Search Results (1,147)

Background/Objectives: Systemic hydrocortisone (HCS) in very low birth weight (VLBW) infants is commonly used to treat early hypotension or prevent bronchopulmonary dysplasia. This study evaluated the associations between postnatal HCS exposure and neurodevelopment in VLBW infants by comparing regional brain volume at term-equivalent age (TEA) with neurodevelopmental outcomes in early infancy. Methods: This retrospective cohort study included VLBW infants admitted to a neonatal intensive care unit (NICU) between 2013 and 2019. The cumulative HCS dose during hospitalization was recorded, and regional brain volumes were analyzed using magnetic resonance imaging at TEA. Neurodevelopmental outcomes were assessed at a corrected age for prematurity of 18–24 months. Results: Among 146 infants, 57 were classified in the high HCS group (>90 mg/kg) and 89 in the low HCS group (≤90 mg/kg HCS). Bronchopulmonary dysplasia, periventricular leukomalacia, and sepsis were more frequent in the high HCS group. Ninety-five infants underwent magnetic resonance imaging, which revealed reduced brain volumes in the high HCS group. At follow-up, cerebral palsy (35.9% vs. 9.1%, p = 0.003), neurodevelopmental impairment (54.0% vs. 23.6%, p = 0.002), and head circumference <10th percentile (64.3% vs. 19.5%, p < 0.001) were more common in the high HCS group. After adjustment, HCS > 90 mg/kg remained independently associated with cerebral palsy (adjusted odds ratio [aOR] 5.44, p = 0.016) and reduced head circumference (aOR 4.45, p = 0.016). Conclusions: High cumulative HC exposure correlated with reduced brain volume at TEA and adverse neurodevelopmental outcomes at 24 months of age. Careful monitoring of dose and treatment duration is essential to balance therapeutic benefits against potential risks. Full article

Background: Vitamin B12 deficiency, hyperhomocysteinemia, and diabetes are emerging determinants of cardiovascular risk, particularly among women. Early detection and treatment represent an important public health opportunity to reduce the burden of disease and promote health equity. Objective: We aimed to quantify the prevalence of vitamin B12 deficiency, hyperhomocysteinemia, and diabetes, and to evaluate the potential impact of detecting and addressing these conditions on reducing CVD risk in adult Mexican women. Methods: We analyzed data from 1197 women aged 20–49 years from Mexico’s 2022–2023 National Health and Nutrition Survey (ENSANUT). Serum vitamin B12, folate, and homocysteine were quantified, and 10-year CVD risk was estimated using Framingham and Globorisk models. Population-attributable fractions and cost–benefit analyses were used to assess preventable CVD cases and the economic feasibility of nationwide vitamin B12 supplementation. Results: Nationwide, 37.2% of women have vitamin B12 deficiency, and 30.6% have borderline levels. In Southern Mexico, the prevalence of vitamin B12 deficiency is higher, reaching 52.4%. Elevated homocysteine levels were detected in 12.3% of women. The predicted number of preventable CVD cases ranged from 10,000 to 14,000, and the benefit–cost ratio exceeded 1, supporting economic feasibility. Conclusions: Vitamin B12 deficiency and hyperhomocysteinemia are very common among Mexican women and are associated with an increased cardiovascular risk, especially in those aged 40 to 49. The analysis showed that implementing a national vitamin B12 supplementation strategy could be a cost-effective preventive measure, with a benefit–cost ratio ranging from 1.93 in the base case to 2.98 when broader societal savings are taken into account. These findings highlight the potential of targeted nutritional interventions to reduce the burden of cardiovascular disease in women. Full article

Background/Objectives: To identify independent predictors of free peritoneal cancer cells (FPCC), and to investigate survival outcomes relative to peritoneal cytology status among patients who underwent intended curative gastrectomy for adenocarcinoma of the stomach or esophagogastric junction. Methods: Medical records of patients who underwent radical surgery between January 2005 and December 2020 were retrospectively reviewed. Clinical data and cytology results were evaluated. Multivariate Cox regression analysis was used to identify independent predictors of FPCC. Kaplan–Meier survival analysis was used to estimate disease recurrence and survival outcomes. Results: Out of the 349 enrolled patients, 188 (53.8%) had negative cytology, 32 (9.2%) were positive, and 129 (36.9%) showed atypical cells in peritoneal cytology. Poor differentiation (adjusted odds ratio [aOR]: 2.63, 95% confidence interval [95%CI]: 1.04–6.82; p = 0.015), pT4 (aOR: 4.62, 95%CI: 1.28–14.34; p = 0.018), pN3 (aOR: 4.13, 95%CI: 1.14–15.03; p = 0.031), and metastatic lymph node ratio >0.40 (aOR: 6.49, 95%CI: 1.44–29.14; p = 0.015) were independent predictors of FPCC. Median overall survival was 34.1 months in the negative group, 13.1 months in the positive group, and 28.7 months in the atypical cell group (p < 0.001). Median time to disease recurrence was 20.5, 4.9, and 11.3 months, respectively (p < 0.001). Survival and recurrence outcomes in the atypical cell group were comparable to those with negative cytology. Conclusions: Poorly differentiated histology, pT4, pN3, and metastatic lymph node ratio >0.40 are independent predictors of FPCC, which is significantly associated with poor survival and disease recurrence outcomes. These findings suggest that high-risk patients may benefit from routine peritoneal cytologic screening during surgery to improve risk stratification and guide postoperative treatment planning. Full article

Background: Chronic heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, and renal dysfunction is common in these patients. Blood urea/creatinine ratio (UCR) has been identified as a potential prognostic marker, reflecting both renal function and neurohormonal activity. We assessed whether a UCR ≥ 95 at discharge from an outpatient service was associated with increased mortality. Methods: This retrospective study reviewed 337 patients (age 72.7 ± 14.3 years; 64.7% Male; Mean LVEF 33.2 ± 8.9%) with HFrEF referred to the Heart Failure Nurse Service at NHS Tayside for optimisation of heart failure medication. Cox proportional hazards models were used to assess the association between UCR and all-cause mortality. Results: Receiver operating characteristic (ROC) analysis identified a UCR threshold of 95 (area under the curve [AUC] 0.701) as predictive of mortality. Results demonstrated that a UCR ≥ 95 was independently associated with increased mortality (HR 1.85, 95% CI 1.09–3.14, p = 0.022). A high UCR was associated with increased mortality even in patients with preserved eGFR, a group typically considered at lower risk (HR 4.03, 95% CI 1.50–10.9, p = 0.006). Conclusions: These findings suggest that UCR could be a useful addition for identifying high-risk patients who may benefit from closer monitoring and more aggressive intervention following optimisation of heart failure medication. Full article

Background/Objectives: Metformin is one of the most frequently used concomitant medications among prostate cancer (PCa) patients. However, the effects of metformin on all-cause and PCa-specific mortality among men diagnosed with advanced/metastatic PCa treated with androgen-deprivation therapy (ADT) remain poorly understood, but they may be specifically explained by emulating a target trial. Methods: We emulated a target trial of metformin therapy and survival using observational data on 7361 patients diagnosed with advanced PCa, who were treated with ADT, from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2008–2019), with completed follow-up until 2020. We included patients with diabetes, and participants were assigned as either “initiator of metformin within 6 months after advanced PCa diagnosis” or “non-initiator of metformin.” We estimated mortality risks using Cox proportional hazards models with adjustment for risk factors via inverse probability weighting using both intention-to-treat and per-protocol analyses. Results: Over 13 years of follow-up, with a maximum 3 years of follow-up after PCa diagnosis, all-cause mortality occurred in 52 metformin initiators (47.7%) versus 3052 non-initiators (42.1%), while PCa-specific mortality occurred in 36 initiators (33.0%) versus 1919 non-initiators (26.5%). In the intention-to-treat analysis, metformin initiation was not associated with all-cause mortality (Hazard Ratio [HR] = 1.38, 95% CI: 0.98–1.95) or PCa-specific mortality (HR = 0.99, 95% CI: 0.63–1.55). Similarly, in per-protocol analysis, there was no evidence of risk reduction with all-cause (HR = 1.20, 95% CI = 0.80–1.81) or PCa-specific mortality (HR = 1.45, 95% CI = 0.88–2.38) after adjusting for time-varying covariates and allowing a 30-day gap for metformin discontinuation, adjusted for via inverse probability weighting. Conclusions: Our findings align with prior randomized trials showing no survival benefit of metformin in advanced PCa patients receiving ADT. Timing of metformin discontinuation also showed no significant effect. However, the small size of the metformin initiator group precluded subgroup analyses for hormone-sensitive (HSPC) and castrate-resistant prostate cancer (CRPC), limiting our ability to explore potential differential effects. Full article

Cannabinoids, compounds that interact with the endocannabinoid system, have shown promising neuroprotective effects in various neurodegenerative diseases, including those affecting the retina. This review evaluates evidence for the presence and action of cannabinoids in the retina, their function in protecting against oxidative stress and modulating neuroinflammation, and the outcomes observed in animal models of retinal diseases such as glaucoma and age-related macular degeneration (AMD), the most common causes of vision loss. Cannabinoids have proven effective in reducing the neurodegeneration seen in these eye diseases, acting via the CB1 and CB2 cannabinoid receptors. The cannabinoid neuroprotective effect is often of a similar magnitude to the other proven therapy of medical dosage of vitamins, though it confers a greater risk due to neurotoxicity with high THC:CBD ratios, making the vitamin therapy of greater efficacy when time is available. Given the increased ratio of THC:CBD in commercial cannabis strains, rising from 10:1 at the beginning of this century to 100:1 now, the risk of neurotoxicity has increased, reducing the neuroprotective benefit. The proven safety and efficacy of vitamin therapy may be a more viable neuroprotective method than cannabinoid use for chronic conditions, with cannabinoids proving their utility in more acute conditions. This review evaluates both the method of action of cannabinoids and the receptor pathway utilized and compares the suggested therapeutic applicability of cannabinoids with proven vitamin therapy. Full article

Background: Diabetic foot ulcers (DFUs) carry high risks of infection, amputation, and mortality. We systematically reviewed randomized controlled trials (RCTs) of negative-pressure wound therapy (NPWT), including single-use systems, for clinically uninfected DFUs (with sensitivity analyses for mixed/infected cohorts). Methods: We searched PubMed and Scopus (1 January 2004–30 June 2024). Dual reviewers performed screening and extraction; risk of bias was assessed with Cochrane Risk of Bias 2 (RoB 2) and certainty of evidence with GRADE. When ≥2 trials reported comparable outcomes, we used random-effects meta-analysis. The DiaFu cohort reported in two publications was counted once across analyses. Results: Eleven RCT publications (n = 1699; 10 unique cohorts) met criteria; eight trials (n = 1456) informed the primary endpoint. Trials largely excluded severe ischemia; findings therefore apply mainly to neuropathic or mixed-etiology DFUs with adequate perfusion. NPWT increased complete healing at 12–16 weeks (risk ratio [RR] 1.46, 95% CI 1.21–1.76; I² = 48%) and shortened time to healing (mean difference –18 days, 95% CI −28 to −8). Effects were similar for conventional and single-use NPWT. Outcomes did not vary systematically within commonly used pressure ranges (approximately −80 to −125 mmHg). Only two RCTs reported direct cost data (exploratory). Moderate heterogeneity (Higgins’ I² 48–68%) reflected variation in ulcer severity, device type/settings, dressing-change frequency, and off-loading protocols. Conclusions: NPWT probably improves short-term healing of clinically uninfected DFUs compared with standard care and may reduce minor amputations, without increasing adverse events. Certainty is moderate for healing and low for most secondary outcomes. Benefits appear consistent across device classes and may support earlier discharge and community-based care. Evidence gaps include ischemia-dominated ulcers, long-term outcomes (recurrence and limb preservation), adherence mechanisms, and contemporary cost-effectiveness. Full article

Objectives: Maternal folic acid supplementation is recommended to prevent neural tube defects (NTDs), yet its influence on offspring neurodevelopmental disorders (NDDs) remains uncertain. This umbrella review aims to evaluate whether maternal folic acid supplementation before and/or during pregnancy affects the risk of NDDs. Methods: We conducted a systematic search in MEDLINE, Cochrane Library, EMBASE, PubMed, and Web of Science from inception to 30 June 2025, to identify systematic reviews (SRs) and meta-analyses (MAs) that synthesized evidence from non-randomized studies on maternal folic acid supplementation and NDDs. Methodological quality was assessed using the AMSTAR-2 assessment and evidence certainty using the GRADE framework. Results: A total of 23 SRs/MAs were included, of which 14 did not perform meta-analysis. Most included SRs/MAs were methodologically limited, with 50.00% rated as very low quality and only 36.37% achieving high or moderate quality. MAs indicated a protective effect of supplementation, with odds ratio (OR) of 0.66 (95% confidence interval (CI): 0.55–0.79) for autism spectrum disorder (ASD), 0.86 (95% CI: 0.78–0.95) for attention-deficit/hyperactivity disorder (ADHD), and 0.75 (95% CI: 0.63–0.91) for behavioral problems. No significant associations were found for motor, intellectual/cognitive, or language development. SRs reported inconsistent conclusions across most outcomes. Conclusions: In summary, maternal folic acid supplementation may reduce the risk of ASD, ADHD, and behavioral problems in offspring. Although the current evidence is of low quality, supplementation guidelines are justified by the well-established benefits for NTDs. Further research is required to address remaining uncertainties. Full article

The numerous uncertainties in the process of water resource development and utilization bring multiple risks to water resource management. To enhance socio-economic benefits while considering ecological benefits, it is urgent to deeply explore risks. In this paper, Nuozhadu, Jinghong, and Ganlanba hydropower stations on the lower reaches of the Lancang River are taken as the objects. To balance the socio-economic and ecological benefits, a multi-objective optimization operation model was constructed. To describe the risk transmission, a VAR model was constructed, and the dynamic transmission among risks was explored. The results show that the ratio of ecological change is 10.38%, and the cascade power generation is 33,243 GWh (2% higher than the designed). The impacts of the perturbation for each risk on itself and others are quantitatively analyzed by the impulse response function. It is concluded that the transmission direction is generally positive, but the increase in ecological risk has negative impacts on risks of output and abandoned water, and risks of power generation and output also negatively affect abandoned water risk. Finally, the risk transmission is quantitatively estimated by the variance decomposition method. It is concluded that the power generation risk contributes most to the output and ecology risks, the ecological risk only contributes significantly to the abandoned water risk (the contribution rate is 6.30%), and the abandoned water risk contributes a lot to the others. Full article

Background: Acute kidney injury (AKI) remains a serious complication among individuals with type 2 diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed and often regarded as kidney-protective, yet post-marketing reports have linked them to AKI. Tirzepatide, a newer dual GIP/GLP-1 agonist, shows well-documented metabolic benefits, but its renal safety in real-world use is not well characterized. Methods: We conducted a disproportionality analysis of the U.S. FDA Adverse Event Reporting System (FAERS) from January 2022 to September 2025. Reporting odds ratios (RORs) and proportional reporting ratios (PRRs) were used to compare AKI reporting between tirzepatide and semaglutide. Results: Among 133,872 reports (92,807 tirzepatide; 41,065 semaglutide), AKI was listed in 432 (0.47%) and 440 (1.07%) cases, respectively. The ROR for tirzepatide versus semaglutide was 0.44 (95% CI, 0.38–0.50), suggesting a lower reporting frequency for AKI with tirzepatide. Conclusions: In this real-world pharmacovigilance analysis, semaglutide but not tirzepatide showed a disproportionality signal for AKI. While causality cannot be confirmed, clinicians should ensure hydration and renal monitoring when initiating GLP-1 RAs, particularly semaglutide. Semaglutide showed a higher AKI reporting rate than tirzepatide, though these findings should be interpreted cautiously given reporting bias and potential confounders. Both agents appear safe, with low AKI frequency in practice. Further studies should determine if differences reflect biological or reporting effects. These findings support the need for larger epidemiologic studies to define risk modifiers and optimize clinical safety strategies. Full article

Patients with chronic obstructive pulmonary disease (COPD) are vulnerable to developing severe SARS-CoV-2 infection. This retrospective study evaluated the effectiveness of remdesivir (RDV) initiated with corticosteroids (CCS) versus CCS only in patients with COPD hospitalized for SARS-CoV-2 infection during the Omicron period from December 2021 to February 2024. The analysis used patient-level data from the large, geographically diverse, US hospital administrative billing PINC AI healthcare database. Inverse probability of treatment weighting was used to adjust for potential confounding and enable a scientifically robust comparative assessment of differences in outcomes between treatment groups. Initiation of RDV with CCS upon admission for SARS-CoV-2 infection was associated with a lower mortality risk at 14 and 28 days with an overall adjusted hazard ratio [95% CI] of 0.74 [0.68–0.80] and 0.76 [0.71–0.82], respectively, compared to initiation of CCS only. The combination of RDV and CCS was also associated with a lower mortality risk at 14 and 28 days for patients across baseline oxygen requirements compared to CCS only. These results highlight the benefit of timely RDV treatment in COPD patients hospitalized with SARS-CoV-2 infection and underscore the value of considering established treatment paradigms in the context of the most recent collective evidence. Full article

Background: Adjunctive antibiotics are frequently used alongside mechanical debridement (MD) for peri-implantitis, yet their additional clinical benefit remains uncertain. Objective: To systematically assess whether adding local or systemic antibiotics to non-surgical MD improves clinical outcomes in peri-implantitis. Methods: The review protocol was registered in PROSPERO (CRD42022380401). We included randomised controlled trials (RCTs) involving peri-implantitis patients treated with MD plus local or systemic antibiotics, compared to MD alone, with at least 3 months of follow-up. Searches were conducted in PubMed, Cochrane Library, LILACS, Web of Science, and Embase up to 9 April 2025. Eleven RCTs (634 patients) were included in the qualitative synthesis. The Cochrane RoB 2.0 tool evaluated the risk of bias. Random-effects meta-analyses of data from 10 studies, adjusting results to an equivalent 6-month follow-up time-frame, assessed treatment efficacy based on changes in probing pocket depth (PPD) and bleeding on probing (BoP), the primary outcomes. Meta-regressions examined the influence of mean patient age and implant-to-patient ratio on adjusted outcomes. Results: Systemic antibiotics resulted in generally greater PPD reduction and BoP reduction over MD alone or plus chlorhexidine, with the greatest benefits observed in amoxicillin-based multi-agent regimens and longer follow-up duration. Comparatively, local antimicrobial adjuncts performed less effectively on PPD reduction. No implant losses were reported, and adverse events were rare. Limitations: Some included trials had a high risk of bias and considerable heterogeneity. Follow-up was limited to the short term, and definitions of clinical “success” varied across studies. Conclusions: Adjunctive systemic antibiotics, particularly amoxicillin-based combinations, substantially improve short-term clinical outcomes of non-surgical peri-implantitis treatment compared to MD alone. Nevertheless, given the variability in study quality and potential risks associated with antibiotic use, their application should be judicious. Further long-term RCTs are warranted to confirm sustained efficacy and safety. Full article

Thyroid nodules, prevalent in 2% to 65% of the general population depending on diagnostic methodology, represent a significant clinical concern despite a low malignancy rate, typically 1% to 5%. A substantial proportion of thyroid cancers are small, indolent lesions, allowing for conservative management with favorable prognoses. Nodule detection commonly occurs via palpation, clinical examination, or incidental radiological findings. Established risk factors include advanced age, female gender, obesity, metabolic syndrome, and estrogen dominance. Despite conservative management potential, a considerable number of thyroid nodules in Europe are unnecessarily referred for surgery, incurring unfavorable risk-to-benefit ratios and increased costs. Minimally invasive techniques (MITs), encompassing ethanol and thermal ablation modalities (e.g., laser, radiofrequency, microwave), offer outpatient, nonsurgical management for symptomatic or cosmetically concerning thyroid lesions. These procedures, performed under ultrasound guidance without general anesthesia, are associated with low complication rates. MITs effectively achieve substantial and sustained nodule volume reduction (57–77% at 5 years), correlating with improved local symptoms. Thermal ablation (TA) is particularly favored for solid thyroid lesions due to its precise and predictable tissue destruction. Optimal TA balances near-complete nodule eradication to prevent recurrence with careful preservation of adjacent anatomical structures to minimize complications. Radiofrequency ablation (RFA) is widely adopted, while microwave ablation (MWA) presents a promising alternative addressing RFA limitations. Percutaneous laser ablation (LA), an early image-guided thyroid ablation technique, remains a viable option for benign, hyperfunctioning, and malignant thyroid pathologies. This review comprehensively evaluates RFA, MWA, and LA for thyroid nodule treatment, assessing current evidence regarding their efficacy, safety, comparative outcomes, side effects, and outlining future research directions. Full article

Hemodialysis (HD) technology, pivotal in managing end-stage kidney disease, has witnessed significant advancements. Yet, the high cost of novel equipment often restricts its usage in resource-limited settings. This study introduces a two-filter adaptation to conventional HD machines, aimed at enhancing toxin removal while maintaining cost-effectiveness. Using a benchtop experimental setup, the performance of the adapted system was compared with that of standard HD. The results demonstrated that the two-filter system improved urea clearance rates by 54% compared with standard HD, without increasing albumin loss or causing additional hemolysis. In a pilot study of four HD patients, the modified setup achieved a higher single-pool Kt/V (1.82) and urea-reduction ratio (80%). These findings underscore the potential of this adaptation to enhance HD machine efficiency without additional patient risks, thereby offering a feasible solution for improving access to advanced renal therapies in under-resourced areas. Further clinical trials with larger populations are warranted to validate these benefits and evaluate middle-molecule clearance for comparison with hemodiafiltration (HDF). Full article

Background and Objectives: The rapid increase of whitening products use raises questions about enamel safety. We compared three high-concentration protocols—Opalescence Quick (45% carbamide peroxide ≈ 15% H₂O₂), Opalescence Boost (40% H₂O₂), and BlancOne Ultra (35% H₂O₂ + LED)—under controlled conditions to balance color change (ΔE) with enamel integrity (microhardness, FTIR). We also constructed a qualitative cytotoxicity risk profile from published data; no biological assays were performed in this study. Methods: Seventy-two matched half-crowns were randomized to Control or one of the three protocols. Outcomes were a change in Vickers microhardness, spectrophotometric color difference, and FTIR carbonate-to-phosphate ratio after 24 h in artificial saliva. We also compiled a qualitative cytotoxicity risk profile from published evidence; no biological assays were performed. One-way ANOVA with Tukey HSD on Δ-scores, Shapiro–Wilk and Levene’s tests for assumptions, Welch’s t-tests for tooth-class comparisons, and Pearson correlation between ΔE and ΔMH. Results: All active protocols produced clearly visible whitening (mean ΔE 5.7–6.3). Hydrogen-peroxide gels showed greater hardness loss and carbonate depletion than the carbamide-peroxide gel under similar contact time. The association between greater shade change and hardness loss was moderate and not predictive for individuals. Conclusions: Under harmonized conditions, all systems whitened effectively. Pursuing changes beyond ~6 units offered little extra benefit while increasing enamel impact. Carbamide-based Opalescence Quick achieved comparable aesthetics with lower acute enamel effects. Clinicians should individualize exposure time and pair in-office whitening with short-term remineralising care. Cytotoxicity comments are qualitative and literature-based only. Full article