Correlations between serum kidney injury molecule-1, cystatin C and immunosuppressants: A cross-sectional study of renal transplant patients in Bahrain.

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment. Serum creatinine is the standard for monitoring kidney function; however, cystatin C (Cys C) and kidney injury molecule-1 (KIM-1) have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function. Here, we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil, tacrolimus, sirolimus, everolimus, or cyclosporine to evaluate kidney function. We used both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation, which is based on creatinine and combined creatinine with Cys C, and the CKD-EPI 2012 equation, which is based on Cys C alone, to estimate glomerular filtration rate (GFR). Then, we assessed the association between serum KIM-1 and GFR < 90 mL per minute per 1.73 m 2. We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine, compared with those with normal serum creatinine. The estimated GFRs based on creatinine were significantly higher than those based on the other equations, while a significant positive correlation was observed among all equations. Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations. A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR < 90 mL per minute per 1.73 m 2. We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients. Therefore, serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

Reduction of Panton-Valentine Leukocidin Production in the Staphylococcal Strain USA300 After In Vitro Ascorbic Acid and Nicotinamide Treatment.

Background Panton-Valentine leukocidin (PVL) is one of the most important determinants of virulence in Staphylococcus aureus. It is associated with a propensity for complicating skin and soft tissue infections and necrotizing pneumonia. This study aims to quantitively examine the effect of ascorbic acid and nicotinamide on PVL production in the reference strain USA300. Methodology Sandwich enzyme-linked immunosorbent assay (ELISA) was used to quantitively measure the production of PVL via the commercial LukS sandwich ELISA kit (IBT Bio-services, MD, USA). Results Incubating USA300 with subinhibitory concentrations of antioxidants resulted in a statistically significant eight-fold reduction in PVL production at 1.25 mg/mL and 30 mg/mL for ascorbic acid and nicotinamide, respectively. Although the mechanism by which antioxidants inhibit PVL production is yet to be elucidated, we suggest that it can be due to interrupting PVL gene expression. Conclusions Ascorbic acid and nicotinamide have the potential to be toxin-suppressing agents that may be effective in supporting the bactericidal effect of antibiotics to improve the outcome of PVL-associated infections; however, further extensive research is required.

Hematologic malignancies of primary bone marrow involvement: a decade's experience in Bahrain

ABSTRACT Introduction: The data on the pattern of primary hematologic malignancies in Bahrain is sparse, although previously published studies suggested rising trends in their incidence. This study aimed to compare with regional and world data and identify any changing trends. Methods: A retrospective cross-sectional chart analysis study was done on all cases of primary hematologic malignancies of bone marrow origin of Bahraini nationals presenting during the 10-year period from January 2005 to December 2014 at the sole oncology referral center in Bahrain during the study period. Results: In a total of 272 cases, the primary hematologic malignancies in decreasing order of frequency with respective median ages at diagnosis were: acute myeloid leukemia (AML; 26.1%, 39 years), acute lymphoblastic leukemia (ALL; 22.8%, 9 years), multiple myeloma (MM, 16.2%, 57 years), chronic myeloid leukemia (CML, 14%, 39.5 years), myelodysplastic syndromes (MDS; 12.5%, 56 years) and chronic lymphocytic leukemia (CLL; 5.5%, 65 years). The overall crude annual incidence rate of these malignancies was 4.8/105 population. Age-specific incidence rates were found to increase dramatically with age, except for ALL, for which it peaked in the pediatric age group. The age-standardized incidence rates (ASIRs) per 105 per year were 1.47 (AML), 1.13 (MM), 0.93 (ALL), 0.85 (MDS), 0.81 (CML) and 0.44 (CLL). Conclusion: The pattern of primary hematologic malignancies in Bahrain shows unique features that distinguish it from trends reported in Eastern and Western world populations.

Multidrug-Resistant Staphylococcus aureus Isolates in a Tertiary Care Hospital, Kingdom of Bahrain.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a ubiquitous pathogen associated with a wide spectrum of human infections. In recent decades, MRSA infections have been increasingly reported in individuals without established risk factors, infecting immunocompetent members of the community. This emergence is attributed to the production of various virulence factors, notably Panton-Valentine leukocidin (PVL). OBJECTIVE: The aim of this study was to better understand the prevalence, antibiotic resistance profiles, and molecular characteristics of S. aureus and MRSA in a tertiary care hospital in the Kingdom of Bahrain. MATERIALS AND METHODS: This cross-sectional study was carried out in a tertiary hospital for a one-year period, from December 2020 to December 2021. A total of 161 consecutive S. aureus isolates were collected. Antibiotic susceptibility was tested using BD Phoenix™ automated identification and susceptibility testing system. Molecular analysis was conducted via conventional PCR and conventional multiplex PCR for SCCmec typing. RESULTS: In this study, 161 S. aureus isolates were investigated, 60% (n=97) were characterized as MRSA, of which, 12% (n=12) were healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) while 88% (n=85) were community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). No statistically significant difference (P>0.05) in antibiotic resistance trends between HA-MRSA and CA-MRSA was detected. Multidrug resistance (MDR) amounted to 19% (n=30) of all S. aureus isolates, 14% (n=9) of methicillin-susceptible Staphylococcus aureus (MSSA) isolates, and 22% (n=21) of MRSA isolates. SCCmec typing demonstrated a high prevalence of type IV (61%, n=59), followed by type V (32%, n=31), then type II (4%, n=4), and type III (3%, n=3). The PVL prevalence was 39% (n=25) in MSSA and 62% (n=60) in MRSA, 33% (n=4) in HA-MRSA, and 66% (n=56) in CA-MRSA. CONCLUSION: This study demonstrated the emergence of PVL-producing CA-MRSA in a tertiary care hospital, as well as the detection of PVL-producing MDR strains. This development prompts serious measures to be taken in order to sustain a healthy clinical environment.

Inherited CD59 deficiency, where neurology and genetics intertwine.

OBJECTIVES: To describe the clinical phenotype of eight children diagnosed with CD59 deficiency and their ultimate neurological outcome. METHODS: The data of our cases were extensively reviewed both clinical and ancillary tests; investigations included: neuroimaging, neurophysiological studies, and laboratory tests. RESULTS: All patients presented during early infancy with Guillain-Barre syndrome later they suffered repeated relapses leading to the diagnosis of chronic axonal neuropathy. Recurrent stroke and acute necrotizing encephalopathy were described, 2 patients in each group. One girl developed acute disseminated encephalomyelitis while one boy developed acute transverse myelitis. Overt hemolytic anemia requiring blood transfusion reported in six patients. CONCLUSION: Inherited CD59 deficiency is an autosomal recessive disorder which can have devastating neurological consequences. First line immunotherapy including intravenous immunoglobin, corticosteroids, and plasma exchange may have transient beneficial effect. Reports of targeted therapy with eculizumab might be lifesaving. Genetic counseling is crucial.

Synergistic antimicrobial effect of ascorbic acid and nicotinamide with rifampicin and vancomycin against SCCmec type IV methicillin-resistant Staphylococcus aureus (MRSA).

Background. Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogenic bacteria involved in a wide spectrum of human diseases. Many virulence factors promote this widespread propagation. One important factor is acquiring antibiotic resistance genes, which leads to a reduction in the availability and efficacy of therapy options. Recently, research has suggested that the remarkable antimicrobial effect of antioxidants against superbugs such as MRSA shows synergistic effects when accompanied by antimicrobial therapy. This paper aims to examine the synergistic effects of ascorbic acid and nicotinamide with a panel of antibiotics used in antimicrobial therapy against MRSA. Material and Methods. Two SCCmec type IV MRSA reference strains (EMRSA-15 and USA300) and 10 MRSA clinical isolates feature in this paper. SCCmec typing was conducted on the 10 clinical isolates via multiplex PCR after identification. Synergy experiments on antioxidants and antibiotics were evaluated via checkerboard assay. The minimum inhibitory concentration (MIC) of each agent was determined in accordance with the Clinical and Laboratory Standards Institute (CLSI) M100 guidelines through twofold microdilution assay. Results and Discussion. Synergy (FIC <0.5) was demonstrated for ascorbic acid (1/2 to 1/4 MIC) with rifampicin (1/2 to 1/8 MIC), and also ascorbic acid (1/2 to 1/16 MIC) when associated with vancomycin (1/2 MIC). Similarly, nicotinamide (1/2 to 1/16 MIC) showed a synergistic effect when paired with low concentrations of rifampicin (1/2 to 1/16 MIC), and also (at 1/4 to 1/16 MIC) with vancomycin (1/2 MIC). All reduced MICs due to synergistic combinations demonstrated statistical significance (P<0.05). Conclusion. The synergistic activity demonstrated in associating antioxidants with antibiotics shows promise in managing superbugs. However, more research is required to better understand the mechanism of the synergy and for utilization in clinical care.

The Effect of Ascorbic Acid and Nicotinamide on Panton-Valentine Leukocidin Cytotoxicity: An Ex Vivo Study.

Background: Panton−Valentine Leukocidin sustains a strong cytotoxic activity, targeting immune cells and, consequently, perforating the plasma membrane and inducing cell death. The present study is aimed to examine the individual effect of ascorbic acid and nicotinamide on PVL cytotoxicity ex vivo, as well as their effect on granulocytes viability when treated with PVL. Materials and Methods: The PVL cytotoxicity assay was performed in triplicates using the commercial Cytotoxicity Detection Kit PLUS (LDH). LDH release was measured to determine cell damage and cell viability was measured via flow cytometry. Results and discussion: A clear reduction in PVL cytotoxicity was demonstrated (p < 0.001). Treatment with ascorbic acid at 5 mg/mL has shown a 3-fold reduction in PVL cytotoxicity; likewise, nicotinamide illustrated a 4-fold reduction in PVL cytotoxicity. Moreover, granulocytes' viability after PVL treatment was maintained when incubated with 5 mg/mL of ascorbic acid and nicotinamide. Conclusions: our findings illustrated that ascorbic acid and nicotinamide exhibit an inhibitory effect on PVL cytotoxicity and promote cell viability, as the cytotoxic effect of the toxin is postulated to be neutralized by antioxidant incubation. Further investigations are needed to assess whether these antioxidants may be viable options in PVL cytotoxicity attenuation in PVL-associated diseases.

Hematologic malignancies of primary bone marrow involvement: a decade's experience in Bahrain.

INTRODUCTION: The data on the pattern of primary hematologic malignancies in Bahrain is sparse, although previously published studies suggested rising trends in their incidence. This study aimed to compare with regional and world data and identify any changing trends. METHODS: A retrospective cross-sectional chart analysis study was done on all cases of primary hematologic malignancies of bone marrow origin of Bahraini nationals presenting during the 10-year period from January 2005 to December 2014 at the sole oncology referral center in Bahrain during the study period. RESULTS: In a total of 272 cases, the primary hematologic malignancies in decreasing order of frequency with respective median ages at diagnosis were: acute myeloid leukemia (AML; 26.1%, 39 years), acute lymphoblastic leukemia (ALL; 22.8%, 9 years), multiple myeloma (MM, 16.2%, 57 years), chronic myeloid leukemia (CML, 14%, 39.5 years), myelodysplastic syndromes (MDS; 12.5%, 56 years) and chronic lymphocytic leukemia (CLL; 5.5%, 65 years). The overall crude annual incidence rate of these malignancies was 4.8/105 population. Age-specific incidence rates were found to increase dramatically with age, except for ALL, for which it peaked in the pediatric age group. The age-standardized incidence rates (ASIRs) per 105 per year were 1.47 (AML), 1.13 (MM), 0.93 (ALL), 0.85 (MDS), 0.81 (CML) and 0.44 (CLL). CONCLUSION: The pattern of primary hematologic malignancies in Bahrain shows unique features that distinguish it from trends reported in Eastern and Western world populations. Compared to previously published reports, ASIR trends decreased in CML and ALL but increased in MDS and MM.

A drug utilization and drug interaction study in renal transplant patients: Implications for an urgent need for drug deprescribing.

BACKGROUND: Renal transplant patients receive several drugs concomitantly. OBJECTIVE: Limited literature exists evaluating the drug use in this population that is at high risk for drug-induced acute kidney injury and complications due to under-or over-dosage of immunosuppressant drugs due to drug-drug interactions. METHODS: A retrospective observational study was carried out in 269 renal transplant patients in whom either oral or parenteral drugs were evaluated. World Health Organization (WHO) indicators of drug utilization such as the average number of drugs prescribed, daily defined dose, and proportion of drugs listed as WHO essential drugs were evaluated. Details on the drugs with nephrotoxic potential were obtained. Drug-drug interactions were assessed concerning the severity (major, moderate, and minor) as well as type (pharmacokinetic, pharmacodynamic, and toxicity). RESULTS: One-hundred and ninety-eight drugs were administered to the study participants. The median (range) total number of drugs received by the study participants was 23 (6-55). The proportion of drugs listed in the WHO essential drug database was 57.1 (16.7-100)%. Forty-six drugs with potential nephrotoxicity and seven drugs that were contra-indicated in patients with chronic renal disease/end-stage renal disease were administered to the study participants. The mean (SD) numbers of drug interactions observed amongst the study participants were 18.4 (10.1). Age (ß: 0.2, 95% CI: 0.1, 0.3) and duration of renal transplantation (ß: -0.3, 95% CI: -0.5, -0.1) were the significant predictors of drug burden. A total of 645 drug interactions were identified amongst the study participants (major - 240; moderate - 270; and minor - 135) of which the majority were pharmacokinetic followed by toxicity risk. Age was significantly associated with the risk of potential drug interaction (OR: 2.6, 95% CI: 1.8, 12.4; p = 0.001). CONCLUSION: Drug treatment in renal transplant patients poses a significant burden in terms of nephrotoxicity potential and drug-drug interactions. A dedicated ambulatory clinical pharmacy service monitoring the drug use coupled with drug deprescribing strategies are the need of the hour in this population.

Effect of foaming parameters on the physical and phytochemical properties of tomato powder.

The objective of this work was to study the effect of foaming parameters on the physical and phytochemical properties of tomato powder. A central composite rotatable design of experiments was defined with two parameters (concentration of soy protein isolate [SPI]: 1-5% and whipping time: 2-14 min) with 5 levels for each parameter. The foam was prepared by whipping tomato puree after adding SPI and dried in a thin layer (4 mm ± 1) at 50 °C. The obtained results showed the predominant effect of the concentration of SPI on the physical and phytochemical properties compared to whipping time. The powder prepared under foaming conditions of 5% SPI and whipping time of 8 min showed an increase of 97, 39, 62, and 46% in the total phenolics, total flavonoids, antioxidant activity, and porosity, respectively, while the bulk density decreased by about 25%.

Trends in methicillin-resistant Staphylococcus aureus in the Gulf Cooperation Council countries: antibiotic resistance, virulence factors and emerging strains.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a ubiquitous pathogen that is increasing in Gulf Cooperation Council (GCC) countries. It is implicated in a wide range of infections, from superficial skin infections to lifethreatening syndromes. MRSA has moved beyond healthcare facilities, affecting individuals in the community without substantial risk factors. Aims: To review the prevalence and molecular characterization of MRSA in GCC countries during 2011-2021. Methods: We comprehensively searched PubMed using the following keywords: MRSA, Staphylococcus aureus, GCC, Kuwait, Saudi Arabia, Bahrain, Oman, Qatar, UAE, prevalence, and molecular characterization for articles published after 2011. Results: Thirty-nine of 111 articles examined, fulfilled the purpose of this review. Most studies were in Kuwait (44%), Saudi Arabia (28%) and United Arab Emirates (10%). Studies from other GCC countries were sporadic. Several studies demonstrated a clear emergence in antibiotic resistance especially against fusidic acid, ciprofloxacin and clindamycin. Regional prevalence of MRSA is reported as 25-35%, with clear dominance of community-acquired (CA)-MRSA. Panton- Valentine leucocidin (PVL)-producing strains accounted for 35-45%, with clear association with CA-MRSA emergence, but there were some sporadic reports of incorporation of PVL in healthcare-associated (HA)-MRSA. The reported dominant strains included EUST80, USA1100 and WA-MRSA-51. Novel strains are more likely to produce PVL and show fusidic acid resistance. Conclusion: There is a need for national and regional MRSA surveillance programmes, especially with the emergence of strains that require no underlying risk factors to cause illness, as well as the propagation of chimeric resistance elements in both HA-MRSA and CA-MRSA.

The Effect of Age, Gender and Comorbidities Upon SARS-CoV-2 Spike Antibody Induction After Two Doses of Sinopharm Vaccine and the Effect of a Pfizer/BioNtech Booster Vaccine.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 emerged in China in 2019 and has since travelled the world infecting millions. SARS-CoV-2 causes Corona Virus Disease (COVID-19), that has to date taken over 4 million lives. The Kingdom of Bahrain's vaccine roll-out has consisted of Sinopharm's BBIBP-CorV (Sinopharm) and Pfizer/BioNtech's BNT162b2 (Pfizer/BioNtech). Testing for SARS-CoV-2 anti-Spike (S) antibodies is a useful technique in estimating an individual's immune protection against the infection. In this study we evaluated S antibody levels by electro-chemiluminescence immunoassay in 379 individuals double vaccinated with Sinopharm and 15 of whom were given a booster with the Pfizer/BioNtech vaccine. Among our double vaccinated cohort, we found a spectrum of S antibody levels. Indeed, we found that a significant proportion of individuals with low S antibody levels had clinical conditions, which were mainly immune-related disorders. Furthermore, a significant proportion of individuals with low S antibody levels were above 50 years of age. Finally, we observed a significant increase in S antibody levels after the Pfizer/BioNtech booster was administered. These findings reveal that while a large proportion of Sinopharm vaccinated individuals did not develop high levels of antibodies against the S protein, a booster dose of the Pfizer/BioNtech vaccine significantly enhances S antibody levels, revealing this "triple dose" vaccination strategy as a useful method of ensuring protective immunity against SARS-CoV-2.

Perception of online and face to face microbiology laboratory sessions among medical students and faculty at Arabian Gulf University: a mixed method study.

BACKGROUND: The COVID-19 pandemic has impacted all spheres of society including medical education and healthcare systems. In response to the pandemic, there has been a transition in medical education practice from traditional forms of teaching to online instruction delivery and virtual learning. Effective clinical microbiology education involves a combination of 'hands-on' practical learning and instructional delivery of scientific knowledge. Microbiology practical laboratories are critical learning environments offering 'hands-on' learning experiences that cannot be replicated through online learning. We conducted a mixed-methods study to understand the perception of online and face-to-face microbiology laboratory sessions among the medical students and microbiology faculty at Arabian Gulf University (AGU). METHODS: The study participants were third and fourth-year undergraduate medical students and faculty involved in delivering microbiology labs at AGU. The questionnaire consisted of questions ranging from perceived learning style to attitude towards online delivery of microbiology curriculum. After the questionnaire administration (google form), focus group discussion (FGD) was conducted for students and microbiology faculty separately. RESULTS: Among 168 students, 50.6% preferred face-to-face lab sessions as compared to 30.4% who preferred online labs, and 51.8% considered online labs to be an essential addition to face-to-face labs. Among the faculty, 85.7% preferred the face-to-face mode of teaching. All the faculty (100%) disagreed that all the microbiology labs teaching should be online. 57.2% considered online labs to be an essential addition to traditional face-to-face labs. Both faculty and students hold that a blended mode of instructional delivery is vital and indispensable for the transfer of skills and knowledge for microbiology students. CONCLUSION: The blended mode of delivering microbiology laboratory sessions in medical school is successful and well-received by both students and faculty. Students take the responsibility for furthering their own learning and understanding of concepts. Instructors have also noticed that blending learning strategies also successfully enhances the development of cognitive skills and problem-solving abilities in students. A review of the microbiology lab curriculum is necessary to identify content areas that can be delivered effectively through online, face-to-face lab sessions, or both, supported with appropriate tools and infrastructure.

Prevalence and determinants of anemia during the third trimester of pregnancy.

BACKGROUND: Anemia during pregnancy is a significant health problem. We aim to measure the prevalence of anemia in the third trimester of pregnancy in a specific geographical area and identify its risk factors. METHODS: A cross-section study was conducted in the antenatal clinic at Beni-Suef University Hospital on 383 pregnant women in the third trimester of pregnancy. All enrolled women were interviewed about age, education, occupation, family income, vitamin intake, medical history, and nutritional history. A blood sample was examined for hemoglobin concentration from each enrolled woman. RESULTS: The prevalence of anemia was 72%. Multiparity, infrequent antenatal visits, irregular intake of iron supplements, low weekly intake of meat and fruits, and frequent daily tea consumption were identified as risk factors for anemia. About 23.6% of the anemic women had small-for-gestational-age fetuses (RR = 25.2). CONCLUSION: Anemia by the third trimester of pregnancy represents a major health problem in Beni-Suef, Egypt.

Utility of inflammatory biomarkers in patients with COVID-19 infections: Bahrain experience.

Aim: COVID-19 pandemic continues and dearth of information remains considering the utility of various inflammatory biomarkers. We carried out the present study to delineate the roles of these biomarkers in various strata of patients with coronavirus infection. Materials & methods: A retrospective study was carried out after obtaining approval from the relevant Ethics Committee. Patients established with COVID-19 infection as shown by positive real-time quantitative PCR test were included. Details on their demographics, diagnosis, whether they received tocilizumab, and the values of the following biomarkers were obtained: IL-6, C-reactive protein (CRP), serum ferritin, D-dimer, procalcitonin, fibrinogen, lactate dehydrogenase and creatinine kinase. Receiver operating characteristic curves were plotted and correlation of biomarkers with IL-6 were estimated. Results: One-hundred and three patients were recruited. We observed that serum ferritin followed by D-dimer had better predictive accuracy in identifying patients with pneumonia compared with asymptomatic; and CRP in addition to the earlier markers had better accuracy for predicting severe illness compared with mild-moderate. Serum IL-6 levels were significantly higher in patients with severe illness admitted in intensive care unit. Significantly, higher levels of IL-6 and serum ferritin were observed in patients receiving tocilizumab. A trend of increased IL-6 levels was observed immediately following the initiation of tocilizumab therapy followed by a drop thereafter. Conclusion: We observed serum ferritin, D-dimer and CRP to accurately predict patients developing severe COVID-19 infections as well as those at risk of developing COVID pneumonia. A trend in IL-6 levels was observed in patients on tocilizumab therapy.

HLA Matching Status Among Patients Requiring Hematopoietic Stem Cell Transplant: The Need for a National and Regional Stem Cell Bank.

OBJECTIVES: Hematopoietic stem cell transplant is a strategic treatment for many malignant and nonmalignant blood diseases. Finding an HLA-matched donor is a requirement for a successful transplantation. The aim of the current study was to explore indications, demographics, and HLA patient-donor matching status among Bahraini patients requiring this transplant. MATERIALS AND METHODS: Records of 100 patients who required hematopoietic stem cell transplant at the Salmaniya Medical Complex, Ministry of Health tertiary hospital in Bahrain were retrospectively studied. Data were analyzed and compared with data from similar studies. RESULTS: For the 100 patients, 294 potential donors were HLA typed. Indications for transplant included malignant diseases (50%) and hereditary blood diseases (50%). For those in the 0- to 5-year age group, the main indication was acute lymphoblastic leukemia, whereas acute myeloid leukemia was the main indication for those who were >5 years old. Sex distribution showed that 55% of patients were males and 45% were females. With regard to age distribution, 22% of patients were less than 5 years old, 30% were 5 to 17 years old, and 48% were 18 years and older. Patient-donor HLA matching status was 50% HLA identical, 32% haploidentical, 15% more than haploidentical, and 3% less than haploidentical. The number of potential donors per patient ranged from 1 to 11 typed for each patient (average of 2.94 ± 1.86). CONCLUSIONS: The rate of finding a family member as HLA-matched donor for hematopoietic stem cell transplant in our study on Bahraini patients was higher than reports in western countries yet close to other reports from countries with almost similar family sizes. We recommend forming a national Bahrain registry in addition to a regional Eastern Mediterranean stem cell bank to increase the success rate of finding an HLA-matched donor.

Prevalence of hepatitis B e antigenemia in Bahraini hepatitis B patients: A retrospective, single-center study.

BACKGROUND AND AIM: Hepatitis B e (HBe) antigen (HBeAg) is commonly encountered among hepatitis B patients and is indicative of active infection. There is a lack of data in the literature about the prevalence of HBeAg among hepatitis B patients in Bahrain and its impact on the disease. The aims of this study were to investigate the prevalence of HBeAg among a sample of hepatitis B patients in Bahrain and to analyze their associated laboratory profile, radiological characteristics, comorbidities, and complications. METHODS: This was a retrospective record-review study conducted on patients' records at Salmaniya Medical Complex hospital in Bahrain during the period of 2011-2016. All records of hepatitis B patients who had HBeAg tests performed were included in this study. RESULTS: Of 323 patients recruited, 18.9% had positive HBeAg. The prevalence of anti-HBe antibodies and hepatitis B core immunoglobulin G (HBc IgG) differed significantly between patients with positive and negative HBeAg (P < 0.001, P = 0.026, respectively). Alanine transferase and gamma-glutamyl transferase were significantly higher among patients with positive HBeAg (P = 0.017, P = 0.016, respectively). There was no significant difference with regard to the prevalence of hepatitis C virus, human immunodeficiency virus, hepatocellular carcinoma, or liver transplantation between HBe-positive and -negative patients (P ≥ 0.05). CONCLUSION: HBeAg is prevalent among hepatitis B patients in Bahrain and is associated with a significantly different laboratory profile.

Celiac disease in children: Increasing prevalence and changing clinical presentations.

BACKGROUND: Celiac disease (CD) is a chronic autoimmune enteropathy. It results from genetic predisposition and exposure to gluten-containing food. The prevalence and presentation of CD vary among populations. PURPOSE: This study aimed to describe the prevalence and clinical characteristics of CD in children in Bahrain. METHODS: We retrospectively reviewed the medical records of children diagnosed with CD in the pediatric department, Salmaniya Medical Complex, Bahrain, in 1988-2018. Their clinical, biochemical, serological, and histopathological findings were documented. Adherence to the recommended gluten-free diet (GFD) was assessed. RESULTS: Of 86 patients with CD, 67 were included. The CD prevalence was 0.02%. A significant increase in prevalence in the last decade was observed (P<0.0001). Thirty-eight patients (56.7%) were males. The median (interquartile range) age at presentation was 4.45 (1.5-7.3) years. A family history of CD was positive in 13 out of 43 patients (30.2%). Pallor and failure to thrive were the most common presentations. The most frequent associated disease was iron-deficiency anemia in 23 patients (69.7%). Positive serology was found in 32 of 45 patients (71.1%). Marsh-Oberhuber type III was found in 16 of 35 patients (45.7%). Seropositive patients were significantly older (P=0.025) and had more severe duodenal histology (P=0.002). Adherence to GFD was poor in 27 patients (64.3%). CONCLUSION: This study revealed a significant increase in CD prevalence over the last decade. Atypical presentations were frequent. Most patients had poor adherence to GFD.

T Regulatory Cells in Rheumatoid Arthritis with Reference to Anti-Citrullinated Peptide Antibody and TNF-alpha Inhibitor Therapy.

T regulatory cells (Tregs) plays an important role in maintaining self-tolerance and preventing autoimmune diseases by inhibiting proliferation and cytokine production of self-reactive T cells. Controversy was reported regarding the frequency of CD4+CD25+ Tregs in the peripheral circulation of rheumatoid arthritis (RA) patients compared to normal controls. Also, some showed that treatment with TNF-α inhibitor restored the capacity of Tregs. This work aimed to study Tregs in the peripheral blood of RA patients versus control in addition to those on TNF-α inhibitor therapy compared to those who have not received it and to correlate with status of anti-cyclic citrullinated peptide antibody (ACPA). Two groups of RA patients were studied; one on TNF-α inhibitor therapy and the other not. Additionally, age-matched apparently healthy controls were studied. The percentage of CD4+CD25+ T cells in the total lymphocytic cell population was determined by flow cytometry analysis while ACPA concentration was measured by a second-generation peptide-based ELISA. Mean level of Tregs was significantly lower in the studied RA patients compared to the control group. Patients in early disease (0-5 years) had low mean Tregs percentage compared to patients with long duration of disease (> 10 years) (P=0.044). Patients on TNF-α blocker therapy had elevated Tregs percentage relative to patients on methotrexate (MTX) (P=0.022) and other therapies. No effect of gender or age was found on Tregs levels. In RA patients, 85.4% were ACPA seropositive and 65.9% of seropositive patients have concentration of > 100U/ml. The mean Treg percentage was significantly lower in ACPA seronegative group compared to the seropositive group (P=0.013). In conclusion, the studied RA patients have low Treg, and TNF-α blocker therapy increased its number, compared to other therapies.

Is there a role for HLA-G in the induction of regulatory T cells during the maintenance of a healthy pregnancy?

PROBLEM: Pregnancy remains an immune challenge for the uterus that has to adapt to a semi-allogeneic fetus using various regulatory mechanisms. Both HLA-G and regulatory T cells (CD4+  CD25+  FOXP3+  Tregs ) are upregulated in successful pregnancy, but not in abortion. It is unclear if HLA-G plays a role in the upregulation of regulatory cells. METHOD OF STUDY: We measured the level of both sHLA-G and Treg  cells in the blood of healthy pregnant multigravida, unexplained recurrent spontaneous abortions (URSA) and healthy non-pregnant and nulliparous females. We cultured peripheral blood lymphocytes of healthy non-pregnant multigravida females who never had an abortion with lymphocytes of their partners at ratio of 1:1, with and without sHLA-G to detect changes in number of Treg  cells, or relevant cytokines. RESULTS: Soluble HLA-G concentrations and Treg  cells percentage were significantly lower in women with URSA as compared to healthy pregnant multigravida women and were comparable to healthy non-pregnant nulliparous women. Percentage of Tregs  increased between zero time and mixed lymphocyte cultures (MLC) in both cultures with and without recombinant sHLA-G but no significant difference between the two cultures. When stimulated with sHLA-G the mean extracellular IL-10 concentration was unchanged, while the mean INF-γ concentration was slightly higher with no significant difference. Intracellular TGF-ß was higher in CD4+  cells after incubation with sHLA-G. CONCLUSION: The results of this study are consistent with previous studies on the role of sHLA-G and Treg  cells in inducing immune-tolerance in pregnancy. The results also suggest a possible role for HLA-G in the enrichment of Treg  cells.