NASH and the Gut Microbiome: Implications for New Therapies.

Content available: Author Audio Recording.

Anal adenocarcinoma: case report, literature review and comparative survival analysis.

INTRODUCTION: Anal adenocarcinoma is a rare malignancy with a poor prognosis. METHODS: We present a case of rare anal adenocarcinoma in a patient with normal screening colonoscopy. Using the Surveillance, Epidemiology and End Result database between 2000 and 2016, we performed survival analysis among individuals>20 years old comparing anal and rectal cancers. RESULTS: Survival analysis showed that anal adenocarcinoma is associated with worse outcomes compared with rectal adenocarcinoma and anal squamous cell carcinoma. DISCUSSION: This case and survival data illustrate the importance of prompt investigation of symptoms irrespective of colorectal cancer screening status with careful attention to examination of the anal area.

Assessing the Effectiveness of Strategies in US Birth Cohort Screening for Hepatitis C Infection.

Chronic hepatitis C infection in the USA is a highly morbid condition and current guidelines recommend one-time screening among the birth cohort (1945-1965). Understanding strategies to optimize screening can help inform future hepatitis C virus (HCV) screening guidelines. A focused literature search was performed using PubMed and manual abstract review from major hepatology conferences over the past 2 years. The search strategy involved using Medical Subject Headings terms for hepatitis C, screening, birth cohort, baby boomers, and 1945-1965. The review was limited to data from the USA. A total of 327 articles were identified and 36 abstracts were included, with studies published between 2012-2019. Strategies including clinician education, electronic medical record alerts, reflex HCV RNA testing, point-of-care testing, multisite (outpatient, inpatient, emergency department, endoscopy suite) initiatives, direct patient solicitation, and utilization of non-physician providers have increased HCV screening rates. However, broad implementation remains less than optimal. Barriers include lack of patient acceptance to screening and engagement in the HCV care cascade. The Veterans Affairs Healthcare System has achieved higher birth cohort screening rates through an integrated approach requiring high-level engagement by leadership and institutional commitment. Multiple strategies for increasing birth cohort screening have been successful, but overall rates of HCV screening remain low. These strategies can inform public health efforts to implement emerging national recommendations for expansion of HCV screening to all U.S. adults age 18 or older.

Do Vertical Soft Tissue and Actual Bony Landmarks Correlate in Le Fort I Orthognathic Surgery?

PURPOSE: Vertical changes in Le Fort I orthognathic surgery are critical to the overall esthetic result. Three-dimensional planning enables vertical measurements from the rendered computed tomographic (CT) scan, but intraoperative points are ascribed partially from soft tissues landmarks. This study compared intraoperative soft tissue vertical measurements with pre- and postoperative CT-based values and attempted to validate intraoperative soft tissue landmarks for vertical positioning. MATERIALS AND METHODS: In this retrospective single-cohort study, the authors examined orthognathic procedures performed by a single surgeon at their institution. Patients were excluded if measurements or pre- and postoperative CT scans were lacking. Demographic information and soft tissue perioperative data were tabulated. Clinical vertical measurements included the left medial canthus to the central incisor, the left medial canthus to the left canine, and the right medial canthus to the right canine. Bone measurements were calculated using pre- and postoperative cone-beam CT scans for the same clinical landmarks. Statistical analysis, including paired Student t test, was performed using SPSS. RESULTS: Forty-two patients were identified (mean age, 23 yr; 57% female). The change in pre- and postoperative measurements was analyzed. There was no significant difference in the absolute value pre- and postoperatively between the 2 modalities (P < .2, .1, .1), but there was a significant difference between bony and soft tissue measurements (P < .01). Subset analysis showed differences in postoperative values between Class II and III cases. CONCLUSIONS: These results show a nonlinear but predictable relation between intraoperative soft tissue (medial canthi and maxillary dentition) and CT-measured bony vertical measurements. Understanding this relation enables effective use of intraoperative measurements to reproducibly achieve the desired bony vertical position and allows adjustments to be made to optimize esthetics.

Harvey Cushing Treated the First Known Patient With Carney Complex.

CONTEXT: Carney complex (CNC) is a syndrome characterized by hyperplasia of endocrine organs and may present with clinical features of Cushing syndrome and acromegaly due to functional adrenal and pituitary gland tumors. CNC has been linked to mutations in the regulatory subunit of protein kinase A type I-alpha (PRKAR1A) gene. DESIGN: Tissue samples were taken from the hypothalamus or thalamus or tumors of patients with pituitary adenomas seen and operated on by neurosurgeon Harvey Cushing between 1913 and 1932. Following DNA extraction, sequencing for genes of interest was attempted, including PRKAR1A, AIP, USP8, GNAS1, and GPR101, to explore the possibility that these mutations associated with acromegaly, CNC, and Cushing syndrome have been conserved over time. RESULTS: We report a patient described by Dr. Cushing in 1914 with a clinical presentation and postmortem findings suggestive of CNC. Genetic sequencing of the hypothalamus and pituitary adenoma revealed a germline heterozygous p.Arg74His mutation in the PRKAR1A gene, a codon previously described as mutated in CNC, but with a novel amino acid change. CONCLUSIONS: This patient is, to our knowledge, the first molecularly confirmed individual with CNC. This case demonstrates the power of modern genetics in studying archived tissues and the importance of recording detailed clinical notes in the diagnosis of disease.

Julius Wagner-Jauregg and the legacy of malarial therapy for the treatment of general paresis of the insane.

Julius Wagner-Jauregg, a preeminent Austrian psychiatrist was awarded the Nobel Prize in Medicine in 1927 for the development of malaria therapy for the treatment of neurosyphilis, or general paresis of the insane. Despite being only one of three psychiatrists to win a Nobel Prize, he has faded from public consciousness and his name recognition pales in comparison to his contemporary and fellow Austrian, Sigmund Freud. This paper explores his contributions to the field of biological psychiatry and also touches upon reasons, such as the growing bioethics movement, his controversial affiliation with the Nazi Party, and the evolution of neurosyphilis, that explain why Wagner-Jauregg is not more widely celebrated for his contributions to the field of psychiatry, even though his malarial treatment could be considered the earliest triumph of biological psychiatry over psychoanalysis.

Successful treatment of recurrent primary sclerosing cholangitis after orthotopic liver transplantation with oral vancomycin.

Primary sclerosing cholangitis (PSC) is a progressive, cholestatic disease of the liver that is marked by inflammation of the bile ducts and damage to the hepatic biliary tree. Approximately 60-70% of patients also have inflammatory bowel disease and progression of PSC can lead to ulcerative colitis and cirrhosis of the liver. Due to limited understanding of the etiology and mechanism of PSC, the only existing treatment option is orthotopic liver transplantation (OLT); however, recurrence of PSC, after OLT is estimated to be between 5% and 35%. We discuss the successful treatment of a pediatric patient, with recurrent PSC, after OLT with oral Vancomycin.