Search Results (2,863)

Background: Disseminated coccidioidomycosis (DCM) often requires prolonged antifungal therapy (AFT). Real-world data on AFT duration in DCM are limited. We evaluated time to AFT discontinuation among patients with DCM in the United States clinical practice. Methods: This retrospective, longitudinal study used STATinMED data (2016–2024). Patients had ≥1 International Classification of Diseases, Tenth Revision (ICD-10) code for DCM (B38.3, B38.4, B38.7, B38.81) during January 2017–December 2023, ≥1 claim for a triazole or amphotericin B within 21 days of the DCM diagnosis (index date), and continuous medical/pharmacy coverage during the 6-month baseline period. Discontinuation was defined as a ≥21-day gap without AFT. Antifungal agent/formulation switches were not considered discontinuations unless accompanied by a qualifying gap. The Kaplan–Meier methods were used to estimate time to discontinuation. Results: We identified 991 patients with DCM. Median age was 52 years (IQR 36, 65); 60.0% were men. Most resided in California (42.8%) or Arizona (33.6%). Initial AFT consisted predominantly of triazoles (96.8%), primarily fluconazole (83.2%). Discontinuation occurred in 27.6%, 40.0%, 54.2%, and 68.0% of patients by 3, 6, 12, and 36 months. Median AFT duration was 9.9 months. Conclusions: In a large US claims cohort, there was substantial variability in AFT duration in routine practice. Many patients had AFT durations under the lower limit of guideline recommendations for DCM, suggesting potential under-treatment, though appropriate clinical justifications may have existed. Full article

Background: Test descriptions from major diagnostic manufacturers do not include ferritin reference intervals (RIs) for individuals aged 60 and older. The absence of older adults-specific RIs contrasts with the widespread use of serum ferritin testing in older adults. We aimed to establish and verify RIs using two common analytical methods. Methods: For this study, 1467 older adults were prospectively enrolled and monitored for morbidity and mortality, and exclusion criteria were applied. Ferritin was measured using chemiluminescent microparticle immunoassay (CMIA) and transferred to an electrochemiluminescence immunoassay (ECLIA) using method comparison. RIs were evaluated using a direct method with a prospective observational study based on healthy individuals according to the Clinical and Laboratory Standards Institute (CLSI) 28-A3c guideline and compared with RIs obtained using an indirect approach based on data obtained in clinical routine outpatients, where normal and abnormal values are supposed to be statistically differentiated to determine RIs. When applied within a countrywide population-based setting in Liechtenstein, the impact of novel RIs on the frequency of abnormal values was analyzed. Results: A total of 386 men and 532 women were included in the direct RI determination. Women (W) had significantly lower ferritin levels than men (M), while age over the age of 60 years had no significant association with ferritin in men and women. RIs were 23–241 ng/mL (W) and 19–396 ng/mL (M) for CMIA and 27–293 ng/mL (W) and 23–480 ng/mL (M) for ECLIA. These RIs are higher than those mentioned in the test descriptions in both tests. In comparison, the indirect method for both assays showed comparably lower reference limits, whereas upper reference limits were only approximately similar. The prevalence of high abnormal ferritin levels was considerably lower with this study’s RIs compared with manufacturer RIs. Conclusions: Employing older adults-specific RIs in clinical routine seems to be advisable. This reduces the frequency of abnormal high values in comparison with the widely applied practice of extrapolating RIs obtained from younger age groups to older adults and therefore leads to fewer follow-up investigations. Full article

Lung cancer remains the leading cause of cancer mortality worldwide, with most cases diagnosed at advanced stages. Conventional tissue biopsy is invasive, and low-dose CT (LDCT) screening—although effective—faces practical and logistical limitations. Liquid biopsy has emerged as a minimally invasive approach to capture tumor-derived material, including circulating tumor DNA (ctDNA), cells, and extracellular vesicles (EVs). Among EVs, exosomes and their microRNA (miRNA) cargo offer a stable, disease-specific signal. Airway-proximal fluids such as bronchial aspirate and bronchoalveolar lavage fluid (BALF) are in direct contact with the tumor microenvironment and may contain higher concentrations of tumor-derived exosomal miRNAs compared with blood. This review synthesizes the limited but promising evidence for exosomal miRNAs in bronchial aspirate and BALF as diagnostic and prognostic biomarkers in lung cancer, examines methodological and standardization challenges, and discusses potential integration into clinical workflows, with particular emphasis on Romania’s lung cancer epidemiology and healthcare context. While only two primary studies in the last five years have explored BALF exosomal miRNAs, these data justify further multicenter investigations aligned with MISEV2023 guidelines. Integrating airway-proximal exosomal miRNA analysis into bronchoscopy procedures could enhance diagnostic precision in resource-limited health systems and support the transition towards personalized thoracic oncology. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of neurotoxic chemotherapy that can affect functioning and quality of life. Currently, duloxetine is the only recommended agent to treat painful CIPN; however, no effective pharmacological treatments have been approved for the prevention or cure of CIPN, highlighting the need to understand non-pharmacological strategies such as exercise. Given significant heterogeneity in the CIPN outcome measures chosen across studies, this scoping review aimed to identify the outcome measures used to evaluate the effectiveness of exercise interventions as a potential countermeasure for CIPN. Following the Arksey and O’Malley framework refined by Levac and colleagues, and the PRISMA-ScR guidelines, four databases were searched, and 20 studies were included in the review. Data were abstracted on study characteristics, cancer and chemotherapy factors, exercise prescription, outcome measures, and CIPN-related findings. Outcome measures varied widely across studies, encompassing various patient-reported, clinical, and functional measures. The most common patient-reported, clinical, and functional measures were the EORTC QLQ-CIPN20, vibration sensation, and maximal isometric strength, respectively. No study satisfied the components of the core outcome measure set proposed by Park and colleagues, limiting cross-study comparisons. These findings underscore the need for standardized CIPN outcome measures in future exercise studies to strengthen evidence synthesis and inform clinical practice. Full article

Severe accidental hypothermia represents a unique and potentially reversible cause of cardiac arrest in which prolonged resuscitation may still result in favorable neurological recovery. Unlike normothermic cardiac arrest, hypothermic cardiac arrest (HCA) is characterized by profound metabolic suppression and temperature-mediated myocardial instability, requiring a fundamentally different therapeutic paradigm. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) provides not only circulatory support but also controlled reperfusion and rewarming, positioning it as the cornerstone of modern management. Recent international guidelines have clarified indications for extracorporeal life support (ECLS) in HCA and have contributed to improved standardization of care. Building upon these recommendations, this narrative review focuses on physiological principles underlying extracorporeal rewarming and their implications for bedside management. We examine mechanisms of ischemia–reperfusion injury, rewarming-associated hemodynamic instability and myocardial stunning, discuss dynamic risk assessment beyond statistical thresholds such as the HOPE score and summarize practical considerations regarding cannulation strategies, differential hypoxia, left ventricular unloading and neurologic evaluation. By integrating current evidence with pathophysiological insight and organizational considerations, this review proposes a clinically oriented framework to support decision-making in hypothermic cardiac arrest and to optimize meaningful neurological recovery. Full article

Background/Objectives: As use of large language models (LLMs) in clinical practice, in medical education, and by patients increases, it is essential to ensure that information provided is accurate and safe. Our objective was to compare stage two hypertension treatment plans generated by popular LLMs. Methods: ChatGPT (GPT-4o), Claude (Claude 4 Sonnet), ClinicalKey AI, Microsoft Copilot (Wave 2), DeepSeek-V3-0324, Dyna AI, Google Gemini (2.5 Flash), Grok (version 3), Meta AI assistant (Llama 4 Maverick), OpenEvidence (version 2.0), Perplexity (Sonar backend model), and Pi (Inflection-2.5) were prompted to generate a treatment plan for stage two hypertension. Six blinded reviewers scored each response in three domains: adherence to clinical guidelines, detail/clarity, and reliability/safety. Results: Perplexity received the highest composite score (8.17 out of 9), followed by OpenEvidence (7.92 out of 9). Dyna AI had the lowest overall score (3.75 out of 9). Perplexity (3.00 out of 3), Grok (2.83 out of 3), and OpenEvidence (2.75 out of 3) had the highest scores for detail/clarity, while Dyna AI had the lowest for both detail/clarity (1.00 out of 3) and reliability/safety (1.00 out of 3). ChatGPT had the highest score for adherence to guidelines (2.75 out of 3) while Pi had the lowest (1.58 out of 3). Kruskal–Wallis test showed p < 0.05 across sub-score domains and composite scores. Conclusions: LLMs tended to adhere to clinical guidelines and provide detailed responses but often did not provide sources or instruct users to see a healthcare professional. There was notable variability in quality, and medicine-specific LLMs were not superior to popular LLMs. Full article

Age-related macular degeneration (AMD) is the most common cause of blindness and vision impairment in individuals over 60 years of age in the United States (US). Despite this, current treatment options have limitations related to drug efficacy and durability. Gene therapy provides a potential solution by providing a more durable and longer- acting treatment option that can decrease treatment burden and improve long-term visual outcomes. This review presents the current treatment approaches, routes of administration, and vectors being investigated for gene therapy delivery in AMD. It also provides an update on the ongoing gene therapy clinical trials for dry and wet AMD. As these therapies advance into later-stage clinical trials, ophthalmologists need to be mindful of the many challenges pertaining to gene therapy delivery, including safety, limitations related to immunogenicity, long-term ocular and systemic side effects, and potential barriers to drug manufacturing and access. Continued efforts are required to improve precision, safety, and efficacy, including identifying the safest and most effective vectors and delivery routes, and minimizing potential adverse effects. In addition, guidelines need to be established to guide appropriate patient selection before gene therapy can be integrated into clinical practice. Full article

The definition of hypertension and the values of systolic and diastolic blood pressure (BP) that should be considered as therapeutic targets have changed over time and vary across scientific societies, which may generate uncertainty in the decision-making process among clinicians and patients. We traced the evolution and described the differences in all the 32 Clinical Practice Guidelines for the management of hypertension released by the following national and international scientific societies: World Health Organization—WHO; International Society of Hypertension—ISH; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure—JNC; American Heart Association—AHA; American College of Cardiology—ACC; European Society of Cardiology—ESC; European Society of Hypertension—ESH; and UK National Institute for Health and Care Excellence—NICE. Throughout the decades, the BP values used for hypertension definition, treatment initiation, and targets to achieve started from SBP/DBP ≥ 160/95 mmHg, established at the end of the 70s, progressively decreased, and were differentiated by individual cardiovascular risk. In the last decade, a divergent approach emerged across scientific societies: while WHO/ISH and NICE recommended thresholds and targets for the general population at SBP/DBP < 140/90 mmHg, ESH/ESC and ACC/AHA guidelines further and markedly reduced both BP threshold values and therapeutic targets, recommending as ideal SBP/DBP values < 130/80 mmHg and encouraging an SBP < 120 mmHg. Discrepancies also emerged in the assessment of the quality of the evidence: although the methodological approaches largely improved over time and across all the institutions assessed, various degrees of incompleteness on the adopted scales were reported, and potentially conflicting situations emerged, particularly when weaker evidence was used to build strong recommendations. Although some degree of discrepancy among guidelines is expected, some of the differences are large and can lead to widely different approaches in the management of BP control. A standardization of the methodology and interpretation of the evidence supporting the guidelines may help to reduce the variability in order to provide the best possible guidance for clinical practice and patient health. Full article

Background/Objectives: Nurses and dialysis technicians are primarily responsible for cannulation in in-center and satellite dialysis units. Despite being a core component of hemodialysis care, existing clinical guidelines offer limited standardization, resulting in practice variability across facilities. Therefore, clinical expertise and adherence to consistent standards are essential to ensure safe and effective vascular access management. The study aimed to investigate the variables related to patients and nurses that contribute to unsuccessful vascular access cannulations, as well as the actions taken in response to cannulation failure, in a tertiary dialysis center in the Eastern Region of Saudi Arabia. Methods: This retrospective analytic study reviewed the records of 228 adult hemodialysis patients at King Fahad Military Medical Complex from 2020 to 2024, analyzing demographic, clinical, vascular access, and nursing variables associated with cannulation failure using descriptive statistics, the chi-square test, and t-tests. Ethical approval was obtained, and data were de-identified and manually extracted from nursing and dialysis documentation. Results: Most patients had hypertension and diabetes, with significant comorbidity burdens. Infiltration (61%) and clot formation (30.7%) were the primary complications of cannulation failure. Significant associations emerged with recurrent stroke and peripheral vascular disease, but not with nurse or patient demographics, suggesting vascular factors outweigh staff variables in cannulation risk. Cannulation failures were most common in patients with vascular comorbidities, while staff experience and education had no significant impact. Conclusions: Recommendations include implementing tailored protocols, providing ongoing nurse education, conducting systematic vascular assessments, and holding regular team reviews to enhance access outcomes and patient safety. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disorder linked to obesity, insulin resistance, and dyslipidemia. Nutrition plays a central role in modulating hepatic lipid metabolism, oxidative stress, and inflammation, yet practical, evidence-based dietary strategies remain limited. This study aimed to develop Mediterranean diet-based meal plans with varying macronutrient compositions and to characterize their nutritional profiles, as well as to evaluate them using established nutritional indices and diet score calculations, such as the Dietary Inflammatory Index, Dietary Antioxidant Index, and dietary lipid indices. Methods: Clinical practice guidelines (CPGs) from various academic and professional organizations were reviewed to assess current non-pharmacological treatments for MASLD, with a focus on determining whether the Mediterranean diet is the most recommended dietary pattern. Traditional, low-carbohydrate, and low-fat MedDiet patterns were translated into food-based meal plans. A 7-day meal plan was developed and analyzed for nutrient composition, then evaluated using the Dietary Inflammatory Index (DII), Dietary Antioxidant Index (DAI), Dietary Lipophilic Index (DLI), and Dietary Lipophilic Load (DLL). A Western diet (WD) that is characterized by ultra-processed food (UPF) was included as a comparative reference. Results: The validated dietary score calculations showed that all MedDiet patterns demonstrated consistently low DII scores (−2.00 to −2.81) and high DAI scores (3 to 20.03), whereas the WD showed high DII scores (5.0 to 6.09) and low DAI scores (−12.47 to −17.99). Despite these variations in macronutrients, the menu developed in the study on three MedDiet patterns showed negative DII and positive DAI scores. When comparing the traditional MedDiet with the WD, which have similar macronutrient distributions, the WD was characterized by less favorable DII and DAI scores. Conclusions: This study provides a descriptive, guideline-informed framework for Mediterranean diet-based meal plans with varying macronutrient compositions. Utilizing DII, DAI, DLI, and DLL offers a potential framework for designing dietary interventions. Further validation through clinical studies is needed to justify the potential for practical and digital translation. Nevertheless, the study provides initial insights that may inform future research on nutritional approaches for MASLD integrating dietary indices. Full article

Background: The Democratic Republic of the Congo accounts for approximately 12–13% of the global malaria burden. While international guidelines oppose the use of Artemisia annua infusions due to risks of sub-therapeutic dosing and resistance selection, the plant remains widely used in resource-limited regions. This study evaluates the clinical acceptability and perceptions of healthcare providers regarding the integration of Artemisia annua tea into formal malaria control in the Maniema province. Methods: A cross-sectional survey was conducted among 337 healthcare professionals in the Kalima health district using the KoboCollect digital platform. Multivariate logistic regression was employed to identify the primary socio-professional determinants of clinical acceptability. Results: The overall clinical acceptability of Artemisia annua integration was 81.0%, with 82.8% of providers perceiving the preparation as effective. Rural residency was the strongest predictor of adherence (AOR = 6.847; p = 0.003), reflecting a pragmatic response to frequent ACT stockouts and high treatment costs. Despite high acceptability, 49.0% of providers identified the lack of clinical evidence as a major barrier, and 91.4% demanded formal training on standardized dosage and biological mechanisms. Conclusions: A significant “policy–practice gap” exists between international guidelines and field realities in the DRC. Healthcare providers demonstrate high readiness for integration but emphasize the absolute necessity of galenic standardization to mitigate resistance risks. To address these concerns, a complementary genomic investigation is currently underway in the same study area, comparing PfKelch13 mutation prevalence among Artemisia tea users versus ACT-treated patients. This molecular surveillance will provide essential evidence to define safety parameters for future phytopharmaceutical integration. Full article

Treatment guidelines for Clostridioides difficile infection (CDI) have been published by infectious disease and gastroenterology professional societies; however, adherence in clinical practice remains poorly characterized, particularly for recurrent disease. We conducted a retrospective chart review of 100 patients with CDI (350 episodes: 115 initial, 235 recurrent) referred to a tertiary complicated CDI clinic between 2018 and 2023. Guideline adherence was assessed by comparing treatment with IDSA/SHEA and ACG recommendations, and referring diagnoses were compared with final specialist diagnoses. Guideline adherence was significantly higher in initial compared to recurrent episodes (70.4% vs. 41.3%, p < 0.0001). Among guideline non-adherent recurrent episodes, 51.3% used standard antibiotic regimens inappropriate for the recurrence tier. Specialist review reclassified 12.0% of episodes, with colonization increasing from 2.6% to 8.9%. Misdiagnosed colonization cases had a 6.2-fold higher treatment failure rate than confirmed CDI (39.3% vs. 6.3%, p < 0.0001). Guideline non-adherence showed a non-significant trend toward treatment failure (10.0% vs. 6.7%, p = 0.31). Guideline adherence for recurrent CDI is inadequate in pre-referral settings, and diagnostic misclassification is common. Early specialist involvement may improve both diagnostic accuracy and treatment appropriateness for patients with recurrent CDI. Full article

Background and Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular (CV) death and heart failure hospitalizations (HFH) in patients with heart failure with reduced ejection fraction (HFrEF). However, data regarding their use in combination with different doses of guideline-directed medical therapy (GDMT) remain limited. This study aimed to evaluate whether SGLT2i combined with low-dose conventional triple therapy is non-inferior to high-dose conventional triple therapy in preventing adverse cardiovascular outcomes. Materials and Methods: This retrospective observational study included 334 patients with HFrEF treated between 31 March 2018 and 31 March 2024. Of these, 110 received SGLT2i plus low-dose conventional triple therapy, and 224 received high-dose conventional triple therapy. A non-inferiority framework was applied to compare outcomes between groups. The primary endpoint was a composite of CV death and HFH, while secondary endpoints included the individual components. Results: The composite endpoint occurred more frequently in the SGLT2i plus low-dose group. After inverse probability of treatment weighting and multivariable Cox analysis, this group demonstrated a significantly higher risk of the composite outcome (adjusted HR 4.10, 95% CI 2.07–8.13; p < 0.001). CV death was similar between groups; however, HFH was significantly more frequent in the SGLT2i plus low-dose group. Conclusions: In patients with HFrEF, SGLT2i combined with low-dose conventional triple therapy did not demonstrate comparable clinical outcomes to high-dose conventional triple therapy in reducing CV death and HFH, particularly in patients with a higher baseline burden of disease severity. These findings underscore the importance of optimizing background GDMT dosing alongside the incorporation of SGLT2i into clinical practice. Full article

Objectives: To evaluate the association between European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores and treatment recommendations from European Society for Medical Oncology, National Comprehensive Cancer Network (NCCN), and American Society of Clinical Oncology (ASCO) in curative and metastatic breast cancer (BC), and to assess inter-guideline concordance. Methods: We conducted a comparative review of 47 systemic BC therapies with published ESMO-MCBS scores (accessed 30 June 2025). Guideline recommendations from ESMO, NCCN, and ASCO were extracted from the most recent versions and harmonized into ordinal tiers. Associations between MCBS scores and recommendation categories were evaluated using Fisher’s exact test and Spearman’s rank correlation in the palliative setting. Curative therapies were analyzed descriptively due to limited variability. Results: Among 38 palliative therapies, 40% achieved high clinical benefit (MCBS 4–5). A significant association was observed between MCBS scores and NCCN recommendations (p = 0.003; ρ = 0.48), with 62% of NCCN Category 1 therapies demonstrating high benefit versus 13% in other categories. No significant associations were observed with ASCO (p = 0.101; ρ = 0.18) or ESMO guideline recommendations (p = 0.073; ρ = 0.19). Inter-guideline concordance was strongest between ASCO and ESMO (p = 0.033; ρ = 0.48). In the curative setting (n = 9), most therapies received an MCBS grade A and top-tier guideline endorsement. Conclusions: Alignment between ESMO-MCBS and guideline recommendations is moderate and framework-dependent, strongest with NCCN in metastatic BC. Discordance primarily reflects differences between magnitude-of-benefit thresholds and evidence-certainty frameworks. ESMO-MCBS may serve as a complementary tool to enhance value-based clinical and policy decision-making. Full article

Background/Objectives: Prostate cancer (PCa) incidence is rising, with radical prostatectomy (RP) as the main curative surgery for localised cases, which includes removing seminal vesicles (SV). SV invasion (SVI) predicts poor oncological outcomes, making accurate preoperative staging to identify SVI crucial for surgical planning. This ensures oncological safety by enabling wide excision when needed, while preserving tissue to maintain function. This review synthesises current evidence on pre-biopsy MRI findings and/or clinicopathological parameters to diagnose SVI in PCa. Methods: A literature search (2005–2025) using OVID for studies assessing pre-biopsy MRI findings, with a priori eligibility for clinicopathological or combined MRI–clinicopathological models (index tests), for detecting SVI (outcome) compared to RP histopathology (standard reference) in patients with primary localised PCa (patients). This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was evaluated with QUADAS-2, and pooled diagnostic accuracy metrics and study heterogeneity were analysed. Results: Five studies qualified, while three used binary mpMRI classification and were quantitatively analysed. No eligible studies assessed clinicopathological predictors or combined MRI–clinicopathological models; all included studies evaluated pre-biopsy MRI findings only, and none included high-dimensional radiomics. The pooled sensitivity was 0.66 (95% CI: 0.52–0.78), specificity 0.94 (0.89–0.97), positive predictive value (PPV) 0.76 (0.60–0.87), negative predictive value (NPV) 0.92 (0.85–0.94), and diagnostic odds ratio 30.13 (12.36–73.47), with moderate heterogeneity. All included studies were retrospective cohorts with considerable risk of bias. Conclusions: In the small number of heterogeneous, single-centre retrospective studies available, pre-biopsy MRI findings show high specificity and NPV for preoperative detection of SVI but only moderate sensitivity, which limits its reliability as a standalone tool. The pooled diagnostic accuracy estimates should be interpreted as exploratory. These findings should therefore be interpreted cautiously. Future studies must integrate MRI with clinicopathological data, addressing this key evidence gap before firm conclusions can be drawn or clinical practice changed. Full article