Esophagogastroduodenoscopy and Esophageal Involvement in Patients with Pemphigus Vulgaris.
Preoperative Endoscopic Findings in Veterans Undergoing Bariatric Surgery: Prevalence and Predictors of Barrett's Esophagus.
Pemphigus vulgaris (PV) is a rare autoimmune blistering disease involving the skin and mucous membranes. The prevalence of esophageal involvement remains uncertain. The aim of our study was to determine the frequency of esophageal involvement in patients with PV. This is a single-center electronic database retrospective review of patients with a diagnosis of PV. Data abstracted included demographics, disease characteristics (biopsy results, symptoms, areas affected, treatments), and esophagogastroduodenoscopy (EGD) reports. Of the 111 patients that met eligibility criteria, only 22 (19.8%) underwent EGD. Demographic data were similar except those who underwent EGD were more likely to be female (77.3% vs. 51.7%, p?=?0.05) and have hypertension (50.0% vs. 24.7%, p?=?0.04). Esophageal symptoms were common in both groups; however, those experiencing dysphagia were more likely to undergo EGD (50.0% vs. 20.2%, p?=?0.007). Those who underwent EGD had more refractory disease (??3 treatment modalities: 100% vs. 58.4%, p?0.001), but did not differ in areas affected. Of those who underwent EGD, only 4 (18.2%) had esophageal abnormalities either prior to PV diagnosis (1) or during a disease flare (3). Those having a flare were more likely to experience odynophagia (69.2%) or weight loss (61.5%), p?=?0.02 and p?=?0.05, respectively. While esophageal symptoms were common in our cohort of PV patients, a minority of patients underwent EGD, and the vast majority of those were unremarkable. This suggests that while esophageal symptoms are common in PV, permanent esophageal injury is more rare.
View details for DOI 10.1007/s00455-019-10055-4
View details for PubMedID 31538221
The effects of a transjugular intrahepatic portosystemic shunt on the diagnosis of hepatocellular cancer.
2018; 13 (12): e0208233
There is no consensus regarding the need for routine esophagogastroduodenoscopy (EGD) in patients before bariatric surgery. The aim of our study is to determine the frequency and predictors of EGD findings in a Veteran population presenting for bariatric surgery.This is a single-center retrospective analysis of Veterans who underwent RYGB or LSG, at a Veterans Affairs hospital between January 2008 and December 2017. All patients received a preoperative EGD. Data abstracted included demographics, comorbidities, preoperative laboratory values, and EGD findings. Univariate and multivariate analyses were performed for common EGD pathologies.Of the 260 Veterans included in our cohort, majority were male (75.0%), Caucasian (73.5%), and aged 54.0 ± 9.0 years old with a BMI of 44.9 ± 7.0 kg/m2. Most had hypertension (78.9%), previously smoked (63.9%), and recently used a proton pump inhibitor (PPI) (53.1%). One third of Veterans had a completely normal preoperative EGD. Common preoperative EGD findings included gastritis (35.8%), hiatal hernia (25.8%), esophagitis (20.8%), duodenitis (10.4%), Barrett's esophagus (7.4%), and Helicobacter pylori infection (4.6%). Preoperative predictors for a normal EGD were female gender, absence of hypertension, and no recent PPI use. Preoperative predictors of Barrett's esophagus included older age, recent PPI use, and recent histamine H2 receptor blocker (H2B) use. Increased age, male gender, and PPI use were associated with a change in surgical and/or medical management.Preoperative factors can be used to identify patients at risk for gastroesophageal pathology. Our data support preoperative EGD especially in older males with a history of PPI or H2B use.
View details for DOI 10.1007/s11695-019-04234-3
View details for PubMedID 31713148
Pex3 and Atg37 compete to regulate the interaction between the pexophagy receptor, Atg30, and the Hrr25 kinase.
2018; 14 (3): 368?84
BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) may be placed to treat complications of portal hypertension by creating a conduit between the hepatic and portal vein. The diagnosis of hepatocellular carcinoma (HCC) is typically made by multiphasic imaging studies demonstrating arterial enhancement with washout on arterial, portal venous, and delayed phase imaging. The aim of our study was to determine how the presence of TIPS would affect the imaging diagnosis of HCC.METHODS: This was a single-center electronic database review of all patients who underwent multiphasic imaging with MRI or CT scan for HCC screening between January 2000 and July 2017 and who were subsequently diagnosed with HCC. Data collected included patient demographics, liver disease characteristics including CPT score, MELD-Na, AFP, type of imaging, tumor stage, and lab values at the time of HCC diagnosis. The diagnosis of HCC was made using LI-RADS criteria on contrast-enhanced CT or MR imaging and confirmed by chart abstraction as documented by the treating clinician. Demographic and imaging characteristics for HCC patients with and without TIPS were compared.RESULTS: A total of 279 patients met eligibility criteria for the study, 37 (13.2%) of whom had TIPS placed prior to diagnosis of HCC. There was no significant difference in demographics or liver disease characteristics between patients with and without TIPS. Compared to cirrhotic patients with no TIPS prior to HCC diagnosis, patients with TIPS had significantly more scans with a longer duration of surveillance until HCC diagnosis. However, LI-RADS criteria and stage of HCC at diagnosis were not significantly different between both groups. There were no differences in outcomes including liver transplant and survival.CONCLUSION: The presence of TIPS does not lead to a delayed diagnosis of HCC. It is associated, however, with greater duration of time from first scan to diagnosis of HCC.
View details for PubMedID 30592722
Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages.
Proceedings of the National Academy of Sciences of the United States of America
2018; 115 (20): E4680?E4689
Macroautophagy/autophagy is a highly conserved process in which subcellular components destined for degradation are sequestered within autophagosomes. The selectivity of autophagy is determined by autophagy receptors, such as Pichia pastoris Atg30 (autophagy-related 30), which controls the selective degradation of peroxisomes (pexophagy) through the assembly of a receptor-protein complex (RPC). Previously, we proved that the peroxisomal acyl-CoA-binding protein, Atg37, and the highly conserved peroxin, Pex3, are required for RPC formation and efficient pexophagy. Here, we describe how Atg37 and Pex3 regulate the assembly and activation of the pexophagic RPC. We demonstrate that Atg30 requires both Atg37 and Pex3 to recruit Atg8 and Atg11 to the pexophagic RPC, because Atg37 depends on Pex3 for its localization at the peroxisomal membrane. We establish that due to close proximity of Atg37- and Pex3-binding sites in the middle domain of Atg30, the binding of these proteins to Atg30 is mutually exclusive within this region. We also show that direct binding of Pex3 and Atg37 to Atg30 regulates its phosphorylation by the Hrr25 kinase, negatively and positively, respectively. Based on these results we present a model that clarifies the assembly and activation of the pexophagic RPC through the phosphoregulation of Atg30.
View details for DOI 10.1080/15548627.2017.1413521
View details for PubMedID 29260977
View details for PubMedCentralID PMC5915033
Improving patient satisfaction in dermatology: a prospective study of an urban dermatology clinic.
2017; 99 (4): 273?78
Activation of liver X receptors (LXRs) with synthetic agonists promotes reverse cholesterol transport and protects against atherosclerosis in mouse models. Most synthetic LXR agonists also cause marked hypertriglyceridemia by inducing the expression of sterol regulatory element-binding protein (SREBP)1c and downstream genes that drive fatty acid biosynthesis. Recent studies demonstrated that desmosterol, an intermediate in the cholesterol biosynthetic pathway that suppresses SREBP processing by binding to SCAP, also binds and activates LXRs and is the most abundant LXR ligand in macrophage foam cells. Here we explore the potential of increasing endogenous desmosterol production or mimicking its activity as a means of inducing LXR activity while simultaneously suppressing SREBP1c-induced hypertriglyceridemia. Unexpectedly, while desmosterol strongly activated LXR target genes and suppressed SREBP pathways in mouse and human macrophages, it had almost no activity in mouse or human hepatocytes in vitro. We further demonstrate that sterol-based selective modulators of LXRs have biochemical and transcriptional properties predicted of desmosterol mimetics and selectively regulate LXR function in macrophages in vitro and in vivo. These studies thereby reveal cell-specific discrimination of endogenous and synthetic regulators of LXRs and SREBPs, providing a molecular basis for dissociation of LXR functions in macrophages from those in the liver that lead to hypertriglyceridemia.
View details for DOI 10.1073/pnas.1714518115
View details for PubMedID 29632203
View details for PubMedCentralID PMC5960280
Peroxisomal Atg37 binds Atg30 or palmitoyl-CoA to regulate phagophore formation during pexophagy.
The Journal of cell biology
2014; 204 (4): 541?57
Patient satisfaction has become an important measure of quality under the Patient Protection and Affordable Care Act. In this study, we assessed and analyzed patient satisfaction, nonattendance rates, and cycle times in an outpatient dermatology clinic. This study provides a snapshot of patient satisfaction in an urban dermatology clinic. Under the Patient Protection and Affordable Care Act, providers will be challenged to increase access to care and to validate quality of care through patient satisfaction.
View details for PubMedID 28492594
Autophagy is a membrane trafficking pathway that sequesters proteins and organelles into autophagosomes. The selectivity of this pathway is determined by autophagy receptors, such as the Pichia pastoris autophagy-related protein 30 (Atg30), which controls the selective autophagy of peroxisomes (pexophagy) through the assembly of a receptor protein complex (RPC). However, how the pexophagic RPC is regulated for efficient formation of the phagophore, an isolation membrane that sequesters the peroxisome from the cytosol, is unknown. Here we describe a new, conserved acyl-CoA-binding protein, Atg37, that is an integral peroxisomal membrane protein required specifically for pexophagy at the stage of phagophore formation. Atg30 recruits Atg37 to the pexophagic RPC, where Atg37 regulates the recruitment of the scaffold protein, Atg11. Palmitoyl-CoA competes with Atg30 for Atg37 binding. The human orthologue of Atg37, acyl-CoA-binding domain containing protein 5 (ACBD5), is also peroxisomal and is required specifically for pexophagy. We suggest that Atg37/ACBD5 is a new component and positive regulator of the pexophagic RPC.
View details for DOI 10.1083/jcb.201307050
View details for PubMedID 24535825
View details for PubMedCentralID PMC3926955