Lymphocyte subtype dysregulation in a group of children with simple obesity

Background: Obesity as a global public health problem is increasing in prevalence. Reports showed that obese children are more liable to infection than lean ones; it was claimed that obese subjects have altered peripheral blood total lymphocyte counts in addition to reduced lymphocyte proliferative response to mitogen stimulation as well as dysregulated cytokine expression.Objective: This study aimed to evaluate the effect of childhood obesity on cell mediated immunity as indicated by peripheral blood lymphocyte phenotyping.Methods: We enrolled 30 school-aged children (mean age 10±3.27 years). They comprised two groups; 20 obese children with a mean body mass index (BMI) of 39.2± 12.5 and 10 matched control subjects with mean BMI of 18.4± 1.9. They were subjected to detailed anthropometric evaluation including weight, height, and waist hip ratio in addition to calculation of BMI, complete blood counting, and flow cytometric assessment of T-helper (CD4), T-cytotoxic/suppressor (CD8), and natural killer (CD56) cell counts .Results: The absolute lymphocyte (CD3) and natural killer cell (CD56) counts were comparable in both groups. However, the CD4%, CD8%, CD4/CD8 ratio were significantly lower in the obese children (p=0.02, 0.03, 0.015 respectively). A significant negative correlation could be elicited between the CD4 count and bodyweight, BMI, and hip waist ratio (p = 0.00); the same was observed for CD4/CD8 ratio (p = 0.00). On the contrary, CD8 correlated positively to the bodyweight, BMI, and waist hip ratio (p = 0.00 for each) .Conclusion: Obesity has an impact on lymphocytic subset counts and further studies are needed to assess its effect on their function.Keywords: obesity, children immunology; CD markers; lymphocytes; BM

CXCR 3 expression on CD4+T cells and in renal tissue of pediatric systemic lupus erythematosus patients

Background: Pediatric systemic lupus erythematosus (pSLE) accounts for about 20% of all cases of Systemic Lupus Erythematosus (SLE), with nephritis occurring in approximately 50% of the patients. Objective: to evaluate the expression of CXCR3 in the kidneys and on CD4+ T cells in pSLE. Methods: This study was conducted on 45 patients with pSLE following up at the Allergy and Immunology Clinic, Children’s Hospital, Ain Shams University and 45 age and sex matched healthy children as a control group. Medical history, clinical examination and routine laboratory investigations for assessment of disease activity were done for all patients, the frequency of CXCR3, CD4+ T cells was determined in all patients and controls. Twenty-five Paraffin blocks of patients with lupus nephritis (LN) (available at the time of the study) underwent immunohistochemistry staining for the frequencies of Chemokine C receptor (CXCR3). Results: The absolute level and percentage of serum CD4+CXCR3+ were significantly lower among our patients as compared to healthy controls. A significant direct correlation was found between serum CD4+CXCR3+ and both the lymphocytic count and quantitative Systemic Lupus erythematosus disease activity index (SLEDAI), as well as a significant inverse correlation between it and 24 hours urinary proteins. Variable degrees of CXCR3expression seemed to have no impact on laboratory tests, British Isles Lupus Assessment Group (BILAG) score and cumulative doses of Immunosuppressives. Conclusion: Serum CD4+CXCR3+ and not renal CXCR3 may be a potential marker of LN activity

Membrane endothelial protein C receptor expression in renal tissue of pediatric lupus nephritis patients

Background: Lupus nephritis (LN) is more common and more severe is pediatric systemic lupus erythematosus (pSLE). Endothelial protein C receptor (EPCR) is an inducer of anti-apoptotic pathways in endothelial cells. Recent studies have taken elevated anti-injury biomarkers as EPCR into consideration regarding their roles to antagonize LN.Objectives: to evaluate the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in pediatric patients with LN.Methods: This study was conducted on 25 patients with pSLE following up at the Allergy and Immunology Clinic, Children’s Hospital, Ain Shams University. The 25 patients have LN proved by a previous renal biopsy. Medical history, clinical examination and routine laboratory investigations for assessment of disease activity were done for all patients. Paraffin blocks of patients’ renal biopsies were subjected to immunohistochemistry staining for the frequency of mEPCR.Results: mEPCR was mainly expressed in the endothelium of the peritubular capillaries. Our results showed that an equal number of patients had nil and mild marker expression (8 patients each, 32%) while 9 patients (36%) showed moderate/strong marker expression. We found that 9 out of 10 (90%) of patients with class II had nil/mild marker expression, 5 patients out of 9 (55.5%) with class III had mild/moderate marker expression, while 5 patients 0ut of 6 (83.3%) with class IV and V had moderate/strong marker expression. We only found a significant statistical difference between the different degrees of mEPCR expression regarding 24 hours urinary proteins. No statistical significance was found between the different degrees of mEPCR expression and different immuno-suppressive therapy dose/kg or renal outcome using the renal British Isles Lupus Assessment Group (BILAG) score; in spite that most of the patients who got improved had nil/mild marker expression.Conclusion: mEPCR -bearing a statistically significant difference in relation to different LN classes- showed more expression in the more aggressive classes; a finding which might suggest a contribution of the endothelium of the renal parenchyma to the pathophysiology of more progressive LN. Hence the tissue marker might emerge as a potential new therapeutic target in the search for more selective treatment for SLE.Keywords: p SLE, mEPCR, renal biopsy, immunohistochemistry, BILAG, lupus nephriti

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care