Mast Cell Activation Syndrome: current understanding and research needs.

Mast cell activation syndrome (MCAS) is a term applied to several clinical entities which have gained increased attention from patients and medical providers. While several descriptive publications about MCAS exist, there are many gaps in knowledge resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell (MC) activation is not well understood. More importantly, the underlying mechanisms and pathways that lead to MC activation in MCAS patients remain to be elucidated. The purpose of this manuscript is to summarize the known literature, identify gaps in knowledge, and highlight research needs. Several topics are covered: 1) Contextualization of MCAS and MCAS-like endotypes and related diagnostic evaluations; 2) Mechanistic research; 3) Management of typical and refractory symptoms, and 4) MCAS-specific education for patients and healthcare providers.

An enhanced IL17 and muted type I interferon nasal epithelial cell state characterizes severe COVID-19 with fungal coinfection.

Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing data set characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our previous study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of Candida species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals. Using matched single-cell transcriptomic profiles of these individuals' respiratory mucosa, we identify epithelial immune signatures suggestive of IL17 stimulation and anti-fungal immunity. Further, we observe a significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggest that IL17 stimulation-in part driven by Candida colonization-and blunted interferon signaling represent a common feature of severe COVID-19 infection. IMPORTANCE: In this paper, we present an analysis suggesting that symptomatic and asymptomatic fungal coinfections can impact patient disease progression during COVID-19 hospitalization. By looking into the presence of other pathogens and their effect on the host immune response during COVID-19 hospitalizations, we aim to offer insight into an underestimated scenario, furthering our current knowledge of determinants of severity that could be considered for future diagnostic and intervention strategies.

Parent-carer experiences using a peer support network: a qualitative study.

INTRODUCTION: Parent-carers of children and young people (CYP) with mental health problems are at greater risk of poor outcomes, such as poor physical and mental health. Peer interventions for parent-carers of CYP with disabilities may improve parent-carer outcomes. This qualitative study investigates parent-carer experiences of using Parental Minds (PM), a multi-component peer support service for parent-carers of CYP with disabilities. METHODS: Twelve current service-users and four staff/volunteers at PM participated in one-to-one semi-structured interviews. All participants were white females, except for one service-user who was male. All interviews were recorded and transcribed verbatim. Thematic analysis of results was used to explore perceived benefits and disadvantages of PM and possible behaviour change mechanisms. RESULTS: Three themes and eight subthemes were identified. Participants identified that internal and external factors influence their self-concept. The identification of themselves as a priority, and empowerment by reassurance and affirmation lead to improved parent-carer self-efficacy and agency to better care for their CYP. Participants described the difficulty of speaking honestly with friends and family about what they experience because it is perceived as different to what "normal" parents experience. From participant accounts, PM enables the construction of a support network and links external services to help manage family circumstances rather than offer curative treatment/intervention. Proactive and immediate advice which is constantly and consistently available was valued by participants. Participants expressed the need for a flexible range of service components which provide holistic support that encompasses both health and social care. CONCLUSIONS: PM was perceived to be beneficial as a multi-component peer support service which increases parenting self-efficacy and empowerment, reduces isolation, improves access to services, and is tailored to individual needs. Parent-carers reported benefits in parenting and wellbeing practices. The development of a refined logic model will inform a future study of the effectiveness of PM on parent-carer outcomes.

Enhanced production of eicosanoids in plasma and activation of DNA damage pathways in PBMCs are correlated with the severity of ancestral COVID-19 infection.

Background: Many questions remain unanswered regarding the implication of lipid metabolites in severe SARS-CoV-2 infections. By re-analyzed sequencing data from the nasopharynx of a previously published cohort, we found that alox genes, involved in eicosanoid synthesis, were up-regulated in high WHO score patients, especially in goblet cells. Herein, we aimed to further understand the roles played by eicosanoids during severe SARS-CoV-2 infection. Methods and findings: We performed a total fatty acid panel on plasma and bulk RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) collected from 10 infected and 10 uninfected patients. Univariate comparison of lipid metabolites revealed that lipid metabolites were increased in SARS-CoV-2 patients including the lipid mediators Arachidonic Acid (AA) and Eicosapentaenoic Acid (EPA). AA, EPA and the fatty acids Docosahexaenoic acid (DHA) and Docosapentaenoic acid (DPA), were positively correlated to WHO disease severity score. Transcriptomic analysis demonstrated that COVID-19 patients can be segregated based on WHO scores. Ontology, KEGG and Reactome analysis identified pathways enriched for genes related to innate immunity, interactions between lymphoid and nonlymphoid cells, interleukin signaling and, cell cycling pathways. Conclusions: Our study offers an association between nasopharynx mucosa eicosanoid genes expression, specific serum inflammatory lipids and, subsequent DNA damage pathways activation in PBMCs to severity of COVID-19 infection.

Immune marker reductions in black and white Americans following sleeve gastrectomy in the short-term phase of surgical weight loss.

BACKGROUND: Surgical weight loss procedures like vertical sleeve gastrectomy (SG) are sufficient in resolving obesity comorbidities and are touted to reduce the burden of pro-inflammatory cytokines and augment the release of anti-inflammatory cytokines. Recent reports suggest a reduced improvement in weight resolution after SG in Black Americans (BA) versus White Americans (WA). The goal of this study was to determine if differences in immunoglobulin levels and general markers of inflammation after SG in Black Americans (BA) and White Americans (WA) may contribute to this differential resolution. METHODS: Personal information, anthropometric data, and plasma samples were collected from 58 participants (24 BA and 34 WA) before and 6 weeks after SG for the measurement of immunoglobulin A (IgA), IgG, IgM, C-reactive protein (CRP), and transforming growth factor (TGFß). Logistic regression analysis was used to determine the relationship of measures of body size and weight and inflammatory markers. RESULTS: Both IgG and CRP were significantly elevated in BA in comparison to WA prior to weight loss. Collectively, IgG, TGFß, and CRP were all significantly reduced at six weeks following SG. CRP levels in BA were reduced to a similar extent as WA, but IgG levels were more dramatically reduced in BA than WA despite the overall higher starting concentration. No change was observed in IgA and IgM. CONCLUSIONS: These data suggest that SG improves markers of immune function in both BA and WA. More diverse markers of immune health should be studied in future work.

Interventions to support parents and carers of young people with mental health difficulties: a systematic review protocol.

INTRODUCTION: Globally, 8%-14% of children and young people (CYP) have a diagnosable mental health condition, many of whom receive no formal interventions. Parents/carers of CYP experience stress and distress owing to the mental health difficulties encountered by their CYP due to the lack of resources and support. Currently, little is known about (1) the content of interventions developed to support parents/carers nor (2) how effective interventions are at improving parents'/carers' well-being. The planned review aims to address these two gaps. METHOD AND ANALYSIS: A systematic review will be conducted to identify any study that describes an intervention aiming at least in part to support parents/carers with the impact of CYP (5-18 years) mental health difficulties, and to review any randomised controlled trials (RCTs) of these interventions. The following databases will be searched: MEDLINE, PsycINFO, CINAHL, AMED, EMBASE, Web of Science Core Collection and Cochrane Library CENTRAL, without any limitations applied. Analysis of the content of interventions will be structured using the Template for Intervention Description and Replication checklist as a framework. The effect of any RCTs on parents'/carers' outcomes (including well-being, satisfaction with parenting, mental health) will be extracted and assessed using the Cochrane Risk-of-Bias Tool. Data will be synthesised narratively, with meta-analysis of RCT results, if appropriate. ETHICAL CONSIDERATION AND DISSEMINATION: The protocol is approved by Coventry University Ethical Committee (reference number: P139611). Results will be shared in academic publications and in accessible formats using social media and public webinars. PROSPERO REGISTRATION NUMBER: CRD42022344453.

Black Inflammatory Bowel Disease Patients Have Lower Response to Antitumor Necrosis Factor Agents Compared With White Patients.

BACKGROUND: Most studies on the safety and efficacy of antitumor necrosis factor alpha (anti-TNF) agents in the treatment of inflammatory bowel disease have included few Black patients. AIMS: We aimed to evaluate the therapeutic response rate in Black IBD patients compared with White patients. METHODS: We conducted a retrospective review of IBD patients who were treated with anti-TNF agents and assessed those with therapeutic drug levels for clinical, endoscopic, and radiologic response to anti-TNF treatment. RESULTS: We identified 118 patients who met the inclusion criteria. Black IBD patients had significantly higher prevalence of endoscopic and radiologic active disease compared with White patients (62% and 34%, respectively; P = .023), despite similar proportions reaching therapeutic titers (67% and 55%, respectively; P = .20). Moreover, Black patients had significantly higher rate of IBD-related hospitalizations than White patients (30% vs 13%, respectively; P = .025) while on anti-TNF agents. CONCLUSIONS: Black IBD patients on anti-TNF agents had a significantly higher prevalence of active disease and more IBD-related hospitalizations than White patients.

This study explores the question of how IBD therapeutic efficacy may vary among racial groups.

Needs of parents and carers of children and young people with mental health difficulties: protocol for a systematic review.

INTRODUCTION: Having a child or young person (CYP) with mental health problems can be highly distressing for parents/carers. The impact can include parental/carer depression, anxiety, lost productivity and poor family relationships. Currently, there is no synthesis of this evidence, which is needed to provide clarity around what support parents/carers may need, to meet the needs of family mental health. This review aims to identify the needs of the parents/carers of CYP who are receiving mental health services. METHODS AND ANALYSIS: A systematic review will be conducted to identify potentially relevant studies that provide evidence concerning the needs and impact on parents/carers linked to their CYP having mental health difficulties. CYP mental health conditions included are anxiety disorders, depression, psychoses, oppositional defiant and other externalising disorders, labels of emerging personality disorders, eating disorders and attention deficit (hyperactive) disorders. The following databases were searched on November 2022 with no date restriction applied: Medline; PsycINFO; CINAHL; AMED; EMBASE; Web of Science; Cochrane Library; WHO International Clinical Trials Registry Platform; Social Policy and Practice; Applied Social Sciences Index and Abstracts; and Open Grey. Only studies reported in English will be included. The quality of the included studies will be assessed using Joanna Briggs Institute Critical Appraisal Checklist for qualitative studies and the Newcastle Ottawa Scale for quantitative studies. Qualitative data will be analysed thematically and inductively. ETHICS AND DISSEMINATION: This review was approved by the ethical committee at Coventry University, UK, reference number P139611. The findings from this systematic review will be disseminated across various key stakeholders and published in peer-reviewed journals.

A focused retrospective study on differences in IBD characteristics between Black and White patients in the south.

BACKGROUND: Most facets of Inflammatory Bowel Disease (IBD) have not been thoroughly compared among minority populations, including Black patients. Our study was designed to characterize the demographics, phenotypes, outcomes, healthcare utilization, and treatment of IBD in a large cohort with 38% Black patients. METHODS: Electronic health records of 3272 IBD patients seen in a tertiary academic medical network from 2012 to July 15th, 2019 were analyzed. RESULTS: Black patients with Crohn's disease were significantly more likely than White patients to suffer from perianal (p < 0.001), fistulizing (p < 0.001), and fibrostenotic phenotypes (p < 0.001). Black patients with IBD were significantly more likely to undergo IBD-related surgery (p = 0.042) and experience an IBD-related complication (p < 0.001). The proportion of patients with at least one colonoscopy, one visit to the gastroenterology clinic, one visit to the emergency department (ED), and one hospital admission were higher in Black patients (p < 0.001, p = 0.005, p < 0.001, and p < 0.001; respectively). CONCLUSIONS: Black IBD patients had more severe disease phenotypes and worse healthcare outcomes than White patients. Black patients also used healthcare facilities and IBD medications to an equal or greater extent, despite being of a lower average socioeconomic class than their White counterparts. Our study suggests that underlying factors that do not pertain to the utilization of healthcare resources may be responsible for these worse outcomes in Black patients.

COVID-19 Plasma Extracellular Vesicles Increase the Density of Lipid Rafts in Human Small Airway Epithelial Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is the causative agent of the COVID-19 disease. COVID-19 viral infection can affect many cell types, including epithelial cells of the lungs and airways. Extracellular vesicles (EVs) are released by virtually all cell types, and their packaged cargo allows for intercellular communication, cell differentiation, and signal transduction. Cargo from virus-infected cells may include virally derived metabolites, miRNAs, nucleic acids, and proteins. We hypothesized that COVID-19 plasma EVs can induce the formation of signaling platforms known as lipid rafts after uptake by normal human small airway epithelial cells (SAECs). Circulating EVs from patients with or without COVID-19 were characterized by nanoparticle tracking analysis, Western blotting using specific antibodies, and transmission electron microscopy. Primary cultures of normal human small airway epithelial cells were challenged with EVs from the two patient groups, and lipid raft formation was measured by fluorescence microscopy and assessed by sucrose density gradient analysis. Collectively, our data suggest that circulating EVs from COVID-19-infected patients can induce the formation of lipid rafts in normal human small airway epithelial cells. These results suggest the need for future studies aimed at investigating whether the increased density of lipid rafts in these cells promotes viral entry and alteration of specific signaling pathways in the recipient cells.

The Current State of Care for Black and Hispanic Inflammatory Bowel Disease Patients.

Research on the care of inflammatory bowel disease (IBD) patients has been primarily in populations of European ancestry. However, the incidence of IBD, which comprises Crohn's disease and ulcerative colitis, is increasing in different populations around the world. In this comprehensive review, we examine the epidemiology, clinical presentations, disease phenotypes, treatment outcomes, social determinants of health, and genetic and environmental factors in the pathogenesis of IBD in Black and Hispanic patients in the United States. To improve health equity of underserved minorities with IBD, we identified the following priority areas: access to care, accurate assessment of treatment outcomes, incorporation of Black and Hispanic patients in therapeutic clinical trials, and investigation of environmental factors that lead to the increase in disease incidence.

In this comprehensive review, we examine the epidemiology, clinical presentations, disease phenotypes, treatment outcomes, social determinants of health, and genetic and environment factors in the pathogenesis of IBD in Black and Hispanic patients in the United States.

Genetically defined individual reference ranges for tryptase limit unnecessary procedures and unmask myeloid neoplasms.

Serum tryptase is a biomarker used to aid in the identification of certain myeloid neoplasms, most notably systemic mastocytosis, where basal serum tryptase (BST) levels >20 ng/mL are a minor criterion for diagnosis. Although clonal myeloid neoplasms are rare, the common cause for elevated BST levels is the genetic trait hereditary α-tryptasemia (HαT) caused by increased germline TPSAB1 copy number. To date, the precise structural variation and mechanism(s) underlying elevated BST in HαT and the general clinical utility of tryptase genotyping, remain undefined. Through cloning, long-read sequencing, and assembling of the human tryptase locus from an individual with HαT, and validating our findings in vitro and in silico, we demonstrate that BST elevations arise from overexpression of replicated TPSAB1 loci encoding canonical α-tryptase protein owing to coinheritance of a linked overactive promoter element. Modeling BST levels based on TPSAB1 replication number, we generate new individualized clinical reference values for the upper limit of normal. Using this personalized laboratory medicine approach, we demonstrate the clinical utility of tryptase genotyping, finding that in the absence of HαT, BST levels >11.4 ng/mL frequently identify indolent clonal mast cell disease. Moreover, substantial BST elevations (eg, >100 ng/mL), which would ordinarily prompt bone marrow biopsy, can result from TPSAB1 replications alone and thus be within normal limits for certain individuals with HαT.

Severe COVID-19 is associated with fungal colonization of the nasopharynx and potent induction of IL-17 responses in the nasal epithelium.

Recent case reports and epidemiological data suggest fungal infections represent an under-appreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing (scRNA-seq) dataset characterizing the upper respiratory microenvironment during COVID-19, and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of Candida species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals, including confirmatory diagnostic testing demonstrating elevated serum (1, 3)-ß-D-glucan and/or confirmed fungal culture of the predicted pathogen. Using matched single-cell transcriptomic profiles of these individuals' respiratory mucosa, we identify epithelial immune signatures suggestive of IL-17 stimulation and anti-fungal immunity. Further, we observe significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggests that IL-17 stimulation - in part driven by Candida colonization - and blunted type I/III interferon signaling represents a common feature of severe COVID-19 infection.

Aspergillus in COVID-19 intensive care unit; what is lurking above your head?

Introduction: Through routine respiratory samples surveillance among COVID-19 patients in the intensive care, three patients with aspergillus were identified in a newly opened general intensive care unit during the second wave of the pandemic. Methodology: As no previous cases of aspergillus had occurred since the unit had opened. An urgent multidisciplinary outbreak meeting was held. The possible sources of aspergillus infection were explored. The multidisciplinary approach enabled stakeholders from different skills to discuss possible sources and management strategies. Environmental precipitants like air handling units were considered and the overall clinical practice was reviewed. Settle plates were placed around the unit to identify the source. Reports of recent water leaks were also investigated. Results: Growth of aspergillus on a settle plate was identified the potential source above a nurse's station. This was the site of a historic water leak from the ceiling above, that resolved promptly and was not investigated further. Subsequent investigation above the ceiling tiles found pooling of water and mould due to a slow water leak from a pipe. Conclusion: Water leaks in patient areas should be promptly notified to infection prevention. Detailed investigation to ascertain the actual cause of the leak and ensure any remedial work could be carried out swiftly. Outbreak meetings that include diverse people with various expertises (clinical and non-clinical) can enable prompt identification and resolution of contaminated areas to minimise risk to patients and staff. During challenging pandemic periods hospitals must not lose focus on other clusters and outbreaks occurring simultaneously.

Sodium-Glucose Cotransporter 2 Inhibitor Use Among Individuals Age <65 with Type 2 Diabetes and Heart Failure with Reduced Ejection Fraction: A Cost-Benefit Analysis.

Background: Type 2 diabetes (T2D) patients face increased risk of heart failure (HF) as they age. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have demonstrated effectiveness in reducing HF hospitalizations in patients with T2D and HF with reduced ejection fraction (HFrEF). Diabetes guidelines recommend SGLT-2i therapy for patients with HFrEF; however, SGLT-2i cost is high. Objective: Study objectives were to assess SGLT-2i utilization and HF hospitalization rates in commercially insured adults (age <65) with T2D and heart failure with reduced ejection fraction (HFrEF) taking metformin with/without SGLT-2i use and conduct a cost-benefit analysis of SGLT-2i use from payer and societal perspectives. Methods: Economic models included HF hospitalization rates from real-world data (RWD) and hospitalization rate reductions from RWD and SGLT-2i clinical trials. Real-world HF hospitalization rates were obtained from claims data (MarketScan Commercial Database, years 2013-2018). Societal perspective analyses included indirect costs. Sensitivity analyses were conducted on key parameters. Results: Among adults with T2D and HFrEF age 30-64, SGLT-2i use increased (1.1% to 17.4%) between 2013 and 2018. The HF hospitalization rate without SGLT-2i use vs with was 15.5% vs 11.0% (absolute risk reduction of 4.5%). Base case scenario net-benefit was negative across all payer perspective models, while positive for societal-perspective. Payer perspective overall net-benefit in 30-64 population: -$1,725,758 (-$4106 per person). Societal perspective net-benefit in 30-64 population: $5,996,851 ($14,269 per person). In sensitivity analyses, estimated per person base case societal net-benefit of $14,269 was most sensitive to changes in baseline HF hospitalization rates, post-discharge mortality rates, and readmission rates. Lowering SGLT-2i prescription costs 50% and 80% resulted in per person net-benefit increases of $1737 and $4004, respectively. Conclusion: SGLT-2i utilization has steadily increased, with lower HF hospitalization rates observed among SGLT-2i users. Societal benefits of SGLT-2i use in this population are substantive; payer benefits are negative unless SGLT-2i cost is drastically reduced.

Prospective Cohort Study to Investigate the Safety of Preoperative Tumor Necrosis Factor Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery.

BACKGROUND & AIMS: Whether preoperative treatment of inflammatory bowel disease (IBD) with tumor necrosis factor inhibitors (TNFis) increases the risk of postoperative infectious complications remains controversial. The primary aim of this study was to determine whether preoperative exposure to TNFis is an independent risk factor for postoperative infectious complications within 30 days of surgery. METHODS: We conducted a multicenter prospective observational study of patients with IBD undergoing intra-abdominal surgery across 17 sites from the Crohn's & Colitis Foundation Clinical Research Alliance. Infectious complications were categorized as surgical site infections (SSIs) or non-SSIs. Current TNFi exposure was defined as use within 12 weeks of surgery, and serum was collected for drug-level analyses. Multivariable models for occurrence of the primary outcome, any infection, or SSI were adjusted by predefined covariates (age, sex, preoperative steroid use, and disease type), baseline variables significantly associated (P < .05) with any infection or SSI separately, and TNFi exposure status. Exploratory models used TNFi exposure based on serum drug concentration. RESULTS: A total of 947 patients were enrolled from September 2014 through June 2017. Current TNFi exposure was reported by 382 patients. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed. In multivariable analysis, current TNFi exposure was not associated with any infection (odds ratio, 1.050; 95% confidence interval, 0.716-1.535) or SSI (odds ratio, 1.249; 95% confidence interval, 0.793-1.960). Detectable TNFi drug concentration was not associated with any infection or SSI. CONCLUSIONS: Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort.

Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease (COPD-ST2OP): a phase 2a, placebo-controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory airway disease. The epithelial-derived IL-33 and its receptor ST2 have been implicated in airway inflammation and infection. We aimed to determine whether astegolimab, a selective ST2 IgG2 monoclonal antibody, reduces exacerbations in COPD. METHODS: COPD-ST2OP was a single-centre, randomised, double-blinded, placebo-controlled phase 2a trial in moderate-to-very severe COPD. Participants were randomly assigned (1:1) with a web-based system to received 490 mg subcutaneous astegolimab or subcutaneous placebo, every 4 weeks for 44 weeks. The primary endpoint was exacerbation rate assessed for 48 weeks assessed with a negative binomial count model in the intention-to-treat population, with prespecified subgroup analysis by baseline blood eosinophil count. The model was the number of exacerbations over the 48-week treatment period, with treatment group as a covariate. Safety was assessed in the whole study population until week 60. Secondary endpoints included Saint George's Respiratory Questionnaire for COPD (SGRQ-C), FEV1, and blood and sputum cell counts. The trial was registered with ClinicalTrials.gov, NCT03615040. FINDINGS: The exacerbation rate at 48 weeks in the intention-to-treat analysis was not significantly different between the astegolimab group (2·18 [95% CI 1·59 to 2·78]) and the placebo group (2·81 [2·05 to 3·58]; rate ratio 0·78 [95% CI 0·53 to 1·14]; p=0·19]). In the prespecified analysis stratifying patients by blood eosinophil count, patients with 170 or fewer cells per µL had 0·69 exacerbations (0·39 to 1·21), whereas those with more than 170 cells per µL had 0·83 exacerbations (0·49 to 1·40). For the secondary outcomes, the mean difference between the SGRQ-C in the astegolimab group versus placebo group was -3·3 (95% CI -6·4 to -0·2; p=0·039), and mean difference in FEV1 between the two groups was 40 mL (-10 to 90; p=0·094). The difference in geometric mean ratios between the two groups for blood eosinophil counts was 0·59 (95% CI 0·51 to 0·69; p<0·001) and 0·25 (0·19 to 0·33; p<0·001) for sputum eosinophil counts. Incidence of treatment-emergent adverse events was similar between groups. INTERPRETATION: In patients with moderate-to-very severe COPD, astegolimab did not significantly reduce exacerbation rate, but did improve health status compared with placebo. FUNDING: Funded by Genentech and National Institute for Health Research Biomedical Research Centres.

Urinary manifestations in African American and Caucasian inflammatory bowel disease patients: a retrospective cohort study.

BACKGROUND: Inflammatory bowel diseases (IBD), like ulcerative colitis (UC) and Crohn's disease (CD), are associated with urinary extra-intestinal manifestations, like urolithiasis and uncomplicated urinary tract infections (UTIs). The literature reviewed for this study identifies an increased association of CD and urolithiasis against the general population as well as UC. Furthermore, the rates in which urinary comorbidities manifest have not been well characterized in cross-race analyses. The purpose of this study is to establish the prevalence of common urinary extra-intestinal manifestations in CD and UC and to further determine at what rate these affect the African American and Caucasian populations. METHODOLOGY: This is a retrospective cohort study using de-identified data collected from a research data base that included 6 integrated facilities associated with one tertiary healthcare center from 2012 to 2019. The electronic chart records for 3104 Caucasian and African American IBD patients were reviewed for frequency of urolithiasis and uncomplicated UTI via diagnosed ICD-10 codes. Comparison between data groups was made using multivariate regressions, t-tests, and chi square tests. RESULTS: Our study included 3104 patients of which 59% were female, 38% were African American, and 43% were diagnosed with UC. Similar proportions of UC and CD diagnosed patients developed urolithiasis (6.0% vs 6.7%, p = 0.46), as well as uncomplicated UTIs (15.6% vs. 14.9%, p = 0.56). Similar proportions of African American and Caucasian patients developed urolithiasis (5.4% vs 7.0%, p = 0.09), but a higher proportion of African Americans developed uncomplicated UTIs (19.4% vs 12.6%, p ≤ 0.001). CONCLUSION: We found similar rates of urolithiasis formation in both UC and CD in this study. Furthermore, these rates were not significantly different between African American and Caucasian IBD populations. This suggests that UC patients have an elevated risk of urolithiasis formation as those patients with CD. Additionally, African Americans with IBD have a higher frequency of uncomplicated UTI as compared to their Caucasian counterparts.