A novel ITGB2 variant with long survival in patients with leukocyte adhesion defect type-I

Leukocyte adhesion deficiency is an autosomal recessive primary immunodeficiency that has been divided into three types: LAD1 (beta-2 integrin (CD18) family deficiency/defect), LAD2 (absence of fucosylated carbonhydrate ligands for selectins) and LAD3 (defective activation of all beta integrins). However, recently LAD4 has been described in cystic fibrosis patients, with a defect in integrin activation reported in monocytes. LAD-I is the most common type and prevalence of 1 in 1,000,000 live births. Clinical features of LAD patients are recurrent bacterial and fungal infections, omphalitis with delayed umbilical stump separation, significant leukocytosis especially neutrophilia during infection periods, impaired pus formation, and delayed traumatic or surgical wound healing. Flow cytometry is considered a useful tool for rapid diagnosis of the disease. The study of CD18 and CD11 (a, b, c) expression patterns in peripheral blood leukocytes helps to distinguish different phenotypes of LAD-I. In general, patients with ≥ 2% CD18 expression tend to have a less severe infection and often survive until adulthood, whereas < 2% CD18 expression often results in death in infancy. In this case report, three siblings, 10, 15, and 17 years old, diagnosed with leukocyte adhesion defect type 1 in adolescence age group, are presented.

     

Convalescent plasma therapy in patients with COVID-19

IntroductionPassive antibody therapy has been used to immunize vulnerable people against infectious agents. In this study, we aim to investigate the efficacy of convalescent plasma (CP) in the treatment of severe and critically ill patients diagnosed with COVID-19.MethodThe data of severe or critically ill COVID-19 patients who received anti-SARS-CoV-2 antibody-containing CP along with the antiviral treatment (n = 888) and an age-gender, comorbidity, and other COVID-19 treatments matched severe or critically ill COVID-19 patients at 1:1 ratio (n = 888) were analyzed retrospectively.ResultsDuration in the intensive care unit (ICU), the rate of mechanical ventilation (MV) support and vasopressor support were lower in CP group compared with the control group (p = 0.001, p = 0.02, p = 0.001, respectively). The case fatality rate (CFR) was 24.7 % in the CP group, and it was 27.7 % in the control group. Administration of CP 20 days after the COVID-19 diagnosis or COVID-19 related symptoms were associated with a higher rate of MV support compared with the first 3 interval groups (≤5 days, 6?10 days, 11?15 days) (p=0.001).ConclusionCP therapy seems to be effective for a better course of COVID-19 in severe and critically ill patients.     

Results of Surgery in General Surgical Patients Receiving Warfarin: Retrospective Analysis of 61 Patients

The aim of this study is to investigate postoperative complications, mortality rates, and to determine the factors affecting mortality on the patients receiving warfarin therapy preoperatively, as well as comparing the results obtained from emergency and elective surgeries. Surgical outcomes of 61 patients on long-term oral anticoagulation with warfarin who underwent surgery in our center were retrospectively reviewed over an 8-year period. Thirty-three (54.1%) patients were female, with a mean age of 53 years. Mitral valve replacement (62.3%) was the most frequent indication for chronic anticoagulation therapy. Twelve out of 61 (19.2%) patients underwent emergency surgery; 59 (96.7%) operations were classified as major surgery. We did not observe any thromboembolic events on patients receiving our bridging therapy protocol. Cardiopulmonary dysfunction (CPD; 19.7%) and hemorrhage (16.4%) were the most encountered postoperative complications. Presence of CPD, bleeding, endocarditis, and mortality were statistically significant for emergency surgeries when compared with the results obtained from elective surgeries. There were 5 (8.2%) deaths observed during follow-up. It was found that advanced age, prolonged duration of operations, and presence of CPD had a statistically significant effect on mortality (P < 0.05). The patients receiving oral anticoagulant had high postoperative complication and mortality rates. This case was more evident in emergency surgeries. It is recommendable that as mortality is more apparent in the patients who undergo emergency surgeries—being older, having long duration of operations as well as CPD. Therefore during the postoperative follow-up process, the patients should be closely monitored.Key words: Emergency, Postoperative complications, Morbidity, Mortality, WarfarinThromboembolism is a major global health concern contributing to more than 0.5 million deaths in Europe and up to 300,000 deaths in the United States each year.¹ Versatile arrays of anticoagulant and/or anti-aggregant agents are available. They are used to treat and prevent thrombosis occurring as a result of venous stasis, valvular heart disease, prosthetic valves, atrial fibrillation, or myocardial infarction. After using these medications, patients who require elective or emergency surgery represent a specific population; moreover, they are prone to developing either excessive bleeding or thrombosis.The annual incidence of major bleeding as a result of oral anticoagulant (OAC) use is reported between 2 and 5%.² Patients on OAC may require elective or sometimes emergency surgical or invasive procedures. There is no consensus on standard protocol to follow for those who require perioperative management.³In the current literature, there are limited numbers of studies regarding the discussions about the operations in general surgery patient population receiving warfarin treatments. In this retrospective study, our aim was to document the complications and outcomes of general surgical procedures implemented on patients receiving warfarin. Along with the comparison of the emergency and elective surgeries performed, we also aimed to determine the factors affecting mortality.     

Pulmonary arteriovenous malformation in children

Although pulmonary arteriovenous malformations (PAVM) are relatively rare in children, they are important in the differential diagnosis of common pulmonary problems, such as hypoxemia, hemoptysis and dyspnea on exertion. We report the cases of two PAVM patients with different presentations and describe the treatment strategies.     

The major histocompatibility complex region marked by HSP70-1 and HSP70- 2 variants is associated with clozapine-induced agranulocytosis in two different ethnic groups

Genes of the major histocompatibility complex (MHC) have been associated with susceptibility to drug-induced adverse reactions. We previously found that clozapine-induced agranulocytosis (CA) is associated with the HLA-DRB1*0402, DRB4*0101, DQB1*0302, DQA1*0301 haplotype in Ashkenazi Jewish patients and with the HLA-DRB1*1601, DRB5*02, DQB1*0502, DQA1*0102 haplotype in non-Jewish patients. In the present study, we tested the hypothesis that the variants of the heat- shock protein 70 (HSP-70) encoded by the HSP-70 loci located within the MHC region and known to be involved in apoptosis and regulation of cell proliferation could play an important role in molecular mechanisms of CA. First, we analyzed HSP70-2 polymorphism in risk-associated haplotypes from HLA homozygous cells and normal individuals and confirmed that the HSP70-2 9-kb variant was associated invariably with DR4 (HLA-DRB1*0402, DQB1*0302) and DR2 (HLA-DRB1*01601, DQB1*0502, DQA1*0102 and HLA-DRB1*1501, DQB1*0602) haplotypes, which were the haplotypes found increased in Jewish and non-Jewish patients with CA, respectively. The 9.0-kb variant was also found to be associated with HLA-B44, DRB1*0401 and HLA-B44, DRB1*07 haplotypes. Second, in patients with CA (12 Ashkenazi Jewish and 20 non-Jewish patients), HSP70-1 A and HSP70-2 9.0-kb variants were associated with the MHC haplotypes found by us to be markers of susceptibility to CA. The clozapine-treated control group had an excess number of HSP70-1 C and HSP70-2 8.5-kb variants, consistent with genetic resistance to CA associated with those variants. This finding supports our hypothesis that a dominant gene within the MHC region (marked by HSP70-1 and HSP70-2), but not necessarily HLA, is associated with CA in two different ethnic groups.