Disease Severity Outcomes Research Articles

Gene Variants of the OAS/RNase L Pathway and Their Association with Severity of Symptoms and Outcome of SARS-CoV-2 Infection.

The interferon pathway plays a critical role in triggering the immune response to SARS-CoV-2, and these gene variants may be involved in the severity of COVID-19. This study aimed to analyze the frequency of three gene variants of OAS and RNASEL with the occurrence of COVID-19 symptoms and disease outcome. This cross-sectional study included 104 patients with SARS-CoV-2 infection, of which 34 were asymptomatic COVID-19, and 70 were symptomatic cases. The variants rs486907 (RNASEL), rs10774671 (OAS1), rs1293767 (OAS2), and rs2285932 (OAS3) were screened and discriminated using a predesigned 5'-nuclease assay with TaqMan probes. Patients with the allele C of the OAS2 gene rs1293767 (OR = 0.36, 95% CI: 0.15-0.83, p = 0.014) and allele T of the OAS3 gene rs2285932 (OR = 0.39, 95% CI: 0.2-0.023, p = 0.023) have lower susceptibility to developing symptomatic COVID-19. The genotype frequencies (G/G, G/C, and C/C) of rs1293767 for that comparison were 64.7%, 29.4%, and 5.9% in the asymptomatic group and 95.2%, 4.8%, and 0% in severe disease (p < 0.05). Our data indicate that individuals carrying the C allele of the OAS2 gene rs1293767 and the T allele of the OAS3 gene rs2285932 are less likely to develop symptomatic COVID-19, suggesting these genetic variations may confer a protective effect among the Mexican study population. Furthermore, the observed differences in genotype frequencies between asymptomatic individuals and those with severe disease emphasize the potential of these variants as markers for disease severity. These insights enhance our understanding of the genetic factors that may influence the course of COVID-19 and underscore the potential for genetic screening in identifying individuals at increased risk for severe disease outcomes.

Greater Disease Severity and Worse Clinical Outcomes in Patients Hospitalised with COVID-19 in Africa.

COVID-19 cardiovascular research from Africa is limited. This study describes cardiovascular risk factors, manifestations, and outcomes of patients hospitalised with COVID-19 in the African region, with an overarching goal to investigate whether important differences exist between African and other populations, which may inform health policies. A multinational prospective cohort study was conducted on adults hospitalised with confirmed COVID-19, consecutively admitted to 40 hospitals across 23 countries, 6 of which were African countries. Of the 5,313 participants enrolled globally, 948 were from African sites (n = 9). Data on demographics, pre-existing conditions, clinical outcomes in hospital (major adverse cardiovascular events (MACE), renal failure, neurological events, pulmonary outcomes, and death), 30-day vitality status and re-hospitalization were assessed, comparing African to non-African participants. Access to specialist care at African sites was significantly lower than the global average (71% vs. 95%), as were ICU admissions (19.4% vs. 34.0%) and COVID-19 vaccination rates (0.6% vs. 7.4%). The African cohort was slightly younger than the non-African cohort (55.0 vs. 57.5 years), with higher rates of hypertension (48.8% vs. 46.9%), HIV (5.9% vs. 0.3%), and Tuberculosis (3.6% vs. 0.3%). In African sites, a higher proportion of patients suffered cardiac arrest (7.5% vs. 5.1%) and acute kidney injury (12.7% vs. 7.2%), with acute kidney injury (AKI) appearing to be one of the strongest predictors of MACE and death in African populations compared to other populations. The overall mortality rate was significantly higher among African participants (18.2% vs. 14.2%). Overall, hospitalised African patients with COVID-19 had a higher mortality despite a lower mean age, contradicting literature that had previously reported a lower mortality attributed to COVID-19 in Africa. African sites had lower COVID-19 vaccination rates and higher AKI rates, which were positively associated with increased mortality. In conclusion, African patients were hospitalized with more severe COVID-19 cases and had poorer outcomes.

Acute Cardiac Events in Hospitalized Older Adults With Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) infection can cause severe respiratory illness in older adults. Less is known about the cardiac complications of RSV disease compared with those of influenza and SARS-CoV-2 infection. To describe the prevalence and severity of acute cardiac events during hospitalizations among adults aged 50 years or older with RSV infection. This cross-sectional study analyzed surveillance data from the RSV Hospitalization Surveillance Network, which conducts detailed medical record abstraction among hospitalized patients with RSV infection detected through clinician-directed laboratory testing. Cases of RSV infection in adults aged 50 years or older within 12 states over 5 RSV seasons (annually from 2014-2015 through 2017-2018 and 2022-2023) were examined to estimate the weighted period prevalence and 95% CIs of acute cardiac events. Acute cardiac events, identified by International Classification of Diseases, 9th Revision, Clinical Modification or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification discharge codes, and discharge summary review. Severe disease outcomes, including intensive care unit (ICU) admission, receipt of invasive mechanical ventilation, or in-hospital death. Adjusted risk ratios (ARR) were calculated to compare severe outcomes among patients with and without acute cardiac events. The study included 6248 hospitalized adults (median [IQR] age, 72.7 [63.0-82.3] years; 59.6% female; 56.4% with underlying cardiovascular disease) with laboratory-confirmed RSV infection. The weighted estimated prevalence of experiencing a cardiac event was 22.4% (95% CI, 21.0%-23.7%). The weighted estimated prevalence was 15.8% (95% CI, 14.6%-17.0%) for acute heart failure, 7.5% (95% CI, 6.8%-8.3%) for acute ischemic heart disease, 1.3% (95% CI, 1.0%-1.7%) for hypertensive crisis, 1.1% (95% CI, 0.8%-1.4%) for ventricular tachycardia, and 0.6% (95% CI, 0.4%-0.8%) for cardiogenic shock. Adults with underlying cardiovascular disease had a greater risk of experiencing an acute cardiac event relative to those who did not (33.0% vs 8.5%; ARR, 3.51; 95% CI, 2.85-4.32). Among all hospitalized adults with RSV infection, 18.6% required ICU admission and 4.9% died during hospitalization. Compared with patients without an acute cardiac event, those who experienced an acute cardiac event had a greater risk of ICU admission (25.8% vs 16.5%; ARR, 1.54; 95% CI, 1.23-1.93) and in-hospital death (8.1% vs 4.0%; ARR, 1.77; 95% CI, 1.36-2.31). In this cross-sectional study over 5 RSV seasons, nearly one-quarter of hospitalized adults aged 50 years or older with RSV infection experienced an acute cardiac event (most frequently acute heart failure), including 1 in 12 adults (8.5%) with no documented underlying cardiovascular disease. The risk of severe outcomes was nearly twice as high in patients with acute cardiac events compared with patients who did not experience an acute cardiac event. These findings clarify the baseline epidemiology of potential cardiac complications of RSV infection prior to RSV vaccine availability.

NLRP3/GSDMD mediated pyroptosis induces lung inflammation susceptibility in diesel exhaust exposed mouse strains

BackgroundGenetic diversity among species influences the disease severity outcomes linked to air pollution. However, the mechanism responsible for this variability remain elusive and needs further investigation. ObjectiveTo investigate the genetic factors and pathways linked with differential susceptibility in mouse strains associated with diesel exhaust exposure. MethodsC57BL/6 and Balb/c mice were exposed to diesel exhaust (DE) for 5 days/week for 30 min/day for 8 weeks. Body weight of mice was recorded every week and airway hyperresponsiveness towards DE exposure was recorded after 24 h of last exposure. Mice were euthanised to collect BALF, blood, lung tissues for immunobiochemical assays, structural integrity and genetic studies. ResultsC57BL/6 mice showed significantly decreased body weight in comparison to Balb/c mice (p < 0.05). Both mouse strains showed lung resistance and damage to elastance upon DE exposure compared to respective controls (p < 0.05) with more pronounced effects in C57BL/6 mice. Lung histology showed increase in bronchiolar infiltration and damage to the wall in C57BL/6 mice (p < 0.05). DE exposure upregulated pro-inflammatory and Th2 cytokine levels in C57BL/6 in comparison to Balb/c mice. C57BL/6 mice showed increase in Caspase-1 and ASC expression confirming activation of downstream pathway. This showed significant activation of inflammasome pathway in C57BL/6 mice with ∼2-fold increase in NLRP3 and elevated IL-1β expression. Gasdermin-D levels were increased in C57BL/6 mice demonstrating induction of pyroptosis that corroborated with IL-1β secretion (p < 0.05). Genetic variability among both species was confirmed with sanger’s sequencing suggesting presence of SNPs in 3’UTRs of IL-1β gene influencing expression between mouse strains. ConclusionsC57BL/6 mice exhibited increased susceptibility to diesel exhaust in contrast to Balb/c mice via activation of NLRP3-related pyroptosis. Differential susceptibility between strains may be attributed via SNPs in the 3'UTRs of the IL-1β gene.

The low expression of matrix metalloproteinases: a key to longevity?

Over the past few decades, it has become clear that an excessive activity of matrix metalloproteinases (MMPs) can accelerate the progression and fatal outcomes of several serious age-related diseases, including atherosclerotic coronary heart disorders and various types of malignancies. These proteolytic enzymes mediate the degradation and remodeling of the extracellular matrix through cleaving its various components, thereby affecting many critical functions of surrounding cells and intercellular communication. Consequently, the low expression levels of MMPs can be important in the prevention and treatment of such chronic life-threatening pathologies, contributing to the better quality of life and longer life expectancy. In this review article, the pathogenic proteolytic roles of MMPs are examined in more detail, especially in the cases of heart attack and stroke as well as cancer invasion and metastasis, showing that these enzymes can be considered not only as diagnostic and prognostic biomarkers but also as important therapeutic targets in the fight against many age- and lifestyle-related serious disorders. The identification and development of suppressing agents with a selective activity towards specific MMPs have, however, still remained a complex and complicated challenge, in which natural plant-derived compounds are increasingly recognized as promising leads for the new-generation inhibitors.

Effects of the Use of Beta-Blockers on Chronic Obstructive Pulmonary Disease Associated with Cardiovascular Comorbities: Systematic Review and Meta-analysis.

Cardiovascular comorbidity is common in individuals with chronic obstructive pulmonary disease (COPD). This factor interferes with pharmacological treatment. The use of β-blockers has been proposed for their known cardioprotective effects. However, due to their adverse reactions, and the risk of causing bronchospasm, there is reluctance to use them. To summarize existing evidence on the effects of β-blocker use in COPD associated with cardiovascular comorbidities in relation to disease severity, exacerbation, and mortality outcomes. EMBASE, Medline, Lilacs, Cochrane Library, and Science Direct databases were used. Observational studies that evaluated the effects of β-blockers on individuals with COPD and cardiovascular comorbidities, and related disease severity, exacerbations, or mortality outcomes were included. Studies that did not present important information about the sample and pharmacological treatment were excluded. Twenty studies were included. Relevance to patient care and clinical practice: The use of β-blockers in individuals with COPD and cardiovascular disease caused positive effects on mortality and exacerbations outcomes, compared with the results of individuals who did not use them. The severity of the disease caused a slight change in forced expiratory volume in 1 second. The odds ratio for mortality was 0.50 (95% confidence interval [CI], 0.39 to 0.63; p&lt;0.00001), and for exacerbations, 0.76 (95% CI, 0.62 to 0.92; p=0.005), being favorable to the group that used β-blockers. Further studies are needed to study the effect of using a specific β-blocker in COPD associated with a specific cardiovascular comorbidity.

Cyclophilin D knockout significantly prevents HCC development in a streptozotocin-induced mouse model of diabetes-linked NASH.

A family of Peptidyl-prolyl isomerases (PPIases), called Cyclophilins, localize to numerous intracellular and extracellular locations where they contribute to a variety of essential functions. We previously reported that non-immunosuppressive pan-cyclophilin inhibitor drugs like reconfilstat (CRV431) or NV556 decreased multiple aspects of non-alcoholic fatty liver disease (NAFLD) in mice under two different non-alcoholic steatohepatitis (NASH) mouse models. Both CRV431 and NV556 inhibit several cyclophilin isoforms, among which cyclophilin D (CypD) has not been previously investigated in this context. It is unknown whether it is necessary to simultaneously inhibit multiple cyclophilin family members to achieve therapeutic benefits or if loss-of-function of one is sufficient. Furthermore, narrowing down the isoform most responsible for a particular aspect of NAFLD/NASH, such as hepatocellular carcinoma (HCC), would allow for more precise future therapies. Features of human diabetes-linked NAFLD/NASH can be reliably replicated in mice by administering a single high dose of streptozotocin to disrupt pancreatic beta cells, in conjunction with a high sugar, high fat, high cholesterol western diet over the course of 30 weeks. Here we show that while both wild-type (WT) and Ppif-/- CypD KO mice develop multipe severe NASH disease features under this model, the formation of HCC nodules was significantly blunted only in the CypD KO mice. Furthermore, of differentially expressed transcripts in a qPCR panel of select HCC-related genes, nearly all were downregulated in the CypD KO background. Cyclophilin inhibition is a promising and novel avenue of treatment for diet-induced NAFLD/NASH. This study highlights the impact of CypD loss-of-function on the development of HCC, one of the most severe disease outcomes.

Novel genetic association of the Furin gene polymorphism rs1981458 with COVID-19 severity among Indian populations

SARS CoV-2, the causative agent for the ongoing COVID-19 pandemic, it enters the host cell by activating the ACE2 receptor with the help of two proteasesi.e., Furin and TMPRSS2. Therefore, variations in these genes may account for differential susceptibility and severity between populations. Previous studies have shown that the role of ACE2 and TMPRSS2 gene variants in understanding COVID-19 susceptibility among Indian populations. Nevertheless, a knowledge gap exists concerning the COVID-19 susceptibility of Furin gene variants among diverse South Asian ethnic groups. Investigating the role of Furin gene variants and their global phylogeographic structure is essential to comprehensively understanding COVID-19 susceptibility in these populations. We have used 450 samples from diverse Indian states and performed linear regression to analyse the Furin gene variant's with COVID-19 Case Fatality Rate (CFR) that could be epidemiologically associated with disease severity outcomes. Associated genetic variants were further evaluated for their expression and regulatory potential through various Insilco analyses. Additionally, we examined the Furin gene using next-generation sequencing (NGS) data from 393 diverse global samples, with a particular emphasis on South Asia, to investigate its Phylogeographic structure among diverse world populations. We found a significant positive association for the SNP rs1981458 with COVID-19 CFR (p < 0.05) among diverse Indian populations at different timelines of the first and second waves. Further, QTL and other regulatory analyses showed various significant associations for positive regulatory roles of rs1981458 and Furin gene, mainly in Immune cells and virus infection process, highlighting their role in host immunity and viral assembly and processing. The Furin protein–protein interaction suggested that COVID-19 may contribute to Pulmonary arterial hypertension via a typical inflammation mechanism. The phylogeographic architecture of the Furin gene demonstrated a closer genetic affinity of South Asia with West Eurasian populations. Therefore, it is worth proposing that for the Furin gene, the COVID-19 susceptibility of South Asians will be more similar to the West Eurasian population. Our previous studies on the ACE2 and TMPRSS2 genes showed genetic affinity of South Asian with East Eurasians and West Eurasians, respectively. Therefore, with the collective information from these three important genes (ACE2, TMPRSS2 and Furin) we modelled COVID-19 susceptibilityof South Asia in between these two major ancestries with an inclination towards West Eurasia. In conclusion, this study, for the first time, concluded the role of rs1981458 in COVID-19 severity among the Indian population and outlined its regulatory potential.This study also highlights that the genetic structure for COVID-19 susceptibilityof South Asia is distinct, however, inclined to the West Eurasian population. We believe this insight may be utilised as a genetic biomarker to identify vulnerable populations, which might be directly relevant for developing policies and allocating resources more effectively during an epidemic.

Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.

Sphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH). Data of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis. Patients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p < 0.001). When divided patients into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge, S1P levels were significantly elevated in the severe group compared to the mild-to-moderate group (admission 259.30 vs. 300.54, p < 0.001; 90-day 275.24 vs. 303.25, p < 0.001). The patients were divided into three groups with different concentration gradients, which showed significant statistical differences in admission mRS scores (3 vs. 4 vs. 5, p < 0.001), 90-day mRS scores (2.5 vs. 3 vs. 4, p < 0.001), consciousness disorders (45.5% vs. 68.2% vs. 69.6%, p = 0.033), ICU admission (29.5% vs. 59.1% vs. 89.1%, p < 0.001), surgery (15.9% vs. 47.7% vs. 82.6%, p < 0.001), intraventricular hemorrhages (27.3% vs. 61.4% vs. 65.2%, p < 0.001) and pulmonary infection (25% vs. 47.7% vs. 84.8%, p < 0.001). Multivariate analysis displayed that S1P level was an independent risk factor for disease severity (OR = 1.037, 95% CI = 1.020-1.054, p < 0.001) and prognosis (OR = 1.018, 95% CI = 1.006-1.030, p = 0.003). ROC curves revealed a predictive value of S1P levels with an area under the curve of 0.7952 (95% CI = 0.7144-0.8759, p < 0.001) for disease severity and 0.7105 (95% CI = 0.6227-0.7983, p < 0.001) for prognosis. Higher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.

Underlying Mental Illness and Risk of Severe Outcomes Associated With COVID-19.

According to the Centers for Disease Control and Prevention, depression and schizophrenia, among other conditions, put individuals at high risk for severe COVID-19 infection. Patients at high risk often are eligible for outpatient therapies, such as antiviral and monoclonal antibody therapies, to prevent severe infection. However, depression and schizophrenia are not considered risk factors for severe COVID-19 infection at the Captain James A. Lovell Federal Health Care Center in North Chicago, Illinois, making patients with these conditions ineligible for outpatient therapy unless they have another high-risk condition. This retrospective cohort study assessed outcomes among patients with mild-to-moderate COVID-19 to determine whether depression and/or schizophrenia impacted the risk of severe disease or negative outcomes. The primary outcome was severe COVID-19 outcomes defined as hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death within 30 days of infection. Patients with depression or schizophrenia had more hospitalizations and deaths, but this difference was not statistically significant (P = .36). Death within 30 days of COVID-19 infection only occurred in patients with depression or schizophrenia. Although there were more hospitalizations and deaths from COVID-19 within 30 days of infection among patients with depression and schizophrenia compared with individuals without these disorders, this finding was not statistically significant.

Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes. We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up. 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22-1.38; p<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44-1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52-2.39; p<0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29-1.56; p<0.0001), 1.98 (95% CI 1.77-2.21; p<0.0001) and 3.05 (95% CI 2.25-4.14; p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01-1.24; p=0.027), for each increment in sputum purulence. Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

Infection with different Neospora caninum strains causes differences in the glycosylation pattern in the uteri and placentae of Neospora caninum-infected heifers

Neospora caninum is an obligate intracellular parasite that causes abortion in ruminants. Different strains produce differences in the severity of disease outcomes. These differences may cause physiological or pathological changes in cells, modifying the intercellular interactions and intracellular transport pathways that could be evidenced by identifying the terminal sugars. This study aimed to characterize the oligosaccharide pattern in the bovine placenta and uterus after infection with tachyzoites of three different strains of N. caninum (Nc-1, Nc-6 Argentina and Nc Spain-7) during early gestation. Fourteen heifers were inoculated intravenously on day 70 of gestation with 2 × 108 N. caninum tachyzoites and samples of placentae and uteri were analysed by histology and lectin histochemistry. In the infected groups, severe placentitis was associated with changes in lectin binding in the vascular endothelium by Lens culinaris agglutinin (LCA), Pisum sativum agglutinin (PSA) and Ricinus communis I (RCA-I) lectins, in the epithelial cells of the endometrial glands by RCA-I, Dolichos biflorus agglutinin (DBA), succinylated wheat germ agglutinin, peanut agglutinin (PNA), concanavalin-A (CON-A), LCA, PSA and Phaseolus vulgaris erythroagglutinin (PHA-e), and in the trophoblast layer by PNA, CON-A, LCA, PSA, PHA-e, soybean agglutinin, RCA-I, DBA and Bandieraea simplicifolia agglutinin (BSA-I). The results suggest that N. caninum causes changes in the glycosylation pattern in the maternofetal interface tissues and might cause abortions in early gestation due to changes in the cellular structure of the placenta.

Healthcare provider Communication and Data-Informed Message Strategies for Encouraging Older Adults to Stay up to Date on COVID-19 Vaccination.

Older adults are a high in risk of severe COVID-19 disease outcomes and experience "vaccine hesitancy." Guided by health communication models such as the Reasoned Action Approach and the Extended Parallel Process Model, online surveys designed to inform statewide public health communication efforts were administered in West Virginia, a primarily rural and fully Appalachian state, in Winter 2021 (n = 272) and Fall 2022 (n = 248). Adults ages 50+ years (N = 520) reported attitudes, intentions, and behaviors regarding COVID-19 vaccination and their related patient-provider communication. Vaccine usefulness/safety, perceived effectiveness, and subjective norms predicted behavior while perceived severity, efficacy, and usefulness/safety predicted intention to get a booster, specifically the updated Fall 2022 Omicron (bivalent) booster. As patient-provider communication (which a minority reported receiving) was a strong predictor of behavioral outcomes, characteristics of effective healthcare provider communication and considerations for public message construction are discussed.

Improved Outcomes in Eosinophilic Esophagitis with Higher Medication Possession Ratio.

Eosinophilic esophagitis (EoE) disease activity can be caused by treatment non-adherence. Medication possession ratio (MPR) is an established metric of medication adherence. A higher MPR correlates with better outcomes in several chronic diseases, but MPR has not been investigated with respect to EoE. A retrospective cohort study was performed using an established EoE registry for the years 2005 to 2020. Treatment periods were identified, MPRs were calculated, and medical records were assessed for histologic remission (<15 eos/hpf), dysphagia, food impaction, stricture occurrence, and esophageal dilation that corresponded to each treatment period. In total, 275 treatment periods were included for analysis. The MPR in the histologic remission treatment period group was 0.91 (IQR 0.63-1) vs. 0.63 (IQR 0.31-0.95) for the non-remission treatment period group (p < 0.001). The optimal MPR cut-point for histologic remission was 0.7 (Sen 0.66, Spec 0.62, AUC 0.63). With MPRs ≥ 0.7, there were significantly increased odds of histologic remission (odds ratio 3.05, 95% confidence interval 1.79-5.30) and significantly decreased odds of dysphagia (OR 0.27, 95% CI 0.15-0.45), food impaction (OR 0.26, 95% CI 0.11-0.55), stricture occurrence (OR 0.52 95% CI 0.29-0.92), and esophageal dilation (OR 0.29, 95% CI 0.15-0.54). Assessing MPR before repeating an esophagogastroduodenoscopy may decrease unnecessary procedures in the clinical management of eosinophilic esophagitis.

Pan-enteric Capsule Endoscopy to Characterize Crohn's Disease Phenotypes and Predict Clinical Outcomes in Children and Adults: The Bomiro Study.

Pan-enteric capsule endoscopy (PCE) provides useful information for the management of Crohn's disease (CD), especially in children. No study has evaluated the ability of PCE to characterize CD phenotypes and outcomes in children and adults. In a prospective multicenter observational study, we recruited patients with CD >6 years from 4 centers in Italy. Patients underwent clinical, biomarker assessment and PCE. Lesions were graded using the PCE system. For each segment, the most common lesion (MCL), the most severe lesion (MSL), and the extent of involvement were defined. Disease severity, extent, and clinical outcomes were compared between children and adults. A logistic regression analysis was used to identify predictive factors for negative outcomes in both age groups. One hundred ninety-four consecutive patients (adults/children: 144/50) were evaluated for a total of 249 procedures. Children were more likely to have extensive disease, particularly in the colon. Higher MCL scores were independently associated with treatment escalation (odds ratio [OR], 4.09; 95% CI, 1.80-9.25; P = .001), while >30% disease extent was more indicative of clinical and endoscopic relapse (OR, 2.98; 1.26-7.08; P = .013). Disease extent was the only factor associated with endoscopic recurrence in children (OR, 4.50; 95% CI, 1.47-13.77; P = .008), while severe lesions in adults provided a better predictor of treatment escalation (OR, 4.31; 95% CI, 1.52-12.1; P = .006). Postexamination, PCE contributed to a change of therapy in 196/249 (79%) of the procedures. PCE allowed the characterization of CD phenotypes in children and adults by assessing disease severity and extent, which are of different importance in predicting clinical outcomes in these age groups.

A Comprehensive Review on Serum Lactate Dehydrogenase (LDH) and Uric Acid in Preeclampsia: Implications for Maternal Health and Disease Severity.

Preeclampsia, a hypertensive disorder unique to pregnancy, remains a significant cause of maternal and fetal morbidity and mortality worldwide. Serum lactate dehydrogenase (LDH) and uric acid have garnered attention as potential biomarkers in understanding preeclampsia's pathophysiology and clinical management. Elevated LDH and uric acid levels have been associated with disease severity and adverse outcomes, highlighting their potential utility in risk stratification and guiding management strategies. This comprehensive review explores the roles of LDH and uric acid in preeclampsia, summarizing current evidence regarding their diagnostic, prognostic, and therapeutic implications. Future research directions are also discussed, including understanding and validation studies. Integrating LDH and uric acid measurements into routine clinical practice may facilitate early detection and intervention, ultimately improving outcomes for preeclamptic pregnancies. This review underscores the importance of serum biomarkers in enhancing our understanding and managing preeclampsia, aiming to optimize maternal and fetal health.

Fungal Infections and Social Determinants of Health: Using Data to Identify Disparities.

Fungal diseases disproportionately affect certain demographic populations, but few studies have thoroughly investigated the drivers of those disparities. We summarize data sources that can be considered to explore potential associations between fungal diseases and social determinants of health in the United States. Sociodemographic disparities are apparent in fungal diseases, and social determinants of health (e.g., income, living conditions, and healthcare access) may be associated with increased risk of infection, severe disease, and poor health outcomes. Numerous data sources are available in the United States to analyze the potential association between fungal diseases and underlying social determinants of health. Each source has benefits and limitations that should be considered in the development of analysis plans. Inherent challenges to all fungal disease data (e.g., underdiagnosis, underreporting, and inability to detect people who do not seek medical care) should be noted and accounted for in interpretation of results.

Dynamics and prognostic value of serum neurofilament light chain in Guillain-Barré syndrome

Neurofilament light chain (NfL) is a biomarker for axonal damage in several neurological disorders. We studied the longitudinal changes in serum NfL in patients with Guillain-Barré syndrome (GBS) in relation to disease severity, electrophysiological subtype, treatment response, and prognosis. We included patients with GBS who participated in a double-blind, randomised, placebo-controlled trial that evaluated the effects of a second course of intravenous immunoglobulin (IVIg) on clinical outcomes. Serum NfL levels were measured before initiation of treatment and at one, two, four, and twelve weeks using a Simoa HD-X Analyzer. Serum NfL dynamics were analysed using linear mixed-effects models. Logistic regression was employed to determine the associations of serum NfL with clinical outcome and the prognostic value of serum NfL after correcting for known prognostic markers included in the modified Erasmus GBS Outcome Score (mEGOS). NfL levels were tested in serum from 281 patients. Serum NfL dynamics were associated with disease severity and electrophysiological subtype. Strong associations were found between high levels of serum NfL at two weeks and inability to walk unaided at four weeks (OR=1.74, 95% CI=1.27-2.45), and high serum NfL levels at four weeks and inability to walk unaided at 26 weeks (OR=2.79, 95% CI=1.72-4.90). Baseline serum NfL had the most significant prognostic value for ability to walk, independent of predictors included in the mEGOS. The time to regain ability to walk unaided was significantly longer for patients with highest serum NfL levels at baseline (p=0.0048) and week 2 (p<0.0001). No differences in serum NfL were observed between patients that received a second IVIg course vs. IVIg and placebo. Serum NfL levels are associated with disease severity, axonal involvement, and poor outcome in GBS. Serum NfL potentially represents a biomarker to monitor neuronal damage in GBS and an intermediate endpoint to evaluate the effects of treatment. Prinses Beatrix Spierfonds W.OR19-24.

Protein Interaction Assessing Mitochondrial Biogenesis as a Next Generation Biomarker in Sepsis: A Prospective Cohort Study

BackgroundMetabolic derangements in sepsis stem from mitochondrial injury and contribute to organ dysfunction and mortality. Thus, repair of mitochondrial damage seems pivotal for recovery and determining clinical outcome in sepsis. However, reliable biomarkers assessing mitochondrial repair noninvasively in peripheral blood are currently lacking. Research QuestionAre different gene transcripts related to mitochondrial repair (i.e., biogenesis, fusion, fission, mitophagy) and the protein interaction assessing mitochondrial biogenesis, both measured in peripheral blood, associated with disease severity and clinical outcome? Study Design and MethodsHealthy controls (n=22), uninfected critically ill control patients (n=13), and 75 sepsis patients were included in this prospective multicentric observational study. Gene products of mitochondrial quality control and mitochondrial DNA were measured on day 1 and 4 in peripheral blood mononuclear cells. In addition, we assessed in the same samples the mitochondrial protein interaction of TFAM-TFB2M using a proximity ligation assay. Septic patients were stratified in the outcome-related subgroups “ICU-free within 1 week” (n=16), “Not ICU-free within 1 week” (n=36), and “30-day non-survivors” (n=23). ResultsTranscript levels of the assessed mRNA markers of septic patients were not associated with disease severity nor did they predict clinical outcome. Strikingly, the mitochondrial protein interaction of TFAM-TFB2M on day 4 (p<0.05) as well as the difference between day 1 and 4 (p<0.001) allowed stratification in the three clinical outcome subgroups. In addition, a decline in TFAM-TFB2M protein interactions between day 1 and day 4 was an independent predicator for 30-day mortality (aHR: 8.34; 95% CI: 2.73 to 25.45, p<0.001). InterpretationSepsis patients with an early activation of mitochondrial biogenesis were more likely to be ICU-free within 1 week. A mitochondrial and clinical recovery can be assessed via the protein interaction of TFAM-TFB2M in peripheral blood. Thus, mitochondrial protein interactions targeting mitochondrial biogenesis provide a promising dimension of novel biomarkers assessing mitochondrial dysfunction in sepsis.

Assessing COVID-19 vaccine roll-out in Uganda: a case study of uptake and associated factors among health care workers and older people

Introduction We conducted a survey to investigate the uptake of COVID-19 vaccination among healthcare workers (HCWs) and older persons (≥ 50 years) in Uganda, groups at particular risk of infection and severe disease outcomes respectively. Methods The survey was conducted between May and August 2021, during the early phase of COVID-19 vaccine roll-out. All HCWs at Entebbe and Kisubi hospitals, Wakiso district (urban/peri-urban) and Villa Maria hospital, Kalungu district (rural), and non-healthcare worker (non-HCW) individuals enrolled in an ongoing older persons’ cohort study in Wakiso district, completed an interviewer-administered questionnaire on socio-demographics, pre-existing medical conditions, attitudes regarding COVID-19 vaccines, and vaccination uptake. Logistic regression was performed to investigate factors associated with uptake. Findings A total of 746 individuals, 597 HCWs and 149 non-HCW older persons, participated. Majority were aged ≤50 years (71.6%), female (63.1%), and had secondary school/other higher-level education (77.8%). COVID-19 uptake was 63.7%, overall; 95.2%, Entebbe Hospital; 75.4%, Kisubi Hospital; 49.5%, Villa Maria Hospital; and 20.8%, non-HCW. Among HCWs, health facility [Entebbe hospital (aOR 18.9, 95% CI 8.9-40.2), Kisubi hospital (aOR 5.2, 95% CI 3.0-9.0) all compared with Villa Maria], age &gt;50 years (aOR 3.1, 95% CI 1.2-8.4) and positive attitude towards COVID-19 vaccines (aOR 5.0, 95% CI 2.1-11.8) were associated with high uptake, while female sex (aOR 0.5, 95% CI 0.3-0.9) was associated with low uptake. Among non-HCW older persons, absence of chronic infectious disease (aOR 4.3, 95% CI 1.1-16.3) good attitude towards COVID-19 vaccines (aOR 29.2, 95% CI 4.1-208.8) were associated with high uptake, while advanced age 70-79 years (aOR 0.1, 95% CI 0.01-0.97) was associated with low uptake. Conclusion COVID-19 vaccine uptake was lowest among rural-based HCWs and non-HCW older persons. Vaccination campaigns during a pandemic need to foster positive attitudes towards vaccines and employ strategies specifically designed to improve vaccine uptake among disadvantaged populations.