Search Results (13,974)

Background and Clinical Significance: Membranoproliferative glomerulonephritis (MPGN) is a rare and heterogeneous pattern of immune-mediated glomerular injury, often associated with infections, autoimmune disorders, or monoclonal gammopathies. Idiopathic cases remain a diagnostic challenge and frequently require empirical immunosuppressive treatment. There is increasing interest in environmental triggers that may activate the immune system in genetically or immunologically predisposed individuals. We report an unusual case of idiopathic immune complex-mediated MPGN with a relapsing course potentially associated with vaccine-induced immune reactivation. Case Presentation: A 35-year-old male with no significant medical history aside from untreated dyslipidemia and active smoking presented with a hypertensive emergency and acute kidney injury (AKI). Laboratory investigations revealed nephrotic-range proteinuria, microscopic hematuria, and reduced estimated glomerular filtration rate (eGFR). Kidney biopsy demonstrated type I immune complex-mediated MPGN with a diffuse endocapillary proliferative pattern and granular subendothelial deposits (IgG+++, C3+++, C1q++). An extensive work-up ruled out secondary causes, supporting a diagnosis of idiopathic MPGN. Immunosuppressive therapy with corticosteroids and mycophenolate mofetil led to a partial clinical response. However, after receiving multiple vaccinations, the patient experienced clinical deterioration. A second biopsy revealed persistent proliferative changes and new deposits of IgM++, C4d++, and both kappa and lambda light chains. This prompted a reintroduction of immunosuppressive therapy, which resulted in subsequent clinical improvement. Conclusions: This case supports the hypothesis that vaccine-induced immune reactivation may serve as a potential trigger for disease relapse in idiopathic MPGN. Clinicians should remain alert to environmental stimuli that may influence disease activity in immune-mediated glomerulopathies. Further research is needed to elucidate the underlying immunopathogenic mechanisms. Full article

Deer tick virus (DTV) is a Tick-Borne Orthoflavivirus endemic to the United States, transmitted to humans through bites from the deer tick, Ixodes scapularis, which is also the primary vector of Borrelia burgdorferi s.l., the causative agent of Lyme disease. Human infection with DTV can result in acute febrile illness followed by central nervous system complications, such as encephalitis and meningoencephalitis. Currently, there are mouse models established for investigating the pathogenesis and clinical outcomes of DTV that mimic human infections, but the strains of mice utilized are refractory to infection with B. burgdorferi s.l. Here, we describe the pathogenesis and clinical outcomes of DTV infection in C3H/HeJ mice. Neurological clinical signs, mortality, and weight loss were observed in all DTV-infected mice during the investigation. Infected animals demonstrated consistent viral infection in their organs. Additionally, neuropathology of brain sections indicated the presence of meningoencephalitis throughout the brain. This data, along with the clinical outcomes for the mice, indicates successful infection and showcases the neuroinvasive nature of the virus. This is the first study to identify C3H/HeJ mice as an appropriate model for DTV infection. As C3H/HeJ mice are already an established model for B. burgdorferi s.l. infection, this model could serve as an ideal system for investigating disease progression and pathogenesis of co-infections. Full article

Background: Chemical eye burns are a serious ophthalmic emergency that can lead to permanent vision loss in severe cases. This study aims to evaluate structural changes in the posterior segment of the eye in individuals who have experienced chemical burns. Methods: The study included 64 eyes from 54 patients with chemical burns (chemical burn group) and 87 healthy eyes from 87 subjects (control group), matched by age and sex. Patients had confirmed burns with limbal ischemia, no glaucoma, normal intraocular pressure, and no major ocular or systemic diseases. Burned eyes were examined during the acute phase and again at 3 months, with some followed up at 6 months if significant retinal asymmetry was detected. Retinal nerve fiber layer (RNFL) thickness was assessed in four quadrants, and ganglion cell complex (GCL++) thickness was analyzed using automated segmentation of optical coherence tomography (OCT) maps. Results: This study compared measurements between the burn group, the control group, and timepoints. OCT analysis revealed no significant difference in total RNFL thickness between burn patients and controls (mean difference: −1.14 µm, 95% CI: −3.92 to 1.64). Similarly, GCL++ thickness did not differ significantly between groups (mean difference: −0.97 µm, 95% CI: −3.31 to 1.37). At 6-month follow-up, a non-significant decline in both RNFL and GCL++ thicknesses was observed. Logistic regression identified higher Dua grade as an independent predictor of RNFL thinning (OR: 4.816, 95% CI: 1.103–21.030; p = 0.037). Patients with severe ocular chemical burns (Dua grade ≥ 3) demonstrated reduced RNFL thickness in all quadrants compared to healthy controls. The most pronounced reductions were observed in the nasal and superior quadrants (p = 0.007 and p = 0.069, respectively); however, after applying Bonferroni correction for multiple comparisons, only the difference in the nasal quadrant remained statistically significant (adjusted p = 0.035). Conclusions: Although overall RNFL and GCL++ thicknesses did not differ significantly between burn patients and healthy controls, patients with severe ocular chemical burns (Dua grade ≥ 3) showed a significant reduction in RNFL thickness, in the nasal quadrant. Higher Dua grade was identified as an independent predictor of RNFL thinning. These findings suggest a potential association between burn severity and posterior segment changes, highlighting the need for further longitudinal studies with larger cohorts. Full article

Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders. Methods: This prospective single-center study included 33 adult patients with R/R AML treated with VEN plus either azacitidine (AZA) or decitabine (DEC) from 2018 to 2021. The primary endpoint was the composite complete remission (cCR) rate and the rate of early and late response, respectively, occurring within two cycles of therapy or later; secondary endpoints included overall survival (OS), relapse-free survival (RFS), time to relapse (TTR), and safety. Results: The cCR was 58%, with complete remission (CR) or CR with incomplete recovery (CRi) achieved in 52% of patients. Median OS was 9 months. No significant differences in OS or TTR were observed between early (≤2 cycles) and late (>2 cycles) responders. Eight responders (42%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), with comparable transplant rates in both groups of responders. Toxicity was manageable. Grade 3–4 neutropenia occurred in all patients, and febrile neutropenia occurred in 44% of patients. An Eastern Cooperative Oncology Group (ECOG) score >2 was associated with inferior response and shorter treatment duration. Conclusions: HMA-VEN therapy is effective and safe in R/R AML, including for patients with delayed responses. The absence of a prognostic disadvantage for late responders supports flexible treatment schedules and suggests that the continuation of therapy may be beneficial even without early blast clearance. Tailored approaches based on performance status and comorbidities are warranted, and future studies should incorporate minimal residual disease (MRD)-based monitoring to refine response assessment. Full article

Background/Objectives: Iron deficiency without anemia (IDWA) is common among female patients with chronic kidney disease (CKD), yet the clinical implications of iron therapy in this population remain uncertain. While iron supplementation is frequently used in anemic CKD patients, evidence regarding its outcomes in non-anemic, iron-deficient individuals is limited and conflicting. Methods: This retrospective cohort study utilized the multi-institutional TriNetX database to examine the 5-year outcomes of iron therapy in adult women with stage 3 CKD, normal hemoglobin (≥12 g/dL), normal mean corpuscular volume (MCV), and low serum ferritin (<100 ng/mL). Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), pneumonia, progression to advanced CKD (estimated glomerular filtration rate ≤30 mL/min/1.73 m²), and gastrointestinal (GI) bleeding. Results: We identified 53,769 eligible non-anemic patients with stage 3 CKD, low serum ferritin levels, and normal MCV. Propensity score matching (1:1) was conducted on demographic variables to compare iron-treated (n = 6638) and untreated (n = 6638) cohorts. Over the 5-year follow-up, iron therapy in non-anemic females with stage 3 CKD, low ferritin levels, and iron supplementation was significantly associated with increased risks of MACE, AKI, pneumonia, CKD progression, and GI bleeding (log-rank p < 0.0001). No significant difference in all-cause mortality was observed. Data on transferrin saturation and the dosage of iron supplementation were unavailable. Conclusions: In non-anemic women with stage 3 CKD and low ferritin levels, iron supplementation was linked to increased MACE, renal, and pneumonia risks without evident survival benefits. These findings suggest that iron therapy in this group of patients may not confer cardiovascular benefit and may pose risks. Full article

African swine fever (ASF) needs to be controlled, and prevention of the spread of African swine fever virus (ASFV) is dependent on enhanced surveillance and early disease detection. Commercial swine operations, especially in North America, Europe, and Asia, are characterized by comparatively large numbers of pigs, and sampling individual pigs, which represents the main strategy for current ASF surveillance, can be both costly and labor intensive. A study performed in Ghana was designed to estimate the diagnostic sensitivity of pen-based aggregate oral fluid testing for ASFV in infected pigs in a pen of 30 animals and to evaluate its utility as a tool to support surveillance of ASF in the US. This study was performed in three phases: (i) virus (Ghana ASFV24) amplification in a target host species to generate the challenge inoculum; (ii) titration of the inoculum (10% spleen homogenate) in target host species to determine the minimum dose inducing acute ASF in pigs with survival up to 5–6 days post-inoculation (dpi); and (iii) the main study, involving 186 pigs, consisting of 6 replicates of 30 pigs per pen and one seeder pig inoculated with wildtype ASFV (highly virulent genotype II) per pen. Daily sampling of aggregate oral fluids, uncoagulated blood, oropharyngeal swabs, fecal and water nipple swabs, and recording of rectal temperatures and clinical observations was carried out. The seeder pigs were each inoculated intramuscularly with 0.5 mL of the 10% spleen homogenate, which induced the desired clinical course of ASF in the pigs, with survival of up to 6 dpi. ASFV DNA was detected in the seeder pigs as early as 1 dpi and 2 dpi in the blood and oropharyngeal swabs, respectively. Transmission of ASFV from the seeder pigs to the contact pig population was detected via positive amplification of ASFV DNA in aggregate oral fluid samples at 3 days post-contact (dpc) in 4 out of 6 pens, and in all 6 pens, at 4 dpc. Testing of oropharyngeal swabs and blood samples from individual pigs revealed a variable number of ASFV-positive pigs between 3 and 5 dpc, with detection of 100% positivity between 6 and 18 dpc, the study endpoint. These findings demonstrate the potential utility of aggregate oral fluid sampling for sensitive and early detection of ASFV incursion into naïve swine herds. It also demonstrates that testing of environmental samples from the premises could further enhance overall ASF early detection and surveillance strategies. Full article

In this paper we aimed to compare seasonality, clinical characteristics, and outcomes of Influenza A and COVID-19 in the context of influenza reemergence and ongoing Omicron circulation. We performed a retrospective comparative analysis at the Teaching Hospital of Infectious Diseases in Cluj-Napoca, Romania. We included adult patients hospitalized with Influenza A or COVID-19 between 1 November 2022 and 31 March 2024. Data were collected on demographics, clinical presentation, complications, and in-hospital mortality. We included 899 COVID-19 and 423 Influenza A patients. The median age was 74 years for COVID-19 and 65 for Influenza A (p < 0.001). The age-adjusted Charlson comorbidity index was higher in COVID-19 patients (5 vs. 3, p < 0.001). Despite this age gap, acute respiratory failure was more common in Influenza A (62.8% vs. 55.7%, p = 0.014), but ventilation rates did not differ significantly. Multivariate models showed Influenza A was associated with increased risk of intensive-care unit (ICU) admission or ventilation, whereas older COVID-19 patients had higher in-hospital mortality (5.67% vs. 3.3%, p = 0.064). Omicron COVID-19 disproportionately affected older patients with comorbidities, contributing to higher in-hospital mortality. However, Influenza A remained a significant driver of respiratory failure and ICU admission, underscoring the importance of preventive measures in high-risk groups. Full article

Background: In high-risk and frail patients with multivessel coronary artery disease (MV CAD), guidelines indicated complete revascularization with or without the use of cardiopulmonary bypass (CPB) bears a high morbidity and mortality risk. In cases where catheter interventions were deemed unsuitable and conventional coronary artery bypass grafting (CABG) posed an unacceptable perioperative risk, patients were scheduled for minimally invasive direct coronary artery bypass (MIDCAB) grafting or minimally invasive multivessel coronary artery bypass grafting (MICS-CABG). We called this approach “palliative revascularization.” This study assesses the safety and impact of palliative revascularization on clinical outcomes and overall survival. Methods: A consecutive series of 57 patients undergoing MIDCAB or MICS-CABG as a palliative surgery between 2008 and 2018 was included. The decision for palliative surgery was met in heart team after carefully assessing each case. The patients underwent single or double-vessel revascularization using the left internal thoracic artery and rarely radial artery/saphenous vein segments, both endoscopically harvested. Inpatient data could be completed for all 57 patients. The mean follow-up interval was 4.2 ± 3.7 years, with a follow-up rate of 91.2%. Results: Mean patient age was 79.7 ± 7.4 years. Overall, 46 patients (80.7%) were male, 26 (45.6%) had a history of atrial fibrillation and 25 (43.9%) of chronic kidney disease. In total, 13 patients exhibited a moderate EuroSCORE II, while 27 were classified as high risk, with a EuroSCORE II exceeding 5%. Additionally, 40 patients (70.2%) presented with three-vessel disease, 17 (29.8%) suffered an acute myocardial infarction within three weeks prior to surgery and 50.9% presented an impaired ejection fraction. There were 48 MIDCAB and nine MICS CABG with no conversions either to sternotomy or to CPB. Eight cases were planned as hybrid procedures and only 15 patients (26.3%) were completely revascularized. During the first 30 days, four patients (7%) died. A myocardial infarction occurred in only one case, no patient necessitated immediate reoperation. The one-, three- and five-year survival rates were 83%, 67% and 61%, respectively. Conclusions: MIDCAB and MICS CABG can be successfully conducted as less invasive palliative surgery in high-risk multimorbid patients with MV CAD. The early and mid-term results were better than predicted. A higher rate of hybrid procedures could improve long-term outcome in selected cases. Full article

Acute kidney injury (AKI) is a serious clinical condition that is linked to markedly higher rates of morbidity and mortality in cirrhosis patients. Its diagnosis is challenging due to overlapping clinical and laboratory features among causes such as hepatorenal syndrome (HRS), acute tubular injury (ATI), and prerenal hypovolemia. In order to address the distinct pathophysiology and clinical context of cirrhosis, the definitions and classification of AKI have changed over time, moving from RIFLE and AKIN to KDIGO and ICA-AKI. Because cirrhosis patients have altered muscle mass and fluid retention, traditional markers like serum creatinine (sCr) and urine output have significant limitations. Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and cystatin C (CysC) are some of the new biomarkers that have shown promise in early AKI detection and in differentiating structural from functional kidney injury. NGAL and KIM-1 are sensitive indicators of tubular damage with potential prognostic implications. IL-18 reflects inflammatory injury, and CysC offers a more reliable measure of glomerular filtration. Incorporating these markers may improve early diagnosis, risk stratification, and treatment decisions, representing a key direction for future research in managing AKI in cirrhosis. Full article

Antibody titer testing can be useful in controlling successful puppy immunization and can reduce unnecessary vaccinations in adult dogs. We evaluated three commercially available point-of-care tests (POCTs) for detecting antibodies against canine parvovirus (CPV-2), canine distemper virus (CDV) and canine adenovirus (CAV-1 and/or -2), comparing them to the reference virus neutralization (VN) assay. Sera from 200 client-owned dogs (13 healthy, 63 chronically diseased, 124 acute) and 60 specific pathogen-free (SPF) dogs, including 20 sera with maternally derived antibodies (MDA), were tested. All three POCTs demonstrated high sensitivity (79.0–100%) and specificity (97.8–100%) for CPV-2. In contrast, specificity for CDV and CAV was lower with POCT-1 (43.5% and 55.3%) and POCT-2 (42.4% and 79.2%), despite high sensitivity (CDV in both POCTs 98.7%; CAV POCT-1: 99.4%, POCT-2: 90.8%). POCT-3, by comparison, showed high specificity (CDV: 94.1%; CAV: 84.4%) but very low sensitivity (CDV: 17.4%; CAV: 33.1%). Only POCT-1 for CPV-2 detected MDA reliably, whereas the other two POCTs, and POCT-1 for CDV and CAV, did not. When compared to VN, the agreement in vaccination recommendations was 82% for POCT-1 and POCT-2, and 62% for POCT-3. In conclusion, all three POCTs reliably detected antibodies against CPV-2, including MDA with POCT-1. However, the lower specificity for CDV and CAV antibody detection in POCT-1 and POCT-2 raises concerns about misclassifying unprotected dogs as immune, while false-negatives with POCT-3 could lead to unnecessary vaccinations. Further optimization of all three POCTs for CDV and CAV is recommended. Full article

In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), antiplatelet therapy is the cornerstone of treatment for secondary prevention. Although dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y₁₂ inhibitor is the current standard of care, being, respectively, recommended for 6 and 12 months in patients with chronic and acute coronary syndrome without a need for oral anticoagulation, the continuous improvement in PCI technology and pharmacology have significantly reduced the need for long-term DAPT. Mounting evidence supports the administration of P2Y₁₂ inhibitor monotherapy, particularly ticagrelor, after a short period of DAPT following PCI as a strategy to reduce bleeding without a trade-off in ischemic events compared to standard DAPT. In addition, there is a growing literature supporting P2Y₁₂ inhibitor monotherapy also for long-term secondary prevention of ischemic events. However, the data to this extent are not as robust as compared to the first-year post-PCI period, with aspirin monotherapy still remaining the mainstay of treatment for most patients. This review aims to summarize the rationale for long-term antiplatelet therapy, the pharmacology of current antiplatelet drugs tested for long-term administration as monotherapy, and current evidence on the available comparisons between different long-term antiplatelet monotherapies in patients with CAD. Full article

Ischemic stroke is a primary cause of cerebrovascular diseases and continues to be one of the leading causes of death and disability among patients worldwide. Pathological processes caused by vascular damage due to stroke occur in a time-dependent manner and are classified into three categories: acute, subacute, and chronic. Current treatments for ischemic stroke are limited to effectiveness in the early stages. In this study, we investigated the therapeutic effect of an oriental medicine, Gosha-jinki-gan (TJ107), on improving chronic ischemic stroke using the mouse model with middle cerebral artery occlusion (MCAO). The changes in the intracerebral inflammatory response (macrophages (F4/80), TLR2•4, IL-23, IL-17, TNF-α, and IL-1β) were examined using real-time RT-PCR. The MCAO mice showed the increased expression of glial fibrillary acidic protein (GFAP) and of F4/80, TLR2, TLR4, IL-1β, TNF-α, and IL-17 in the brain tissue from the MCAO region. This suggests that they contribute to the expansion of the ischemic stroke infarct area and to the worsening of the neurological symptoms of the MCAO mice in the chronic phase. On the other hand, the administration of TJ107 was proven to reduce the infarct area, with decreased GFAP expression, suppressed macrophage infiltration in the brain, and reduced TNF-α, IL-1β, and IL-17 production compared with the MCAO mice. This study first demonstrated Gosha-jinki-gan’s therapeutic effects on the chronic ischemic stroke. Full article

Blood-based biomarkers allow monitoring of an individual’s health status and provide insights into metabolic and inflammatory processes in conditions like obesity, cardiovascular, and liver diseases. However, selecting suitable biomarkers and optimizing analytical assays presents challenges, is time-consuming and laborious. Moreover, knowledge of potential sex differences remains incomplete as research is often carried out in men. This study aims at enabling researchers to make informed choices on the type of biomarkers, analytical assays, and dilutions being used. More specifically, we analyzed plasma concentrations of >90 biomarkers using commonly available ELISA or electrochemiluminescence-based multiplex methods, comparing normal weight (BMI < 25; n = 40) with obese (BMI > 30; n = 40) adult blood donors of comparable age. To help choose optimal biomarker sets, we grouped frequently employed biomarkers into biological categories (e.g., adipokines, acute-phase proteins, complement factors, cytokines, myokines, iron metabolism, vascular inflammation), first comparing normal-weight with obese persons, and thereafter exploratively comparing women and men within each BMI group. Many biomarkers linked to chronic inflammation and dysmetabolism were elevated in persons with obesity, including several adipokines, interleukins, chemokines, acute-phase proteins, complement factors, and oxidized LDL. Further exploration suggests sex disparities in biomarker levels within both normal-weight and obese groups. This comprehensive dataset of biomarkers across diverse biological domains constitutes a reference resource that may provide valuable guidance for researchers in selecting appropriate biomarkers and analytical assays for own studies. Moreover, the dataset highlights the importance of taking possible sex differences into account. Full article

Background: Quality care of individuals with sickle cell disease (SCD) is dependent upon education of the providers on their care team. Previous studies demonstrate lack of resident and provider comfort regarding care of patients with SCD, yet none have assessed these in medical students. Objective: This study aims to evaluate the adequacy of the research instrument for measuring medical students’ knowledge, confidence, and comfort regarding SCD and related complications prior to wider distribution. Methods: A self-assessment survey was distributed to medical students at two universities to evaluate their knowledge, confidence, and comfort in general SCD topics, in all clinical settings, and regarding common complications. Results: Of the 98 responses, knowledge (p < 0.001) and confidence (p = 0.02) were significantly different between topics, including epidemiology and genetics, pathophysiology, and treatment options. For “treatment options”, there were significant differences in knowledge (p = 0.02) and confidence (p = 0.02) between medical students at different levels of training. Students felt least knowledgeable and least comfortable with care of pregnant women and most knowledgeable and most comfortable with acute pain management. Caring for patients with specific SCD-related conditions increased knowledge and comfort across all domains. Conclusions: This instrument was adequate for measuring knowledge, confidence, and comfort in caring for those with SCD across all clinical settings. We identified a lack of knowledge, confidence, and comfort regarding treatment for those with SCD starting early in medical careers, which improves after caring for patients with various complications. Thus, educating and providing SCD patient experiences is crucial for medical student management confidence related to SCD. Full article

Background/Objectives: Historically, echocardiographic imaging of the right heart has been challenging because its abnormal geometry is not conducive to reproducible anatomical and functional assessment. With the development of advanced echocardiographic techniques, it is now possible to complete an integrated assessment of the right heart that has fewer assumptions, resulting in increased accuracy and precision. Echocardiography continues to be the first-line imaging modality for diagnostic analysis and the management of acute and chronic right heart failure because of its portability, versatility, and affordability compared to cardiac computed tomography, magnetic resonance imaging, nuclear scintigraphy, and positron emission tomography. Virtually all echocardiographic parameters have been well-validated and have demonstrated prognostic significance. The goal of this narrative review of the echocardiographic parameters of the right heart chambers and hemodynamic alterations associated with right ventricular dysfunction is to present information that must be acquired during each examination to deliver a comprehensive assessment of the right heart and to discuss their clinical significance in right heart failure. Methods: Using a literature search in the PubMed database from 1985 to 2025 and the Cochrane database, which included but was not limited to terminology that are descriptive of right heart anatomy and function, disease states involving acute and chronic right heart failure and pulmonary hypertension, and the application of conventional and advanced echocardiographic modalities that strive to elucidate the pathophysiology of right heart failure, we reviewed randomized control trials, observational retrospective and prospective cohort studies, societal guidelines, and systematic review articles. Conclusions: In addition to the conventional 2-dimensional echocardiography and color, spectral, and tissue Doppler measurements, a contemporary echocardiographic assessment of a patient with suspected or proven right heart failure must include 3-dimensional echocardiographic-derived measurements, speckle-tracking echocardiography strain analysis, and hemodynamics parameters to not only characterize the right heart anatomy but to also determine the underlying pathophysiology of right heart failure. Complete and point-of-care echocardiography is available in virtually all clinical settings for routine care, but this imaging tool is particularly indispensable in the emergency department, intensive care units, and operating room, where it can provide an immediate assessment of right ventricular function and associated hemodynamic changes to assist with real-time management decisions. Full article