Malcolm Wells

Meta‐analysis: vasoactive medications for the management of acute variceal bleeds

Vasoactive medications such as vasopressin, somatostatin and their analogues (terlipressin, vapreotide and octreotide) are commonly used for the treatment of acute variceal bleeding. However, the risks and benefits of these interventions are not well understood.

A cross-sectional study of the association between overnight call and irritable bowel syndrome in medical students

BACKGROUND Shift work has been associated with irritable bowel syndrome (IBS), which includes gastrointestinal symptoms such as abdominal pain, constipation and diarrhea. Overnight call shifts also lead to a disruption of the endogenous circadian rhythm. HYPOTHESIS Medical students who perform intermittent overnight call shifts will demonstrate a higher prevalence of IBS symptoms when compared with medical students who perform no overnight call shifts. METHODS First- and second-year (preclinical) medical students have no overnight call requirements, whereas third- and fourth-year medical (clerkship) students do have overnight call requirements. All medical students at the Schulich School of Medicine and Dentistry (London, Ontario) were invited to complete an anonymous, web-based survey or an identical paper copy that included demographic data, the Rome III questionnaire and the IBS-Quality of Life measure (IBS-QOL). The prevalence of IBS symptoms and quality of life secondary to those symptoms were determined. RESULTS Data were available for 247 medical students (110 preclinical students, 118 clerkship students and 19 excluded surveys). There was no significant difference in the presence of IBS between preclinical and clerkship students (21 of 110 [19.1%] versus 26 of 118 [22.0%]; P=0.58). The were no significant differences in mean (± SD) IBS-QOL score of those with IBS between preclinical (43.5±8.3) and clerkship students (45.7±13.8) (P=0.53). CONCLUSIONS Participation in overnight call was not associated with the development of IBS or a lower quality of life secondary to IBS in medical students.

Sleep disruption secondary to overnight call shifts is associated with irritable bowel syndrome in residents: a cross-sectional study.

Objectives:Sleep disruption has been associated with irritable bowel syndrome (IBS). We hypothesized that residents with greater sleep disruption secondary to intermittent overnight call shifts would have a higher prevalence of IBS.Methods:Postgraduate residents completed a Web-based survey including demographic data, frequency and characteristics of call shifts, the Rome III questionnaire, and the IBS–quality of life measure.Results:For every hour of sleep deprivation while on call vs. off call, the odds ratio for an increased likelihood of IBS was 1.32, after adjustment for age and gender. The mean number of calls per block, sleep deprivation while on call, and specialty program vs. family practice each predicted the severity of IBS.Conclusions:Sleep disruption secondary to overnight call in residents was associated with an increased prevalence of IBS.

Comparing outcomes of donation after cardiac death versus donation after brain death in liver transplant recipients with hepatitis C: A systematic review and meta-analysis

BACKGROUND Liver transplantation (LT) using organs donated after cardiac death (DCD) is increasing due, in large part, to a shortage of organs. The outcome of using DCD organs in recipients with hepatits C virus (HCV) infection remains unclear due to the limited experience and number of publications addressing this issue. OBJECTIVE To evaluate the clinical outcomes of DCD versus donation after brain death (DBD) in HCV-positive patients undergoing LT. METHODS Studies comparing DCD versus DBD LT in HCV-positive patients were identified based on systematic searches of seven electronic databases and multiple sources of gray literature. RESULTS The search identified 58 citations, including three studies, with 324 patients meeting eligibility criteria. The use of DCD livers was associated with a significantly higher risk of primary nonfunction (RR 5.49 [95% CI 1.53 to 19.64]; P=0.009; I2=0%), while not associated with a significantly different patient survival (RR 0.89 [95% CI 0.37 to 2.11]; P=0.79; I2=51%), graft survival (RR 0.40 [95% CI 0.14 to 1.11]; P=0.08; I2=34%), rate of recurrence of severe HCV infection (RR 2.74 [95% CI 0.36 to 20.92]; P=0.33; I2=84%), retransplantation or liver disease-related death (RR 1.79 [95% CI 0.66 to 4.84]; P=0.25; I2=44%), and biliary complications. CONCLUSIONS While the literature and quality of studies assessing DCD versus DBD grafts are limited, there was significantly more primary nonfunction and a trend toward decreased graft survival, but no significant difference in biliary complications or recipient mortality rates between DCD and DBD LT in patients with HCV infection. There is insufficient literature on the topic to draw any definitive conclusions.

Thalamic infarct presenting as catastrophic life-threatening event in an older adult

An 84 year old woman with history of moderate Alzheimer’s disease, depression, and an anxiety disorder presented to our emergency room at Victoria Hospital, London, Ontario in an ‘unresponsive’ state. The patient was akinetic with mutism, and clonic perseveration induced in the upper limbs was evident while she was examined. Heart attack, massive stroke, or intracranial bleed were ruled out, and an electroencephalogram showed no epileptiform activity. Despite a normal CT, a magnetic resonance scan was ordered and showed bilateral acute paramedian thalamogeniculate infarction arising from occlusion of the artery of Percheron. Bilateral thalamic infarcts can cause sudden onset of akinetic mutism with clonic perseveration, which may be confused with coma and seizures due to life threatening conditions such as a massive stroke. Thorough clinical assessment and early use of MRI scanning will assist physicians with a more accurate diagnosis of older adults with this kind of presentation.

Clinical Impact of Portal Vein Thrombosis Prior to Liver Transplantation: A Retrospective Cohort Study

BACKGROUND The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico. MATERIAL AND METHODS In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed. RESULTS The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p < 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p > 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p < 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-plate-let-ratio-index score among HCV-patients. CONCLUSION A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.INTRODUCTION To identify the impact of portal vein thrombosis (PVT) and associated medical and surgical factors on outcomes post liver transplant (LT). MATERIAL AND METHODS Two analyses were performed. Analysis One: cohort study of 505 consecutive patients who underwent LT (Alberta) between 01/2002-12/2012. PVT was identified in 61 (14%) patients. Analysis Two: cohort study of 144 consecutive PVT patients from two sites (Alberta and London) during the same period. Cox multivariable survival analysis was used to identify independent associations with post-LT mortality. RESULTS In Analysis One (Alberta), PVT was not associated with post-LT mortality (log rank p = 0.99). On adjusted analysis, complete/occlusive PVT was associated with increased mortality (Hazard Ratio (HR) 8.4, p < 0.001). In Analysis Two (Alberta and London), complete/occlusive PVT was associated with increased mortality only on unadjusted analysis (HR 3.7, p = 0.02). On adjusted analysis, Hepatitis C (HR 2.1, p = 0.03) and post-LT portal vein re-occlusion (HR 3.2, p = 0.01) were independently associated with increased mortality. CONCLUSION Well-selected LT patients who had PVT prior to LT had similar post-LT outcomes to non-PVT LT recipients. Subgroups of PVT patients who did worse post-LT (complete/occlusive thrombosis pre-LT, Hepatitis C or post-LT portal vein re-occlusion) warrant closer evaluation in listing and management post-LT.

Abernethy malformation: Congenital absence of the portal vein

1Department of Internal Medicine; 2Department of Gastroenterology and Hepatology, Western University, London, Ontario; 3Department of Gastroenterology, King Khalid University Hospital, King Saud University, Saudi Arabia Correspondence: Dr Lukasz Kwapisz, Department of Internal Medicine, Western University, 147 Ocean Pearl Street, Whitby, Ontario L1N 0C7. Telephone 226-919-4034, e-mail lukaszkwapisz84@hotmail.com Received for publication June 29, 2014. Accepted September 17, 2014 CASE PRESENTATION A 20-year-old previously well man presented with unintentional 6.75 kg (15 lb) weight loss over a six-month period, vague abdominal discomfort and bilateral patchy rash. Blood work was notable for elevations in alanine aminotransferase (75 U/L [normal range <41 U/L]), aspartate aminotransferase (101 U/L [<40 U/L]), alkaline phosphatase (310 U/L [40 U/L to 129 U/L]) and total bilirubin (15.7 μmol/L [3.4 μmol/L to 17 μmol/L]) levels. An abdominal ultrasound revealed hepatic nodules. On further characterization, magnetic resonance imaging revealed a portosystemic shunt (PSS) between the main portal vein and inferior vena cava (IVC) (Figure 1). Both vessels were dilated, with no definite intrahepatic portal venous branches identified (Figure 2). Multiple large regenerative nodules could also be identified. Hepatic portal venous Doppler confirmed an extrahepatic PSS, with a markedly distended infrahepatic IVC (Figure 3). The confluence of the splenic vein and superior mesenteric vein drained directly into the IVC. The morphology suggested a type Ib Abernethy malformation.

Increased duration of dual pegylated interferon and ribavirin therapy for genotype 1 hepatitis C post-liver transplantation increases sustained virologic response: a retrospective review.

Background/Aim: In patients with advanced post-transplant hepatitis C virus (HCV) recurrence, antiviral treatment (AVT) with interferon and ribavirin is indicated to prevent graft failure. The aim of this study was to determine and report Canadian data with respect to the safety, efficacy, and spontaneous virologic response (SVR) predictors of AVT among transplanted patients with HCV recurrence. Patients and Methods: A retrospective chart review was performed on patients transplanted in London, Ontario and Edmonton, Alberta from 2002 to 2012 who were treated for HCV. Demographic, medical, and treatment information was collected and analyzed. Results: A total of 85 patients with HCV received pegylated interferon with ribavirin post-liver transplantation and 28 of the 65 patients (43%) with genotype 1 achieved SVR. Of the patients having genotype 1 HCV who achieved SVR, there was a significantly lower stage of fibrosis (1.37 ± 0.88 vs. 1.89 ± 0.96; P = 0.03), increased ribavirin dose (total daily dose 1057 ± 230 vs. 856 ± 399 mg; P = 0.02), increased rapid virologic response (RVR) (6/27 vs. 0/31; P = 0.05), increased early virologic response (EVR) (28/28 vs. 18/35; P = 0.006), and longer duration of therapy (54.7 ± 13.4 weeks vs. 40.2 ± 18.7; P = 0.001). A logistic regression model using gender, age, RVR, EVR, anemia, duration of therapy, viral load, years’ post-transplant, and type of organ (donation after cardiac death vs. donation after brain death) significantly predicted SVR (P < 0.001), with duration of therapy having a significant odds ratio of 1.078 (P = 0.007). Conclusions: This study identified factors that predict SVR in HCV-positive patients who received dual therapy post-transplantation. Extending therapy from 48 weeks to 72 weeks of dual therapy is associated with increased SVR rates. Future studies examining the role of extended therapy are needed to confirm these findings, since the current study is a retrospective one.

Acute pleural effusion from aortic aneurysm rupture.

A 78-year-old man was admitted to hospital with a urinary tract infection; on the second day of his hospital stay, he experienced a sudden onset of severe nonradiating pleuritic retrosternal chest pain, along with severe shortness of breath. An initial examination showed a blood pressure of 160/90

A treatable mimicker of cholangiocarcinoma.

1Department of Gastroenterology and Hepatology; 2Department of Pathology, Western University, London, Ontario; 3Department of Medicine, Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia Correspondence: Dr Bandar Al-Judaibi, E2-314, University Hospital, London Health Sciences Centre, 339 Windermere, London, Ontario N6A 5A5. Telephone 519-685-8500, e-mail bandaraljudaibi@gmail.com Received for publication February 3, 2015. Accepted February 8, 2015 CASE PRESENTATION A 68-year-old female nonsmoker, nondrinker with a medical history of hypertension presented with new-onset painless jaundice and pruritus, a three-month history of 9.9 kg weight loss and chronic diarrhea with four to five loose bowel movements per day. Medications included vitamin D, amlodipine and eprosartan. Physical examination was normal except for jaundice and muscle wasting. Recent colonoscopy had been normal. Total and direct bilirubin levels were 6.84 mg/dL (116.96 μmol/L) and 9.18 mg/dL (156.98 μmol/L), respectively. Other results included an international normalized ratio of 1.0, alanine aminotransferase level 247 U/L (normal <33 U/L), aspartate aminotransferase level 139 U/L (normal <32 U/L) and alkaline phosphatase level 524 U/L (normal 35 to 104 U/L). Viral hepatitis serologies, and antimitochondrial antibody and anti-smooth muscle antibody tests were negative. Her alpha-fetoprotein level was 2.4 ng/mL (normal <5 ng/mL), total immunoglobulin (Ig) G was 1880 mg/dL (normal <640 mg/dL), carbohydrate antigen 19-9 was 856 U/mL (normal <33 U/mL) and IgG4 was 890 g/L (normal <3 g/L). Doppler ultrasound, magnetic resonance cholangiopancreatography and magnetic resonance imaging of the liver were suspicious for a subtly enhancing mass (2.8 cm to 4.2 cm in diameter) in the region of the hilum and porta hepatis, obstructing both the right and left hepatic ducts. Endoscopic retrograde cholangiopancreatography identified strictures in the central portions of the right and left hepatic duct, which was concerning for cholangiocarcinoma (Figure 1). Biliary brushings were negative for malignancy.