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Fibrinogen Changes Before and After Intravenous Thrombolysis as Predictors of Cerebral Injury and Clinical Outcomes in Acute Ischemic Stroke: A Multicenter Prospective Cohort Study.

OBJECTIVE: Plasma fibrinogen is essential in thrombosis and fibrinolysis, yet its dynamic changes pre- and post-intravenous thrombolysis (IVT) for predicting brain injury severity and prognosis in acute ischemic stroke (AIS) patients remain unclear. AIMS: This study examined how fibrinogen trends before and after IVT correlate with brain injury severity and clinical outcomes in IVT-treated patients. METHODS: This multicenter study prospectively enrolled AIS patients treated with IVT at 16 hospitals and recorded their fibrinogen trends before and after thrombolysis. Levels of brain injury mar

Characterizing cardiac phenotype in Friedreich's ataxia: The CARFA study.

BACKGROUND: Friedreich's ataxia is an autosomal recessive mitochondrial disease caused by a triplet repeat expansion in the frataxin gene (FXN), exhibiting cerebellar sensory ataxia, diabetes and cardiomyopathy. Cardiac complications are the major cause of early death. AIMS: To characterize the cardiac phenotype associated with Friedreich's ataxia, and to assess the evolution of the associated cardiopathy over 1 year. METHODS: This observational single-centre open label study consisted of two groups: 20 subjects with Friedreich's ataxia and 20 healthy controls studied over two visits over 1

White matter damage, neuroinflammation, and neuronal integrity in HAND.

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and tot

[Pulmonary hypertension in hemodialysis patients: Prevalence and associated factors].

BACKGROUND AND OBJECTIVE: Pulmonary hypertension (PH) is a progressive disorder that can be caused by several underlying conditions or an intrinsic alteration of the pulmonary vasculature. Chronic increased pressure in the pulmonary vasculature leads to changes in the architecture of the vessels that can perpetuate PH and produce right ventricular dysfunction. These structural and functional alterations can decrease survival and quality of life of patients on hemodialysis; however, there is a lack of evidence about this problem in this population. The aim of this study is to establish the prev

Circulating levels of biomarkers of collagen synthesis and ventricular function and dyssynchrony in adolescents and young adults after repair of tetralogy of Fallot.

BACKGROUND: Circulating carboxy-terminal propeptide of type I procollagen (PICP) and amino-terminal propeptide of type III procollagen (PIIINP) are biomarkers of collagen synthesis. We tested the hypothesis that circulating PICP and PIIINP are altered and may correlate with ventricular volume load and function in patients with repaired tetralogy of Fallot (TOF). METHODS AND RESULTS: Serum PICP and plasma PIIINP levels were determined in 39 patients with repaired TOF aged 17.7 ± 4.1 years and 25 healthy controls and correlated with right ventricular (RV) and left ventricular (LV) volumes, func

Opioid use in treated and untreated obstructive sleep apnoea: remifentanil pharmacokinetics and pharmacodynamics in adult volunteers.

BACKGROUND: Patients with obstructive sleep apnoea (OSA) are considered more sensitive to opioids and at increased risk of opioid-induced respiratory depression. Nonetheless, whether OSA treatment (continuous positive airway pressure, CPAP; or bilevel positive airway pressure, BIPAP) modifies this risk remains unknown. Greater opioid sensitivity can arise from altered pharmacokinetics or pharmacodynamics. This preplanned analysis of a previous cohort study of remifentanil clinical effects in OSA tested the null hypothesis that the pharmacokinetics, pharmacodynamics, or both of remifentanil, a

Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome.

IMPORTANCE: Alzheimer disease (AD) is the leading cause of death in individuals with Down syndrome (DS). Previous studies have suggested that the APOE ɛ4 allele plays a role in the risk and age at onset of dementia in DS; however, data on in vivo biomarkers remain scarce. OBJECTIVE: To investigate the association of the APOE ɛ4 allele with clinical and multimodal biomarkers of AD in adults with DS. DESIGN, SETTING, AND PARTICIPANTS: This dual-center cohort study recruited adults with DS in Barcelona, Spain, and in Cambridge, UK, between June 1, 2009, and February 28, 2020. Included individua

Caveolae in smooth muscles: nanocontacts.

Smooth muscle cell (SMC) caveolae have been investigated by quantitative and qualitative analysis of transmission electron microscopy (TEM) images of rat stomach, bladder and myometrium, guinea pig taenia coli, human ileum, and rat aortic SMCs. Ultrathin (below 30 nm) serial sections were used for examination of caveolar morphology and their connections with SMC organelles. Average caveolar diameter was smaller in vascular SMCs (70 nm, n=50) than in visceral SMCs (77 nm, n=100), but with the same morphology. Most of the caveolae, featured as flask-shaped plasma membrane (PM) invaginations, ope

Changes in Protein Metabolism and Early Development of Sarcopenia in Mice With Cholestatic Liver Disease.

BACKGROUND: Sarcopenia is a frequent complication of liver cirrhosis. Here, we chose a mouse model of cholestatic liver disease (CLD) to gain mechanistic insights into the development of sarcopenia from the earliest stages of chronic liver injury. Particular attention was paid to protein metabolism, metabolite profiles, and mediators of CLD-induced muscle wasting. METHODS: Male C57BL/6 J mice underwent bile duct ligation (BDL), sham surgery, or served as untreated controls. The observation phase lasted from the preoperative stage to postoperative day 14. Metabolic cage experiments were perfor

Long-term neurological outcomes of burn injury and the potential mediating role of plasma metabolite profiles and brain structural alterations: A prospective cohort study.

BACKGROUND: Burn injury is a common traumatic event that can lead to long-term neurological sequelae, yet the underlying mechanisms remain poorly understood. We aimed to investigate the associations between burn injury and long-term neurological outcomes, and to examine the potential mediating roles of plasma metabolite profiles and brain structural alterations. METHODS: We conducted a prospective cohort study using data from UK Biobank. Neurological outcomes-including stroke, limb weakness, hearing loss, cognitive decline, depression, anxiety, and insomnia-were assessed. Plasma metabolomics

A Reversal of Heat Stress-Induced Impairments in Boar Endocrine and Reproductive Function by Complex Liposomal Vitamin, Zinc Gluconate, and Betaine Supplementation.

Rising global temperatures are increasing the risk of heat stress (HS), with breeding boars being particularly vulnerable due to the high sensitivity of testicular function to elevated temperatures and oxidative stress. This pilot study evaluated whether a complex liposomal preparation containing vitamins A, D3, E, and C, zinc gluconate, and betaine could mitigate HS-induced impairments in boar endocrine function and semen quality. Nine clinically healthy boars (Landrace, Piétrain, and Maxter; n = 3 each; 2-4 years old) were studied across three consecutive stages: euthermic conditions (17°C-2

Proteomic Mediators of Chronic Obstructive Pulmonary Disease Phenotypes and Coronary Artery Calcification Burden in Ever Smokers.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) increases cardiovascular disease risk. Coronary artery calcification (CAC) predicts cardiovascular events and mortality in COPD. We hypothesized that plasma proteins linked to pulmonary phenotypes mediate CAC burden. METHODS: Pulmonary function, emphysema, airway wall thickening, Agatston CAC scores (inverse normal transformed), and relative abundance of 1305 plasma proteins (log-transformed) were assessed in 989 Phase 1 COPDGene (Genetic Epidemiology of COPD) participants. Proteins associated with both pulmonary phenotypes (FEV1[forced

Favipiravir for Lassa fever: an open-label, randomized controlled phase 2 trial.

Lassa fever (LF) is a viral hemorrhagic fever endemic to West Africa, with high case fatality in hospitalized patients and limited treatment options, including ribavirin. Preclinical evidence suggests high-dose favipiravir is a promising antiviral treatment alternative. We conducted a randomized controlled open-label phase 2 clinical trial at two reference hospitals in Nigeria to evaluate favipiravir in the treatment of LF. Primary endpoints were the description of classic pharmacokinetic parameters (maximum plasma concentration, time to reach maximum plasma concentration, area under the curve

Association of baseline and longitudinal plasma retinol-binding protein 4 with all-cause mortality in maintenance hemodialysis patients.

INTRODUCTION: Elevated levels of retinol-binding protein 4 (RBP4) have been linked to conditions including cardiovascular disease, type 2 diabetes, obesity, and insulin resistance. However, the associations between baseline and longitudinal RBP4 levels with all-cause mortality in maintenance hemodialysis patients remain uncertain. The aim of this study was to investigate this issue. METHODS: A total of 342 consecutive patients undergoing maintenance hemodialysis at a single hemodialysis center between 2010 and 2022 were assessed. Enzyme-linked immunosorbent assay was used to quantify plasma R

[Personalised treatment of patients with immune thrombotic thrombocytopenic purpura].

BACKGROUND: Treatment of immune thrombotic thrombocytopenic purpura (iTTP) includes plasma exchange (PEX) and immunosuppression (glucocortic … in, haptoglobin, lactate dehydrogenase activity, ADAMTS13, ADAMTS13 inhibitor titre, number of PEX, plasma volume replaced, time to increase platelet count > 150×109/L, achievement of partial and complete remission were analyzed. Data are presented as median and interquartile range. RESULTS: From 2021 to 2025, the diagnosis of TTP was confirmed in 102 patients …

Changes in Myocardial Light Chain Amyloid Burden After Plasma Cell Therapy.

BACKGROUND: Current therapies for light chain (AL) amyloidosis target the plasma cell dyscrasia, but their effect on myocardial amyloid fibril burden remains poorly defined. OBJECTIVES: The authors aimed to assess longitudinal changes in myocardial amyloid burden after plasma cell-directed chemotherapy. METHODS: This prospective study included 81 patients (58 with AL amyloid cardiomyopathy and 23 with AL amyloidosis without cardiomyopathy) with recently diagnosed, biopsy-proven AL amyloidosis, who underwent serial 18F-florbetapir positron emission tomography/computed tomography and cardiac m

The Changes in Relative Blood Volume during Dialysis Are Characterized by Ultrafiltration Rate and Predialysis Blood Test Values.

INTRODUCTION: Continuous monitoring of relative blood volume (percentage BV) in hemodialysis (HD) is critical for determining dry weight and preventing intradialytic hypotension. However, the cause of the BV variation remains unknown. This research aimed to examine factors that influence the percentage BV. METHODS: We devised a formula based on coefficients ("a," "τ," and "b") to predict changes in percentage BV. "a" denotes a significant decrease in percentage BV in the early stages of HD. "τ" represents the transition from early to late phase of HD. "b" denotes the slope of the decrease in

Optimization of Transcardiac Perfusion for More Accurately Evaluating Biodistribution of Large Molecules.

The accurate assessment of drug concentrations in biodistribution studies is crucial for evaluating the efficacy and toxicity of compounds in drug development. As the concentration of biologics in plasma can be higher than in tissue due to their potentially low volume of distribution, transcardiac perfusion is commonly employed to reduce the influence of excess drugs in residual blood. However, there is a lack of consistency in the literature on the conditions and methods of perfusion. To enhance blood removal during transcardiac perfusion, sodium nitrite (NaNO2), a vasodilator, has been widel

Plasma Methylated DNA Markers for Melanoma Surveillance.

PURPOSE: Surveillance after primary melanoma treatment aims to detect early signs of low-volume systemic disease. The current standard of care, surveillance imaging, is costly and difficult to access. We therefore sought to develop methylated DNA markers (MDMs) as promising alternatives for disease surveillance. METHODS: We used reduced representation bisulfite sequencing (RRBS) to identify MDMs in DNA samples obtained from metastatic melanoma, benign nevi, and normal skin tissues. The identified MDMs underwent validation in an independent cohort of tissue and buffy coat DNA samples. Subseque

Principles of Therapeutic Apheresis in Neurological Disease.

BackgroundTherapeutic plasma exchange (TPE) is a well-known apheresis technology since many years and is available worldwide. Myasthenia gravis is one of the first neurological diseases successfully treated with TPE. TPE is also frequently applied in acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome). Both neurological disorders are immunologically mediated and might cause life-threatening symptoms in patients.SummaryThere is a large body of evidence from many randomized controlled trials (RCTs) that the application of TPE in myasthenia gravis crisis or in acute

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… The processed volumes during apheresis range from 1.0 to 1.5 plasma volumes per apheresis session which shows the best efficacy (e.g., reduction of autoantibodies). … Usually, TPE with a frequency of five plasma volumes over 10 days was performed, or IVIG within 2 weeks of onset with 2 g/kg body weight over 2 days. …