Diffuse-Type Pancreatic Ductal Adenocarcinoma Mimicking Autoimmune Pancreatitis.

Pancreatic ductal adenocarcinoma (PDAC) classically presents as a solitary mass on cross-sectional imaging. Diffuse-type PDAC is an unusual variant that accounts for 1%-5% of PDACs. Owing to its rarity, there are no established radiographic or endosonographic definitions. We report a unique case of diffuse-type PDAC presenting with imaging findings of 2 distinct masses in the pancreatic head and tail and with endoscopic ultrasound findings of diffuse gland enlargement mimicking autoimmune pancreatitis. The case illustrates the importance of sampling several areas of the pancreas when diffuse enlargement is present on endoscopic ultrasound and multiple masses are seen on cross-sectional imaging.

Drug-Induced Liver Injury Caused by "Khat," an Herbal Stimulant.

We describe a case of Catha edulis (Khat) drug-induced liver injury in a 28-year-old man from Yemen. The patient presented with jaundice, fatigue, and anorexia. Extensive workup, including liver biopsy, was performed. This is the first reported case in the United States without definite autoimmune hepatitis. Diagnosis requires high clinical suspicion and extensive workup. Increasing migration and differences in cultural practices lead to the need for an increased awareness of this type of cases, which is underreported.

Similar Sustained Virologic Response in Real-World and Clinical Trial Studies of Hepatitis C/Human Immunodeficiency Virus Coinfection.

BACKGROUND: Clinical trials evaluating efficacy of direct-acting antiviral (DAA) therapies demonstrate sustained virologic response (SVR) rates greater than 90% in patients infected with hepatitis C (HCV) and human immunodeficiency virus (HIV). However, generalizability of this data to real-world coinfected populations is unknown. AIM: We aim to compare efficacy data from clinical trials to effectiveness data of real-world observational studies that evaluate oral interferon-free HCV treatment regimens in patients infected with HIV and HCV. METHODS: We included English-language studies on PubMed and MEDLINE databases from inception until October 2017. Eight clinical trials and 11 observational studies reporting on efficacy data and effectiveness data, respectively, of interferon-free oral DAA regimens in HCV/HIV coinfected patients, were included. RESULTS: Of patients in the eight clinical trials evaluated, 93.1% (1218/1308) achieved SVR12; of the 11 real-world observational studies, 90.8% (2269/2499) achieved SVR12. Relative risk between those treated in clinical trials versus observational studies was 0.98. Patients with genotype 1 infection, African-American patients, cirrhotic patients, and patients with prior HCV treatment experience had similar rates of SVR in real-world and clinical trial cohorts. CONCLUSION: SVR among real-world HCV/HIV coinfected populations treated with DAA regimens is similar to SVR of patients studied in clinical trials. Historically negative predictors of achieving SVR during the era of interferon-based treatments, such as those with cirrhosis, prior HCV treatment failure, GT1 infection, and African-American race, are not associated with a significantly lower SVR in real-world populations treated with various DAA regimens.

Hepatitis C and human immunodeficiency virus coinfection in the era of direct-acting antiviral agents: No longer a difficult-to-treat population.

The treatment of chronic hepatitis C (HCV) in human immunodeficiency virus 1 (HIV)-infected individuals has been historically marked by low sustained virologic response (SVR) rates in comparison to those without HIV infection, resulting in the Food and Drug Administration labeling those coinfected as a "special population with an unmet medical need." We systematically reviewed the treatment of chronic HCV infection in those infected with HIV. We propose that with the advent of direct-acting antiviral (DAA) agents, patients coinfected with HCV and HIV have similar SVR rates as HCV-monoinfected persons and that DAAs address an unmet medical need in this population. A review was performed using Medical Subject Heading terms within the PubMed, EMBASE, and Cochrane Library databases to search for studies dated between January 2004 and July 2017. Keywords used in the study included "hepatitis C," "HIV," "coinfection," and "direct-acting antiviral." SVR rates for those with HCV and HIV coinfection treated with interferon-based therapies were substantially lower that SVR rates of HCV-monoinfected individuals. The advent of DAA agents has resulted in similar SVR rates between monoinfected and coinfected individuals, with SVR >93%. These medications have been demonstrated to have improved safety, efficacy, and tolerability in comparison to interferon-based regimens. CONCLUSION: The designation of a "special population" for those with coinfection requires reconsideration; DAA therapies have resulted in similarly high rates of SVR for HCV infection in those with and without HIV infection; despite these improvements, however, clinicians must be cognizant of negative predictors of SVR and barriers to treatment that may be more common in the coinfected population. (Hepatology 2018;67:847-857).

Clinical Food Addiction Is Not Associated with Development of Metabolic Complications in Liver Transplant Recipients.

Background and Aims: Given the increased risk of post-transplant metabolic syndrome (PTMS; defined by hypertension, diabetes mellitus and hyperlipidemia), we aimed to identify the potential role of food addiction in the development of metabolic complications in the post-liver transplant population. Methods: Inclusion criteria included adult liver transplant recipients followed at our institution between June 2016 and November 2016. Participants were administered a demographic survey as well as the Yale Food Assessment Scale 2.0, a 35-item questionnaire used to assess frequency of food addiction in accordance with the DSM-V guidelines of substance use disorders. Demographic and clinical data were collected. Results: Our study included 236 liver transplant recipients (139 males, 97 females). The median (interquartile range [IQR]) BMI of participants was 26.8 kg/m2 (24.2, 30.4), and median (IQR) time since transplantation was 50.9 months (19.6, 119.8). The prevalence rates of hypertension, hypercholesterolemia and diabetes mellitus were 54.7%, 25.0% and 27.1%, respectively. Twelve participants (5.1%) were found to have a diagnosis of food addiction. A diagnosis of food misuse was made in 94 (39.8%) of the transplant recipients. Conclusions: Our findings are consistent with prior data that indicate high prevalence of metabolic complications among liver transplant recipients. Food addiction was not predictive of metabolic complications within this population. Nevertheless, we found that this population was at high risk of demonstrating symptoms of food misuse, and they were not likely to appreciate the risks of pathologic patterns of eating. Given the increasing risk of cardiovascular morbidity and mortality in this population, efforts should be made to identify risk factors for the development of PTMS.

Rat animal model for preclinical testing of microparticle urethral bulking agents.

OBJECTIVES: To develop an economic, practical and readily available animal model for preclinical testing of urethral bulking therapies, as well as to establish feasible experimental methods that allow for complete analysis of hard microparticle bulking agents. METHODS: Alumina ceramic beads suspended in hyaluronic acid were injected into the proximal urethra of 15 female rats under an operating microscope. We assessed overall lower urinary tract function, bulking material intraurethral integrity and local host tissue response over time. Microphotographs were taken during injection and again 6 months postoperatively, before urethral harvest. Urinary flow rate and voiding frequency were assessed before and after injection. At 6 months, the urethra was removed and embedded in resin. Hard tissue sections were cut using a sawing microtome, and processed for histological analysis using scanning electron microscopy, light microscopy and immunohistochemistry. RESULTS: Microphotographs of the urethra showed complete volume retention of the bulking agent at 6 months. There was no significant difference between average urinary frequency and mean urinary flow rate at 1 and 3 months postinjection as compared with baseline. Scanning electron microscopy proved suitable for evaluation of microparticle size and integrity, as well as local tissue remodeling. Light microscopy and immunohistochemistry allowed for evaluation of an inflammatory host tissue reaction to the bulking agent. CONCLUSIONS: The microsurgical injection technique, in vivo physiology and novel hard tissue processing for histology, described in the present study, will allow for future comprehensive preclinical testing of urethral bulking therapy agents containing microparticles made of a hard material.

Bisphosphonate-related osteonecrosis of the jaw: what we have learned.

Bisphosphonate related osteonecrosis of the jaws (BRONJ) is an entity that has become prevalent upon the dental and medical community for more than 10 years. This entity is unfortunate because both oral and intravenous nitrogen containing bisphosphonates have beneficial effects for patients for certain conditions. The exact pathology of BRONJ has yet to be determined, although many hypotheses have been put forth. Since its prevalence, a clinical staging system has been developed and radiological findings have been described. BRONJ can be prevented if oral healthcare is undertaken before the start of bisphosphonate therapy or after a short time from the start of their use. However, after BRONJ has developed in patients, a myriad of treatments have been proposed that may help these patients.

The role of Bacillus anthracis RecD2 helicase in DNA mismatch repair.

DNA mismatch repair (MMR) systems can be classified as either MutH-dependent or MutH-independent. In bacteria, extensive studies have been conducted with the MutH-dependent MMR in Escherichia coli and its close relatives. The picture of MutH-independent MMR in other bacteria is less clear, as MMR components other than MutS and MutL have not been identified in the majority of bacteria. Bacillus anthracis is one of the MutH-less Gram(+) bacteria in the phylum of Firmicutes. We used papillation as a tool to search for B. anthracis new mutator strains and identified a spontaneous mutator that carries a minitransposon insertion in the BAS4289 locus. The mutational frequency and specificity exhibited in this mutant were comparable to that of MMR-deficient strains with knockouts of mutL or mutS. It retained a similar UV sensitivity profile as that of the wild type. BAS4289 encodes a putative DNA helicase RecD2 that shares 30% sequence identity with Deinococcus radiodurans RecD2, a well characterized superfamily 1B helicase whose homologs are widely present in Firmicutes complete genomes. We demonstrated that the N-terminal region of RecD2, a unique sequence extension used to distinguish RecD2 from RecD1, was important for B. anthracis RecD2, as mutations in the N-terminal conserved motifs affected its DNA repair function. This is the first report of a RecD2 helicase being associated with MMR. RecD2 and our recently described YycJ protein are likely to be two additional components in the B. anthracis MutH-independent MMR system.

Papillation in Bacillus anthracis colonies: a tool for finding new mutators.

Colonies of Bacillus anthracis Sterne allow the growth of papillation after 6 days of incubation at 30°C on Luria-Bertani medium. The papillae are due to mutations that allow the cells to overcome the barriers to continued growth. Cells isolated from papillae display two distinct gross phenotypes (group A and group B). We determined that group A mutants have mutations in the nprR gene including frameshifts, deletions, duplications and base substitutions. We used papillation as a tool for finding new mutators as the mutators generate elevated levels of papillation. We discovered that disruption of yycJ or recJ leads to a spontaneous mutator phenotype. We defined the nprR/papillation system as a new mutational analysis system for B. anthracis. The mutational specificity of the new mutator yycJ is similar to that of mismatch repair-deficient strains (MMR⁻) such as those with mutations in mutL or mutS. Deficiency in recJ results in a unique specificity, generating only tandem duplications.