Citations

SummaryObjectiveThymic neuroendocrine tumour (TH‐NET) accounts for almost 20% of multiple endocrine neoplasia type 1 (MEN1)‐associated mortality. Identifying risk factors for the development of these rare tumours and prognostic factors for clinical outcomes will be helpful in clinical practice.Design and PatientsWe performed a retrospective analysis of patients treated for TH‐NET associated with MEN1 in a single institution and meta‐analysis of literature reports. We used a fixed effect model to pool results across studies to evaluate the prevalence, clinical features and prognosis.ResultsTH‐NET was detected in 9 (7.4%) of 121 patients with MEN1 seen in our institution, and 5 (55.6%) were women. Seven additional studies were identified through a systematic review of the literature. The pool estimate of TH‐NET prevalence was 3.7% (n = 99) in MEN1 (n = 2710), sex ratio was 79:20 (male vs female), and the median age at diagnosis was 43.0 years (range, 16.0‐72.0 years). Forty‐three patients died with a median survival time of 8.4 years. Older age at diagnosis (HR = 1.4, 95% CI = 1.0‐1.8, P = .03), maximum tumour diameter (HR = 1.5, 95% CI = 1.0‐2.3, P = .04) and presence of metastasis (HR = 1.6, 95% CI = 1.0‐2.5, P = .04) were associated with worse outcome. A male predominance (91.9% vs 59.5%, P < .001) and history of smoking (59.0% vs 23.5%, P = .015) were more common in American/European series compared to Asian reports.ConclusionTH‐NET is a rare but fatal component of MEN1. Earlier detection of TH‐NET in patients with MEN1 may be recommended which should theoretically result in better outcomes. Different genetic backgrounds (race) appear to result in clinical difference.

Objective We describe a novel way to calculate estimated blood loss (EBL) using an intraoperative pictographic tool in gynecologic surgery. Methods A pictographic tool to estimate sponge saturation was developed to calculate EBL during surgery. A prospective cohort of women 18 years or older undergoing benign vaginal hysterectomy with planned adnexal surgery at Mayo Clinic were consented for use of the pictographic tool. Demographic, preoperative, intraoperative, and postoperative data were abstracted. Estimated blood loss was compared among surgeons, anesthesia providers, and the pictographic tool and then correlated with change in hemoglobin. Results Eighty-one patients met inclusion with mean age of 45.3 ± 8.7 years. Successful vaginal hysterectomy was achieved in all patients with successful completion of planned adnexectomy in 69 (85.2%). Mean EBL among surgeons, anesthesia providers, and pictographic estimates, respectively, was as follows: 199.4 ± 81.9 mL, 195.5 ± 152.2 mL, and 288.5 ± 186.6 mL, with concordance correlation coefficients for surgeons and anesthesia providers versus pictographic tool of 0.40 (95% confidence interval, 0.29–0.51) and 0.68 (95% confidence interval, 0.57–0.79), respectively. The mean postoperative change in hemoglobin was −1.8 g/dL; there were no postoperative transfusions. Change in hemoglobin was more correlated with blood loss estimates from surgeons ( r = −0.31, P = 0.008) and anesthesia providers ( r = −0.37, P = 0.003) than the pictographic tool ( r = −0.19, P = 0.11). Conclusions Use of a pictographic tool to objectively estimate blood loss demonstrated significant overestimations compared with both anesthesia providers’ and surgeons’ estimates because the pictographic tool was less correlated with postoperative change in hemoglobin than anesthesia provider and surgeon estimates.

Purpose This study compared orofacial strength between adults with dysarthria and neurologically normal (NN) matched controls. In addition, orofacial muscle weakness was examined for potential relationships to speech impairments in adults with dysarthria. Method Matched groups of 55 adults with dysarthria and 55 NN adults generated maximum pressure (P max ) against an air-filled bulb during lingual elevation, protrusion and lateralization, and buccodental and labial compressions. These orofacial strength measures were compared with speech intelligibility, perceptual ratings of speech, articulation rate, and fast syllable-repetition rate. Results The dysarthria group demonstrated significantly lower orofacial strength than the NN group on all tasks. Lingual strength correlated moderately and buccal strength correlated weakly with most ratings of speech deficits. Speech intelligibility was not sensitive to dysarthria severity. Individuals with severely reduced anterior lingual elevation P max (< 18 kPa) had normal to profoundly impaired sentence intelligibility (99%–6%) and moderately to severely impaired speech (26%–94% articulatory imprecision; 33%–94% overall severity). Conclusions Results support the presence of orofacial muscle weakness in adults with dysarthrias of varying etiologies but reinforce tenuous links between orofacial strength and speech production disorders. By examining individual data, preliminary evidence emerges to suggest that speech, but not necessarily intelligibility, is likely to be impaired when lingual weakness is severe.

Abstract Introduction: Outcomes for pts with refractory aggressive NHL are poor with current therapies (Crump, ASCO 2016). Results from the interim analysis of (n=62) of ZUMA-1, the 1st multicenter trial of an anti-CD19 chimeric antigen receptor (CAR) T cell, axi-cel, in refractory aggressive NHL, showed an objective response rate (ORR) of 79% (complete response [CR] 52%; Blood 2016;128:LBA-6). Here we present results from the primary analysis of ZUMA-1. Methods: Pts received a target dose of 2 × 106 anti-CD19 CAR T cells/kg after lowdose conditioning with cy/flu. Eligible pts (≥18 y) had diffuse large B cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMBCL) or transformed follicular lymphoma (TFL); an ECOG performance status (PS) 0-1; and refractory disease (progressive or stable disease as best response to last prior therapy, or relapsed ≤12 m of autologous stem cell transplant [ASCT]). The primary endpoint for this analysis was ORR in the combined DLBCL, PMBCL, and TFL population. Key secondary endpoints were duration of response (DOR), overall survival (OS), and frequency of adverse events (AEs). The primary analysis was triggered when 92 pts had at least 6 m of follow-up. Results: As of January 27, 2017, 111 pts from 22 institutions were enrolled; 101 pts (91%) received axi-cel. Median age was 58 y (range, 23-76), 67% male, 85% stage IIIIV, 47% IPI 3-4, 77% refractory to ≥2nd line of therapy, and 21% relapsed ≤12 m of ASCT. Axi-cel was successfully manufactured in 110/111 (99%) pts with an average turnaround time from apheresis to the clinical site of 17 d. With an ORR of 82% (n = 92; P&lt;.0001) the study met the primary endpoint. The ORR in the mITT analysis set of 101 pts was 82% (CR 54%, PR 28%), and was consistent across key covariates including disease subtype, refractory status, stage, and IPI score. At a median follow up of 8.7 m, 44% of pts were in response and 39% were in CR. The median DOR was 8.2 m overall and not reached for pts who achieved a CR. Median OS was not reached; 80% of pts remained alive at 6 m. The most common Gr ≥3 treatmentemergent AEs were neutropenia (66%), leukopenia (44%), anemia (43%), febrile neutropenia (31%), and encephalopathy (21%). Gr ≥3 cytokine release syndrome (CRS) and neurologic events (NE) occurred in 13% and 28% of pts, respectively. All CRS and all NE resolved except 1 Gr 1 memory impairment. As previously reported, there were 3 Gr 5 AEs (3%). Peak and cumulative CAR T levels post-axi-cel were associated with durable responses. Conclusions: Axi-cel significantly improved ORR in patients with refractory aggressive NHL. The CR rate was 7-fold higher compared to historical controls (Crump, ASCO 2016) and nearly half the patients have an ongoing response. Axi-cel demonstrated significant clinical benefit with a manageable safety profile in pts lacking curative treatment options.[F.L.L. and S.S.N. contributed equally to this study.] Funding source: Kite Pharma and in part by funding from the Leukemia & Lymphoma Society (LLS) Therapy Acceleration Program treatment options. Citation Format: Frederick L. Locke, Sattva S. Neelapu, Nancy L. Bartlett, Lazaros J. Lekakis, David Miklos, Caron A. Jacobson, Ira Braunschweig, Olalekan Oluwole, Tanya Siddiqi, Yi Lin, John Timmerman, Jonathan W. Friedberg, Adrian Bot, John Rossi, Lynn Navale, Yizhou Jiang, Jeff Aycock, Meg Elias, Jeff Wiezorek, William Y. Go. Primary results from ZUMA-1: a pivotal trial of axicabtagene ciloleucel (axicel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT019. doi:10.1158/1538-7445.AM2017-CT019

This study builds on previous research that identified fears and concerns heard by procurement coordinators during the donation discussion and that classified those concerns according to the ease with which they can be addressed. In this study, 53 coordinators working for 4 procurement agencies provided data on 323 donation discussions, including fears and concerns expressed by families. The fears and concerns were analyzed by outcome (consent or refusal), race and ethnicity of the family, frequency of reports, and difficulty in addressing. This research confirms many of the findings of the earlier study. The results also indicate that the types of concerns expressed by donor and non–donor families vary somewhat by the family's race and ethnicity. The results can be used to provide training targeted at raising consent rates and to train minority requestors.

Abstract Objectives The purpose of this systematic review is to provide a comprehensive overview on the clinical course, perinatal outcome, and effectiveness of prenatal management options for pericardial teratoma. Methods A comprehensive search including Ovid MEDLINE, Ovid EMBASE, and Scopus was conducted from inception to September 2016. All studies that reported the prenatal course of pericardial teratoma in singleton or twin gestations were considered eligible. Standardized forms were used for data abstraction by two independent reviewers. Results Out of 217 screened abstracts, 59 studies reporting 67 fetuses with pericardial teratoma were included. Twenty‐three singleton fetuses and 3 fetuses in twin gestations underwent prenatal treatment, and 20 (76.9%) of them were hydropic at the time of intervention. Of those, 15/20 (75%) had a favorable outcome. In the non‐intervention group ( n = 41), 26 (63.4%) developed hydrops, and out of those, 8 (30.8%) had a favorable outcome. Conclusion Prenatal fluid drainage and other prenatal techniques have been utilized in the treatment of intrapericardial teratoma. While most fetuses tolerated pericardiocentesis, the neonatal benefit of this procedure is still uncertain, and outcomes of other interventions had variable success. Prenatal intervention for pericardial teratoma may be an option in specialized units but, given the maternal and fetal risks, needs careful consideration. © 2017 John Wiley & Sons, Ltd.

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