Recurrent urinary tract infections and prophylactic antibiotic use in women: cross-sectional study.

BACKGROUND: Despite the considerable morbidity caused by recurrent UTIs (rUTIs), and the wider personal and public health implications from frequent antibiotic use, few studies adequately describe the prevalence and characteristics of women with rUTIs or those who use prophylactic antibiotics. AIM: To describe the prevalence, characteristics, and urine profiles of women with rUTIs with and without prophylactic antibiotic use in Welsh primary care. DESIGN AND SETTING: Retrospective cross-sectional study in Welsh General Practice using the SAIL Databank. METHOD: We describe the characteristics of women aged ≥18 years with rUTIs or using prophylactic antibiotics from 2010-2020, and associated urine culture results from 2015 - 2020. RESULTS: 6.0% of women (n=92,213) had rUTIs, and 1.7% (n=26,862) were prescribed prophylactic antibiotics. Only 49% of prophylactic antibiotic users met the definition of rUTIs before initiation. 81% of women with rUTIs had a urine culture result in the preceding 12 months with high rates of resistance to trimethoprim and amoxicillin. 64% of women taking prophylactic antibiotics had a urine culture result before initiation, and 18% (n=320) of women prescribed trimethoprim had resistance to it on the antecedent sample. CONCLUSION: A substantial proportion of women had rUTIs or incident prophylactic antibiotic use. However, 64% of women had urine cultured before starting prophylaxis. There was a high proportion of cultured bacteria resistant to two antibiotics used for rUTI prevention and evidence of resistance to the prescribed antibiotic. More frequent urine cultures for rUTI diagnosis and before prophylactic antibiotic initiation could better inform antibiotic choices.

Myocardial infarction and stroke subsequent to urinary tract infection (MISSOURI): protocol for a self-controlled case series using linked electronic health records.

INTRODUCTION: There is increasing interest in the relationship between acute infections and acute cardiovascular events. Most previous research has focused on understanding whether the risk of acute cardiovascular events increases following a respiratory tract infection. The relationship between urinary tract infections (UTIs) and acute cardiovascular events is less well studied. Therefore, the aim of this study is to determine whether there is a causal relationship between UTI and acute myocardial infarction (MI) or stroke. METHODS AND ANALYSIS: We will undertake a self-controlled case series study using linked anonymised general practice, hospital admission and microbiology data held within the Secure Anonymised Information Linkage (SAIL) Databank. Self-controlled case series is a relatively novel study design where individuals act as their own controls, thereby inherently controlling for time-invariant confounders. Only individuals who experience an exposure and outcome of interest are included.We will identify individuals in the SAIL Databank who have a hospital admission record for acute MI or stroke during the study period of 2010-2020. Individuals will need to be aged 30-100 during the study period and be Welsh residents for inclusion. UTI will be identified using general practice, microbiology and hospital admissions data. We will calculate the incidence of MI and stroke in predefined risk periods following an UTI and in 'baseline' periods (without UTI exposure) and use conditional Poisson regression models to derive incidence rate ratios. ETHICS AND DISSEMINATION: Data access, research permissions and approvals have been obtained from the SAIL independent Information Governance Review Panel, project number 0972. Findings will be disseminated through conferences, blogs, social media threads and peer-reviewed journals. Results will be of interest internationally to primary and secondary care clinicians who manage UTIs and may inform future clinical trials of preventative therapy.

Myeloid-Derived Suppressor Cells and Clinical Outcomes in Children With COVID-19.

Background: Although children with COVID-19 account for fewer hospitalizations than adults, many develop severe disease requiring intensive care treatment. Critical illness due to COVID-19 has been associated with lymphopenia and functional immune suppression. Myeloid-derived suppressor cells (MDSCs) potently suppress T cells and are significantly increased in adults with severe COVID-19. The role of MDSCs in the immune response of children with COVID-19 is unknown. Aims: We hypothesized that children with severe COVID-19 will have expansion of MDSC populations compared to those with milder disease, and that higher proportions of MDSCs will correlate with clinical outcomes. Methods: We conducted a prospective, observational study on a convenience sample of children hospitalized with PCR-confirmed COVID-19 and pre-pandemic, uninfected healthy controls (HC). Blood samples were obtained within 48 h of admission and analyzed for MDSCs, T cells, and natural killer (NK) cells by flow cytometry. Demographic information and clinical outcomes were obtained from the electronic medical record and a dedicated survey built for this study. Results: Fifty children admitted to the hospital were enrolled; 28 diagnosed with symptomatic COVID-19 (10 requiring ICU admission) and 22 detected by universal screening (6 requiring ICU admission). We found that children with severe COVID-19 had a significantly higher percentage of MDSCs than those admitted to the ward and uninfected healthy controls. Increased percentages of MDSCs in peripheral blood mononuclear cells (PBMC) were associated with CD4+ T cell lymphopenia. MDSC expansion was associated with longer hospitalizations and need for respiratory support in children admitted with acute COVID-19. Conclusion: These findings suggest that MDSCs are part of the dysregulated immune responses observed in children with severe COVID-19 and may play a role in disease pathogenesis. Future mechanistic studies are required to further understand the function of MDSCs in the setting of SARS-CoV-2 infection in children.

Innate and adaptive immune activation in the brain of MPS IIIB mouse model.

Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with severe neurological manifestations due to alpha-N-acetylglucosaminidase (NaGlu) deficiency. The mechanism of neuropathology in MPS IIIB is unclear. This study investigates the role of immune responses in neurological disease of MPS IIIB in mice. By means of gene expression microarrays and real-time quantitative reverse transcriptase-polymerase chain reaction, we demonstrated significant up-regulation of numerous immune-related genes in MPS IIIB mouse brain involving a broad range of immune cells and molecules, including T cells, B cells, microglia/macrophages, complement, major histocompatibility complex class I, immunoglobulin, Toll-like receptors, and molecules essential for antigen presentation. The significantly enlarged spleen and lymph nodes in MPS IIIB mice were due to an increase in splenocytes/lymphocytes, and functional assays indicated that the T cells were activated. An autoimmune component to the disease was further suggested by the presence of putative autoantigen or autoantigens in brain extracts that reacted specifically with serum IgG from MPS IIIB mice. We also demonstrated for the first time that immunosuppression with prednisolone alone can significantly slow the central nervous system disease progression. Our data indicate that immune responses contribute greatly to the neuropathology of MPS IIIB and should be considered as an adjunct treatment in future therapeutic developments for optimal therapeutic effect.