Tools to Measure the Impact of Structural Racism and Discrimination on Gastrointestinal and Hepatology Disease Outcomes: A Scoping Review.

BACKGROUND & AIMS: Structural racism and discrimination (SRD) are important upstream determinants of health perpetuated by discriminatory laws and policies. Therefore, measuring SRD and its impact on health is critical to developing interventions that address resultant health disparities. We aimed to identify gastrointestinal (GI) or liver studies that report measures of SRD or interventions to achieve health equity in these domains by addressing upstream determinants of health. METHODS: We conducted a scoping review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses scoping reviews guidelines. Studies that used an SRD measure or examined an upstream intervention in GI or liver disease were included. Studies that described health disparities in GI or liver conditions without mentioning SRD were excluded. Study characteristics, findings, and limitations were extracted. RESULTS: Forty-six articles (19 studies using SRD measures and 27 studies of upstream interventions) were identified. Measures of residential racial segregation were reported most frequently. SRD was associated with poorer health outcomes for racial and ethnic minority populations. Although upstream intervention studies focused primarily on policies related to colon cancer screening and organ graft allocation, racial and ethnic disparities often persisted post-intervention. CONCLUSIONS: To achieve health equity in GI and liver conditions, there is an urgent need for research that goes beyond describing health disparities to incorporating measures of SRD and implementing interventions that address this understudied determinant of health.

Ambulatory Reflux Monitoring Guides Proton Pump Inhibitor Discontinuation in Patients With Gastroesophageal Reflux Symptoms: A Clinical Trial.

BACKGROUND AND AIMS: Proton pump inhibitor (PPI) therapy fails to provide adequate symptom control in up to 50% of patients with gastroesophageal reflux symptoms. Although a proportion do not require ongoing PPI therapy, a diagnostic approach to identify candidates appropriate for PPI cessation is not available. This study aimed to examine the clinical utility of prolonged wireless reflux monitoring to predict the ability to discontinue PPIs. METHODS: This double-blinded clinical trial performed over 3 years at 2 centers enrolled adults with troublesome esophageal symptoms of heartburn, regurgitation, and/or chest pain and inadequate PPI response. Participants underwent prolonged wireless reflux monitoring (off PPIs for ≥7 days) and a 3-week PPI cessation intervention. Primary outcome was tolerance of PPI cessation (discontinued or resumed PPIs). Symptom burden was quantified using the Reflux Symptom Questionnaire electronic Diary (RESQ-eD). RESULTS: Of 128 enrolled, 100 participants met inclusion criteria (mean age, 48.6 years; 41 men). Thirty-four participants (34%) discontinued PPIs. The strongest predictor of PPI discontinuation was number of days with acid exposure time (AET) > 4.0% (odds ratio, 1.82; P < .001). Participants with 0 days of AET > 4.0% had a 10 times increased odds of discontinuing PPI than participants with 4 days of AET > 4.0%. Reduction in symptom burden was greater among the discontinued versus resumed PPI group (RESQ-eD, -43.7% vs -5.3%; P = .04). CONCLUSIONS: Among patients with typical reflux symptoms, inadequate PPI response, and absence of severe esophagitis, acid exposure on reflux monitoring predicted the ability to discontinue PPIs without symptom escalation. Upfront reflux monitoring off acid suppression can limit unnecessary PPI use and guide personalized management. (ClinicalTrials.gov, Number: NCT03202537).

Optimal Wireless Reflux Monitoring Metrics to Predict Discontinuation of Proton Pump Inhibitor Therapy.

INTRODUCTION: Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response. METHODS: This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to > 8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks. RESULTS: Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01). DISCUSSION: This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy.

Biomarkers of Reflux Disease.

Gastroesophageal reflux disease (GERD) encompasses an array of disorders unified by the reflux of gastric contents. Because there are many potential disease manifestations, esophageal and extraesophageal, there is no single biomarker of the entire disease spectrum; a set of GERD biomarkers that each quantifies specific aspects of GERD-related pathology might be needed. We review recent reports of biomarkers of GERD, specifically in relation to endoscopically negative esophageal disease and excluding conventional pH-impedance monitoring. We consider histopathologic biomarkers, baseline impedance, and serologic assays to determine that most markers are based on manifestations of impaired esophageal mucosal integrity, which is based on increased ionic and molecular permeability, and/or destruction of tight junctions. Impaired mucosal integrity quantified by baseline mucosal impedance, proteolytic fragments of junctional proteins, or histopathologic features has emerged as a promising GERD biomarker.

The utility of pulmonary function testing in predicting outcomes following liver transplantation.

Although pulmonary function tests (PFTs) are routinely performed in patients during the evaluation period before liver transplantation (LT), their utility in predicting post-LT mortality and morbidity outcomes is not known. The aim of this study was to determine the impact of obstructive and/or restrictive lung disease on post-LT outcomes. We conducted a retrospective analysis of patients who had pre-LT PFTs and underwent a subsequent LT (2007-2013). We used statistical analyses to determine independent associations between PFT parameters and outcomes (graft/patient survival, time on ventilator, and hospital/intensive care unit [ICU] length of stay [LOS]). A total of 415 LT recipients with available PFT data were included: 65% of patients had normal PFTs; 8% had obstructive lung disease; and 27% had restrictive lung disease. There was no difference in patient and graft survival between patients with normal, obstructive, and restrictive lung disease. However, restrictive lung disease was associated with longer post-LT time on ventilator and both ICU and hospital LOS (P < 0.05). More specific PFT parameters (diffusing capacity of the lungs for carbon monoxide, total lung capacity, and residual volume) were all significant predictors of ventilator time and both ICU and hospital LOS (P < 0.05). Although pre-LT PFT parameters may not predict post-LT mortality, restrictive abnormalities correlate with prolonged post-LT ventilation and LOS. Efforts to identify and minimize the impact of restrictive abnormalities on PFTs might improve such outcomes. Liver Transplantation 22 805-811 2016 AASLD.

Advances in the endoscopic evaluation of eosinophilic esophagitis.

PURPOSE OF REVIEW: Endoscopic detection of mucosal healing has emerged as a primary therapeutic endpoint in inflammatory bowel disease. Endoscopically identified esophageal features are increasingly being utilized in diagnostic and therapeutic decisions in eosinophilic esophagitis (EoE). RECENT FINDINGS: Studies over the past 5 years have demonstrated the validity, accuracy, and clinical relevance of a systematic, endoscopic assessment of esophageal abnormalities in EoE. The initial severity of EoE endoscopic findings has important implications with regard to therapeutic options, including the need for dilations, and may be an important predictor of the effectiveness of medical therapies. Moreover, endoscopic parameters can serve as reliable therapeutic endpoints that substantiate the interpretation of currently used metrics of patient-reported symptom outcomes and eosinophil density. Finally, tools such as endosonography and functional luminal imaging probe are providing fundamental insights regarding the remodeling consequences of EoE that are the central determinants of disease complications. SUMMARY: Endoscopic features are having an increasing role in the diagnosis, phenotype characterization, and choice of therapies for EoE. Comprehensive assessment of therapeutics in EoE should ideally incorporate symptoms, histology, and endoscopic healing.

Heparin-induced thrombocytopenia testing is over-utilized in cirrhosis & correlates with poor clinical outcomes.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is a serious complication seen in hospitalized, medically-ill patients. Evaluation for HIT using a commercially-available ELISA-based test has become increasingly common; however, it does have a high false positive rate. Implications of HIT testing in patients with cirrhosis have not yet been reported. MATERIAL AND METHODS: We conducted a single-institution, retrospective review of all patients with cirrhosis admitted over a 29-month period. The student's t-test and the χ2 test were used for comparisons. We performed a stratified survival analysis using Kaplan-Meier and log rank testing. RESULTS: A total of 1,305 patients had a HIT Ab sent during the study period. Of these patients, 106 had cirrhosis and were included in the study. Eighteen (17%) of the patients with cirrhosis were HIT Ab positive and four of the eighteen had a positive Serotonin Release Assay (SRA) confirmatory test. No difference was found in platelet nadir, thrombotic rate, length of stay, and patient survival between patients with positive HIT Ab and negative HIT Ab testing. No consistent treatment was used among patients who were HIT Ab positive, despite hematology service consultation. Patients who were HIT Ab negative were more likely to have undergone liver transplantation compared to those who were positive (27 vs. 5.5%, respectively; p = 0.048). CONCLUSION: Our data suggest that HIT Ab testing is over-used in patients with cirrhosis and is poorly predictive of outcomes. With a poor positive predictive value, HIT testing may add unnecessary complexity to an already complicated patient population.

Interpretation and management of hepatic abnormalities in pregnancy.

The spectrum of liver disease in pregnancy includes liver disease unrelated to pregnancy, liver diseases that occur with increased frequency or severity in pregnancy, and liver disease specific to pregnancy. Diseases of the liver unique to pregnancy reliably occur at specific points in the gestational spectrum. Thus, gestational age, a comprehensive history, and a clinically driven diagnostic evaluation is critical in approaching a pregnant patient with abnormal liver chemistries or function. Early recognition of these conditions is important and although management may be expectant, some patients require targeted therapy or necessitate prompt delivery, which can be life-saving to both mother and child.

Antibacterial agent-releasing scaffolds in dental tissue engineering.

It seems quite challenging in tissue engineering to synthesize a base material with a range of essential activities, including biocompatibility, nontoxicity, and antimicrobial activities. Various types of materials are synthesized to solve the problem. This study aimed to provide the latest relevant information for practitioners about antibacterial scaffolds in dental tissue engineering. The PubMed search engine was used to review the relevant studies with a combination of the following terms as search queries: tissue engineering, scaffolds, antimicrobial, dentistry, dental stem cells, and oral diseases. It is noteworthy to state that only the terms related to tissue engineering in dentistry were considered. The antimicrobial scaffolds support the local tissue regeneration and prevent adverse inflammatory reactions; however, not all scaffolds have such positive characteristics. To resolve this potential defect, different antimicrobial agents are used during the synthesis process. Innovative methods in guided tissue engineering are actively working towards new ways to control oral and periodontal diseases.

Care of the Postablation Patient: Surveillance, Acid Suppression, and Treatment of Recurrence.

Endoscopic eradication therapy is effective and durable for the treatment of Barrett's esophagus (BE), with low rates of recurrence of dysplasia but significant rates of recurrence of intestinal metaplasia. Identified risk factors for recurrence include age and length of BE before treatment and may also include presence of a large hiatal hernia, higher grade of dysplasia before treatment, and history of smoking. Current guidelines for surveillance following ablation are limited, with recommendations based on low-quality evidence and expert opinion. New modalities including optical coherence tomography and wide-area tissue sampling with computer-assisted analysis show promise as adjunctive surveillance modalities.

Autoimmune hepatitis in patients with human immunodeficiency virus (HIV): Case reports of a rare, but important diagnosis with therapeutic implications.

RATIONALE: Chronic liver disease is a major cause of morbidity and mortality in patients with HIV. However, autoimmune hepatitis (AIH) in patients with HIV has rarely been reported. Our aim was to evaluate a cohort of patients with HIV and AIH and identify clinical presentations and outcomes. PATIENT CONCERNS: Management of autoimmune hepatitis in context of human immunodeficiency virus, long-term outcomes, and safety in setting of underlying immunocompromised state. DIAGNOSES: Autoimmune Hepatitis, Human Immunodeficiency Virus, Hepatotoxicity, Liver Injury, Liver Transplantation. INTERVENTIONS: We retrospectively reviewed the charts of patients with HIV and AIH based on histological, serologic, biochemical demographic, and clinical data. OUTCOMES: Five patients were identified with autoimmune hepatitis; 4 of 5 were women, and all were African or African-American. The age at the time of AIH diagnosis was 46.6 ±â€Š13.4 years. All patients acquired HIV sexually and all had CD4 counts >250 cells/uL (456-1011 cells/uL) and undetectable HIV viral loads at the time of AIH diagnosis. One patient presented with acute liver failure necessitating liver transplantation and developed AIH posttransplantation. At the time of diagnosis, the AST were 350 ±â€Š448 U/L, ALT 247 ±â€Š190 U/L, bilirubin 7 ±â€Š12 mg/dL, and alkaline phosphatase 126 ±â€Š53 U/L. All patients had histologic evidence of AIH on liver biopsies. Patients were successfully treated with prednisone and azathioprine, without a decrease in CD4 <250 cells/uL, infectious complications or significant side effects. LESSONS: AIH occurs in patients with well-controlled HIV. In our patient cohort, immunosuppressive therapy with prednisone and azathioprine was safe and effective in inducing remission, without significant complications or development of opportunistic infections.

Targeting human telomerase RNA component using antisense oligonucleotide induces rapid cell death and increases ATO-induced apoptosis in APL cells.

The impressive advances carried out in designing pharmacological strategies with the aim of telomerase inhibition in cancers emerged a consensus that telomerase-targeted therapies could be exciting prospect in repertoire of future cancer strategies. The results of the present study indicated that targeting telomerase using an oligonucleotide-based molecule against human telomerase RNA template (hTR ASODN) reduced the survival rate of NB4 cells and induced a caspase-3-dependent apoptosis. Our finding was even noticeable in the synergistic experiments, where we found an enhanced reduction in the viability of the cells after short-term treatment with ATO in combination with the inhibitor. The resulting data delineated that short-term treatment of the cells with hTR ASODN either as single agent or in combination with ATO resulted in apoptotic cell death through activation of DNA damage response via up-regulation of p73 and ATM coupled with down-regulation of c-Myc. Moreover, we found that induction of p21 and subsequent disturbance of the death promoter to death repressor genes may contribute to the enhanced growth suppressive effect of the drugs combination. Overall, our findings support the idea that telomerase activity may have pivotal role in attenuating ATO effectiveness and combination of ATO with telomerase inhibitor seems to be a novel promising strategy, which may increase APL cure rates.