Sepsis endotypes identified by host gene expression across global cohorts.

BACKGROUND: Sepsis from infection is a global health priority and clinical trials have failed to deliver effective therapeutic interventions. To address complicating heterogeneity in sepsis pathobiology, and improve outcomes, promising precision medicine approaches are helping identify disease endotypes, however, they require a more complete definition of sepsis subgroups. METHODS: Here, we use RNA sequencing from peripheral blood to interrogate the host response to sepsis from participants in a global observational study carried out in West Africa, Southeast Asia, and North America (N = 494). RESULTS: We identify four sepsis subtypes differentiated by 28-day mortality. A low mortality immunocompetent group is specified by features that describe the adaptive immune system. In contrast, the three high mortality groups show elevated clinical severity consistent with multiple organ dysfunction. The immunosuppressed group members show signs of a dysfunctional immune response, the acute-inflammation group is set apart by molecular features of the innate immune response, while the immunometabolic group is characterized by metabolic pathways such as heme biosynthesis. CONCLUSIONS: Our analysis reveals details of molecular endotypes in sepsis that support immunotherapeutic interventions and identifies biomarkers that predict outcomes in these groups.

Sepsis is a life-threatening multi-organ failure caused by the body's immune response to infection. Clinical symptoms of sepsis vary from one person to another likely due to differences in host factors, infecting pathogen, and comorbidities. This difference in clinical symptoms may contribute to the lack of effective interventions for sepsis. Therefore, approaches tailored to targeting groups of patients who present similarly are of great interest. This study analysed a large group of sepsis patients with diverse symptoms using laboratory markers and mathematical analysis. We report four patient groups that differ by risk of death and immune response profile. Targeting these defined groups with tailored interventions presents an exciting opportunity to improve the health outcomes of patients with sepsis.

Establishing a Sickle Cell Disease Registry in Africa: Experience From the Sickle Pan-African Research Consortium, Kumasi-Ghana.

Sickle cell disease (SCD) is the most common clinically significant hemoglobinopathy, characterized by painful episodes, anemia, high risk of infection, and other acute and chronic complications. In Africa, where the disease is most prevalent, large longitudinal data on patients and their outcomes are lacking. This article describes the experiences of the Kumasi Center for SCD at the Komfo Anokye Teaching Hospital (KCSCD-KATH), a Sickle Pan-African Research Consortium (SPARCO) site and a SickleInAfrica Consortium member, in establishing a SCD registry for the evaluation of the outcomes of patients. It also provides a report of a preliminary analysis of the data. The process of developing the registry database involved comprehensive review of the center's SCD patient medical records, incorporating data elements developed by the SickleInAfrica Consortium and obtaining ethical clearance from the local Institutional Review Board. From December 2017 to March 2020, 3,148 SCD patients were enrolled into the SCD registry. Enrollment was during the SCD outpatient clinic visits or through home visits. A significant proportion of the patients was from the newborn screening cohort (50.3%) and was males (52.9%). SCD-SS, SCD-SC, and Sß +thalassemia were seen in 67.2, 32.5, and 0.3% patients, respectively. The majority of the patients were in a steady state at enrollment; however, some were enrolled after discharge for an acute illness admission. The top two clinical diagnoses for SCD-SS patients were sickle cell painful events and acute anemia secondary to hyperhemolysis with incidence rates of 141.86 per 10,000 person months of observation (PMO) and 32.74 per 10,000 PMO, respectively. In SCD-SC patients, the top two diagnoses were sickle cell painful events and avascular necrosis with incidence rates of 203.09 per 10,000 PMO and 21.19 per 10,000 PMO, respectively. The SPARCO Kumasi site has developed skills and infrastructure to design, manage, and analyze data in the SCD registry. The newborn screening program and alternative recruitment methods such as radio announcement and home visits for defaulting patients were the key steps taken in enrolling patients into the registry. The registry will provide longitudinal data that will help improve knowledge of SCD in Ghana and Africa through research.

Sports anaemia and anthropometric evaluation of footballers at Kwame Nkrumah University of Science and Technology (KNUST).

INTRODUCTION: Sports anaemia is a physiological activity that occurs amongst footballers and may be due to poor diet, over-training, as well as an increase in plasma volume in endurance training activities. High plasma volume leads to changes in haematological parameters that may impact on endurance of footballers. The objective of the study was to determine the correlation between haematological and an-thropometric indices and their role in sports anaemia in a tropical setting. METHODS: Venous blood was taken into EDTA for 12 soccer players of KNUST soccer team before training and after training for the first (W1) and fifth (W5) weeks of training sessions. Complete blood count analysis was done for each blood sample and anthropometric parameters such as height, weight, body mass index, body fat percent and lean body mass were also measured. Cross-tabulations with mean and standard deviation or median and range were computed. Paired t-test & and Mann-Whitney test for parametric and non-parametric data computations were carried out and a p-value ≤ 0.05 was taken to rep-resent significant difference between data groups. RESULTS: There was significant reduction in haemoglobin (p = 0.003), haematocrit (p = 0.002), mean cell volume (MCV) (p = 0.034) and red blood cell (RBC) count (p = 0.011) as a result of a significant expansion of plasma volume (p= 0.006). Neutrophil, lymphocyte and eosinophil counts were reduced significantly (p= 0.043, 0.001 and 0.007, respectively) after the training at W5. Lean body mass (LBM) inversely correlated with haemoglobin (r = -0.787, p = 0.002) and haematocrit (r = -0.588, p = 0.044). Body fat percentage (BFP) also negatively correlated with lymphocyte count (r = -0.700, p = 0.011). Furthermore, there was a positive correlation between body mass index (BMI) and plasma volume change after the training programme (r = 0.689, p = 0.013). CONCLUSION: The results suggest that sports anaemia was induced by an increase in plasma volume that resulted in changes in haematological parameters.

Diagnostic accuracy of blood centers in the screening of blood donors for viral markers.

INTRODUCTION: Blood transfusion still remains a life saving intervention in almost all healthcare facilities worldwide. Screening of blood donors/blood units is done in almost every blood bank facility before the blood units/blood components are transfused to prevent transfusion-transmissible infections. The kind of testing kits or the methods used by a facility and the technical expertise of the personnel greatly affects the screening results of a facility. This study was aimed at evaluating the diagnostic accuracy of five hospital-based blood bank testing facilities (Komfo Anokye Teaching Hospital KNUST, Kwame Nkrumah University of Science and Technology, Agogo, Bekwai and Sunyani) that used rapid immunochromatograhic assays (RIA) in screening blood donors/blood units in Ghana. METHODS: Blood samples (300) from the five testing facilities and their screening results for hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (HCV) and human immunodeficiency virus (HIV) using RIAs were obtained. All the samples were then analysed for the three viral markers using 3(rd) generational enzyme linked immunosorbent assay (ELISA) kit as the gold standard. RESULTS: The mean false positive for HBsAg was 2.2% with Bekwai testing facility having the highest of 4.4%. For HCV, the mean false positive was 2.8% with Agogo and Bekwai testing facilities having the highest of 8.7% respectively. For HIV screening, the mean false positive was 11.1% with Bekwai testing facility having the highest of 28.0%. The mean false negative for the facilities were 3.0% for HBV, 75.0% for HCV and 0.0% for HIV with KATH having the highest of 6.3% for HBV, Bekwai having the highest of 100% for HCV and no facility showing false negative for HIV. Mean sensitivity of the screening procedure for the facilities was 97.0%, 25.0% and 100.0% whilst the mean specificity was 97.8%, 97.2% and 88.9% for HBV, HCV and HIV respectively. Statistical comparison among the testing facilities showed no significant differences among the various testing centres for HBV screening; however, significant differences were obtained for HCV and HIV screening. CONCLUSION: This study has shown that there is no standardised screening procedure for blood bank testing facilities in the country. There is therefore an urgent need for an internal and external control body to oversee screening procedures in blood banks across the country.

Changes in potassium and sodium concentrations in stored blood.

Potassium is the principal intracellular cation with sodium being the principal extracellular cation. Maintenance of the distribution of potassium and sodium between the intracellular and the extracellular compartments relies on several homeostatic mechanisms. This study analysed the effect of blood storage on the concentrations of potassium and sodium in stored blood and also determine any variations that may exist in their concentrations. 50 mls of blood was sampled each from 28 units of evenly mixed donated blood in citrate phosphate dextrose adenine (CPDA-1) bags immediately after donation into satellite bag and stored at 4oC. Potassium and sodium concentration determinations were done on each of the 28 samples on day 0 (before blood was initially stored in the fridge), day 5, day 10, day 15 and day 20 of storage using the Roche 9180 ISE Electrolyte Analyser (Hoffmann-La Roche Ltd, Switzerland). data analysis showed significant changes in the potassium and sodium concentrations with a continuous rise in potassium and a continuous fall in sodium. A daily change of 0.59 mmol/l and 0.50 mmol/l was observed in the potassium and sodium concentrations respectively. We showed steady but increased daily concentrations of potassium and decrease concentrations of sodium in blood stored over time at 4oC.

The prevalence of hepatitis B virus E antigen among Ghanaian blood donors.

Hepatitis B viral infection is an important clinical problem due to its worldwide distribution and potential of adverse sequelae, including hepatocellular carcinoma (HCC). We studied the prevalence of hepatitis B virus 'e' antigen (HBeAg) among individuals determined to be hepatitis B virus (HBV) surface antigen-positive and analyzed the gender/age category associated with more active HBV infection and whether alteration in the levels of alanine aminotransferase could be associated with HBeAg positivity. A total of 150 prospective blood donors who tested positive for hepatitis B surface antigen (HBsAg) at the blood transfusion center of the Komfo Anokye Teaching Hosptital (KATH), Kumasi were randomly selected for the study. The serum samples were further tested for HBsAg and HBeAg using a lateral flow immunochromatographic assay. Twenty (20) individuals were found to be HBeAg-positive giving an overall prevalence of 13.3%, of which 18 (15.5%) were males and 2 (5.9%) were females. Our results also revealed that the prevalence of HBeAg was higher in patients between the age group of 10-20 years and appeared to decrease with increase in age. There was no statistical difference between the HBeAg positive and negative individuals with respect to alanine aminotransferase (ALT) levels. We show for the first time that approximately 1/10 of HBV-infected individuals are HBeAg positive in the Ashanti Region of Ghana, suggestive of active viral replication and liver-cell infectivity thereby contributing to an increased HBV-transmission pool within the Ghanaian population.