Search Results (9,502)

Background: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or depression both frequently report debilitating exhaustion, yet the two conditions differ in their etiological and diagnostic clarity, and clinical management. This study aimed to examine differences in the use and perceived helpfulness of a broad range of conventional treatments and complementary interventions, including nutritional approaches, between patients with ME/CFS and depression. Methods: A cross-sectional online survey was conducted in 2024. A total of 819 participants self-identified as having either ME/CFS (n = 576) or depression (n = 243). Participants (80% female) reported their use and perceived helpfulness of 52 treatments and interventions, encompassing behavioral therapies, medications, and dietary supplements. Group differences were examined using multivariate analyses of variance and covariance (MANOVA/MANCOVA). Open-ended responses were analyzed descriptively using thematic grouping and frequency counts. Results: Participants with depression most commonly reported the use of psychotherapy (M = 2.49, SD = 1.00) and antidepressant medication (M = 2.44, SD = 2.30), and they rated fewer interventions as helpful compared to participants with ME/CFS. In contrast, participants with ME/CFS reported a significantly broader engagement with diverse intervention modalities, particularly pacing (M = 2.73, SD = 0.80) and dietary supplements (M = 2.43, SD = 1.09), and perceived many of them as helpful. Group differences remained significant after controlling for age, gender, and whether treatment was medically recommended. Supplements targeting energy metabolism (e.g., CoQ10, NADH) were especially favored among ME/CFS participants. Conclusions: Findings suggest that participants with ME/CFS tend to adopt an exploratory and expansive intervention approach, potentially reflecting the lack of standardized guidelines and limited effectiveness of available treatment options. Participants with depression, in contrast, appeared to follow more guideline-concordant, evidence-based treatment pathways. Taken together, the findings point to a need for further development and evaluation of empirically supported, patient-centered treatment and intervention strategies for ME/CFS and suggest differences in clinical care structures between ME/CFS and depression. Full article

Background: Adverse Drug Reactions (ADRs) are a significant public concern because of their impact on healthcare systems. Spontaneous reporting of ADRs is crucial for monitoring drug safety and recognizing possible risk factors. The objective of this study was to characterize ADR reports from the Allergy and Clinical Immunology Unit of the G. Martino University Hospital, Messina, Italy. Methods: A retrospective analysis was conducted, including all ADRs spontaneously reported from patients attending the clinic because of at least one previous ADR, from June 2022 to June 2024. Results: A total of 388 reports were collected, mainly from females (71.1%) and adult patients (84.3%). ADRs were mostly immediate, from antibiotics and anti-inflammatory drugs (61.5%), with a high prevalence of cutaneous and respiratory disorders. Delayed reactions were mostly from endocrine therapies, vaccines, and antiepileptics. Anaphylactic shock was present only in 13 ADR reports (3.35%). A higher risk of developing serious ADRs was found in elderly patients aged ≥65 years (p = 0.012). An original finding was that a positive history of allergies (p = 0.023) and past medical history of ADRs (p = 0.045) were negatively correlated to the occurrence of a serious ADR, probably because patients had been previously followed in an allergy setting and alerted about ADRs. Conclusions: This study underlines the role of ADR follow-up in allergy settings to identify preventable traits and related risk factors; appropriate ADR reporting and collaboration between allergists and pharmacovigilance centers can be a winning strategy for ADR prevention. Full article

Non-homologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway that operates throughout the cell cycle to maintain the genomic stability of the cell. Unlike homologous recombination (HR), NHEJ is capable of repairing DSBs without the need for a homologous template, making it a rapid response mechanism, but potentially prone to errors. Central to NHEJ function and essential for the ligation through the recruitment and activation of additional repair factors, such as Artemis, XRCC4, and DNA ligase IV, is the DNA-dependent protein kinase (DNA-PK) complex. Dysregulation in the NHEJ pathway contributes to genomic instability, oncogenesis, and resistance to genotoxic therapies. Consequently, inhibitors of DNA-PK have emerged as promising therapeutic agents to sensitize tumor cells to radiation and DNA-damaging chemotherapeutics. Inhibiting the DNA-PK ability to recruit the protein complex needed for successful DSB repair promotes cell death through apoptosis or mitotic catastrophe. While inhibitors of DNA-PK can be used to enhance the effects of genotoxic therapies, the field still struggles to address critical problems: how to best exploit the differential DNA repair capacities among tumor subtypes, how to maximize radiosensitization of cancerous cells while sparing normal tissues, and how to translate preclinical studies into clinical benefits. Given that NHEJ constitutes the primary line of defense against radiation-induced damage, rapidly repairing the majority of double-strand breaks throughout the cell cycle, this review concentrates on targeting the DNA-PK complex, as the master regulator of this rapid-response mechanism, highlighting why its inhibition represents a strategic action to overcome intrinsic radioresistance. The implementation of DNA-PK inhibitors into medical practice can enable the stratification of oncologic patients into two categories, based on the tumors’ vulnerability to NHEJ disruptions. Thus, the therapeutic pathways of patients with NHEJ tumors could branch, combining traditional genotoxic therapies (radiation and DNA-damaging chemotherapeutics) with DNA-PK inhibitors to achieve an enhanced effect and improved survival outcomes. Full article

Residual congestion (RC) at discharge predicts adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Its impact on the implementation of guideline-directed medical therapies (GDMT) remains unclear. N-terminal pro-B-type natriuretic peptide (NT-proBNP) trajectory during hospitalisation reflects RC and may be associated with GDMT implementation. The aim was to assess whether discharge NT-proBNP and a fall in NT-proBNP < 30% during hospitalisation (ΔNT-proBNP < 30%) predict GDMT underuse in acute HFrEF. In this prospective observational study, NT-proBNP was measured at hospital admission and 48–72 h before discharge. Provision of individual GDMT drug classes was assessed and GDMT underuse was defined as prescription of <3 key GDMT drug classes at discharge. 391 HFrEF patients (mean age, 69.9 ± 13.1years, 67.3% male) were included. ΔNT-proBNP < 30% was identified in 108 (27.6%). Higher discharge NT-proBNP was independently associated with lower likelihood of prescribing ACE-inhibitors, sacubitril/valsartan, eplerenone/spironolactone, or empagliflozin/dapagliflozin. ΔNT-proBNP < 30% was associated with 17% higher odds of GDMT underuse (95% confidence interval, 1.10–1.31, p < 0.001), regardless of clinical characteristics or in-hospital management. Patients with ΔNT-proBNP < 30% were discharged on lower doses of titratable GDMT medications. In-hospital NT-proBNP burden and trajectory, as markers of RC, are associated with GDMT underutilisation at discharge in acute HFrEF. Addressing RC may impact treatment quality in acute HFrEF. Full article

Bleeding and thromboembolism are among the leading causes of mortality worldwide. Thrombosis encompasses both arterial forms—primarily associated with atherosclerosis and leading to heart attacks or strokes—and venous forms. Microvascular thrombosis typically arises in the context of sepsis or systemic inflammation, and it became particularly prominent during the COVID-19 pandemic, substantially contributing to increased mortality. Given this burden, the rapid development of new therapies using advanced techniques and materials to prevent and treat these conditions is essential. This review summarizes recent advances in the design of antithrombotic polymers, discussing mechanisms of action, surface-modification strategies, and current clinical and preclinical applications. It also outlines criteria for evaluating hemocompatibility, describes in vitro and in vivo testing methods, and highlights key barriers to translating these materials into clinical practice. The review concludes by identifying promising directions for future research, including multifunctional approaches that combine antifouling properties, controlled drug release, and bioresistance strategies with the greatest potential to reduce thromboembolic complications associated with medical materials. It further evaluates the progress made to date in combating thrombotic diseases and identifies remaining gaps in the development and clinical implementation of new antithrombotic materials. Full article

Both obesity and chronic kidney disease (CKD) are increasingly recognized as global epidemics. Their escalating incidence and far-reaching health implications highlight the urgent need for comprehensive prevention and management strategies. This review aims to clarify how obesity interacts with end-stage kidney disease (ESKD) and how to improve the management of obese patients receiving kidney replacement therapy. It also explores underlying mechanisms, current treatments, future directions, and ongoing controversies. By highlighting this intricate relationship, the review seeks to enhance clinical practice and promote further research toward more personalized care for this vulnerable population. Obesity is frequent in dialysis patients and creates challenges related to body composition, metabolism, and treatment. While higher body mass index (BMI) may appear to improve survival, this paradox does not offset the cardiovascular and functional risks of visceral and sarcopenic obesity. Obesity also increases post-transplant complications and can limit access to transplantation. Lifestyle changes rarely achieve lasting weight loss, whereas bariatric surgery—especially sleeve gastrectomy—can improve transplant eligibility with fewer complications. Weight-loss medications may be used before transplantation but remain insufficiently studied in ESKD. After transplantation, weight-reduction efforts should continue, with pharmacotherapy preferred over bariatric surgery. Comprehensive assessment strategies and individualized management approaches in ESKD patients are essential to optimize outcomes in this growing patient population. Full article

Wound healing has been studied extensively in humans and lab animals, but not in dolphins. Severe human wounds require extensive medical intervention to avoid infection. Yet severe wounds on free-ranging dolphins heal without infection in microbial-infested seas, a compelling distinction. An eye-witnessed shark attack on a yearling bottlenose dolphin yielded 8 years of macroscopic markers on a live recuperating dolphin by known days of healing. In total, 106 healing histories were generated from the author’s 20-year ethological study of free-ranging bottlenose dolphins (Tursiops truncatus) in St. Petersburg, FL, USA. Results show that unaided wound healing at sea involves two consecutive macroscopic pigment patterns, wounds form preliminary seals by 4–8 weeks, and most heal to atrophic scars that remodel for years. Macroscopic markers in live recuperating dolphins show strong matches with macroscopic wound patterns in stranded Fraser’s dolphins (Lagenodelphis hosei), demonstrating links between macroscopic markers and immune activities. This is the first study to link macroscopic markers visible as healing-related pigment patterns to immunity. Macroscopic markers are conservation tools for tracking anthropogenic impacts on increased susceptibility to infection at sea and could lead to novel therapies in veterinary and human regenerative medicine. Full article

This review explores the transformative role of three-dimensional (3D) printing in radiation therapy for cancer treatment, emphasizing its potential to deliver patient-specific, cost-effective, and sustainable medical devices. The integration of 3D printing enables rapid fabrication of customized boluses, compensators, immobilization devices, and GRID collimators tailored to individual anatomical and clinical requirements. Comparative analysis reveals that additive manufacturing surpasses conventional machining in design flexibility, lead time reduction, and material efficiency, while offering significant cost savings and recyclability benefits. Case studies demonstrate that 3D-printed GRID collimators achieve comparable dosimetric performance to traditional devices, with peak-to-valley dose ratios optimized for spatially fractionated radiation therapy. Furthermore, emerging applications of artificial intelligence (AI) in conjunction with 3D printing promise automated treatment planning, generative device design, and real-time quality assurance, and are paving the way for adaptive and intelligent radiotherapy solutions. Regulatory considerations, including FDA guidelines for additive manufacturing, are discussed to ensure compliance and patient safety. Despite challenges such as material variability, workflow standardization, and large-scale clinical validation, evidence indicates that 3D printing significantly enhances therapeutic precision, reduces toxicity, and improves patient outcomes. This review underscores the synergy between 3D printing and AI-driven innovations as a cornerstone for next-generation radiation oncology, offering a roadmap for clinical adoption and future research. Full article

Background/Objectives: Blood thinners (anticoagulants) remain the first line pharmacotherapy for the management of cardiovascular and thromboembolic disorders. The increased utilization of polypharmacy, likely driven by the greater burden of comorbidities, elevates the risk of potential drug–drug interactions (pDDIs) and creates a significant challenge in anticoagulant management. The aim of the study was to assess the prescribing trend and impact of polypharmacy and pDDIs in patients receiving anticoagulant drug therapy in a public hospital providing secondary care. Methods: A cross-sectional observational study was undertaken between January–June 2023. Data from electronic medical records of prescriptions for anticoagulants were collected, analyzed for prescribing patterns, and checked for pDDIs using Micromedex database 2.0^®. Utilizing binary logistic regression, the relationship between polypharmacy and sociodemographic factors was assessed. Multivariate logistic regression analysis served to uncover determinants linked to pDDIs. Results: Of the total 130 patients, females were predominant (58.46%), with a higher prevalence among those aged 61–90 years. Atrial fibrillation emerged as the main clinical reason and apixaban (51.53%) ranked as the top prescribed anticoagulant in our cohort. Among the 766 pDDIs identified, the majority [401 (52.34%)] were categorized as moderate in severity. Polypharmacy was strongly linked to age (p = 0.001), the Charlson comorbidity index (CCI) (p = 0.040), and comorbidities (p = 0.005) in the binary logistic regression analysis. In the multivariable analysis, the number of medications remain a strong predictor of pDDIs (adjusted OR: 30.514, p = 0.001). Conclusions: Polypharmacy and pDDIs were exhibited in a significant segment of cohort receiving anticoagulant therapy, with strong correlations to age, CCI, comorbidities, and the number of medications. A multidimensional approach involving collaboration among healthcare providers assisted by clinical decision support systems can help optimize the management of polypharmacy, minimize the risks of pDDIs, and ultimately enhance health outcomes. Full article

Neurocysticercosis (NCC) remains a major public health problem in endemic countries. Clinical manifestations and therapeutic strategies vary depending on the location of the parasite. While the benefits of cysticidal treatment are well established for parenchymal and subarachnoid NCC, the optimal management of intraventricular NCC (IVNCC) remains controversial. We conducted a retrospective study of 51 patients: 37 (72.54%) received cysticidal treatment as initial therapy and 14 (27.45%) underwent neurosurgical intervention. Although six months after treatment, the proportion of patients with inactive disease was higher in the surgical group, no significant difference was observed after one year. Patients in both groups showed significant improvement in functionality as measured by the Karnofsky Index (KI), with no significant difference between groups. These results are consistent with cysticidal treatment being a valid therapeutic option for IVNCC, with the choice of management largely determined by the available medical infrastructure and the degree of specialization of healthcare personnel. Full article

Background/Objectives: Anti-mGluR1 encephalitis is a rare form of autoimmune encephalitis predominantly manifesting as acute/subacute cerebellar ataxia. We describe a newly diagnosed case series from our center and conduct a comprehensive review of reported cases worldwide to compare clinical manifestations, treatment options, and outcomes. Methods: We consecutively identified 11 patients at Peking Union Medical College Hospital, and additionally extracted clinical data from 42 previously published cases identified via PubMed and Google Scholar (search updated to 1 August 2025). Demographics, phenotypes, laboratory findings, imaging, treatment, and outcomes were systematically summarized. This pooled review was not prospectively registered, and extracted data from 21 published articles were analyzed alongside our 11 newly diagnosed cases. Results: The integrated cohort comprised 53 patients with anti-mGluR1 encephalitis, including 29 males and 24 females, with patients reported from Asia (n = 18), North America (n = 11), and Europe (n = 24). The median age at onset was 50 years (IQR 29.5–58.5; range 3–81), with North American patients presenting later than their Asian and European counterparts (median 60 vs. 48 and 45 years, respectively; all p < 0.05). Disease onset was subacute in most cases (58.7%). Comorbid tumors were present in nine patients, most commonly lymphomas. Clinical phenotypes were classified as pure cerebellar syndrome (n = 31), cerebellar ataxia with encephalitic features (n = 20), and non-cerebellar presentations (n = 2). Baseline severity differed across phenotypes (χ² = 35.7, p < 0.001). Regional variability in severity was observed but did not reach significance. CSF analyses revealed pleocytosis in 59% (23/39), elevated protein in 31.3% (5/16), and oligoclonal bands in 52.2% (12/23). MRI abnormalities were detected in 34.7% (17/49) of patients, with 21.9% (7/32) developing cerebellar atrophy on follow-up. Therapeutic strategies varied significantly across regions (p = 0.041), with Asian cohorts more frequently receiving long-term immunosuppression, European cohorts favoring combined regimens, and North American cases relying predominantly on first-line therapies. Overall, 65.9% (29/44) of patients clinically improved, 13.6% (6/44) relapsed and 20.5% (9/44) remained unaffected. Conclusions: Anti-mGluR1 encephalitis presents with significant clinical heterogeneity, ranging from cerebellar-dominant ataxia to neuropsychiatric or non-cerebellar phenotypes, and demonstrates differences in reported age of onset, disease severity, and therapeutic approaches across publication regions. Our findings underscore the importance of early recognition, sustained immunotherapy, and international collaboration to establish standardized, evidence-based management for this rare but disabling disorder. Full article

Background/Objectives: Hemodynamic and neurohormonal factors, including renal perfusion and venous pressure, may affect diuretic response, which may be modulated by body position. This study aimed to assess whether supine versus upright positioning influences diuretic efficacy and neurohormonal activation during early decongestion in patients with AHF and reduced ejection fraction (HFrEF). Methods: This single-center, prospective, pilot randomized study enrolled 12 hospitalized patients with decompensated HFrEF receiving guideline-directed medical therapy. Participants were randomized (1:1) to remain in either the supine or upright/seated position during intravenous furosemide administration (1 mg/kg: half of the dose administered as a bolus, half as a 2-h infusion). Serial measurements of urine volume, electrolyte excretion, and neurohormonal biomarkers (renin, aldosterone, catecholamines) were performed at baseline, 2, and 6 h after diuretic administration. Results: No significant differences were found between supine and upright groups in total urine output, urine dilution, sodium excretion, or weight change after 6 h. There were no statistically significant differences in renin and aldosterone levels across subsequent timepoints; however, renin concentration tended to be higher in upright than in supine individuals. Interestingly, supine participants demonstrated greater urinary adrenaline concentration after furosemide administration, alone and after adjustment for urinary creatinine. Conclusions: No clinically meaningful differences were found between supine versus upright position patients with AHF, receiving neurohormonal blockade. Full article

Background/Objectives: Patients with eosinophilic chronic obstructive pulmonary disease (COPD) often remain symptomatic despite optimized triple inhaled therapy. Dupilumab is a fully human monoclonal antibody that blocks the IL-4 receptor alpha subunit, thereby inhibiting IL-4 and IL-13 signaling. Evidence from randomized trials supports dupilumab for add-on treatment of type 2-high COPD, but data referring to short-term effectiveness in clinical practice are quite limited. Methods: We conducted an observational, compassionate-use study enrolling 13 consecutive outpatients with eosinophilic COPD (blood eosinophils ≥ 300 cells/µL) receiving add-on biologic therapy with dupilumab 300 mg every two weeks. Clinical (CAT, mMRC), functional (spirometry and body plethysmography), and inflammatory parameters (blood eosinophils/basophils, fibrinogen, FeNO) were evaluated at baseline and after four weeks of treatment. Safety was monitored after injection in a clinical setting, as well as via weekly phone follow-up. Results: Participants (84.6% male; mean age 67.08 ± 11.42 years) experienced rapid and clinically meaningful improvements at four weeks. CAT score decreased from baseline 21.40 ± 6.22 to 14.00 ± 5.58 (p < 0.001) and mMRC scale from 2.90 ± 0.73 to 1.80 ± 0.63 (p < 0.0001), respectively. Pre-bronchodilator FEV₁ increased from baseline 1.35 ± 0.65 L to 1.59 ± 0.84 L (p < 0.05), and FVC from 2.36 ± 0.92 L to 2.83 ± 1.11 L (p < 0.01). A marked lung deflation was observed: indeed, residual volume declined from baseline 4.17 ± 1.98 L to 3.47 ± 2.07 L (p < 0.05), with a concomitant reduction in specific effective airway resistance (from baseline 3.15 ± 1.77 to 2.43 ± 1.44 kPa·s; p < 0.05) associated with significant increases in mid-expiratory flow (FEF₂₅₋₇₅: from baseline 0.62 ± 0.38 to 0.86 ± 0.71 L/s; p < 0.05) and peak expiratory flow (3.80 ± 1.40 to 4.48 ± 1.79 L/s; p < 0.01). Type 2 inflammatory biomarkers changed as follows: blood eosinophil count fell from baseline 390.0 ± 43.75 to 190.0 ± 65.47 cells/µL (p < 0.001); blood basophil number decreased from baseline 37.50 ± 13.89 to 26.25 ± 13.02 cells/µL (p < 0.001); plasma fibrinogen lowered from baseline 388.4 ± 54.81 to 334.9 ± 72.36 mg/dL (p < 0.01); FeNO levels dropped from baseline 23.95 ± 18.10 to 14.00 ± 2.04 ppb (p < 0.0001). Dupilumab was well tolerated, and no treatment-related serious adverse events or discontinuations were detected. Conclusions: Within an exploratory context of daily medical activity referring to eosinophilic COPD already treated with maximal inhaled therapy, we found relevant therapeutic effects of a four-week add-on treatment with dupilumab. In particular, our patients manifested rapid improvements in symptoms, airflow limitation, and lung hyperinflation, paralleled by significant decrements of type 2 inflammatory signatures. Such encouraging results were associated with a favorable short-term safety profile. However, larger and longer studies are necessary to corroborate these preliminary findings. Full article

Introduction: Radiotherapy plays a critical role in the management of head and neck squamous-cell carcinoma (HNSCC); however, the influence of overall treatment time on patient outcomes remains an area of ongoing investigation. The use of radiation, either in conjunction with concurrent chemotherapy or on its own, is crucial when treating HNSCC. Despite the longstanding hypothesis that treatment gaps may adversely affect tumor response and overall survival, there is a paucity of literature on this particular area. This study aims to bridge the knowledge gap and assess the correlation of treatment gaps on recurrences in HNSCC patients. Materials and Methodology: This retrospective study is based on an analysis of data obtained from a single institution between 2017 and 2021. Patients were selected on the basis of the presence of treatment gaps. Data were extracted from medical records and analyzed to evaluate the association between overall treatment time and various patient and treatment-related factors. Various factors thought to contribute to treatment gaps, such as age, TNM Stage, radiation dose, and use of concurrent chemotherapy, were also examined. Results: A total of 212 patients with treatment gaps were evaluated. Of these, 80 individuals experienced recurrences. It was observed that compared to distant metastases, locoregional failure was more frequent (n = 2, 4.2% vs. n = 45, 95.74%). The patients underwent both adjuvant and definitive therapy and were treated with a dose range of 60–70 Gy and concurrent cisplatin chemotherapy. It was noticed that this cohort had a range of 4–43 days of treatment gaps. Notably, 19 out of 47 patients had treatment gaps ≤ 5 days, while 28 out of 47 had gaps exceeding 5 days. It was also observed that patients with treatment gaps of >5 days had poorer quality of life and overall survival. Conclusions: This study identified that the Overall Treatment Time (OTT) had a strong statistical correlation with the development of recurrences. Further, the age of the patient, presence of neutropenia and the duration of the treatment gap were also identified to significantly correlate with the chance of developing recurrences. Full article

Silymarin—a standardized extract from the seeds of milk thistle (Silybum marianum L. Gaertn.)—is mainly used for the treatment of hepatitis and other liver diseases. In recent years, the attention of researchers has been directed to its use in dermatology and wound treatment. Despite the promising results, there are still many unresolved issues in this area. The aim of the present study is to develop and characterize hydrogel chitosan–pectin films containing silymarin as an active ingredient with potential medical application. Six variants of hydrogel films (control and silymarin-loaded) were obtained from chitosan and pectin solutions by the casting method and analyzed in terms of their physicochemical, structural, mechanical and optical properties, as well as the in vitro dissolution profile of silymarin. The highest tensile strength was measured for the chitosan-based films—23.35 ± 1.74 MPa (control) and 22.01 ± 2.67 MPa (silymarin-loaded), while the barrier properties to UV and visible light were the strongest for chitosan–pectin films with silymarin. The antioxidant potential of the films was determined by DPPH assay and it was found that the variants with silymarin have over 20 times higher antioxidant activity (from 2.020 ± 0.048 to 2.106 ± 0.190 mg TE/g) than the corresponding controls. The results showed that chitosan–pectin films with incorporated silymarin could find application as potential hydrogel dressings in the therapy of wounds and superficial burns. Full article