Morbidity In Adults Research Articles

Abstract 14365: Interrogating Diastolic Dysfunction Using a Novel Stem Cell Model of Restrictive Cardiomyopathy

Introduction: Diastolic dysfunction is an important cause of morbidity and mortality in both children and adults. Unfortunately, investigation of new therapies is limited by a lack of in vitro models of diastolic dysfunction. Idiopathic Restrictive Cardiomyopathy (RCM) is a serious genetic condition in which children have an isolated defect in myocardial relaxation. Though some of the genetic lesions have been identified, there is still an incomplete understanding of the mechanisms that lead to diastolic dysfunction in this condition. Hypothesis: Cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) derived from patients with RCM will provide an in vitro model of diastolic dysfunction and will allow elucidation of cellular and molecular pathways involved in myocardial relaxation. Methods: Patients with RCM and a known pathogenic sarcomeric mutation were identified through speaking with providers in our heart failure and cardiac transplant program. hiPSCs were derived from patient blood samples and differentiated into cardiomyocytes. Isogenic controls were generated using CRISPR-mediated homologous directed repair. Calcium handling, contraction kinetics, and resting tension of RCM hiPSC-CMs were compared to control hiPSC-CMs on substrates with defined stiffness using high-throughput quantitative imaging techniques. Results: hiPSC-CMs derived from a patient with a pathogenic mutation in troponin T (TNNT2) display prolonged calcium kinetics and relaxation times compared to controls, as well as increased resting tension. Conclusions: RCM hiPSC-CMs represent a novel model of diastolic dysfunction that can be interrogated on a high-throughput platform. We plan to use these cells to perform proteome-scale functional screens, providing a novel opportunity to discover previously unknown contributors to diastolic dysfunction.

Entry of the Varicellovirus Canid herpesvirus 1 into Madin-Darby canine kidney epithelial cells is pH-independent and occurs via a macropinocytosis-like mechanism but without increase in fluid uptake.

Canid herpesvirus 1 (CHV-1) is a Varicellovirus that causes self-limiting infections in adult dogs but morbidity and mortality in puppies. Using a multipronged approach, we discovered the CHV-1 entry pathway into Madin-Darby canine kidney (MDCK) epithelial cells. We found that CHV-1 triggered extensive host cell membrane lamellipodial ruffling and rapid internalisation of virions in large, uncoated vacuoles, suggestive of macropinocytosis. Treatment with inhibitors targeting key macropinocytosis factors, including inhibitors of Na+ /H+ exchangers, F-actin, myosin light-chain kinase, protein kinase C, p21-activated kinase, phosphatidylinositol-3-kinase and focal adhesion kinase, significantly reduced viral replication. Moreover, the effect was restricted to exposure to the inhibitors early in infection, confirming a role for the macropinocytic machinery during entry. The profile of inhibitors also suggested a role for signalling via integrins and receptor tyrosine kinases in viral entry. In contrast, inhibitors of clathrin, caveolin, microtubules and endosomal acidification did not affect CHV-1 entry into MDCK cells. We found that the virus colocalised with the fluid-phase uptake marker dextran; however, surprisingly, CHV-1 infection did not enhance the uptake of dextran. Thus, our results indicate that CHV-1 uses a macropinocytosis-like, pH-independent entry pathway into MDCK cells, which nevertheless is not based on stimulation of fluid uptake. TAKE AWAYS: CHV-1 enters epithelial cells via a macropinocytosis-like mechanism. CHV-1 induces extensive lamellipodial ruffling. CHV-1 entry into MDCK cells is pH-independent.

Critical Connections Among Embedding of Childhood Adversity and Adult Chronic Gastrointestinal and Genitourinary Disorders: A Review of the Literature

A gap in the literature exists demonstrating associations between adverse child experiences (ACEs) as potential a priori contributing factors and gastrointestinal (GI)/genitourinary (GU) disorders. A narrative review of the literature was conducted to explore critical connections between ACEs and GI/GU disorders with a working hypothesis of a dose-responsive relationship existing among them. A literature search was conducted using MEDLINE, Cumulative Index of Nursing and Allied Health Literature, PubMed, and Web of Science using search terms adverse childhood experiences, childhood adversity, obesity, gastrointestinal disorders, and genitourinary disorders, and secondary searches of obesity and specific GI/GU disorders (eg, irritable bowel syndrome, pelvic pain). Duplicates and articles with inappropriate focus were discarded after review. A total of 58 articles were included. Research identified showed that ACEs do play a role in adult GI and GU morbidities in a dose-response manner, and selected factors such as socioeconomic status, race, gender identity, and physiologic state (eg, obesity) confer higher risk. Research also suggested that genetic/epigenetic mechanisms are at play in disease occurrence, and the impact of ACEs may be mitigated with positive life experiences. Research on the relationship between ACEs and GI/GU disorders is heterogeneous, notably due to wide variations in how types of ACEs are defined and screening methods used. Despite this limitation, associations are demonstrated. Awareness of a possible correlation between ACEs and risk of GI/GU disorders has the potential to improve patient care, especially through trauma-informed strategies.

Clinical Characteristics of Severe Acute Chest Syndrome in Children with Sickle Cell Disease

Background: Acute chest syndrome (ACS) is a form of acute lung injury that is a leading cause of morbidity and mortality in children and adults with sickle cell disease (SCD). Despite advances in health maintenance and disease-modifying therapies for SCD, ACS remains a common and often severe complication. There is still limited understanding of why some patients suffer more severe ACS episodes. Few studies have specifically investigated clinical parameters associated with severe ACS in the pediatric population. The purpose of this study is to determine the association between hematologic and radiologic clinical findings and severe ACS in children and adolescents with SCD.Methods: We conducted a single-institution retrospective chart review of 120 pediatric patients with HbSS or HbSβ 0 thalassemia and at least one documented episode of ACS, and then further classified patients by their most severe ACS event. We extracted laboratory and radiologic data to compare clinical findings. Infections reported in patient encounters were verified by documented viral PCR and blood cultures. Continuous variables were analyzed using Welch's t-test; categorical variables were analyzed using Fisher's exact test.Results: Eighty patients in the moderate ACS group were excluded for this analysis. Twenty patients (median age 5.6 years, SD 4.20) had mild ACS defined by no supplemental oxygen requirement, only one segmental or lobar infiltrate on chest radiography, and transfusion of less than 3 units (or 15 cc/kg) of red blood cells. Twenty patients (median age 7.6 years, SD 4.01) had severe ACS characterized by acute respiratory failure requiring mechanical (invasive or non-invasive) ventilation and/or exchange transfusion. Median length of stay for patients with severe ACS was longer than for the mild cohort (mean: 8 days vs 2 days, p <0.001). The median absolute neutrophil count (ANC) was significantly higher in the severe ACS cohort (19.8 x 10 3µL vs. 9.4 x 10 3 µL, p = 0.004). The median platelet count nadir was significantly lower in the severe ACS group compared to the mild group (165 x 10 3 µL vs. 309 x 10 3 µL, p <0.001). Review of radiologic data showed that the median number of lobes affected in the severe ACS group were 3, compared to 1 lobe in the mild group (p <0.001). Approximately 65% of patients with mild ACS had left-sided disease (p = 0.18), while 85% of patients with severe ACS had bilateral disease (p = 0.002). The risk of pleural effusions was also significantly increased with severe ACS [OR 76.00 (95% CI 9.235-825.6), p <0.001]. When we analyzed infection at time of ACS, the proportion of laboratory-confirmed viral infections were twice as high in the mild ACS cohort (41.2%), compared to the severe ACS cohort (20.0%, p = 0.279). There were no bloodstream bacterial infections found in either cohort.Conclusion: Severe ACS in children is a clinically distinct phenotype associated with longer length of stay, higher ANC and lower platelet nadir counts during active ACS, increased involvement of 3 or more lung lobes, and presence of pleural effusions. A lower proportion of confirmed viral infections were found in the severe ACS cohort compared to mild ACS patients, although did not reach statistical significance. Future prospective studies investigating the utility of these specific laboratory and radiographic parameters as components of an ACS severity prediction score are warranted. DisclosuresTubman: Forma Pharmaceuticals: Consultancy; Novartis Pharmaceuticals: Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Perkin Elmer: Honoraria. Fasipe: Emmaus: Consultancy; Bluebird Bio: Consultancy; Global Blood Therapeutics: Consultancy, Other: Grant Review Committee ; Novartis: Consultancy; Pfizer: Research Funding.

Prevalence and Factors Associated with Echocardiographic Abnormalities in Children with Sickle Cell Disease; Results from the Displace Study

IntroductionCardiopulmonary complications remain a leading cause of morbidity and mortality in adults with sickle cell disease (SCD) particularly for people with sickle cell anemia (SCA) who have lower hemoglobin and higher baseline hemolysis. Many cardiovascular complications are not identified until adulthood when patients have developed irreversible pathology. Previous studies have suggested that SCD-specific therapies like hydroxyurea (HU) may be beneficial in reducing the hemolysis associated vascular dysfunction and reducing cardiopulmonary complications. This study describes the prevalence of and factors associated with left ventricular hypertrophy (LVH), left atrial dilation and high tricuspid regurgitant jet velocity (TRJV) in children with SCA. We also describe the association between patent foramen ovale (PFO) and ischemic stroke in children with SCA.MethodThis crossectional study used data collected as part of the Dissemination and Implementation Stroke Prevention Looking at the Care Environment (DISPLACE) study. American society of echocardiography (ASE) guidelines and cutoff values were used to define abnormalities in the echocardiographic variables.ResultsA total of 1414 children were included in the analysis. The median age was 9 years (range 5-12 years) and median hemoglobin of 8.6 g/dl. The most common abnormal findings on echocardiogram was left atrial dilatation (61% of the children), LVH (20% of children) and high TRJV (23% of children). Children with abnormal echocardiographic variables were more likely to have lower hemoglobin level. Children with LVH were more likely to have left atrial dilation, high TRJV and abnormal left ventricular end diastolic diameter (LVIDD). Multivariable analysis of LVH was conducted and included variables: age, sex, hemoglobin, reticulocyte count, treatment with chronic red cell transfusion therapy (CRCT) or hydroxyurea therapy (HU). Baseline hemoglobin levels were associated with the lower odds of having LVH (OR: 0.71, 95% CI: 0.60 - 0.84). The odds of LVH increases for every one-year increase in age (OR: 1.07, 95%CI: 1.02-1.13). Similarly, the odds of LVH was lower among males than females (OR:0.59, 95%CI: 0.38-0.93). The odds of LVH were higher among those on HU compared to no therapy (OR: 1.83, 95% CI: 1.41 - 2.37).Although not all children had a bubble, study, a total of 90(6.3%) had an identified PFO. We assessed the relationship between PFO and ischemic stroke. 102 (7.2%) of the 1414 children had an ischemic stroke. Out of this 5 (5.6%) had PFO. We also assessed the relationship between PFO and abnormal TCD. 142 (10.0%) of the 1414 had abnormal TCD and only 9 (10%) of the 142 had PFO. There is no evidence that the odds of having stroke was higher among those with PFO compared to those without (OR: 1.49, 95% CI: 0.20- 11.03, p = 0.6994). Similarly, no evidence that the odds of having abnormal TCD is higher among those with PFO compared to those without (OR: 0.85, 95% CI: 0.17- 4.25, p = 0.8463).ConclusionOverall results of the study showed echocardiographic abnormalities are common in and occur at an early age in children with SCA. The risk of LVH increases with increasing age and with lower hemoglobin. Further, we found higher use of HU among those with LVH, suggesting that possibly children with more severe disease requiring HU are also at increased risk of cardiopulmonary complications.Given the fact that high TRJV is an independent risk factor for death in adults with SCD and left atrial dilatation has been shown to be an independent predictor of cardiac events, our data support further investigation into identifying early biomarkers of cardiovascular morbidity in children with SCD. [Display omitted] DisclosuresKanter: Fulcrum Therapeutics, Inc.: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Forma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beam: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Graphite Bio: Consultancy; GuidePoint Global: Honoraria; Fulcrum Tx: Consultancy.

Diminished Pneumococcal-Specific CD4+ T-Cell Response is Associated With Increased Regulatory T Cells at Older Age.

Respiratory infection caused by Streptococcus pneumoniae is a leading cause of morbidity and mortality in older adults. Acquired CD4+ T cell mechanism are essential for the protection against colonization and subsequent development of infections by S. pneumoniae. In this study, we hypothesized that age-related changes within the CD4+ T-cell population compromise CD4+ T-cell specific responses to S. pneumoniae, thereby contributing to increased susceptibility at older age. To this end, we interrogated the CD4+ T-cell response against the immunogenic pneumococcal protein AliB, part of the unique oligopeptide ABC transporter system responsible for the uptake of nutrients for the bacterium and crucial for the development of pneumococcal meningitis, in healthy young and older adults. Specifically, proliferation of CD4+ T cells as well as concomitant cytokine profiles and phenotypic markers implied in immunosenescence were studied. Older adults showed decreased AliB-induced CD4+ T-cell proliferation that is associated with an increased frequency of regulatory T cells and lower levels of active CD25+CD127+CTLA-4−TIGIT-CD4+T cells. Additionally, levels of pro-inflammatory cytokines IFNy and IL-17F were decreased at older age. Our findings indicate that key features of a pneumococcal-specific CD4+ T-cell immune response are altered at older age, which may contribute to enhanced susceptibility for pneumococcal infections.

Safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, administered concomitantly with influenza vaccine in healthy adults aged ≥50 years: a randomized phase 3 trial (PNEU-FLU)

ABSTRACT Streptococcus pneumoniae and influenza viruses are associated with significant morbidity and mortality in older adults. Concomitant vaccination against these agents reduces hospitalization and mortality rates. This phase 3 trial evaluated safety, tolerability, and immunogenicity of concomitant and non-concomitant administration of V114, a 15-valent pneumococcal conjugate vaccine containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F, and quadrivalent inactivated influenza vaccine (QIV), in healthy adults aged ≥50 years. Participants (N = 1,200) were randomized 1:1 to receive either V114 administered concomitantly with QIV (concomitant group) or QIV plus placebo (non-concomitant group) on Day 1, followed by placebo (concomitant group) or V114 (non-concomitant group) 30 days later. Randomization was stratified by age and history of pneumococcal polysaccharide vaccine receipt. Overall, 426 (71.0%) and 438 (73.5%) participants in the concomitant and non-concomitant groups experienced solicited injection-site adverse events (AEs); 278 (46.3%) and 300 (50.3%) reported solicited systemic AEs. Most solicited AEs were mild or moderate in severity and of short duration. Non-inferiority for pneumococcal- and influenza-specific antibody responses (lower bound 95% confidence interval of opsonophagocytic activity [OPA] and hemagglutination inhibition geometric mean titers [GMTs] ratios ≥0.5) was demonstrated for concomitant versus non-concomitant administration for all 15 pneumococcal serotypes and all four influenza strains. Consistent with previous studies, a trend was observed toward lower pneumococcal OPA GMTs in the concomitant versus the non-concomitant group. V114 administered concomitantly with QIV is generally well tolerated and immunologically non-inferior to non-concomitant administration, supporting coadministration of both vaccines.

Lung ultrasound volume sweep imaging for respiratory illness: a new horizon in expanding imaging access

BackgroundRespiratory illness is a leading cause of morbidity in adults and the number one cause of mortality in children, yet billions of people lack access to medical imaging to assist...

“A STUDY OF ATHEROSCLEROSIS OF RIGHT CORONARY ARTERY AND THORACIC AORTA IN POST MORTEM CASES”

Background: Atherosclerosis is a chronic disease which primarily affects the intima of large and medium sized muscular arteries, commonly involving aorta, coronary arteries and cerebral arteries. The contribution of atherosclerosis in morbidity and mortality of young adults is on the rise. Objective: To demonstrate histopathological spectrum of atherosclerotic lesions in Right Coronary Artery and Thoracic aorta and to compare the age, gender and BMI variation in prevalence of atherosclerotic lesions. 150 specime Materials And Methods: ns of heart with intact coronary arteries and thoracic aorta received by Department of pathology, Shimoga Institute of Medical Sciences, Shivamogga. Heart was grossly examined and sections were taken from Right Coronary Artery and Thoracic Aorta which were processed and stained with Haematoxylin and Eosin. Microscopically typing of the atherosclerotic lesion was made using American Heart Association classication of atherosclerosis. Of the Results: 150 cases, males 91% and females 9% were affected. Majority of the cases were in the age group of 30-40 years (33.33%) and BMI range of 18.6- 24.9 (72.67%). Commonest type of atherosclerosis in Right coronary artery was type 5 (Fibroatheroma) (25.33%) and in Thoracic aorta was type 3 (Preatheroma) (30%). Grade 1 Luminal narrowing (1-25% obstruction) was most commonly seen in Right coronary Artery (50% cases). Conclusion: Due to increase in cardiac death rates screening of cardiovascular risk factors, preventive measures, life style modication and having healthy dietary habits should be implemented early in 3rd decades of young Indians to retard the progression of atherosclerosis.

TMEM2 Combined with IDH and 1p19q in Refining Molecular Subtypes for Predicting Survival of Patients with Glioma.

Gliomas are common intracranial tumors with high morbidity and mortality in adults. Transmembrane protein 2 (TMEM2) is involved in the malignant behavior of solid tumors. TMEM2 regulates cell adhesion and metastasis as well as intercellular communication by degrading nonprotein components of the extracellular matrix. This study aimed to evaluate the relationship between TMEM2 expression levels and glioma subtypes or patient prognosis. Our findings revealed that TMEM2 expression was abnormally upregulated in high-grade glioma. Moreover, combining TMEM2, the status of isocitrate dehydrogenase (IDH) and 1p19q, we subdivided molecular subtypes with significant differences in survival. Patients in the MT-codel-low subgroup had better prognosis than those in the WT-no-codel-high subgroup, who fared the worst. Additionally, correlation analysis of TMEM2 and immune cell infiltration indicated an altered tumor microenvironment (TME) and cell redistribution in the TMEM2 high-expression subtype. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that focal adhesion and PI3K-Akt signaling pathways were enriched in the TMEM2-expressing group. In conclusion, aberrant TMEM2 expression can be used as an independent prognostic marker for refining glioma molecular subtyping and accurate prognosis. These findings will improve rational decision making to provide individualized therapy for patients with glioma.

PREVALENCE OF HYPERTENSION AND ITS SOCIO-DEMOGRAPHIC FACTORS AMONG ADULT POPULATION IN A RURAL COMMUNITY OF KANTI BLOCK, MUZAFFARPUR

Hypertension is a major contributor to the cardiovascular morbidity and mortality in industrialized countries. The recent reports suggest that hypertension is rapidly increasing in developing countries like India. Non-communicable diseases (NCDs) are the leading causes of death globally and also the leading cause of adult mortality and morbidity worldwide now days. The NCD like hypertension is emerging as a major health problem in India with increasing prevalence signicantly in both urban and rural population. The objectives of the study were to nd out the prevalence of hypertension and its association with socio-demographic factors among the study subjects, if any. A community-based cross-sectional study was conducted in rural communities of Kanti block, Muzaffarpur, Bihar from May, 2020 to April, 2021. We studied among 671 individuals, aged 21 years or above of both sexes except pregnant and seriously ill subjects. The data were collected about education, type of family, family history of hypertension, income etc. The overall prevalence of hypertension was 25.7% (male 21.7% and female 29.8%). Prevalence increased with increase in age group. Muslim religion, less education and sedentary life styles were found to be signicantly associated with hypertension; while socio-economic status had no association with hypertension. Summary: The prevalence of hypertension in the rural population was found to be on the higher side compared to previous reports from India. Strong public health measures need to be seriously implemented to combat hypertension and its consequences.

Elevated Anthropometric and Metabolic Indicators among Young Adult Offspring of Mothers with Pregestational Diabetes: Early Results from the Transgenerational Effect on Adult Morbidity Study (the TEAM Study).

Exposure to maternal diabetes in utero increases the risk in the offspring for a range of metabolic disturbances. However, the timing and variability of in utero hyperglycemic exposure necessary to cause impairment have not been elucidated. The TEAM Study was initiated to evaluate young adult offspring of mothers with pregestational diabetes mellitus. This paper outlines the unique enrollment challenges of the TEAM Study and preliminary analysis of the association between exposure to diabetes in pregnancy and adverse metabolic outcomes. The TEAM Study enrolls offspring of women who participated in a Diabetes in Pregnancy (DiP) Program Project Grant between 1978 and 1995. The DiP Study collected medical and obstetric data across pregnancy. The first 96 eligible offspring of women with pregestational diabetes were age-, sex-, and race-matched to adults from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 with an OGTT. Descriptive and regression analyses were employed to compare TEAM participants to NHANES participants. Among a subset of TEAM participants, we compared the metabolic outcomes across maternal glucose profiles using a longitudinal data clustering technique that characterizes level and variability, in maternal glucose across pregnancy. By comparing categories of BMI, TEAM Study participants had over 2.0 times the odds of being obese compared to matched NHANES participants (for class III obesity, OR = 2.81; 95% confidence interval (CI): 1.15, 6.87). Increasing levels of two-hour glucose were also associated with in utero exposure to pregestational diabetes in matched analyses. Exposure to pregestational diabetes in utero may be associated with an increased risk of metabolic impairment in the offspring with clinical implications.

Frailty Syndrome: Implications for Nursing Practice

Frailty is a life-limiting medical syndrome associated with morbidity and mortality in older adults. The concept of frailty as a syndrome adds to our knowledge of aging and helps to expand the identification of risk factors and interventions to reduce disability and improve outcomes. Early identification through the use of validated risk assessment tools and targeted management of the frailty state in older adults is clinically important for nurse practitioners. Primary care and specialty care nurse practitioners are optimally positioned to facilitate comprehensive assessment and management of this evolving phenomena in the care of older adults.

Carbon Dots: An Innovative Tool for Drug Delivery in Brain Tumors.

Simple SummaryThe pharmacological treatment of tumors of the central nervous system poses major challenges due to the presence of physical obstacles, i.e., the blood-brain barrier, impeding the delivery of anticancer drugs to the tumor site. Hence, the development of innovative therapeutic strategies to overcome these obstacles is of pivotal importance to reach significant clinical advances in brain tumor treatment. In this review, we report the latest studies on carbon dots as an innovative tool for brain tumor drug delivery.Brain tumors are particularly aggressive and represent a significant cause of morbidity and mortality in adults and children, affecting the global population and being responsible for 2.6% of all cancer deaths (as well as 30% of those in children and 20% in young adults). The blood-brain barrier (BBB) excludes almost 100% of the drugs targeting brain neoplasms, representing one of the most significant challenges to current brain cancer therapy. In the last decades, carbon dots have increasingly played the role of drug delivery systems with theranostic applications against cancer, thanks to their bright photoluminescence, solubility in bodily fluids, chemical stability, and biocompatibility. After a summary outlining brain tumors and the current drug delivery strategies devised in their therapeutic management, this review explores the most recent literature about the advances and open challenges in the employment of carbon dots as both diagnostic and therapeutic agents in the treatment of brain cancers, together with the strategies devised to allow them to cross the BBB effectively.

Identification of SLITRK6 as a Novel Biomarker in hepatocellular carcinoma by comprehensive bioinformatic analysis

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the adult liver and morbidity are increasing in recent years, however, there is still no effective strategy to prevent and diagnose HCC. Therefore, it is urgent to research the effective biomarker to predict clinical outcomes of HCC tumorigenesis. In the current study, differentially expressed genes in HCC and normal tissues were investigated using the Gene Expression Omnibus (GEO) dataset GSE144269 and The Cancer Genome Atlas (TCGA). Gene differential expression analysis and weighted correlation network analysis (WGCNA) methods were used to identify nine and 16 key gene modules from the GEO dataset and TCGA dataset, respectively, in which the green module in the GEO dataset and magenta module in TCGA were significantly correlated with HCC occurrence. Third, the enrichment score of gene function annotation results showed that these two key modules focus on the positive regulation of inflammatory response and cell differentiation, etc. Besides, PPI network analysis, mutation analysis, and survival analysis found that SLITRK6 had high connectivity, and its mutation significantly impacted overall survival. In addition, SLITRK6 was found to be low expressed in tumor cells. To summarize, SLITRK6 mutation was found to significantly affect the occurrence and prognosis of HCC. SLITRK6 was confirmed as a new potential gene target for HCC, which may provide a new theoretical basis for personalized diagnosis and chemotherapy of HCC in the future.

Cardiovascular risk profile and clinical characteristics of diabetic patients: a cross-sectional study in China.

Background:Cardiovascular (CV) disease is the leading cause of morbidity and mortality in adults with type 2 diabetes (T2D). The aim of this study was to determine the CV risk in Chinese patients with T2D based on the 2019 European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) guidelines on diabetes, pre-diabetes, and CV diseases.Methods:A total of 25,411 patients with T2D, who participated in the study of China Cardiometabolic Registries 3B study, were included in our analysis. We assessed the proportions of patients in each CV risk category according to 2019 ESC/EASD guidelines.Results:Based on the 2019 ESC/EASD guidelines, 16,663 (65.6%), 1895 (7.5%), and 152 (0.6%) of patients were included in “very high risk,” “high risk,” and “moderate risk” categories, respectively. The proportions of patients in each category varied based on age, sex, body mass index, and duration. While 58.7% (9786/16,663) of elderly patients were classified to “very high risk” group, 89.6% (3732/4165) of patients with obesity were divided into “very high risk” group. Almost all patients with a duration of diabetes >10 years had “very high risk” or “high risk.” However, 6701 (26.4%) of Chinese T2D patients, who had shorter duration, and one or two risk factors, could not be included in any category (the “unclear risk” category).Conclusions:In China, most patients with T2D have “very high” or “high” CV risk based on 2019 ESC/EASD guidelines. However, the risk of patients in “unclear risk” group needs to be further classified.

Risk factors and outcomes for recurrent paediatric in-hospital cardiac arrest: Retrospective multicenter cohort study

Aim of studyRecurrent in-hospital cardiac arrest (IHCA) is associated with morbidity and mortality in adults. We aimed to describe the risk factors and outcomes for paediatric recurrent IHCA. MethodsRetrospective cohort study of patients ≤18 years old with single or recurrent IHCA. Recurrent IHCA was defined as ≥2 IHCA within the same hospitalization. Categorical variables expressed as percentages and compared via Chi square test. Continuous variables expressed as medians with interquartile ranges and compared via rank sum test. Outcomes assessed in a propensity match cohort. ResultsFrom July 1, 2015 to January 26, 2021, 139/894 (15.5%) patients experienced recurrent IHCA. Compared to patients with a single IHCA, recurrent IHCA patients were more likely to be trauma and less likely to be surgical cardiac patients. Median duration of cardiopulmonary resuscitation (CPR) was shorter in the recurrent IHCA (5 vs. 11 min; p < 0.001) with no difference in IHCA location or immediate cause of CPR. Patients with recurrent IHCA had worse survival to intensive care unit (ICU) discharge (31% vs. 52%; p < 0.001), and worse survival to hospital discharge (30% vs. 48%; p < 0.001) in unadjusted analyses and after propensity matching, patients with recurrent IHCA still had worse survival to ICU (34% vs. 67%; p < 0.001) and hospital (31% vs. 64%; p < 0.001) discharge. ConclusionWhen examining those with a single vs. a recurrent IHCA, event and patient factors including more pre-existing conditions and shorter duration of CPR were associated with risk for recurrent IHCA. Recurrent IHCA is associated with worse survival outcomes following propensity matching.

Raised Childhood Obesity and Its Consequences: Alarming Worldwide for Primordial Prevention

Childhood Obesity is defined as excess or abnormal increase of fat accumulation in the body. Early, developed countries were facing this childhood obesity but now it has moved to developing countries. According to World Health Organization (WHO), 39 million children under the age of 5 are obese and overweight in 2020 and 340 million adolescents and children aged between 5-19 were obese and overweight in 2016. According to Center for Disease Control, prevalence of obesity in United States was 19.3% and affected about 14.4 million adolescents and children in 2018. Moreover, in the adult population morbidity and mortality is increased in individuals who were overweight in adolescence, even if they lose the extra weight during adulthood. Diabetes, high blood pressure and high cholesterol, gastro intestinal disturbance, respiratory problems, orthopedic disorders once considered as adult problems now has become major health issue in children’s. Timely action must be initiated to combat the rising epidemic of childhood obesity and its consequences. However, by periodic surveillance on nutrition and childhood obesity in community, using various strategies at home and providing needy based intervention by schools care services, formulating and implementing structured policies will reduce the impact of childhood obesity worldwide.

Raised Childhood Obesity and Its Consequences: Alarming Worldwide for Primordial Prevention

Childhood Obesity is defined as excess or abnormal increase of fat accumulation in the body. Early, developed countries were facing this childhood obesity but now it has moved to developing countries. According to World Health Organization (WHO), 39 million children under the age of 5 are obese and overweight in 2020 and 340 million adolescents and children aged between 5-19 were obese and overweight in 2016. According to Center for Disease Control, prevalence of obesity in United States was 19.3% and affected about 14.4 million adolescents and children in 2018. Moreover, in the adult population morbidity and mortality is increased in individuals who were overweight in adolescence, even if they lose the extra weight during adulthood. Diabetes, high blood pressure and high cholesterol, gastro intestinal disturbance, respiratory problems, orthopedic disorders once considered as adult problems now has become major health issue in children’s. Timely action must be initiated to combat the rising epidemic of childhood obesity and its consequences. However, by periodic surveillance on nutrition and childhood obesity in community, using various strategies at home and providing needy based intervention by schools care services, formulating and implementing structured policies will reduce the impact of childhood obesity worldwide.

Persistent eosinopenia is associated with in-hospital mortality among older patients: unexpected prognostic value of a revisited biomarker

IntroductionInfection is one of the major causes of mortality and morbidity in older adults. Available biomarkers are not associated with prognosis in older patients. This study aimed to analyze the value of eosinopenia (eosinophil count< 100/mm3) as a prognosis marker among older patients with suspected or confirmed bacterial infection.MethodsA retrospective study was performed from 1 January to 31 December 2018 among patients in a geriatrics ward suffering from a bacterial infection treated with antibiotics. Biomarker data including the eosinophil count, neutrophil count and C-reactive protein (CRP) were collected within 4 days after patient diagnosis. Persistent eosinopenia was defined as a consistent eosinophil count< 100/mm3 between Day 2 and Day 4. The association of biomarkers with 30-day hospital mortality in a multivariate analysis was assessed and their predictive ability using the area under the ROC curve (AUC) was compared.ResultsOur study included 197 patients with a mean age of 90 ± 6 years. A total of 36 patients (18%) died during their stay in hospital. The patients who died were more likely to have persistent eosinopenia in comparison to survivors (78% versus 34%, p < 0.001). In the multivariate analysis, persistent eosinopenia was associated with in-hospital mortality with an adjusted HR of 8.90 (95%CI 3.46–22.9). The AUC for eosinophil count, CRP and neutrophil count between Day 2 and Day 4 were 0.7650, 0.7130, and 0.698, respectively.ConclusionPersistent eosinopenia within 4 days of diagnosis of bacterial infection appeared to be a predictor of in-hospital mortality in older patients.