Faculty Bibliography

OBJECTIVES/OBJECTIVE:We aimed to describe the frequency of upper endoscopy and associated outcomes in subjects hospitalized with upper GI bleeding (UGIB) and pulmonary embolism (PE). METHODS:We performed a cross-sectional study using the Nationwide Inpatient Sample from 2007 to 2014. The association between upper endoscopy and in-hospital mortality was evaluated using propensity score matching. RESULTS:A total of 44,412 subjects had a coexistent PE and UGIB. 63.5% had an inpatient upper endoscopy with a lower likelihood of in-hospital death and a shorter length of stay. CONCLUSIONS:A substantial proportion of inpatients with PE and UGIB undergo endoscopy with a relatively low-mortality rate.

CONTEXT/BACKGROUND:Corticosteroid-binding globulin (CBG) and albumin transport circulating cortisol. Cleavage of high-affinity CBG (haCBG) by neutrophil elastase at inflammatory sites causes cortisol release into tissues, facilitating immunomodulatory effects. OBJECTIVE:To determine whether depletion of haCBG is related to mortality in septic shock. DESIGN/METHODS:A single-center prospective observational cohort study of patients recruited with critical illness or septic shock, using serum samples collected at 0, 8, 24, 48 and 72 hours. Serum total and haCBG, and total and free cortisol were assayed directly. Glucocorticoid treatment was an exclusion criterion. Mortality was assessed at 28 days from Intensive Care Unit admission. RESULTS:Thirty septic shock (SS) and 42 nonseptic critical illness (CI) patients provided 195 serum samples. SS/CI patients had lower total CBG, haCBG and low-affinity CBG (laCBG) than controls. Total CBG and haCBG were significantly lower in septic shock patients who died than in those that survived (P < 0.009, P = 0.021, respectively). Total and free cortisol were higher in septic than nonseptic individuals. Free/total cortisol fractions were higher in those with low haCBG as observed in septic shock. However, cortisol levels were not associated with mortality. Albumin levels fell in sepsis but were not related to mortality. CONCLUSIONS:Low circulating haCBG concentrations are associated with mortality in septic shock. These results are consistent with an important physiological role for haCBG in cortisol tissue delivery in septic shock.

Introduction/UNASSIGNED:Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT) but have a low incidence. Arising from the interstitial cells of Cajal, GISTs occur at different sites in the GIT with stomach being the most common. They can rarely be seen at sites outside the GIT such as omentum, retroperitoneum and are called as extraintestinal GISTs (EGIST). They have a spindle or epithelioid cell morphology and show positivity by immunohistochemistry (IHC) for CD117. Our aim was to study the clinicopathological and immunohistochemical profile of our cases of EGISTs. Materials and Methods/UNASSIGNED:A cross-sectional study of EGISTs received from 2010 to 2015 was done. IHC with CD117 and discovered on GIST1 (DOG1) was performed and tumors were scored based on the percentage of cells that stained positive. Thirteen abdominal non-GIST spindle cell tumors were included in the study as controls. Results/UNASSIGNED:Seven cases of EGIST were included (four-omental, three-retroperitoneal). All cases stained positive for CD117 and DOG1. One case of epithelioid EGIST scored 4 + with DOG1 and 2 + with CD117. Another case with mixed morphology scored 2 + with DOG1 and 4 + with CD117. All controls were negative for both markers. Conclusion/UNASSIGNED:EGISTs are one of the rare differentials for spindle cell lesions outside the GIT. Although both markers stain positive, DOG1 showed higher score with epithelioid GISTs.

INTRODUCTION/BACKGROUND:HLA-B*5701 screening identifies patients at increased risk for abacavir (ABC) hypersensitivity reaction (HSR). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and HIV treatment guidelines in 2008. Company meta-analyses of trials pre-HLA-B*5701 screening reported HSR rates of 4% to 8%. We analyzed the effectiveness of HLA-B*5701 screening on reducing HSR rates using clinical trial, observational (OPERA) cohort, and spontaneous reporting data. METHODS:A meta-analysis examined 12 trials in 3063 HLA-B*5701-negative patients receiving an ABC-containing regimen from April 9, 2007 to September 22, 2015. Potential cases were identified using pre-specified MedDRA preferred terms (drug hypersensitivity, hypersensitivity, anaphylactic reaction, anaphylaxis) and adjudicated against a Company ABC HSR case definition. Investigator-diagnosed cases were identified and rates were calculated. In the OPERA cohort, 9619 patients initiating their first ABC-containing regimen from January 1, 1999 to January 1, 2016 were identified. Patients were observed from regimen start until the earliest-following censoring event: ABC discontinuation, loss to follow-up, death, or study end (July 31, 2016). OPERA physicians evaluated events against OPERA definitions for definite/probable cases of ABC HSR; rates were calculated pre- and post-2008. The Company case definition was used to identify spontaneously reported cases for four marketed ABC-containing products; reporting rates were calculated using estimated exposure from sales data, through December 31, 2016. RESULTS:Suspected ABC HSR rates were 1.3% or less in the meta-analysis. In the OPERA cohort, the rate was 0.4% among patients initiating ABC post-2008 versus 1.3% pre-2008 (p<0.0001). Spontaneous reporting rates were low post-2008 (54 to 22 cases per 100,000 patient-years exposure [PYE]) versus pre-2008 (618 to 55 cases per 100,000 PYE). CONCLUSIONS:Clinically suspected ABC HSR rates were 1.3% or less in HLA-B*5701-negative patients. Recognizing their limitations, data from the OPERA cohort and spontaneous reporting indicate that HLA-B*5701 screening has reduced reporting rates of suspected HSR in clinical practice. Where screening for HLA-B*5701 is standard care, patients should be confirmed negative for this allele before starting ABC treatment.

OBJECTIVE:The objective of the study is to examine the validity of body mass index z score (zBMI) as a measure of percent body fat in prepubertal children. METHODS:One hundred eleven multiethnic, healthy, Tanner 1 children aged 6-12 years had fat percent and fat mass measured by the four-compartment method as part of the Paediatric Rosetta Body Composition Cohort. Multiple regression models were developed with fat percent as the dependent variable and zBMI, age, sex and ethnicity as independent variables. RESULTS:0.81). The average percent error was 7.2% in girls and 8.7% in boys. Age was associated with percentage body fat (P < 0.01), while ethnicity was not (P > 0.05). CONCLUSIONS:scores are associated with significantly lower absolute percent errors in girls and boys.

This retrospective cohort study sought to assess the effectiveness of comprehensive geriatric assessment (CGA) for older patients at an HIV clinic in a large US city. We systematically reviewed medical records of all patients who underwent CGA from June 2013 to July 2017. In addition, physicians and social workers completed an anonymous survey about the impact of CGA on their patients. For the 76 patients (median age 67.2; Q1, Q3 = 60.9, 72.6) seen by geriatricians at the clinic, there were 184 recommendations, 54 instances of counseling, and 11 direct actions. Overall adherence to recommendations was 32.8%, 34.9% for patient-directed, and 31.7% for provider-directed recommendations. No demographic or CGA variables were associated with adherence. Despite this lack of adherence, surveyed providers reported that they usually or always followed recommendations; the most frequently cited barrier to implementation was lack of feasibility. Further research will be needed to determine how CGA can improve outcomes for this population.

OBJECTIVE:To investigate the effects of epigallocatechin-3-gallate (EGCG) on proliferation and apoptosis of human gastric cancer SGC7901 cells under a hypoxic state. MATERIALS AND METHODS/METHODS:Human gastric cancer SGC7901 cells were sub-cultured, and the cobalt chloride (CoCl2) hypoxia model was established. The blank control group (normoxia group), hypoxia control group (hypoxia group) and hypoxia + different concentrations of EGCG subgroups (20, 40, 60, 80, 100 μg/mL EGCG) were set up. Cell viability was detected via methyl thiazolyl tetrazolium (MTT) assay, apoptosis was detected via flow cytometry, and expressions of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were detected via reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. RESULTS:Relatively low concentrations of EGCG (20-80 μg/mL) presented no significant inhibiting effect on SGC7901 cell growth within a short time (24 h) (p>0.05). The increasing concentration of EGCG inhibited cell proliferation under a hypoxia state (p<0.05). EGCG induced apoptosis in a dose-dependent manner under hypoxia (p<0.05). EGCG could significantly impede expressions of HIF-1α and VEGF proteins (p<0.05), and down-regulate the level of VEGF mRNA (p<0.05), but it showed no significant effect on the HIF-1α mRNA expression (p>0.05). CONCLUSIONS:EGCG inhibited cell proliferation under hypoxia via the downregulation of HIF-1α and its downstream target gene VEGF levels, providing a theoretical basis for the early diagnosis and treatment of gastric cancer in clinic.