Outcomes of home-isolated coronavirus disease 2019 patients in Bahrain.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic resulted in a huge burden on healthcare systems and necessitated a risk assessment of patients and an update of the treatment protocol to include home isolation for low-risk patients. The primary objective was to describe the outcome of home isolation and the characteristics of patients at higher risk of admission. The secondary objectives were to determine the proportion of patients with pneumonia and hypoxemia and the correlation between cycle of the threshold (CT) value and severity of the disease. MATERIALS AND METHODS: For this study, 394 patients were randomly selected from a total of 8000 home-isolated COVID-19 patients during July to October 2020, and were followed by Bahrain International Hospital (BIH). All data were obtained from a live Excel sheet completed by physicians covering BIH during the study period. Data analysis included Chi-square test to determine significant association between categorical variable, Pearson correlation, and logistic regression analysis. RESULTS: Of the 394 home-isolated patients followed, 18 patients with missing data were excluded. The overall admission rate was 50% for ≥50 age group compared to 13.3% for 18-49 age group, while only 2.8% in <18 age group. Moreover, Intensive Care Unit (ICU) admissions were significantly higher in the older age group: 15.2% for ≥50 age group (P < 0.001). About 14% of the patients with comorbidities needed ICU admission, compared with 1.8% of those without comorbidities (P < 0.001). Of the home-isolated patients, 6.3% were diagnosed with pneumonia and 9.9% of those presenting had low oxygen saturation. The CT value was significantly correlated with the severity of symptoms and the need for admission. CONCLUSION: Home isolation of low-risk patients with monitoring and follow-up was a safe and necessary step in dealing with the COVID-19 pandemic.

Evaluation of Rapid Antigen Tests Using Nasal Samples to Diagnose SARS-CoV-2 in Symptomatic Patients.

INTRODUCTION: The best way to mitigate an outbreak besides mass vaccination is via early detection and isolation of infected cases. As such, a rapid, cost-effective test for the early detection of COVID-19 is required. METHODS: The study included 4,183 mildly symptomatic patients. A nasal and nasopharyngeal sample obtained from each patient was analyzed to determine the diagnostic ability of the rapid antigen detection test (RADT, nasal swab) in comparison with the current gold-standard (RT-PCR, nasopharyngeal swab). RESULTS: The calculated sensitivity and specificity of the RADT was 82.1 and 99.1%, respectively. Kappa's coefficient of agreement between the RADT and RT-PCR was 0.859 (p < 0.001). Stratified analysis showed that the sensitivity of the RADT improved significantly when lowering the cut-off RT-PCR Ct value to 24. CONCLUSION: Our study's results support the potential use of nasal swab RADT as a screening tool in mildly symptomatic patients, especially in patients with higher viral loads.

Papillary carcinoma in thyroglossal duct cyst: Diagnosis by fine-needle aspiration cytology and immunocytochemistry.

Carcinoma associated with thyroglossal duct cyst (TDC) is extremely rare and when it occurs it is invariably papillary carcinoma. A 36-year-old man presented with a midline swelling in the upper part of neck, which was a cystic lesion with multiple septae in ultrasonogram, indicating a thyroglossal duct cyst. The CT scan findings also corroborated the ultrasound report. Fine needle aspiration (FNA) smears showed hemosiderin laden cyst macrophages and occasional papillary cluster of neoplastic cells with central psammoma body and rare intranuclear cytoplasmic inclusions. The neoplastic cells revealed positive reaction for thyroglobulin, galectin3, and CD44. FNA cytodiagnosis was thyroglossal duct cyst with cytologic features suggestive of papillary carcinoma. The histopathological diagnosis of the resected lesion, however, was metastatic papillary thyroid carcinoma in lymph node with cystic changes; there was positive reaction for thyroglobulin, galectin3, HBME1, and CK. Following this histopathology report, thyroidectomy was performed, which revealed lymphocytic thyroiditis and no evidence of papillary carcinoma. Review of paraffin sections of upper midline neck mass showed a cavity bound by thick fibrocollageneous wall and lined partly by epithelium consistent with papillary carcinoma. The cyst wall showed dense lymphomononuclear cell infiltration and germinal center formation. There were foci of papillary carcinoma in the cyst wall with frequent nuclear grooves, cerebriform nuclei and intranuclear cytoplasmic inclusions. The reviewed histopathological diagnosis was consistent with papillary carcinoma in thyroglossal duct cyst. Thus, the FNA cytodiagnosis of a rare case of papillary carcinoma in thyroglossal duct cyst, led to review and change in histopathological diagnosis achieving cyto-histopathological correlation.

Production and assessment of ovine antisera for the manufacture of a veterinary adder antivenom.

Medically important venomous snakes in Western Europe are Vipera ammodytes, Vipera aspis, Vipera berus and Vipera latastei. Envenomation of dogs and other animals by these snakes receives limited attention despite the relative frequency and potential mortality and morbidity. This reflects, in part, the lack of a dedicated veterinary antivenom. Successful antivenoms are derived from antisera containing high levels of specific polyclonal antibodies that bind to, and neutralise, all the toxins present. This requires a careful choice of immunogen, animals and immunisation schedule. We detected proteomic variation in the venoms of V ammodytes, V aspis, V berus and V latastei by SDS-PAGE (sodium dodecyl sulphate-polyacrylamide gel electrophoresis) gel electrophoresis. Consequently, we used a mixture containing equal amounts of venom from these species to immunise a flock of sheep. We demonstrate that immunisation resulted in antisera containing high levels of specific antibodies directed against the majority of toxic components found in all four snake venoms using immunoblotting, ELISA and small-scale affinity chromatography assays. The latter shows that all 25 sheep responded quickly and maintained high levels of specific antibodies throughout the two-year period of study. This ensures a consistent starting material for the manufacture of a reproducible veterinary antivenom, ViperaVet. Our next objectives are to purify the antibodies from our antisera and demonstrate their preclinical neutralising efficacy in murine animal studies prior to undertaking a clinical trial in envenomed patients.

Population prevalence of asthma and its determinants based on European Community Respiratory Health Survey in the United Arab Emirates.

BACKGROUND: No population study has explored the population distribution of adult asthma in the United Arab Emirates (UAE). The objective is to estimate asthma prevalence in general population in UAE. METHODS: Using standard European Community Respiratory Health Survey (ECRHS) questionnaires and tools, this is a cross-sectional assessment of a random sample of the population in established quotas of the seven Emirates in the UAE. We surveyed 1,220 participants, of which 63.2% were male, and 20.1% were UAE Nationals, with a mean (SD) age of 32.9 (14.1) years. RESULTS: Prevalence of individual respiratory symptoms from the ECRHS screening questionnaire in all participants were generally ranging 8 - 10%, while participants 20-44 years presented lower prevalence in all symptoms (p < 0.05). The expected male:female ratio of reported wheezing and asthma attacks and its treatment by age was not observed. Participating women reported more individual symptoms than men. Overall, there were 15.4% (95% C.I. 13.5 - 17.5) participants who fulfilled our screening criteria for asthma, while for consistency with ECRHS, there were 12.1% (95% C.I. 10.4 - 14.1) participants who fulfilled the ECRHS asthma definition, being 9.8% (95% C.I. 7.8 - 12.2) of those 20-44 years, that is 8.6% of male and 11.8% of female young adults participating. CONCLUSION: We conclude that asthma is common in the UAE, and gender differences are not observed in reported asthma symptoms in young adults. This being the first population based study exploring the prevalence of asthma and its determinants in the United Arab Emirates based on the ECRHS.

Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3ß.

Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor κB signaling that represses tumor invasion and metastasis. Glycogen synthase kinase-3ß (GSK3ß) suppresses tumor progression by downregulating multiple oncogenic pathways including Wnt signaling and cyclin D1 activation. Here, we show that RKIP binds GSK3 proteins and maintains GSK3ß protein levels and its active form. Depletion of RKIP augments oxidative stress-mediated activation of the p38 mitogen activated protein kinase, which, in turn, inactivates GSK3ß by phosphorylating it at the inhibitory T390 residue. This pathway de-represses GSK3ß inhibition of oncogenic substrates causing stabilization of cyclin D, which induces cell-cycle progression and ß-catenin, SNAIL, and SLUG, which promote epithelial to mesenchymal transition. RKIP levels in human colorectal cancer positively correlate with GSK3ß expression. These findings reveal the RKIP/GSK3 axis as both a potential therapeutic target and a prognosis-based predictor of cancer progression.

Tubulolobular carcinoma of the breast with grooved and cerebriform nuclei: failure to identify this specific subtype in a case during routine fine needle aspiration cytology and histopathological diagnosis.

Tubulolobular carcinoma (TLC) is a rare tumor of the breast in which histologic features of both tubular and lobular carcinoma are combined. We report a case of TLC, in which the specific subtype was missed at routine cytologic and histopathological examination. A 69-year-old woman presented with a right breast lump. Imaging studies indicated a malignant lesion in right upper quadrant. Routine fine needle aspiration (FNA) cytology diagnosis was a duct cell carcinoma (small cell type). In a setting of cystic thyroid lesions, presence of excessive nuclear grooves, and rare intranuclear cytoplasmic inclusion, metastatic papillary thyroid carcinoma was also considered. However, both these possibilities were not supported by immunocytochemical findings (estrogen receptor+, thyroglobulin-, and chromogranin-). The histopathology diagnosis was invasive duct cell carcinoma. Review of FNA smears and paraffin sections led to the diagnosis of TLC, which was supported by positive immunohistochemical stainings for markers like e-cadherin and ß-catein.

Expression of estrogen receptor alpha and estrogen receptor beta in fine needle aspirates of breast carcinoma.

OBJECTIVE: To evaluate the expression of estrogen receptor beta (ERbeta) in fine needle aspirates (FNAs) and correlate the findings with its expression in tissue sections. STUDY DESIGN: In 38 cases of breast carcinoma, expression of estrogen receptor alpha (ERalpha) and ERbeta in aspirates and tissue sections was correlated with the cytologic and histologic grade of the tumor. RESULTS: ERalpha and ERbeta were expressed as nuclear staining in 80% and 90% of the cases in tissue sections and 47% and 45% of the cases in aspirates, respectively. Tissue expression of ERalpha (grade 1, 81%; grade 2, 100%) and ERbeta (grade 1, 94%; grade 2, 100%) was greater than in grade 3 tumors (ERalpha, 50%; ERbeta, 70%). In FNAs they were equally distributed in the different cytologic grades. In aspirates 30% of ERalpha negative tumors were positive for ERbeta, while in tissues 75% of ERalpha-negative tumors were positive for ERbeta (p = 0.007). CONCLUSION: Demonstration of ERbeta on FNA smears is feasible. It helps identify the specific subcohort of ERbeta-positive tumors in ERalpha-negative breast cancers; that may have therapeutic importance.

Beneficial effects of ketogenic diet in obese diabetic subjects.

OBJECTIVE: Obesity is closely linked to the incidence of type II diabetes. It is found that effective management of body weight and changes to nutritional habits especially with regard to the carbohydrate content and glycemic index of the diet have beneficial effects in obese subjects with glucose intolerance. Previously we have shown that ketogenic diet is quite effective in reducing body weight. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. In this study the effect of ketogenic diet in obese subjects with high blood glucose level is compared to those with normal blood glucose level for a period of 56 weeks. MATERIALS AND METHODS: A total of 64 healthy obese subjects with body mass index (BMI) greater than 30, having high blood glucose level and those subjects with normal blood glucose level were selected in this study. The body weight, body mass index, blood glucose level, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, urea and creatinine were determined before and at 8, 16, 24, 48, and 56 weeks after the administration of the ketogenic diet. RESULTS: The body weight, body mass index, the level of blood glucose, total cholesterol, LDL-cholesterol, triglycerides, and urea showed a significant decrease from week 1 to week 56 (P < 0.0001), whereas the level of HDL-cholesterol increased significantly (P < 0.0001). Interestingly these changes were more significant in subjects with high blood glucose level as compared to those with normal blood glucose level. The changes in the level of creatinine were not statistically significant. CONCLUSION: This study shows the beneficial effects of ketogenic diet in obese diabetic subjects following its long-term administration. Furthermore, it demonstrates that in addition to its therapeutic value, low carbohydrate diet is safe to use for a longer period of time in obese diabetic subjects.

Raf kinase inhibitor protein expression in a survival analysis of colorectal cancer patients.

PURPOSE: Raf kinase inhibitor protein (RKIP) inhibits the Raf and nuclear factor kappa B signaling pathways, and suppresses metastasis in animal models. We examined whether RKIP expression in primary colorectal cancers (CRCs) correlates with the risk of metastasis and overall survival. PATIENTS AND METHODS: RKIP expression was examined immunohistochemically in three separate cohorts: a tissue microarray containing 276 samples from human tumors and normal tissues, and retrospective studies of 268 CRC patients and 65 early-stage CRCs. Overall and metastasis-free survival rates were measured. RESULTS: RKIP was expressed in normal epithelia but was reduced in metastatic tumors. RKIP expression in primary CRC was an independent prognostic marker for survival using multivariate Cox regression analysis (hazard ratio, 2.808; 95% CI, 1.58 to 4.96; P = .0002), independent of Dukes' stage. Patients with Dukes' C RKIP-positive tumors had similar 5-year survival rates as early-stage patients if tumors had equivalent RKIP expression levels. An independent study of early-stage CRCs confirmed that reduced RKIP expression predicted metastatic recurrence and reduced disease-free survival (hazard ratio, 4.5; 95% CI, 1.7 to 12.3; P = .003). RKIP expression was independent of sex, age, mitotic index, lymphatic and vascular invasion, depth of invasion, and tumor site, but correlated positively with apoptotic index (P = .024). Weak or loss of RKIP expression was the most significant and independent prognostic marker using a multivariate regression equation (hazard ratio, 4.5; 95% CI, 1.7 to 12.3; P = .003). CONCLUSION: RKIP expression in primary CRCs correlates with overall and disease-free survival, and can be useful for identifying early-stage CRC patients at risk of relapse.

Apical sparing in tako-tsubo cardiomyopathy.

BACKGROUND: Tako-tsubo cardiomyopathy (TTC) is an acute reversible cause of segmental myocardial dysfunction that is poorly understood. We have noted a variant of this condition where a tiny segment at the apex retains some contractile function. This paper delineates the frequency of this variant relative to the classical form and the clinical differences between patients suffering from the two forms. METHODS: All cases of TTC (n = 35) were identified from our infarct angiography database and separated on the basis of apical sparing (n = 14) or no apical sparing (n = 21). RESULTS: Compared with the classical form, those with apical sparing were significantly younger (63 +/- 12 vs 72 +/- 13 years) and were more likely premenopausal (5/14 vs 0/21) and had higher ejection fractions (35 +/- 6% vs 32 +/- 4%). There was a trend towards higher recurrence (4/21 vs 0/14). There were no differences in time or season of presentation, precipitant stressor, premorbid drug therapy, haemodynamics at catheterization or acute outcomes. CONCLUSION: The apical sparing variant of TTC is common, accounting for 40% of cases. While the patients are younger and more likely premenopausal, there are no other distinguishing features between the classical and the variant form.

Long term effects of ketogenic diet in obese subjects with high cholesterol level.

OBJECTIVE: Various studies have convincingly shown the beneficial effect of ketogenic diet (in which the daily consumption of carbohydrate is less than 20 grams, regardless of fat, protein and caloric intake) in reducing weight in obese subjects. However, its long term effect on obese subjects with high total cholesterol (as compared to obese subjects with normal cholesterol level is lacking. It is believed that ketogenic diet may have adverse effect on the lipid profile. Therefore, in this study the effect of ketogenic diet in obese subjects with high cholesterol level above 6 mmol/L is compared to those with normocholesterolemia for a period of 56 weeks. MATERIALS AND METHODS: In this study, 66 healthy obese subjects with body mass index (BMI) greater than 30, having high cholesterol level (Group I; n = 35) and those subjects with normal cholesterol level (Group II; n = 31) were selected. The body weight, body mass index, total cholesterol, LDL-cholesterol, HDL-cholesterol, urea, creatinine, glucose and triglycerides were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored at 8, 16, 24, 32, 40, 48 and 56 weeks of the treatment. RESULTS: The body weight and body mass index of both groups decreased significantly (P < 0.0001). The level of total cholesterol, LDL cholesterol, triglycerides and blood glucose level decreased significantly (P < 0.0001), whereas HDL cholesterol increased significantly (P < 0.0001) after the treatment in both groups. CONCLUSION: This study shows the beneficial effects of ketogenic diet following its long term administration in obese subjects with a high level of total cholesterol. Moreover, this study demonstrates that low carbohydrate diet is safe to use for a longer period of time in obese subjects with a high total cholesterol level and those with normocholesterolemia.

Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse.

A substantial number of patients with early-stage colorectal cancer relapse from metastatic disease. Identification of these patients by genetic profiling of their primary tumours may allow more informed follow-up and tailored administration of adjuvant therapy. Primary tumours from 70 patients with early-stage and largely microsatellite-stable colorectal cancer were profiled using metaphase-based comparative genomic hybridization (CGH) and the aberrations confirmed independently in a subset of patients using microarray-based CGH. Of the 70 cancers, 61 were amenable to CGH, and follow-up data was available from 56 patients. Genomic aberrations were correlated with patients' survival using univariate, multivariate and Kaplan-Meier survival curves. Metastatic primary tumours exhibited more complex genomic aberrations than non-metastatic primary tumours. Loss of chromosome 4p was an independent prognostic factor in early-stage colorectal cancer using multivariate analysis (Hazard ratio, 9.6; 95% CI, 3.3-28; P = 0.0001). Loss of both chromosome arms 8p and 18q had a statistically significant negative effect on disease-free survival. Moreover, primary tumours with loss of both chromosomes 4 and 14q bestowed poorer prognosis than tumours with loss of any one of the two chromosomes (P<0.0001). Genetic profiling of primary tumours of patients with early-stage colorectal cancer is of significant value in identifying the subset of patients who may relapse with metastatic disease. Accordingly, the molecular genetic features of primary tumours should be considered in the mainstream management of patients with this specific stage of the disease.

Beta-thalassemia major and its effect on amino acid metabolism and growth in patients in the United Arab Emirates.

BACKGROUND: There may be a marked reduction in essential amino acids in the serum of children with thalassemia major and this is related to decreased growth in affected children. METHODS: One hundred patients with beta-thalassemia and 50 control children selected from among those who had presented with minor disorders unrelated to hematological disease were recruited. Urine and heparinized blood were collected from fasting thalassemic patients. After deproteinization and dilution, amino acid concentrations were measured using ion-exchange chromatography. RESULTS: Isoleucine (p<0.0001), phenylalanine (p<0.05), tyrosine (p<0.0001), taurine (p<0.0001) and glutamine (p<0.01) were significantly decreased in the plasma of thalassemic patients compared to the control group. Whereas glutamate (p<0.0001), serine (p<0.05) and proline (p<0.05) were significantly higher in thalassemic patients, threonine, glycine, alanine, valine, methionine, leucine, ornithine, lysine, histidine and arginine values were not different. The essential amino acids taurine (p<0.0001), methionine (p<0.01), valine (p<0.01), phenylalanine (p<0.01) and leucine (p<0.05) were significantly decreased in urine of thalassemic patients vs. controls, but threonine and ornithine were not different. The mean urinary excretion rate of beta-aminoisobutyric acid was not different (69+/-96 in thalassemics vs. 41+/-52 in controls). However, most plasma and urinary essential amino acids were found to be lower in thalassemics. Thalassemic patients were also found to be significantly growth impaired for age, both in height and weight compared to controls. CONCLUSION: Lower plasma values of essential amino acids and a decrease in urinary amino acids occur in thalassemic patients. Growth impairment both in height and weight also occurs in thalassemic patients compared to a control population.

Assessment of an ovine antivenom raised against venom from the desert black cobra (Walterinnesia aegyptia).

The desert black cobra (Walterinnesia aegyptia) is an elapid widely distributed throughout the deserts of Saudi Arabia and currently available antivenoms are ineffective in the treatment of its envenoming. Walterinnesia aegyptia venom was assessed for several of its physicochemical, enzymatic and biological characteristics. An antivenom was raised in sheep using a low-dose immunization schedule and digested with papain to provide Fab fragments. The antivenom neutralized all of the above enzymatic and biological activities and provided good protection in mice (ED50 0.25 g/kg), whereas the commercial polyspecific products showed only partial neutralization and did not protect mice.

First clinical experiences with specific sheep Fab fragments in snake bite. Report of a multicentre study of Vipera berus envenoming.

OBJECTIVES: To evaluate the efficacy and safety of specific, ovine Fab fragments in the treatment of envenoming by the common adder, Vipera berus. DESIGN: Open study with historical controls. SETTING: Multicentre study involving patients (n = 30) with V. berus envenoming, treated in 18 Swedish hospitals during 1991-94. MAIN OUTCOME MEASURES: Initial symptoms, clinical course after treatment, duration of hospital stay and adverse effects of the antivenom were evaluated. Two earlier studied patient groups, given either equine F(ab)2 antivenom (n = 30) or no antivenom (n = 16), were used as controls. RESULTS: Specific ovine Fab fragments influenced favourably the acute symptomatology as well as the long term clinical course. Acute symptoms such as hypotension, shock, vomiting, diarrhoea and CNS-depression resolved quickly. The incidence of extensive swelling involving the trunk and the length of hospital stay were both reduced significantly compared to nontreated patients (23 vs. 88% and 3.5 vs. 6 days). Also the incidence of anaemia was reduced (23 vs. 44%). These results were consistent with those obtained with equine F(ab')2 antivenom, but with ovine Fab there were no immediate anaphylactic reactions or serum sickness. CONCLUSION: Specific Fab fragments produced from sheep immunized with V. berus venom were safe and effective in counteracting the effects of V. berus bite in humans. These results justify further studies of this new treatment for snake envenoming.

Development and clinical application of immunoassays for European adder (Vipera berus berus) venom and antivenom.

An ovine affinity purified Fab antivenom was used in a clinical trial in Sweden to treat European adder (Vipera berus berus) envenoming. Immunoassays were developed to measure V. b. berus venom and antivenom concentrations in clinical samples to help assess the efficacy of treatment. A radioimmunoassay (RIA) was developed, optimized and validated to measure plasma levels of V. b. berus venom and compared with a conventional ELISA. Both showed a similar variation of zero binding in biological samples and the results obtained correlated closely. However, the ELISA was quicker and more sensitive (0.8 compared with 2 micrograms/litre). Before administration of antivenom, V. b. berus venom concentrations in plasma ranged from 10 to 53 micrograms/litre; 12 hr after the Fab infusion, no patient had measurable levels. However, two patients had low venom levels 24 hr after treatment. ELISA and RIA were also developed, optimized and used to measure concentrations of free Fab in plasma. There was a biexponential fall of Fab concentration with a fast distribution phase (t 1/2 = 0.9 hr) and a slower elimination phase (t 1/2 = 18 hr). The amount of Fab excreted in urine was low.

A comparison of ovine and equine antivenoms.

Commercial antivenoms produced in horses were compared with monospecific antivenoms raised in sheep against Crotalus durissus terrificus, Crotalus atrox, Crotalus adamanteus, Micrurus fulvius fulvius, Naja naja, Naja kaouthia, Echis ocellatus, Vipera lebetina deserti, Vipera berus berus and Vipera ammodytes ammodytes venom. Antibodies raised by immunizing sheep with C. d. terrificus venom were more effective than their equine counterparts in preventing lethal toxicity in mice (ED50), in inhibiting the venom's pharmacological effects (haemolysis, platelet aggregation and coagulation), and in neutralizing phospholipase A2 activity. Comparison of one ovine and three equine F(ab)2 products raised against V. a. ammodytes venom showed that all were at least 95% pure; that all protected mice; and that all contained antibody populations directed against most components of V. a. ammodytes and V. b. berus venoms. The ovine antivenoms generally contained a higher concentration of specific antibodies than the equine products. Finally, the ovine antivenoms raised against E. ocellatus, V. lebetina deserti, V. b. berus, M. f. fulvius and N. naja venoms provided better in vivo protection to mice than the equine antivenoms, but the equine antivenoms to N. kaouthia and C. atrox were more protective than the ovine product.