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Peptic ulceration with fistula formation into the inferior vena cava is rare, difficult to diagnose, and associated with high mortality. The nonspecific signs and symptoms make diagnosis challenging, delaying optimal treatment. Although there have been reports on duodeno-caval fistulas, gastric communication with the inferior vena cava is very rare. We report the second case of a fatal gastro-caval fistula and performed a review of the literature on entero-caval fistulas to emphasize the importance of early suspicion and to understand the most common presentation, as well as the best diagnostic and treatment modalities of this rare pathology.

BACKGROUND: Drug-induced liver injury (DILI) and herbal/dietary supplements (HDS) related liver injury present unique diagnostic challenges. Collaboration between the clinician and the pathologist is required for an accurate diagnosis and management. AIM: To report our experience on the clinical-pathological findings of hepatic injury caused by drugs/HDS. METHODS: A retrospective review of clinically proven cases of DILI/HDS who presented to our institution from January 1, 2013 to December 31, 2017 was performed. Slides were reviewed for histopathological patterns of injury and correlated with the causative agent. Out of 600 patients presenting with unexplained rise in liver enzymes undergoing biopsy, 107 were suspected to have DILI/HDS. Of these, 53 had a directly linked exposure to drug/herbal supplements. Fifteen patients were excluded for concurrent known liver disease. Thirty-eight patients with clinically proven DILI/HDS were finally included. RESULTS: Thirty-eight cases of DILI/HDS with a male:female of 1:1.5 and mean age of 51 ± 3 years were identified. DILI was identified in 84.2% cases while HDS injury in 15.8%. Acute hepatitis (42.1%) was the most common pattern of injury while granulomatous hepatitis (2.6%) was the least common. We found one case of acute-cholestasis due to rivaroxaban and two cases of cholestatic-hepatitis due to rizatriptan and trimethobenzamide-hydrochloride that, to the best of our knowledge, have not been previously reported. One case of steatohepatitis due to trimethoprim-sulfamethoxazole and three unusual cases of cholestatic-hepatitis with bile duct injury and steatosis due to dronedarone, C4-Extreme and hydroxycut, were also seen. Of our cohort, 81.6% of the patients fared well with discontinuation of drug and 18.4% underwent transplant; of which 42.9% were deceased. CONCLUSION: We describe the clinical findings, histopathological patterns of injury and clinical outcomes caused by drugs. In particular, we report a few previously unreported/ rarely observed clinical and histopathological patterns of hepatic injury.

Patients with inflammatory bowel disease (IBD) have been known to be at significantly higher risk of colorectal cancer (CRC), likely due to the high degree of inflammation. Aggressive surveillance protocols and better endoscopic techniques have contributed to the declining incidence rates of CRC, but they remain above average compared to the general population. Recent studies have examined the role of genetic alteration and microbiota in carcinogenesis. Current American and European guidelines recommend initiating a screening and surveillance protocol 8 years after the initial diagnosis of IBD in most patients. Endo-histological appearance during colonoscopy as well as factors such as family history of colon cancer, personal history of primary sclerosing cholangitis (PSC), or stricturing disease among other factors can be used to dictate the interval between surveillance exams. Higher rates of interval cancers has been a major concern, and focus has been on a higher-quality colonoscopic evaluation and formulating the appropriate interval between the exams in these high-risk patients. Higher-quality exams should emphasize better methods for detecting flat and invisible lesions. These methods include better definition, higher pixel range, and use of chromoendoscopy. In this chapter, we will review these methods in addition to discussing the utility of artificial intelligence and computer-aided detection of polyps to further reduce the chances of missed dysplastic lesions and prevent interval cancers.

Esophageal adenocarcinoma is an increasingly common cause of morbidity and mortality in developed countries. Most cases are considered the consequence of chronic gastroesophageal reflux disease, with subsequent Barrett's metaplasia and dysplasia. Because progression from Barrett's metaplasia to cancer occurs over many years, endoscopic screening and surveillance programs have been established, albeit with little or no consideration for cost-effectiveness. As an alternative to the expensive and resource-demanding endoscopic surveillance, the Cytosponge has been developed to sample the esophageal mucosa efficiently. The device is a compressed mesh sponge encapsulated in an ingestible gelatin pill attached to a string. After swallowing, the capsule dissolves allowing the sponge to expand in the stomach. As it is pulled out, cells are collected from the esophagogastric junction and throughout the esophagus. The cellular samples can be analyzed by cytology, immunohistochemistry, and molecular markers. We conducted a systematic review of all recent relevant studies to help define the role of this novel technology, including studies of screening and surveillance of Barrett's esophagus, esophageal squamous dysplasia detection, detection of eosinophilic esophagitis, and evaluation of benign esophageal diseases. With the major limitation that most studies were performed by a single investigative group that developed the technology, the device yielded overall impressive results against the endoscopy/biopsy gold standard. Patient acceptability was high. If these promising early results are validated by other investigators in other populations, the Cytosponge represents an important new advance in the detection of esophageal pathology that could potentially decrease the burden of endoscopic esophageal sampling.

Introduction Acute cholangitis (AC) is a clinical condition that requires prompt medical management with IV fluids, antibiotics, and biliary drainage (BD). The optimal timing for BD remains unclear. Aim To investigate the effect of biliary drainage timing on clinical outcomes in AC. Material and methods We conducted a retrospective study of patients with AC admitted to the ICU using the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database. Emergency department to BD time, hospital death, length of stay (LOS), and severity scores were extracted from the database. We investigated the effect of BD timing on mortality rates, persistent organ failure, and LOS. Results A total of 177 patients were included; 50% were males; median age was 75 years, in-hospital mortality was 9.6%, mean time-to-ERCP was 32 h (range: 0.42-229.6) with 76% meeting the Tokyo Guidelines (TG13) criteria for severe cholangitis, and median Simplified Acute Physiology Score II (SAPS II) was 42 (IQR: 33-51). Using 24 h as a cut-off, patients who underwent BD ≤ 24 h had less persistent organ failure (OR = 0.49; 95% CI: 0.26-0.96, p = 0.040), shorter ICU LOS (3.25 vs. 4.95 days, p = 0.040), shorter hospital LOS (7.71 vs. 13.57 days, p = 0.001), but no difference in either in-hospital mortality (OR = 0.47, 95% CI: 0.17-1.29, p = 0.146) or 28-day mortality (OR = 0.61, 95% CI: 0.24-1.53, p = 0.297). Conclusions In critically-ill patients with acute cholangitis, early biliary drainage ≤ 24 h is associated with less persistent organ failure and shorter length of stay but had no effect on patient survival.

Introduction Post-transplant infections have been studied widely but data on comparisons of deceased donor liver transplants (DDLT) and living donor liver transplants (LDLT), type and timings of infections, and their relations to outcomes are not explored. Material and methods We analysed data from 612 participants of the Adult-to-Adult Living Donor Liver Transplantation Study (A2ALL), a retrospective data set of LDLT and DDLT. We compared the type and timing of the first post-transplant infection in relation to transplant outcomes between the two groups. Results Out of 611 patients, 24.5% experienced the first post-transplant infection, the majority of which were bacterial (35.3%), followed by fungal (11%) and viral infections (4.2%). There was no significant difference in the rate, type or timing of infection between LDLT and DDLT. Patients with late (> 1 year) first infection were 1.8 times more likely to die (95% CI: 1.12-2.98, p = 0.015) and 9 times more likely to have graft failures (95% CI: 3.26-24.8, p < 0.001). DDLT recipients who experienced bacterial infection had a significantly lower survival rate compared to LDLT recipients (p < 0.001). Conclusions Late infection is associated with lower survival in both DDLT and LDLT. Bacterial infection might be more detrimental for DDLT than LDLT. Late infection should be managed aggressively to improve outcomes.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The rising incidence, genetic heterogeneity, multiple etiologies, and concurrent chronic liver diseases make diagnosis, staging, and selection of treatment options challenging in patients with HCC. The best approach to optimize the management of HCC is one that utilizes a core multidisciplinary liver tumor board, consisting of hepatologists, pathologists, interventional radiologists, oncologists, hepatobiliary and transplant surgeons, nurses, and general practitioners. In most cases, HCC is diagnosed by abdominal imaging studies, preferably with a triphasic computed tomography scan of the abdomen or magnetic resonance imaging of the abdomen. Histopathological diagnosis using a guided liver biopsy may be needed in noncirrhotic patients or when radiological diagnostic criteria are not fulfilled in the setting of cirrhosis. The Barcelona Clinic Liver Cancer staging system facilitates a standardized therapeutic strategy based on the tumor burden, extent of metastasis, severity of hepatic decompensation, comorbid medical illnesses, functional status of patient, HCC-related symptoms, and preference of the patient. Treatment options include curative surgery (hepatic resection and liver transplantation) and palliative measures (radiofrequency ablation, transarterial chemoembolization, and chemotherapy with sorafenib). The role of the multidisciplinary team is crucial in promptly reconfirming the diagnosis, staging the HCC, and formulating an individualized treatment plan. In potential liver transplant candidates, timely liver transplant evaluation and coordinating bridging/downsizing treatment modalities, such as radiofrequency ablation and transarterial chemoembolization, can be time-consuming. In summary, a multidisciplinary team approach provides a timely, individualized treatment plan, which can vary from curative surgery in patients with early-stage HCC to palliative/hospice care in patients with metastatic HCC. In most tertiary care centers in the US, a multidisciplinary liver tumor board has become the standard of care and a key component of best practice protocol for patients with HCC.

Hepatic encephalopathy (HE) is a complex disease requiring a multidisciplinary approach among specialists, primary care team, family, and caregivers. HE is currently a diagnosis of exclusion, requiring an extensive workup to exclude other possible etiologies, including mental status changes, metabolic, infectious, traumatic, and iatrogenic causes. The categorization of HE encompasses a continuum, varying from the clinically silent minimal HE (MHE), which is only detectable using psychometric tests, to overt HE, which is further divided into four grades of severity. While there has been an increased effort to create fast and reliable methods for the detection of MHE, screening is still underperformed due to the lack of standardization and efficient methods of diagnosis. The management of HE requires consultation from various disciplines, including hepatology, primary care physicians, neurology, psychiatry, dietician/nutritionist, social workers, and other medical and surgical subspecialties based on clinical presentation and clear communication among these disciplines to best manage patients with HE throughout their course. The first-line therapy for HE is lactulose with or without rifaximin. Following the initial episode of overt HE, secondary prophylaxis with lactulose and/or rifaximin is indicated with the goal to prevent recurrent episodes and improve quality of life. Recent studies have demonstrated the negative impact of MHE on quality of life and clinical outcomes. In light of all this, we emphasize the importance of screening and treating MHE in patients with liver cirrhosis, particularly through a multidisciplinary team approach.

Background Acute gastrointestinal bleeding (AGIB) is responsible for over 140,000 hospitalizations annually. Cardiovascular-related deaths account for 30% of the patients surviving the initial episode of AGIB. The purpose of this study was to identify the impact of elevated troponin on short-term mortality and length of stay (LOS) of these patients. Methods From July 2013 to July 2016, 290 patients admitted with a diagnosis of AGIB and who had cardiac troponin I measured within 24 h of presentation were retrospectively reviewed. Clinical variables including 30-day mortality, 30-day readmission and LOS were then compared between the groups of troponin elevation and no troponin elevation. Results The overall 30-day mortality among patients with AGIB was 6.5% (19/290). Cardiac troponin was elevated in 10% of patients (29/290). Among patients with normal troponin, 5% (13/261) died within 30 days. In patients with troponin elevation, 21% died in the same period (6/29, P = 0.001). The LOS was also higher in patients with troponin elevation (6 vs. 5 days, P = 0.02). There was no difference in 30-day readmission among the two groups. Past history of coronary artery disease, congestive heart failure, hypertension, aspirin use and elevated creatinine was more common in patients with troponin elevation. On multivariate analysis, troponin elevation on presentation is associated with increased mortality (odds: 5.50, CI: 1.73 - 17.47, P = 0.004). Conclusion In patients admitted to the inpatient service with AGIB, elevated troponin I on presentation is associated with high short-term mortality and longer hospital stay.

Background and Aims Acute cholangitis is characterized by abdominal pain, fever, and jaundice. Most patients respond to medical management with intravenous hydration and antibiotics. About 20% to 30% require biliary drainage, and ERCP is the procedure of choice. We conducted a systematic review and meta-analysis to evaluate the impact of emergent biliary drainage on patient outcomes. Methods A comprehensive literature review was conducted by searching the Embase and PubMed databases from inception to April 2019 to identify all studies that evaluated the impact of timing of ERCP on patient outcomes. Our primary outcome was in-hospital mortality (IHM), and secondary outcomes were length of stay (LOS), organ failure, and 30-day mortality. Fixed and random effects models were used to generate pooled measures of IHM, 30-day mortality, and LOS. Results Nine observational studies involving 7534 patients were included in the primary meta-analysis. IHM was significantly lower in patients who underwent emergent biliary drainage within 48 hours (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.28-0.98). As a sensitivity analysis, we pooled the data from 2 population registry studies of 81,893 patients, which yielded consistent results for the main outcomes. LOS was also significantly lower in patients who underwent ERCP within 48 hours with a mean difference of 5.56 days (95% CI, 1.59-9.53). Patients who underwent emergent ERCP also had lower odds of 30-day mortality (OR, 0.39; 95% CI, 0.14-1.08) and organ failure (OR, 0.69; 95% CI, 0.33-1.46). Conclusions Our study reveals that performing emergent ERCP within 48 hours in patients with acute cholangitis is associated with lower IHM, 30-day mortality, organ failure, and shorter LOS.

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. The ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, but the United States (U.S.) is following closely behind with prevalence increasing from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and hepatocellular carcinoma. The increasing prevalence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

Non-alcoholic fatty liver disease (NAFLD), the most common cause of liver disease, affects approximately 75 to 100 million Americans. Patients with concurrent NAFLD and type 2 diabetes mellitus have a higher risk of progressing to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics. Lifestyle modifications, including weight loss, remain the mainstay of treatment for NAFLD, as there are no medications currently indicated for this disease state. Anti-diabetic pharmacologic therapies aimed at improving insulin sensitivity and decreasing insulin production have been studied to determine their potential role in slowing the progression of NAFLD. In this review, we focus on the evidence surrounding anti-diabetic medications and their ability to improve disease progression in patients with NAFLD.

Background: Many expectant parents wish to have a normal child. Unfortunately this does not always happen and some of them may have a child with birth defects leading to detrimental psychological effects on the parents. One of the common presentations generally observed is depression. The presence of depressive symptoms amongst such parents needs to be recorded to find out its prevalence. The results of such finding can help shape future programs for the prevention and treatment in this population group. This study will therefore explore the extent of depressive symptoms amongst parents of children with congenital anomalies. Methods: A case control study design was chosen. Ethical Review Board gave approval for the study on December 31, 2010, and the collection of data was started on January 5, 2011. Two randomly chosen samples of 132 parents each were collected from National Institute of Child Health (NICH), Ida Rieu, and Civil Hospital Karachi (CHK) over 8 months. First group consisted of parents of children with congenital anomalies and the second group was chosen as the control group from general population. Zung scale was used to record the presence of depressive symptoms in these two populations. Mann-Whitney test was performed to compare the depression scores. Results: The scale was completed by 132 parents in both sets. The parents of children with congenital anomalies showed greater (p < 0.0001) depressive symptoms. Mothers displayed greater (p = 0.029) depressive symptoms than fathers. Conclusion: The parents of children with anomalies (60.6%) had more depressive symptoms than parents of normal children (27.3%).

Background and Aims: Nonalcoholic steatohepatitis (NASH) is the most rapidly growing indication for liver transplantation (LT) in the United States and is on a trajectory to become the leading indication for LT in the next decade. We aimed to study the trends in NASH-related LT among persons born between 1945 and 1965, the baby boomer (BB) generation. Methods: We performed a retrospective cohort analysis using population-based data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry from 2004–2015 to evaluate the birth cohort-specific trends in liver transplant waitlist registrations and liver transplant surgeries in patients with NASH. We stratified our study population into three birth cohorts: 1) birth before 1945, 2) birth between 1945 and 1965, and 3) birth after 1965. Results: The overall rates of NASH-related waitlist registrations and liver transplant surgeries steadily increased from 2004 to 2015 and were reflective of a sharp rise noted in the NASH BB sub-group. From 2004 to 2015, the proportion of BB patients with NASH added to LT waitlist demonstrated an incremental growth, 60.6% in 2004 versus 83.2% in 2015 (p < 0.01). Among the liver transplant recipients with NASH, the proportion represented by the BB cohort increased from 56.3% in 2004 to 80.0% in 2015 (p < 0.01). Conclusions: We report rising rates of waitlist registration and LT for the indication of NASH. More importantly, the BB sub-cohort was mainly responsible for these alarming trends.

ST segment elevation is associated with non-cardiac pathologies but is not as well reported as myocardial infarction. We present a case of a 63-year-old man who was admitted for an overdose on cyclobenzaprine with signs of anti-cholinergic toxicity. He developed signs of ileus on imaging and became progressively obtunded. He was noted to have ST segment elevations on electrocardiogram (EKG) with no troponin elevation. Patient required urgent catheterization which showed normal coronary arteries. His bowel was decompressed subsequently resulting in resolution of the ST segment changes. Other cases of ST segment elevations with gastrointestinal pathologies including cholecystitis, pancreatitis and gastric dilation have been reported but the etiology is still unclear. This case illustrates the importance of understanding EKGs in the clinical context. ST segment elevation on EKG, if there is contradicting symptomology and lab reports, should be further investigated to prevent unnecessary work-up and potentially dangerous therapies. [Full article available at http://rimed.org/rimedicaljournal-2016-11.asp].

Objectives Typhoid remain an increasing problem in Third world countries like Pakistan. A reliable, easy and affordable rapid diagnostic test is a need for our clinicians, many of whom consider Typhidot to be promising. Typhidot has been used as the only tool to diagnose typhoid fever by general practitioners and consultants despite its low sensitivity and specificity causing misdiagnosis and treatment. We therefore conducted this study to evaluate the sensitivity and specificity of Typhidot in patients with fever. Methods A retrospective analysis of a total of 145 febrile patients was done. Blood culture and Typhidot along with other relevant investigations had been performed in each case. Sensitivity, specificity and the association of Typhidot to the diagnosis was found using SPSS v16.0. Results Out of 145 patients, 15(10.3%) had positive blood culture for Salmonella typhi, 7 (4.8%) had positive culture for salmonella paratyphi and 94(64.8%) had positive culture for other organisms. Twenty nine (20%) patients had negative culture results. Forty seven (32.4%) patients had only IgM positive on Typhidot, 7(4.8%) had both IgM and IgG positive and 91(62.8%) had both IgM and IgG negative. Amongst the 130 patients with diseases other than typhoid, 50(38.5%) showed a positive Typhidot result. Amongst the 15 patients with typhoid, 11(73.3%) showed a negative Typhidot result. The sensitivity of Typhidot was found to be 26.7% and the specificity was 61.5%. The Positive Predictive Value (PPV) was 7.4% and the Negative Predictive Value (NPV) was 87.9%. Conclusion Even though Typhidot is rapid, easy and affordable, its use should be discouraged due to low sensitivity and specificity and insignificant (p=0.067) association to the disease.

Background Prevention of Hepatitis C virus (HCV) infection and its associated health complications are a national priority. To achieve optimal health outcomes, people with HCV must receive the diagnosis, link to and retain in care and receive treatment. Despite recent progress in increasing capacity and improving access to care for patients with HCV in the United States, there continues to be a need to improve Hepatitis C care especially in primary care settings. This study sought to assess HCV care in a resident-run primary care clinic of a community hospital. Methods Retrospective study of active patients ≥18 years with a diagnosis of Hepatitis C in the electronic medical records (EMR) at 2 outpatient medicine clinics at a community hospital in Rhode Island. Patients were identified by searching the following diagnoses in the EMR: “chronic hepatitis C”, “chronic hepatitis C without coma,” “chronic hepatitis C with coma,” “reactive HCV serology,” “hepatocellular carcinoma.” Patients with HIV coinfection were excluded as these patients are usually referred to a specialty clinic outside the hospital’s network. Results Of 12,482 outpatients, 306 had a diagnosis of Hepatitis C. One hundred and fifty-nine (54%) of these patients had HCV RNA detected indicating chronic infection, 51 (17%) patients had reactive HCV antibodies and undetected HCV RNA indicating past infection, and 84 (29%) patients had positive serology to HCV but lacked HCV RNA testing. Obesity was associated with not having HCV RNA checked (OR 2.9, 95% CI 1.66-5.24). No differences observed for other variables although patients with a history of alcohol use had a tendency towards lacking HCV RNA testing (P = 0.08). The prevalence of confirmed chronic hepatitis C was 1.6%. Twenty-three (21%) patients with chronic hepatitis C had cirrhosis and 5 had hepatocellular carcinoma however only a minority of them (11%) had received or were receiving direct acting antivirals. Hepatitis B vaccination in HCV infected patients was low (39%). Conclusion A significant proportion of patients with reactive serology to HCV in our primary care clinics miss the critical step of having HCV RNA checked. Other medical conditions such as obesity may take priority over HCV care. Implementation of HCV targeted interventions could improve HCV care in primary care. Disclosures All authors: No reported disclosures.

Dengue fever is on the rise in developing nations like India, Pakistan, Sri Lanka and Bangladesh. There is no antiviral chemotherapy or vaccine for dengue virus and management of the disease is done on supportive measures. The decline in the thrombocyte count leads to dengue haemorrhagic fever accounting for complications and mortality. Oral administration of Carica papaya leaves extract is said to have a positive impact on thrombocyte count. A 23-year-old man was administered a calculated dose for five days. Blood samples were tested for complete blood count before and after the administration of the juice. Thrombocyte count had increased from 28000/micro liter to 138000/micro liter at the end of five days. We present our experience here.

To compare the expected (perceptions of their environment at the beginning of their 1st year) versus actual perceptions (perceptions at the end of 1st year) of 1st year students at Dow University of Health Sciences.The 'expected' perceptions of the students were recorded at the beginning of their 1st year (n = 411) of medical education when they entered the medical school using Dundee Ready Educational Environment Measure (DREEM). DREEM is a validated and self-administered inventory which focuses on learning, teachers, self-confidence and academic as well as social environment. The 'actual' perceptions were then recorded at the end of their first year (n = 405) of education when they had received adequate exposure of their environment. The 2 records were then compared.The total expected DREEM score was 118/200 and the total actual DREEM score was 113/200. The expected domain (Students' perceptions of learning, students' perceptions of teachers, students' academic self-perceptions, students' perceptions of atmosphere, and students' social self-perceptions) scores were 28/48, 26/44, 20/32, 28/48, and 16/28. The actual domain scores were 27/48, 23/44, 19/32, 27/48, 16/28. However both the actual and expected scoring displayed satisfactory environment for learning. Significant differences (p0.0001) were found in the two samples.In general the results displayed that the students perceived the environment positively but the significant difference found in the two samples, demonstrated that their expectations were not met.