Gut microbiota composition in patients with Crohn's disease in Saudi Arabia.

Crohn's disease (CD) entails intricate interactions with gut microbiome diversity, richness, and composition. The relationship between CD and gut microbiome is not clearly understood and has not been previously characterized in Saudi Arabia. We performed statistical analysis about various factors influencing CD activity and microbiota dysbiosis, including diagnosis, treatment, and its impact on their quality of life as well as high-throughput metagenomic V3-V4 16S rRNA encoding gene hypervariable region of a total of eighty patients with CD, both in its active and inactive state with healthy controls. The results were correlated with the demographic and lifestyle information, which the participants provided via a questionnaire. α-diversity measures indicated lower bacterial diversity and richness in the active and inactive CD groups compared to the control group. Greater dysbiosis was observed in the active CD patients compared to the inactive form of the disease, showed by a reduction in microbial diversity. Specific pathogenic bacteria such as Filifactor, Peptoniphilus, and Sellimonas were identified as characteristic of CD groups. In contrast, anti-inflammatory bacteria like Defluviitalea, Papillibacter, and Petroclostridium were associated with the control group. Among the various factors influencing disease activity and microbiota dysbiosis, smoking emerged as the most significant, with reduced α-diversity and richness for the smokers in all groups, and proinflammatory Fusobacteria was more present (p<0.05). Opposite to the control group, microbial diversity and richness were lower in CD participants of older age compared to younger ones, and male CD participants showed less diversity compared to women participants from the same groups. Our results describe the first report on the relationship between microbiota and Crohn's disease progress in Saudi Arabia, which may provide a theoretical basis for the application of therapeutic methods to regulate gut microbes in CD.

Outcome of Respiratory Viral Infections in Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Respiratory viral infections (RVIs) commonly cause morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. This study aimed at the prevalence of RVIs in adult HSCT recipients and their outcomes. METHODS: A retrospective observational cohort study was conducted on all adult patients who underwent HSCT in the period between January 2016 and December 2020. Data were retrospectively abstracted from electronic medical records from a total of 400 patients. All cases with polymerase chain reaction-confirmed RVIs based on real-time reverse transcription polymerase chain reaction were included in the data analysis. RESULT: A total of 79 patients had positive results. Sixty-three patients had allogeneic stem cell transplants. Women were 53% of the patients, and the mean age was 32 years (±13.5). The prevalence of documented respiratory virus infections was around 20% during the 4 years of the study. The most common virus was rhinovirus (60.76%), followed by respiratory syncytial virus (15.19%), then parainfluenza (11.39%). Among the 9 patients (11%) who required intensive care unit admission, 67% had lymphopenia (P = .03), 71% had abnormal chest computed tomography scan with pleural effusion (P = .03), 22% required renal support (P = .057), and 2 patients (22%) died (P = .057). CONCLUSIONS: The study highlights the associated morbidity and mortality with RVIs among HSCT recipients and the need for more preventive measures and treatment studies.

Epidemiology and clinical characteristics of Morganella morganii infections: A multicenter retrospective study.

BACKGROUND: Morganella morganii is a Gram-negative, opportunistic pathogen that can cause a variety of infections, including bloodstream infections, especially in those with compromised immune systems. It is often resistant to antibiotics, making it a difficult organism to treat. Limited studies have addressed M. morganii, but the organism is becoming increasingly recognized as a public health threat. More research is needed to understand the epidemiology and virulence factors of M. morganii in Saudi Arabia, as well as to develop effective treatment strategies. METHODS: This retrospective study included all M. morganii bloodstream infections patients admitted to five tertiary care hospitals in Saudi Arabia between 2015 and 2022. RESULTS: The study population included 75 patients (45 males and 30 females) between the age of 53-72 with a 54% ICU admission rate. The most comorbidities were hypertension followed by diabetes. The most common symptoms were fever, cough, shortness of breath, vomiting, and fatigue. The study also found that M. morganii was often resistant to multiple antibiotics, including ciprofloxacin, trimethoprim/sulfamethoxazole, gentamicin, amoxicillin, nitrofurantoin, and colistin. The most common treatment for M. morganii bacteremia was carbapenems, followed by aminoglycosides, ciprofloxacin, and colistin. Source control measures, such as surgery, line removal, drainage, and tissue removal, were also used in some cases. The study found that the in-hospital mortality rate for M. morganii bacteremia was 41%. The risk of mortality was increased in patients who were admitted to the ICU, who were older than 65 years, and who had Klebsiella pneumoniae co-infection. CONCLUSION: M. morganii bacteremia is a serious infection that is often resistant to antibiotics. Elderly patients and patients with comorbidities are at increased risk of mortality. Source control measures and appropriate antibiotic therapy are important for improving outcomes.

Diagnosis and Treatment of Chronic Non-bacterial Osteomyelitis: A Survey on Current Practices Adopted by Pediatric Rheumatologists in Saudi Arabia.

INTRODUCTION: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease usually managed by pediatric rheumatologists (PRs). There is a need for a consensus treatment plan to minimize the diversity in clinical practice in the diagnosis and management of CNO. In this study, we explored the practice of PRs in Saudi Arabia on the diagnosis and treatment of patients with CNO. METHODS: This is a cross-sectional study that was conducted among PRs in Saudi Arabia (May to September 2020). A survey was performed among PRs registered in the Saudi Commission for Health Specialties using an electronic-based questionnaire. The survey consisted of 35 closed-ended questions about the diagnosis and management of CNO patients. We explored the approaches adopted by PRs in diagnosing and monitoring the disease activity, their awareness of clinical possibilities that necessitate ordering bone biopsy, and the treatment choices they considered for CNO patients. RESULTS: We scrutinized data from a total of 77% (n=41/53) PRs who responded to our survey. Magnetic resonance imaging (MRI) was reported as the most frequently used modality in suspected CNO (82%, n=27/33), followed by plain X-ray (61%) and bone scintigraphy (58%). Magnetic resonance imaging of a symptomatic site is the imaging modality of choice for the diagnosis of CNO (82%), Followed by X-ray (61%) and bone scintigraphy (58%). The reasons for performing bone biopsy were unifocal lesions (82%), unusual sites of presentation (79%), and multifocal lesions (30%). The preferred treatment regimens were bisphosphonates (53%), non-steroidal anti-inflammatory drugs alone (43%), or biologics with bisphosphonates (28%). The reasons to upgrade the treatment in CNO included the development of vertebral lesions (91%), the development of new lesions in MRI (73%), and the elevation of inflammatory markers (55%). The disease activity was assessed by history and physical examination (91%), inflammatory markers (84%), MRI of targeted symptomatic site (66%), and a whole-body MRI (41%). CONCLUSIONS: The approach to diagnosis and treatment of CNO varies among PRs in Saudi Arabia. Our findings provide a background for the development of a consensus treatment plan for challenging CNO patients.

Antibiotic Exposure Concurrently with Anti-PD1 Blockade Therapy Reduces Overall Survival in Patients with Child-Pugh Class A Advanced Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide with a poor prognosis. Treatment with immune checkpoint inhibitors (ICIs) has improved overall survival in patients with HCC. However, not all patients benefit from the treatment. In this study, 59 patients with HCC were enrolled from two medical centers in Saudi Arabia, with 34% using antibiotics concurrently with their Nivolumab (anti-PD1 blockade). The impact of antibiotic use on the clinical outcomes of patients with HCC undergoing treatment with anti-PD1 blockade was examined. The patients' overall survival (OS) was 5 months (95% CI: 3.2, 6.7) compared to 10 months (95% CI: 0, 22.2) (p = 0.08). Notably, patients with Child-Pugh A cirrhosis receiving anti-PD1 blockade treatment without concurrent antibiotic use showed a significantly longer median OS reaching 22 months (95% CI: 6.5, 37.4) compared to those who were given antibiotics with a median OS of 6 months (95% CI: 2.7, 9.2) (p = 0.02). This difference in overall survival was particularly found in Child-Pugh class A patients receiving anti-PD1 blockade. These findings suggest that antibiotic use may negatively affect survival outcomes in HCC patients undergoing anti-PD1 blockade, potentially due to antibiotic-induced alterations to the gut microbiome impacting the anti-PD1 blockade response. This study suggests the need for careful consideration when prescribing antibiotics to patients with HCC receiving anti-PD1 blockade.

Transcriptome Changes and Metabolic Outcomes After Bariatric Surgery in Adults With Obesity and Type 2 Diabetes.

Context: Bariatric surgery has been shown to be effective in inducing complete remission of type 2 diabetes in adults with obesity. However, its efficacy in achieving complete diabetes remission remains variable and difficult to predict before surgery. Objective: We aimed to characterize bariatric surgery-induced transcriptome changes associated with diabetes remission and the predictive role of the baseline transcriptome. Methods: We performed a whole-genome microarray in peripheral mononuclear cells at baseline (before surgery) and 2 and 12 months after bariatric surgery in a prospective cohort of 26 adults with obesity and type 2 diabetes. We applied machine learning to the baseline transcriptome to identify genes that predict metabolic outcomes. We validated the microarray expression profile using a real-time polymerase chain reaction. Results: Sixteen patients entered diabetes remission at 12 months and 10 did not. The gene-expression analysis showed similarities and differences between responders and nonresponders. The difference included the expression of critical genes (SKT4, SIRT1, and TNF superfamily), metabolic and signaling pathways (Hippo, Sirtuin, ARE-mediated messenger RNA degradation, MSP-RON, and Huntington), and predicted biological functions (ß-cell growth and proliferation, insulin and glucose metabolism, energy balance, inflammation, and neurodegeneration). Modeling the baseline transcriptome identified 10 genes that could hypothetically predict the metabolic outcome before bariatric surgery. Conclusion: The changes in the transcriptome after bariatric surgery distinguish patients in whom diabetes enters complete remission from those who do not. The baseline transcriptome can contribute to the prediction of bariatric surgery-induced diabetes remission preoperatively.

Safety and Efficacy of Maxitrol in Pediatric Age Group Below Two Years With Adenoid Hypertrophy: A Retrospective Cohort Study.

Introduction Adenoid hypertrophy, a common condition in children, represents one of the common indications for surgery in pediatrics. Medical treatment alone is not effective, and most of the time patients are managed by surgical removal of the adenoid. The aim of this study is to assess the safety and efficacy of intranasal Maxitrol® drops (Novartis Pharmaceuticals, Basel, Switzerland) in pediatric patients with adenoid hypertrophy aged less than two years and to document any side effects during its use. Methods This retrospective cohort study was conducted at King Abdullah Specialist Children's Hospital (KASCH). We reviewed the charts of 86 pediatric patients aged less than two years who were diagnosed with adenoid hypertrophy between 2015 and 2018. Patients were grouped according to the type of intervention (use of Maxitrol®, and no use). The follow-up time was up to one year. Results Out of 86 patients, 55 (63.9%) patients had adenoid hypertrophy alone and 31 (36.1%) had adenoid hypertrophy plus another disease. Patients with obstructive sleep apnea symptoms (p=0.026) and grade of adenoid (p=0.040) showed a significant relationship with surgery booking after one year. The probability of booking for surgery for those who used Maxitrol® was 1.394 times higher than for those who were not using it (odds ratio [OR]=1.394; 95% confidence interval [CI]=0.549-3.537). Suppression of growth and eye complications were not reported in any of our patients. Conclusion In this small sample, the use of Maxitrol® in the pediatric age group below two years with adenoid hypertrophy was safe and effective in relieving nasal symptoms; however, eventually, surgery was needed in most of our patients. Suppression of growth and eye complications were not reported in any of our patients during the follow-up time.

The Incidence and Risk Factors of Cholelithiasis Development After Bariatric Surgery in Saudi Arabia: A Two-Center Retrospective Cohort Study.

Background: Rapid weight loss after bariatric surgery is a known risk factor for cholelithiasis development. This study aimed to estimate the incidence of cholelithiasis following bariatric surgery among morbidly obese patients who underwent bariatric surgery. Methods: This is a retrospective cohort study of all morbidly obese patients who underwent bariatric surgery in King Abdulaziz Medical City (Riyadh, Saudi Arabia) or King Abdulaziz Hospital (Al Ahsa, Saudi Arabia) between January 2015 and December 2018. Patients with a history of cholecystectomy or previous bariatric surgery were excluded. We estimated the incidence rate of cholelithiasis among the cohort. We also examined the associated risk factors of cholelithiasis development. Results: The study cohort contained 490 patients (38.7% males; 61.43% females) with a mean age of 36.87 ± 11.44 years. Most patients (58.54%) were followed up for 12 months. The incidence of cholelithiasis post-operation was 6.53% (n = 32). The average period of cholelithiasis formation was 12-24 months. The percentage of total weight loss (TWL%) was significantly associated with the development of cholelithiasis post-operatively. Conclusion: A significant association was found between weight loss following bariatric surgery and the incidence of cholelithiasis. Gender, age, and comorbidities were not associated with the formation of cholelithiasis. We recommend regular follow-up appointments with thorough patient education about gradual weight loss to reduce the risk of developing cholelithiasis.

A Trial of Favipiravir and Hydroxychloroquine combination in Adults Hospitalized with moderate and severe Covid-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. TRIAL DESIGN: This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. PARTICIPANTS: All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. INTERVENTION AND COMPARATOR: The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . MAIN OUTCOMES: The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). RANDOMISATION: Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. BLINDING (MASKING): This is an Open label study and only the analyst will be blinded during the study conduct. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). TRIAL STATUS: Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04392973 , 19 May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels.

MERS-CoV seronegative and seropositive camels received a single intramuscular dose of ChAdOx1 MERS, a replication-deficient adenoviral vectored vaccine expressing MERS-CoV spike protein, with further groups receiving control vaccinations. Infectious camels with active naturally acquired MERS-CoV infection, were co-housed with the vaccinated camels at a ratio of 1:2 (infected:vaccinated); nasal discharge and virus titres were monitored for 14 days. Overall, the vaccination reduced virus shedding and nasal discharge (p = 0.0059 and p = 0.0274, respectively). Antibody responses in seropositive camels were enhancedby the vaccine; these camels had a higher average age than seronegative. Older seronegative camels responded more strongly to vaccination than younger animals; and neutralising antibodies were detected in nasal swabs. Further work is required to optimise vaccine regimens for younger seronegative camels.