Citations

ABSTRACTThe rapid increase and poor survival of esophageal adenocarcinoma (EAC) have led to significant efforts to promote early detection. Given that the premalignant lesion of Barrett's esophagus (BE) is the major known risk factor for EAC, multiple investigators have studied biomarker signatures that can predict malignant progression of BE to EAC. MicroRNAs, a novel class of gene regulators, are small non‐coding RNAs and have been associated with carcinogenesis. MicroRNAs are ideal biomarkers because of their remarkable stability in fixed tissues, a common method for collection of clinical specimens, and in blood either within exosomes or as microRNA‐protein complexes. Multiple studies show potential of microRNAs as tissue and blood biomarkers for diagnosis and prognosis of EAC but the results need confirmation in prospective studies. Although head‐to‐head comparisons are lacking, microRNA panels require less genes than messenger RNA panels for diagnosis of EAC in BE. MicroRNA diagnostic panels will need to be compared for accuracy against global measures of genome instability that were recently shown to be good predictors of progression but require sophisticated analytic techniques. Early studies on blood microRNA panels are promising but have found microRNA markers to be inconsistent among studies. MicroRNA expression in blood is different between various microRNA sub‐compartments such as exosomes and microRNA‐protein complexes and could affect blood microRNA measurements. Further standardization is needed to yield consistent results. We have summarized the current understanding of the tissue and blood microRNA signatures that may predict the development and progression of EAC. J. Cell. Biochem. 117: 1288–1295, 2016. © 2016 Wiley Periodicals, Inc.

Malignant cells may subvert and escape endogenous host immune surveillance by up‐regulation of immune inhibitory signals known as immune checkpoints. These checkpoints are important therapeutic targets, and antibodies that block checkpoint signaling have shown remarkable efficacy in some solid tumors as well as in some refractory hematologic malignancies. In hematologic cancers, the mechanism of these checkpoints is complex, as the tumor and immune system are one and the same. In this review, we evaluate the biology of checkpoint inhibition, review the current data on its efficacy in lymphoid tumors, and explore uncertainties in the field, including those involving the precise mechanisms of action, the appropriate timing of therapy, and the differences in response rate between lymphoid tumor types.

SummaryBackgroundBardet–Biedl syndrome (BBS) is a rare genetic condition with manifestations that can impact anesthetic and perioperative care. There is a void of literature describing the perioperative anesthetic management in this complex patient population.ObjectivesThe purpose of this retrospective series was to describe the perioperative care of patients diagnosed with BBS at a large academic tertiary referral center with experience in caring for these patients.MethodsAll patients receiving anesthesia during the time between July 10, 1997 and Jan 1, 2015 were identified. Anesthetic and perioperative records were reviewed in detail for demographic, echocardiographic, preoperative, intraoperative, and postoperative data.ResultsWe identified 12 patients with BBS undergoing 40 anesthetics at our institution. The study identified a high risk for difficult airway with need for advanced airway techniques (67% of patient's ≥18 years of age required either awake fiberoptic or video laryngoscopy techniques), cardiac abnormalities, renal impairment, morbid obesity, and intellectual disability as the main syndrome manifestations of interest to the anesthesiologist. No patient had perioperative complications directly related to BBS; however, each underwent thorough perioperative evaluation with emphasis on the systemic comorbidities associated with the syndrome. This report illustrates that patients with BBS can safely undergo anesthesia, but a detailed and often multidisciplinary preoperative evaluation is prudent.

AbstractObjectivesThe objective was to describe perceptions of practicing emergency physicians (EPs) regarding the appropriateness and medicolegal implications of using shared decision‐making (SDM) in the emergency department (ED).MethodsWe conducted a cross‐sectional survey of EPs at a large, national professional meeting to assess perceived appropriateness of SDM for different categories of ED management (e.g., diagnostic testing, treatment, disposition) and in common clinical scenarios (e.g., low‐risk chest pain, syncope, minor head injury). A 21‐item survey instrument was iteratively developed through review by content experts, cognitive testing, and pilot testing. Descriptive and multivariate analyses were conducted.ResultsWe approached 737 EPs; 709 (96%) completed the survey. Two‐thirds (67.8%) of respondents were male; 51% practiced in an academic setting and 44% in the community. Of the seven management decision categories presented, SDM was reported to be most frequently appropriate for deciding on invasive procedures (71.5%), computed tomography (CT) scanning (56.7%), and post‐ED disposition (56.3%). Among the specific clinical scenarios, use of thrombolytics for acute ischemic stroke was felt to be most frequently appropriate for SDM (83.4%), followed by lumbar puncture to rule out subarachnoid hemorrhage (73.8%) and CT head for pediatric minor head injury (69.9%). Most EPs (66.8%) felt that using and documenting SDM would decrease their medicolegal risk while a minority (14.2%) felt that it would increase their risk.ConclusionsAcceptance of SDM among EPs appears to be strong across management categories (diagnostic testing, treatment, and disposition) and in a variety of clinical scenarios. SDM is perceived by most EPs to be medicolegally protective.

Takotsubo cardiomyopathy (TC) or stress-induced cardiomyopathy is also popularly referred to as “broken heart syndrome” or “apical ballooning syndrome”. [...]

BACKGROUNDAlthough colorectal cancer (CRC) screening guidelines recommend initiating screening at age 50 years, the percentage of cancer cases in younger patients is increasing. To the authors' knowledge, the national treatment patterns and outcomes of these patients are largely unknown.METHODSThe current study was a population‐based, retrospective cohort study of the nationally representative Surveillance, Epidemiology, and End Results registry for patients diagnosed with CRC from 1998 through 2011. Patients were categorized as being younger or older than the recommended screening age. Differences with regard to stage of disease at diagnosis, patterns of therapy, and disease‐specific survival were compared between age groups using multinomial regression, multiple regression, Cox proportional hazards regression, and Weibull survival analysis.RESULTSOf 258,024 patients with CRC, 37,847 (15%) were aged <50 years. Young patients were more likely to present with regional (relative risk ratio, 1.3; P<.001) or distant (relative risk ratio, 1.5; P<.001) disease. Patients with CRC with distant metastasis in the younger age group were more likely to receive surgical therapy for their primary tumor (adjusted probability: 72% vs 63%; P<.001), and radiotherapy also was more likely in younger patients with CRC (adjusted probability: 53% vs 48%; P<.001). Patients younger than the recommended screening age had better overall disease‐specific survival (hazards ratio, 0.77; P<.001), despite a larger percentage of these individuals presenting with advanced disease.CONCLUSIONSPatients with CRC diagnosed at age <50 years are more likely to present with advanced‐stage disease. However, they receive more aggressive therapy and achieve longer disease‐specific survival, despite the greater percentage of patients with advanced‐stage disease. These findings suggest the need for improved risk assessment and screening decisions for younger adults. Cancer 2016;122:929–34. © 2016 American Cancer Society.

Abstract Aims We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy. Methods and results We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice-daily SQ BNP 10 µg/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (−39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P &lt; 0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo. Conclusion Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF.

Driveline infections (DLI) are a cause of morbidity after continuous-flow left ventricular assist device (CF-LVAD) implantation. Because driveline trauma contributes to DLI, we assessed whether intraoperative placement of a temporary external anchoring suture (EAS) influenced DLI rate. We analyzed 161 consecutive patients with CF-LVAD (HMII 82; HW 79) implantation. Two groups were defined: placement of EAS (n = 85) or No EAS (n = 76). For NO EAS patients, the driveline was permanently anchored internally to the rectus fascia. Cox proportional analysis was performed to assess the effect of EAS on time to first confirmed DLI. Baseline characteristics were comparable between groups (all p = 0.3). Mean follow-up time was 0.93 years. A total of 18 (11.1%) patients developed confirmed culture positive DLI, with “first infection” rate of 0.13 events/year. Mean time to confirmed DLI was 0.69 years. Driveline infection was less likely (hazard ratio [HR] = 0.28, 0.95 confidence interval [CI] = 0.06–1.25, p = 0.056) to occur in NO EAS (2/18) then in EAS (16/18). Confirmed DLI was comparable between device types (p = 0.3). Multivariable regression adjusted for age, BMI, blood product use, device type, and diabetes showed equivocal effect of EAS (HR = 0.33, 0.95 CI = 0.07–1.54, p = 0.12). Patients with a temporary EAS may have an increased risk of confirmed DLI after device implantation.