Randomized trial comparing general anesthesia with anesthesiologist-administered deep sedation for ERCP in average-risk patients.

BACKGROUND AND AIMS: General anesthesia (GA) or monitored anesthesia care (MAC) is increasingly used to perform ERCP. The definitive choice between the 2 sedative types remains to be established. This study compared outcomes of GA with MAC in ERCP performed in patients at average risk for sedation-related adverse events (SRAEs). METHODS: At a tertiary referral center, patients with American Society of Anesthesiologists (ASA) class ≤III were randomly assigned to undergo ERCP with MAC or GA. The main outcome was a composite of hypotension, arrhythmia, hypoxia, hypercapnia, apnea, and procedural interruption or termination defined as SRAEs. In addition, ERCP procedural time, success, adverse events, and endoscopist and patient satisfaction were compared. RESULTS: Of 204 randomized, 203 patients were evaluated for SRAEs (MAC, n = 96; GA, n = 107). SRAEs developed in 35% of the MAC cohort (34/96) versus 9% in the GA cohort (10/107), which was statistically significant (P < .001). Mean induction time for GA was significantly longer than that for MAC (10.3 ± 10 minutes vs 6.5 ± 10.8 minutes, respectively; P < .001). ERCP procedure time, recovery time, cannulation time and success, and procedure-related adverse events were not statistically different between the 2 sedative groups. The use of GA improved endoscopist and patient satisfaction (P < .001). CONCLUSION: GA is safe with fewer SRAEs than MAC in patients with ASA scores ≤III undergoing ERCP. Apart from prolonging induction time, use of GA does not change the procedural success or ERCP-related adverse events and offers greater endoscopist and patient satisfaction. Hence, GA is a consideration in patients undergoing ERCP in this population group. (Clinical trial registration number: NCT04099693.).

High Efficacy of ombitasvir/paritaprevir/ritonavir plus dasabuvir in hepatitis C genotypes 4 and 1-infected patients with severe chronic kidney disease.

BACKGROUND & AIMS: Limited data have shown high efficacy of co-formulated ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in the treatment of hepatitis C virus (HCV) genotype (GT)-4, and combined with dasabuvir (DSV) in GT1 patients, with chronic kidney disease (CKD) stages 4-5 (<30 mL/min/1.73 m2 ). We assessed real-world safety and efficacy of OBV/PTV/r ± DSV in GT1- and 4-infected patients. METHODS: In this observational cohort (n = 67), we enrolled stages 4-5 CKD treatment-naïve or Peginterferon/RBV-experienced GT4-infected patients (n = 32) treated for 12-24 weeks with OBV/PTV/r ± RBV, and plus DSV in GT1 patients (n = 35, including 3 with GT1/4 co-infection). RBV was dosed by physician discretion between 200 mg weekly and 200 mg daily. Primary endpoints were SVR12, calculated on intention-to-treat (ITT) basis, and occurrence of serious adverse events. RESULTS: The mean age of the cohort was 45.7 ± 12.7 years, 50.7% were females, 20.9% had cirrhosis, 35.8% were treatment-experienced and 97% were on haemodialysis. Three patients (F4) received 24-week treatment, 2 with GT4, and 1 with GT1a; and 19.4% were treated without RBV, including 9 GT1, and 4 GT4. Overall, 65 (97.1%) patients achieved SVR12, including 100% of those with a post-treatment follow-up (modified ITT analysis). Of the two patients without SVR12, one died from sepsis-related complications and the other from a myocardial infarction 2 weeks after completing therapy. Grades 3-4 anaemia occurred in 8.9%. CONCLUSION: A 12-week regimen of OBV/PTV/r ± DSV with or without RBV is highly effective with a favourable safety profile amongst GT4 and GT1 patients with CKD stages 4-5. SVR12 rates were high regardless of patient characteristics.

Gastrointestinal Basidiobolomycosis: A Case Series.

Gastrointestinal basidiobolomycosis (GIB) is a rare fungal infection caused by Basidiobolus ranarum, a saprophytic fungus that belongs to the class of Basidiobolomycetes. It mainly infects immunocompetent individuals and is mainly found in arid tropical and subtropical regions, including Southwestern America, Saudi Arabia, Africa, and Asia. Not surprisingly, a great number of human infections have been reported from these warm, humid climate regions that are felicitous for the growth of this fungus, especially from the southern region of Saudi Arabia and Arizona in the United States of America. GIB is easily misdiagnosed as malignancy, inflammatory bowel disease, diverticulitis, lymphoma, and chronic intestinal infections due to its rarity. In this case series, we summarize the clinical features, imaging, histopathological features, and treatment of patients diagnosed with GIB in our institution.

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma.

BACKGROUND: Limited data exists for the efficacy and outcomes of nivolumab as a second-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of nivolumab in patients with uHCC who experienced disease progression during sorafenib treatment. METHODS: In this retrospective, observational, multicenter study, adult Child-Turcotte-Pugh A/7B patients with uHCC who tolerated sorafenib therapy but showed disease progression switched to second-line intravenous nivolumab (n = 42). A similar number of consecutive, unselected patients who were maintained on sorafenib therapy, regardless of tumoral response or progression, served as historical controls (n = 38). The primary endpoint was overall survival (OS, defined as the time from starting sorafenib in either group up to death due to any cause) and analyzed by intention-to-treat. RESULTS: The mean age of the overall cohort was 72.4 ± 10.1 years, of whom 87.5% were males and 58.8% had underlying viral etiology. Patients in the two cohorts were similar, except those who received nivolumab had more co-morbidities (70.0% vs. 15.4%), ECOG-2 status (21.4% vs. 15.8%), BCLC stage C (81.0% vs. 47.4%), and extravascular invasion (54.4% vs. 21.8%) (p < 0.05 for all). More patients in the nivolumab arm were Child-Turcotte-Pugh B (35.7% vs. 21.1%, p = 0.15). Median OS was 22.2 months (95% CI: 8.9-49.8) on second-line nivolumab and 11.0 months (95% CI: 3.6-18.4) on sorafenib alone (HR 1.93; 95% CI: 1.1-3.3, p = 0.014). Median OS after starting nivolumab was 10.2 months, and time-to-progression was 4.9 months (95% CI: 3.2-6.3). CONCLUSION: Nivolumab is an effective second-line treatment option in patients with uHCC who progress on sorafenib, with significantly improved OS. These early real-life data offer encouraging results, similar to those shown in Phase I/IIa clinical trials. Further investigations are warranted for the use of nivolumab as a monotherapy.

Hepatitis B virus infection in Saudi Arabia and the UAE: Public health challenges and their remedial measures.

BACKGROUND: Hepatitis B virus (HBV) infection is a major public health concern globally with higher prevalence in Middle Eastern countries. Both Saudi Arabia and the UAE face critical challenges in HBV treatment and management despite the implementation of a mass vaccination program. This review aimed to understand the gaps and unmet needs related to HBV infection, public health challenges associated with its diagnosis, and treatment barriers in Saudi Arabia and the UAE. Additionally, the review aimed to provide the best practices in the HBV care pathway for effective remedial measures and disease reduction. METHODS: The literature search was done from Pubmed. RESULTS: The lack of disease awareness and knowledge about disease transmission among patients and their family members and healthcare professionals, lack of proper screening, underdiagnosis, social stigma, lack of established referral system, and treatment cost are the primary barriers to HBV diagnosis and management. CONCLUSION: Appropriate healthcare initiatives should be undertaken to lower the disease burden in Saudi Arabia and the UAE.

Retrospective Analysis of Characteristics, Indications and Outcomes of Endoscopic Retrograde Cholangiopancreatography (ERCP) in a Tertiary Referral Center in Saudi Arabia.

BACKGROUND:  Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic procedure that is an essential tool in the management of pancreaticobiliary diseases. There is limited data available on the indications and outcomes of ERCP from this region. Therefore, we aim to report the characteristics of patients, indications and outcomes of ERCP in Saudi Arabia.  Methods: We retrospectively looked at ERCP procedures done at a tertiary referral center covering the western region of Saudi Arabia from August 2018 until July 2020. Data were collected from the hospital's electronic patient record and endoscopy database. RESULTS:  Of 1001 ERCPs performed, full data was available on 712 procedures on 581 patients that were included in the final analysis. Mean age was 53.1 years. Four hundred four (56.7%) were female. Board-certified consultants performed all ERCPs. The most common intervention was sphincterotomy, which was performed in 563 (96.9%) patients who underwent first-ever ERCP, followed by dilatation and stenting. The commonest indication of ERCP was confirmed or suspected choledocholithiasis (52.6%), followed by replacement or removal of a biliary stent (15.7%), 55 (7.7%) for suspected ascending cholangitis, 54 (7.5%) for acute biliary pancreatitis and 15 (2%) for suspected sphincter of Oddi dysfunction. The commonest finding among all patients was choledocholithiasis in 57.9%, debris in 15.2% and biliary stricture in 14.8%. The commonest complication was pancreatitis in 22 (3.1%) followed by post-sphincterotomy bleeding in 16 (2.2%) and perforation in nine (1.2%). Bleeding was controlled by endoscopic intervention in four (25%) and one (6.2%) patient underwent surgery. One (0.14%) patient had procedure-related mortality secondary to post-procedure pulmonary embolism and one had significant morbidity and prolonged hospitalization because of complicated perforation. The deeper common bile duct (CBD) cannulation rate was 97.3%. CONCLUSION: Our study results revealed that ERCP performed in the western region of Saudi Arabia has similar indications and findings as reported in the international literature. ERCP is successful in achieving the therapeutic objectives with complication rates consistent with published data.

Infliximab-Associated Xanthogranulomatous Pyelonephritis: A Rare Complication.

Xanthogranulomatous pyelonephritis (XGP) is one of the rare diseases characterized by chronic inflammation and destruction of the renal parenchyma, and it is usually associated with renal infection, and nephrolithiasis. Infliximab is an anti-tumor necrosis factor-alpha (anti-TNF-α) monoclonal antibody, which is widely used for treating inflammatory bowel disease, and it is known to increase the risk of rare and opportunistic infections. In this study, we report a case of XGP presenting after the initiation of infliximab treatment. We highlight one of the possible complications associated with immunosuppression due to infliximab. Furthermore, the importance of increasing the awareness among physicians for early recognition of this rare complication.

Self-Expanding Metallic Stents for Palliation of Esophageal Cancer: A Single Center Experience From Saudi Arabia.

BACKGROUND: Self-expanding metallic stents (SEMSs) are increasingly used as a non-surgical alternative for the palliation of advanced esophageal cancer (EC). However, there is a scarcity of real-life experience with the use of these stents exclusively in EC. The aim of this study is to evaluate the efficacy of SEMS in inoperable ECs in the western region of Saudi Arabia. METHODS: A retrospective review of SEMS placed in a tertiary referral hospital for histologically proven inoperable EC from 2016 to 2019. Demographics data, procedure success, complication, re-intervention, and mortality were analyzed. RESULTS: Forty-eight SEMS placed in 35 patients for palliation of dysphagia. The median age of patients was 68 years (range 31-95). 69% (24) patients have a lower third of EC and the rest have a middle third. SEMSs were placed successfully in all cases with symptomatic improvement. No major stent-related complication was seen. 28% (13) patients required re-intervention with additional SEMS placement, nine of which were for tissue in growth and four for distal migration. Median survival was 114 days (range 30-498). Most of the complications seen in fully covered SEMS compared to the partially covered 50% (8/16) vs 17% (5/30), respectively, p = 0.04. Chemo and/or radiotherapy were given to 51% (18) of the patients without any significant benefit on survival (p = 0.79) or re-intervention rate (p = 0.47) compared to those who did not. CONCLUSION: SEMS is effective in palliating dysphagia in inoperable EC without major complications. Rates of tumors in growth and migration were comparable to other studies. SEMS provides long-term palliation.

Real life efficacy of ledipasvir/sofosbuvir in hepatitis C genotype 4-infected patients with advanced liver fibrosis and decompensated cirrhosis.

Limited clinical trial data has shown high efficacy of co-formulated ledipasvir/sofosbuvir (LDV/SOF) in the treatment of hepatitis C virus (HCV) genotype (GT)-4 infected cirrhotic patients. We assessed real-world safety and efficacy of LDV/SOF with or without ribavirin (RBV) in GT4-infected patients with compensated and decompensated cirrhosis. PATIENTS & METHODS: This observational cohort (n = 213) included GT4 treatment-naïve (59.6%) and -experienced (40.4%) patients with advanced fibrosis (F3, Metavir; n = 30), compensated (F4, n = 135) and decompensated cirrhosis (n = 48) treated for 12 (n = 202) or 24 weeks (n = 11) with LDV/SOF. RBV was dosed by physician discretion between 600-1200 mg daily. Patients with prior DAA failure were excluded from the analysis. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12) on an intention-to-treat analysis, and occurrence of serious adverse events (SAEs). RESULTS: The mean age of the overall cohort was 59.6 ±â€¯12.1 years and 125 (58.7) were female. Overall, 197 (92.5%) of the patients achieved SVR12, including 93.3% of F3 fibrosis, 93.3% of compensated cirrhotics and 89.6% of the decompensated cirrhotics (P = 0.686). Addition of RBV (68.5%) did not enhance efficacy (91.8% vs. 94.0% without RBV, P = 0.563), including in F3 fibrosis, compensated and decompensated cirrhosis (P > 0.05, for all). There was no difference in SVR12 rates with 24 and 12 weeks therapy (90.9% and 92.6%, respectively; P = 0.586). Treatment failure (n = 16) was mostly related to relapse (n = 11), while on-treatment death (n = 3) and breakthrough (n = 2) comprised a minority. SAEs occurred in 9 (4.2%) patients requiring early treatment discontinuation in 4 (3 on-treatment deaths and 1 pregnancy). CONCLUSION: LDV/SOF therapy yielded high SVR12 rates in both compensated and decompensated cirrhotic GT4 patients. The addition of RBV to this regimen did not improve efficacy. The safety profile of this regimen was comparable with that reported for other HCV genotypes.

Tuberculosis presenting as broncho-oesophageal fistula in a young healthy man.

A 21-year-old Saudi man presented with a history of dysphagia and choking. CT scan of the chest showed clear evidence of chronic recurrent aspiration pneumonia in the left lung. It also showed a fistula connecting the left main bronchus to the oesophagus. Endoscopy showed clear opening on the oesophageal side. Bronchoscopy also confirmed the presence of a broncho-oesophageal fistula on the left bronchial side with the presence of secretions on swallowing. Bronchoalveolar lavage (BAL) was done and sent for mycobacterial tuberculosis culture. The fistula was closed with clips under endoscopic guidance, which alleviated his symptoms of dysphagia and choking. The BAL culture grew mycobacterial tubercle bacilli. The patient showed marked improvement after starting antitubercular therapy and was discharged to be followed up in the clinic.

Effects of chronic hepatitis C genotype 1 and 4 on serum activins and follistatin in treatment naïve patients and their correlations with interleukin-6, tumour necrosis factor-α, viral load and liver damage.

The importance of activins and follistatin in liver diseases has recently emerged. The aim of the present study was to measure the influence of chronic infection with viral hepatitis C (CHC) genotype 1 and 4 on serum levels of activin-A, activin-B and follistatin, and to determine their correlations with viral load, liver damage, interleukin-6 (IL-6) and tumour necrosis factor (TNF)-α. Sera samples collected from 20 male and 20 female treatment naïve CHC genotype 1 and 4 Saudi patients (ten males and ten females for each genotype), and 40 gender- and age-matched healthy participants were analysed for activin-A, activin-B and follistatin using enzyme-linked immunosorbent assay and their levels were correlated with IL-6, TNF-α, viral load and AST platelet ratio index (APRI). Serum activin-A, activin-B, IL-6 and TNF-α were significantly increased, while serum follistatin was significantly decreased, in both genders of CHC patients compared with control subjects, In both viral genotypes, activin-A was strongly and positively correlated with the viral load, APRI, IL-6 and TNF-α, and negatively with albumin (P < 0.01). Activin-B showed the same correlations of activin-A only in CHC genotype 1 patients, but it was weaker than activin-A. No correlation was detected with follistatin. Serum activins, particularly activin-A, and follistatin are significantly altered by CHC genotype 1 and 4. This dysregulation of activins/follistatin axis may be associated with viral replication, host immune response and liver injury. Further studies are needed to illustrate the definite role(s) and clinical value of activins and follistatin in CHC.

Serum Activins and Follistatin during the Treatment of Chronic Hepatitis C Genotypes 1 and 4 and Their Correlations with Viral Load and Liver Enzymes: A Preliminary Report.

Aims. To measure the effect of pegylated interferon- α therapy on serum activin-A, activin-B, and follistatin and their correlation with viral load and liver fibrosis in chronic hepatitis C (CHC). Methods. This study was cross-sectional and sera were collected from 165 participants classified into 7 groups: 40 healthy negative control, 33 treatment naïve patients as positive control, 19 patients at week 4, 22 at week 12, and 19 at week 24 of treatment initiation and 21 responders and 11 nonresponders at the end of 48-week treatment protocol. Serum candidate proteins were measured using ELISA and liver fibrosis was assessed by AST platelet ratio index (APRI). Results. CHC significantly increased activins and decreased follistatin compared to negative control (P < 0.05). Activin-A and follistatin levels returned to the levels of negative control group at weeks 4, 12, and 24 following treatment initiation and were significantly different from positive control (P < 0.05). Both proteins were significantly different between responders and nonresponders. Activin-A correlated positively and significantly with the viral load and APRI. Conclusion. CHC modulates serum activin-A and follistatin and they appear to be influenced by pegylated interferon- α therapy. Further studies are needed to explore the role of activins in CHC.

Liver abscess presentation and management in Saudi Arabia and the United Kingdom.

BACKGROUND AND OBJECTIVES: Liver abscess (LA) is a well-described disease in the medical literature; however, information about its characteristics and outcome in the Middle East is lacking. We compared the mode of presentation, risk factors, management and outcome of LA patients in Saudi Arabia with cases from the United Kingdom (UK). DESIGN AND SETTING: Retrospective review of LA patients from three tertiary care centers (2 from Saudi Arabia and 1 from the UK) over a period of 10 years, from 1995 to 2005. PATIENTS AND METHODS: Data collected included demographic characteristics; clinical presentation; biochemical, microbiological and radiological findings; treatment modalities; and outcome. RESULTS: A total of 83 patients were diagnosed with LA, including 48 patients from Saudi Arabia and 35 patients from the UK. The mean (SD) age was 45.2 (20.3) years for those from Saudi Arabia and 55.4 (18.8) years for those from the UK (P=.022). The majority of the patients were males (70% from Saudi Arabia and 80% from the UK). Upper abdominal pain and fever were the commonest symptoms, each reported in 87% of the cases. Alkaline phosphatase elevation was the commonest liver function abnormality, seen in 66 (80%) patients. Organisms were isolated in 43 (52%) cases and the majority of these were coliforms (58%). Amebic liver abscesses occurred in 19 (23%) patients and all of those patients were either from or had traveled recently to the Indian subcontinent. Complete resolution of the abscesses was achieved in 66 (80%) patients with aspiration and/or antibiotics, and 9 (10.8%) patients died. On multivariate analysis, underlying malignancy, hypotension and chest signs at presentation were predictors of poor outcome (P=.008, .029 and .001, respectively). CONCLUSIONS: Successful resolution of LA is achievable in the majority of the cases, although underlying malignancy is associated with poor outcome. Amebic liver abscesses must be considered in patients with a history of travel to endemic areas.