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Keywords = adverse composite outcomes

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24 pages, 3915 KiB  
Article
Prothrombotic Genetic Mutations Are Associated with Sub-Clinical Placental Vascular Lesions: A Histopathological and Morphometric Study
by Viorela-Romina Murvai, Anca Huniadi, Radu Galiș, Gelu Florin Murvai, Timea Claudia Ghitea, Alexandra-Alina Vesa and Ioana Cristina Rotar
Curr. Issues Mol. Biol. 2025, 47(8), 612; https://doi.org/10.3390/cimb47080612 (registering DOI) - 4 Aug 2025
Abstract
Background: Inherited thrombophilia is increasingly recognized as a contributing factor to placental vascular pathology and adverse pregnancy outcomes. While the clinical implications are well-established, fewer studies have systematically explored the histopathological changes associated with specific genetic mutations in thrombophilic pregnancies. Materials and Methods: [...] Read more.
Background: Inherited thrombophilia is increasingly recognized as a contributing factor to placental vascular pathology and adverse pregnancy outcomes. While the clinical implications are well-established, fewer studies have systematically explored the histopathological changes associated with specific genetic mutations in thrombophilic pregnancies. Materials and Methods: This retrospective observational study included two cohorts of placental samples collected between September 2020 and September 2024 at a tertiary maternity hospital. Group 1 included women diagnosed with hereditary thrombophilia, and Group 2 served as controls without known maternal pathology. Placentas were examined macroscopically and histologically, with pathologists blinded to group allocation. Histological lesions were classified according to the Amsterdam Consensus and quantified using a composite score (0–5) based on five key vascular features. Results: Placental lesions associated with maternal vascular malperfusion—including infarctions, intervillous thrombosis, stromal fibrosis, villous stasis, and acute atherosis—were significantly more frequent in the thrombophilia group (p < 0.05 for most lesions). A combination of well-established thrombophilic mutations (Factor V Leiden, Prothrombin G20210A) and other genetic polymorphisms with uncertain clinical relevance (MTHFR C677T, PAI-1 4G/4G) showed moderate-to-strong correlations with histopathological markers of placental vascular injury. A composite histological score ≥3 was significantly associated with thrombophilia (p < 0.001). Umbilical cord abnormalities, particularly altered coiling and hypertwisting, were also more prevalent in thrombophilic cases. Conclusions: Thrombophilia is associated with distinct and quantifiable placental vascular lesions, even in pregnancies without overt clinical complications. The use of a histological scoring system may aid in the retrospective identification of thrombophilia-related placental pathology and support the integration of genetic and histologic data in perinatal risk assessment. Full article
(This article belongs to the Special Issue Feature Papers in Molecular Medicine 2025)
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11 pages, 2215 KiB  
Article
Dysbiosis in the Nasal Mycobiome of Infants Born in the Aftermath of Hurricane Maria
by Ruochen Wang, David de Ángel Solá, Félix E. Rivera-Mariani, Benjamín Bolaños Rosero, Nicolás Rosario Matos and Leyao Wang
Microorganisms 2025, 13(8), 1784; https://doi.org/10.3390/microorganisms13081784 - 31 Jul 2025
Viewed by 318
Abstract
Hurricanes and flooding events substantially elevate indoor fungal spore levels, which have been associated with increased risks of developing childhood asthma and other adverse respiratory outcomes. Although environmental fungal compositions following major hurricanes have been well characterized, the fungal communities within the nasal [...] Read more.
Hurricanes and flooding events substantially elevate indoor fungal spore levels, which have been associated with increased risks of developing childhood asthma and other adverse respiratory outcomes. Although environmental fungal compositions following major hurricanes have been well characterized, the fungal communities within the nasal cavity (i.e., the nasal mycobiome) of exposed individuals remain unexplored. We collected nasal swab samples from infants following Hurricane Maria in San Juan, Puerto Rico, during two periods (March to August 2018 and February to September 2019). We processed a total of 58 samples (26 from the first year and 32 from the second year post-Hurricane Maria) and performed internally transcribed spacer (ITS) rRNA gene sequencing to characterize and compare the infant nasal mycobiome between the two groups. Although alpha-diversity did not differ significantly, beta-diversity analyses revealed significantly different fungal compositions between the two groups (p <0.01). Infants exposed during the first year post-Hurricane Maria had significantly higher abundances of Alternaria, Eutypella, Schizophyllum, and Auricularia, compared to infants from the second year. Alternaria was also more prevalent in the first-year than in the second-year infants (42% vs. 9%, p = 0.01). Our study provides evidence linking early-life hurricane exposures to elevated risks of developing childhood asthma. Full article
(This article belongs to the Special Issue Fungi and Health)
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18 pages, 955 KiB  
Article
Unequal Burdens: Exploring Racial Disparities in Cardiovascular and SLE Outcomes Using National Inpatient Database 2016–2021
by Freya Shah, Siddharth Pravin Agrawal, Darshilkumar Maheta, Jatin Thukral and Syeda Sayeed
Rheumato 2025, 5(3), 10; https://doi.org/10.3390/rheumato5030010 - 30 Jul 2025
Viewed by 240
Abstract
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant racial and ethnic disparities in prevalence, disease severity, and outcomes. Cardiovascular complications, including pericarditis, myocarditis, valvular disease, and conduction abnormalities, contribute to increased morbidity and mortality in SLE patients. This study [...] Read more.
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant racial and ethnic disparities in prevalence, disease severity, and outcomes. Cardiovascular complications, including pericarditis, myocarditis, valvular disease, and conduction abnormalities, contribute to increased morbidity and mortality in SLE patients. This study examines racial and ethnic disparities in cardiovascular outcomes among hospitalized SLE patients in the United States. Methods: This retrospective study utilized the National Inpatient Sample (NIS) database from 2016 to 2021 to analyze hospitalizations of adult patients (≥18 years) with a primary or secondary diagnosis of SLE. Patients were stratified into racial/ethnic groups: White, Black, Hispanic, Asian, Native American, and Other. Primary outcomes include major adverse cardiovascular events (MACEs), which are a composite of in-hospital mortality, myocardial infarction (MI), sudden cardiac death, and other SLE-related outcomes including cardiac, pulmonary, and renal involvement. Statistical analyses included multivariable logistic regression models adjusted for demographic, socioeconomic, and hospital-related factors to assess racial disparities. Results: The study included 514,750 White, 321,395 Black, and 146,600 Hispanic patients, with smaller proportions of Asian, Native American, and Other racial groups. Black patients had significantly higher odds of in-hospital mortality (OR = 1.17, 95% CI = 1.08–1.26, p < 0.001) and sudden cardiac death (OR = 1.64, 95% CI = 1.46–1.85, p < 0.001) compared to White patients. Asian patients also exhibited increased mortality risk (OR = 1.37, 95% CI = 1.14–1.63, p = 0.001) as compared to Whites. Conversely, Black (OR = 0.90, 95% CI = 0.85–0.96, p = 0.01) and Hispanic (OR = 0.87, 95% CI = 0.80–0.96, p = 0.03) patients had lower odds of MI. Racial disparities in access to care, socioeconomic status, and comorbidity burden may contribute to these differences. Conclusion: Significant racial and ethnic disparities exist in cardiovascular outcomes among hospitalized SLE patients. Black and Asian individuals face higher in-hospital all-causes mortality and sudden cardiac death risks, while Black and Hispanic patients exhibit lower MI rates. Addressing social determinants of health, improving access to specialized care, and implementing targeted interventions may reduce disparities and improve outcomes in minority populations with SLE. Full article
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15 pages, 826 KiB  
Article
Composite RAI, Malnutrition, and Anemia Model Superiorly Predicts 30-Day Morbidity and Mortality After Surgery for Adult Spinal Deformity
by Aladine A. Elsamadicy, Paul Serrato, Shaila D. Ghanekar, Justice Hansen, Ethan D. L. Brown, Syed I. Khalid, Daniel Schneider, Sheng-fu Larry Lo and Daniel M. Sciubba
J. Clin. Med. 2025, 14(15), 5379; https://doi.org/10.3390/jcm14155379 - 30 Jul 2025
Viewed by 228
Abstract
Background/Objective: This study examines the composite influence of frailty, malnutrition, and anemia on postoperative outcomes for patients with adult spinal deformity (ASD). Methods: In this retrospective cohort study using the 2011–2022 NSQIP database, we utilized CPT and ICD codes to identify ASD patients [...] Read more.
Background/Objective: This study examines the composite influence of frailty, malnutrition, and anemia on postoperative outcomes for patients with adult spinal deformity (ASD). Methods: In this retrospective cohort study using the 2011–2022 NSQIP database, we utilized CPT and ICD codes to identify ASD patients who underwent PSF. Subjects were stratified based on frailty status. Frail patients were then classified according to malnutrition and anemia status. Frailty was determined using the revised risk analysis index (RAI-rev). Our primary outcomes were extended length of stay (LOS), non-routine discharge (NRD), 30-day adverse events (AE), and 30-day mortality. For each outcome, we fitted four nested multivariable logistic regression models (RAI-rev + anemia + malnutrition, RAI-rev + anemia, RAI-rev + malnutrition, and RAI-rev alone) and compared the incremental discrimination of each model using receiver operating characteristic (ROC) analysis. Results: Of 3639 patients, 460 were frail alone, 266 were frail + anemic, 37 were frail + malnourished, 121 were frail + anemic + malnourished, and 2755 were not frail. RAI-rev (aOR: 1.84, 95% CI: 1.45–2.35), anemia (aOR: 1.84, 95% CI: 1.45–2.35), and malnourishment (aOR: 2.34, 95% CI: 1.69–3.24) were independent predictors of extended LOS. RAI-rev (aOR: 1.07, 95% CI: 1.04–1.11) and anemia (aOR: 2.09, 95% CI: 1.66–2.61) were associated with an increased risk of 30-day AEs. RAI-rev and malnutrition were independent predictors of NRD (RAI-rev: aOR: 1.11, 95% CI: 1.06–1.16; Malnutrition: aOR: 1.57, 95% CI: 1.08–2.29) and 30-day mortality (RAI-rev: aOR: 1.10, 95% CI: 1.04–1.17; Malnutrition: aOR: 3.79, 95% CI: 1.24–11.60). Based on ROC analysis, RAI-rev + anemic + malnourished was a superior predictor of LOS and 30-day AEs (both p < 0.001). Compared to RAI-rev, RAI-rev + anemic superiorly predicted LOS and 30-day AEs, and RAI-rev + malnutrition superiorly predicted LOS (all p < 0.001). Conclusions: Our results reveal RAI-rev combined with malnutrition and anemia superiorly predicts 30-day AEs and LOS in postoperative ASD patients. Future studies should investigate the feasibility and efficacy of these models for perioperative risk stratification and optimized recovery planning to improve outcomes for ASD patients. Full article
(This article belongs to the Section Orthopedics)
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11 pages, 622 KiB  
Article
Prevalent Cardiovascular Disease and Atrial Fibrillation in Relation to Cerebral Small Vessel Disease Burden
by Oluchi Ekenze, Adlin Pinheiro, Alexa S. Beiser, Vasileios-Arsenios Lioutas, Hugo J. Aparicio, Emelia J. Benjamin, Ramachandran S. Vasan, Charles DeCarli, Sudha Seshadri, Serkalem Demissie and Jose R. Romero
Brain Sci. 2025, 15(8), 813; https://doi.org/10.3390/brainsci15080813 - 29 Jul 2025
Viewed by 228
Abstract
Background/Objectives: Cardiovascular disease (CVD) contributes to stroke and dementia. Individuals with CVD have high risk for adverse cognitive outcomes and stroke, possibly due to shared risk factors between CVD, stroke, and dementia, which may be attributed to cerebral small vessel disease (CSVD). We [...] Read more.
Background/Objectives: Cardiovascular disease (CVD) contributes to stroke and dementia. Individuals with CVD have high risk for adverse cognitive outcomes and stroke, possibly due to shared risk factors between CVD, stroke, and dementia, which may be attributed to cerebral small vessel disease (CSVD). We aim to determine the association between prevalent CVD and atrial fibrillation (AF) with CSVD. Methods: Composite of CVD [coronary heart disease, heart failure (HF)], its individual components, and AF were assessed. Multi-marker CSVD score was used to reflect increasing CSVD burden (cerebral microbleeds (CMBs), high-burden perivascular spaces, extensive white matter hyperintensity, cortical superficial siderosis, or covert brain infarcts were assigned 1 point each, with a range of 0–5). We related prevalent CVD, its individual components, and AF to multi-marker CSVD score and individual CSVD markers using logistic regression analyses adjusted for age, sex, FHS cohort, time between MRI and clinic exam (model-1), and vascular risk factors (model-2). Results: In 3413 participants (mean age: 59 ± 14 years, 53.4% women), 11% had prevalent CVD or AF, 8% had prevalent CVD, and 4% had prevalent AF. One CSVD marker was seen in 23% participants, and 9% had ≥ 2 markers. In multivariable-adjusted analyses, composite prevalent CVD and AF was associated with the presence of one CSVD marker (OR: 1.38, 95% confidence interval [CI]: 1.05–1.84). The association with ≥2 CSVD markers was not significant. Only CMBs were associated with components of CVD and AF, with the highest odds of association with HF. Conclusions: Prevalent CVD (including AF) is associated with the presence of CSVD, with all components associated with CMBs. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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11 pages, 784 KiB  
Article
Application and Outcomes of Minimal-Dose Versus Standard-Dose Radiation in Peripheral Endovascular Intervention (KAR Endovascular Study)
by Subrata Kar and Clifton Espinoza
J. Cardiovasc. Dev. Dis. 2025, 12(8), 284; https://doi.org/10.3390/jcdd12080284 - 25 Jul 2025
Viewed by 215
Abstract
Background: Peripheral endovascular intervention (PEVI) is routinely performed using standard-dose radiation (SDR), which is associated with elevated levels of radiation. No study has evaluated the outcomes of minimal-dose radiation (MDR) in PEVI. Methods: We performed a prospective observational study of 184 patients (65 [...] Read more.
Background: Peripheral endovascular intervention (PEVI) is routinely performed using standard-dose radiation (SDR), which is associated with elevated levels of radiation. No study has evaluated the outcomes of minimal-dose radiation (MDR) in PEVI. Methods: We performed a prospective observational study of 184 patients (65 ± 12 years) at an academic medical center from January 2019 to March 2020 (mean follow-up of 3.9 ± 3.6 months) and compared the outcomes of MDR (n = 24, 13.0%) and SDR (n = 160, 87.0%) in PEVI. Primary endpoints included air kerma, dose area product (DAP), fluoroscopy time, and contrast use. Secondary endpoints included all-cause mortality, cardiac mortality, acute myocardial infarction, acute kidney injury, stroke, repeat revascularization, vessel dissection/perforation, major adverse limb event, access site complications, and composite of complications. Results: For MDR (68 ± 10 years, mean follow-up of 4.3 ± 5.2 months), the primary endpoints were significantly less than SDR (65 ± 12 years, mean follow-up of 3.8 ± 3.2 months; p < 0.001). Regarding the secondary endpoints, one vessel dissection occurred using MDR, while 36 total complications occurred with SDR (p = 0.037). Conclusions: PEVI using MDR was safe and efficacious. MDR showed a significant decrement in radiation parameters and fluoroscopy time. Therefore, MDR can serve as an effective alternative for PEVI in acute or critical limb ischemia. Full article
(This article belongs to the Section Acquired Cardiovascular Disease)
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15 pages, 2999 KiB  
Article
Sex Differences and Long-Term Outcomes in Patients with Left Bundle Branch Area Pacing Compared with Right Ventricular Pacing
by Po-Wei Yang, Uei Chen, Po-Jui Wu, Shaur-Zheng Chong, Yen-Nan Fang, Yung-Lung Chen, Mien-Cheng Chen and Huang-Chung Chen
J. Clin. Med. 2025, 14(15), 5256; https://doi.org/10.3390/jcm14155256 - 24 Jul 2025
Viewed by 380
Abstract
Background: Long-term right ventricular pacing (RVP) can cause electrical and mechanical dyssynchrony, resulting in adverse outcomes. Recently, left bundle branch area pacing (LBBAP) has emerged as a physiological pacing modality and is considered a promising alternative. To date, the long-term outcomes of [...] Read more.
Background: Long-term right ventricular pacing (RVP) can cause electrical and mechanical dyssynchrony, resulting in adverse outcomes. Recently, left bundle branch area pacing (LBBAP) has emerged as a physiological pacing modality and is considered a promising alternative. To date, the long-term outcomes of LBBAP compared with RVP, particularly with respect to sex differences, remain unclear. Methods: Between January 2017 and July 2024, 1211 patients who underwent de novo pacemaker implantation were enrolled and categorized into RVP (n = 789) and LBBAP (n = 422). The primary outcome was a composite of all-cause mortality, heart failure hospitalization (HFH), and pacing-induced cardiomyopathy (PICM). Propensity score matching (PSM) was employed to minimize the selection bias and achieve comparability among the study population. A post hoc power analysis based on the observed effect size and sample size showed a power of 80%, confirming sufficient sensitivity to detect group differences. Results: After PSM, 764 patients were analyzed. The mean age of the patients was 74.6 ± 10.5 years in RVP and 74.5 ± 9.8 years in LBBAP, respectively, and 52.3% patients were male. Patients with LBBAP had a lower incidence of the primary outcome (8.6% vs. 24.6%, p < 0.001), HFH (2.6% vs. 13.6%, p < 0.001), and all-cause mortality (6.5% vs. 13.9%, p < 0.001) compared with RVP. There were no significant differences in the clinical outcomes, including the primary outcome, HFH and all-cause mortality, between the sexes in the group with either RVP or LBBAP. However, during a 2-year follow-up period for survival analysis, male patients with LBBAP had a significant lower incidence of all the endpoints, whereas female patients with LBBAP had a lower incidence of HFH [HR 0.14 (95% CI 0.06–0.32), p = 0.001] compared with those with RVP. Conclusions: Regardless of sex, patients with LBBAP had a lower risk of poor clinical outcomes, including HFH and all-cause mortality, compared to those with RVP. Moreover, compared with RVP, LBBAP decreased the risks of all the major endpoints in male patients and the risk of HFH particularly in female patients. Further research is needed to establish the sex-specific responses to LBBAP. Full article
(This article belongs to the Section Cardiology)
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14 pages, 1209 KiB  
Article
Investigation of Growth Differentiation Factor 15 as a Prognostic Biomarker for Major Adverse Limb Events in Peripheral Artery Disease
by Ben Li, Farah Shaikh, Houssam Younes, Batool Abuhalimeh, Abdelrahman Zamzam, Rawand Abdin and Mohammad Qadura
J. Clin. Med. 2025, 14(15), 5239; https://doi.org/10.3390/jcm14155239 - 24 Jul 2025
Viewed by 302
Abstract
Background/Objectives: Peripheral artery disease (PAD) impacts more than 200 million individuals globally and leads to mortality and morbidity secondary to progressive limb dysfunction and amputation. However, clinical management of PAD remains suboptimal, in part because of the lack of standardized biomarkers to predict [...] Read more.
Background/Objectives: Peripheral artery disease (PAD) impacts more than 200 million individuals globally and leads to mortality and morbidity secondary to progressive limb dysfunction and amputation. However, clinical management of PAD remains suboptimal, in part because of the lack of standardized biomarkers to predict patient outcomes. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied extensively in cardiovascular disease, but its investigation in PAD remains limited. This study aimed to use explainable statistical and machine learning methods to assess the prognostic value of GDF15 for limb outcomes in patients with PAD. Methods: This prognostic investigation was carried out using a prospectively enrolled cohort comprising 454 patients diagnosed with PAD. At baseline, plasma GDF15 levels were measured using a validated multiplex immunoassay. Participants were monitored over a two-year period to assess the occurrence of major adverse limb events (MALE), a composite outcome encompassing major lower extremity amputation, need for open/endovascular revascularization, or acute limb ischemia. An Extreme Gradient Boosting (XGBoost) model was trained to predict 2-year MALE using 10-fold cross-validation, incorporating GDF15 levels along with baseline variables. Model performance was primarily evaluated using the area under the receiver operating characteristic curve (AUROC). Secondary model evaluation metrics were accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Prediction histogram plots were generated to assess the ability of the model to discriminate between patients who develop vs. do not develop 2-year MALE. For model interpretability, SHapley Additive exPlanations (SHAP) analysis was performed to evaluate the relative contribution of each predictor to model outputs. Results: The mean age of the cohort was 71 (SD 10) years, with 31% (n = 139) being female. Over the two-year follow-up period, 157 patients (34.6%) experienced MALE. The XGBoost model incorporating plasma GDF15 levels and demographic/clinical features achieved excellent performance for predicting 2-year MALE in PAD patients: AUROC 0.84, accuracy 83.5%, sensitivity 83.6%, specificity 83.7%, PPV 87.3%, and NPV 86.2%. The prediction probability histogram for the XGBoost model demonstrated clear separation for patients who developed vs. did not develop 2-year MALE, indicating strong discrimination ability. SHAP analysis showed that GDF15 was the strongest predictive feature for 2-year MALE, followed by age, smoking status, and other cardiovascular comorbidities, highlighting its clinical relevance. Conclusions: Using explainable statistical and machine learning methods, we demonstrated that plasma GDF15 levels have important prognostic value for 2-year MALE in patients with PAD. By integrating clinical variables with GDF15 levels, our machine learning model can support early identification of PAD patients at elevated risk for adverse limb events, facilitating timely referral to vascular specialists and aiding in decisions regarding the aggressiveness of medical/surgical treatment. This precision medicine approach based on a biomarker-guided prognostication algorithm offers a promising strategy for improving limb outcomes in individuals with PAD. Full article
(This article belongs to the Special Issue The Role of Biomarkers in Cardiovascular Diseases)
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16 pages, 818 KiB  
Article
Predictive Value of Frailty, Comorbidity, and Patient-Reported Measures for Hospitalization or Death in Older Outpatients: Quality of Life and Depression as Prognostic Red Flags
by Dimitrios Anagnostou, Nikolaos Theodorakis, Sofia Kalantzi, Aikaterini Spyridaki, Christos Chitas, Vassilis Milionis, Zoi Kollia, Michalitsa Christodoulou, Ioanna Nella, Aggeliki Spathara, Efi Gourzoulidou, Sofia Athinaiou, Gesthimani Triantafylli, Georgia Vamvakou and Maria Nikolaou
Diagnostics 2025, 15(15), 1857; https://doi.org/10.3390/diagnostics15151857 - 23 Jul 2025
Viewed by 235
Abstract
Objectives: To identify clinical, functional, laboratory, and patient-reported parameters associated with medium-term risk of hospitalization or death among older adults attending a multidisciplinary outpatient clinic, and to assess the predictive performance of these measures for individual risk stratification. Methods: In this [...] Read more.
Objectives: To identify clinical, functional, laboratory, and patient-reported parameters associated with medium-term risk of hospitalization or death among older adults attending a multidisciplinary outpatient clinic, and to assess the predictive performance of these measures for individual risk stratification. Methods: In this cohort study, 350 adults aged ≥65 years were assessed at baseline and followed for an average of 8 months. The primary outcome was a composite of hospitalization or all-cause mortality. Parameters assessed included frailty and comorbidity measures, functional parameters, such as gait speed and grip strength, laboratory biomarkers, and patient-reported measures, such as quality of life (QoL, assessed on a Likert scale) and the presence of depressive symptoms. Predictive performance was evaluated using univariable logistic regression and multivariable modeling. Discriminative ability was assessed via area under the ROC curve (AUC), and selected models were internally validated using repeated k-fold cross-validation. Results: Overall, 40 participants (11.4%) experienced hospitalization or death. Traditional clinical risk indicators, including frailty and comorbidity scores, were significantly associated with the outcome. Patient-reported QoL (AUC = 0.74) and Geriatric Depression Scale (GDS) scores (AUC = 0.67) demonstrated useful overall discriminatory ability, with high specificities at optimal cut-offs, suggesting they could act as “red flags” for adverse outcomes. However, the limited sensitivities of individual predictors underscore the need for more comprehensive screening instruments with improved ability to identify at-risk individuals earlier. A multivariable model that incorporated several predictors did not outperform QoL alone (AUC = 0.79), with cross-validation confirming comparable discriminative performance. Conclusions: Patient-reported measures—particularly quality of life and depressive symptoms—are valuable predictors of hospitalization or death and may enhance traditional frailty and comorbidity assessments in outpatient geriatric care. Future work should focus on developing or integrating screening tools with greater sensitivity to optimize early risk detection and guide preventive interventions. Full article
(This article belongs to the Special Issue Risk Factors for Frailty in Older Adults)
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18 pages, 665 KiB  
Article
The Effects of 8-Week Hydrogen-Rich Water Consumption on Appetite, Body Composition, Sleep Quality, and Circulating Glucagon-like Peptide-1 in Obese Men and Women (HYDRAPPET): A Randomized Controlled Trial
by Nikola Todorovic, Sonja Baltic, David Nedeljkovic, Jovan Kuzmanovic, Darinka Korovljev, Dejan Javorac, Katarina Bijelic, Nebojsa Kladar, Alex Tarnava and Sergej M. Ostojic
Medicina 2025, 61(7), 1299; https://doi.org/10.3390/medicina61071299 - 18 Jul 2025
Viewed by 555
Abstract
Background and Objectives: Preliminary studies indicate that dihydrogen (H2) may affect molecular pathways involved in appetite regulation; however, its role in influencing patient-reported appetite outcomes in individuals with obesity remains uncertain. This randomized, placebo-controlled, double-blind trial aimed to evaluate the effects [...] Read more.
Background and Objectives: Preliminary studies indicate that dihydrogen (H2) may affect molecular pathways involved in appetite regulation; however, its role in influencing patient-reported appetite outcomes in individuals with obesity remains uncertain. This randomized, placebo-controlled, double-blind trial aimed to evaluate the effects of H2 supplementation on appetite, body composition, sleep quality, obesity-specific quality of life, and related biomarkers in obese men and women. Materials and Methods: The study included 36 participants (24 females; age 42.1 ± 13.2 years; BMI 30.8 ± 4.2 kg/m2) randomized to receive either 1.0 L of hydrogen-rich water (15 mg of H2) or 1.0 L of control water (0 mg of H2) daily for eight weeks. Results: The results demonstrated that hydrogen-rich water significantly mitigated cravings (p = 0.05), improved subjective sleep quality (p = 0.05), reduced total cholesterol (p = 0.02) and LDL cholesterol (p = 0.04), and increased plasma glucagon-like peptide-1 levels (p = 0.05) compared to the control. No severe adverse effects were reported throughout the trial. Conclusions: These findings suggest that hydrogen-rich water may serve as a safe and effective dietary strategy to address appetite regulation and related metabolic indices in individuals with obesity. The study is registered at ClinicalTrials.gov (NCT06722326). Full article
(This article belongs to the Special Issue Breakthroughs in Clinical Diabetes, Obesity and Metabolic Diseases)
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13 pages, 1017 KiB  
Systematic Review
Systematic Review of Nutritional Guidelines for the Management of Gestational Diabetes Mellitus: A Global Comparison
by Angelo Sirico, Maria Giovanna Vastarella, Eleonora Ruggiero and Luigi Cobellis
Nutrients 2025, 17(14), 2356; https://doi.org/10.3390/nu17142356 - 18 Jul 2025
Viewed by 524
Abstract
Background: Gestational diabetes mellitus (GDM) affects 7–9% of pregnancies worldwide and is associated with adverse maternal and neonatal outcomes. Nutritional therapy is a key component of GDM management. However, inconsistencies exist across international and national guidelines regarding macronutrient distribution, glycemic targets, and micronutrient [...] Read more.
Background: Gestational diabetes mellitus (GDM) affects 7–9% of pregnancies worldwide and is associated with adverse maternal and neonatal outcomes. Nutritional therapy is a key component of GDM management. However, inconsistencies exist across international and national guidelines regarding macronutrient distribution, glycemic targets, and micronutrient supplementation. This systematic review aims to compare updated nutritional recommendations for GDM across major health organizations and identify areas of consensus, divergence, and evidence gaps. Methods: This systematic review was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251026194). A comprehensive literature search was performed in PubMed, Scopus, and Google Scholar (concluding March 2025), along with manual searches of official websites of professional health organizations (e.g., ADA, WHO, NICE, IDF). Guidelines published within the last 10 years (or the most relevant national guideline if slightly older), available in English or with access to translation, and including explicit nutritional recommendations for GDM were included. Data were extracted on macronutrient composition, glycemic targets, and micronutrient supplementation, with evaluation of the supporting evidence and regional context, incorporating findings from recent key guideline updates. Results: In total, 12 guidelines met the inclusion criteria. While all guidelines emphasized carbohydrate moderation and adequate fiber intake, significant discrepancies were found in carbohydrate quality recommendations (e.g., low-glycemic index focus vs. total carbohydrate restriction), postprandial glucose targets (e.g., 1-h vs. 2-h measurements and varying thresholds like <120 vs. <140 mg/dL), and the use of non-routine micronutrients such as chromium, selenium, and omega-3 fatty acids (generally lacking endorsement). Recent updates from key bodies like ADA, Diabetes Canada, and KDA largely maintain these core stances but show increasing emphasis on dietary patterns and acknowledgement of CGM technology, without resolving key discrepancies. Cultural adaptability and behavioral counselling strategies were minimally addressed across most guidelines. Conclusions: Despite general agreement on the principal recommendations of nutritional management in GDM, substantial variation persists in specific recommendations, even considering recent updates. Consistent, evidence-based, and culturally adaptable guidelines incorporating implementation strategies are needed to optimize care and reduce disparities in GDM management across regions. Full article
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14 pages, 637 KiB  
Article
Impact of Pulmonary Hypertension and Patent Ductus Arteriosus in Preterm Infants with Presumed Pulmonary Hypoplasia
by Sol Kim, Yumi Seo, Moon-Yeon Oh, Min Soo Kim and Sook Kyung Yum
Biomedicines 2025, 13(7), 1725; https://doi.org/10.3390/biomedicines13071725 - 15 Jul 2025
Viewed by 304
Abstract
Objectives: Pulmonary hypertension and hemodynamically significant PDA (hsPDA) involve seemingly opposite physiological features—decreased pulmonary blood flow and pulmonary overcirculation, respectively—but the literature demonstrates variable respiratory consequences in association with each of these morbidities. The aim of this study is to evaluate whether [...] Read more.
Objectives: Pulmonary hypertension and hemodynamically significant PDA (hsPDA) involve seemingly opposite physiological features—decreased pulmonary blood flow and pulmonary overcirculation, respectively—but the literature demonstrates variable respiratory consequences in association with each of these morbidities. The aim of this study is to evaluate whether the two factors representing pulmonary circulation provide different contributions to respiratory outcomes in preterm infants with and without pulmonary hypoplasia. Methods: The medical records of preterm very low birth weight (VLBW) infants admitted to our unit during the study period from January 2013 to December 2020 were retrospectively reviewed. Preterm VLBW infants were divided into groups according to the presence of presumed pulmonary hypoplasia (PPH). Multivariable logistic regression analysis was performed to assess the association of PPH and pulmonary hypertension or delayed PDA closure with in-hospital outcomes. Results: Postnatal age at final treatment for PDA was significantly later [median 33 vs. 19 days, p = 0.025] in the PPH group. Multivariable analysis indicated that early pulmonary hypertension was significantly associated with neonatal death [aOR (95%CI) 11.575 (2.988–44.833) for no-PPH vs. 9.981 (1.334–74.647) for PPH]. Delayed PDA closure was associated with increased odds of adverse respiratory and composite outcomes [aOR (95%CI) 4.929 (1.613–15.055) and 3.320 (1.048–10.515), respectively] but decreased odds of neonatal death in the no-PPH group. However, Cox proportional hazards models did not demonstrate statistically significant associations for PPH, early pulmonary hypertension, or delayed PDA closure with mortality, likely due to time-varying effects and the absence of death events in the subgroup of infants with both PPH and delayed PDA closure. Conclusions: PPH is associated with a higher prevalence of air leak syndrome and pulmonary hypertension. Delayed PDA closure exerts different effects on respiratory outcomes in preterm VLBW infants with and without PPH. Although early pulmonary hypertension appears to be a key circulatory factor contributing to neonatal death, its effect may vary over time. These findings underscore the importance of accounting for time-dependent effects when interpreting pulmonary circulatory risk factors in clinical practice. Full article
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16 pages, 2023 KiB  
Article
The Prognostic Implication of Left Atrial Strain Parameters with Conventional Left Atrial Parameters for the Prediction of Adverse Outcomes in Asian Patients with Hypertrophic Cardiomyopathy—An Echocardiographic Study
by Andre Seah, Tony Y. W. Li, Novi Yanti Sari, Chi-Hang Lee, Tiong-Cheng Yeo, James W. L. Yip, Yoke Ching Lim, Kian-Keong Poh, William K. F. Kong, Weiqin Lin, Ching-Hui Sia and Raymond C. C. Wong
J. Cardiovasc. Dev. Dis. 2025, 12(7), 261; https://doi.org/10.3390/jcdd12070261 - 8 Jul 2025
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Abstract
Background/Objectives: Left atrial function can be a tool for risk stratification for hypertrophic cardiomyopathy (HCM). Over the past decade, there has been growing interest in the application of strain analysis for earlier and more accurate prediction of cardiovascular disease prognosis. This study aimed [...] Read more.
Background/Objectives: Left atrial function can be a tool for risk stratification for hypertrophic cardiomyopathy (HCM). Over the past decade, there has been growing interest in the application of strain analysis for earlier and more accurate prediction of cardiovascular disease prognosis. This study aimed to investigate the performance of left atrial strain analysis compared to conventional left atrial measures in predicting clinical outcomes in Asian patients with HCM. Methods and Results: This was a retrospective study involving 291 patients diagnosed with HCM between 2010 and 2017. Left atrial volumes were assessed using the method of discs in orthogonal plans at both end diastole and end systole. Left atrial (LA) strain was obtained using a post-hoc analysis with TOMTEC software. We tested the various left atrial parameters against outcomes of (1) heart failure hospitalization and (2) event-free survival from a composite of adverse events, including all-cause mortality, ventricular tachycardia (VT)/ventricular fibrillation (VF) events, appropriate device therapy if an implantable cardioverter defibrillator (ICD) was implanted, stroke, and heart failure hospitalization. The patients had a mean age of 59.0 ± 16.7 years with a male preponderance (71.2%). The cumulative event-free survival over a follow-up of 3.9 ± 2.7 years was 55.2% for patients with an abnormal LA strain versus 82.4% for patients without one (p < 0.001). Multivariable Cox regression analyses were performed separately for each LA parameter, adjusting for age, sex, LV mass index, LV ejection fraction (EF), E/e’, the presence of LV outflow tract (LVOT) obstruction at rest, and atrial fibrillation. An analysis showed that all parameters except for LAEF demonstrated an independent association with heart failure hospitalization. Left atrial strain outperformed the rest of the parameters by demonstrating an association with a composite of adverse events. Conclusions: In Asian patients with HCM, measures of left atrial strain were independently associated with heart failure hospitalization and a composite of adverse outcomes. Left atrial strain may be used as a tool to predict adverse outcomes in patients with HCM. Full article
(This article belongs to the Special Issue Role of Cardiovascular Imaging in Heart Failure)
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14 pages, 1751 KiB  
Article
Associations Between Low-Density Lipoprotein Cholesterol Levels and Cardiovascular Outcomes in Patients Undergoing Dialysis: A Nationwide Cohort Study
by Byung Sik Kim, Jiyeong Kim, Nayeon Choi, Hyun-Jin Kim and Jeong-Hun Shin
J. Clin. Med. 2025, 14(14), 4845; https://doi.org/10.3390/jcm14144845 - 8 Jul 2025
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Abstract
Background/Objectives: Low-density lipoprotein cholesterol (LDL-C) is a causal factor in the development of atherosclerosis and a predictor of cardiovascular disease. However, the association between LDL-C levels and cardiovascular outcomes in patients undergoing dialysis remains controversial, with current guidelines advising against initiating statin therapy [...] Read more.
Background/Objectives: Low-density lipoprotein cholesterol (LDL-C) is a causal factor in the development of atherosclerosis and a predictor of cardiovascular disease. However, the association between LDL-C levels and cardiovascular outcomes in patients undergoing dialysis remains controversial, with current guidelines advising against initiating statin therapy in this population. This study investigated the relationship between LDL-C levels and cardiovascular outcomes in Korean adults undergoing dialysis, using nationwide data. Methods: A total of 21,692 patients with end-stage kidney disease undergoing dialysis between 2009 and 2017 were identified from the Korean National Health Insurance Service database. Statin non-users (primary cohort) and users (secondary cohort) comprised 15,414 and 6278 patients, respectively. LDL-C levels were categorized, and cardiovascular outcomes including composites of cardiovascular death, myocardial infarction, and ischemic stroke were analyzed. Results: Among statin non-users, LDL-C levels > 100 mg/dL were significantly associated with an increased risk of the composite outcome, in a dose-dependent manner, compared with LDL-C levels < 70 mg/dL. Specifically, participants with LDL-C levels ≥ 160 mg/dL demonstrated a 43% increased risk of the composite outcome and a 2.25-fold higher risk of myocardial infarction compared to those with LDL-C levels < 70 mg/dL. Among statin users, LDL-C levels > 130 mg/dL were associated with an increased risk of the composite outcome. Conclusions: This study highlights the significant association between elevated LDL-C levels and adverse cardiovascular outcomes in patients undergoing dialysis. These findings underscore the importance of close monitoring and proactive management of LDL-C levels in this high-risk population. Future research should focus on developing tailored lipid-lowering strategies to improve cardiovascular outcomes in these patients. Full article
(This article belongs to the Section Cardiovascular Medicine)
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18 pages, 251 KiB  
Protocol
Glucose Homeostasis, Metabolomics, and Pregnancy Outcomes After Bariatric Surgery (GLORIA): Protocol for a Multicentre Prospective Cohort Study
by Ellen Deleus, Niels Bochanen, Dries Ceulemans, Hanne Debunne, Bénédicte Denys, Roland Devlieger, Ina Geerts, Annouschka Laenen, Lisbeth Jochems, Els Lannoey, Matthias Lannoo, Anne Loccufier, Toon Maes, Joke Marlier, Astrid Morrens, Nele Myngheer, Luna Tierens, Griet Vandenberghe, Annick Van den Bruel, Lien Van den Haute, Bart Van der Schueren, Inge Van Pottelbergh and Katrien Benhalimaadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(13), 4782; https://doi.org/10.3390/jcm14134782 - 7 Jul 2025
Viewed by 476
Abstract
Background: Metabolic bariatric surgery is a highly effective and long-lasting treatment for obesity and related chronic conditions. Women of reproductive age represent the largest group undergoing these procedures. Observational studies suggest an increased risk of preterm birth and impaired foetal growth in this [...] Read more.
Background: Metabolic bariatric surgery is a highly effective and long-lasting treatment for obesity and related chronic conditions. Women of reproductive age represent the largest group undergoing these procedures. Observational studies suggest an increased risk of preterm birth and impaired foetal growth in this population, though the underlying mechanisms remain unclear. A key hypothesis is that altered glucose metabolism, characterised by frequent hypoglycaemia and glycaemic fluctuations, may contribute to these adverse outcomes. While glycaemic variability following metabolic bariatric surgery has been documented, its pattern during pregnancy and impact on pregnancy outcomes are still underexplored. Methods: In this Belgian multicentre prospective cohort study, we will investigate glycaemic patterns during pregnancy in women who have undergone metabolic bariatric surgery. Women aged 18–45 years with a confirmed singleton pregnancy up to 11 weeks and 6 days and a history of Roux-en-Y gastric bypass or sleeve gastrectomy will be eligible for inclusion. Women with pregestational diabetes or those taking medication known to interfere with glucose metabolism will be excluded. All participants will receive blinded continuous glucose monitoring (Dexcom® G6) for a 10-day period at four time points throughout the pregnancy. Foetal body composition and growth will be measured during routine ultrasound; skinfolds will be measured in the neonate. The primary outcome is the association between mean glycemia and glycaemic variability on continuous glucose monitoring and birth weight. The planned sample size is ninety-five women. Linear mixed models for repeated measurements will be used for analysis. Confounders such as smoking, micronutrient deficiency, and surgery-to-conception interval will be added to the model as covariates. In a second exploratory phase, each participant in the surgical group will be matched with a control participant—without a history of metabolic bariatric surgery—based on pre-pregnancy BMI and age. Control participants will undergo the same study procedures, allowing for exploratory comparison of glycaemic patterns and other study outcomes. Discussion: This prospective longitudinal study will be the largest study using continuous glucose monitoring to investigate glucose metabolism during pregnancy after metabolic bariatric surgery and its impact on foetal growth and newborn body composition. Trial registration: ClinicalTrials.gov: NCT05084339. Registration date: 15 October 2021. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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