Is There a Relationship between Abdominal Aortic Aneurysms and Alpha1-antitrypsin Deficiency (PiZ)?

AbstractObjective:to determine if the frequency of α1AT deficiency (PiZ) is increased in patients with abdominal aortic aneurysm (AAA), and, to investigate whether aneurysmal stiffness and other clinical characteristics differ in AAA patients with and without α1AT deficiency.Methods:we identified α1AT-deficient individuals by a monoclonal-antibody ELISA technique, in 102 consecutive patients with AAA. Positive ELISA samples were further phenotyped by isoelectric focusing to differentiate between the heterozygosity (PiZ) and homozygosity (PiZZ) state. Aneurysmal diameter and stiffness was measured using echotracking sonography and blood pressure measurements.Results:the frequency of heterozygous α1AT deficiency (PiZ) in patients with AAA was similar to that in the general population (6.8% and 4.7%, respectively,p>0.3). The frequency of popliteal and femoral aneurysm was similar in male PiZ-carriers and non-carriers with AAA, as were age at diagnosis of AAA, aneurysmal diameter, aneurysmal stiffness, and presence of factors that may be associated with AAA (i.e. smoking, hypertension, diabetes mellitus, and family history of AAA). Occurrence of ischaemic heart disease was more frequent in male non-PiZ-carriers than in male PiZ-carriers with AAA (p=0.03).Conclusions:the frequency of α1AT deficiency (PiZ) was not increased in our series of patients with AAA and patients in whom the two disorders coexisted did not appear to have different clinical characteristics except for the lower occurrence of ischaemic heart disease among the PiZ-carriers

SnoRNAs and miRNAs networks underlying COVID-19 disease severity

There is a lack of predictive markers for early and rapid identification of disease progression in COVID-19 patients. Our study aims at identifying microRNAs (miRNAs)/small nucleolar RNAs (snoRNAs) as potential biomarkers of COVID-19 severity. Using differential expression analysis of microarray data (n = 29), we identified hsa-miR-1246, ACA40, hsa-miR-4532, hsa-miR-145-5p, and ACA18 as the top five differentially expressed transcripts in severe versus asymptomatic, and ACA40, hsa-miR-3609, ENSG00000212378 (SNORD78), hsa-miR-1231, hsa-miR-885-3p as the most significant five in severe versus mild cases. Moreover, we found that white blood cell (WBC) count, absolute neutrophil count (ANC), neutrophil (%), lymphocyte (%), red blood cell (RBC) count, hemoglobin, hematocrit, D-Dimer, and albumin are significantly correlated with the identified differentially expressed miRNAs and snoRNAs. We report a unique miRNA and snoRNA profile that is associated with a higher risk of severity in a cohort of SARS-CoV-2 infected patients. Altogether, we present a differential expression analysis of COVID-19-associated microRNA (miRNA)/small nucleolar RNA (snoRNA) signature, highlighting their importance in SARS-CoV-2 infection

Complement C5a and clinical markers as predictors of COVID-19 disease severity and mortality in a multi-ethnic population

Coronavirus disease-2019 (COVID-19) was declared as a pandemic by WHO in March 2020. SARS-CoV-2 causes a wide range of illness from asymptomatic to life-threatening. There is an essential need to identify biomarkers to predict disease severity and mortality during the earlier stages of the disease, aiding treatment and allocation of resources to improve survival. The aim of this study was to identify at the time of SARS-COV-2 infection patients at high risk of developing severe disease associated with low survival using blood parameters, including inflammation and coagulation mediators, vital signs, and pre-existing comorbidities. This cohort included 89 multi-ethnic COVID-19 patients recruited between July 14th and October 20th 2020 in Doha, Qatar. According to clinical severity, patients were grouped into severe (n=33), mild (n=33) and asymptomatic (n=23). Common routine tests such as complete blood count (CBC), glucose, electrolytes, liver and kidney function parameters and markers of inflammation, thrombosis and endothelial dysfunction including complement component split product C5a, Interleukin-6, ferritin and C-reactive protein were measured at the time COVID-19 infection was confirmed. Correlation tests suggest that C5a is a predictive marker of disease severity and mortality, in addition to 40 biological and physiological parameters that were found statistically significant between survivors and non-survivors. Survival analysis showed that high C5a levels, hypoalbuminemia, lymphopenia, elevated procalcitonin, neutrophilic leukocytosis, acute anemia along with increased acute kidney and hepatocellular injury markers were associated with a higher risk of death in COVID-19 patients. Altogether, we created a prognostic classification model, the CAL model (C5a, Albumin, and Lymphocyte count) to predict severity with significant accuracy. Stratification of patients using the CAL model could help in the identification of patients likely to develop severe symptoms in advance so that treatments can be targeted accordingly

Vitamin D Deficiency and Its Health Consequences in Africa

Africa is heterogeneous in latitude, geography, climate, food availability, religious and cultural practices, and skin pigmentation. It is expected, therefore, that prevalence of vitamin D deficiency varies widely, in line with influences on skin exposure to UVB sunshine. Furthermore, low calcium intakes and heavy burden of infectious disease common in many countries may increase vitamin D utilization and turnover. Studies of plasma 25OHD concentration indicate a spectrum from clinical deficiency to values at the high end of the physiological range; however, data are limited. Representative studies of status in different countries, using comparable analytical techniques, and of relationships between vitamin D status and risk of infectious and chronic diseases relevant to the African context are needed. Public health measures to secure vitamin D adequacy cannot encompass the whole continent and need to be developed locally

Hypotension: An unusual presentation of vitamin B 12 deficiency, with complete recovery following cyanocobalamin therapy

Vitamin B 12 deficiency and its sequelae are well described and reported, especially in vegetarians. However, its association with haemodynamic instability is not well identified. We report a case of a young man, previously healthy, presenting with fever, hypotension requiring vasopressors and pancytopenia. Extensive workup was unrevealing for possible infective, inflammatory or endocrine causes except for vitamin B 12 deficiency. Fever and haematological parameters stabilised after adequate supplementation of cyanocobalamin (vitamin B 12). - BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.Scopu

Strong link between the alpha1‐antitrypsin PiZ allele and Wegener's granulomatosis

Abstract. Objectives. To ascertain whether a relationship exists between the PiZ alpha1‐antitrypsin (α1AT) variant and antineutrophil cytoplasm antibodies (ANCA)‐positive vasculitis in a large group of Swedish patients, and whether analysis for the presence of the PiZ variant might be useful for diagnostic or prognostic purposes. Design. Retrospective cross‐sectional study. Setting. The Department of Internal Medicine, Malmö General Hospital, and the Department of Nephrology, University of Lund, Sweden. Subjects and main outcome measures. Serum samples from 105 proteinase 3‐ANCA‐positive patients were analysed using an elisa with a monoclonal antibody specific for the PiZ‐gene product. Complete clinical data were retrieved for 84% (88/105) of the patients, for diagnosis and survival analysis. Results. We identified 17 heterozygotes and one homozygote (P 0.2 for all comparisons). During follow‐up, 38% (6/16) of the PiZ heterozygotes died, compared with 17% (11/66) of noncarriers of the variant (P = 0.02), which suggests that PiZ heterozygosity may be a marker of poor prognosis. PiZ heterozygotes with systemic vasculitis would not appear to be identifiable by their pretreatment plasma α1AT concentrations, as all such patients in the present study had concentrations within or above the normal range. Conclusion. We conclude that heterozygotes for the PiZ variant of the α1AT gene are at greater risk of than the general population of developing WG. Knowledge of such a genetic factor may not only aid our understanding of the mechanism involved in this illness but may also serve as significant prognostic factor in following the course of the disease. 1994 Blackwell Publishing Lt

Acute psychosis and concurrent rhabdomyolysis unveiling diagnosis of hypothyroidism

Neuropsychiatric and muscular symptoms can develop as part of hypothyroidism. However, frank psychosis or rhabdomyolysis due to hypothyroidism are uncommon and have been reported rarely as the first presenting features of hypothyroidism. We report a case of a 44-year-old man who presented with a 2-week history of delusions, hallucinations and mild bilateral leg pain, without apparent signs of myxedema. Investigations revealed raised thyroid stimulation hormone >100 mIU/L and high creatine kinase >21 000 U/L. Diagnosis of hypothyroidism-induced psychosis and rhabdomyolysis was made. He received thyroxine, olanzapine and a short course of steroids. His symptoms improved after 2 weeks of treatment and he remained free of symptoms at 6 months of follow-up. To the best of our knowledge, this is the first case of concomitant psychosis and rhabdomyolysis leading to hypothyroidism diagnosis. This case highlights the importance of hypothyroidism screening when faced with unexplained psychosis or rhabdomyolysis, especially if combined. - BMJ Publishing Group Limited 2019.Scopu