Marker Of Disease Severity Research Articles

Lung parenchymal and cardiac appearances on CTPA impact survival in chronic thromboembolic pulmonary hypertension: results from the ASPIRE Registry

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is commonly evaluated using CT pulmonary angiography (CTPA). We evaluated the frequency and impact of parenchymal and cardiac abnormalities on survival in CTEPH.MethodsPatients were identified from the ASPIRE (Assessing-the-Spectrum-of-Pulmonary-Hypertension-Identified-at-a-Referral-Centre) Registry. Kaplan-Meier analysis was used to assess survival.Results290 patients (55% female, mean age 65±14 years) with CTEPH were included. Mosaic perfusion was noted in 83%, lung infarction in 73% and parenchymal lung disease in 28%. The severity of mosaic perfusion and lung infarction correlated with markers of disease severity (p<0.001). Whereas the presence of mosaic perfusion was associated with improved survival in all patients (p=0.03), it did not predict outcome in those undergoing pulmonary endarterectomy (PEA) (p=0.6) and those not undergoing PEA (p=0.22). The presence of lung infarction had no impact on mortality. The presence of co-existing lung disease was associated with a worse survival (p<0.008), in patients not undergoing PEA. Mosaic perfusion was less common in patients with parenchymal lung disease (65%) compared to those without parenchymal lung disease (90%), p<0.001. Increased right: left ventricular ratio and aortic diameter predicted worse outcome (p<0.002).ConclusionLung parenchymal and cardiac changes on CTPA predict outcome in CTEPH. Co-existing parenchymal lung disease is not uncommon and when present may mask the presence of mosaic perfusion. This study highlights the importance of systematically evaluating the lung parenchyma and cardiac changes in patients with CTEPH.

Role and mechanism of myonectin in severe acute pancreatitis: a crosstalk between skeletal muscle and pancreas

BackgroundSevere acute pancreatitis (SAP) is characterized by high mortality rates and various complications, including skeletal muscle atrophy, which significantly exacerbates its outcomes. Despite its clinical relevance, the mechanistic understanding of the relationship between skeletal muscle and the pancreas in SAP remains limited. Our study aimed to elucidate this “organ crosstalk” and its potential implications.MethodsWe established an SAP mouse model through pancreatic duct ligation (PDL) and evaluated pancreatic necrosis, skeletal muscle atrophy, and myonectin expression levels. Recombinant myonectin protein was administered in vivo and in vitro to assess its effects on acinar cell necrosis. Mechanistic insights were gained through RNA-seq data analysis and experimental validation. Serum samples from AP patients and healthy controls were collected to investigate the correlation between serum myonectin levels and disease severity.ResultsThe mouse model exhibited severe pancreatic necrosis, skeletal muscle atrophy, and elevated myonectin levels, with myonectin administration exacerbating model severity. We identified iron accumulation-induced ferroptosis as a key pathway contributing to myonectin-mediated acinar cell necrosis. A total of 22 healthy controls and 52 patients with varying degrees of AP were included in the serum samples and clinical data (36.5% females, age 49.79 ± 16.53). Analysis of serum samples revealed significantly higher myonectin levels in AP patients, correlating with disease severity (R = 0.28, P = 0.041).ConclusionsOur findings underscore the significant role of myonectin in SAP progression and its potential as a prognostic marker for disease severity in AP patients. This study contributes to a deeper understanding of the pathophysiology of SAP and highlights potential therapeutic targets for intervention.

Peripheral Blood Biomarkers as differential diagnostic markers of Disease Severity in Neonates with Hyperbilirubinemia

Peripheral Blood Biomarkers as differential diagnostic markers of Disease Severity in Neonates with Hyperbilirubinemia

Red Cell Distribution Width as a Marker of Disease Severity and In-hospital Mortality in Patients with ST-segment Elevation Myocardial Infarction

Red Cell Distribution Width as a Marker of Disease Severity and In-hospital Mortality in Patients with ST-segment Elevation Myocardial Infarction

Deep medullary veins integrity and relationships with small vessel disease and interstitial diffusivity measures in patients with a recent small subcortical infarct.

The role of the venous compartment in cerebral small vessel disease has yet to be fully understood. As such, we evaluated how deep medullary veins integrity relates to MRI-based small vessel disease severity markers and glymphatic function assessed by DTI measures in patients with a recent small subcortical infarct. We gathered demographic, clinical, and 3 Tesla-MRI imaging data from 50 patients with a recent small subcortical infarct. We evaluate the venular integrity using two visual scales based on their appearance on SWI. We assessed the number of lacunes and microbleeds, white matter hyperintensities volume, perivascular spaces volume in basal ganglia and white matter, summary-small vessel disease score, and brain volume. Diffusivity measures in normal-appearing white matter included free water fraction, mean diffusivity and fractional anisotropy with and without free water correction, and DTI along the perivascular spaces. After categorizing the cohort in quartiles according to both venular scores, we assessed their correlations with small vessel disease markers and diffusivity measures using multivariable ordinal regression analyses adjusting for age, sex, smoking, and summary small vessel disease score. In univariate analysis most of the imaging variables, except for microbleeds, perivascular spaces in white matter and DTI-along the perivascular spaces, were associated with one or both venular scores. In multivariate analysis (OR, 95% CI), free water (1.33, 1.03-1.73), mean diffusivity (4.56, 1.32-15.81), fractional anisotropy (0.77, 0.63-0.93), free water-corrected mean diffusivity and fractional anisotropy (2.39, 1.06-5.39;0.78, 0.65-0.94, respectively), associated with vein appearance, while only brain volume (0.48, 0.25-0.94), fractional anisotropy with and without free water correction (0.82,0.86-0.99; 0.83, 0.7-0.99, respectively) remained significant for vein count. In patients with a recent small subcortical infarct, disruption of the deep medullary veins, increased extracellular water, and white matter injury appear to be associated. SVD=small vessel disease; DMV=deep medullary veins; WMH=white matter hyperintensities; PVS=perivascular spaces; DTI-ALPS=diffusion tensor image analysis along the perivascular spaces; FW=free water; MD=mean diffusivity; FA= fractional anisotropy; BG=basal ganglia.

Association of Fibroblast Growth Factor 23 and Cardiac Mechanics in the Cardiovascular Health Study.

Elevated levels of fibroblast growth factor 23 (FGF23) are associated with left ventricular hypertrophy and heart failure (HF) in individuals with and without kidney disease. Prior studies investigated the association of FGF23 and structural cardiac changes using conventional echocardiography, which is limited in its ability to detect early cardiac dysfunction. We investigated the relationship between FGF23 levels and cardiac dynamics using two-dimensional speckle tracking echocardiography (2D-STE), a novel imaging modality. This was a cross-sectional analysis of data from the Cardiovascular Health Study, an ongoing prospective, population-based cohort study. The study population included 506 participants from CHS with available c-terminal (cFGF23) and intact FGF23 (iFGF23) measurements from 1996-1997 and 2D-STE images from 1994-1995. Forty two percent of the study population had CKD, defined as an eGFR < 60 ml/min/1.73m2, and the mean eGFR was 63 ml/min/1.73m2. The primary exposures were cFGF23 and iFGF23. The primary outcomes were six 2D-STE parameters performed at the 1994-1995 study visit. Linear regression models were used to examine the independent associations of FGF23 with six cardiac 2D-STE indices adjusting for demographics, cardiovascular risk factors, markers of kidney disease severity, and inflammation. cFGF23 levels were moderately correlated with iFGF23 levels in the CHS population. In fully adjusted models, cFGF23 was associated with left atrial dysfunction, but no other cardiac imaging parameter (β estimate -2.47; 95% Confidence Interval -4.68, -0.25; Table 2). iFGF23 was not associated with any of the six 2D-STE indices. Limitations include small sample size and noncurrent FGF23 measurements and 2D-STE imaging. In a limited sample of individuals enrolled in the CHS with c- and i-FGF23 measurements, we did not find consistent associations between FGF23 levels and 2D-STE parameters. Further investigations in a larger population with concurrent 2D-STE are needed to better understand the associations of FGF23 with early changes in cardiac mechanics.

Short-term effects of opioids during therapeutic hypothermia for neonatal encephalopathy.

To examine the effects of opioids during therapeutic hypothermia (TH) on short-term outcomes in neonates with neonatal encephalopathy (NE). Multicenter retrospective study of neonates with moderate/severe NE from Jan. 2013-Feb 2021. Opioid exposure was classified as positive (>0.1 mg/kg) or negative (no exposure or ≤0.1 mg/kg) based on cumulative morphine milligram equivalents (MME). Negative binomial regression models were used to evaluate clinical outcomes. One hundred and twenty neonates were included. Adjusted analyses indicated that opioid exposure was associated with an increase in (1) length of hospitalization, (2) hypotension/use of vasopressors, and (3) need for and longer duration of mechanical ventilation. Many findings persisted even after adjusting for site and the presence of confirmed seizures (a marker of disease severity). Opioid use during TH was associated with adverse effects on short-term outcomes. Caution should be exercised when using opioids during TH until longer-term neurodevelopmental outcome studies can be conducted in larger cohorts.

Abstract 4124506: Short Physical Performance Battery as a Marker of Severity and Predictor of Clinical Outcomes in Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Background: ATTR-CM has an age dependent prevalence and is a disorder that almost exclusively affects older adults. Objective evaluations of function are critical to assessing and managing ATTR-CM in older adults. The short physical performance battery (SPPB) is a valid measure of functional capacity that predicts morbidity and mortality in older adults but its utility in ATTR-CM remains unknown. Aims/hypothesis: To establish SPPB as a useful marker of disease severity and predictor of outcomes in ATTR-CM. We hypothesized that SPPB scores would correlate with validated markers of ATTR-CM severity and improve clinical prediction. Methods: This is a retrospective analysis of patients referred to the Columbia University Cardiac Amyloid Program. Patients were stratified into low (SPPB 0-6), moderate (7-9), and high (10-12) cohorts based on initial SPPB score and baseline characteristics were compared between groups. Cox proportional hazard models and Kaplan Meier (KM) curves were generated to assess associations with mortality as well as a composite of death and cardiovascular (CV) hospitalization in follow-up. Results: A total of 263 patients, age 78 years (IQR 73, 84), 86% male, 22% with ATTRv (variant) and 78% with ATTRwt (wild type) were studied. SPPB showed no limitation in 59%, mild limitation in 33%, and severe limitation in 8%. Lower SPPB was associated (p &lt;0.05) with older age, prior stroke/TIA, shorter 6-minute walk test, elevated NT-proBNP and HS-troponin, worse quality of life metrics on Kansas City Cardiomyopathy Questionnaire, more advanced NYHA and Mayo stages, and higher Columbia scores. On multivariate regression (adjusted for age, sex, genotype, NYHA), SPPB was independently associated with the composite of mortality and CV hospitalization, with each point increase corresponding to 13% lower incidence of the outcome (HR 0.87, p=0.01). Chair stands score, one of three SPPB subdomains, was independently associated with the composite and mortality. KM curves showed significant association with SPPB and both the composite and mortality (Fig. 1). Conclusions: SPPB score is a marker of ATTR-CM severity, associated with validated biomarkers and staging systems, and independently predicts clinical outcomes.

Prognostic Value of Serum D-dimer in Predicting Outcomes in COVID-19 Positive Pregnant Women

Background: Combined effects of pregnancy induced hypercoagulability and SARS-CoV-2 infection place pregnant women with COVID-19 disease at high risk of severe outcome. COVID-19 severity has also been associated with serum D-dimer, a biomarker reflecting coagulation and fibrin degradation, in general populations. Despite its prognostic value in pregnant women, the prognostic value of this finding particularly in maternal outcomes remains less understood. The aim of this study was to determine whether elevated serum D-dimer levels in pregnant COVID-19 positive women are of prognostic significance for severe maternal outcomes. Methods: This retrospective observational study included 62 third trimester COVID 19 positive pregnant women admitted to the Department of Obstetrics and Gynecology, BSMMU, Dhaka from March 2019 to February 2020. Serum D-dimer were measured at admission and day 7, 14. D-dimer levels were related to clinical outcomes and statistically evaluated using chi square tests and logistic regression at p &lt; 0.05. Results: Significantly associated with higher risk of severe outcomes, all of which included ICU admission, respiratory complications and adverse pregnancy events is elevated D-dimer levels (≥1.5 mg/L). In logistic regression analysis, patients with D-dimer levels of ≥1.5 mg/L had 3.5-fold greater odds of severe outcomes (OR 3.486; 95% CI, 1.184 to 10.263; p = 0.023). D-dimer had a sensitivity of 64.29%, 67.55% specificity in predicting severe outcomes. Conclusion: Serum D-dimer is valuable prognostic marker of disease severity in pregnant COVID-19 positive women and may be used for early risk assessment and clinical decision making. Routine measurement may help identify early high risk cases in order to improve maternal outcomes.

Prevalence, Risk Factors, and Mortality of New-Onset Atrial Fibrillation in Mechanically Ventilated Critically Ill Patients.

Background/Objectives: Critically ill patients admitted to the intensive care unit (ICU) frequently develop new-onset atrial fibrillation (NOAF) due to numerous risk factors. While NOAF has been associated with increased mortality, it remains unclear whether it serves merely as a marker of illness severity or directly contributes to adverse outcome. This study aimed to determine the incidence and risk factors for NOAF in a homogenized population of mechanically ventilated patients at ICU admission, excluding well-established predisposing factors. Additionally, we examined the impact of NOAF on mortality in this context. Methods: We prospectively studied consecutive patients over a 3-year period to identify triggers for NOAF. Factors associated with 30-day mortality during the ICU stay were recorded. Demographic data, medical history, laboratory findings, and the severity of illness at admission were compared between patients who developed NOAF and those remaining in sinus rhythm. In NOAF patients, the course of atrial fibrillation (resolution, persistence, or recurrence) was evaluated during the 30-day ICU stay. Results: Of the 1330 patients screened, 685 were eligible for analysis, with 110 (16.1%) developing NOAF. Septic episodes occurred more frequently in the NOAF group compared to the no-NOAF group (92.7% vs. 58.1%, p < 0.001). Notably, 80% of NOAF patients developed a septic episode concurrently with the atrial fibrillation, often stemming from secondary infections, and 85.3% presented with septic shock. When focusing on patients with at least one septic episode during the 30-day ICU stay, 23.4% of them developed NOAF. Additionally, patients with NOAF were older and had a higher prevalence of hypertension; disease severity at admission was not a triggering factor. Mainly sepsis, but also advanced age, and a history of hypertension remained independent factors associated with its occurrence. Sepsis, primarily, along with advanced age and a history of hypertension, was identified as independent factors associated with the occurrence of NOAF. Mortality was higher in the NOAF group compared to the control group (39 patients (35.5%) vs. 138 patients (24%), p = 0.01). NOAF occurrence, sepsis, disease severity at admission, and age were associated with increased ICU mortality; however, NOAF was not found to be an independent predictor of ICU mortality in multivariate analysis. Instead, sepsis, age, and disease severity at admission remained independent predictors of 30-day mortality. Sinus rhythm was restored in 60.9% of NOAF patients within 48 h, with the improvement or stabilization of sepsis being crucial for rhythm restoration. Conclusions: NOAF is a common complication in intubated ICU patients and is independently associated with sepsis, advanced age, and hypertension. While NOAF is linked to increased ICU mortality, it is more likely a marker of disease severity than a direct cause of death. Sepsis improvement appears critical for restoring and maintaining sinus rhythm.

MicroRNAs in congenital diaphragmatic hernia: insights into prenatal and perinatal biomarkers and altered molecular pathways

BackgroundCongenital diaphragmatic hernia (CDH) is characterized by a diaphragmatic defect, leading to herniation of abdominal organs into the chest, lung compression, and impaired lung development, often resulting in pulmonary hypertension and lung hypoplasia. Prenatal imaging techniques like ultrasound and MRI provide anatomical predictors of outcomes, but their limitations necessitate novel biomarkers for better prognostic accuracy. ObjectiveThis study aims to identify unique circulating maternal, fetal, and neonatal microRNAs (miRNAs) that can distinguish CDH pregnancies from healthy controls and assess their potential as markers of disease severity. Study DesignWe conducted a prospective study involving third-trimester maternal blood, amniotic fluid, cord blood, and neonatal blood samples from pregnancies complicated by CDH and healthy controls. miRNA expression was analyzed using RNA-sequencing, and random forest analysis identified miRNAs distinguishing CDH survivors from nonsurvivors. Pathway enrichment analyses were performed to explore the biological relevance of differentially expressed miRNAs. ResultsSignificant miRNA expression differences were observed between CDH and control samples across all sample types. In infant blood, 148 miRNAs were up-regulated, and 36 were down-regulated in CDH cases. Pathway analysis revealed that dysregulated miRNAs in CDH targeted pathways related to protein binding, transcription regulation, and signaling pathways implicated in pulmonary hypertension and lung hypoplasia. Random forest analysis identified miRNAs in maternal blood (miR-7850-5p_L-1R+2, miR-942-3p, and miR-197-3p) that distinguished CDH survivors from nonsurvivors, with an receiver operating characteristic area under the curve of 1.0. ConclusionCirculating miRNAs in maternal blood offer promising biomarkers for predicting CDH outcomes. miRNAs from infant blood provide mechanistic insights and potential targets for therapeutic intervention in critical pathways of pulmonary hypertension and lung hypoplasia. Further studies with larger cohorts are needed to validate these findings and explore the clinical application of miRNA biomarkers in CDH management.

Tracking myasthenia gravis severity over time: Insights from the French health insurance claims database.

Few data are available on the course of myasthenia gravis (MG) regarding disease severity and stability over time in real-world settings. This study used the French National Health Insurance Database (SNDS) to assess markers of disease severity in patients with MG longitudinally. All patients with MG-related claims in the SNDS between 2013 and 2020 were identified. Patients were followed for up to 8 years after the first claim. Intensive care unit (ICU) stays, treatment with intravenous immunoglobulin (IVIg) or plasma exchange (PE), and death were documented throughout the follow-up period. Standardized mortality rates were estimated, and mortality-related variables were identified using a Cox model. In all, 14,459 individuals constituted the full study population, including 6354 incident patients. In the incident population, 2199 (34.6%) were admitted to ICUs at least once, principally during the first year after the index date (N = 1477; 23.3%). This proportion decreased progressively to reach 3.0% in the seventh year. A total of 2817 patients received IVIg and 432 PE, again principally in the first year. In the full study population, the standardized mortality rate was 1.08 (95% confidence interval [CI] 1.03-1.13), being lower in men (0.95, 95% CI 0.89-1.02) than in women (1.15, 95% CI 1.07-1.23) and in patients aged >65 years (1.06, 95% CI 1.01-1.11) than in younger patients (1.50, 95% CI 1.24-1.76). Male gender, older age and higher comorbidity were independently associated with mortality. A subgroup of patients with MG require ICU admission and rescue therapy with IVIg or PE, indicative of poor disease control. New therapies are needed to improve disease control and reduce disease burden.

Assessment of sestrin 2 as a sepsis marker and predictor of disease severity

Introduction Sestrin 2 is considered a stress-inducible antioxidant protein. This study was aimed to evaluate sestrin 2 in subjects with sepsis, and its correlation with clinical severity and mortality. Methods Sepsis and control group patients were followed from admission to discharge. A blood sample was taken at admission for determination of serum sestrin 2 level. Results Of the total 42 patients with sepsis, there were 25 females and the mean age was 74.9 years. The sestrin 2 levels were significantly higher in the sepsis group. The optimum sestrin 2 cut-off point of ≥3.13 ng/mL had 95.2% sensitivity and 71.4% specificity for sepsis (p < .001). Sestrin 2 levels were higher in patients who needed renal replacement therapy (p = .018), patients who needed vasopressor therapy (p = .001) and patients with organ dysfunction (p = .002). The sestrin 2 level was significantly correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Nutrition Risk in the Critically Ill (NUTRIC) Score, C-reactive protein and albumin. Sestrin 2 levels were not associated with 30 d mortality in sepsis patients. Conclusions Sestrin 2 was significantly higher in the sepsis patients and associated with sepsis related adverse clinical outcomes. These results provided information concerning the clinical utility of sestrin 2.

Clinical profile and immediate outcomes of balloon mitral valvotomy in low gradient rheumatic mitral stenosis

ObjectivesThe objective of this study was to assess the clinical, hemodynamic characteristics and immediate outcomes of Percutaneous Balloon Mitral Valvotomy (PBMV) in low gradient severe rheumatic mitral stenosis (LGMS) with normal cardiac index. BackgroundThe optimal management of LGMS remains incompletely understood. MethodsWe examined 200 consecutive patients with severe rheumatic mitral stenosis (MS) who underwent PBMV between January 2014 and March 2020. ResultsOf the 149 patients (who satisfied inclusion criteria), 51 (34.2 %) had LGMS. The mean diastolic pressure gradient (DPG) was 8.70 ± 1.34 mm of Hg in LGMS as compared to 16.2 ± 4.3 mm of Hg in HGMS (p < 0.001). Patients of LGMS were older (39.5 ± 9.7 vs.34.9 ± 11.0 years, p = 0.012), had lower baseline heart rate (76.8 ± 9.5 vs 81.9 ± 12.5, p = 0.010), higher Mitral valve area (MVA) (1.16 ± 0.19 vs 0.99 ± 0.21 cm2,p < 0.001),higher Wilkins score (5.8 ± 1.7 vs 4.9 ± 1.5, p = 0.002) and elevated left ventricular end diastolic pressure (LVEDP) (9.2 ± 2.8 vs 5.8 ± 1.2 mm of Hg,p=<0.001) but lower Pulmonary artery systolic pressure (PASP) (53.1 ± 14.5 vs 62.6 ± 17.8 mm of Hg, p = 0.001) and left atrial (LA) pressure (18.0 ± 3.1vs 22.0 ± 4.4 mm of Hg,p=<0.001). Although, the procedural success rate of PBMV was comparable between LGMS and HGMS (92.2 % vs 96.9 % p = 0.231) but increment in MVA and fall in DPG were significantly higher in HGMS in comparison to LGMS (p-value<0.05). ConclusionsSignificant MS may have "low" gradients during catheterization and yet be symptomatic, and thus low gradients cannot be alone used as a marker of disease severity. LGMS with normal CI is characterized by unique clinical and hemodynamic features. The immediate outcome of PBMV is comparable to HGMS but the hemodynamic parameters to monitor the success of PBMV are significantly different.

Enhancing the Understanding of Abdominal Trauma During the COVID-19 Pandemic Through Co-Occurrence Analysis and Machine Learning.

This study examines the impact of the COVID-19 pandemic on abdominal trauma management by comparing pre-pandemic (17 February 2018-26 February 2020) and pandemic periods (27 February 2020-7 March 2022). Analyzing data from 118 patients at the Emergency County Clinical Hospital of Craiova, we identified significant shifts in clinical practices affecting patient outcomes. During the pandemic, a moderate increase in surgical interventions for specific abdominal traumas indicated the effective adaptation of the medical system. Prioritizing critical cases and deferring non-urgent procedures optimized limited resources. Demographic and clinical factors-including age, sex, body mass index (BMI), and red cell distribution width (RDW)-significantly influenced the hospitalization duration and recovery outcomes. Gender disparities in mortality lessened during the pandemic, possibly due to standardized interventions and the physiological effects of SARS-CoV-2. The link between occupation and obesity highlighted how work environments impact trauma severity, especially as lifestyle changes affect BMI. While age remained a major predictor of mortality, its influence slightly decreased, potentially due to improved protocols for elderly patients. RDW emerged as an important prognostic marker for disease severity and mortality risk. Employing advanced co-occurrence analysis enhanced with machine learning, we uncovered complex relationships between clinical and demographic variables often overlooked by traditional methods. This innovative approach provided deeper insights into the collective impact of various factors on patient outcomes. Our findings demonstrate the healthcare system's rapid adaptations during the pandemic and offer critical insights for optimizing medical strategies and developing personalized interventions in global crises.

Risk-stratified treatment for drug-susceptible pulmonary tuberculosis

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54–0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07–1.91; extensive disease: HR 2.02, 95%CI 1.07–3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

Elevated serum preptin levels as a marker for non-alcoholic fatty liver disease severity in type 2 diabetes mellitus patients

Elevated serum preptin levels as a marker for non-alcoholic fatty liver disease severity in type 2 diabetes mellitus patients

Individual-level metabolic connectivity from dynamic [18F]FDG PET reveals glioma-induced impairments in brain architecture and offers novel insights beyond the SUVR clinical standard.

This study evaluates the potential of within-individual Metabolic Connectivity (wi-MC), from dynamic [18F]FDG PET data, based on the Euclidean Similarity method. This approach leverages the biological information of the tracer's full temporal dynamics, enabling the direct extraction of individual metabolic connectomes. Specifically, the proposed framework, applied to glioma pathology, seeks to assess sensitivity to metabolic dysfunctions in the whole brain, while simultaneously providing further insights into the pathophysiological mechanisms regulating glioma progression. We designed an index (Distance from Healthy Group, DfHG) based on the alteration of wi-MC in each patient (n = 44) compared to a healthy reference (from 57 healthy controls), to individually quantify metabolic connectivity abnormalities, resulting in an Impairment Map highlighting significantly compromised areas. We then assessed whether our measure of metabolic network alteration is associated with well-established markers of disease severity (tumor grade and volume, with and without edema). Subsequently, we investigated disruptions in wi-MC homotopic connectivity, assessing both affected and seemingly healthy tissue to deepen the pathology's impact on neural communication. Finally, we compared network impairments with local metabolic alterations determined from SUVR, a validated diagnostic tool in clinical practice. Our framework revealed how gliomas cause extensive alterations in the topography of brain networks, even in structurally unaffected regions outside the lesion area, with a significant reduction in connectivity between contralateral homologous regions. High-grade gliomas have a stronger impact on brain networks, and edema plays a mediating role in global metabolic alterations. As compared to the conventional SUVR-based analysis, our approach offers a more holistic view of the disease burden in individual patients, providing interesting additional insights into glioma-related alterations. Considering our results, individual PET connectivity estimates could hold significant clinical value, potentially allowing the identification of new prognostic factors and personalized treatment in gliomas or other focal pathologies.

Evaluation of TNF-α and TNF-R1 immunomarkers in Renal Failure Patients in Karbala province

Renal failure is characterized by height level of pro-inflammatory cytokines, mainly Tumor necrosis factor-alpha (TNF-α) and its receptor TNF-R1. The aim was to investigate the association of TNF-α and TNF-R1 levels in Renal Failure.This study was carried out from February 2022 to March 2023 in the labs of Thi-Qar University's Col1ege of Education for Pure Sciences. In partnership with Al-Hussein Teaching Hospital, Nasiriyah General Hospital, and Thi-Qar Center for Nephrology and Dialysis in Thi-Qar Province .The study comprised (100) patients for both sex : (40 patients with diabetes mellitus), (40 patients without diabetes mellitus) whose serum urea level and serum creatinine level were examined, and (40 healthy).The level of biochemical indicators were measured, which included urea, creatinine, albumin and total protein where the study discovered a considerable rise in urea and creatinine levels compared to healthy subjects and standard rates, and this increase is related 'with a decrease GFR', while there is decrease in rate of albumin and total protein. The statistical analysis' findings revealed a considerable difference (p &lt;0.05) in patients with RF in concentration of the TNF-α and TNF-R1, where they were examined for 80 samples of RF patients, and 40 healthy samples in the control group. The number of RF patients in Thi-Qar province showed a marked increase in the yearly rate of hemodialysis. A third of all patients had a considerable prevalence of RF linked to hypertension. The study concluded that a significant effect of TNF-α is associated with markers of kidney disease severity and distant organ dysfunction among patients with RF. In addition, this study found a correlation between the effects of TNF- α on end-stage renal disease. Extensive studies are needed to confirm these relationships.

Mitral valve phenotypes in SMAD3-related thoracic aortic disease: insights from the Montalcino Aortic Consortium

Abstract Background SMAD3 pathogenic variants (PV) predispose to heritable thoracic aortic aneurysms and dissections (HTAD). Mitral annular disjunction (MAD) associated with mitral valve prolapse (MVP) and mitral regurgitation (MR) was identified as a potential new marker of disease severity in Marfan syndrome. The prevalence and prognostic impact of these mitral phenotypes in other forms of HTAD are less known. Purpose We hypothesize that mitral abnormalities are increased in SMAD3-related HTAD and are associated with increased risk for valve and aortic complications. Methods The Montalcino Aortic Consortium (MAC) registry has enrolled participants with PV in 15 HTAD genes. Subjects &amp;gt;16 years old with complete imaging and clinical data were included in this study. MVP was defined according to current guidelines. MR was classified as mild, moderate, or severe. MAD was defined by a &amp;gt;3-millimeter gap between the posterior mitral valve leaflet hinge point and the inferolateral myocardium as confirmed by direct measurement of echocardiogram images. Frequencies of MVP, MR, and MAD were compared between MAC participants with SMAD3 PV and other HTAD PV. Associations between clinical and echo characteristics and the composite outcome of arrhythmia, aortic surgery, aortic dissection, or congestive heart failure was evaluated with multivariable logistic regression. Results In 671 MAC participants (129 with SMAD3 PV, 36 [IQR 19-51] years, 49% female), the prevalence of MVP was 15% and the prevalence of MR was 22%. Both MVP (31/129, 24%, vs. 67/542, 12%, OR 2.2 [1.4-3.6], P&amp;lt;0.001) and MR (40/129, 31%, vs. 108/542, 20%, OR 1.8 [1.2-2.8], P&amp;lt;0.006) were more common in participants with SMAD3 PV compared to other PV and were further enriched in cases with SMAD3 missense PV compared to loss of function PV (MR or MVP: 26/48, 54% vs. 7/30, 23%, OR 3.9 [1.4-10.8], P&amp;lt;0.007). Images were available from 238 MAC participants (67 with SMAD3 PV) to assess for MAD. MAD (29/67, 43%, vs. 28/171, 16%, OR 3.9 [2.1-7.3], P&amp;lt;0.0001), or the composite of MR, MVP, or MAD (42/67, 63%, vs. 69/171, 35%, OR 3.2 [1.8-5.7], P&amp;lt;0.0001) was more common with SMAD3 PV compared to other PV (Figure 1). Twelve participants with SMAD3 PV (18%) had prominent mitral phenotypes (&amp;gt;mild MR, &amp;gt;10 mm MAD, or MAD with MVP) but no significant aortic dilation (Z&amp;lt;3). When controlling for age and sex, MR or MVP, but not MAD, was independently associated with the composite outcome (OR 16 [2.4-110], Figure 2). Conclusion Mitral valve pathology, including MVP, MR, and MAD, is increased in individuals with SMAD3 PV compared to other HTAD PV. Prominent mitral phenotypes related to SMAD3 missense PV may identify a high-risk subgroup with adverse cardiovascular outcomes. Because congenital mitral disease may be the primary presenting feature of SMAD3 PV, genetic testing for HTAD should be considered for such patients, especially if they also have a family history of thoracic aortic disease.