Biallelic TLR4 deficiency in humans.

BACKGROUND: Toll-like receptors (TLRs) mediate functions for host defense and inflammatory responses. TLR4 recognizes LPS, a component of gram-negative bacteria as well as host-derived endogenous ligands such as S100A8 and S100A9 proteins. OBJECTIVE: We sought to report phenotype and cellular function of individuals with complete TLR4 deficiency. METHODS: We performed genome sequencing and investigated exome and genome sequencing databases. Cellular responses were studied on primary monocytes, macrophages, and neutrophils, as well as cell lines using flow cytometry, reporter, and cytokine assays. RESULTS: We identified 2 individuals in a family of Qatari origin carrying a homozygous stop codon variant p.Q188X in TLR4 presenting with a variable phenotype (asymptomatic and inflammatory bowel disease consistent with severe perianal Crohn disease). A third individual with homozygous p.Y794X was identified in a population database. In contrast to hypomorphic polymorphisms p.D299G and p.T399I, the variants p.Q188X and p.Y794X completely abrogated LPS-induced cytokine responses whereas TLR2 response was normal. TLR4 deficiency causes a neutrophil CD62L shedding defect, whereas antimicrobial activity toward intracellular Salmonella was intact. CONCLUSIONS: Biallelic TLR4 deficiency in humans causes an inborn error of immunity in responding to LPS. This complements the spectrum of known primary immunodeficiencies, in particular myeloid differentiation primary response 88 (MYD88) or the IL-1 receptor-associated kinase 4 (IRAK4) deficiency that are downstream of TLR4 and TLR2 signaling.

Prevalence and trends of transfusion transmissible infections among blood donors in the State of Qatar, 2013-2017.

BACKGROUND: Millions of lives around the world are being saved annually through blood transfusion. However, blood transfusion is among the essential vehicles for transmitting infections. The overall prevalence of Transfusion Transmissible Infections among blood donors differs around the world, reflecting the variation in the prevalence of these infections. This study aims to assess the prevalence and trends of Transfusion Transmissible Infections among blood donors in Qatar. METHODS: This is a cross-sectional study utilizing donation records of 5 years from January 2013 to December 2017. We included in the study results for all screening and confirmatory tests for Hepatitis B Virus, Hepatitis C Virus, Human T-lymphotropic Virus-I/II, Syphilis and Malaria. RESULTS: Among the 190,509 donations received at the donation centre during the study period, about 91% of donations were received from males and 9% from females. The overall positivity rate for all tests was 1.87, 2.23, 1.78, 2.31, 2.67% for the years 2013 through 2017, with an increasing yearly trend by 6% each year. The overall positivity rates for Hepatitis C Virus, Human T-lymphotropic Virus-I/II, Hepatitis B Virus, Syphilis and Malaria (2013-2017) were 0.60, 0.18, 0.30, 0.43 and 0.20%, respectively. CONCLUSION: The overall positivity rate of all tests combined for the Transfusion Transmissible Infections demonstrated a gradually increasing trend from 2013 to 2017. However, the trend for each infection (Hepatitis C Virus, Hepatitis B Virus, Syphilis and Malaria) was fluctuating except for Human T-lymphotropic Virus-I/II, which was increasing. Supporting the development of effective prevention and control strategies requires further comprehensive investigations for better estimation of the burden of these infections.

Mean Platelet Volume, Red Cell Distribution Width to Platelet Count Ratio, Globulin Platelet Index, and 16 Other Indirect Noninvasive Fibrosis Scores: How Much Do Routine Blood Tests Tell About Liver Fibrosis in Chronic Hepatitis C?

BACKGROUND AND AIM: Many indirect noninvasive scores to predict liver fibrosis are calculated from routine blood investigations. Only limited studies have compared their efficacy head to head. We aimed to compare these scores with liver biopsy fibrosis stages in patients with chronic hepatitis C. MATERIALS AND METHODS: From blood investigations of 1602 patients with chronic hepatitis C who underwent a liver biopsy before initiation of antiviral treatment, 19 simple noninvasive scores were calculated. The area under the receiver operating characteristic curves and diagnostic accuracy of each of these scores were calculated (with reference to the Scheuer staging) and compared. RESULTS: The mean age of the patients was 41.8±9.6 years (1365 men). The most common genotype was genotype 4 (65.6%). Significant fibrosis, advanced fibrosis, and cirrhosis were seen in 65.1%, 25.6, and 6.6% of patients, respectively. All the scores except the aspartate transaminase (AST) alanine transaminase ratio, Pohl score, mean platelet volume, fibro-alpha, and red cell distribution width to platelet count ratio index showed high predictive accuracy for the stages of fibrosis. King's score (cutoff, 17.5) showed the highest predictive accuracy for significant and advanced fibrosis. King's score, Göteborg university cirrhosis index, APRI (the AST/platelet count ratio index), and Fibrosis-4 (FIB-4) had the highest predictive accuracy for cirrhosis, with the APRI (cutoff, 2) and FIB-4 (cutoff, 3.25) showing the highest diagnostic accuracy.We derived the study score 8.5 - 0.2(albumin, g/dL) +0.01(AST, IU/L) -0.02(platelet count, 10(9)/L), which at a cutoff of >4.7 had a predictive accuracy of 0.868 (95% confidence interval, 0.833-0.904) for cirrhosis. CONCLUSIONS: King's score for significant and advanced fibrosis and the APRI or FIB-4 score for cirrhosis could be the best simple indirect noninvasive scores.

Down the wrong road - a case report of inadvertent nasogastric tube insertion leading to lung laceration and important pearls to avoid complications.

Nasogastric tube (NGT) insertion is a common procedure performed by residents and nursing staff to access the stomach. Although an apparently simple procedure, it is associated with technical difficulties and complications if proper care is not taken during insertion. We present a case of a 79-year-old female with multiple comorbidities who had a percutaneous enteral gastrostomy tube removed due to infection of an insertion site wound and a NGT was inserted for feeding. A few minutes post-insertion the patient developed shortness of breath and a drop in oxygen saturation. An immediate chest X-ray showed the NG tube traversing along the course of the trachea and the right main bronchus into the right upper abdomen with right-sided pneumothorax. The NG tube was immediately removed and a right chest drain inserted. Subsequent imaging showed right-sided pneumothorax with evidence of lung laceration and underlying lung collapse and diaphragmatic injury. The patient underwent a prolonged course of hospitalisation due to hospital-acquired pneumonia before being discharged upon clinical improvement. We highlight the fact that a simple and routine procedure such as NGT insertion can have devastating complications if due care is not taken. Along with a literature review, we provide and compare different methods to confirm correct placement of a NGT. The article also discusses important pearls for practising physicians and nursing staff to avoid such complications. Owing to the frequency of the procedure in hospitals and long-term care units, appropriate awareness among medical staff is necessary.

Emerging role for colorectal cancer screening in Asian countries.

BACKGROUND AND AIM: Colorectal cancer (CRC) is one of the leading causes of cancer related mortality globally. Though Asia has traditionally been considered a relatively low incidence area for colorectal cancer, the incidence is reportedly increasing. The Asia Pacific Working Group for Colorectal Cancer has recommended screening of individuals at average risk starting from 50 years of age. Based on these recommendations we conducted a pilot study to assess the need and feasibility of a colorectal cancer screening program in the state of Qatar. METHODS AND RESULTS: We screened 1385 individuals by fecal immunochemical testing for occult blood, at the primary health center level and positive cases were referred for colonoscopy. Among those who tested positive for fecal occult blood, we picked up five patients with cancers and seven with neoplastic polyps. CONCLUSION: Our results compare with the yield of screening programs in western countries thus suggesting an emerging role for colorectal cancer screening in Asian countries.

Uncommon gastrointestinal complications of enteric fever in a non-endemic country.

Enteric fever is a systemic illness with varying presentation. It is an important infectious disease in developing countries and also in industrialized countries where many migrants reside. Enteric fever can result in complications in different organ systems and delay in identification and prompt treatment can be fatal. The important gastrointestinal complications of enteric fever include hepatitis, intestinal ulcers, bleeding and bowel perforation. We report three relatively uncommon complications of enteric fever in Qatar, a non-endemic country, ileal ulcer presenting with hematochezia; duodenal ulcer with polyserositis, cholestatic hepatitis and bone marrow suppression; enteric fever related peritonitis.

Gastric glomus tumor presenting with massive upper GI bleeding: A challenging to diagnose and treat tumor.

Glomus tumors are infrequent benign tumors that originate from the glomus body and can be found anywhere in the body including the gastrointestinal tract. It is rare that gastric glomus tumors present with life-threatening upper GI bleeding. Diagnosis of gastric glomus tumors poses a challenge due to overlapping endoscopic and endosonographic features with other gastric subepithelial lesions, and the final diagnosis may not be clear until after surgical resection and pathological examination. We report the case of a 61-year-old patient who presented with massive upper GI bleeding secondary to an ulcerated gastric glomus tumor that was eventually treated with surgical wedge resection of the tumor.

High Adenoma Detection Rates in Fecal Immunochemical Test-Based Colorectal Cancer Screening: Interim Results of the National Bowel Cancer Screening Program in Qatar.

INTRODUCTION: Colorectal cancer is one of the most common cancers globally. Recent reductions in mortality rates have been primarily attributed to screening programs. The State of Qatar established a national bowel cancer screening program in 2016. METHODOLOGY: Fecal immunochemical testing (FIT) was used for average-risk individuals aged 50 to 74 years. Fecal immunochemical testing -positive participants were referred for total colonoscopy to detect polyps and cancers. RESULTS: Among 32,751 FIT invitees, 11,130 took the test, and 758 (6%) of those were FIT positive. Of these, 375 (56.13%) participants underwent a colonoscopy, and polyps were detected in 198 (52.8%) and cancers in 19 (5.1%) participants. The adenoma detection rate exceeded 40%. DISCUSSION AND CONCLUSION: The high yield of polyps and cancers in the screening program justifies an active, resource-intensive, and organized bowel cancer screening effort. The high adenoma detection rate in a FIT-based program warrants recalibration of target adenoma detection rates in screening programs.

Reporting of RT-PCR cycle threshold (Ct) values during the first wave of COVID-19 in Qatar improved result interpretation in clinical and public health settings.

Introduction. The cycle threshold (Ct) value in real-time PCR (RT-PCR) is where a target-specific amplification signal becomes detectable and can infer viral load, risk of transmission and recovery. Use of Ct values in routine practice is uncommon.Gap Statement. There is a lack of routine use of Ct values when reporting RT-PCR results in routine practice.Aim. To automatically insert Ct values and interpretive comments when reporting SARS-CoV-2 RT-PCR to improve patient management.Methodology. Routine Ct values across three different RT-PCR platforms were reviewed for concordance at presentation and clearance in patients with COVID-19. An indicative threshold (IT) linked to viral clearance kinetics was defined at Ct30 to categorize Ct values as low and high, reflecting high and low viral loads respectively.Results. The different gene targets of each platform showed high correlation and kappa score agreement (P<0.001). Average Ct values were automatically generated with values ≤Ct30 reported as positive and >Ct30 as reactive; interpretive comments were added to all reports. The new reporting algorithm impacted on: physician interpretation of SARS-CoV-2 results; patient management and transfer; staff surveillance; length of stay in quarantine; and redefinition of patient recovery.Conclusion. Incorporation of Ct values into routine practice is possible across different RT-PCR platforms and adds useful information for patient management. The use of an IT with interpretive comments improves clinical interpretation and could be a model for reporting other respiratory infections. Withholding Ct values wastes useful clinical data and should be reviewed by the profession, accreditation bodies and regulators.

Prognostic tools and candidate drugs based on plasma proteomics of patients with severe COVID-19 complications.

COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients.

Percutaneous Endoscopic Gastrostomy Tube Insertion in Patient With Situs Inversus Totalis.

Situs inversus totalis (SIT) is a rare congenital condition in which the abdominal and thoracic organs are completely reversed from right to left, and their diagnosis is usually incidental. However, patients with SIT need a comprehensive radiological evaluation before undertaking any invasive procedures. Percutaneous endoscopic gastrostomy (PEG) insertion is an effective procedure for enteral feeding in patients with difficulty swallowing. Many post-procedural complications have been reported after the PEG procedure. We performed PEG insertion in an 85-year-old Qatari SIT patient, who was admitted to the hospital as a case of aspiration pneumonia and on nasogastric feeding tube (NGT). The procedure was started while the patient was in left lateral decubitus position as in normal anatomy patients after careful examination and in accordance with the general principles of PEG insertion. No complications were seen, neither intraoperative nor postoperative in two months follow-up. We suggest that in a patient with SIT, PEG insertion can be performed while the patient is in left decubitus position with no additional risk or extra intraoperative time if the pre-operative anatomical position of vital organs is carefully evaluated.

Hidden Nematode Causing Recurrent Pancreatitis: A Case Report.

Even though hepatobiliary ascariasis has been found to cause pancreatitis, it is rare in Qatar and other countries in the Middle East. In this report, we present a case of biliary duct ascariasis causing recurrent pancreatitis. A 46-year-old woman from the Philippines presented with recurrent clinical and biochemical features of acute pancreatitis and was found to have hepatobiliary ascariasis. She was successfully treated with endoscopic retrograde cholangiopancreatography (ERCP) and antihelminthic medication. Although hepatobiliary ascariasis as a cause of pancreatitis is rare, it should be considered in patients with recurrent pancreatitis without an obvious cause, especially in those from endemic areas or those who have visited endemic areas.

Myalgia during interferon therapy--does it warrant monitoring muscle enzymes?

Myositis during interferon therapy is a known but rare adverse event. However the clinician may overlook the symptom-complex of proximal muscle weakness and myalgia, seen in myositis, since myalgia is a commonly reported side effect of therapy. In this context then, is there a role for monitoring muscle enzymes to detect subclinical myositis in patients on interferon therapy? We prospectively monitored the creatine kinase (CK) and lactate dehydrogenase (LD) levels in all our patients who reported myalgia during treatment and noted that muscle enzymes remained within normal range throughout the duration of treatment. This excluded the possibility of subclinical myositis in myalgic patients and thus led us to conclude that routine monitoring of muscles enzymes is neither necessary nor beneficial.

Jejunal Varices Bleeding in a Patient with Extensive Portomesenteric Thrombosis Secondary to Factor V Leiden Mutation: A Management Dilemma.

Ectopic varices are portosystemic collaterals that occur away from the gastroesophageal junction and account for 1-5% of all variceal bleeding. Its occurrence in the jejunum is rare. Most common cause of ectopic jejunal varices is portal hypertension especially in those patients who have undergone prior abdominal surgery. Portomesenteric thrombosis is a rare cause of ectopic jejunal varices. Ectopic varices are rare cause of obscure GI bleeding and hence should be always suspected in patients with history of portal hypertension who present with GI bleeding and have negative upper and lower GI endoscopies. Management of patients with ectopic varices is often very challenging and requires multidisciplinary approach. Therapeutic options include endoscopic therapy, interventional radiologic procedures, surgically creating shunting, or surgical resection. We present the case of a 52-year-old patient who was on anticoagulation for extensive portomesenteric thrombosis secondary to factor V Leiden heterozygous mutation and presented with melena and symptomatic anemia. Investigations showed bleeding jejunal varices as the cause of anemia. We discuss the therapeutic options and dilemma in the management of such cases.

An overview of the Hepatitis C control plan in Qatar.

Since the development and approval of new direct-acting antiviral (DAA) drugs, chronic hepatitis C virus (HCV) infection is now considered a curable disease. However, the emphasis on DAA therapies might disregard other preventive measures, and limits the strategy for a clinical cure rather than comprehensive disease control. The Qatar National plan for HCV control was launched in December 2014 to prioritize and proactively manage HCV with the ultimate aim of eliminating viral hepatitis. The plan is based on four pillars: primary prevention, early detection, clinical management, and continuous monitoring. This report describes the activities undertaken in Qatar to prepare for the programme and the early results of its initial phase, given the fact that countries with comprehensive HCV plans are providing better access to care and prevention.

Demographics and Epidemiology of Hepatitis B in the State of Qatar: A Five-Year Surveillance-Based Incidence Study.

Background: Expatriates represent >80% of Qatar's population, mostly arriving from countries in Africa and Asia that are endemic with many diseases. This increases the risk for introducing new pathogens into the country and provides a platform for maintenance of endemic pathogen circulation. Here, we report on the incidence and epidemiological characteristics of hepatitis B in Qatar between 2010 and 2014. Methods: We performed a retrospective epidemiological data analysis using the data available at the surveillance system of the Ministry of Public Health (MOPH) in Qatar. Data were collected from distinctive public and private incorporates around the nation. Reported cases of hepatitis B patients represent those who met the stringent case definition as per World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines and eventually reported to MOPH. Results: The annual incidence rates of hepatitis B cases were 30.0, 34.2, 30.5, 39.4, and 19.8 per 100,000 population in 2010, 2011, 2012, 2013, and 2014, respectively. There was no specific trend or seasonality for the reported cases. The incidence rates were higher in females compared to males between 2010 and 2012, but similar in 2013 and 2014. The highest incidence rates were reported among individuals between 25 and 34 years of age. No cases were reported in children younger than five years in 2013 and 2014. Rates of hepatitis B cases declined dramatically in 2014, in both Qataris and non-Qataris, as compared to the previous years. Conclusion: Our results indicate a dramatic decline of hepatitis B cases in Qatar but mandate improved surveillance and vaccination efforts in expatriates in the nation.