Receptor binding and escape from Beta antibody responses drive Omicron-B.1.1.529 evolution

On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.

Immune checkpoint CD47 molecule engineered islets mitigate instant blood-mediated inflammatory reaction and show improved engraftment following intraportal transplantation.

Instant blood-mediated inflammatory reaction (IBMIR) causes significant destruction of islets transplanted intraportally. Myeloid cells are a major culprit of IBMIR. Given the critical role of CD47 as a negative checkpoint for myeloid cells, we hypothesized that the presence of CD47 on islets will minimize graft loss by mitigating IBMIR. We herein report the generation of a chimeric construct, SA-CD47, encompassing the extracellular domain of CD47 modified to include core streptavidin (SA). SA-CD47 protein was expressed in insect cells and efficiently displayed on biotin-modified mouse islet surface without a negative impact on their viability and function. Rat cells engineered with SA-CD47 were refractory to phagocytosis by mouse macrophages. SA-CD47-engineered islets showed intact structure and minimal infiltration by CD11b+ granulocytes/macrophages as compared with SA-engineered controls in an in vitro loop assay mitigating IBMIR. In a syngeneic marginal mass model of intraportal transplantation, SA-CD47-engineered islets showed better engraftment and function as compared with the SA-control group (87.5% vs 14.3%). Engraftment was associated with low levels of intrahepatic inflammatory cells and mediators of islet destruction, including high-mobility group box-1, tissue factor, and IL-1ß. These findings support the use of CD47 as an innate immune checkpoint to mitigate IBMIR for enhanced islet engraftment with translational potential.

Seasonal Influence on Postoperative Complications after Total Knee Arthroplasty

PURPOSE: This study is aimed at investigating whether inpatient complications and surgical site infections (SSIs) occurred more commonly in patients undergoing total knee arthroplasty (TKA) during the summer season. MATERIALS AND METHODS: A total of 725 patients who underwent unilateral or bilateral TKA were included in this study. A total of 241 patients (33.2%) underwent TKA between May and August. Our outcomes of interest were the incidence of postoperative complications and length of stay. RESULTS: May–August surgeries were associated with a higher risk of postoperative inpatient complications (p=0.003). May–August surgeries (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.18 to 3.85), postoperative transfusion (OR, 2.46; 95% CI, 1.43 to 4.26), postoperative special care unit stay (OR, 4.68; 95% CI, 1.99 to 11.0) and chronic kidney disease (OR, 3.27; 95% CI, 1.15 to 9.28) were associated with a higher odds of developing inpatient complications. No association was present between summer surgeries and SSIs (p=0.486). CONCLUSIONS: The results of this study show that overall complication rates following TKA exhibit a seasonal trend, with a peak during the summer months. These results may have some implication in clinical practice and stricter approaches to hospital guidelines during the summer months.

Population dynamics and tuberculosis: a cross sectional study of an overlooked disease in Saudi Arabia.

BACKGROUND: International travel, migration and human population movements facilitate the spread of tuberculosis (TB). OBJECTIVE: To study the impact of poorly screened expatriates working in Saudi Arabia on the local incidence of TBs. PATIENTS AND METHODS: This cross sectional study was carried out in the Chest Disease Hospital, Taif. All confirmed cases of TB from June 2009 to May 2010 admitted to the hospital were enrolled. Inclusion criteria were diagnosed cases of TB (pulmonary & extra-pulmonary) in patients between the ages of 14 to 65 years. Patients with HIV and coexistent malignancies were excluded. The age, gender and ethnic group of each patient was recorded, and patients were divided into two groups. Of the two groups, Group A consisted of Taif residents and group B of patients referred from other cities in the country. RESULTS: Of the 686 cases studied, 370 (54%) were Saudi nationals (Group A = 80 & Group B = 290) and 316 (46%) cases were from other countries. Males outnumbered females and most of the patients were aged 20 to 29 years. The number of cases from the areas close to the pilgrimage sites, i.e. Makah (233) and Jeddah (275), outnumbered those in Taif (110). CONCLUSIONS: Our study identifies an increased prevalence of TB cases in areas close to the pilgrimage (Group B). The higher proportion of non-Saudi TB patients in group B is most likely explained by the higher number of poorly screened illegal expatriates in the region.