Ali H. Hajeer

Low-dose hydrocortisone in patients with cirrhosis and septic shock: a randomized controlled trial

Background Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis. However, the effect of corticosteroid replacement on mortality in this high-risk group remains unclear. We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock. Methods We enrolled patients with cirrhosis and septic shock aged 18 years or older in a randomized double-blind placebo-controlled trial. Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin. Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved, followed by steroid tapering over eight days. The primary outcome was 28-day all-cause mortality. Results The trial was stopped for futility at interim analysis after 75 patients were enrolled. Relative adrenal insufficiency was diagnosed in 76% of patients. Compared with the placebo group (n = 36), patients in the hydrocortisone group (n = 39) had a significant reduction in vasopressor doses and higher rates of shock reversal (relative risk [RR] 1.58, 95% confidence interval [CI] 0.98–2.55, p = 0.05). Hydrocortisone use was not associated with a reduction in 28-day mortality (RR 1.17, 95% CI 0.92–1.49, p = 0.19) but was associated with an increase in shock relapse (RR 2.58, 95% CI 1.04–6.45, p = 0.03) and gastrointestinal bleeding (RR 3.00, 95% CI 1.08–8.36, p = 0.02). Interpretation Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock. Despite initial favourable effects on hemodynamic parameters, hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects. (Current Controlled Trials registry no. ISRCTN99675218.)

Middle East Respiratory Syndrome

The Middle East respiratory syndrome is caused by a coronavirus that was first identified in Saudi Arabia in 2012. Periodic outbreaks continue to occur in the Middle East and elsewhere. This report provides the latest information on MERS.

Chances of finding an HLA-matched sibling: The Saudi experience.

Hematopoietic cell transplantation (HCT) remains the fundamental procedure to treat many diseases. Its success depends greatly on the degree of HLA matching between donor and recipient. Although the number of successful HCT procedures carried out worldwide increases every year, many patients remain unable to receive this treatment because of the difficulty of finding an HLA-matching donor. In our center, we identified the HLA types for all HCT candidates and their siblings in an attempt to determine the chance of finding a full HLA-matching sibling. Overall, 60% of patients had a chance of finding an HLA-matching sibling. The chance of finding a matching sibling was 43% in patients aged birth to 5 years, compared with 68% in those aged 20+ years. In our Saudi population, patients in need of HCT have a greater chance of finding an HLA-matching sibling than is reported in most Western countries. This is mainly because of the larger number of siblings in most Saudi families. Younger children requiring HCT have a lesser chance of finding an HLA-matching sibling. Our data demonstrate that even in a country with relatively large families, it is still essential to consider alternative donor strategies, such as adult unrelated donors, unrelated umbilical cord blood units, and haploidentical donors.

Novel point mutations and mutational complexes in the enhancer II, core promoter and precore regions of hepatitis B virus genotype D1 associated with hepatocellular carcinoma in Saudi Arabia

In this study, a cohort of 182 patients [55 hepatocellular carcinoma (HCC) and 127 non‐HCC] infected with hepatitis B virus (HBV) in Saudi Arabia was investigated to study the relationship between sequence variation in the enhancer II (EnhII), basal core promoter (BCP) and precore regions of HBV genotype D (HBV/D) and the risk of HCC. HBV genotypes were determined by sequencing analysis and/or enzyme‐linked immunosorbent assay. Variations in the EnhII, BCP and precore regions were compared between 107 non‐HCC and 45 HCC patients infected with HBV/D, followed by age‐matched analysis of 40 cases versus equal number of controls. Age and male gender were significantly associated with HCC (p = 0.0001 and p = 0.03, respectively). Serological markers such as aspartate aminotransferase, albumin and anti‐HBe were significantly associated with HCC (p = 0.0001 for all), whereas HBeAg positivity was associated with non‐HCC (p = 0.0001). The most prevalent HBV genotype was HBV/D (94%), followed by HBV/E (4%), HBV/A (1.6%) and HBV/C (0.5%). For HBV/D1, genomic mutations associated with HCC were T1673/G1679, G1727, C1741, C1761, A1757/T1764/G1766, T1773, T1773/G1775 and C1909. Age‐ and gender‐adjusted stepwise logistic regression analysis indicated that mutations G1727 [odds ratio (OR) = 18.3; 95% confidence interval (CI) = 2.8–118.4; p = 0.002], A1757/T1764/G1766 (OR = 4.7; 95% CI = 1.3–17.2; p = 0.01) and T1773 (OR = 14.06; 95% CI = 2.3–84.8; p = 0.004) are independent predictors of HCC development. These results implicate novel individual and combination patterns of mutations in the X/precore region of HBV/D1 as predictors of HCC. Risk stratification based on these mutation complexes would be useful in determining high‐risk patients and improving diagnostic and treatment strategies for HBV/D1.

Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia.

Efficacy testing will be challenging because of the small pool of donors with sufficiently high antibody titers.

HLA class I and class II polymorphisms in Saudi patients with myasthenia gravis

Myasthenia gravis (MG) is a rare autoimmune disease of the neuromuscular junction. MG has been shown to be associated with many HLA antigens in different populations. Here we have analysed the frequency of HLA‐A, B, DR and DQ in a group of Saudi MG patients and compared their results to a group of healthy controls. MG in Saudi patients is found to be associated with HLA‐A*23, B*08, B*18, DRB1*16 and DRB1*13. The strongest association was with HLA‐B*08, which was associated with young age at onset and female gender. Our results are in line with other published results from around the world and warrant fine mapping of the area using microsatellite to map the disease gene.

HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 allele and haplotype frequencies in Saudis using next generation sequencing technique

Next generation sequencing (NGS) is a promising technique that can reveal the entire gene sequences and to the highest possible resolution without any phase ambiguities. We have used this technique to investigate the frequencies of HLA-A, -B, -C, -DRB1 and -DQB1 in a Saudi cohort of healthy individuals. We used NGS using the 454 genome sequence (GS) FLX System and Conexio assign atf 454 software to human leukocyte antigen (HLA) genotype eight class I and class II loci. A total of 158 healthy Saudi adults were analyzed. The most frequently observed allele for HLA-A was HLA-A*02:01:01:01 (13.6%); for HLA-B, HLA-B*50:01:01 (15.8%); for HLA-C, HLA-C*06:02:01:01 (18.7%); for HLA-DRB1, HLA-DRB1*07:01:01:01 (26.6%); and for HLA-DQB1, HLA-DQB1*02:01:01 (20.3%). The most common four loci haplotypes in the Saudi population were HLA-A*24:02:01:01-B*08:01:01-C*07:02:01:01-DRB1*03:01:01:01 and HLA-A*23:01:01-B*50:01:01-C*06:02:01:01-DRB1*07:01:01:01.. We have used a highly informative technique for HLA typing of a Saudi healthy cohort to establish allele and haplotype frequencies. These results should prove useful for population studies, disease associations and future planning of the unrelated bone marrow donor registry.

Etomidate and mortality in cirrhotic patients with septic shock.

BackgroundClinical effects and outcomes of a single dose etomidate prior to intubation in the intensive care setting is controversial. The aim of this study is to evaluate the association of a single dose effect of etomidate prior to intubation on the mortality of septic cirrhotic patients and the impact of the subsequent use of low dose hydrocortisone.MethodsThis is a nested-cohort study within a randomized double blind placebo controlled study evaluating the use of low dose hydrocortisone in cirrhotic septic patients. Cirrhotic septic patients ≥ 18 years were included in the study. Patients who received etomidate prior to intubation were compared to those who did not receive etomidate for all cause 28-day mortality as a primary outcome.ResultsSixty two intubated patients out of the 75 patients randomized in the initial trial were eligible for this study. Twenty three of the 62 intubated patients received etomidate dose prior to intubation. Etomidate use was not associated with all cause 28-day mortality or hospital mortality but was associated with significantly higher ICU mortality (91% vs. 64% for etomidate and controls groups, respectively; p = 0.02). Etomidate patients who received subsequent doses of hydrocortisone required lower doses of vasopressors and had more vasopressor-free days but no improvement in mortality.ConclusionsIn this group of septic cirrhotic patients with very high mortality, etomidate increased ICU mortality. Subsequent use of hydrocortisone appears to have no benefit beyond decreasing vasopressor requirements. The lowest mortality was observed in patients who did not receive etomidate but received hydrocortisone.

Association between antibiotic use and risk of prostate cancer

The association between antibiotics and risk of cancer has been addressed in different studies, most of which were addressing breast cancer. The objective of this study was to assess the association between antibiotics use and risk of prostate cancer. We carried out a population‐based case‐control study using data from Saskatchewan Health administrative databases (Canada) between the years 1981 and 2000. Cases identified by the Saskatchewan Cancer Agency were matched to 4 controls, using incidence density sampling. The effect of dosage and timing of antibiotic use, over a minimum of 15 years before diagnosis, on prostate cancer risk was assessed. Number of prescriptions and number of tablets were used as exposure definitions. Moreover, the effect of different classes of antibiotics on prostate cancer was also studied. A total of 4,052 prostate cancer cases and 16,208 matched controls were included in this study. Antibiotics exposure (number of prescriptions) during the period of 1–15 years in the past was significantly associated with an increased risk of prostate cancer; RR = 1.69, 2.61, 2.71, and 2.83 for the 4 quartiles, respectively, p‐trend = 0.0001. When number of units was taken as the exposure definition, similar results were found. We did not find any effect of the timing or class of antibiotic exposure on prostate cancer risk. We found a dose‐dependent association between antibiotics exposure up to 15 years in the past and risk of prostate cancer. However, the lack of temporal trends and the absence of class specific effects suggest a noncausal relationship.

Comparison of the tuberculin skin test and Quanti-FERON-TB Gold In-Tube (QFT-G) test for the diagnosis of latent tuberculosis infection in dialysis patients

Dialysis patients are more likely than the general population to develop active tuberculosis (TB). In these patients, the availability of a highly sensitive and specific test to diagnose latent TB will ensure earlier treatment and decreased progression to active disease. In the current study, the Quanti-FERON-TB Gold In-Tube (QFT-G) test was compared with the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI) among 200 hemodialysis patients and 15 confirmed TB disease cases in a tertiary care center in Saudi Arabia. Among the LTBI cases, 26 (13%) were TST positive, and 65 (32.5%) were positive by the QTF-G test, with an overall agreement between the 2 tests of 75.5% (k=0.34) being observed. Among the confirmed tuberculosis disease cases, none were positive by TST, and 10 (66.7%) were positive by the QTF-G test, resulting in an overall agreement of 33.3% (k=0). A comparison between the TST and the QTF-G test was performed based on the sensitivity, specificity, and area under the curve (AUC) obtained for the tests. The QTF-G test was more sensitive and less specific than the TST in predicting the confirmed TB disease cases. When we tested the correspondence of the AUC values between the 2 diagnostic modalities, the obtained p-value was 0.0003. In conclusion, the AUCs of the examined diagnostic modalities are significantly different in predicting LTBI and tuberculosis.