Citations

Summary: This EEG Guideline incorporates the practice of structuring a report of results obtained during routine adult electroencephalography. It is intended to reflect one of the current practices in reporting an EEG and serves as a revision of the previous guideline entitled “Writing an EEG Report.” The goal of this guideline is not only to convey clinically relevant information, but also to improve interrater reliability for clinical and research use by standardizing the format of EEG reports. With this in mind, there is expanded documentation of the patient history to include more relevant clinical information that can affect the EEG recording and interpretation. Recommendations for the technical conditions of the recording are also enhanced to include post hoc review parameters and type of EEG recording. Sleep feature documentation is also expanded upon. More descriptive terms are included for background features and interictal discharges that are concordant with efforts to standardize terminology. In the clinical correlation section, examples of common clinical scenarios are now provided that encourages uniformity in reporting. Including digital samples of abnormal waveforms is now readily available with current EEG recording systems and may be beneficial in augmenting reports when controversial waveforms or important features are encountered.

Summary: This revision to the EEG Guidelines is an update incorporating current EEG technology and practice. “Standards of practice in clinical electroencephalography” (previously Guideline 4) has been removed. It is currently undergoing revision through collaboration among multiple medical societies and will become part of “Qualifications and Responsibilities of Personnel Performing and Interpreting Clinical Neurophysiology Procedures.” The remaining guidelines are reordered and renumbered.

SummaryBackgroundRefractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome.AimTo create a prognostic model to estimate survival of patients with refractory coeliac disease.MethodsWe evaluated predictors of 5‐year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5‐year mortality.ResultsThe multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11–63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5‐year follow‐up (cumulative 5‐year all‐cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5‐year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38–3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22–6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61–0.85). A simple weighted three‐factor risk score was created to estimate 5‐year survival.ConclusionsUsing data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5‐year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow‐up.

Abstract Background Patients with mild autosomal dominant polycystic kidney disease (ADPKD) are less likely to be informative in randomized clinical trials (RCTs). We previously developed an imaging classification of ADPKD (typical diffuse cyst distribution Class 1A–E and atypical cyst distribution Class 2) for prognostic enrichment design in RCTs. We investigated whether using this classification would have increased the power to detect a beneficial treatment effect of rigorous blood pressure (BP) control on HALT-PKD participants with early disease (Study A). Methods Post hoc analysis of the early disease HALT-PKD study, an RCT that studied the effect of rigorous versus standard BP control on rates of total kidney volume (TKV) increase and estimated glomerular filtration rate (eGFR) decline in ADPKD patients with eGFR >60 mL/min/1.73 m2. Results Five hundred and fifty-one patients were classified by two observers (98.2% agreement) into Class 1A (6.2%), 1B (20.3%), 1C (34.1%), 1D (22.1%), 1E (11.8%) and 2 (5.4%). The TKV increase and eGFR decline became steeper from Class 1A through 1E. Rigorous BP control had been shown to be associated with slower TKV increase, without a significant overall effect on the rate of eGFR decline (faster in the first 4 months and marginally slower thereafter). Merging Classes 1A and 2 (lowest severity), 1B and 1C (intermediate severity) and 1D and 1E (highest severity) detected stronger beneficial effects on TKV increase and eGFR decline in Class 1D and E with a smaller number of patients. Conclusions Strategies for prognostic enrichment, such as image classification, should be used in the design of RCTs for ADPKD to increase their power and reduce their cost.

Abstract Background: Known gene mutations account for approximately 50% of the risk for breast cancer. However, a considerable fraction of heritable risk remains unexplained. Fifteen percent of the risk is accounted for by BRCA1/2 and another 3% by TP53, PTEN, LKB1 and CDH1. CHEK2, ATM, PALB2, BRIP1, RAD51C, RAD51D and BARD1 account for 4%, while SNPs discovered from large multicenter genome-wide association studies explain another 14% of the heritable risk. Founder mutations in the DNA repair pathway genes such as BRCA1 and BRCA2 account for the majority of AJ breast cancer mutations. Methods: We performed exome sequencing of 49 early onset (age <35) breast cancer cases, and 85 BRCA wild type familial breast cancer cases, all of Ashkenazi Jewish (AJ) from the New York City area. A recurrent truncating mutation was then analyzed in 3131 breast cancer cases and 2716 unaffected women of Ashkenazi ancestry from New York and Israel. Using CRISPR and overexpression systems on the human mammary epithelial cell line HMLE, transcript and protein levels were assayed for the mutant and compared to wild-type. Treatment with IlludinS and UVC were performed to assess DNA damage response. Finally, clonogenic survival assay was also performed. Results: Amongst the DNA repair pathway genes, exome sequencing revealed a heterozygous recurrent truncating mutation in ERCC3 (R109X) in 2 of 49 early onset breast cancer cases of AJ ancestry and 4 familial AJ probands. Taqman genotyping in a case control setting from New York and Israel revealed 54 mutation carriers in 3131 cases and 32 in the 2716 controls. In total, there were 60 heterozygotes detected in 3209 cases and 32 in 2716 controls [OR 1.59 (95% CI 1.01-2.50)]; p = 0.02 Fisher one- tailed). Functional studies using CRISPR and overexpression systems on human mammary epithelial cells, show that the mutation results in lower transcript levels and this reduction is effected by nonsense mediated decay of the mutant transcript. Western blotting showed that the mutation resulted in a smaller protein (∼12kDa). Clonogenic assays showed similar survival rate of mutant and wildtype under UVC exposure, however the mutant cell line showed significantly smaller colony size demonstrating a growth disadvantage that was further increased upon DNA damage. Treatment with fungal sesquiterpene IlludinS, a known sensitizer to mutant ERCC3 cell lines, showed drastically reduced survival when compared to the wild type human mammary epithelial cells. Conclusions: We demonstrate that ERCC3 is a moderate risk gene for breast cancer in individuals of Ashkenazi ancestry. ERCC3 is somatically mutated in multiple cancers including breast, ovarian and pancreatic cancers, however its role as a cancer susceptibility gene requires further elucidation. Additional functional and population genetic studies to further characterize this novel ERCC3 variant are underway. Citation Format: Joseph Vijai, Sabine Topka, Kara Maxwell, Vignesh Ravichandran, Tinu Thomas, Danylo Villano, Ann Maria, Pragna Gaddam, Anne Lincoln, Steven Hart, Susan Neuhausen, Mark Robson, Jeffrey Weitzel, Mark Daly, Katherine Nathanson, Fergus Couch, Gadi Rennert, Kenneth Offit. ERCC3 R109X is a moderate risk breast cancer risk variant in Ashkenazi Jews. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 796.

Abstract Pancreatic adenocarcinoma generally presents with a poor prognosis and an extremely low response rate to first line therapies. There is a critical unmet need to discover and implement effective diagnostic panels to stratify outcomes and tailor treatment strategies to improve survival. The BERG Interrogative Biology® platform utilizes Artificial Intelligence to analyze and integrate multi-omic profiles with clinical annotation to define novel biomarkers and improve treatment interventions. Herein, we analyzed the serum proteome, signaling lipidome, structural lipidome, and metabolome of 163patients at multiple timepoints (pancreatic cancer: 115; pancreatitis: 15; and age-matched healthy controls: 33). Utilizing the power of the Bayesian Network learner, bAIcis™ (BERG Artificial Intelligence Clinical Information System), multi-omic profiles were aligned to the longitudinal clinical information and subjected to AI-algorithms to infer probabilistic cause-and-effect relationships among molecular and clinical variables explicitly explaining pancreatic cancer status, cancer progression, and survival, and defining the interconnectivity of molecular features with clinical phenotype. Network features linking into clinical endpoints and key network pressure points were identified as molecular drivers. The drivers of clinical endpoints were analyzed to rank potential biomarkers. Novel biomarkers were discovered that demonstrate diagnostic potential for pancreatic cancer detection, disease prognosis including metastatic disease progression, patient stratification associated with survival, and response to standard chemotherapy agents like Gemcitibine. A prospective study is underway to validate the biomarkers and discover additional diagnostic and therapeutic molecules to improve the outcomes for patients affected by adenocarcinoma of the pancreas. Citation Format: Niven R. Narain, A James Moser, Ramesh Ramanathan, John Crowley, Amy Stoll-D’Astice, Yezhou Sun, Leonardo O. Rodrigues, Eric M. Grund, Emily Chen, Vivek K. Vishnudas, Michael A. Kiebish, Viatcheslav R. Akmaev, Rangaprasad Sarangarajan. Project Survival: Interrogative Biology® platform mediated discovery of molecular markers for detection, stratification and outcomes in pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 786.

Purpose To provide evidence-based guidance on the optimum management of chronic pain in adult cancer survivors. Methods An ASCO-convened expert panel conducted a systematic literature search of studies investigating chronic pain management in cancer survivors. Outcomes of interest included symptom relief, pain intensity, quality of life, functional outcomes, adverse events, misuse or diversion, and risk assessment or mitigation. Results A total of 63 studies met eligibility criteria and compose the evidentiary basis for the recommendations. Studies tended to be heterogeneous in terms of quality, size, and populations. Primary outcomes also varied across the studies, and in most cases, were not directly comparable because of different outcomes, measurements, and instruments used at different time points. Because of a paucity of high-quality evidence, many recommendations are based on expert consensus. Recommendations Clinicians should screen for pain at each encounter. Recurrent disease, second malignancy, or late-onset treatment effects in any patient who reports new-onset pain should be evaluated, treated, and monitored. Clinicians should determine the need for other health professionals to provide comprehensive pain management care in patients with complex needs. Systemic nonopioid analgesics and adjuvant analgesics may be prescribed to relieve chronic pain and/or to improve function. Clinicians may prescribe a trial of opioids in carefully selected patients with cancer who do not respond to more conservative management and who continue to experience distress or functional impairment. Risks of adverse effects of opioids should be assessed. Clinicians should clearly understand terminology such as tolerance, dependence, abuse, and addiction as it relates to the use of opioids and should incorporate universal precautions to minimize abuse, addiction, and adverse consequences. Additional information is available at www.asco.org/chronic-pain-guideline and www.asco.org/guidelineswiki .

AbstractBackgroundDiagnosis of suspected basal cell carcinoma (BCC) is typically confirmed with incisional biopsy before referral to final surgery.ObjectiveTo investigate the clinical confidence and accuracy of physicians making a diagnosis of BCC based on dermoscopic and reflectance confocal microscopy (RCM) features.MethodsThis study was designed as a simulation to determine the certainty and willingness to refer to surgery without previous biopsy confirmation of BCC. Study subjects were identified with suspected BCC. Dermoscopic and RCM lesion images were obtained before biopsy. Eight clinicians with various expertise levels blindly interpreted these images and chose among four hypothetical treatment options: definite BCC, refer directly to surgery without biopsy; other malignancy, perform biopsy for diagnosis; uncertain diagnosis, perform biopsy; benign, do not biopsy. Decisions for treatment were based on dermoscopic images alone and, subsequently, on dermoscopic and RCM images combined.ResultsThe sensitivity for referral to surgery without biopsy was 67.6% with the use of dermoscopy; the positive predictive value (PPV) was 97.0%. Adding RCM increased the sensitivity to 76.5% and the PPV to 98.6%.ConclusionsDermoscopy provides a high PPV for BCC. The addition of RCM to dermoscopy increases diagnostic sensitivity, particularly in less experienced dermoscopists. Physician behavior might be different if actual referrals were made for surgery without biopsy.

Background— Approximately one third of patients with symptomatic aortic stenosis have reduced left ventricular ejection fraction (LVEF) before transcatheter aortic valve replacement. The incidence, predictors, and significance of early LVEF recovery after CoreValve transcatheter aortic valve replacement have not been described. Methods and Results— We studied 156 patients from the CoreValve Extreme and High-Risk trials with LVEF ≤40% at baseline who had 30-day LVEF data. All patients underwent core laboratory echocardiographic assessment of LVEF at baseline, post procedure, discharge, 30 days, 6 months, and 1 year. Early LVEF recovery was defined as an absolute increase of ≥10% in EF at 30 days. One-year outcomes were compared between patients with and without early recovery. Multivariable analysis was performed to determine independent predictors of early recovery. Early LVEF recovery occurred in 62% of patients, generally before discharge. By 30 days LVEF increased >17% compared with baseline in the early recovery group with minimal increase in the no–early recovery group (48.9±8.8% versus 31.5±6.9%; P <0.001). One-year all-cause mortality was numerically (but not statistically) higher in the no–early recovery group (24% versus 12%; P =0.07). Absence of previous myocardial infarction (odds ratio, 0.44; 95% confidence interval, 0.19–1.03) and baseline mean gradient ≥40 mm Hg (odds ratio, 4.59; 95% confidence interval, 1.76–11.96) were identified as predictors of early LVEF recovery. Conclusions— Nearly two thirds of patients with reduced LVEF will have a marked early improvement after transcatheter aortic valve replacement. Early LVEF recovery is associated with improved clinical outcomes and is most likely among patients with higher baseline aortic valve gradients and no previous myocardial infarction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01240902.