Marker Of Disease Severity Research Articles

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

ObjectiveTo examine the effects of opioids during therapeutic hypothermia (TH) on short-term outcomes in neonates with neonatal encephalopathy (NE).MethodsMulticenter 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.ResultsOne 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).DiscussionOpioid 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 <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 < 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.

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.

MicroRNAs in Congenital Diaphragmatic Hernia: Insights into Prenatal and Perinatal Biomarkers and Altered Molecular Pathways: microRNAs in Congenital Diaphragmatic Hernia for Pathway Analysis and Prognostic Biomarkers

Congenital 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. This 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. We 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 non-survivors. Pathway enrichment analyses were performed to explore the biological relevance of differentially expressed miRNAs. Significant 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 non-survivors, with an ROC area under the curve of 1.0. Circulating 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.

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

Background: 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). Methods: Analyzing data from 118 patients at the Emergency County Clinical Hospital of Craiova, we identified significant shifts in clinical practices affecting patient outcomes. Results: 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. Conclusions: 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.

Sustained paradoxical vasodilation and blood pressure lowering in response to sympathetic stimulation as markers of disease severity and poor survival in primary AL amyloidosis.

Abstract Background AL patients present sustained paradoxical vasodilation in response to sympathetic stimulation by cold pressor test (CPT). The clinical relevance of this finding is unknown. Purpose We investigated the association between CPT-induced vascular and hemodynamic responses with clinical characteristics of the disease in AL amyloidosis. Methods We consecutively recruited 113 newly diagnosed patients with AL amyloidosis before treatment initiation. High resolution ultrasonography was used to measure the maximum vasodilation of the brachial artery in response to a cold stimulus and 3 minutes after its withdrawal. Systolic (SBP) and diastolic blood pressure (DBP) were measured at the same timepoints. Clinical and laboratory makers of autonomic dysfunction were also measured in a subgroup of the population. All-cause and cardiovascular (CV) mortality were defined as end-points of the study. Results Sustained vasodilation post CPT (%pCPT) was associated with markers of autonomic dysfunction, namely dipping status (p&amp;lt;0.05) and sudomotor dysfunction (p=0.064) and with NYHA stage, baseline NTproBNP and heart failure (p&amp;lt;0.05 for all). DBP%pCPT was associated with the neuropathy symptom scale (NSS Autonomous, p=0.032), while SBP%pCPT was inversely associated with Mayo stage. Vasodilation%pCPT was independently associated with CV death (adjusted HR=1.154, p=0.017) while both DBP%pCPT (HR=0.955, p=0.027) and SBP%pCPT (HR=0.947, p=0.04) were independently associated with all cause death (adjusted for the core model including age, sex, SBP, Mayo stage and nerve involvement). Overall survival was worse in AL patients who demonstrated a decrease in SBP%pCPT than in those who exhibited an increase or kept it stable (log rank test, p=0.024). The same applies to DBP%pCPT(log rank test, p=0.002). Regarding CV death, Vasodilation%pCPT above 5.86% was associated with increased risk of CV death (log rank test, p=0.002). Conclusions In AL amyloidosis, sustained paradoxical vasodilation and decreased SBP and DBP in response to sympathetic stimulation were associated with autonomic dysfunction, more severe cardiac involvement and poor survival.

Association of thyroid hormones with the severity of chronic kidney disease: a cross-sectional observational study at Tabuk, Saudi Arabia.

The interplay between chronic kidney disease (CKD) and thyroid dysfunction is becoming more evident in the biomedical community. However, the intricacies of their relationship warrant deeper investigation to understand the clinical implications fully. This study aims to systematically evaluate the correlation between thyroid hormone levels, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), and markers of renal disease severity. These markers include serum creatinine, urea, and parathyroid hormone (PTH) levels in individuals diagnosed with CK). We conducted a cross-sectional observational study involving a cohort of 86 participants with CKD recruited from the renal clinic at King Fahad Hospital in Tabuk. Biochemical parameters, encompassing plasma electrolytes and thyroid hormone concentrations, were quantitatively assessed. These measurements were performed with the aid of a Roche Cobas E411 analyzer. The Pearson correlation coefficient was employed to delineate the strength and direction of the associations between the thyroid function markers and renal disease indicators. The statistical analysis highlighted a generally weak correlation between the concentrations of thyroid hormones and the indicators of renal disease severity, with Pearson correlation coefficients between -0.319 and 0.815. Critically, no significant correlation was found between creatinine and thyroid hormones (TSH, T3, T4), nor was any substantial correlation between urea and thyroid hormones. Conversely, a robust positive correlation was noted between the levels of parathyroid hormone and serum creatinine (r=0.718, p<0.001). The data suggests that thyroid hormone levels have a minimal correlation with the severity of renal disease markers. In contrast, the pronounced correlation between PTH and creatinine underscores the importance of considering PTH as a significant factor in managing and therapeutic intervention of CKD complications. These initial findings catalyze further research to thoroughly investigate the pathophysiological relationships and potential therapeutic targets concerning thyroid dysfunction in patients with renal impairment.

Predictors of B-line count in hospitalized patients with COVID-19

Abstract Background B-lines on lung ultrasound (LUS) are non-specific signs of increased density within lung tissue, which can be secondary to pulmonary congestion, pneumonia, or fibrosis. LUS is recommended for managing acute heart failure (HF); however, its value in non-HF populations is less clear. Purpose To identify clinical, laboratory, and echocardiographic predictors of B-lines in a population with Coronavirus disease 2019 (COVID-19). Methods In the ECHOVID-19 study, hospitalized non-ICU patients ≥18 years with confirmed laboratory diagnosis of COVID-19 in Eastern Denmark underwent 8-zone LUS and echocardiography. We used trend and regression analyses to identify associations with the number of B-lines and adjusted for potential confounders (age, sex, body mass index, C-reactive protein, and pandemic wave). Results Among 270 (89%) patients with adequate LUS images, the mean age was 69±14 years, 58% were male and 11% had prior HF. Median time from hospital admission to LUS was 4 [2-8] days. In total, 263 (97%) had ≥1 B-line (median B-line number 14 [9-22]) and median left ventricular ejection fraction [LVEF] was 59 [54-63]). In adjusted models, more B-lines were associated with higher levels of C-reactive protein with an incidence rate ratio (IRR) of 16% (95%CI: 8%-24%) per log-unit increase (P&amp;lt;0.001) and higher Early Warning Score (IRR 5% [95%CI: 1%-0%] per point, P=0.02). Higher tricuspid regurgitation gradient was associated with more B-lines: IRR 2% (95%CI: 1%-3%) per mmHg, P&amp;lt;0.001) (Figure 1). Echocardiographic measures of left ventricular (LV) function (including LVEF and global longitudinal strain, left atrial volume, and LV filling pressures (E/e’)) and right ventricular function were not significantly associated with the number of B-lines. B-lines were not associated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, even in patients with established HF. Lastly, B-lines were not associated with 30-day mortality. Conclusions Among hospitalized patients with COVID-19, B-lines on LUS are associated with markers of infectious disease severity and pulmonary hypertension but not with markers of left-sided HF.Figure1.Predictors of B-lines

Release of sputum neutrophil granules is associated with pulmonary function and disease severity in childhood asthma

BackgroundMyeloperoxidase (MPO) and human neutrophil lipocalin or neutrophil gelatinase-associated lipocalin (HNL/NGAL) are stored in neutrophil granulocytes and secreted upon activation of the cells. They have been proposed to reflect the degree of inflammation in the airways. However, their role as potential markers of disease severity in childhood asthma remains unknown. This study investigated the relationship between the expression of MPO and HNL/NGAL and childhood asthma.MethodsA total of 83 pediatric patients with asthma and 59 controls were enrolled. Using enzyme-linked immunosorbent assays, the human MPO and HNL/NGAL levels were measured in sputum supernatants. Assessments including spirometry, methacholine challenge test, and atopy test were conducted.ResultsNo difference in sputum neutrophil counts was observed between pediatric patients with asthma and controls. However, sputum MPO and HNL/NGAL levels were significantly higher in patients with asthma than in controls (p = 0.021 and p < 0.001, respectively), especially in patients with moderate-to-severe persistent asthma. In patients with asthma, sputum MPO and HNL/NGAL levels showed a positive correlation with sputum neutrophil counts (MPO, r = 0.433, p < 0.001; HNL/NGAL, r = 0.584, p < 0.001) and with each other (r = 0.628, p < 0.001). Moreover, sputum HNL/NGAL level demonstrated better ability to accurately reflect current pulmonary function, airway inflammation, and limitations than MPO level in this study.ConclusionsSputum MPO and HNL/NGAL levels, which reflect neutrophil activation in airways, were increased in pediatric patients with asthma. Moreover, sputum MPO and HNL/NGAL may serve as appropriate assessment indicators of asthma severity in pediatric patients.

Plasma bioactive adrenomedullin predicts mortality and need for dialysis in critical COVID-19

COVID-19 is a severe respiratory disease affecting millions worldwide, causing significant morbidity and mortality. Adrenomedullin (bio-ADM) is a vasoactive hormone regulating the endothelial barrier and has been associated with COVID-19 mortality and other adverse events. This prospective cohort pilot study included 119 consecutive patients with verified SARS-CoV-2 infection admitted to two intensive care units (ICUs) in Southern Sweden. Bio-ADM was retrospectively analysed from plasma on ICU admission, and days 2 and 7. Information on comorbidities, adverse events and mortality was collected. The primary outcome was 90-day mortality, and secondary outcomes were markers of disease severity. The association between bio-ADM and outcomes was analysed using survival analysis and logistic regression. Bio-ADM on admission, day 2, and day 7 only moderately predicted 90-day mortality in univariate and multivariate Cox regression. The relative change in bio-ADM between sample times predicted 90-day mortality better even when adjusting for the SAPS3 score, with an HR of 1.09 (95% CI 1.04–1.15) and a C-index of 0.82 (95% CI 0.72–0.92) for relative change between day 2 and day 7. Bio-ADM had a good prediction of the need for renal replacement therapy in multivariate Cox regression adjusting for creatinine, where day 2 bio-ADM had an HR of 3.18 (95% CI 1.21–8.36) and C-index of 0.91 (95% CI 0.87–0.96). Relative changes did not perform better, possibly due to a small sample size. Admission and day 2 bio-ADM was associated with early acute kidney injury (AKI). Bio-ADM on ICU admission, day 2 and day 7 predicted 90-day mortality and dialysis needs, highlighting bio-ADM’s importance in COVID-19 pathophysiology. Bio-ADM could be used to triage patients with a risk of adverse outcomes and as a potential target for clinical interventions.

Elevated Cardiac Troponin Levels as a Predictor of Increased Mortality Risk in Non-Cardiac Critically Ill Patients Admitted to a Medical Intensive Care Unit.

Background: Cardiac troponin I (TnI) is a specific marker of myocardial damage used in the diagnosis of acute coronary syndrome (ACS). TnI levels can also be elevated in patients without ACS, which is linked to a worse prognosis and mortality. We evaluated the clinical implications and prognostic significance of serum TnI levels in critically ill non-cardiac patients admitted to the intensive care unit (ICU) at a tertiary-level hospital. Materials and Methods: A three-year retrospective study including the years 2017-2020 was conducted to evaluate in-hospital mortality during ICU stay and mortality rates at 28 and 90 days, as well as one and two years after admission, in 557 patients admitted to the medical ICU for non-cardiac causes. Results: TnI levels were elevated in 206 (36.9%) patients. Patients with elevated TnI levels were significantly older and had higher rates of comorbidities, including chronic heart failure, coronary heart disease, and chronic kidney disease (p < 0.05 for all). Patients with elevated TnI levels required more invasive mechanical ventilation, vasopressor infusion, and dialysis in the ICU and experienced more shock within the first 72 h (p = 0.001 for all). High TnI levels were associated with higher Acute Physiological and Chronic Health Evaluation (APACHE) II (27.6 vs. 20.3, p = 0.001) and Sequential Organ Failure assessment (8.8 vs. 5.26, p = 0.001) scores. Elevated TnI levels were associated with higher mortality rates at 28 days (58.3% vs. 19.4%), 90 days (69.9% vs. 35.0%), one year (78.6% vs. 46.2%), and two years (82.5% vs. 55.6%) (p < 0.001 for all). Univariate logistic regression analysis revealed that high TnI levels were a strong independent predictor of mortality at all time points: 28 days (OR = 1.2, 95% CI: 1.108-1.3, p < 0.001), 90 days (OR = 1.207, 95% CI: 1.095-1.33, p = 0.001), one year (OR = 1.164, 95% CI: 1.059-1.28, p = 0.002), and two year (OR = 1.119, 95% CI: 1.026-1.22, p = 0.011). Multivariate analysis revealed that age, albumin level, APACHE II score, and requirements for dialysis and vasopressor use in the ICU were important predictors of mortality across all timeframes, but elevated TnI levels were not. Conclusions: Elevated TnI levels in critically ill non-cardiac patients are markers of disease severity. While elevated TnI levels were significant predictors of mortality in the univariate analysis, they lost significance in the multivariate model when adjusted for other factors. Patients with elevated TnI levels had higher mortality rates across all timeframes, from 28 days to two years.

Transpulmonary Pressure as a Predictor of Successful Lung Recruitment: Reanalysis of a Multicenter International Randomized Clinical Trial.

Recruitment maneuvers are used in patients with ARDS to enhance oxygenation and lung mechanics. Heterogeneous lung and chest-wall mechanics lead to unpredictable transpulmonary pressures and could impact recruitment maneuver success. Tailoring care based on individualized transpulmonary pressure might optimize recruitment, preventing overdistention. This study aimed to identify the optimal transpulmonary pressure for effective recruitment and to explore its association with baseline characteristics. We performed post hoc analysis on the Esophageal Pressure Guided Ventilation (EpVent2) trial. We estimated the dose-response relationship between end-recruitment end-inspiratory transpulmonary pressure and the change in lung elastance after a recruitment maneuver by using logistic regression weighted by a generalized propensity score. A positive change in lung elastance was indicative of overdistention. We examined how patient characteristics, disease severity markers, and respiratory parameters predict transpulmonary pressure by using multivariate linear regression models and dominance analyses. Of 121 subjects, 43.8% had a positive change in lung elastance. Subjects with a positive change in lung elastance had a mean ± SD transpulmonary pressure of 15.1 ± 4.9 cm H2O, compared with 13.9 ± 3.9 cm H2O in those with a negative change in lung elastance. Higher transpulmonary pressure was associated with increased probability of a positive change in lung elastance (adjusted odds ratio 1.35 per 1 cm H2O of transpulmonary pressure, 95% CI 1.13-1.61; P = .001), which indicated an S-shaped dose-response curve, with overdistention probability > 50% at transpulmonary pressure values > 18.3 cm H2O. The volume of recruitment was transpulmonary pressure-dependent (P < .001; R2 = 0.49) and inversely related to a change in lung elastance after adjusting for baseline lung elastance (P < .001; R2= 0.43). Negative correlations were observed between transpulmonary pressure and body mass index, PEEP, Sequential Organ Failure Assessment score, and PaO2 /FIO2 , whereas baseline lung elastance showed a positive correlation. The body mass index emerged as the dominant negative predictor of transpulmonary pressure (ranking 1; contribution to R2 = 0.08), whereas pre-recruitment elastance was the sole positive predictor (contribution to R2 = 0.06). Higher end-recruitment transpulmonary pressure increases the volume of recruitment but raises the risk of overdistention, providing the rationale for transpulmonary pressure to be used as a clinical target. Predictors, for example, body mass index, could guide recruitment maneuver individualization to balance adequate volume gain with overdistention.