Intravenous methylprednisolone with or without tocilizumab in patients with severe COVID-19 pneumonia requiring oxygen support: A prospective comparison.

BACKGROUND: Cytokine storm is a marker of severity and severe mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia. Immunomodulatory treatments may reduce morbidity and mortality. OBJECTIVES: To determine whether a 7-day course of methylprednisolone (MP) administered with and without tocilizumab improves outcomes in patients with severe COVID-19 (SARS-CoV-2) pneumonia requiring oxygen therapy, relative to historical controls. STUDY DESIGN AND METHOD: In this randomized controlled study, patients hospitalized with severe COVID-19 at Rashid Hospital, Dubai, in June 2020 were randomized 1:1 to receive intravenous MP (40 mg twice daily for 7 days) with or without a single dose of intravenous tocilizumab (400 mg). While data from the control arm, consisting of patients administered usual care, were obtained through retrospective review of their electronic medical records. The patients in the three arms were matched by disease severity and inclusion and exclusion criteria. The primary outcomes were day 45 all-cause mortality after randomization, rate of admission to the intensive care unit (ICU), length of ICU stay, days on ventilators, and length of hospital stay. RESULTS: In total, 76 patients were recruited, including 23 treated with MP, 26 with MP plus tocilizumab, and 27 historical controls. The rates of admission to the ICU and invasive mechanical ventilation were lowest in patients treated with MP alone, with the rates in this group being significantly lower than the rates in the control group (p = 0.04). Time on a ventilator was lowest in the MP group (1.09 ± 3.68 days) and highest in the control group (7.93 ± 14.86 days). The number of days in the ICU was significantly lower in the MP group than in the control and MP plus tocilizumab groups (p = 0.043). One patient (4.3%) in the MP group and five (18.5%) in the control arm died within 45 days. Survival was highest in patients treated with MP alone, with the addition of tocilizumab not improving survival or any of the other outcomes significantly. INTERPRETATION/CONCLUSION: In patients with severe COVID-19 pneumonia on oxygen support, administration of MP daily for 7 days had reduced mortality at 45 days and was associated with significantly lower ICU admission and ventilation rates compared with usual. Adding tocilizumab to MP did not improve any of the studied outcomes significantly.

Molecular Characterization of Staphylococcus aureus Isolates Associated with Nasal Colonization and Environmental Contamination in Academic Dental Clinics.

Aim: To determine the genetic makeup of methicillin-sensitive/methicillin-resistant Staphylococcus aureus (MSSA/MRSA) from nasal colonization and environmental contamination in dental clinics. Materials and Methods: Nasal swabs from students and health care workers and environmental swabs were obtained at two academic dental clinics in the United Arab Emirates. The StaphyType DNA microarray-based assay was used for molecular characterization. Results: Forty-eight S. aureus isolates were identified phenotypically (nasal: n = 43; environmental: n = 5), but 6 of these were assigned to S. argenteus by genotyping. These were CC(argenteus)2596, CC(arg)2250-MSSA, CC(arg)2250-MSSA-(Panton Valentine leukocidin [PVL]+) (n = 2), and CC(arg)2198-MSSA (n = 2). MRSA nasal colonization rate was 5.4% (n/N = 8/146) with the following strain affiliations: CC5-MRSA-[IV+fus+ccrAB], "Maltese Clone"; CC6-MRSA-IV, "WA MRSA-51"; CC22-MRSA-IV (PVL+/tst+); CC22-MRSA-[IV+fus+ccrAA/(C)]; and two each of CC5-MRSA-[VI+fus] and CC97-MRSA-[V/VT+fus]. The SCC-borne fusidic acid resistance (fusC) gene was detected in MRSA (n = 5) and MSSA (n = 1). Some MSSA strains, CC1-MSSA-[fus+ccrAB1] and ST1278-MSSA-[ccrA1], harbored recombinase genes. A CC30-MSSA harbored ACME locus/arc-genes, while ST1278-MSSA-[ccrA1] had an ACME-III element. Enterotoxin genes were commonly carried, but tst-1 gene was found in only CC22, CC30, and CC34 strains, while pvl genes were identified in CC(arg)2250 and CC22-MRSA-IV. Of the 51 noncoagulase staphylococci (CoNS) identified, 18 were mecA positive. Conclusion: The findings demonstrate the first report of rare strains (ST1278 MSSA, CC(arg)2198, CC(arg)2596, and PVL+CC(arg)2250) in our region. Detection of MSSA with recombinase genes and ACME loci alongside mecA-positive CoNS is of clinical significance as this could provide a milieu for acquisition and transfer of SCC-elements, either with different ACME types, with fusC or the mecA gene resulting in conversion of MSSA into MRSA.

A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in ß-thalassemia major (CORDELIA).

Randomized comparison data on the efficacy and safety of deferasirox for myocardial iron removal in transfusion dependent patients are lacking. CORDELIA was a prospective, randomized comparison of deferasirox (target dose 40 mg/kg per day) vs subcutaneous deferoxamine (50-60 mg/kg per day for 5-7 days/week) for myocardial iron removal in 197 ß-thalassemia major patients with myocardial siderosis (T2* 6-20 milliseconds) and no signs of cardiac dysfunction (mean age, 19.8 years). Primary objective was to demonstrate noninferiority of deferasirox for myocardial iron removal, assessed by changes in myocardial T2* after 1 year using a per-protocol analysis. Geometric mean (Gmean) myocardial T2* improved with deferasirox from 11.2 milliseconds at baseline to 12.6 milliseconds at 1 year (Gmeans ratio, 1.12) and with deferoxamine (11.6 milliseconds to 12.3 milliseconds; Gmeans ratio, 1.07). The between-arm Gmeans ratio was 1.056 (95% confidence interval [CI], 0.998, 1.133). The lower 95% CI boundary was greater than the prespecified margin of 0.9, establishing noninferiority of deferasirox vs deferoxamine (P = .057 for superiority of deferasirox). Left ventricular ejection fraction remained stable in both arms. Frequency of drug-related adverse events was comparable between deferasirox (35.4%) and deferoxamine (30.8%). CORDELIA demonstrated the noninferiority of deferasirox compared with deferoxamine for myocardial iron removal. This trial is registered at www.clinicaltrials.gov as #NCT00600938.

Hemoglobinopathy carrier prevalence in the United Arab Emirates: first analysis of the Dubai Health Authority premarital screening program results.

The aim of this study was to determine the prevalence of hemoglobinopathy carriers in United Arab Emirates (UAE) nationals subjected to mandatory premarital screening in Dubai over a 4-year period. Data from UAE nationals who underwent premarital screening by the Dubai Health Authority between January 2007 and December 2010 were collected and analyzed. Premarital screening in Dubai is based on complete blood counts (CBC) and hemoglobin (Hb) high performance liquid chromatography (HPLC). Among the 6,420 UAE nationals screened, 8.5% (n = 545) were suspected to be carriers. The following carrier frequencies were observed: ß-thalassemia (ß-thal), 4.56% (n = 293); Hb S [ß6(A3)Glu→Val, GAG>GTG; HBB: c.20A>T], 2.9% (n = 186); Hb D-Punjab [ß121(GH4)Glu→Gln, GAA>CAA; HBB: c.364G>C], 0.78% (n = 50); Hb Lepore (뫧 hybrid gene) with an undetermined molecular genotype, 0.17% (n = 11); Hb E [ß26(B8)Glu→Lys, GAG>AAG; HBB: c.79G>A], 0.03% (n = 2); and hereditary persistence of fetal Hb (HPFH), 0.016% (n = 1). Hb E-Hb S and Hb E-ß-thal also occurred at a rate of 0.016% (n = 1) each; and 0.87% (n = 56) subjects were suspected of carrying silent ß-thal. The prevalence of ß-thal trait was consistent with the prevalence published by others in the region. Silent ß-thal is challenging for screening programs, and is expected to arise in populations with a high prevalence of ß-thal carriers. The prevalence of Hb S trait observed in this study was lower than that in other reports for the region. New cases of ß-thal major (ß-TM) still arise because many fertile couples got married before the screening programs were implemented, and pregnancy termination is not widely practiced in the UAE due to religious restraints. Moreover, some couples choose not to have prenatal diagnosis (PND) or pre implantation genetic diagnosis (PGD), even if they are aware of their risk status. The prevalence of ß-thal trait in the UAE is high. This justifies efforts to control the disease by holding regular community awareness and screening programs, performing premarital screening and genetic counseling, and making PND and PGD available to couples who request it.

Prevalence of iron overload complications among patients with b-thalassemia major treated at Dubai Thalassemia Centre.

BACKGROUND AND OBJECTIVES: Authors and team members of the Dubai Thalassemia Centre obtained data on the prevalence of iron overload complications among patients with b-thalassemia major (b-TM) and compared it to international data to improve patient care and evaluate the effectiveness of earlier used treatment modalities. The information obtained is also expected to be useful in genetic counseling. DESIGN AND SETTING: Cross-sectional study of all living transfusion-dependent b-TM patients registered at the Thalassemia Centre in Dubai, United Arab Emirates, until the end of 2007 (n=382). PATIENTS AND METHODS: Diagnosis of TM was based on clinical history and laboratory confirmation by hemoglobin electrophoresis and DNA testing. All were uniformly treated with desferrioxamine and monitored by serial serum ferritin. results: The mean (SD) age of patients was 15.4 (7.6) years, with 50.5% males. Mean (SD) serum ferritin was 2597.2 (1976.8) micro g/L. The frequency of iron overload complications were as follows: hypogonadism (n=99, 52.7%), hypoparathyroidism (n=40, 10.5%), diabetes mellitus (n=40, 10.5%), hypothyroidism (n=24, 6.5%) and cardiomyopathies (n=7, 1.8%). Hypogonadism was the most common endocrine abnormality in our study and other reported series. However, cardiomyopathies were less prevalent among our patients with higher rates of diabetes and hypoparathyroidism compared to rates reported internationally. Females had statistically significant lower serum ferritin (2530.8 (1931.2), P < .05) with a lower cardiomyopathies rate. CONCLUSION: Iron overload related complications among our patients with thalassemia major were different from those reported internationally. Studying the genetic status of patients from our area may uncover the underlying genetic modifiers of iron overload mediated organs injury.

Misdiagnosis of Hb D-Punjab/ß-thalassemia is a potential pitfall in hemoglobinopathy screening programs: a case report.

Compound heterozygosity for Hb D-Punjab [ß121(GH4)Glu→Gln, GAA>CAA] /ß-thalassemia (ß-thal) must be carefully differentiated from homozygous Hb D-Punjab in premarital screening. This is essential when the partner is a carrier of ß-thal trait. The case of a baby born affected with ß-thal major (ß-TM), from a marriage between a mother with ß-thal trait and a father with Hb D-Punjab/ß-thal, is presented. The father had been misdiagnozed as homozygous Hb D-Punjab during premarital screening, even though the screening program utilized complete blood counts and high performance liquid chromatography (HPLC). The factors that may have contributed to this midsiagnosis are presented and discussed. It is recommended that cases of Hb D-Punjab, or any other hemoglobin (Hb) variant appearing as homozygous, are carefully evaluated if microcytic hypochromic parameters not associated with α-thal are present. In all cases of suspected hemizygosis, molecular analysis should always be performed, and in particular if one partner is a ß-thal carrier.

Serum ferritin levels and endocrinopathy in medically treated patients with ß thalassemia major.

The association between iron overload indices and pathology of the heart and liver in transfusion-dependent patients with ß thalassemia major (TM) has been extensively studied. Nonetheless, data on endocrine disease remains limited. This was a cross-sectional study of 382 TM patients treated with regular transfusions and desferrioxamine at the Thalassemia Center in Dubai, UAE. Retrieved data included demographics, splenectomy status, steady-state serum ferritin levels, and the presence of endocrinopathies (diabetes mellitus, hypothyroidism, hypoparathyroidism, and hypogonadism). Multivariate logistic regression analyses were used to determine which variables were independently associated with the occurrence of each endocrinopathy. The mean age of patients was 15.4 ± 7.6 years, with an equal sex distribution. The mean serum ferritin level was 2597.2 ± 1976.8 µg/l. The frequencies of specific endocrinopathies were diabetes mellitus (10.5%), hypothyroidism (6.3%), hypoparathyroidism (10.5%), and hypogonadism (25.9%). On multivariate logistic regression analysis, patients with a serum ferritin level >2,500 µg/l, but not >1,000-2,500 µg/l, were 3.53 times (95% CI 1.09-11.40) more likely to have diabetes mellitus, 3.25 times (95% CI 1.07-10.90) more likely to have hypothyroidism, 3.27 times (95% CI 1.27-8.39) more likely to have hypoparathyroidism, and 2.75 times (95% CI 1.38-5.49) more likely to have hypogonadism compared to patients with a serum ferritin level ≤1,000 µg/l. However, splenectomized patients with serum ferritin levels ≤2,500 µg/l had comparably high rates of all endocrinopathies as patients with serum ferritin levels >2,500 µg/l. Endocrinopathy is common in TM patients treated with desferrioxamine therapy, especially in patients with serum ferritin levels >2,500 µg/l or those splenectomized.

Risk factors for pulmonary hypertension in patients with ß thalassemia intermedia.

BACKGROUND: Pulmonary hypertension (PHT) is a common yet poorly understood complication of ß thalassemia intermedia (TI). METHODS: We herein evaluated risk factors for PHT in TI, through comparing 64 TI patients with evidence of PHT by symptomatology and echocardiography (Group I) to age- and sex-matched TI patients without PHT (Group II). Retrieved data included demographics, laboratory parameters, clinical characteristics, and received treatments that may influence PHT development; and reflected the period prior to PHT occurrence in Group I. RESULTS: The mean age of Group I patients at development of PHT was 37.3±10.6years; with 44% being males. Among studied parameters, Group I patients were more likely to be splenectomized (4.9-times), transfusion-naive (3.5-times); hydroxyurea-naive (2.6-times), or iron chelation-naive (2.3-times); and have nucleated red blood cell count ≥300×10(6)/l (2.59-times) or a previous history of thromboembolic events (3.69-times). CONCLUSION: TI patients who eventually develop PHT may be identified early on by being splenectomized, having high nucleated red blood cell counts and a previous history of thromboembolism. Prospective clinical trials that evaluate the efficacy, safety, and cost effectiveness of transfusion, iron chelation, and hydroxyurea therapy in preventing PHT in TI are invited.

Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study.

Despite recent advances in understanding the pathophysiologic mechanisms behind the thalassemia intermedia (TI) phenotype, data on the effects of treatment are deficient. To provide such data, we evaluated 584 TI patients for the associations between patient and disease characteristics, treatment received, and the rate of complications. The most common disease-related complications were osteoporosis, extramedullary hematopoeisis (EMH), hypogonadism, and cholelithiasis, followed by thrombosis, pulmonary hypertension (PHT), abnormal liver function, and leg ulcers. Hypothyroidism, heart failure, and diabetes mellitus were less frequently observed. On multivariate analysis, older age and splenectomy were independently associated with an increased risk of most disease-related complications. Transfusion therapy was protective for thrombosis, EMH, PHT, heart failure, cholelithiasis, and leg ulcers. However, transfusion therapy was associated with an increased risk of endocrinopathy. Iron chelation therapy was in turn protective for endocrinopathy and PHT. Hydroxyurea treatment was associated with an increased risk of hypogonadism yet was protective for EMH, PHT, leg ulcers, hypothyroidism, and osteoporosis. Attention should be paid to the impact of age on complications in TI, and the beneficial role of splenectomy deserves revisiting. This study provides evidence that calls for prospective evaluation of the roles of transfusion, iron chelation, and hydroxyurea therapy in TI patients.