Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.

IL-31 levels correlate with pruritus in patients with cholestatic and metabolic liver diseases and is farnesoid X receptor responsive in NASH.

BACKGROUND AND AIMS: Pruritus is associated with multiple liver diseases, particularly those with cholestasis, but the mechanism remains incompletely understood. Our aim was to evaluate serum IL-31 as a putative biomarker of pruritus in clinical trials of an farnesoid X receptor (FXR) agonist, cilofexor, in patients with NASH, primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC). APPROACH AND RESULTS: Serum IL-31 was measured in clinical studies of cilofexor in NASH, PSC, and PBC. In patients with PSC or PBC, baseline IL-31 was elevated compared to patients with NASH and healthy volunteers (HVs). IL-31 correlated with serum bile acids among patients with NASH, PBC, and PSC. Baseline IL-31 levels in PSC and PBC were positively correlated with Visual Analog Scale for pruritus and 5-D itch scores. In patients with NASH, cilofexor dose-dependently increased IL-31 from Week (W)1 to W24. In patients with NASH receiving cilofexor 100 mg, IL-31 was higher in those with Grade 2-3 pruritus adverse events (AEs) than those with Grade 0-1 pruritus AEs. IL-31 weakly correlated with C4 at baseline in patients with NASH, and among those receiving cilofexor 100 mg, changes in IL-31 and C4 from baseline to W24 were negatively correlated. IL-31 messenger RNA (mRNA) was elevated in hepatocytes from patients with PSC and NASH compared to HVs. In a humanized liver murine model, obeticholic acid increased IL-31 mRNA expression in human hepatocytes and serum levels of human IL-31. CONCLUSIONS: IL-31 levels correlate with pruritus in patients with cholestatic disease and NASH, with FXR agonist therapy resulting in higher serum levels in the latter group. IL-31 appears to derive in part from increased hepatocyte expression. These findings have therapeutic implications for patients with liver disease and pruritus.

Mapping the hepatic immune landscape identifies monocytic macrophages as key drivers of steatohepatitis and cholangiopathy progression.

BACKGROUND AND AIMS: The progression of chronic liver diseases towards liver cirrhosis is accompanied by drastic tissue changes. This study combines elaborate transcriptomic and histological methods aiming at spatially resolving the hepatic immune microenvironment in NAFLD (including NASH, primary sclerosing cholangitis, primary biliary cholangitis, and severe alcoholic hepatitis). APPROACH AND RESULTS: Human liver samples were subjected to RNA-sequencing (n=225) and imaging cytometry (n=99) across 3 independent patient cohorts. Liver samples from alcoholic hepatitis and primary biliary cholangitis patients were used for comparison. Myeloid populations were further characterized in corresponding mouse models. Imaging, clinical, and phenotypical data were combined for multidimensional analysis. NAFLD/NASH and primary sclerosing cholangitis disease stages were associated with loss of parenchymal areas, increased ductular cell accumulation, and infiltration of immune cells. NASH patients predominantly exhibited myeloid cell accumulation, whereas primary sclerosing cholangitis patients additionally had pronounced lymphoid cell responses. Correlating to disease stage, both etiologies displayed intense IBA1 + CD16 low CD163 low macrophage aggregation in nonparenchymal areas, with a distinct spatial proximity to ductular cells. Mouse models revealed that disease-associated IBA1 + hepatic macrophages originated from bone marrow-derived monocytes. Using an unbiased, machine learning-based algorithm, IBA1 in combination with hepatocyte and ductular cell immunostaining-predicted advanced cirrhosis in human NASH, primary sclerosing cholangitis, and alcoholic hepatitis. CONCLUSIONS: Loss of hepatocytes and increased ductular reaction are tightly associated with monocyte-derived macrophage accumulation and represent the most prominent common immunological feature revealing the progression of NAFLD, primary sclerosing cholangitis, primary biliary cholangitis, and alcoholic hepatitis, suggesting IBA1 + CD163 low macrophages are key pathogenic drivers of human liver disease progression across diverse etiologies.

Identification of brain-enriched proteins in CSF as biomarkers of relapsing remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a clinically and biologically heterogenous disease with currently unpredictable progression and relapse. After the development and success of neurofilament as a cerebrospinal fluid (CSF) biomarker, there is reinvigorated interest in identifying other markers of or contributors to disease. The objective of this study is to probe the predictive potential of a panel of brain-enriched proteins on MS disease progression and subtype. METHODS: This study includes 40 individuals with MS and 14 headache controls. The MS cohort consists of 20 relapsing remitting (RR) and 20 primary progressive (PP) patients. The CSF of all individuals was analyzed for 63 brain enriched proteins using a method of liquid-chromatography tandem mass spectrometry. Wilcoxon rank sum test, Kruskal-Wallis one-way ANOVA, logistic regression, and Pearson correlation were used to refine the list of candidates by comparing relative protein concentrations as well as relation to known imaging and molecular biomarkers. RESULTS: We report 30 proteins with some relevance to disease, clinical subtype, or severity. Strikingly, we observed widespread protein depletion in the disease CSF as compared to control. We identified numerous markers of relapsing disease, including KLK6 (kallikrein 6, OR = 0.367, p < 0.05), which may be driven by active disease as defined by MRI enhancing lesions. Other oligodendrocyte-enriched proteins also appeared at reduced levels in relapsing disease, namely CNDP1 (carnosine dipeptidase 1), LINGO1 (leucine rich repeat and Immunoglobin-like domain-containing protein 1), MAG (myelin associated glycoprotein), and MOG (myelin oligodendrocyte glycoprotein). Finally, we identified three proteins-CNDP1, APLP1 (amyloid beta precursor like protein 1), and OLFM1 (olfactomedin 1)-that were statistically different in relapsing vs. progressive disease raising the potential for use as an early biomarker to discriminate clinical subtype. CONCLUSIONS: We illustrate the utility of targeted mass spectrometry in generating potential targets for future biomarker studies and highlight reductions in brain-enriched proteins as markers of the relapsing remitting disease stage.

Design of the Intervention to Reduce Early Peanut Allergy in Children (iREACH): A practice-based clinical trial.

BACKGROUND: Introducing peanut products early can prevent peanut allergy (PA). The "Addendum guidelines for the prevention of PA in the United States" (PPA guidelines) recommend early introduction of peanut products to low and moderate risk infants and evaluation prior to starting peanut products for infants at high risk for PA (those with severe eczema and/or egg allergy). Rapid adoption of guidelines could aid in lowering the prevalence of PA. The Intervention to Reduce Early (Peanut) Allergy in Children (iREACH) trial was designed to promote PPA guideline adherence by pediatric clinicians. METHODS: A two-arm, cluster-randomized, controlled clinical trial was designed to measure the effectiveness of an intervention that included clinician education and accompanying clinical decision support tools integrated in electronic health records (EHR) versus standard care. Randomization was at the practice level (n = 30). Primary aims evaluated over an 18-month trial period assess adherence to the PPA guidelines using EHR documentation at 4- and 6-month well-child care visits aided by natural language processing. A secondary aim will evaluate the effectiveness in decreasing the incidence of PA by age 2.5 years using EHR documentation and caregiver surveys. The unit of observation for evaluations are individual children with clustering at the practice level. CONCLUSION: Application of this intervention has the potential to inform the development of strategies to speed implementation of PPA guidelines.

Formaldehyde gas sensors based on a quartz crystal microbalance modified with aniline-doped polyvinyl acetate nanofibers.

Real-time detection of formaldehyde in the atmosphere remains challenging. The available gaseous formaldehyde sensing methods offer limited sensitivity, selectivity, and robustness. We modified a quartz crystal microbalance (QCM) system for selective detection of formaldehyde in air. The QCM surface was functionalized with polyvinyl acetate (PVAc) nanofibers and doped with 2, 4, and 6 wt% aniline to improve the selectivity and sensitivity of the sensor. The chemical content and morphological structure of PVAc nanofibers doped with aniline were confirmed by Fourier-transform infrared (FTIR) spectroscopy, energy-dispersive X-ray (EDX) spectroscopy, and scanning electron microscopy (SEM). The results showed that the modified QCM sensor had a sensitivity of 0.056 Hz ppm-1 with a response and recovery times of 200 s and 90 s, respectively. It gave limits of detection (LOD) and limit of quantification (LOQ) of 28 ppm and 96 ppm, respectively. Moreover, the modified QCM was selective towards formaldehyde compared to the other gases. The current workplace exposure limit (WEL) for formaldehyde is 2 ppm, with a time-weighted average over eight hours. Future work will focus on improving the reported QCM sensor to meet the required LOD for formaldehyde detection in the environment and industrial sites.

Epidemiology and the Growing Epidemic of Food Allergy in Children and Adults Across the Globe.

PURPOSE OF REVIEW: Food allergies are immune-mediated, complex disorders, which are the source of increasing health concern worldwide. The goal of this review is to present an updated summary of the food allergy (FA) burden among children and adults across different populations, focusing on research from the past 5 years. RECENT FINDINGS: FAs impact a growing number of global residents-particularly those residing in higher-income, industrialized regions. Moreover, growing epidemiologic evidence suggests that the population health burden of non-IgE-mediated FAs, such as food protein-induced enterocolitis syndrome, may also be higher than previously reported. FA is a complex trait that impacts infants, children, as well as adults across the globe. The population health burden of both IgE- and non-IgE-mediated FAs is likely to grow in the absence of rapid advances and widespread implementation of effective FA prevention and treatment interventions. Systematic epidemiological research initiatives are needed, both nationally and globally, to better understand and reduce the burden of these allergic diseases.

A review of posterior chamber phakic intraocular lenses.

PURPOSE OF REVIEW: Posterior chamber phakic intraocular lenses (pIOLs) are increasing in popularity as a viable alternative to laser refractive surgery. The purpose of this review is to evaluate the recent updates to pIOLs and to assess the advancements and safety of the procedure. RECENT FINDINGS: Accurate lens sizing is the key determinant to suitable vault prediction, advancements to sizing formulae including the use of very high frequency (VHF) digital ultrasound and the application of artificial intelligence and machine learning has led to improved vault prediction and safety. The introduction of the central aquaport has been shown to reduce the formation of cataract and is now adopted in most myopic pIOLs. Recently published studies have demonstrated that pIOLs have an excellent safety profile with no increased risk of retinal detachment or endothelial cell loss. Advancements have led to the introduction of extended depth of focus pIOLs for the correction of presbyopia, further research is required to evaluate the efficacy of new lens designs. SUMMARY: pIOL surgery is experiencing traction with improved lens design and increased lenses choices such as larger optical zone and presbyopic options. Accuracy of implantable collamer lens sizing is paramount to the safety and clinical outcomes, greater predictability is likely to encourage more posterior chamber pIOL users due to fewer sizing related complications.

Gut microbiome is associated with asthma and race in children with food allergy.

BACKGROUND: The composition of the gut microbiome has been associated with development of atopic conditions such as food allergy (FA) and asthma. African American or Black children with FA have higher rate of asthma compared to their White counterparts. OBJECTIVE: We sought to investigate whether the diversity and relative abundance (RA) of gut microbiota is different between children with FA from different racial backgrounds living in the same cities. Furthermore, we aimed to understand whether the difference in the gut microbiota is associated with asthma in children with FA. METHODS: We analyzed and compared the stool microbiome of a cohort of Black and White children with FA by shotgun genomic sequencing. RESULTS: A total of 152 children with IgE-mediated FA enrolled onto FORWARD (Food Allergy Outcomes Related to White and African American Racial Differences); 30 Black and 122 White children were included. The RA of several bacteria was associated with race and asthma. Most notably the RA of Bacteroides thetaiotaomicron, Chlamydia thrachomatis, Parabacteroides goldsteinii, and Bacteroides eggerthii were significantly higher, while the RA of Bifidobacterium sp CAG:754, Parabacterium johnsonii, Bacteroides intestinalis, and Bifidobacterium breve were significantly lower in stool samples of Black children compared to White children. Asthma was associated with lower RA of B breve, Bifidobacterium catenulatum, Prevotella copri, Veilloella sp CAG:933, and Bacteroides plebius, and higher RA of 3 Bacteroides species. CONCLUSIONS: The observed variations in the gut microbiota of Black and White children such as differences in the Bacteroides and Bifidobacterium species along with their association to history of asthma in our cohort is indicative of their potential role in the higher rate of asthma observed among Black children with FA.

Bone marrow plasma metabonomics of idiopathic acquired aplastic anemia patients using 1H nuclear magnetic resonance spectroscopy.

INTRODUCTION: Idiopathic acquired aplastic anemia (AA) is a bone marrow failure disorder where aberrant T-cell functions lead to depletion of hematopoietic stem and progenitor cells in the bone marrow (BM) microenvironment. T-cells undergo metabolic rewiring, which regulates their proliferation and differentiation. Therefore, studying metabolic variation in AA patients may aid us with a better understanding of the T-cell regulatory pathways governed by metabolites and their pathological engagement in the disease. OBJECTIVE: To identify the differential metabolites in BM plasma of AA patients, AA follow-up (AAF) in comparison to normal controls (NC) and to identify potential disease biomarker(s). METHODS: The study used 1D 1H NMR Carr-Purcell-Meiboom-Gill (CPMG) spectra to identify the metabolites present in the BM plasma samples of AA (n = 40), AAF (n = 16), and NC (n = 20). Metabolic differences between the groups and predictive biomarkers were identified by using multivariate analysis and receiver operating characteristic (ROC) module of Metaboanalyst V5.0 tool, respectively. RESULTS: The AA and AAF samples were well discriminated from NC group as per Principal Component analysis (PCA). Further, we found significant alteration in the levels of 17 metabolites in AA involved in amino-acid (Leucine, serine, threonine, phenylalanine, lysine, histidine, valine, tyrosine, and proline), carbohydrate (Glucose, lactate and mannose), fatty acid (Acetate, glycerol myo-inositol and citrate), and purine metabolism (hypoxanthine) in comparison to NC. Additionally, biomarker analysis predicted Hypoxanthine and Acetate can be used as a potential biomarker. CONCLUSION: The study highlights the significant metabolic alterations in the BM plasma of AA patients which may have implication in the disease pathobiology.

Photoactive hydrogels for pre-concentration, labelling, and controlled release of proteins.

We report a novel hydrogel for pre-concentration, fluorescent labelling, and light-triggered release of proteins for detection of low abundance biomarkers. The hydrogel was a co-polymer of acrylamide/bisacrylamide and methacrylamide attached to fluorescein isothiocyanate via a light cleavable bond and a poly(ethylene glycol) spacer arm of molecular weight of 3400 g mol-1. Unlike previous work, proteins were captured by an irreversible chemical reaction rather than by non-covalent affinity binding or physical entrapment. Because the protein-reactive group was attached to fluorescein, which in turn was coupled to the hydrogel by a photocleavable bond, on release the protein was labelled with fluorescein. Our hydrogel offered a pre-concentration factor of up to 236 for a model protein, streptavidin. Each protein molecule was labelled with 85 fluorescein molecules, and 50% of the proteins in the hydrogel were released after UV exposure for ∼100 s. The proteins released from the hydrogel were captured in biotinylated microtitre plates and detected by fluorescence, allowing measurement of at least 0.01 ppm (or ∼166 pM) of protein in sample solutions. The reported hydrogel is promising for detection of low abundance proteins while being less laborious than enzyme-linked immunosorbent assay and less affected by changes in environmental conditions than label-free biosensors.

Prevalence and burden of coconut allergy in the United States.

BACKGROUND: Epidemiologic data on coconut allergy remains sparse in the United States despite the labeling requirement by the Food Allergen Labeling and Consumer Protection Act for products containing coconut. OBJECTIVE: To provide current estimates of the prevalence, severity, determinants, and distribution of coconut allergy in the United States. METHODS: A comprehensive food allergy prevalence survey was administered to a nationally representative, probability-based sample of US households between October 1, 2015 and September 30, 2016. Eligible respondents included adults who were able to complete self- and parent-proxy report surveys in English or Spanish by means of web or phone. RESULTS: Using survey responses from 78,851 individuals, 0.39% (95% confidence interval [CI], 0.33-0.45) of the US general population were categorized as having convincing coconut allergy. Among children, 0.22% (95% CI, 0.16-0.30) were estimated to have coconut allergy compared with 0.43% (95% CI, 0.37-0.51) of adults, whereas only 0.12% (95% CI, 0.08-0.18) of these children and 0.20% (95% CI, 0.16-0.24) of adults with convincing immunoglobulin E (IgE)-mediated coconut allergy reported physician-confirmed diagnoses. A current epinephrine prescription was reported by 40.1% (95% CI, 33.3-47.4) of those with convincing coconut allergy. Reactions involving multiple organ systems were reported by 47.5% (95% CI, 40.1-54.9) of those with convincing coconut allergy. CONCLUSION: Roughly 1 in 260 Americans report symptoms consistent with an IgE-mediated allergy to coconut, although fewer than half of these individuals report receiving a physician diagnosis. Our data indicate that most individuals with reported coconut allergy meeting symptom-based criteria for convincingly IgE-mediated disease have comorbid FAs, and for many patients, clinical management seems to be suboptimal.

The epidemiology of food allergy in adults.

The prevalence and awareness of food allergy (FA) among US adults is arguably at a historical high, both with respect to primary immunoglobulin E-mediated food hypersensitivity and other food-triggered conditions that operate through a variety of immunologic mechanisms (eg, pollen-FA syndrome, alpha-gal syndrome, food protein-induced enterocolitis syndrome, eosinophilic esophagitis). Worryingly, not only are many adults retaining childhood-onset food allergies as they age into adulthood, it seems that many adults are experiencing adult-onset allergies to previously tolerated foods, with correspondingly adverse physical, and psychological health impacts. Consequently, this review aims to summarize what is currently known about the epidemiology and population-level burden of FA among adult populations in North America and around the globe. This article also provides insights into the natural history of these conditions and what we need to know as we look to the future to support effective care and prevent FA.

The epidemiology of multifood allergy in the United States: A population-based study.

BACKGROUND: Immunoglobulin E (IgE)-mediated food allergies (FAs) are increasingly common among US children and adults. Not only can living with FA impose considerable physical health impacts, but it also imposes economic burden and can negatively affect quality of life. Limited data indicate that allergy to multiple foods (multi-FA) also may be common, but much remains unknown about its distribution and determinants. OBJECTIVE: To characterize the prevalence, characteristics, determinants, psychosocial burden, and distribution of multi-FA among a large, nationally representative sample of US children and adults. METHODS: A US population-based survey was administered. Estimates of multi-FA prevalence, conditional frequencies of multi-FA combinations, and associated factors were derived. Latent class analyses were conducted using 9 dichotomized indicators of specific FA prevalence, which were used to determine factors associated with latent class membership and characterize FA-related psychosocial burden within each class. RESULTS: Surveys were completed for 38,408 children and 40,443 adults. Among children and adults meeting established symptom-report criteria for FA, an estimated 40% and 48% had multi-FA, respectively. Among pediatric and adult populations with convincing FAs, the lifetime reported prevalence of physician-diagnosed atopic comorbidities increased significantly as the number of reported current convincing FAs increased, as did the proportion reporting multi-FA-related health care utilization and higher perceived psychosocial burden. Latent class analyses suggested the existence of the following 4 key latent phenotypes of multi-FA: milk and egg-dominant, seafood-dominant, peanut and tree nut-dominant, and broadly multi-food allergic. CONCLUSION: The US population-level burden of multi-FA is high among both children and adults, and data indicate the presence of 4 major phenotypes of multi-FA in both populations.

Proposed solutions by the American College of Allergy, Asthma, and Immunology and advocacy experts to address racial disparities in atopic dermatitis and food allergy.

Atopic dermatitis (AD) and food allergies are more prevalent and more severe in people with skin of color than White individuals. The American College of Allergy, Asthma, and Immunology (ACAAI) sought to understand the effects of racial disparities among patients with skin of color with AD and food allergies. The ACAAI surveyed its members (N = 200 completed), conducted interviews with health care providers and advocacy leaders, and hosted a roundtable to explore the challenges of diagnosis and management of AD and food allergies in people with skin of color and to discuss potential solutions. Most of the survey respondents (68%) agreed that racial disparities make it difficult for people with skin of color to receive adequate treatment for AD and food allergies. The interviews and roundtable identified access to care, burden of costs, policies and infrastructure that limit access to safe foods and patient education, and inadequate research involving people with skin of color as obstacles to care. Proposed solutions included identifying ways to recruit more people with skin of color into clinical trials and medical school, educating health care providers about diagnosis and treating AD and food allergy in people with skin of color, improving access to safe foods, creating and disseminating culturally appropriate materials for patients, and working toward longer appointment times for patients who need them. Challenges in AD and food allergy in persons with skin of color were identified by the ACAAI members. Solutions to these challenges were proposed to inspire actions to mitigate racial disparities in AD and food allergy.

Risk factors for SARS-CoV-2 infection and transmission in households with children with asthma and allergy: A prospective surveillance study.

BACKGROUND: Whether children and people with asthma and allergic diseases are at increased risk for severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: Our aims were to determine the incidence of SARS-CoV-2 infection in households with children and to also determine whether self-reported asthma and/or other allergic diseases are associated with infection and household transmission. METHODS: For 6 months, biweekly nasal swabs and weekly surveys were conducted within 1394 households (N = 4142 participants) to identify incident SARS-CoV-2 infections from May 2020 to February 2021, which was the pandemic period largely before a vaccine and before the emergence of SARS-CoV-2 variants. Participant and household infection and household transmission probabilities were calculated by using time-to-event analyses, and factors associated with infection and transmission risk were determined by using regression analyses. RESULTS: In all, 147 households (261 participants) tested positive for SARS-CoV-2. The household SARS-CoV-2 infection probability was 25.8%; the participant infection probability was similar for children (14.0% [95% CI = 8.0%-19.6%]), teenagers (12.1% [95% CI = 8.2%-15.9%]), and adults (14.0% [95% CI = 9.5%-18.4%]). Infections were symptomatic in 24.5% of children, 41.2% of teenagers, and 62.5% of adults. Self-reported doctor-diagnosed asthma was not a risk factor for infection (adjusted hazard ratio [aHR] = 1.04 [95% CI = 0.73-1.46]), nor was upper respiratory allergy or eczema. Self-reported doctor-diagnosed food allergy was associated with lower infection risk (aHR = 0.50 [95% CI = 0.32-0.81]); higher body mass index was associated with increased infection risk (aHR per 10-point increase = 1.09 [95% CI = 1.03-1.15]). The household secondary attack rate was 57.7%. Asthma was not associated with household transmission, but transmission was lower in households with food allergy (adjusted odds ratio = 0.43 [95% CI = 0.19-0.96]; P = .04). CONCLUSION: Asthma does not increase the risk of SARS-CoV-2 infection. Food allergy is associated with lower infection risk, whereas body mass index is associated with increased infection risk. Understanding how these factors modify infection risk may offer new avenues for preventing infection.

The Effect of Sepsis and Septic Shock on the Viscoelastic Properties of Clot Quality and Mass Using Thromboelastometry: A Prospective Observational Study.

Background: Sepsis is associated with wide variable coagulation abnormalities. Thromboelastography (TEG) effectively measures the viscoelastic properties of the clots. This study aims to illustrate the viscoelastic properties of clot quality and mass in sepsis and septic shock patients using TEG, as an effective tool over standard coagulation tests. Materials and methods: A single-center, prospective observational study was conducted. 50 patients each meeting the criteria for sepsis and septic shock, and a healthy group of 30 patients was included in the study. Blood samples were obtained and analyzed for standard coagulation tests, platelet count, fibrinogen, and TEG study. Results: A total of 130 patients were included. Septic shock patients had a higher sequential (sepsis-related) organ failure score. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were increased significantly as compared to the sepsis and control groups. TEG markers such as alpha angle, and maximum amplitude (MA) were significantly prolonged while reaction time (R time), was significantly shortened in the sepsis group as compared to the healthy group, suggestive of a hypercoagulable state in sepsis patients. While in septic shock patients, MA and Lysis Index 30 (LY 30) were significantly prolonged and, R time was significantly shortened compared to all other groups. Even though LY30 in sepsis patients was found to be within the normal range (p < 0.001), 18% of patients had prolonged LY30 indicating a hypercoagulable state with impaired fibrinolysis. Conclusion: Thromboelastography, as a point-of-care test combined with conventional coagulation tests can provide additional, clinically relevant information on coagulopathy, and outcome, and thus help guide treatment modality in sepsis and septic shock-induced coagulopathy. How to cite this article: Mohapatra P, Kumar A, Singh RK, Gupta R, Hussain M, Singh S, et al. The Effect of Sepsis and Septic Shock on the Viscoelastic Properties of Clot Quality and Mass Using Thromboelastometry: A Prospective Observational Study. Indian J Crit Care Med 2023;27(9):625-634.

High-Dimensional Clustering of 4000 Irritable Bowel Syndrome Patients Reveals Seven Distinct Disease Subsets.

BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) is a pain disorder classified by bowel habits, disregarding other factors that may influence the clinical course. The aim of this study was to determine if IBS patients can be clustered based on clinical, dietary, lifestyle, and psychosocial factors. METHODS: Between 2013 and 2020, the Mayo Clinic Biobank surveyed and received 40,291 responses to a questionnaire incorporating Rome III criteria. Factors associated with IBS were determined and latent class analysis, a model-based clustering, was performed on IBS cases. RESULTS: We identified 4021 IBS patients (mean 64 years; 75% women) and 12,063 controls. Using 26 variables separating cases from controls, the optimal clustering revealed 7 latent clusters. These were characterized by perceived health impairment (moderate or severe), psychoneurological factors, and bowel dysfunction (diarrhea or constipation predominance). Health impairment clusters demonstrated more pain, with the severe cluster also having more psychiatric comorbidities. The next 3 clusters had unique enrichment of psychiatric, neurological, or both comorbidities. The bowel dysfunction clusters demonstrated less abdominal pain, with diarrhea cluster most likely to report pain improvement with defecation. The constipation cluster had the highest exercise score and consumption of fruits, vegetables, and alcohol. The distribution of clusters remained similar when Rome IV criteria were applied. Physiologic tests were available on a limited subset (6%), and there were no significant differences between clusters. CONCLUSIONS: In this cohort of older IBS patients, 7 distinct clusters were identified demonstrating varying degrees of gastrointestinal symptoms, comorbidities, dietary, and lifestyle factors. Further research is required to assess whether these unique clusters could be used to direct clinical trials and individualize patient management.

Early intervention and prevention of allergic diseases.

Food allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of (1) an intact epidermal barrier to prevent epicutaneous antigen presentation, (2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and (3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.

Real-world challenges in the management of acute myeloid leukemia: a single-center experience from North India.

BACKGROUND: The outcome of acute myeloid leukemia (AML) in low-middle-income countries (LMIC) is dismal due to delayed clinical presentation and infection-related complications. We aimed to analyze the outcome of patients with AML and the factors associated with its prognosis. METHODS: A retrospective observational study was conducted at a tertiary care university hospital in North India from January 2015 to December 2019. RESULTS: A total of 137 AML patients (median age 32 year (3-66 years) received intensive chemotherapy during study period. The median delay from diagnosis to treatment was 45 days (6-177 days). Among the 352 febrile neutropenia (FN) episodes analyzed, 175 (49.7%) were culture positive; Gram-negative multi-drug resistant organism (MDRO) sepsis during induction being 57.4% with 34.5% infections due to carbapenem-resistant Enterobacteriaceae (CRE) leading to a mortality rate of 14.6%. The median EFS and OS were 12.0 ± 1.57 (95% CI 8.91-15.08) and 15.0 ± 2.44 (95% CI 10.21-19.78) months respectively. Multivariable analysis revealed significant difference in median OS between favorable vs high risk AML groups (20.0 (95% CI: 12.50-27.49) vs 9.0 (95% CI: 2.99-15.01) months; p = 0.002); time from diagnosis to treatment (< 30 days vs ≥ 30 days; not reached vs 9.0 (95% CI: 6.81-11.18) months; p = 0.001), performance status (1 vs 2 vs 3; not reached vs 12.0 (95% CI: 10.32-13.67) vs 4.0 (95% CI:2.77-5.22); p = 0.001), and attainment of complete remission vs induction failure (not reached vs 6.0 (95% CI: 3.78-8.21); p = 0.002). CONCLUSION: Patient-related factors like delayed treatment initiation and high incidence of MDRO-associated sepsis are critical determinants of AML outcome in LMIC.