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Breakthrough infections post-COVID-19 vaccination occur with the emerging variants of the SARS-CoV virus which might be either due to the newer variants escaping immune response or the waning of antibodies over time. However, there is lack of long-term follow-up evidence on the waning of immune response following inactivated COVID-19 vaccine.A retrospective, observational study was conducted on serum samples of individuals who had received two doses of BBIBP-CorV vaccine. Individual's antibody responses were evaluated based on IgG anti-S and neutralizing antibodies measurements. Antibody samples were categorized into four groups, defined by the time interval from the individual's receipt of the BBIBP-CorV vaccine:30 days, 30-90 days, 91-180 days and180 days.A total of 6668 serum samples from inactivated BBIBP-CorV vaccine recipients were analyzed for IgG anti-S and neutralizing antibodies. 571 (8.6%) samples were tested during the first 29 days interval post vaccination, 3642 (54.6%) were tested during 30-90 days interval, 2173 (32.6%) samples were tested during 91 to 180 days interval and 282(4.2%) were tested at180 days interval post vaccination. We found that more than 50% of the individuals had antibody titers below the average cut-off range at the 91-180 days interval post vaccination. Older age (60 years), male gender, chronic kidney disease, hypertension, immunodeficiencies and increased interval post vaccination emerged as independent risk factors associated with lower immune response.Inactivated BBIBP-CorV vaccine recipients, based on age, gender and associated comorbid conditions might need booster doses at an earlier interval than the currently followed six months interval.

Introduction Asthma is a chronic inflammatory disease of the airways which is usually characterized by remodeling, hyperresponsiveness and episodic obstruction of the airways. The underlying chronic airway inflammation leads to pathological restructuring of both the large and small airways. Since the effects of current asthma medications on airway remodeling have been met with contradictions, many therapeutic agents have been redirected from their primary use for the treatment of asthma. Such treatments that could target several signaling molecules implicated in the inflammatory and airway remodeling processes of asthma would be an ideal choice. Areas covered Statins are effective serum cholesterol-lowering agents that were found to have potential anti-inflammatory and anti-remodeling properties. Literature search was done for the past ten years to include research and review articles in the field of statins and asthma complications. In this review, we discuss the role of statins in airway tissue remodeling and their potential therapeutic modalities in asthma. Expert opinion With improved understanding in the role of statins in airway remodeling and inflammation, statins represent a potential therapeutic option for various asthma phenotypes. Further research is warranted to optimize statins for asthma therapy through inhalation as a possible route of administration.

A strong association between obesity and COVID-19 complications and a lack of prognostic factors that explain the unpredictable severity among these patients still exist despite the various vaccination programs. The expression of angiotensin converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is enhanced in obese individuals. The occurrence of frequent genetic single nucleotide polymorphisms (SNPs) in ACE2 is suggested to increase COVID-19 severity. Accordingly, we hypothesize that obesity-associated ACE2 polymorphisms increase the severity of COVID-19. In this study, we profiled eight frequently reported ACE2 SNPs in a cohort of lean and obese COVID-19 patients (n = 82). We highlight the significant association of rs2285666, rs2048683, rs879922, and rs4240157 with increased severity in obese COVID-19 patients as compared to lean counterparts. These co-morbid-associated SNPs tend to positively correlate, hence proposing possible functional cooperation to ACE2 regulation. In obese COVID-19 patients, rs2285666, rs879922, and rs4240157 are significantly associated with increased blood nitrogen urea and creatinine levels. In conclusion, we highlight the contribution of ACE2 SNPs in enhancing COVID-19 severity in obese individuals. The results from this study provide a basis for further investigations required to shed light on the underlying mechanisms of COVID-19 associated SNPs in COVID-19 obese patients.

The ability of Vitamin D (VitD) to modulate antiviral responses through induction of antimicrobial peptide is well established. However, the effect of VitD on host responses to SARS-CoV-2 is not well investigated. We here report the ability of VitD to enhance host IFN-alpha/beta (a/β) signaling both in vitro and among severe COVID-19 patients treated with VitD. Blood and saliva specimens were obtained from severe COVID-19 patients treated (43 patients), or not (37 patients), with vitD, during their stay in intensive care unit. Patients were followed up to 29 days following admission, and patient survival outcomes were collected. Higher activity levels of RIG-1/MDA-5 and JAK-STAT signaling pathways were observed with significantly higher gene and protein levels of antiviral interferon stimulating genes (ISGs) such as MX-1 and ISG-15; both in vitro, following treatment of PBMCs with vitD, and in whole blood and saliva specimens of VitD treated patients. Moreover, VitD treated patients had lower risk of all-cause mortality by day 29 compared to untreated patients (adjusted hazard ratio, 0.37, 95% confidence interval of 0.14–0.94; P = 0.038). The herein uncovered regulatory role of VitD on type I IFNs suggests the importance of insuring a normal level of VitD for the prevention and probably treatment of SARS-CoV-2 infection. Additional mechanistic studies, however, are needed to fully elucidate the antiviral effects of VitD particularly in the setting of COVID-19 infection.

Severe viral infections, including SARS-COV-2, could trigger disruption of the balance between pro-oxidant and antioxidant mediators; the magnitude of which could reflect the severity of infection and lung injury. Using publicly available COVID-19 transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 125 oxidative stress genes, including 37 pro-oxidant genes, 32 oxidative-responsive genes, and 56 antioxidant genes. Seven oxidative stress genes were found to be upregulated in whole blood and lung autopsies (MPO, S100A8, S100A9, SRXN1, GCLM, SESN2, and TXN); these genes were higher in severe versus non-severe COVID-19 leucocytes. Oxidative genes were upregulated in inflammatory cells comprising macrophages and CD8+ T cells isolated from bronchioalveolar fluid (BALF), and neutrophils isolated from peripheral blood. MPO, S100A8, and S100A9 were t/opmost upregulated oxidative markers within COVID-19's lung autopsies, whole blood, leucocytes, BALF derived macrophages and circulating neutrophils. The calprotectin's, S100A8 and S100A9 were upregulated in SARS-COV-2 infected human lung epithelium. To validate our in-silico analysis, we conducted qRT-PCR to measure MPO and calprotectin's levels in blood and saliva samples. Relative to uninfected donor controls, MPO, S100A8 and S100A9 were significantly higher in blood and saliva of severe versus asymptomatic COVID-19 patients. Compared to other different viral respiratory infections, coronavirus infection showed a prominent upregulation in oxidative stress genes with MPO and calprotectin at the top of the list. In conclusion, SARS-COV-2 induce the expression of oxidative stress genes via both immune as well as lung structural cells. The observed correlation between oxidative stress genes dysregulation and COVID-19 disease severity deserve more attention. Mechanistical studies are required to confirm the correlation between oxidative stress gene dysregulation, COVID-19 severity, and the net oxidative stress balance., Graphical abstract Image 1

BACKGROUND/AIM Limited data exist on the expression pattern of TNFAIP3/A20, as assayed by immunohistochemistry (IHC), in breast cancer tissues. This study aimed to assess A20 expression pattern in breast cancer. MATERIALS AND METHODS The expression of A20 was analysed using IHC in 50 breast cancer cases retrieved from the Sharjah Breast Cancer Center at the University Hospital Sharjah, United Arab Emirates. Omics survival data were also used to analyse its association with survival in endocrine-treated subgroups. RESULTS A20 expression in breast cancer tissues was 'tumor-specific', and as compared to normal tissue areas, its expression was associated with both intensity and extent in early grade 1 (p

The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people and crippled economies worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for this pandemic has triggered avid research on its pathobiology to better understand the pathophysiology of COVID-19. In the absence of approved antiviral therapeutic strategies or vaccine platforms capable of effectively targeting this global threat, the hunt for effective therapeutics has led to many candidates being actively evaluated for their efficacy in controlling or preventing COVID-19. In this review, we gathered current evidence on the innate nucleic acid-sensing pathways expected to be elicited by SARS-CoV-2 and the immune evasion mechanisms they have developed to promote viral replication and infection. Within the nucleic acid-sensing pathways, SARS-CoV-2 infection and evasion mechanisms trigger the activation of NOD-signaling and NLRP3 pathways leading to the production of inflammatory cytokines, IL-1β and IL-6, while muting or blocking cGAS-STING and interferon type I and III pathways, resulting in decreased production of antiviral interferons and delayed innate response. Therefore, blocking the inflammatory arm and boosting the interferon production arm of nucleic acid-sensing pathways could facilitate early control of viral replication and dissemination, prevent disease progression, and cytokine storm development. We also discuss the rationale behind therapeutic modalities targeting these sensing pathways and their implications in the treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is strongly linked to dysregulation of various molecular, cellular, and physiological processes that change abundance of different biomolecules including metabolites that may be ultimately used as biomarkers for disease progression and severity. It is important at early stage to readily distinguish those patients that are likely to progress to moderate and severe stages.This study aimed to investigate the utility of saliva and plasma metabolomic profiles as a potential parameter for risk stratifying COVID-19 patients.LC-MS/MS-based untargeted metabolomics were used to profile the changes in saliva and plasma metabolomic profiles of COVID-19 patients with different severities.Saliva and plasma metabolites were screened in 62 COVID-19 patients and 18 non-infected controls. The COVID-19 group included 16 severe, 15 moderate, 16 mild, and 15 asymptomatic cases. Thirty-six differential metabolites were detected in COVID-19 versus control comparisons. SARS-CoV-2 induced metabolic derangement differed with infection severity. The metabolic changes were identified in saliva and plasma, however, saliva showed higher intensity of metabolic changes. Levels of saliva metabolites such as sphingosine and kynurenine were significantly different between COVID-19 infected and non-infected individuals; while linoleic acid and Alpha-ketoisovaleric acid were specifically increased in severe compared to non-severe patients. As expected, the two prognostic biomarkers of C-reactive protein and D-dimer were negatively correlated with sphingosine and 5-Aminolevulinic acid, and positively correlated with L-Tryptophan and L-Kynurenine.Saliva disease-specific and severity-specific metabolite could be employed as potential COVID-19 diagnostic and prognostic biomarkers.

The ability of vitamin D (VitD) to modulate immune responses in the clinical setting of COVID-19 infection is not well investigated. This study aimed to evaluate the ability of VitD to attenuate inflammatory responses in patients with severe COVID-19.Blood samples and nasopharyngeal swabs were obtained from patients with severe COVID-19 who had been treated (20 patients), or not (25 patients), with VitD, during their stay in the intensive care unit. Western blotting was used to evaluate the expressions of STAT3, JNK and AKT signaling pathways and ELISA was used to measure levels of IL-6, IL-17, and IL-1β in blood of these patients.Reduced levels of STAT3, JNK and AKT pathways and lower levels of proinflammatory cytokines such as IL-6, IL-17, and IL-1β were observed in VitD treated patients (50,000 IU of cholecalciferol weekly for 3 weeks), and in vitro following treatment of poly I:C stimulated PBMCs with VitD (50 nM of calcitriol). Moreover, lower circulatory levels of these proinflammatory cytokines following treatment with VitD were associated with lower serum levels of COVID-19-related severity markers such as D-dimer and C-reactive proteins (P 0.001) which in overall resulted in shorter length of ICU stay for VitD treated compared to untreated patients (18 days for VitD treated vs. 28 days for VitD untreated; P = 0.01).This study reveals that VitD plays immunomodulatory role during COVID-19 infection, which further emphasizes the importance of maintaining a normal level of this vitamin for the prevention of hyperinflammatory conditions associated with COVID-19.

Galloway-Mowat syndrome is a rare autosomal recessive disease characterized by a unique combination of renal and neurological manifestations, including early-onset steroid-resistant nephrotic syndrome, microcephaly, psychomotor delay, and gyral abnormalities of the brain. Most patients die during early childhood. Here, we identified a novel homozygous O-sialoglycoprotein endopeptidase (OSGEP) variant, NM_017807.3:c.973C>G (p.Arg325Gly), in four affected individuals in an extended consanguineous family from Saudi Arabia. We have described the detailed clinical characterization, brain imaging results, and muscle biopsy findings. The described phenotype varied from embryonic lethality to early pregnancy loss or death at the age of 9. Renal disease is often the cause of death. Protein modeling of this OSGEP variant confirmed its pathogenicity. In addition, proteomic analysis of the affected patients proposed a link between the KEOPS complex function and human pathology and suggested potential pathogenic mechanisms.

Introduction. There are limited data on human immunodeficiency viruses (HIV) infected people in the UAE and the Gulf region. This study aimed at assessing the prevalence and risk factors for potential clinically significant drug interactions (CSDIs) in a cohort of 181 HIV infected people in Dubai. Methods. A retrospective study was conducted at the outpatient infectious diseases clinic of Rashid hospital. Consecutive HIV seropositive people on anti-retroviral therapy (ART) were included. All potential CSDIs were analyzed and classified using Liverpool HIV drug interactions database. Results. Nucleoside reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs) were the most frequently used antiretroviral agents (ARVs), while the most common (non-ARV) were cardiovascular medication followed by antilipidemic statins. A total of 140 potential CSDIs were found in nearly half (n=86, 47.5%) of the 181 included HIV persons. Of the 140 potential CSDIs, 27 (19%) were of weak clinical relevance, 108 (77%) were of potential clinical relevance, and 5 (4%) were of contraindicated clinical relevance interactions. Moreover, 52 (37.14%) of CSDIs were between two ARVs and 88 (62.85%) were between ARV and non-ARV drugs. In the univariate analysis, age, dyslipidemia, number of medications, analgesics use, statin use, supplement intake, time since diagnosis of HIV, number of ART, and use of a protease inhibitor (PI) were significant. In the logistic regression, factors independently associated with CSDIs were the number of medications (odds ratio [OR] 1.165, 95% CI 1.021-1.329, P = 0.023) and the time since diagnosis of HIV (OR 1.156, 95% CI 1.008-1.327, P = 0.038). Conclusion. The frequency of CSDIs between ART and co-medications is high in HIV seropositive people. Awareness of the risk factors may assist clinicians to recognize and manage CSDIs.

Cytokines are major players in orchestrating inflammation, disease pathogenesis and severity during COVID-19 disease. However, the role of IL-19 in COVID-19 pathogenesis remains elusive. Herein, through the analysis of transcriptomic datasets of SARS-CoV-2 infected lung cells, nasopharyngeal swabs, and lung autopsies of COVID-19 patients, we report that expression levels of IL-19 and its receptor, IL-20R2, were upregulated following SARS-CoV-2 infection. Of 202 adult COVID-19 patients, IL-19 protein level was significantly higher in blood and saliva of asymptomatic patients compared to healthy controls when adjusted for patients’ demographics (P −1) than those who received tocilizumab (39.2 pg mL−1) or corticosteroids (42.5 pg mL−1). Our findings indicate that high saliva IL-19 level was associated with COVID-19 infectivity and disease severity.

Background Breast cancer is the most frequently reported cancer among women in the Middle East and North Africa (MENA) region. However, the available data about women breast cancer from the MENA and particularly from the Northern Emirates region of the United Arab Emirates (UAE) are scarce and inconsistent. Therefore, this study estimated the incidence, patient-specific factors including 25(OH)D levels, and clinicopathological features of breast cancer in women from the Northern Emirates. Methods We conducted this retrospective case-control study on 1,048 women who were referred to the Sharjah Breast Care Centre at University Hospital Sharjah between March 2016 and July 2018. Multivariate logistic regression was used for the statistical analysis of clinical data. Results Out of 1048 women with breast-related conditions referred to our canter, 94 (10%) were diagnosed with breast cancer (1 in 11), and approximately 1 in 5 of these women was younger than 40 years. After adjusting for age, body mass index and menopause status, women with serum 25-hydroxyvitamin D [25(OH)D] levels lower than 20 ng/mL were found to be at higher risk of breast cancer (odd ratio, 4.63; 95% CI, 2.61-8.23). The majority of breast cancer cases had invasive-ductal carcinoma with hormone-positive receptor molecular subtype (78 cases out of 94, 83%). HER2 overexpressing tumor (3+ by immunohistochemistry (IHC) or by fluorescence in situ hybridization (FISH)) was seen more in women younger than 40 years as compared to older women (7 cases out of 19 HER2 expressed tumors, p=0.007). Conclusion Our study cohort showed a mean age of diagnosis of breast cancer in women a decade earlier than in the developed countries. Furthermore, women with breast cancer tend to be serum 25(OH)D deficient at diagnosis and to have luminal A tumors.

Background Insulin-resistant individuals are known to have dyslipidemia and are predicted to be at high risk of cardiovascular events. Vitamin D deficiency was shown to be associated with dyslipidemia; however, the type of dyslipidemia associated with vitamin D deficiency in insulin-resistant individuals is not determined. Furthermore, there is evidence linking insulin resistance with low-grade inflammation suggesting levels of pro-inflammatory cytokines to be increased in insulin-resistant states. Objective This study was performed to evaluate the impact of vitamin D deficiency, defined as serum level of 25(OH)D below 20 ng/mL, on lipid profile and inflammatory markers such as interleukin (IL-6) and IL-8, as well as soluble thrombomodulin (TM) in the serum of insulin-resistant individuals. Methods A total of 4114 individuals had simultaneous serum 25(OH)D, insulin, and lipid panel testing during 2013 as part of the United Arab Emirates National Diabetes and Lifestyle (UAEDIAB) study. Multivariate logistic regression analysis was used to assess the association between serum level of 25(OH)D and lipid profile in insulin-sensitive versus -resistant individuals. The lipid panel was stratified into high total cholesterol (TC: >6.2 mmol/L) , high low-density lipoprotein-cholesterol (LDL-C: >2.59 mmol/L), high triglycerides (TG: >2.3 mmol/L), and low high-density lipoprotein-cholesterol (HDL-C

Background Advanced colorectal has poor survival and are difficult to treat. Therefore, there is an urgent need for biomarkers to diagnose this cancer at earlier manageable stages. Micro-RNAs (miRNAs) are amongst the most significant biomarkers that have shown promise in improving management and early detection of different types of cancers. However, since MiRNAs are non-coding, the main limitation of using them as biomarkers is that they do not have associated phenotype and therefore difficult to validate using other techniques. This makes it difficult to understand the mechanism of miRNA is disease initiation and progression, therefore any methodology that can provide semantics to miRNA expression would enhance the understanding of the role of miRNA in disease. Methods Here we report an integrative meta-analysis and bioinformatics methodology that showed microRNA-21 and its associated target mRNA to be the most significant predictive biomarkers for colorectal adenoma and adenocarcinoma. After drawing key inferences by meta-analysis, the authors then developed a bioinformatics method to identify mir-21 gene targeting in a specific tissue using two different bioinformatics approaches; absolute GSEA (Gene Set Enrichment Analysis) and LIMMA (Linear Models for MicroArray data) to identify differentially expressed genes of miRNA-21. Results Results from GSEA intersection with mir-21 gene targets was a subset of longer gene list that was obtained from the GEO2R intersect. In our study, both of longer GEO2R gene target list and the more focused GSEA list established the fact that mir-21 target numerous functional pathways that are mostly interconnected. Our three steps bioinformatics approach identified ABCB1, HPGD, BCL2, TIAM1, TLR3, and PDCD4 as common targets for mir-21 in both of adenoma as well as adenocarcinoma suggesting they are biomarkers for early CRC. Conclusions The approach in this study proposed combining the big data from the scientific literature together with novel bioinformatics to bring about a methodology that can be used to first identify which microRNAs are involved in a specific disease, and then to identify a panel of biomarkers derived from the microRNAs target genes, and from these target genes the functional significance of these microRNAs can be inferred providing better clinical value for the surgeon.

Sotrovimab, an anti-severe acute respiratory syndrome-coronavirus 2 monoclonal antibody is being utilized to prevent progression of coronavirus disease 2019 (COVID-19). Therefore, to understand its benefits, we have conducted a retrospective analysis of all non-hospitalized patients with symptomatic COVID-19 who received a single infusion of sotrovimab and/or oral favipiravir at any Dubai COVID-19 related healthcare center between July 1, 2021, and October 31, 2021. The main outcome was to evaluate the risk of hospitalization for patients with COVID-19 or all-cause death within 28 days of treatment initiation. In this analysis, which included 10,882 patients (1,135 in the sotrovimab group, 2,653 in the sotrovimab/favipiravir group, and 7,094 in the favipiravir group), sotrovimab or sotrovimab/favipiravir reduced the risk of hospitalization (13 patients (1.5%) in the sotrovimab group and 71 patients (2.9%) in the sotrovimab/favipiravir group vs. 251 patients (4%) in the favipiravir group; hazard ratio (HR) for sotrovimab: 0.16, 95% confidence interval (CI): 0.09-0.28, P 0.001; and for sotrovimab/favipiravir, HR: 0.42, 95% CI: 0.32-0.56, P 0.001), or death by day 28 from the start of treatment (no death in the sotrovimab group and 2 deaths in the the sotrovimab/favipiravir group vs. 10 deaths in the favipiravir group; odds ratio: 0.18, 95% CI: 0.04 to 0.81, P = 026). Safety was assessed in all the 3,788 patients in the sotrovimab and sotrovimab/favipiravir groups, and the reported adverse events were by 34 patients (1%). In conclusion, sotrovimab was found to reduce the risk of progression of COVID-19 when administrated early to non-hospitalized patients with symptomatic COVID-19. No safety concern was detected.

There is emerging evidence that age-dependent differences in susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlate with stronger innate immune response in the upper respiratory tract in children compared to adults. The efficient induction of interferon (IFN) alpha and beta (α and β) signaling, and interferon-stimulated genes (ISGs) is fundamental to the host antiviral response. In-silico transcriptomic analyses was conducted to determine the expression levels of IFN α/β pathway genes as well as 524 human ISGs in upper and lower airways of children and adults at baseline and post respiratory infections including coronavirus disease 2019 (COVID-19). To validate our in-silico analysis, we conducted qRT-PCR to measure ISGs levels in children and adult's nasal epithelial samples. At baseline, children had significantly higher levels of IFN α/β and ISGs genes compared to adults. More distinction was also seen in bronchial compared to nasal basal levels. Children nasal epithelial cells exhibited superior antiviral IFN α/β and associated ISGs response following ex-vivo poly (I:C) treatment model, and in clinical samples of SARS-CoV-2 infected patients. This was also confirmed in nasal epithelial samples using qRT-PCR validation. No gender-based difference in type I IFN levels across both age groups were observed. Understanding the biological basis for children resistance against severe COVID-19 is a challenge that has substantial clinical importance. More mechanistic studies are needed to carefully quantify how much of early IFN levels is needed to bypass the viral evasion mechanism and prevent its further replication and dissemination to lower airways and the rest of the body.

It is still controversial whether chronic lung inflammation increases the risk for COVID-19. One of the risk factors for acquiring COVID-19 is the level of expression of SARS-CoV-2 entry receptors, ACE2 and TMPRSS2, in lung tissue. It is, however, not clear how lung tissue inflammation affects expression levels of these receptors. We hence aimed to determine the level of SARS-CoV-2 receptors in lung tissue of asthmatic relative to age, gender, and asthma severity, and to investigate the factors regulating that. Therefore, gene expression data sets of well-known asthmatic cohorts (SARP and U-BIOPRED) were used to evaluate the association of ACE2 and TMPRSS2 with age, gender of the asthmatic patients, and also the type of the underlying lung tissue inflammatory cytokines. Notably, ACE2 and to less extent TMPRSS2 expression were upregulated in the lung tissue of asthmatics compared to healthy controls. Although a differential expression of ACE2, but not TMPRSS2 was observed relative to age within the moderate and severe asthma groups, our data suggest that age may not be a key regulatory factor of its expression. The type of tissue inflammation, however, associated significantly with ACE2 and TMPRSS2 expression levels following adjusting with age, gender and oral corticosteroids use of the patient. Type I cytokine (IFN-γ), IL-8, and IL-19 were associated with increased expression, while Type II cytokines (IL-4 and IL-13) with lower expression of ACE2 in lung tissue (airway epithelium and/or lung biopsies) of moderate and severe asthmatic patients. Of note, IL-19 was associated with ACE2 expression while IL-17 was associated with TMPRSS2 expression in sputum of asthmatic subjects. In vitro treatment of bronchial fibroblasts with IL-17 and IL-19 cytokines confirmed the regulatory effect of these cytokines on SARS-CoV-2 entry receptors. Our results suggest that the type of inflammation may regulate ACE2 and TMPRSS2 expression in the lung tissue of asthmatics and may hence affect susceptibility to SARS-CoV-2 infection.

(1) Background: Vitamin D deficiency is a common public health problem in the United Arab Emirates (UAE) and globally, and interestingly, improvements in diabetic neuropathy after taking Vitamin D supplementation for a short time have been reported. Despite living in a country that is sunny all year round, hypovitaminosis D, indicated by an obvious low serum vitamin D level, has been recurrently noted in the UAE, as well as in the surrounding Arabian Gulf countries. This problem is receiving much attention and attracting clinical and academic interest. Therefore, the main objective of the present study is to identify the association, if any, between vitamin D deficiency and the development of diabetic neuropathy in the UAE population with T2DM. (2) Methods: a total of 600 Emirati patients (male and female) with T2DM, aged between 20 and 80, were recruited from University Hospital Sharjah (UHS). The medical records of the patients were reviewed and analyzed. (3) Results: The results of the present study showed that among the 600 patients, 50% were affected with diabetic neuropathy. Vitamin D level in patients with neuropathy were estimated to be around 20 ng/mL (IQR 14–25), and vitamin D levels were significantly higher (33 ng/mL (IQR 20–42)) among patients without neuropathy, with p < 0.001. Another important finding was that patients without neuropathy had a better vitamin D status, with only 19% being deficient and 18% having insufficient vitamin D levels, compared to patients with neuropathy, where 39% were deficient (vitamin D < 20 ng/mL) and 44% had insufficient vitamin D levels (20–30 ng/mL). (4) Conclusion: The findings of the present study show that the prevalence of vitamin D deficiency (low serum 25-hydroxy vitamin D 25-OHD level) is significantly high in diabetic neuropathy in Emirati patients with T2DM.

Backgrounds Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated. Methods Ovalbumin (OVA)- sensitized BALB/c female mice were treated intranasally (IN) or intraperitoneally (IP) with abatacept 4 hrs before the OVA challenge. The effects of abatacept IN or IP on the lungs and blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and ELISA assay. Results Treating OVA- sensitized asthmatic mice model with abatacept, IN or IP, reduced lung inflammation. IN treatment with abatacept increased the frequency of IL-35 and IL-10 producing Bregs in the lung tissues to a higher level compared to IP treatment. Moreover, the frequency of lungs LAG3+ Tregs was significantly increased following treatment. This was also associated with a reduction in lung tissue and serum IL-17 levels of treated mice. Conclusions These results suggest that abatacept by enhancing IL-35+IL-10+ Bregs and LAG3+ Tregs might reverse IL-17 induced lung inflammation during asthma.

Acceptance of COVID-19 vaccine among health-care workers (HCWs) is crucial for controlling the pandemic and ensuring HCW and patient safety. Information on the acceptance of different COVID-19 vaccines is lacking. Despite the United Arab Emirates (UAE) having vaccinated most of its population, vaccine acceptance still raises concerns. This study explores COVID-19 vaccine acceptance, vaccine choice, and associated factors among HCWs in the UAE. An online national cross-sectional study was conducted among 517 HCWs. Acceptance and choice of COVID-19 vaccines were assessed, and logistic regression analysis identified predictors for vaccine acceptance. More than half (58%) of HCWs were willing to take the vaccine and give it to their family. Reasons for taking the vaccine were concerns for families contracting COVID-19 (67%) and social responsibility (64%). Reasons for refusals included concerns with side-effects (61%). Most HCWs knew of the Pfizer (79%) and Sinopharm (57%) vaccines; however, acceptance was higher for Pfizer (35%) and AstraZeneca (21%) vaccines. Being male and being influenza vaccinated predicted willingness to take the vaccine (aOR: 2.34; 95% CI:1.34-4.08; p ≤ 0.001) and (aOR: 2.13; 95% CI: 1.29-3.51; p ≤ 0.001), respectively. HCWs who expressed concerns with inadequate safety data were less likely to take the vaccine (aOR: 0.17; 95% CI: 0.10-0.30; p ≤ 0.001). Additionally, side effects, perception of risk, and level of trust of company and country of manufacture predicted acceptance and choice of vaccines. Effective vaccine policy campaigns to improve acceptance should target HCW's knowledge and awareness of perceived risks of COVID-19, safety data, social responsibility, and individual preferences for vaccine choice.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4%80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals70 years, 2.3% between 70 and 80 years, and 6.3%80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.

BACKGROUND The prognostic value of vascular endothelial growth factor-A (VEGFA) and epithelial cadherin (E-cadherin) expression in patients with metastatic colorectal cancer (mCRC) is controversial. MATERIALS AND METHODS In this prospective study, patients diagnosed with mCRC between August 1, 1998, and August 30, 2003, at the Turku University Hospital, Finland were included. Expression of E-cadherin (membranous and cytoplasmic pattern) and VEGFA in tumour samples was assessed by immunohistochemistry. Tumours were classified as E-cadherin expressers if they demonstrated moderate or strong cytoplasmic or membranous staining, while those positive for VEGFA expression showed a moderate or strong cytoplasmic staining. Of particular interest was the association between membranous or cytoplasmic expression of E-cadherin and VEGFA. The value of strong VEGF-A staining and membranous or cytoplasmic expression of E-cadherin as a predictor of disease outcome over a 6-year period was another point of interest in this study. RESULTS Of the 67 patients with mCRC, 43 (64%) had tumours positive for cytoplasmic E-cadherin, while in 24 cases (36%), E-cadherin expression was membranous. Strong VEGFA staining was present in half of the cases (n=36, 54% of all 67 mCRC cases). VEGFA expression was significantly correlated with cytoplasmic E-cadherin expression in that 28/36 cases of VEGFA-positive tumours were also positive for cytoplasmic E-cadherin (p=0.012). In addition, among the patients with intense VEGFA expression (n=36), those who had positive cytoplasmic E-cadherin in their tumours had a lower response-rate to first-line therapy with irinotecan, fluorouracil and leucovorin regimen: 5 out of 36 (14%) were chemosensitive. This is in contrast to the patients with VEGFA-positive tumours and membranous E-cadherin (8/36, 22% chemosensitive (p=0.004). The former group also had more ominous prognosis (p

The efficacy of corticosteroids and its use for the treatment of SARS-CoV-2 infections is controversial. In this study, using data sets of SARS-CoV-2 infected lung tissues and nasopharyngeal swabs, as well as in vitro experiments, we show that SARS-CoV-2 infection significantly downregulates DUSP1 expression. This downregulation of DUSP1 could be the mechanism regulating the enhanced activation of MAPK pathway as well as the reported steroid resistance in SARS-CoV-2 infection. Moreover, chloroquine, an off labeled COVID-19 drug is able to induce DUSP1 and attenuate MAPK pathway; and is expected to improve sensitivity to steroid treatment. However, further mechanistic studies are required to confirm this effect.

Background: The main mechanism of viral entry in COVID-19 infection is through the angiotensin-converting enzyme 2 (ACE2) receptor present in the lungs. Numerous studies suggested a clinical significance of risk factors, such as gender, obesity, and diabetes on the soluble form of ACE2 (sACE2) and related miRNAs in COVID-19 infection. This study aims to investigate the serum level of sACE2 and 4 miRNAs (miR-421, miR-3909, miR-212-5p, and miR-4677-3p) in COVID-19 patients and assess their associations with clinicopathological parameters. Methods: Serum samples were collected from non-diabetic and diabetic COVID-19 patients and healthy controls. sACE2 levels were quantified using ELISA, and serum miRNA levels were measured using qPCR. In addition, laboratory blood tests were retrieved from the clinical records of COVID-19 patients. Results: sACE2 levels were upregulated in COVID-19 patients regardless of sex, diabetes status, or obesity. Furthermore, the four investigated miRNAs were upregulated in COVID-19 patients and were positively correlated with each other. Furthermore, miR-421, miR-3909, and miR-4677-3p were positively associated with sACE2, suggesting a strong link between these markers. Notably, miR-212-5p was selectively upregulated in moderate, male, and non-obese COVID-19 patients. Interestingly, miR-212-5p was correlated with D-dimer, while sACE2 was correlated with coagulation tests, such as aPTT and platelets, indicating their potential as markers of coagulopathy in COVID-19. Additionally, there was a positive correlation between sACE2 and C-reactive protein in diabetic COVID-19 patients, indicating a promising role of this marker in the inflammatory status of these patients. Conclusions: sACE2 and its regulatory miRNAs were upregulated and correlated with laboratory investigations of COVID-19 patients, thus indicating their clinical significance as biomarkers in COVID-19 infection.

Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact between different subpopulations. Emerging evidence from different parts of the world showed significantly poor outcome among males compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for a more effective and targeted response to the outbreak. For that reason, here we try to investigate the molecular basis of the gender variations in mortality rates related to COVID-19 infection. To achieve this, we used our in-house pipeline to process publicly available lung transcriptomic data from 141 females compared to 286 males. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Our results showed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (AGTR1, CHM, DDX3X, FGFR3, SFRP2, and NLRP2), which is also believed to be essential for lung immune response and antimicrobial activity in the lung tissues in males compared to females. In contrast, our results showed an upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation. Interestingly, recent reports and experimental animal models highlight an important role of this receptor in SARS-Coronavirus lung damage as well as pulmonary edema, suggesting a possible role of its blockers like losartan and olmesartan as potential therapeutic options for COVID-19 infection. Finally, our results also showed a differential expression of different genes that are involved in the immune response including the NLRP2 and PTGDR2, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed between both genders during the COVID-19 outbreak. This might be essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.

Fatemeh Saheb Sharif-Askari,1 Narjes Saheb Sharif-Askari,1 Adnane Guella,2 Ali Alabdullah,1,* Hour Bashar Al Sheleh,1,* Afnan Maher Hoory AlRawi,1,* Enad Sami Haddad,1,* Qutayba Hamid,1,3 Rabih Halwani,1,3,4 Rifat Hamoudi1,3 1Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 2Department of Nephrology, University Hospital Sharjah, Sharjah, United Arab Emirates; 3Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 4Prince Abdullah Ben Khaled Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia*These authors contributed equally to this workCorrespondence: Rifat Hamoudi; Rabih HalwaniCollege of Medicine, University of Sharjah, Sharjah, United Arab EmiratesEmail rhamoudi@sharjah.ac.ae; rhalwani@sharjah.ac.aeBackground: Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the most common uropathogens causing UTI (urinary tract infection) in type 2 diabetes mellitus (T2DM). Circulatory inflammatory markers such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) are usually dysregulated during UTI. However, the differential regulation of these inflammatory signatures during E. coli and K. pneumoniae UTI in T2DM has not been determined.Methods: A case–control study on 466 patients was performed to investigate the inflammatory signatures indicative of ESBL-E. coli and K. pneumoniae UTIs in T2DM. Serum CRP levels and blood NLR for these patients were determined and associated with E. coli and K. pneumoniae ESBL uropathogen using multivariate logistic regression analysis. Urinary interleukin 8 (IL-8) levels were also assessed and associated with these two UTI uropathogens in T2DM. The association of the two ESBL-uropathogens with the survival outcomes of T2DM patients was also analyzed using Cox-proportional hazard model.Results: T2DM patients with ESBL-E. coli UTI had lower serum CRP levels (median, CRP mg/dL 33.7 vs 39.8, respectively; P=0.023) and higher blood NLR (median, NLR 3.2 vs 2.6, respectively; P=0.010) compared to those with K. pneumoniae UTIs (P< 0.001). Moreover, in T2DM, the urinary IL-8 levels was higher in ESBL-E. coli compared to those with K. pneumoniae UTIs (P< 0.0001). After adjusting for confounders, including age, gender, serum albumin, hemoglobulin, leukocytes, and platelet counts, T2DM patients with blood NLR ≥ 3.5 were at higher risk for ESBL-E. coli UTIs than ESBL-K. pneumoniae UTIs (odds ratio [OR], 3.61, 95% confidence interval, Cl, 1.49– 8.73; P=0.004). Moreover, T2DM patients with ESBL-E. coli UTIs had higher all-cause mortality (hazard ratio [HR], 4.09; 95%, 1.14– 14.59) than those with K. pneumoniae UTIs.Conclusion: Serum CRP levels, blood NLR, and IL-8 urinary levels differentiate ESBL-E. coli from K. pneumoniae UTIs in T2DM.Keywords: extended-spectrum ß-lactamase, Klebsiella pneumoniae, Escherichia coli, urinary tract infection, C-reactive protein, survival

Background Lung cancer is the most common cancer globally. Protein arginine methyltransferase 5 (PRMT5) is identified to be involved in gene transcriptional regulation and cell division. PRMT5 is highly expressed in lung adenocarcinoma, hepatocellular carcinoma, and melanoma, raising evidence that PRMT5 might be involved in tumorigenesis. The aim of this study is to examine potential selective anti-neoplastic activity of PRMT5 inhibitor, Arginine methyltransferase inhibitor 1 (AMI-1) and cisplatin on lung adenocarcinoma. Methods Effect of AMI-1 on PRMT5 activity inhibition in lung adenocarcinoma cell line, A549, in response to standard chemotherapeutic agent, cisplatin, was assessed. Bioinformatic analyses were carried out to identify the prognostic value of PRMT5 and its major functional pathways in lung adenocarcinoma. Cell viability, PMRT5 protein levels, extent of cell migration, survival of cancer cells, and cell cycle progression and apoptosis were examined. Drug combination was also evaluated in human bronchial epithelial cells (HBEpC). Results Bioinformatics identified apoptosis, DNA damage, and cell cycle progression as the main PRMT5 associated functional pathways, and survival analysis linked the increased PRMT5 gene expression to worse overall survival. Combination treatment with 10 µM AMI-1 and of Cisplatin significantly reduced viable cell percentages. Cell cycle arrest in A549 cells was evident after AMI-1, which was reinforced after combination treatment. Apoptosis was observed after treatment with both drugs. Western blot analysis showed reduction in demethylation histone 4, a PRMT5- downstream target, after treatment with AMI-1 alone or in combination with cisplatin. While combination approach tackled lung cancer cell survival, it exhibited cytoprotective abilities on normal epithelial cells. Finally, treatment with both drugs led to a decreased cell migration rate. Conclusions This study highlights evidence of novel selective antitumor additive activity of AMI-1 in combination with cisplatin in lung adenocarcinoma cells. Survival of normal bronchial epithelial cells was not affected by using AMI-1.

Background Insulin-resistant individuals are known to have dyslipidemia and are predicted to be at high risk of cardiovascular events. Vitamin D deficiency was shown to be associated with dyslipidemia; however, the type of dyslipidemia associated with vitamin D deficiency in insulin-resistant individuals is not determined. Furthermore, there is evidence linking insulin resistance with low-grade inflammation suggesting levels of pro-inflammatory cytokines to be increased in insulin-resistant states. Objective This study was performed to evaluate the impact of vitamin D deficiency, defined as serum level of 25(OH)D below 20 ng/mL, on lipid profile and inflammatory markers such as interleukin (IL-6) and IL-8, as well as soluble thrombomodulin (TM) in the serum of insulin-resistant individuals. Methods A total of 4114 individuals had simultaneous serum 25(OH)D, insulin, and lipid panel testing during 2013 as part of the United Arab Emirates National Diabetes and Lifestyle (UAEDIAB) study. Multivariate logistic regression analysis was used to assess the association between serum level of 25(OH)D and lipid profile in insulin-sensitive versus -resistant individuals. The lipid panel was stratified into high total cholesterol (TC: >6.2 mmol/L) , high low-density lipoprotein-cholesterol (LDL-C: >2.59 mmol/L), high triglycerides (TG: >2.3 mmol/L), and low high-density lipoprotein-cholesterol (HDL-C

Severe asthma and lung cancer are both heterogeneous pathological diseases affecting the lung tissue. Whilst there are a few studies that suggest an association between asthma and lung cancer, to the best of our knowledge, this is the first study to identify common genes involved in both severe asthma and lung cancer. Publicly available transcriptomic data for 23 epithelial brushings from severe asthmatics and 55 samples of formalin-fixed paraffin-embedded (FFPE) lung cancer tissue at relatively early stages were analyzed by absolute gene set enrichment analysis (GSEA) in comparison to 37 healthy bronchial tissue samples. The key pathways enriched in asthmatic patients included adhesion, extracellular matrix, and epithelial cell proliferation, which contribute to tissue remodeling. In the lung cancer dataset, the main pathways identified were receptor tyrosine kinase signaling, wound healing, and growth factor response, representing the early cancer pathways. Analysis of the enriched genes derived from the pathway analysis identified seven genes expressed in both the asthma and lung cancer sets: BCL3, POSTN, PPARD, STAT1, MYC, CD44, and FOSB. The differential expression of these genes was validated in vitro in the cell lines retrieved from different lung cancer and severe asthma patients using real-time PCR. The effect of the expression of the seven genes identified in the study on the overall survival of lung cancer patients (n = 1925) was assessed using a Kaplan–Meier plot. In vivo validation performed in the archival biopsies obtained from patients diagnosed with both the disease conditions provided interesting insights into the pathogenesis of severe asthma and lung cancer, as indicated by the differential expression pattern of the seven transcripts in the mixed group as compared to the asthmatics and lung cancer samples alone.

Background Little is known about the adverse drug reaction (ADR) related admissions among heart failure (HF) patients. Objective The aim of this study was to determine the rate, factors, and medications associated with ADR-related hospitalisations among HF patients. Setting Two government hospitals in Dubai, United Arab Emirates. Methods This was a prospective, observational study. Consecutive adult HF patients who were admitted between December 2011 and November 2012 to the cardiology units were included in this study. The circumstances of their admission were analysed. Main outcome measures ADRs-related admissions of HF patients to cardiology units were identified and further assessed for their nature, causality, and preventability. Results Of 511 admissions, 34 were due to ADR-related hospitalisation (6.65, 95 % confidence interval 4.8–8.5 %). Number of medications taken by HF patients was the only predictors of ADR-related hospitalisations, where higher number of medications was associated with the odd ratio of 1.11 (95 % CI, 1.03–1.20, P = 0.005). More than one-third of ADR-related hospitalisations (35 %) were preventable The most frequent drugs causing ADR-related hospitalisation were diuretics (32 %), followed by non-steroidal anti-inflammatory drugs (15 %), thiazolidinediones (9 %), anticoagulants (9 %), antiplatelets (6 %), and aldosterone blockers (6 %). Conclusion ADR-related hospitalisations account for 6.7 % of admissions of HF patients to cardiac units, one-third of which are preventable. Number of medications taken by HF patients is the only predictors of ADR-related hospitalisations. Diuretic induced volume depletion, and sodium and water retention caused by thiazolidinediones and NSAIDs medications are the major causes of ADR-related hospitalisations of HF patients.

Aims To compare the baseline characteristics, pharmacological treatment, and in-hospital outcomes across hospitalized heart failure (HF) patients with preserved LVEF (HF-PEF) and those with reduced LVEF (HF-REF). Method and results This was a prospective analysis of consecutive patients admitted with decompensated HF at two government hospitals in the United Arab Emirates, from 1 December 2011 to 30 November 2012. Multivariate factors of HF-PEF vs. HF-REF included elevated systolic blood pressure [odds ratio (OR) 1.02; 95% confidence interval (CI) 1.01–1.03], heart rate (OR 0.98; 95% CI 0.97–0.99), age (OR 1.02; 95% CI 1.01–1.04), female sex (OR 2.38; 95% CI 1.41–4.03), angina or myocardial infarction (OR 0.42; 95% CI 0.25–0.71), AF (OR 1.82; 95% CI 1.05–3.15), COPD or asthma (OR 2.80; 95% CI 1.47–5.35), Charlson Comorbidity Index score (OR 0.75; 95% CI 0.64–0.88), and anaemia (OR 2.97; 95% CI 1.64–5.38). In-hospital outcomes were similar between the two groups. However, patients with HF-PEF were less likely to be prescribed HF medication, and used more anticoagulants and fewer antiplatelet medications. Conclusion These results suggest that patients with HF-PEF are older, more often female, and have higher prevalence of respiratory diseases and AF. Compared with developed countries, hospitalized HF patients in the Middle East are 10 years younger and have a higher prevalence of diabetes mellitus, and the majority have HF-REF.

Increased body mass index (BMI) has been associated with an increased prevalence of asthma in children, however the association between BMI status and asthma severity has been less well defined. The aim of this study was to describe the association between childhood obesity and asthma severity, frequency of hospital and emergency department visits as well as pattern of aeroallergen sensitization. A retrospective study was conducted at pediatric outpatient clinics in University Hospital Sharjah. All consecutive patients aged 6 years and above, with confirmed diagnosis of asthma visiting the outpatient pediatric clinics during 2018 were included in this study. Sources of information were the patient's medical file, laboratory data, pharmacy data, as well as reports from the pediatric in charge. This study included 164 children with asthma. 63% of asthma patients were male. The vast majority of patients were from Arab ethnicities (n = 154, 94%), majority had mild asthmatic conditions (n = 133, 81%), and one-third were either overweight or obese (n = 52, 32%). Overweight or obese asthmatic children with BMI percentile of equal or more than 85% was associated with more asthma severity (odds ratio [OR]: 3.27, 95% confidence interval [CI]: 1.42-7.54; P = 0.005), as well as more frequent asthma related hospital visits (OR: 2.53, 95% CI: 1.22-5.26; P = 0.013). Overweight asthmatic children with BMI between the 85th and 94th percentiles and obese asthmatic children with BMI equal to or greater than 95th percentile are associated with more severe asthma phenotype and more frequent hospital and emergency department visits.

Patients with chronic kidney disease (CKD) are at increased risk for both thrombotic events and bleeding. The early stages of CKD are mainly associated with prothrombotic tendency, whereas in its more advanced stages, beside the prothrombotic state, platelets can become dysfunctional due to uremic-related toxin exposure leading to an increased bleeding tendency. Patients with CKD usually require anticoagulation therapy for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of anticoagulant-induced bleeding. Treatment of patients with CKD should be based on evidence from randomized clinical trials, but usually CKD patients are excluded from these trials. In the past, unfractionated heparins were the anticoagulant of choice for patients with CKD because of its independence of kidney elimination. However, currently low-molecular-weight heparins have largely replaced the use of unfractionated heparins owing to fewer incidences of heparin-induced thrombocytopenia and bleeding. We undertook this review in order to explain the practical considerations for the management of anticoagulation in these high risk population.

Patients with chronic kidney disease (CKD) are at increased risk for both thrombotic events and bleeding. The early stages of CKD are mainly associated with prothrombotic tendency, whereas in its more advanced stages, beside the prothrombotic state, platelets can become dysfunctional due to uremic-related toxin exposure leading to an increased bleeding tendency. Patients with CKD usually require anticoagulation therapy for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of anticoagulant-induced bleeding. Treatment of patients with CKD should be based on evidence from randomized clinical trials, but usually CKD patients are excluded from these trials. In the past, unfractionated heparins were the anticoagulant of choice for patients with CKD because of its independence of kidney elimination. However, currently low-molecular-weight heparins have largely replaced the use of unfractionated heparins owing to fewer incidences of heparin-induced thrombocytopenia and bleeding. We undertook this review in order to explain the practical considerations for the management of anticoagulation in these high risk population.

Background Burden of adverse drug reactions (ADRs), in home-environment and domestic settings, is unknown. Objective To discuss the epidemiology of reported ADRs to 13-Aban drug and poison information center (DPIC) and to discuss the burden of hospitalization caused by these ADRs from commonly implicated therapeutic groups. Methods A retrospective analysis of the yellow card schemes of suspected ADRs reported to the 13-Aban DPIC was conducted from 21 March 2013 to 21 November 2016 inclusive. Main outcome measures Characteristics of the ADRs, such as the sex and age of the patient, the therapeutic group involved, and the medical outcome of the exposure, were examined. ADR Hospitalization (ADRH) index was calculated for each drug group by dividing the number of ADR-related hospitalizations with total number of reported ADR cases (n = 748), and then multiplying by 100. Results ADRs were reported for 748 patients representing 5 cases per 1000 enquiries to the 13-Aban DPIC over almost 4-years of the study period. Public were responsible for reporting every 4 out of 5 ADR cases (n = 651, 87%) and the remaining 1 out of 5 ADR cases was reported by the health care professionals (n = 97, 13%). Most of the ADRs had a medical outcome documented as having a minor effect or were minimally bothersome to the patients (n = 509, 68%), and less than 4.9% (n = 37) were documented as having a major effect or were life-threatening. Overall, 7.4% (n = 55) of ADRs were resulted in hospitalization. Antibacterials for systemic use represented the therapeutic group with the highest hospitalization index (1.7%). Conclusions The study concluded that ADRs to antibiotics are common and some of them resulted in hospitalization.

To compare the baseline characteristics, pharmacological treatment, and in-hospital outcomes across hospitalized heart failure (HF) patients with preserved LVEF (HF-PEF) and those with reduced LVEF (HF-REF).This was a prospective analysis of consecutive patients admitted with decompensated HF at two government hospitals in the United Arab Emirates, from 1 December 2011 to 30 November 2012. Multivariate factors of HF-PEF vs. HF-REF included elevated systolic blood pressure [odds ratio (OR) 1.02; 95% confidence interval (CI) 1.01–1.03], heart rate (OR 0.98; 95% CI 0.97–0.99), age (OR 1.02; 95% CI 1.01–1.04), female sex (OR 2.38; 95% CI 1.41–4.03), angina or myocardial infarction (OR 0.42; 95% CI 0.25–0.71), AF (OR 1.82; 95% CI 1.05–3.15), COPD or asthma (OR 2.80; 95% CI 1.47–5.35), Charlson Comorbidity Index score (OR 0.75; 95% CI 0.64–0.88), and anaemia (OR 2.97; 95% CI 1.64–5.38). In-hospital outcomes were similar between the two groups. However, patients with HF-PEF were less likely to be prescribed HF medication, and used more anticoagulants and fewer antiplatelet medications.These results suggest that patients with HF-PEF are older, more often female, and have higher prevalence of respiratory diseases and AF. Compared with developed countries, hospitalized HF patients in the Middle East are 10 years younger and have a higher prevalence of diabetes mellitus, and the majority have HF-REF.

Background Adverse drug reactions (ADRs) represent a major burden on the healthcare system. Chronic kidney disease (CKD) patients are particularly vulnerable to ADRs because they are usually on multiple drug regimens, have multiple comorbidities, and because of alteration in their pharmacokinetics and pharmacodynamic parameters. Therefore, one step towards reducing this burden is to identify patients who are at increased risk of an ADR. Objective To develop a method of identifying CKD patients who are at increased risk for experiencing ADRs during hospitalisation. Materials and Methods Factors associated with ADRs were identified by using demographic, clinical and laboratory variables of patients with CKD stages 3 to 5 (estimated glomerular filtration rate, 10–59 ml/min/1.73 m2) who were admitted between January 1, 2012, and December 31, 2012, to the renal unit of Dubai Hospital. An ADR risk score was developed by constructing a series of logistic regression models. The overall model performance for sequential models was evaluated using Akaike Information Criterion for goodness of fit. Odd ratios of the variables retained in the best model were used to compute the risk scores. Results Of 512 patients (mean [SD] age, 60 [16] years), 62 (12.1%) experienced an ADR during their hospitalisation. An ADR risk score included age 65 years or more, female sex, conservatively managed end-stage renal disease, vascular disease, serum level of C-reactive protein more than 10 mg/L, serum level of albumin less than 3.5 g/dL, and the use of 8 medications or more during hospitalization. The C statistic, which assesses the ability of the risk score to predict ADRs, was 0.838; 95% CI, 0.784–0.892). Conclusion A score using routinely available patient data can be used to identify CKD patients who are at increased risk of ADRs.