Coordinated Targeting of Galanin Receptors on Cholangiocytes and Hepatic Stellate Cells Ameliorates Liver Fibrosis in Multidrug Resistance Protein 2 Knockout Mice.

Galanin (Gal) is a peptide with a role in neuroendocrine regulation of the liver. In this study, we assessed the role of Gal and its receptors, Gal receptor 1 (GalR1) and Gal receptor 2 (GalR2), in cholangiocyte proliferation and liver fibrosis in multidrug resistance protein 2 knockout (Mdr2KO) mice as a model of chronic hepatic cholestasis. The distribution of Gal, GalR1, and GalR2 in specific liver cell types was assessed by laser-capture microdissection and confocal microscopy. Galanin immunoreactivity was detected in cholangiocytes, hepatic stellate cells (HSCs), and hepatocytes. Cholangiocytes expressed GalR1, whereas HSCs and hepatocytes expressed GalR2. Strategies were used to either stimulate or block GalR1 and GalR2 in FVB/N (wild-type) and Mdr2KO mice and measure biliary hyperplasia and hepatic fibrosis by quantitative PCR and immunostaining of specific markers. Galanin treatment increased cholangiocyte proliferation and fibrogenesis in both FVB/N and Mdr2KO mice. Suppression of GalR1, GalR2, or both receptors in Mdr2KO mice resulted in reduced bile duct mass and hepatic fibrosis. In vitro knockdown of GalR1 in cholangiocytes reduced α-smooth muscle actin expression in LX-2 cells treated with cholangiocyte-conditioned media. A GalR2 antagonist inhibited HSC activation when Gal was administered directly to LX-2 cells, but not via cholangiocyte-conditioned media. These data demonstrate that Gal contributes not only to cholangiocyte proliferation but also to liver fibrogenesis via the coordinate activation of GalR1 in cholangiocytes and GalR2 in HSCs.

Eosinophilic pancreatitis presenting as possible malignancy.

Eosinophilic pancreatitis is a rare form of chronic pancreatitis that is often mistaken for malignancy due to nonspecific presenting symptoms and noncontributory auxiliary exams. This clinical case report highlights a unique presentation of chronic pancreatitis. A middle-aged man developed abdominal pain, and repeat imaging showed an interval increase in size of a known pancreatic lesion. A core biopsy showed benign pancreatic tissue with eosinophilic-rich inflammation; IgE levels were also elevated. The patient was started on a prednisone taper, and repeat computed tomography 3 months later showed a decreased size of the pancreatic lesion. Correct and timely diagnosis of eosinophilic pancreatitis may avoid invasive unnecessary surgical procedures and allow for earlier initiation of appropriate therapy.

Diagnosis and treatment of malignant-appearing arteriovenous malformation.

Arteriovenous malformations (AVM) are most commonly found in the gastrointestinal tract, and presentation can range from asymptomatic to massive gastrointestinal hemorrhage. This case highlights a unique presentation of AVMs. During a screening colonoscopy, a 5-cm mass was discovered in the transverse colon encompassing 25% to 50% of the circumference of the lumen. Biopsies showed polypoid AVM with overlying inflammatory polyps without evidence of malignancy or dysplasia. There are many treatment options for AVM removal. In this case, since suspicion for malignancy was high, the patient underwent surgery and will be closely monitored.

Prevalence of cannabinoid hyperemesis syndrome and its financial burden on the health care industry.

Cannabis is the most commonly consumed recreational drug in the world. As more states legalize cannabis use in some form, the incidence of cannabinoid hyperemesis syndrome (CHS) is expected to rise. CHS is a constellation of symptoms including severe cyclical nausea and vomiting and epigastric or periumbilical abdominal pain as a result of long-term cannabis use. Recognizing the diagnosis and educating patients on the benefits of cessation is essential, as these patients often undergo extensive and repeated evaluations in the clinic, emergency department, and inpatient setting that could be avoided with extensive history taking and early recognition of the syndrome. In this study, we compared costs incurred by patients in various settings to determine if there is a difference between patients with and without CHS. Although there were not statistically significant cost differences between groups for all cost categories, it is clear that patients with CHS consume considerably more health care dollars than patients who deny cannabis use, and obtaining a detailed social history is imperative to prevent unnecessary workups and increased financial burden on the health care industry.

Comparison of Mid-Turbinate and Nasopharyngeal Specimens for Molecular Detection of SARS-CoV-2 Among Symptomatic Outpatients at a Pediatric Drive-Through Testing Site.

BACKGROUND: Nasopharyngeal (NP) specimen testing by reverse transcriptase polymerase chain reaction (RT-PCR) is the standard of care for detecting SARS-CoV-2. Data comparing the sensitivity and specificity of the NP specimen to the less invasive, mid-turbinate (MT) nasal specimen in children are limited. METHODS: Paired clinical NP and research MT specimens were collected from children <18 years with respiratory symptoms and tested by molecular assays to detect SARS-CoV-2 RNA. Sensitivity, specificity, and agreement (Cohen's kappa [κ]) were calculated for research MT specimens compared to the clinical NP specimens. RESULTS: Out of 907 children, 569 (62.7%) had parental consent and child assent when appropriate to participate and provided paired MT and NP specimens a median of 4 days after symptom onset (range 1-14 days). 16.5% (n = 94) of MT specimens were positive for SARS-CoV-2 compared with 20.0% (n = 114) of NP specimens. The sensitivity of research MT compared to clinical NP specimens was 82.5% (95% CI: 74.2%, 88.9%), specificity was 100.0% (95% CI: 99.2%, 100.0%), and overall agreement was 96.1% (κ = 0.87). The sensitivity of MT specimens decreased with time from 100% (95% CI: 59.0%, 100.0%) on day 1 of illness to 82.1% (95% CI: 73.8%, 88.7%) within 14 days of illness onset; sensitivity was generally >90% when specimens were collected within the first week of illness. CONCLUSION: MT specimens, particularly those collected within the first week of illness, have moderately reduced sensitivity and equivalent specificity to less-tolerated NP specimens in pediatric outpatients. MT specimen use in children may represent a viable alternative to NP specimen collection.