediction of post-discharge outcomes. Methods: This retrospective cohort study included 11,508 ED visits from a single medical center where patients underwent two ECGs and were directly discharged. We stratified the mortality risk of patients as low risk, medium risk, and high risk based on the first and follow-up ECG prior to discharge using AI-enabled ECG models. The Area Under the Curve (AUC) was calculated for the predictive performance of the two ECGs. Kaplan–Meier (KM) curves were used for 90-day mortality analysis, and the Cox proportional hazards model was utilized to compare the risk of death across categories. Results: The AI-enabled ECG risk prediction model, based on the initial and follow-up ECGs prior to discharge, indicated risk transitions among different groups. The AUC for mortality risk was 78.6% for the first ECG and 83.3% for the follow-up ECG. KM curves revealed a significant increase in 90-day mortality for patients transitioning from low to medium/high risk upon discharge (Hazard Ratio: 6.01; Confidence Interval: 1.70–21.27). Conclusions: AI-enabled ECGs obtained prior to discharge provide superior mortality risk stratification for ED patients compared to initial ECGs. Patients classified as medium- or high-risk at discharge require careful consideration, whereas those at low risk can generally be discharged safely. Although AI-ECG alone does not replace comprehensive risk assessment, it offers a practical tool to support clinical judgment, particularly in the dynamic ED environment, by aiding safer discharge decisions. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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23 pages, 454 KiB  
Article
Gastric Cancer Surgery Before and During the COVID-19 Pandemic in Turkey: A Multicenter Comparison of Prognostic Factors, Mortality, and Survival
by Yasin Dalda, Sami Akbulut, Zeki Ogut, Serkan Yilmaz, Emrah Sahin, Ozlem Dalda, Adem Tuncer and Zeynep Kucukakcali
Medicina 2025, 61(8), 1336; https://doi.org/10.3390/medicina61081336 - 24 Jul 2025
Viewed by 298
Abstract
Background/Objectives: The COVID-19 pandemic disrupted global cancer care. This study compared gastric cancer surgical outcomes before and during the pandemic in Turkey. We also aimed to analyze the impact of the pandemic and factors on survival and mortality in gastric cancer patients. Materials [...] Read more.
Background/Objectives: The COVID-19 pandemic disrupted global cancer care. This study compared gastric cancer surgical outcomes before and during the pandemic in Turkey. We also aimed to analyze the impact of the pandemic and factors on survival and mortality in gastric cancer patients. Materials and Methods: This retrospective, multicenter cohort study included 324 patients from three tertiary centers in Turkey who underwent gastric cancer surgery between January 2018 and December 2022. Patients were stratified into Pre-COVID-19 (n = 150) and COVID-19 Era (n = 174) groups. Comprehensive demographic, surgical, pathological, and survival data were analyzed. To identify factors independently associated with postoperative mortality, a multivariable logistic regression model was applied. For evaluating predictors of long-term survival, multivariable Cox proportional hazards regression analysis was conducted. Results: The median time from diagnosis to surgery was comparable between groups, while the time from surgery to pathology report was significantly prolonged during the pandemic (p = 0.012). Laparoscopic surgery (p = 0.040) and near-total gastrectomy (p = 0.025) were more frequently performed in the Pre-COVID-19 group. Although survival rates between groups were similar (p = 0.964), follow-up duration was significantly shorter in the COVID-19 Era (p < 0.001). Comparison between survivor and non-survivor groups showed that several variables were significantly associated with mortality, including larger tumor size (p < 0.001), greater number of metastatic lymph nodes (p < 0.001), elevated preoperative CEA (p = 0.001), CA 19-9 (p < 0.001), poor tumor differentiation (p = 0.002), signet ring cell histology (p = 0.003), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001). Multivariable logistic regression identified total gastrectomy (OR: 2.14), T4 tumor stage (OR: 2.93), N3 nodal status (OR: 2.87), and lymphovascular invasion (OR: 2.87) as independent predictors of postoperative mortality. Cox regression analysis revealed that combined tumor location (HR: 1.73), total gastrectomy (HR: 1.56), lymphovascular invasion (HR: 2.63), T4 tumor stage (HR: 1.93), N3 nodal status (HR: 1.71), and distant metastasis (HR: 1.74) were independently associated with decreased overall survival. Conclusions: Although gastric cancer surgery continued during the COVID-19 pandemic, some delays in pathology reporting were observed; however, these did not significantly affect the timing of adjuvant therapy or patient outcomes. Importantly, pandemic timing was not identified as an independent risk factor for mortality in multivariable logistic regression analysis, nor for survival in multivariable Cox regression analysis. Instead, tumor burden and aggressiveness—specifically advanced stage, lymphovascular invasion, and total gastrectomy—remained the primary independent determinants of poor prognosis. While pandemic-related workflow delays occurred, institutional adaptability preserved oncologic outcomes. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
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16 pages, 1417 KiB  
Article
Survival Modelling Using Machine Learning and Immune–Nutritional Profiles in Advanced Gastric Cancer on Home Parenteral Nutrition
by Konrad Matysiak, Aleksandra Hojdis and Magdalena Szewczuk
Nutrients 2025, 17(15), 2414; https://doi.org/10.3390/nu17152414 - 24 Jul 2025
Viewed by 268
Abstract
Background/Objectives: Patients with stage IV gastric cancer who develop chronic intestinal failure require home parenteral nutrition (HPN). This study aimed to evaluate the prognostic relevance of nutritional and immune–inflammatory biomarkers and to construct an individualised survival prediction model using machine learning techniques. Methods: [...] Read more.
Background/Objectives: Patients with stage IV gastric cancer who develop chronic intestinal failure require home parenteral nutrition (HPN). This study aimed to evaluate the prognostic relevance of nutritional and immune–inflammatory biomarkers and to construct an individualised survival prediction model using machine learning techniques. Methods: A secondary analysis was performed on a cohort of 410 patients with TNM stage IV gastric adenocarcinoma who initiated HPN between 2015 and 2023. Nutritional and inflammatory indices, including the Controlling Nutritional Status (CONUT) score and lymphocyte-to-monocyte ratio (LMR), were assessed. Independent prognostic factors were identified using Cox proportional hazards models. A Random Survival Forest (RSF) model was constructed to estimate survival probabilities and quantify variable importance. Results: Both the CONUT score and LMR were independently associated with overall survival. In multivariate analysis, higher CONUT scores were linked to increased mortality risk (HR = 1.656, 95% CI: 1.306–2.101, p < 0.001), whereas higher LMR values were protective (HR = 0.632, 95% CI: 0.514–0.777, p < 0.001). The RSF model demonstrated strong predictive accuracy (C-index: 0.985–0.986) and effectively stratified patients by survival risk. The CONUT score exerted the greatest prognostic influence, with the LMR providing additional discriminatory value. A gradual decline in survival probability was observed with an increasing CONUT score and a decreasing LMR. Conclusions: The application of machine learning to immune–nutritional data offers a robust tool for predicting survival in patients with advanced gastric cancer requiring HPN. This approach may enhance risk stratification, support individualised clinical decision-making regarding nutritional interventions, and inform treatment intensity adjustment. Full article
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15 pages, 867 KiB  
Article
Prognostic Factors and Survival Outcomes in Resected Biliary Tract Cancers: A Multicenter Retrospective Analysis
by Michele Ghidini, Fausto Petrelli, Matteo Paccagnella, Massimiliano Salati, Francesca Bergamo, Margherita Ratti, Caterina Soldà, Barbara Galassi, Ornella Garrone, Massimo Rovatti, Arianna Zefelippo, Lucio Caccamo, Enrico Gringeri, Alessandro Zerbi, Guido Torzilli, Silvia Bozzarelli, Lorenza Rimassa and Gianluca Tomasello
Cancers 2025, 17(15), 2445; https://doi.org/10.3390/cancers17152445 - 23 Jul 2025
Viewed by 186
Abstract
Background/Objectives: Biliary tract cancers (BTCs) are aggressive malignancies with a poor prognosis. Surgery remains the only curative option, yet recurrence rates are high, and the role of adjuvant chemotherapy remains debated. This study aims to evaluate the impact of adjuvant chemotherapy and [...] Read more.
Background/Objectives: Biliary tract cancers (BTCs) are aggressive malignancies with a poor prognosis. Surgery remains the only curative option, yet recurrence rates are high, and the role of adjuvant chemotherapy remains debated. This study aims to evaluate the impact of adjuvant chemotherapy and prognostic factors on survival outcomes in resected BTCs. Methods: We conducted a retrospective multicenter study analyzing patients diagnosed with intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA) or gallbladder cancer (GBC) who underwent curative-intent surgical resection between 1999 and 2023. Demographic, clinicopathological, and treatment data were collected from institutional databases. Survival outcomes were assessed using Kaplan–Meier analysis, and prognostic factors were identified through Cox proportional hazards regression. Results: A total of 155 patients were included, with a median follow-up of 84.6 months. The cohort comprised 38.7% iCCA, 31.6% eCCA, and 29.7% GBC. R0 resection was achieved in 77.4% of cases, while lymph node involvement was present in 39.4%. Median overall survival (OS) significantly varied by stage (p < 0.001), ranging from >60 months for stage I to ~12 months for stage IVA. Eastern Cooperative Oncology Group (ECOG) performance status (PS) emerged as the strongest independent prognostic factor for OS (p < 0.001). Adjuvant chemotherapy, administered to 49.0% of patients, did not significantly improve OS in the overall cohort (p = 0.899). However, subgroup analyses suggested potential benefits in iCCA and eCCA but not in GBC. High CA19-9 levels and vascular invasion were associated with poorer survival outcomes. Conclusions: This study highlights the prognostic significance of ECOG PS, resection margin status, lymph node involvement, and CA19-9 levels in resected BTCs. The lack of a clear survival benefit from adjuvant chemotherapy underscores the need for improved therapeutic strategies. Future research should focus on refining risk stratification models and identifying more effective adjuvant treatments to enhance long-term survival outcomes in patients with BTC. Full article
(This article belongs to the Special Issue Clinical Surgery for Hepato-Pancreato-Biliary (HPB) Cancer)
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13 pages, 934 KiB  
Article
Inhaled Corticosteroids and Risk of Staphylococcus aureus Isolation in Bronchiectasis: A Register-Based Cohort Study
by Andrea Arlund Filipsen, Karen Hougaard Frost, Josefin Eklöf, Louise Lindhardt Tønnesen, Anna Kubel Vognsen, Jonas Bredtoft Boel, Mette Pinholt, Christian Østergaard Andersen, Ram Benny Christian Dessau, Tor Biering-Sørensen, Sofie Lock Johansson, Jens-Ulrik Jensen and Pradeesh Sivapalan
J. Clin. Med. 2025, 14(15), 5207; https://doi.org/10.3390/jcm14155207 - 23 Jul 2025
Viewed by 342
Abstract
Objectives: Non-cystic fibrosis bronchiectasis (BE) is a chronic airway disease with increasing prevalence, reduced quality of life, and increased mortality. Inhaled corticosteroids (ICS) are used in BE despite limited evidence of effect on lung function parameters. ICS may increase the risk of Staphylococcus [...] Read more.
Objectives: Non-cystic fibrosis bronchiectasis (BE) is a chronic airway disease with increasing prevalence, reduced quality of life, and increased mortality. Inhaled corticosteroids (ICS) are used in BE despite limited evidence of effect on lung function parameters. ICS may increase the risk of Staphylococcus aureus (S. aureus) infections in patients with BE, but this is unexplored. We examined the association between ICS use prior to BE diagnosis at different doses and the risk of S. aureus isolation in patients with BE. Methods: We conducted a national register-based cohort study including Danish patients with a BE diagnosis code between 2001 and 2018 with a 1-year follow-up time from the date of diagnosis. ICS exposure was categorized based on accumulated prescriptions redeemed 365 days before BE diagnosis and divided into none, low, moderate, or high use based on clinically relevant doses. A cause-specific Cox proportional hazards regression model was used to estimate the risk of S. aureus isolation. A sensitivity analysis, an inverse probability of treatment weighted model (IPTW), was performed. Results: A total of 5093 patients were included in this study. S. aureus was isolated in 156 patients (3.1%). High-dose ICS was associated with an increased risk of S. aureus isolation, HR 3.81 (95% CI 2.51; 5.79). No association for low or moderate use was found, low-dose HR 1.22 (95% CI 0.77; 1.93), and moderate-dose HR 1.24 (95% CI 0.72; 2.16). IPTW analysis yielded similar results. Conclusions: High-dose ICS use in patients with BE was associated with an increased risk of S. aureus isolation. ICS should be used cautiously in patients with BE. Full article
(This article belongs to the Section Respiratory Medicine)
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23 pages, 811 KiB  
Article
Overcoming Barriers to Exclusive Breastfeeding in Lao PDR: Social Transfer Intervention Randomised Controlled Trial
by Najmeh Karimian-Marnani, Elizabeth Tilley and Jordyn T. Wallenborn
Nutrients 2025, 17(15), 2396; https://doi.org/10.3390/nu17152396 - 22 Jul 2025
Viewed by 173
Abstract
Background/Objectives: Despite the numerous health benefits of exclusive breastfeeding (EBF) for the infant and the mother, EBF rates in Lao People’s Democratic Republic, Lao PDR, remain at 40%. We investigate how barriers to EBF were overcome by a social transfer intervention. Methods [...] Read more.
Background/Objectives: Despite the numerous health benefits of exclusive breastfeeding (EBF) for the infant and the mother, EBF rates in Lao People’s Democratic Republic, Lao PDR, remain at 40%. We investigate how barriers to EBF were overcome by a social transfer intervention. Methods: Data from the Social Transfers for Exclusive Breastfeeding ongoing randomised controlled trial (RCT) (n = 298) in Vientiane, Lao PDR, was used. Mothers in the RCT were randomised equally into a control group, an unconditional transfer group and a conditional transfer group and followed up to six months (n = 280). We used logistic and Cox proportional hazards regression models to investigate the association of predictor variables with EBF at six months and the risk of EBF cessation in each of the three groups. Results: Greater breastfeeding self-efficacy increased the odds of EBF at six months in both intervention groups (unconditional transfer OR 1.39 [95% CI 1.09, 1.87, p = 0.02] and conditional transfer OR 1.26 [1.01, 1.61, p = 0.05]) and reduced the risk of EBF cessation (unconditional transfer HR 0.87 [0.77, 0.98, p = 0.02]). Maternal secondary and tertiary education in the intervention groups showed higher odds of EBF at six months and lower EBF cessation risk. Participants in the intervention group that intended to exclusively breastfeed in pregnancy showed a reduced EBF cessation risk in both intervention groups. Conclusions: Social transfers helped overcome the exclusive breastfeeding barrier of a higher education level and working status and improved EBF outcomes for mothers who intended to exclusively breastfeed and wanted the pregnancy. Breastfeeding self-efficacy positively influences EBF outcome, regardless of whether the mother received a social transfer or not. Full article
(This article belongs to the Section Nutrition and Public Health)
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19 pages, 5678 KiB  
Article
Transcriptomic Profile of Perineural Invasion in Prostate Cancer Identifies Prognostic Gene Signatures
by Cagdas Aktan, Swati Mamidanna, Caryn Cobb, Ceren Atalar, Jacqueline Chan, Christina M. Breneman, Okan Argun and Mutlay Sayan
Biomedicines 2025, 13(8), 1789; https://doi.org/10.3390/biomedicines13081789 - 22 Jul 2025
Viewed by 332
Abstract
Background: Prostate cancer is a common malignancy among men worldwide, with various histopathologic features that influence its progression and prognosis. One such feature is perineural invasion (PNI), which has been associated with aggressive disease. In this retrospective study, we analyzed genomic alterations associated [...] Read more.
Background: Prostate cancer is a common malignancy among men worldwide, with various histopathologic features that influence its progression and prognosis. One such feature is perineural invasion (PNI), which has been associated with aggressive disease. In this retrospective study, we analyzed genomic alterations associated with PNI in patients who underwent radical prostatectomy. Methods: A total of 421 prostate cancer patients who underwent radical prostatectomy without neoadjuvant therapy were identified from The Cancer Genome Atlas. PNI was present in 378 patients (89.8%) and absent in 43 (10.2%). Differentially expressed genes were identified, and mRNA expression levels of key genes were analyzed. The prognostic significance of these genes was evaluated using log-rank tests and Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals. Results: Levels of COL9A3, ASPN, ESR1, MUC1, PIP, SFRP4, KRT19, CLDN1, and COMP were significantly higher in the tumor tissues of patients in the PNI group compared to those in the non-PNI group (q < 0.05), and RYR2, MME, and AZGP1 expression levels were significantly higher in the non-PNI group (q < 0.05). A high mRNA expression level of AZGP1 was associated with longer disease-free survival, whereas high mRNA expressions of ASPN, COMP, RYR2, and SFRP4 were associated with shorter disease-free survival. Conclusions: Prostate cancer patients with genomic alterations associated with PNI may face a higher risk of disease progression after prostatectomy, highlighting the need for further prospective studies to validate these findings. Full article
(This article belongs to the Special Issue Prostate Cancer Pathology: Recent Advances and Future Perspectives)
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10 pages, 303 KiB  
Article
Mortality from Pleural and Lung Cancer in Railway Maintenance Workers
by Leonardo Scarso, Marco Novelli, Eva Lorenza Negri, Carlotta Zunarelli, the Pleural Cancer 2024 Study Group and Francesco Saverio Violante
Life 2025, 15(7), 1155; https://doi.org/10.3390/life15071155 - 21 Jul 2025
Viewed by 230
Abstract
(1) Background: Occupational exposure to asbestos remains a significant public health concern due to its association with pleural cancer and other cancers. This cohort study examines the incidence of asbestos-related diseases among railway carriage maintenance workers exposed to asbestos between 1960 and 1979 [...] Read more.
(1) Background: Occupational exposure to asbestos remains a significant public health concern due to its association with pleural cancer and other cancers. This cohort study examines the incidence of asbestos-related diseases among railway carriage maintenance workers exposed to asbestos between 1960 and 1979 in Bologna, Italy. (2) Methods: A cohort of 2197 male workers was followed from 1960 onwards, with data collected on asbestos exposure, smoking habits, and mortality outcomes. The association of asbestos exposure and smoking with the risk of pleural cancer and lung cancer was assessed using Cox proportional hazards regression models. (3) Results: This study identified a substantial burden of asbestos-related pleural cancer, with an exponential increase in risk over time since the beginning of exposure. Our results suggest the lack of a multiplicative effect of asbestos exposure and smoking on lung cancer risk. The Cox models showed a significant association between smoking and lung cancer risk, with a hazard ratio of 3.26 (95% CI: 1.10–9.64, p = 0.03), less significant for asbestos exposure, with a hazard ratio of 1.42 (95% CI: 0.66–3.06). (4) Conclusions: This study provides valuable insights into the long-term health effects of occupational asbestos exposure and underscores the complex interaction between asbestos exposure and smoking in the development of lung cancer. Full article
(This article belongs to the Section Epidemiology)
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13 pages, 789 KiB  
Article
Vitamin D Deficiency as an Independent Predictor for Plaque Vulnerability and All-Cause Mortality in Patients with High-Grade Carotid Disease
by Stephanie Kampf, Olesya Harkot, Rodrig Marculescu, Svitlana Demyanets, Markus Klinger, Wolf Eilenberg, Johann Wojta, Christoph Neumayer and Stefan Stojkovic
J. Clin. Med. 2025, 14(14), 5163; https://doi.org/10.3390/jcm14145163 - 21 Jul 2025
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Abstract
Objectives: The mechanisms linking vitamin D deficiency to carotid artery stenosis (CAS) remain unclear. Data on cardiovascular outcomes in CAS patients with vitamin D deficiency are limited. We investigated the association of vitamin D deficiency with carotid plaque morphology and patient outcomes in [...] Read more.
Objectives: The mechanisms linking vitamin D deficiency to carotid artery stenosis (CAS) remain unclear. Data on cardiovascular outcomes in CAS patients with vitamin D deficiency are limited. We investigated the association of vitamin D deficiency with carotid plaque morphology and patient outcomes in high-grade CAS. Methods: A total of 332 patients undergoing carotid endarterectomy for symptomatic (n = 113, 34%) or asymptomatic (n = 219, 66%) CAS were included. Preoperative vitamin D levels were measured, and duplex sonography was used to assess luminal narrowing. Associations of vitamin D with clinical presentation were analyzed using univariate and multivariate linear regression. For vitamin D deficiency and the prediction of major adverse cardiovascular events (MACE) and all-cause mortality, the Cox proportional hazard regression model was used. Results: The median age was 69 years (interquartile range (IQR) 64–74), and 94 (29.3%) patients were female. Vitamin D deficiency was present in 84 (25%) patients. Symptomatic patients had significantly lower vitamin D levels (41.2 nmol/L, IQR 25.1–63.5) than asymptomatic patients (51.6 nmol/L, IQR 30.5–74.3, p = 0.011). Patients with echolucent (44.9 nmol/L, IQR 27.4–73.7) or mixed plaques (39.2 nmol/L, IQR 22.9–63.5) had lower vitamin D levels than those with echogenic plaques (52.3 nmol/L, IQR 34.1–75.7). Vitamin D deficiency predicted MACE and all-cause mortality with an adjusted HR of 1.6, 95% CI of 1.1–2.6, and p = 0.030 and an HR of 2.2, 95% CI of 1.3–3.6, and p = 0.002, respectively, in a multivariable Cox proportional hazard regression model. Conclusions: A deficiency in vitamin D was correlated with unstable plaque characteristics and symptomatic CAS. Furthermore, vitamin D deficiency was associated with long-term adverse cardiovascular outcomes and mortality, suggesting its potential as a modifiable risk factor for improved risk stratification in patients undergoing carotid endarterectomy. Full article
(This article belongs to the Section Cardiovascular Medicine)
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15 pages, 1398 KiB  
Article
Lymphovascular Invasion Is a Predictor of Clinical Outcomes in Bladder Cancer Patients Treated with Radical Cystectomy
by Daniel-Vasile Dulf, Anamaria Larisa Burnar, Patricia-Lorena Dulf, Doina-Ramona Matei, Raluca Maria Hendea, Iulia Andraș, Miruna Grecea, Cătălina Bungărdean, Antonio De Leo, Tudor-Eliade Ciuleanu, Nicolae Crișan and Camelia Alexandra Coada
J. Clin. Med. 2025, 14(14), 5120; https://doi.org/10.3390/jcm14145120 - 18 Jul 2025
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Abstract
Background/Objectives: Lymphovascular invasion (LVI) has been consistently linked to poor outcomes in patients with bladder cancer (BC), yet its independent prognostic value, especially after adjusting for established pathological features, remains debated. This study aimed to evaluate the prognostic value of LVI in the [...] Read more.
Background/Objectives: Lymphovascular invasion (LVI) has been consistently linked to poor outcomes in patients with bladder cancer (BC), yet its independent prognostic value, especially after adjusting for established pathological features, remains debated. This study aimed to evaluate the prognostic value of LVI in the context of other pathological features of patients undergoing radical cystectomy. Methods: We conducted a retrospective cohort study including 200 patients treated at the Municipal Clinical Hospital in Cluj-Napoca, Romania. Associations between LVI and overall survival (OS) were assessed using univariable and multivariable Cox proportional hazards models, with Kaplan–Meier curves used for visualizing survival distributions. Results: In univariable analysis, increasing age, presence of LVI, advanced pathological tumor stage (pT ≥ 2), and nodal involvement (pN ≥ 1) were significantly associated with worse OS. LVI was a strong predictor of poor survival (HR 3.13; 95% CI: 2.09; 4.69; p < 0.001). However, in multivariable analysis, only tumor stage (HR 4.85; 95% CI: 2.19; 10.77; p < 0.001) and nodal involvement (HR 1.87; 95% CI: 1.13; 3.09; p = 0.015) remained independently associated with OS. In patients with incomplete nodal staging (Nx), LVI was significantly associated with OS (p = 0.028). Conclusions: Our findings reinforce the prognostic relevance of LVI in bladder cancer and support its role as a marker of aggressive tumor biology, highlighting its value in clinical risk assessment, especially in patients with incomplete nodal staging. Routine reporting of LVI in pathology and consideration in treatment planning are warranted. Full article
(This article belongs to the Special Issue Advances and Perspectives in Cancer Diagnostics and Treatment)
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