Search Results (2,377)

There are no data available on the effectiveness and safety of isavuconazole (ISA) for treating breakthrough invasive fungal infections (bIFIs). A retrospective and prospective cohort study was conducted between January 2020 and March 2025 in 13 centers in Argentina. Hematologic diseases (HD) and hematopoietic cell transplantation (HCT) patients who received ISA for IFI were included and followed for 12 weeks. Patients with proven and probable bIFIs and non-bIFIs were compared. One hundred and sixty-three patients were included. IFIs were classified as proven (13.5%), probable (26.9%) and possible (59.5%). Among 66 proven and probable IFIs, 53% were bIFIs, with aspergillosis and mucormycosis being the most common. Twenty-three (34.8%) patients had acute myelogenous leukemia, and 40.9% had received HCT. Forty-eight (72.7%) patients experienced neutropenia, with a median duration of 26 days (interquartile range [IQR] 16–44). Fluconazole and posaconazole were the most frequently received antifungal prophylaxis. ISA was prescribed as first-line therapy in 31 (46.9%) patients. The other 35 received ISA as a continuation therapy, mainly as a step-down therapy after liposomal amphotericin B. Four (6.1%) patients developed adverse effects, and one discontinued ISA. The 90-day overall clinical response between patients with bIFI vs. non-bIFI was 91.4% vs. 70.9% (p = 0.052). The 90-day overall and IFI-related mortality rates were, respectively, 11.4% vs. 32.3% (p = 0.068) and 5.7% vs. 9.7% (p = 0.659). The study data evidence ISA effectiveness and safety for the treatment of HD and HCT patients with and without bIFIs. Full article

Background and Clinical Significance: Granulomatosis with polyangiitis (GPA), an immune-mediated systemic small-vessel vasculitis affecting the upper/lower respiratory tracts and kidneys, frequently presents with non-specific nasal symptoms that lead to misdiagnosis. Case Presentation: We report a case of a 55-year-old female with GPA complicated by Bartter syndrome. She presented with one month of left nasal congestion, rhinorrhea, epistaxis, and headache. Initial diagnosis was acute sinusitis. Computed tomography (CT) revealed left maxillary and ethmoid sinus inflammation with bone destruction, while metagenomic next-generation sequencing (mNGS) suggested conventional bacterial infection. Postoperative pathology demonstrated chronic mucosal inflammation with lymphoid tissue hyperplasia. GPA was ultimately diagnosed based on PR3-ANCA seropositivity and chest CT findings of cavitary pulmonary nodules. Postoperatively, severe hypokalemia and hypomagnesemia secondary to Bartter syndrome emerged. Following electrolyte correction, induction therapy with glucocorticoids and cyclophosphamide was initiated. Conclusions: This case underscores that GPA’s head and neck manifestations are frequently misdiagnosed as infections or malignancies. Early diagnosis requires vigilance for GPA ‘red flags’, such as refractory nasal symptoms to conventional therapy (e.g., bloody rhinorrhea), characteristic CT findings (e.g., sinus opacification without ostiomeatal complex obstruction), and nasal endoscopy findings (e.g., ulcers/crusting). Otolaryngologists play a pivotal role in recognizing early disease onset and initiating timely treatment. Full article

Although acute kidney injury (AKI) is common among patients with coronavirus disease 2019 (COVID-19), there are only limited data on its occurrence at intensive care unit (ICU) admission. Assessing the factors associated with AKI is essential for early diagnosis and intervention. This study aims to compare the clinical and laboratory characteristics and survival outcomes of COVİD-19 patients with and without AKI at ICU admission and determine the factors associated with AKI. In this study, patients with SARS-CoV-2 infection were categorized based on the presence (AKI group) or absence (non-AKI group) of AKI. Clinical and laboratory data and outcomes were analyzed retrospectively. Of the 712 patients included in this study, 198 were assigned to the AKI group and 514 were assigned to the non-AKI group. Patients with AKI had more comorbidities and higher disease severity; higher rates of invasive mechanical ventilation, vasopressor therapy, and mortality; and longer hospital stays (p < 0.05). Our multivariate analysis identified advanced age, a high Acute Physiology and Chronic Health Evaluation II score, a high neutrophil-to-lymphocyte ratio, a low albumin level, and the presence of comorbidities as independent factors associated with AKI. In patients with COVID-19, AKI observed at ICU admission is associated with advanced age and increased disease severity. The early diagnosis and monitoring of patients may improve clinical outcomes. Full article

Background/Objectives: Alcohol-associated hepatitis (AH) is an acute inflammatory condition of alcohol-associated liver disease (ALD) with rapid progression and high mortality. The Age-Bilirubin-INR-Creatinine (ABIC) score is a static algorithm that predicts survivability in AH. The roles of alcohol drinking patterns and nutritional status in AH progression and risk of death are understudied. This study evaluates the impact of alcohol drinking patterns and nutrition on AH progression and mortality. Methods: Sixty-one adult patients diagnosed with AH were stratified by the Model for End-Stage Liver Disease (MELD) as non-severe (MELD < 20, n = 26, Gr.1) and severe (MELD ≥ 20, n = 35, Gr.2). Each group was further subdivided by ABIC: low- (<6.71), intermediate- (6.71–9), and high- (>9) risk categories. We assessed different demographics: nutrition using the Controlling Nutritional Status (CONUT) score; lifetime drinking history (LTDH); recent alcohol use (AUDIT); laboratory measures (complete metabolic panel, complete blood count, and coagulation), and clinical measures (Maddrey DF, Child–Turcotte–Pugh, and Lille). Results: All patients showed a significant and positive correlation between ABIC and LTDH (r = 0.538, p = 0.004), particularly in Gr.2 (r = 0.554, p = 0.011). The low-risk Gr.2 exhibited the highest AST:ALTs. AST:ALTs were significantly associated with LTDH, AUDIT, and CONUT (R² = 0.539, p = 0.031). In all AH patients with intermediate mortality risk, AST:ALTs were strongly linked to CONUT and LTDH (R² = 0.657, p = 0.017). Conclusions: Severe AH demonstrates rapid liver injury progression even when the mortality risk is low. Chronic and recent heavy alcohol consumption and poor nutrition adversely impact AH severity and mortality risk. Alcohol intake and nutritional assessments in routine clinicals could identify high-risk patients, thereby improving treatment and a favorable prognosis. Full article

Background: Plaque erosion (PE) ranks as the second most prevalent pathology associated with acute coronary events, following plaque rupture. PE is characterized by endothelial denudation and the development of neutrophil extracellular traps. Specific clinical and laboratory predictors were shown to be associated with PE in patients with acute coronary syndrome. The aim of this study was to evaluate the clinical and laboratory results, as well as the outcomes of ACS patients with a high likelihood of PE. Methods: A total of 696 ACS patients were categorized into the suspected PE group and the less likely PE group based on the five validated predictors of PE. Baseline clinical characteristics and laboratory evaluations were analyzed between the two groups. Major adverse cardiovascular events were compared between the two groups at 20 months. Results: The group suspected of PE comprised 41% of patients, whereas the group with a lower likelihood of PE constituted 59%. The suspected PE group exhibited a greater incidence of current smokers and a higher BMI. Both CRP and fibrinogen levels were decreased; the incidence of one coronary vessel disease was elevated. The suspected PE group exhibited a markedly reduced incidence of MACEs at 20 months (7.4% compared to 28.8%, p = 0.0001). The recurrence of non-fatal coronary events tended to occur later in the suspected PE group (15 months (6–20) compared to 9 months (6–13), p = 0.062). A reduced coronary plaque burden and a low level of systemic inflammation characterized the distinctive features of the suspected PE cohort. Conclusions: The suspected PE group exhibited a more favorable prognosis at the 20-month follow-up, characterized by a considerably reduced mortality rate from all causes, whereas non-fatal coronary events tended to manifest at a later time. Full article

Background: Cardiopulmonary resuscitation (CPR) is a highly effort-intensive intervention and, in cases of cardiac arrest, the ability to predict a return of spontaneous circulation (ROSC) is of great importance for the efficient use of resources. This real-time assessment approach offers a practical advantage by increasing the applicability of prognostic models during acute resuscitation in an emergency department. Method: In this study, the data of patients who underwent CPR in the emergency department of a tertiary care hospital between 1 June 2019 and 1 June 2024 and underwent cardiopulmonary resuscitation were retrospectively analyzed. The patients’ demographics, comorbidities, CPR characteristics, and laboratory findings were evaluated using logistic regression and ROC curve analysis to identify the predictors of ROSC. Result: Our study revealed that cases with shockable rhythms and a shorter CPR duration were more likely to achieve ROSC. Elevated levels of albumin, creatine kinase, glucose, hemoglobin, and white blood cells were significantly associated with ROSC, while higher levels of creatinine, base excess, and eosinophils were more common in non-survivors. Atrial fibrillation and neurodegenerative disease were associated with lower ROSC rates. Conclusions: Although the criteria for the termination of cardiac arrest resuscitation are not definitive, certain patient characteristics and laboratory findings may guide the prediction of ROSC or the identification of cases requiring prolonged CPR. The integration of these real-time predictors into clinical algorithms may support decision making in crowded emergency departments. Full article

Background/Objectives: Gout, a complex metabolic disorder of increasing global incidence, remains incompletely understood in its pathogenesis. Current diagnostic approaches exhibit significant limitations, including insufficient specificity and the requirement for invasive joint aspiration, highlighting the need for non-invasive, sensitive biomarkers for early detection. Methods: Urine metabolites were extracted from 28 healthy controls, 13 asymptomatic hyperuricemia (HUA) patients, and 29 acute gouty arthritis (AGA) patients. The extracted metabolites were analyzed by UHPLC-MS/MS for untargeted metabolomics. Differential metabolites were screened by partial least squares discriminant analysis (PLS-DA) and volcano plot analysis. Pathway analysis determined the core disorder pathway of gout progression. Results: A total of 278 differential metabolites associated with gout progression were identified. The most pronounced metabolic alterations were observed between the AGA and control groups, indicative of substantial metabolic reprogramming during disease transition. Metabolic pathway analysis revealed four significantly dysregulated pathways: histidine metabolism, nicotinate and nicotinamide metabolism, phenylalanine metabolism, and tyrosine metabolism. Receiver operating characteristic (ROC) curve analysis revealed that three urine markers with high diagnostic efficacy—oxoamide, 3-methylindole, and palmitic acid—exhibited progressive alterations across the disease continuum. Conclusions: This metabolomics study identified core regulatory metabolites and newly discovered metabolic pathways underlying gout pathogenesis, along with novel urinary biomarkers capable of predicting HUA-to-AGA progression. The aberrant levels of key metabolites in the disordered pathway implicate neuroimmune dysregulation, energy metabolism disruption, and oxidative stress in gout pathogenesis. These findings provide new foundations and strategies for the daily monitoring and prevention of gout. Full article

Interleukin-24 (IL-24) is a cytokine known for its role in immune regulation and apoptosis, with potential implications in viral infections like COVID-19. This study aimed to investigate the association between IL-24 serum levels and the severity of COVID-19 disease. In this prospective bi-center cross-sectional study, we enrolled 41 COVID-19 patients from two hospitals in Germany. Serial blood samples were collected from a subset of patients, resulting in 88 total blood samples. Patients were categorized into critical, severe, moderate, and mild disease groups based on WHO criteria. IL-24 serum levels were measured during the acute or convalescent phase using an ELISA assay. Inflammatory markers, and kidney and liver function parameters were also evaluated. Statistical analysis included non-parametric tests and correlation analysis. Elevated IL-24 serum levels were observed in ambulant patients (mild disease), compared to hospitalized patients (critical, severe, moderate disease, p < 0.05). IL-24 levels were also significantly higher in patients without oxygenation disorder compared to those with oxygenation therapy (p < 0.05). A negative correlation was found between IL-24 levels and markers of inflammation and liver/kidney function. Elevated IL-24 serum levels were associated with milder COVID-19 courses, suggesting a protective role in modulating immune responses and promoting antiviral apoptosis. Conversely, reduced IL-24 in severe cases may reflect impaired immune regulation, highlighting its potential as a biomarker and therapeutic target. Full article

Acute aortic syndromes (AAS) include a spectrum of life-threatening conditions that pose considerable diagnostic challenges, particularly in emergency care settings. Clinical scores and circulating biomarkers have become essential in improving diagnostic accuracy, risk stratification, and guiding clinical decision-making. Tools such as the Aortic Dissection Detection Risk Score (ADD-RS) and the AORTAs score offer structured methods for identifying patients at elevated risk; however, their diagnostic performance can be further enhanced through integration with biomarker testing and imaging modalities. Biomarkers including D-dimer, NT-proBNP, cardiac troponins, and novel candidates such as soluble ST2 (sST2) and matrix metalloproteinase-8 and 9 (MMP-8, MMP-9), have demonstrated potential in refining diagnostic and prognostic assessments with an outstanding sensibility. ADAMTS-1 and ADAMTS-4 appear to have the best diagnostic accuracy, whereas certain non-coding DNAs (miR-15a) achieve an exceptionally high negative predictive value. These biomarkers reflect key underlying mechanisms such as inflammation, oxidative stress, and vascular injury, offering valuable insights into disease severity and progression. However, limitations related to specificity, inter-cohort variability, and assay standardization currently hinder their widespread clinical adoption. Further validation through large-scale, multi-center studies is essential to establish their role within integrated diagnostic pathways. Full article

Enteroviruses, a diverse genus within the Picornaviridae family, are responsible for a wide range of human infections, including hand, foot, and mouth disease, respiratory disease, aseptic meningitis, encephalitis, myocarditis, and acute flaccid paralysis. Despite their substantial global health burden and the frequent emergence of outbreaks, no specific antiviral therapies are currently approved for clinical use against non-polio enteroviruses. This review provides a comprehensive overview of the current landscape of antiviral strategies targeting enteroviruses, including direct-acting antivirals such as capsid binders, protease inhibitors, and viral RNA polymerase inhibitors. We also examine the potential of host-targeting agents that interfere with virus–host interactions essential for replication. Emerging strategies such as immunotherapeutic approaches, RNA interference, CRISPR-based antivirals, and peptide-based antivirals are also explored. Furthermore, we address key challenges, including viral diversity, drug resistance, and limitations in preclinical models. By highlighting recent advances and ongoing efforts in antiviral development, this review aims to guide future research and accelerate the discovery of effective therapies against enterovirus infections. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) share overlapping pathophysiological mechanisms, including insulin resistance and chronic inflammation. Recent evidence suggests that Orosomucoid-2 (ORM2), an acute-phase immunomodulatory protein, may play a role in metabolic regulation; however, its specific involvement in MAFLD remains unclear. This study examined the association between circulating ORM2 levels and the severity of hepatic steatosis, insulin resistance, and T2DM in a cohort of 449 adults. MAFLD was assessed using FibroScan^® with hepatic steatosis categorized by Controlled Attenuation Parameter (CAP) scores, while plasma ORM2 levels were measured via ELISA. Statistical analyses using Spearman correlation and multiple logistic regression revealed that elevated ORM2 levels were significantly correlated with greater hepatic steatosis, insulin resistance, triglycerides, ALT, and hip circumference (p < 0.001). Individuals with severe steatosis (CAP > 290 dB/m) had markedly higher ORM2 levels (312.3 ng/mL) compared to those with normal CAP scores (210.4 ng/mL; p < 0.001). ORM2 was identified as an independent predictor of steatosis severity and after adjusting for several metabolic variables (AOR = 1.005; 95% CI: 1.002–1.007). ROC analysis incorporating ORM2 and metabolic variables demonstrated strong predictive capability for MAFLD (AUC = 0.864, 95% CI: 0.825–0.902). These findings support ORM2 as a promising non-invasive diagnosis for MAFLD, involving only blood sampling without direct invasion of the liver and associated metabolic dysfunction. Full article

Acute myeloid leukemia (AML) proliferation is significantly influenced by the interactions between leukemia blasts and the bone marrow (BM) microenvironment. Specifically, bone marrow mesenchymal stem cells (BMSCs) derived from AML patients (AML-MSCs) are known to support leukemia growth and facilitate disease progression. Studies have demonstrated that the transfer of mitochondria from MSCs to AML blasts not only aids in disease progression but also contributes to chemotherapy resistance. Furthermore, BM stromal cells can trigger a metabolic shift in malignant cells from mitochondrial respiration to glycolysis, which enhances both growth and chemo-resistance. This study focuses on identifying transcriptional and metabolic alterations in AML-MSCs to uncover potential targeted therapies for AML. We employed RNA sequencing and microarray analysis on MSCs cocultured with leukemic cells (MLL-AF9) and on MSCs isolated from both non-leukemic and MLL-AF9 leukemic mice. The Gene Set Enrichment Analysis (GSEA) indicated a significant downregulation of gene sets associated with oxidative phosphorylation and glycolysis in AML-MSCs. Furthermore, coculture of MSCs from wild-type mice (WT-MSCs) and a healthy donor individual (HD-MSCs) with AML cells demonstrated reduced oxidative phosphorylation and glycolysis. These metabolic changes were consistent in AML-MSCs derived from both leukemic mice and patients. Our results indicate that AML cells diminish the metabolic capacity of MSCs, specifically targeting oxidative phosphorylation and glycolysis. These findings suggest potential metabolic vulnerabilities that could be exploited to develop more effective therapeutic strategies for AML. Full article

Syphilis is a systemic infection with a broad spectrum of ocular involvement that can affect every segment of the eye. Clinical presentations range from interstitial keratitis, conjunctivitis, episcleritis, and scleritis to anterior, intermediate, and posterior uveitis; acute syphilitic posterior placoid chorioretinitis; retinitis; retinal vasculitis; neuroretinitis; optic neuritis; exudative retinal detachment; and optic nerve dysfunction. These manifestations may occur at any stage of infection and are frequently nonspecific, contributing to diagnostic delays. Diagnosis requires a high index of suspicion and is established by combined non-treponemal and treponemal serologic testing, with cerebrospinal fluid analysis when neurosyphilis is suspected. Multimodal imaging, including optical coherence tomography, fluorescein angiography, fundus autofluorescence, and visual field testing, enhances the detection of subclinical and atypical diseases. Management mandates prompt intravenous penicillin G, with adjunctive corticosteroids to mitigate Jarisch–Herxheimer reactions and control inflammation; ceftriaxone or doxycycline serve as alternatives for penicillin-allergic patients. Long-term follow-up with serial serologies and neurologic evaluation is essential to detect relapse or progression to neurosyphilis. Despite effective therapy, diagnostic delays contribute to irreversible visual loss in a significant proportion of cases. This review integrates current knowledge on ocular syphilis, emphasizing its varied presentations and the importance of early recognition to prevent vision-threatening complications, and calls for multidisciplinary, mechanism-based research to optimize outcomes. We conducted a literature search in Pubmed and Embase for articles published between 2000 and 2025, using the terms “ocular syphilis,” “syphilitic uveitis,” and “neurosyphilis,” with a focus on epidemiology, clinical features, diagnostics, therapeutics, and co-infections. Full article

Background: Acute SARS-CoV-2 infection may induce cardiac arrhythmias associated with viral myocarditis, which typically disappear in the convalescent phase after healing of the myocardial inflammation. Methods: We report the case of a 37-year-old woman with a childhood history of atrial septal defect repair and stable normofrequent atrial rhythm, who presented two months post-COVID-19 with palpitations and dizziness. Diagnostic evaluation included cardiac magnetic resonance imaging (CMR), 24 h Holter electrocardiogram (ECG) monitoring, and laboratory assessments over a 3-year period. Results: CMR suggested subacute myocarditis, and Holter ECG revealed multiple discernible complex cardiac arrhythmias including atrial bradycardia, intermittent junctional rhythm (JR), atrial fibrillation (AF), and non-sustained ventricular tachycardia. Laboratory results showed a moderate but transient increase in lactate dehydrogenase, persistently mildly elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP), and immunoglobulin A (IgA), with all other cardiac, inflammatory, immunologic, and organ function parameters remaining normal. In spite of chaotic cardiac rhythm with alternating JR, AF, and atrial normofrequent rhythm with frequent blocked supraventricular beats and increasing atrioventricular conduction time, no therapeutic intervention was necessary during follow-up, and a conservative treatment approach was agreed with the patient. Two years post-COVID-19 infection, the patient returned to a normofrequent atrial rhythm with a markedly prolonged PQ time (500 ms) and a different P wave morphology compared to pre-COVID, without other rhythm disturbances. Conclusions: This case demonstrates a rare pattern of post-viral arrhythmias first emerging in the convalescent phase and resolving spontaneously after two years. It underscores the need for long-term rhythm surveillance following COVID-19, even in patients with prior structural heart disease and a stable baseline rhythm. Full article

Background/Objectives: Metabolic (dysfunction)-associated steatotic liver disease (MASLD), the hepatic consequence of metabolic syndrome, affects 30% of the global population. Studies in animals and humans investigating the effect of fructose on MASLD present conflicting findings, while in vitro methods often fail to add meaningful evidence due to acute exposures (<72 h) and non-physiological concentrations. This study aimed to determine the effect of fructose on triglyceride (TG) accumulation in HepG2 cells following acute and chronic exposures and assess its effect on the expression of genes related to de novo lipogenesis (DNL). Methods: TG concentration was measured after 48 h in response to fructose (20 mM) or glucose (20 mM), with or without a fatty acid mixture (oleic acid/palmitic acid 110 µM/55 µM), in low (5.5 mM)- and high (25.5 mM)-glucose media. To model chronic exposure, cells were maintained in fructose, glucose, or fatty acids for 28 days and the TG concentration was determined every 7 days. The effect of fructose on DNL regulators (SREBPF1, NR1H3, FASN, and ACACA) was determined using qPCR. Results: Neither fructose nor glucose, with or without fatty acids, changed the TG levels in cells at 48 h and the media glucose concentration had no effect on this result. Similarly, fructose did not increase TG levels after 28 days. While fructose and glucose did not affect key DNL genes at 6 h, the fatty acid mixture reduced FASN by 41%. Conclusions: This study shows that fructose did not significantly impact TG synthesis or DNL gene expression in the HepG2 cell model. Future studies should consider using primary human hepatocytes or more complex in vitro models. Full article