Histo-blood group antigen contains oligosaccharides that serve as receptors for norovirus (NoV) and rotavirus (RV). The receptors are only present on the surface of intestinal mucosal epithelial ...cells of secretors; therefore, secretors are susceptible to NoV and RV diarrhea and nonsecretors are resistant. The prevalence of secretors in different countries varies between 50% and 90%. Secretor rates evolved in response to environmental pressures such as infectious diseases.
Introduction
Obesity is associated with endothelial dysfunction, haemostatic and fibrinolytic disturbances, however the impact of obesity on von Willebrand factor (VWF) is unclear.
Aim
The aim of ...this study was to test our hypothesis that the prevalence of obesity is higher among participants with low VWF (LVWF) compared to type 1 von Willebrand disease (T1VWD).
Methods
A retrospective review of the ATHNdataset as of March 2018 was performed. Participants were categorized as T1VWD if their VWF ristocetin cofactor activity was 30 IU/dL and LVWF if the values were 30–50 IU/dL, and by the NIH definitions for body mass index (BMI) for adult participants (≥ 18 years of age) or BMI z‐score for paediatric participants (< 18 years).
Results
The prevalence of obesity was not significantly different between adults with T1VWD (n = 186) and LVWF (n = 362) (32% vs 36%; p = .345). The mean factor VIII (FVIII) increased with increasing BMIs in both groups. In the paediatric cohort (T1VWD, n = 583; LVWF, n = 1702), there was no difference in the prevalence of obesity, but BMI was positively correlated with mean FVIII (p < .001). Children < 10 years were 27.6% more likely to be diagnosed with T1VWD compared to > 10 years.
Conclusion
Among participants in the ATHNdataset, the prevalence of obesity was similar among those with LVWF and T1VWD. However, higher BMI levels were associated with elevated FVIII. Further research is needed to evaluate the impact of obesity on bleeding phenotype and treatment practices.
Selection pressure due to exposure to infectious pathogens endemic to Africa may explain distinct genetic variations in immune response genes. However, the impact of those genetic variations on human ...immunity remains understudied, especially within the context of modern lifestyles and living environments, which are drastically different from early humans in sub Saharan Africa. There are few data on population differences in constitutional immune environment, where genetic ancestry and environment are likely two primary sources of variation. In a study integrating genetic, molecular and epidemiologic data, we examined population differences in plasma levels of 14 cytokines involved in innate and adaptive immunity, including those implicated in chronic inflammation, and possible contributing factors to such differences, in 914 AA and 855 EA women. We observed significant differences in 7 cytokines, including higher plasma levels of CCL2, CCL11, IL4 and IL10 in EAs and higher levels of IL1RA and IFNα2 in AAs. Analyses of a wide range of demographic and lifestyle factors showed significant impact, with age, education level, obesity, smoking, and alcohol intake, accounting for some, but not all, observed population differences for the cytokines examined. Levels of two pro-inflammatory chemokines, CCL2 and CCL11, were strongly associated with percent of African ancestry among AAs. Through admixture mapping, the signal was pinpointed to local ancestry at 1q23, with fine-mapping analysis refined to the Duffy-null allele of rs2814778. In AA women, this variant was a major determinant of systemic levels of CCL2 (p = 1.1e-58) and CCL11 (p = 2.2e-110), accounting for 19% and 40% of the phenotypic variance, respectively. Our data reveal strong ancestral footprints in inflammatory chemokine regulation. The Duffy-null allele may indicate a loss of the buffering function for chemokine levels. The substantial immune differences by ancestry may have broad implications to health disparities between AA and EA populations.
Summary
Although haemoglobin SC (HbSC) accounts for 30% of sickle cell disease (SCD) in the United States and United Kingdom, evidence‐based guidelines for genotype specific management are lacking. ...The unique pathology of HbSC disease is complex, characterized by erythrocyte dehydration, intracellular sickling and increased blood viscosity. The evaluation and treatment of patients with HbSC is largely inferred from studies of SCD consisting mostly of haemoglobin SS (HbSS) patients. These studies are underpowered to allow definitive conclusions about HbSC. We review the pathophysiology of HbSC disease, including known and potential differences between HbSS and HbSC, and highlight knowledge gaps in HbSC disease management. Clinical and translational research is needed to develop targeted treatments and to validate management recommendations for efficacy, safety and impact on quality of life for people with HbSC.
Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA) could lead to early identification of high-risk patients, better screening ...strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate. We first investigated candidate genetic polymorphisms in well-characterized SCA pediatric cohorts from three prospective NHLBI-supported clinical trials: HUSTLE, SWiTCH, and TWiTCH. We also performed whole exome sequencing to identify novel genetic variants, using both a discovery and a validation cohort. Among candidate genes, DARC rs2814778 polymorphism regulating Duffy antigen expression had a clear influence with significantly increased WBC and neutrophil counts, but did not affect the maximum tolerated dose of hydroxyurea therapy. The APOL1 G1 polymorphism, an identified risk factor for non-diabetic renal disease, was associated with albuminuria. Whole exome sequencing discovered several novel variants that maintained significance in the validation cohorts, including ZFHX4 polymorphisms affecting both the leukocyte and neutrophil counts, as well as AGGF1, CYP4B1, CUBN, TOR2A, PKD1L2, and CD163 variants affecting the glomerular filtration rate. The identification of robust, reliable, and reproducible genetic markers for disease severity in SCA remains elusive, but new genetic variants provide avenues for further validation and investigation.
Objective
To examine the association between perioperative red blood cell (RBC) transfusion and postoperative venous thromboembolism (VTE) in pediatric surgical patients.
Methods
Retrospective cohort ...study using the National Surgical Quality Improvement Project Pediatric, a validated registry of 118 United States children's hospitals. Patients under 19 years of age undergoing a surgical procedure between 2012 and 2017 were included, with the main exposure being RBC transfusion in the perioperative period (48 hours prior to operation to 72 hours after operation). The primary 30‐day outcome of interest was a postoperative VTE requiring therapy. Risk‐adjusted odds ratios (aOR) were calculated using multiple logistic regression. Subgroup analyses were performed across multiple surgical specialties. Sensitivity analyses were performed after (a) imputation for missing variables and (b) propensity score matching.
Results
During the study years, 482 867 pediatric patients (56.7% male; median age, 6 years interquartile range, 1–12 years) underwent an operation. Of these, 30 879 (6.4%) received at least one perioperative RBC transfusion. Postoperative VTE requiring therapy occurred in 618 patients (0.13%). After adjustment for multiple risk factors, perioperative RBC transfusion was associated with an increased risk of VTE (aOR 2.4; 95% CI, 1.9–3.0). The increased VTE risk persisted after imputation of missing demographic and clinical data as well as after 1:1 propensity score matching (29 811 matched pairs, aOR 2.2; 95% CI, 1.7–2.8).
Conclusions
Perioperative RBC transfusion is associated with an increased, albeit still very low, risk of postoperative VTE in pediatric patients. Patients receiving blood in the perioperative period may benefit from additional monitoring or VTE prophylaxis.
Venous thromboembolism (VTE) in pediatric surgical patients is a rare event. The risk factors for VTE in pediatric general surgery patients undergoing abdominopelvic procedures are unknown.
The ...American College of Surgeon’s National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database (2012–2015) was queried for patients with VTE after abdominopelvic general surgery procedures. Patient and operative variables were assessed to identify risk factors associated with VTE and develop a pediatric risk score.
From 2012-2015, 68 of 34,813 (0.20%) patients who underwent abdominopelvic general surgery procedures were diagnosed with VTE. On multivariate analysis, there was no increased risk of VTE based on concomitant malignancy, chemotherapy, inflammatory bowel disease, or laparoscopic surgical approach, while a higher rate of VTE was identified among female patients. The odds of experiencing VTE were increased on stepwise regression for patients older than 15 years and those with preexisting renal failure or a diagnosis of septic shock, patients with American Society of Anesthesia (ASA) classification ≥ 2, and for anesthesia time longer than 2 h. The combination of age > 15 years, ASA classification ≥ 2, anesthesia time > 2 h, renal failure, and septic shock was included in a model for predicting risk of VTE (AUC = 0.907, sensitivity 84.4%, specificity 88.2%).
VTE is rare in pediatric patients, but prediction modeling may help identify those patients at heightened risk. Additional studies are needed to validate the factors identified in this study in a risk assessment model as well as to assess the efficacy and cost-effectiveness of prophylaxis methods.
Level III, retrospective comparative study.
With increasing early and upfront use of rituximab and caplacizumab in the modern management of immune-mediated thrombotic thrombocytopenic purpura (iTTP), the risk of refractory disease is expected ...to decline. However, despite the use of adequate initial therapy, a small subset of patients develop a refractory disease which is difficult to manage. Bortezomib has come to be known as a safe and effective treatment option for refractory iTTP, but its use in children is limited. Here, we describe the case of an adolescent patient with refractory iTTP who had a satisfactory and sustained response to the use of bortezomib.
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