Successful treatment of chronic hepatitis C infection with crushed elbasvir/grazoprevir administered via a percutaneous endoscopic gastrostomy tube.

WHAT IS KNOWN AND OBJECTIVE: Elbasvir/grazoprevir is an all-oral regimen approved for patients with hepatitis C virus (HCV) genotypes 1 and 4, and in renal insufficiency. However, to date, no data exist on the efficacy of this regimen when it is crushed and administered through a percutaneous endoscopic gastrostomy (PEG) tube. Here, we illustrate the case of a 63-year-old man who is the only known patient with HCV infection in the English literature to have successfully achieved a sustained viral response (SVR) when elbasvir/grazoprevir oral combination was administered through a PEG tube. CASE SUMMARY: A 63-year-old man with worsening HCV-associated membranoproliferative glomerulonephritis was referred to the gastroenterology clinic for prompt HCV treatment. He had history of high-grade mucoepidermoid carcinoma of the parotid status post-resection and was expected to develop severe mucositis and dysphagia during radiation precluding typical oral therapy of his HCV. He received a PEG tube for nutrition and underwent a 16 week course of crushed Elbasvir/Grazoprevir for HCV treatment through the PEG. At the end of the therapy he achieved SVR and his kidney function also improved. WHAT IS NEW AND CONCLUSION: We present the first known clinical case of a non-cirrhotic patient with HCV genotype 1A with HCV-related MPGN treated successfully with crushed Elbasvir/Grazoprevir administered through a PEG tube. With the prevalence of PEG tube insertion and HCV on a rise, we expect these 2 population cohorts to intersect in the future. Our report may serve as a guidance in such clinical scenario.

Acute liver failure with amiodarone infusion: A case report and systematic review.

WHAT IS KNOWN AND OBJECTIVE: Amiodarone, a commonly used class III antiarrhythmic agent notable for a relatively long half-life of up to 6 months and its pronounced adverse effect profile, is used for both acute and chronic management of cardiac arrhythmias. Chronic use of amiodarone has been associated with asymptomatic hepatotoxicity; however, acute toxicity is thought to be uncommon. There are only six reported cases of acute liver failure (ALF) secondary to amiodarone. In all these cases the outcome of death during the same hospitalization resulted. We aimed to report the only case of acute liver failure secondary to amiodarone infusion in the existing literature where the patient survived. CASE SUMMARY: A 79-year-old woman admitted with atrial flutter was being treated with intravenous (IV) amiodarone when she abruptly developed coagulopathy, altered mental status and liver enzyme derangement. She was diagnosed with acute liver failure (ALF) secondary to an amiodarone adverse drug reaction, with a calculated score of seven on the Naranjo adverse drug reaction probability scale. Amiodarone was immediately withheld, and N-acetylcysteine (NAC) was initiated. Clinical improvement was seen within 48 hours of holding the drug and within 24 hours of initiating NAC. On post-hospital follow-up visit she was reported to have complete recovery. WHAT IS NEW AND CONCLUSION: This report emphasizes the importance of monitoring liver enzymes and mental status while a patient is being administered IV amiodarone. N-acetylcysteine administration may have possibly contributed to the early and successful recovery from ALF in our patient. To date, she is the only patient in the existing literature who has been reported to survive ALF secondary to amiodarone administration.

The prevalence and impact of psychiatric comorbidities on hospitalized inflammatory bowel disease patients in the United States: insights from the National Inpatient Sample from 2009-2018.

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of anxiety and mood disorders. This study examines the temporal trends and clinical impact of anxiety and mood disorder diagnoses in hospitalized IBD patients in the United States during a 10-year period. Methods: Using the National Inpatient Sample from 2009-2018, all IBD-related discharges in adults were analyzed. Primary outcomes were the prevalence and temporal trends of mood disorder and anxiety diagnoses for IBD-related admissions. The impact of the psychiatric comorbidities on clinical outcomes was also evaluated. Results: A total of 1,718,736 IBD-related discharged were identified. A diagnosis of anxiety or a mood disorder was found to have a prevalence of 16.44% and 18.97%, respectively, amongst IBD-related admissions. The prevalence of anxiety disorders amongst hospitalized IBD patients increased significantly (from 12.13% to 20.26%), whereas the prevalence of mood disorders did not (17.46% and 18.9%). IBD admissions with psychiatric comorbidities had lower rates of IBD-related complications or mortality during hospitalization compared to IBD admissions without comorbid psychiatric diagnoses. This population, however, was more likely to experience certain comorbidities such as Clostridioides difficile, pneumonia, and venous thromboembolism, as well as a longer hospitalization. Conclusions: The prevalence of comorbid anxiety among hospitalized IBD patients in the United States matches or exceeds the prevalence of anxiety in the general hospitalized population. Given its association with more in-hospital complications and a longer hospital stay, it is important to further understand how psychological screening and mental health services can improve the management of hospitalized IBD patients.

Protective effects of resveratrol against osteonecrosis at the extraction site in bisphosphonate-treated rats.

Resveratrol (RSV) is a phytoestrogen with a wide range of therapeutic effects, including antioxidant and anti-inflammatory effects. This study was performed to evaluate the protective role of RSV against osteonecrosis after tooth extraction in rats treated with bisphosphonates. Thirty-nine male Wistar rats, weighing 300-350 g, were divided into three groups (n = 13) according to the planned drug regimen: alendronate + dexamethasone (AL/DEX), alendronate + dexamethasone + RSV (AL/DEX/RSV), and no drugs (control group). The first and second molars of each rat were extracted and the extraction sites were analysed histologically 14 days later. The data collected were subjected to statistical analysis by means of Kruskal-Wallis, Mann-Whitney, χ2, and Fisher's exact tests using IBM SPSS software at a significance level of 0.05. The incidence of osteonecrosis was significantly lower in the AL/DEX/RSV group (P = 0.001) and control group (P = 0.041) than in the AL/DEX group, while the amount of new bone formation did not differ significantly between the AL/DEX/RSV and AL/DEX groups (P > 0.05). RSV showed a protective effect by significantly reducing osteonecrosis, which could be due to its antioxidant effects.

Health Indicators for Renal Replacement Therapy in Saudi Arabia.

The renal replacement therapy in Saudi Arabia has 3 main modalities: hemodialysis, peritoneal dialysis, and renal transplantation. Hemodialysis is one of the fastest growing industries of health care providers in Saudi Arabia. OBJECTIVE: We aimed to review the health indicators of renal replacement therapy. MATERIALS AND METHODS: We used the Saudi Center for Organ Transplantation Annual Report 2016. RESULTS: Patients with end-stage renal disease on hemodialysis and peritoneal dialysis totaled 17,687. Saudi Arabia increased the numbers of dialysis centers and also added 2 more sectors. The Ministry of Health hospitals have 55% of the centers, government non-Ministry of Health has 9%, private and charitable hospitals have 21%, the King Abdullah Hemodialysis Project has 2%, and the outsourcing dialysis programs have 13%. There are 243 dialysis units in Saudi Arabia. Most dialysis centers are in the central region (30%); 27% are in the western region, 19% are in the southern region, 13% are in the eastern region, and 11% are in the northern region. The average net increase of dialysis patients is 6.2% annually and is projected to reach 22,000 by 2020. Causes of renal failure are mainly diabetic nephropathy (40%) and hypertensive nephropathy (38%). Hepatitis C virus positivity is at 12% and hepatitis B surface antigen positivity is at 4%. From the year 2000 renal transplantation from deceased and living donation has tripled in number, with a total of 798 kidneys transplanted. CONCLUSION: Renal replacement therapy is increasing and dialysis center numbers are expected to increase. Renal transplantation numbers have improved both from living and deceased donors but further actions toward the promotion of the organ donation in Saudi Arabia is essential.

Performance of Khorana Risk Score for Prediction of Venous Thromboembolism in Patients With Hepatocellular Carcinoma.

Cancer-associated venous thromboembolism (VTE) is one of the leading causes of mortality and morbidity among patients with malignancy. The Khorana risk score (KRS) is currently the best validated risk assessment model to stratify risks of VTE development in ambulatory patients with cancer. In the current study, we assessed the performance of KRS in patients with hepatocellular carcinoma (HCC). We retrospectively analyzed patients with diagnosis of HCC (screened by International Classification of Diseases [ ICD-9] and ICD-10 code, confirmed with radiographic examination and/or histopathology) at a large public hospital over 15 years (January 2000 through July 2015). Cases with VTE were identified through radiographic examination and blindly adjudicated. Khorana risk score was calculated for each patient, and its association with VTE development and mortality was assessed. Among 270 patients with HCC, 16 (5.9%) cases of VTE were identified, including 7 (43.8%) pulmonary embolism, 4 (25%) peripheral deep vein thrombosis, and 6 (37.5%) intra-abdominal thrombosis. One hundred eighty-four (68.1%) patients had a KRS of 0 and 86 (31.9%) patients had a KRS >0. Most of the thrombotic (n = 9, 56%) events occurred in the low-risk group. In univariate analysis, only prechemotherapy leukocyte count equal to or greater than 11 000/µL was statistically significant in the prediction of VTE incidence. After adjusting for confounding factors in multivariate analysis, KRS >0 was not predictive of VTE (hazard ratio [HR] = 1.83, 95% confidence interval [CI] = 0.81-4.15, P = .15) or mortality (HR = 1.61, 95% CI = 0.92-2.81, P = .09). Khorana risk score did not predict VTE development or mortality in patients with HCC. Design of HCC-specific risk assessment model for VTE development is necessary.

Characteristics and Impacts of Venous Thromboembolism in Patients with Hepatocellular Carcinoma.

INTRODUCTION: Venous thromboembolism (VTE) is a common complication in cancer patients, and is associated with worse prognosis in such population. Hepatocellular carcinoma (HCC) poses high risk for VTE; however, data is scarce regarding the characteristics and consequences of VTE in HCC patients. METHOD: We retrospectively reviewed the electronic medical records (EMR) of 270 patients diagnosed with HCC from 2000 to 2015 in Cook County Health and Hospitals System. We report the cumulative incidence of VTE in the present cohort, and identified through multivariate logistic regression the independent risk factors of the development of VTE. Overall prognosis of patients with and without VTE were presented and compared. RESULTS: Sixteen cases (5.93%) of VTE were documented in the present study. In multivariate analysis, obesity, Child B cirrhosis, intra-hepatic lesions more than 3, and multi-organ extrahepatic metastasis were significantly associated with VTE development (p < 0.05). The presence of VTE was an independent risk factor for mortality in multivariate analysis (HR = 3.62, p = 0.021), together with male gender, Child C cirrhosis, and extrahepatic metastasis. CONCLUSIONS: Obesity, Child B cirrhosis, more intra-hepatic lesions, and multi-organ extrahepatic metastasis are associated with cancer-associated VTE. VTE will adversely affect the prognosis of patients with HCC; therefore, primary thromboprophylaxis may be warranted in such population.

Successful use of kidneys from deceased donors with acute renal failure.

BACKGROUND: Kidneys from deceased donors with acute renal failure are not widely used. OBJECTIVE: To compare outcomes for recipients of kidneys from donors with acute renal failure at organ recovery with outcomes for recipients of kidneys from donors with normal serum levels of creatinine. METHODS: Records of deceased donors and recipients of their organs at the Saudi Center for Organ Transplantation from 2003 to 2005 were reviewed. A total of 33 donors (donating 65 kidneys to 65 recipients) with elevated serum levels of creatinine (>1.7 mg/dL) and 94 donors (donating 188 kidneys to 188 recipients) with normal (<1.1 mg/dL) serum levels of creatinine at organ recovery and their respective recipients were compared. Both groups had normal creatinine levels at admission. RESULTS: Recipients in both groups had similar renal function at discharge and follow-up. Delayed graft function occurred more often (P= .009) in the recipients of kidneys from donors with acute renal failure (47.7%) than in recipients of kidneys from donors with normal creatinine levels (29.8%). Elevation of serum level of creatinine at organ recovery did not correlate significantly with kidney function at discharge or last follow-up or with graft survival. CONCLUSIONS: Survival of patients or grafts at 1, 2, and 3 years did not differ significantly between the recipients in the 2 groups. Only the frequency of delayed graft function differed between the 2 groups.

A proposed Saudi approach to the ethical utilization of living unrelated kidney donation.

We outline a proposal for the use of living unrelated kidney donors for transplantation. This proposal, although recommended by the Saudi National Committee on Renal Transplantation, is still under discussion and has not been implemented yet. We feel that this proposal is ethical with airtight safeguards against commercialization and for the protection of the well-being of the donor with assurance that he or she has not been coerced into donation.

Resveratrol-induced inactivation of human gastric adenocarcinoma cells through a protein kinase C-mediated mechanism.

Resveratrol, a polyphenolic phytochemical present in berries, grapes, and wine, has emerged as a promising chemopreventive candidate. Because there is scant information regarding natural agents that prevent, suppress, or reverse gastric carcinogenesis, the aim of the present study was to determine the chemopreventive potential of resveratrol against gastric cancer by investigating cellular and molecular events associated with resveratrol treatment of human gastric adenocarcinoma cells. We determined the action of resveratrol on cellular function and cellular integrity by measuring DNA synthesis, cellular proliferation, cell cycle distribution, cytolysis, apoptosis, and phosphotransferase activities of two key signaling enzymes, protein kinase C (PKC) and mitogen-activated protein kinases (ERK1/ERK2), in human gastric adenocarcinoma KATO-III and RF-1 cells. Resveratrol inhibited [3H]thymidine incorporation into cellular DNA of normally proliferating KATO-III cells and of RF-1 cells whose proliferation was stimulated with carcinogenic nitrosamines. Treatment with resveratrol arrested KATO-III cells in the G(0)/G(1) phase of the cell cycle and eventually induced apoptotic cell death, but had a minimal effect on cell lysis. Resveratrol treatment had no effect on ERK1/ERK2 activity but significantly inhibited PKC activity of KATO-III cells and of human recombinant PKCalpha. Results indicate that resveratrol has potential as a chemopreventive agent against gastric cancer because it exerts an overall deactivating effect on human gastric adenocarcinoma cells. Resveratrol-induced inhibition of PKC activity and of PKCalpha, without any change in ERK1/ERK2 activity, suggests that resveratrol utilizes a PKC-mediated mechanism to deactivate gastric adenocarcinoma cells.

MAPK activity is down-regulated in human colon adenocarcinoma: correlation with PKC activity.

Cellular growth is regulated by a cascade of kinases, among which mitogen activated protein kinase (MAPK) is an integral member of the Ras-mediated pathway, while protein kinase C (PKC) is recognized as the intracellular receptor of tumor promoters. To assess the role of these two signal transduction enzymes in colonic carcinogenesis, we measured MAPK and PKC activities in cytosol and membrane compartments of: 1) normal colon, 2) colon adenocarcinoma, and 3) histologically normal colonic tissue taken from the margin of resection of neoplastic colon. Both MAPK and PKC activities were down-regulated in solubilized membranes from the cancers. MAPK activity was also down-regulated in the tissue adjacent to the cancer and designated as histologically normal (by routine histopathology). Therefore, MAPK activity appears to be more suitable than PKC as a marker for early detection of colonic transformation.

Cytoskeletal PKC and ERK/MAPK activation in response to N-nitrosamines and phorbol 12-myristate 13-acetate in gastric adenocarcinoma cells.

Phorbol 12-myristate 13-acetate (PMA) exerts its tumor promotional action by targeting cellular PKC. Carcinogenic nitrosamines (NA) induce tumor formation in the absence of a tumor promoter, and have not been implicated as modulators of signal transduction events. We measured the distribution of PKC and ERK/MAPK activities between cytosol, plasma membranes and cytoskeleton of human gastric adenocarcinoma RF-1 cells after 60 minute and 24 hour treatments with 50 microM NA or 100 nM PMA. At 60 minutes, PMA caused translocation of PKC from cytosol to plasma membranes and increased plasma membrane ERK/MAPK activities; 24-hour treatment with PMA resulted in downregulation of membrane PKC and ERK/MAPK, but an increase in cytoskeletal PKC and ERK/MAPK. NA treatment targeted only cytoskeletal activities, producing a sharp increase in PKC at 60 minutes with further increase after 24 hours. Cytoskeletal ERK/MAPK was elevated only after 24 hours with NA. The converging action of NA and PMA on cytoskeletal PKC and ERK/MAPK activities suggests that both agents may focus on a common cellular target.

Marked asymmetry of LES: important element of LES barrier in subsets of patients with reflux symptoms.

Computerized axial manometry (CAM) of the lower esophagus measures squeeze pressure at multiple points in each segment of the lower esophageal sphincter (LES), calculates several unique parameters of LES function, and constructs a 3-D display of the LES. Whether parameters derived from CAM, such as the radial mean pressure (LESrmp), Asymmetry (Asym), and Vector Volume (VV), have relevance to function of the LES remains undefined. This study compares the results of CAM in patients with gastroesophageal reflux disease (GERD) and controls. There were 54 patients with GERD and 21 volunteers; all underwent CAM as part of their evaluation; GERD was defined by clinical and endoscopic examinations, and all patients had abnormal 24-hour pH tests. Statistical evaluation was performed. The LESrmp and the Vector Volume were significantly correlated in both groups of patients and differed significantly in both. Asymmetry of the LES was a significant negative factor in LES strength as shown by VV and LESrmp. Asymmetry alone, however, did not show a strong correlation with reflux. Asymmetry is indirectly correlated with the major determinants of LES strength; in patients with low VV, asymmetry might be a critical factor. When a high VV is present, asymmetry has no particular relevance. CAM provides invaluable measurements of the LES.

Impact of recipient and donor nonimmunologic factors on the outcome of deceased donor kidney transplantation.

OBJECTIVE: To study the influence of nonimmunologic factors on the outcome of extended criteria deceased donor (DD) kidney transplants. METHOD: This is a retrospective study of DD transplantation carried out from January 1, 2003 to December 31, 2007, to investigate the impact on graft survival and function of donor renal function at retrieval, cold ischemia time (CIT), delayed graft function (DGF), acute rejection episodes (ARE), age, and weight of donors and recipients, transplant center activities, cause of donor death, donor-recipient gender pairing and size of the donating intensive care unit (ICU). RESULTS: At retrieval, the frequency of donors with a creatinine clearance <60 mL/min, using the Cockcroft-Gault formula, and age >40 years were 31.7% and 32%, respectively. CIT > 24 hours, DGF, and ARE occurred in 27.1%, 33.4%, and 16.5% of cases, respectively. The overall 1- and 5-year graft and patient survival rates were 88% and 79.8% and 96.6% and 92.3%, respectively. The graft function was inferior with occurrences of ARE (P = .0001), DGF (P = .0001), CIT > 20 hours (P = .005), nontraumatic the donor death (P = .022), and donor ICUs bed capacity <20 (P = .03). The odds ratio (OR) for graft loss with DGF, ARE, and donors right kidneys were 7.74 (95% confidence interval [CI] 6-13.4; P = .0001), 4.47 (95% CI, 2.6-7.6; P = .0001) and 1.7 (95% CI, 1-2.8; P = .045), respectively. Graft function was not influenced by donor renal function at retrieval, donor weight, or donor- recipient gender pairings. CONCLUSION: CIT and ARE had an impact on both graft survival and function. DGF and cerebrovascular accidents as the cause of donor death negatively affected graft function during follow-up. ICU center experience had a positive impact on graft survival. Patient survival was affected by recipient age >50 years and female to male donation versus other gender pairings. Neither donor age nor acute terminal rise in the donor serum creatinine affected graft function or survival, or patient mortality.

Serological markers of autoimmunity in patients infected with hepatitis C virus: impact of HIV co-infection.

OBJECTIVES: We sought to evaluate the prevalence, predictors and significance of autoantibody expression in patients with chronic hepatitis C (CHC) with or without HIV co-infection. METHODS: Retrospective review of laboratory and histologic data for all patients with CHC who had a liver biopsy available. HIV status was documented in all patients. Results analyzed in SPSS10, Chicago, IL, a p value <0.05 was considered significant. RESULTS: 170 patients with hepatitis C viremia, including 107 (63%) HIV co-infection, who had testing for anti-nuclear antibody (ANA) or anti-smooth muscle antibody (ASMA) and anti-mitochondrial antibody (AMA) were included in the study. Overall, 63% (74/117) of patients were ASMA seropositive and 6% (9/153) were positive for ANA. All 117 patients tested for AMA were negative. HIV co-infected patients were significantly more likely to be ASMA positive 71% (53/75) compared to those with hepatitis C alone (50%) [P=0.026]. There were no significant differences in age, gender, race, risk group, alanine aminotransferase (ALT) levels or grade of inflammation on histology between autoantibody positive and negative patients. ASMA positive patients had significantly higher globulin levels (P=0.036) and a trend towards more bridging fibrosis or cirrhosis. Patients with autoantibody expression rarely had histologic features of AIH. CONCLUSION: We found a high rate of ASMA seropositivity in our cohort of patients with chronic hepatitis C, and HIV co-infection was associated with significantly higher rates of ASMA expression. Autoantibody expression was not associated with demographic or clinical characteristics and does not necessarily preclude antiviral therapy.

Apoprotein A-1 is a cofactor independent substrate of protein kinase C.

Apoprotein A-1 (apo A-1), the predominant protein constituent of high density lipoproteins (HDL), was phosphorylated by protein kinase C (PKC). Optimal phosphorylation of lipid-free apo A-1 occurs in the absence of calcium, phosphatidyl serine (PS), and diolein (DO). However, HDL-bound apo A-1 was not phosphorylated by PKC. Furthermore, addition of either native or reconstituted HDL particles to lipid-free apo A-1 resulted in a concentration-dependent inhibition of phosphorylation. It appears that the phosphorylatable sites on apo A-1 are involved in hydrophobic interaction with the lipids of HDL. Apo A-1 is a novel substrate of PKC because it does not require calcium and lipid cofactors for optimal phosphorylation.

Small cell carcinoma of the esophagus. Report of three cases and review of the literature.

Small cell carcinoma has been described in the lung, stomach, pancreas, small intestine, larynx, hypopharynx, thymus, kidney, prostate, breast, cervix, skin, and esophagus. Our three cases and review of the literature confirm that the clinical presentation and eventual evolution of small cell carcinomas of the esophagus appear to be basically similar to those of the far more frequently occurring squamous and glandular carcinomas. However, certain differences in age and sex distribution of cases should be noted. Although squamous cell carcinomas occur three to four times more commonly in males, the male-to-female ratio in SCC in 1.6. Squamous cell carcinomas of the esophagus reach a peak in the fifth and sixth decades of life; SCC cases occur a decade later. All of our patients had history of heavy smoking more than 50 pack-years, a factor that has also been implicated in predisposition to squamous cell carcinoma of the esophagus. History of smoking to this extent was also mentioned in three other patients. There are also some differences in the location of the tumor. SCC rarely occurs in the upper third of the esophagus. The most common location of this tumor is the lower third where APUD cells are most abundant. On the other hand, a majority of squamous cell carcinomas of the esophagus are localized to the middle third, the upper and lower third being involved in equal proportions of the cases. Despite the above reported differences in clinical symptoms and course of these two tumors, their gross appearance is similar. Mean survival of both diseases also seems to be similar.(ABSTRACT TRUNCATED AT 250 WORDS)