Citations

As potential treatments for C9ORF72‐associated amyotrophic lateral sclerosis (c9ALS) approach clinical trials, the identification of prognostic biomarkers for c9ALS becomes a priority. We show that levels of phosphorylated neurofilament heavy chain (pNFH) in cerebrospinal fluid (CSF) predict disease status and survival in c9ALS patients, and are largely stable over time. Moreover, c9ALS patients exhibit higher pNFH levels, more rapid disease progression, and shorter survival after disease onset than ALS patients without C9ORF72 expansions. These data support the use of CSF pNFH as a prognostic biomarker for clinical trials, which will increase the likelihood of successfully developing a treatment for c9ALS. Ann Neurol 2017;82:139–146

IntroductionAdult prostatic sarcoma (PS) is a rare disease. While surgery is considered the standard approach, the role of other therapies is not completely established. We report results of the largest multicentric contemporary cohort of PS patients.Materials and MethodsThis study included 61 adult PS patients treated in 16 American and European Institutions. Median age was 64.4 years (range: 22‐87). Curative surgery was delivered in 48 patients (prostatectomy = 26, cystoprostatectomy = 22), usually with lymphadenectomy (n = 40). Curative radiotherapy (RT) was delivered in 32 patients, as radical (n = 5), neoadjuvant (n = 10), or postoperative treatment (n = 17). Eighteen patients received chemotherapy. None of the patients received hormonal therapy.ResultsMedian follow‐up was 72 months (95%CI: 55‐not reached). Five‐year local control (LC), overall survival (OS), cancer‐specific survival, disease‐free survival, and metastases‐free rates were 47%, 53%, 56%, 35%, and 35%, respectively. Notably, curative RT (neoadjuvant, adjuvant, or definitive) was associated with improved 5‐year LC (55% vs. 31%, P = 0.02) and OS (59% vs. 46%, P = 0.1). Surgically treated patients presenting with a cT3‐4 tumor (n = 31), who received RT (n = 24), had a significantly improved 5‐year LC (68% vs, 33%, P = 0.004) and OS (65% vs. 21%, P < 0.001) rates compared to patients not receiving RT. cT4 patients demonstrated a significantly lower 5‐year OS (43% vs. 61%, P = 0.006) and LC (29% vs. 69%, P < 0.001) rates. Histologic subtype was not associated with LC and OS, but patients with prostatic stromal sarcoma, rhabdomyosarcoma, or sarcomatoid carcinoma had worse 5‐year LC compared to other types (47% vs. 55%) and OS (49% vs. 58%).ConclusionAdult PS has a poor prognosis. Locally advanced tumors have poor LC and OS rates. Curative RT should be considered part of the multidisciplinary approach to PS.

AbstractBackgroundAn international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro‐esophageal reflux disease (GERD).MethodsLiterature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings.Key ResultsReflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter‐based or wireless pH‐monitoring or pH‐impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH‐impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom‐reflux association in the absence of pathological AET defines hypersensitivity to reflux.Conclusions and InferencesThe consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled.

Abstract Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is associated with increased morbidity and mortality, but the identification of LVAD candidates at risk for RVF remains challenging. We undertook a systematic review and meta-analysis of observational studies of risk factors associated with RVF after LVAD implant. Thirty-six studies published between 1 January 1995 and 30 April 2015, comprising 995 RVF patients out of a pooled final population of 4428 patients, were identified. Meta-analysed prevalence of post-LVAD RVF was 35%. A need for mechanical ventilation [odds ratio (OR) 2.99], or continuous renal replacement therapy (CRRT; OR 4.61, area under the curve 0.78, specificity 0.91) were the clinical variables with the highest effect size (ES) in predicting RVF. International normalized ratio [INR; standardized mean difference (SMD) 0.49] and N-terminal pro-brain natriuretic peptide (NT-proBNP) (SMD 0.52) were the biochemical markers that best discriminated between RVF and No-RVF populations, though NT-proBNP was highly heterogeneous. Right ventricular stroke work index (RVSWI) and central venous pressure (CVP) (SMD −0.58 and 0.47, respectively) were the haemodynamic measures with the highest ES in identifying patients at risk of post-LVAD RVF; CVP was particularly useful in risk stratifying patients undergoing continuous-flow LVAD implant (SMD 0.59, P &lt; 0.001, I2 = 20.9%). Finally, pre-implant moderate to severe right ventricular (RV) dysfunction, as assessed qualitatively (OR 2.82), or a greater RV/LV diameter ratio (SMD 0.51) were the standard echocardiographic measurements with the highest ES in comparing RVF with No-RVF patients. Longitudinal systolic strain of the RV free wall had the highest ES (SMD 0.73) but also the greatest heterogeneity (I2 = 74%) and was thus only marginally significant (P = 0.05). Patients on ventilatory support or CRRT are at high risk for post-LVAD RVF, similarly to patients with slightly increased INR, high NT-proBNP or leukocytosis. High CVP, low RVSWI, an enlarged right ventricle with concomitant low RV strain also identify patients at higher risk.

Poly(GP) proteins are a promising pharmacodynamic marker for developing and testing therapeutics for treating C9ORF72 -associated amyotrophic lateral sclerosis.

Background— It is not known whether abnormal blood pressure (BP) responses during dobutamine stress echocardiography (DSE) are associated with abnormal test results, nor if such results indicate obstructive coronary artery disease (CAD). We sought to define the frequency of abnormal BP responses during DSE and their impact on accuracy of test results. Methods and Results— We studied 21 949 patients who underwent DSE at Mayo Clinic, Rochester, MN, grouped by peak systolic BP achieved during the test. We also analyzed a subgroup who underwent coronary angiography within 30 days after positive DSE. The positive predictive value of DSE was calculated for each BP group. Patients with hypertensive response (n=1905; 9%) were more likely to have positive DSE than those with normal (n=19 770; 90%) or hypotensive (n=274; 1%) BP responses (32% versus 21% versus 23%, respectively; P <0.0001). Angiography, performed in 1126 patients, showed obstructive CAD (≥50% stenosis) in 814 patients and severe CAD (≥70% stenosis) in 708 patients. Positive predictive value of DSE was similar for patients who had hypertensive and normal BP responses (69% versus 73%; P =0.3), considering 50% stenosis cut point. The proportion of severe CAD (≥70% stenosis) was lower in patients who had hypertensive response compared with those who had normal BP response (54% versus 65%; P =0.005). Conclusions— Patients with hypertensive response during DSE are more likely to have stress-induced myocardial ischemia compared with those with normal or hypotensive BP responses but are not more likely to have false-positive DSE results. They are, however, less likely to have higher grade or multivessel CAD.