Poly(ADP-ribose) polymerases have shown true promise in early clinical studies due to reported activity in BRCA-associated cancers. PARP inhibitors may represent a potentially important new class of chemotherapeutic agents directed at targeting cancers with defective DNA-damage repair. In order to widen the prospective patient population that would benefit from PARP inhibitors, predictive biomarkers based on a clear understanding of the mechanism of action are required. In addition, a more sophisticated understanding of the toxicity profile is required if PARP inhibitors are to be employed in the curative, rather than the palliative, setting. PARP inhibitors have successfully moved into clinical practice in the past few years, with approval granted from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) within the past two years. The United States FDA approval of olaparib applies to fourth-line treatment in germline BRCA-mutant ovarian cancer, and European EMA approval of olaparib for maintenance therapy in both germline and somatic BRCA-mutant platinum-sensitive ovarian cancer. This review covers the current understanding of PARP, its inhibition, and the basis of the excitement surrounding these new agents. It also evaluates future approaches and directions required to achieve full understanding of the intricate interplay of these agents at the cellular level.

Increases in cardiac troponin-I, indicative of myocardial injury, are common and prognostic in COVID-19. • Troponin-I elevation is an accurate predictor of mortality in hospitalized patients with COVID-19. • A normal cardiac troponin-I level on admission has a very high negative predictive value for all-cause in-hospital mortality. • A normal cardiac troponin-I level on admission is a very strong and independent indicator of hospital survival. • Cardiac troponin-I may facilitate COVID-19 stage classification and risk-stratification.

Background Limited data is available for reliable and accurate predictors of in-hospital mortality in patients diagnosed with COVID-19. Methods This scientific study is a retrospective cohort study of patients without a known history of liver diseases who were hospitalized with COVID-19 viral infection. Patients were stratified into low score groups (Model of End-Stage Liver Disease [MELD] score <10) and high score groups (MELD ≥10). Clinical outcomes were evaluated, including in-hospital mortality, hospital length of stay, and intensive care unit length of stay (ICU LOS). Results Our cohort of 186 COVID-19 positive patients included 88 (47%) women with a mean age of 60 years in the low score group and mean age of 73 years in the high score group. Patients in the high score group were older in age (p<0.0001) and more likely to have history of diabetes mellitus (p=0.0020), stage 3 chronic kidney disease (CKD) (p=0.0013), hypertension (p<0.0001), stroke/transient ischemic attack (TIA) (p=0.0163), asthma (p=0.0356), dementia (p<0.0001), and chronic heart failure (p=0.0055). The in-hospital mortality or discharge to hospice rate was significantly higher in the high-score group as opposed to the low-score group (p=0.0014). Conversely, there was no significant difference among both groups in the hospital length of stay (LOS) and ICU LOS (p=0.6929 and p=0.7689, respectively). Conclusion Patients hospitalized with COVID-19 infection and found to have a MELD score greater than or equal to 10 were found to have a higher mortality as compared to their counterparts. Conversely a low MELD score is a very strong indicator of a more favorable prognosis, indicating hospital survival. We propose using the MELD score as an adjunct for risk stratifying patients diagnosed with COVID-19 without prior history of liver dysfunction.

Barrett’s esophagus (BE) is a change in the distal esophageal mucosal lining, whereby metaplastic columnar epithelium replaces squamous epithelium of the esophagus. This change represents a pre-malignant mucosal transformation which has a known association with the development of esophageal adenocarcinoma. Gastroesophageal reflux disease is a risk factor for BE, other risk factors include patients who are Caucasian, age > 50 years, central obesity, tobacco use, history of peptic stricture and erosive gastritis. Screening for BE remains selective based on risk factors, a screening program in the general population is not routinely recommended. Diagnosis of BE is established with a combination of endoscopic recognition, targeted biopsies, and histologic confirmation of columnar metaplasia. We aim to provide a comprehensive review of the epidemiology, pathogenesis, screening and advanced techniques of detecting and eradicating Barrett’s esophagus.