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Hereditary angioedema (HAE) is a potentially life-threatening autosomal dominant disorder affecting roughly 1:50,000 individuals. It is commonly characterized by swelling of the larynx, gastrointestinal tract, extremities, and skin. There is growing genetic heterogeneity associated with this disease but more than 95% of mutations are found in SERPING1, the gene which encodes complement 1 inhibitor (C1-INH). HAE cohorts from several populations have been published but no large scale study has been reported from the Arab world to date. Here we document the clinical and genetic findings of HAE patients from a single Saudi institution, which is a major referral center at the national level. A total of 51 patients across 17 unrelated families were recruited including two large multi-generational families, of which one contained an in-frame exonic deletion that was resolved through MLPA. Two cases were negative for all the genes we tested (including F12, PLG, ANGPT1, MYOF, KNG1, and HS3ST6). The predominant HAE subtype in our cohort was type I, at 76%. We were able to uncover a mutation in 49 patients (96%). No type III (normal C1-INH) patients were encountered in the clinic, suggesting that this subtype does not play a major role in HAE pathogenesis in Saudi Arabia. Additionally, the existence of four patients with consistently normal complement 4 (C4) levels alongside abnormal C1-INH profiles highlights the utility of dual screening for both proteins in suspected patients.

Saad AlShareef,1 Christine F McDonald,2– 4 Joy Lee2,5 1Department of Medicine, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 13317-4233, Saudi Arabia; 2Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Australia; 3Institute for Breathing and Sleep, Heidelberg, Australia; 4Faculty of Medicine, University of Melbourne, Melbourne, Australia; 5School of Public Health & Preventive Medicine, Monash University, Melbourne, AustraliaCorrespondence: Saad AlShareef, Email drsaad321@hotmail.comBackground: Although there have been indirect comparisons of the relative efficacy of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in severe asthma patients, long-term direct head-to-head comparisons are lacking. Here, we (i) examined the effect of mepolizumab, benralizumab, and omalizumab on symptom control and lung function parameters over time; and (ii) compared the efficacy of mepolizumab and benralizumab on symptom control and lung function outcomes.Methods: This was a retrospective study of patients with severe asthma taking anti-IgE (omalizumab; n = 24), anti-IL5 (mepolizumab, n = 23), or anti-IL-Rα (benralizumab; n = 12) therapy. Data were extracted on (i) Asthma Control Questionnaire (ACQ-5) scores; (ii) forced expiratory volume over 1 second (FEV1); and (iii) peak expiratory flow rate (PEFR) at 4– 6 months and 1 year and documented reductions in exacerbations. Clinical and lung function outcomes were compared between patients taking mepolizumab and benralizumab and over time.Results: There were significant decreases in ACQ-5 scores (3.3 ± 0.93 to 1.7 ± 0.98 for mepolizumab, 3.5 ± 0.72 to 1.6 ± 0.89 for benralizumab, and 3.5 ± 0.95 to 1.7 ± 1.1 for omalizumab; t-test, all p < 0.0001) but not increases in FEV1 and PEFR for all three agents after 4– 6 months of therapy, which persisted but did not decrease further at one year. There were trends toward a greater percentage increase in FEV1 and PEFR from baseline and a decrease in the number of exacerbations in patients taking benralizumab than those taking mepolizumab.Conclusion: Although limited by a small sample size, this real-world, head-to-head comparison of mepolizumab and benralizumab is consistent with comparative data on asthma biologicals and indirect comparisons showing no major difference in efficacy. The study also generates new testable hypotheses about the efficacy of asthma biologicals in different patient populations.Keywords: asthma, benralizumab, exacerbations, omalizumab, mepolizumab, monoclonal antibody

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-alpha/beta (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-gamma is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling. ANRS Nord-Sud ; CIBSS ; CODI ; Comité para el Desarrollo de la Investigación ; Fulbright Future Scholarship

Background: Protocols for bowel management have been used adequately among postoperative patients to maintain the normal GIT function and prevention of ileus among critically ill patients. Objectives: Evaluating the knowledge, attitude and practice (KAP) of medical students about paralytic ileus after colon surgery at Kingdom of Saudi Arabia (KSA). Methods: It is a randomized cross sectional study that was conducted during the period from March 2018 to June 2018, at Saudi Arabia among 320 medical students at the 5 thacademicyear.The study was based on a questionnaire sheet with an interview that included questions about knowledge, attitude and practice pattern of the students about paralytic ileus after surgery. Results: The study included 320 medical students from different universities at the stage of fifth academic year. All of the included subjects had good knowledge about the definition of ileus, its symptoms and the initial treatment with intravenous fluids. Most of them have adequate knowledge about effect of epidural anesthesia on the duration of ileus (82.5%), the complications of ileus (67.5%), the paralysis of the bowel (86.3%) and the diagnostic importance of CT (87.8%). The attitude of most of the participants was good toward the importance of good nursing and efficient doctors to overcome the risks of postoperative ileus, the efficiency of bowel protocols and increasing the knowledge of the staff is adequate for prevention of ileus. The practice pattern was found to be adequate among the majority of participants as 81 % would take care while using analgesics and sedatives and 90% would encourage movement of patient when possible. All of the subjects had adequate practice toward managing dietary nutrition, constipation and diarrhea. Conclusion: The level of knowledge was adequate among most of the students which resulted in proper attitude and practicing pattern that encourage educating the health staff about ileus and how to be efficient in managing the bowel protocols.

Hemorrhoid ailment is one of the most common factor patients seek analysis by a colon and anal specialist. Most of piles can be managed nonoperatively with medical management or office-based procedures. In this paper surgical treatment methods, their indications and complications are reviewed. Conducted a detailed search among electronic databases: MEDLINE, EMBASE, and Google scholar, searching in literature for articles related to surgical options and indication of hemorrhoidectomy. Studies were included as publication up to 2018. The surgical alternatives for the therapy of hemorrhoids are lots of; and although the majority of surgical strategies are based upon the ligation and excision principles, more recent methods are made to lessen tissue breakdown with the goal of decreasing postoperative discomfort and bleeding. Indications for surgical hemorrhoidectomy include symptomatic hemorrhoids too comprehensive for nonoperative management, failure of medical therapy, and concomitant conditions, such as anal fissures or ulcers, that call for surgery. Standard hemorrhoidectomy, including open and shut methods, is accepted as the gold-standard for surgical treatment of hemorrhoids worldwide.