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ABSTRACT Introduction The aim of this study was to test the clinimetric properties of the Comprehensive Cervical Dystonia Rating Scale. This is a modular scale with modifications of the Toronto Western Spasmodic Torticollis Rating Scale (composed of three subscales assessing motor severity, disability, and pain) now referred to as the revised Toronto Western Spasmodic Torticollis Scale‐2; a newly developed psychiatric screening instrument; and the Cervical Dystonia Impact Profile‐58 as a quality of life measure. Methods Ten dystonia experts rated subjects with cervical dystonia using the comprehensive scale. Clinimetric techniques assessed each module of the scale for reliability, item correlation, and factor structure. Results There were 208 cervical dystonia patients (73% women; age, 59 ± 10 years; duration, 15 ± 12 years). Internal consistency of the motor severity subscale was acceptable (Cronbach's alpha = 0.57). Item to total correlations showed that elimination of items with low correlations (<0.20) increased alpha to 0.71. Internal consistency estimates for the subscales for disability and pain were 0.88 and 0.95, respectively. The psychiatric screening scale had a Cronbach's alpha of 0.84 and satisfactory item to total correlations. When the subscales of the Toronto Western Spasmodic Torticollis Scale‐2 were combined with the psychiatric screening scale, Cronbach's alpha was 0.88, and construct validity assessment demonstrated four rational factors: motor; disability; pain; and psychiatric disorders. The Cervical Dystonia Impact Profile‐58 had an alpha of 0.98 and its construction was validated through a confirmatory factor analysis. Conclusions The modules of the Comprehensive Cervical Dystonia Rating Scale are internally consistent with a logical factor structure. © 2016 International Parkinson and Movement Disorder Society

SummaryThe rituximab extended schedule or retreatment trial (RESORT; E4402) was a phase 3 randomized prospective trial comparing maintenance rituximab (MR) versus a retreatment (RR) dosing strategy in asymptomatic, low tumour burden indolent lymphoma. A planned exploratory sub‐study compared the two strategies for small lymphocytic (SLL) and marginal zone lymphomas (MZL). Patients responding to rituximab weekly × 4 were randomized to MR (single dose rituximab every 3 months until treatment failure) or RR (rituximab weekly × 4) at the time of each progression until treatment failure. The primary endpoint was time to treatment failure (TTTF). Patients with SLL (n = 57), MZL (n = 71) and unclassifiable small B‐cell lymphoma (n = 3) received induction rituximab. The overall response rate (ORR) was 40% [95% confidence interval (CI) 31–49%; SLL ORR 22·8%; MZL ORR 52·1%]; all 52 responders were randomized. At a median of 4·3 years from randomization, treatment failure occurred in 18/23 RR and 15/29 MR. The median TTTF was 1·4 years for RR and 4·8 years for MR (P = 0·012); median time to first cytotoxic therapy was 6·3 years for RR and not reached for MR (P = 0·0002). Survival did not differ (P = 0·72). In low tumour burden SLL and MZL patients responding to rituximab induction, MR significantly improved TTTF as compared with RR.

CONTEXT:The effectiveness of many interventions aimed at reducing the risk of retinopathy has not been well established.OBJECTIVE:To estimate the effectiveness of nutritional interventions, oxygen saturation targeting, blood transfusion management, and infection prevention on the incidence of retinopathy of prematurity (ROP).DATA SOURCES:A comprehensive search of several databases was conducted, including Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through March 2014.STUDY SELECTION:We included studies that evaluated nutritional interventions, management of supplemental oxygen, blood transfusions, or infection reduction and reported the incidence of ROP and mortality in neonates born at &lt;32 weeks.DATA EXTRACTION:We extracted patient characteristics, interventions, and risk of bias indicators. Outcomes of interest were any stage ROP, severe ROP or ROP requiring treatment, and mortality.RESULTS:We identified 67 studies enrolling 21 819 infants. Lower oxygen saturation targets reduced the risk of developing any stage ROP (relative risk [RR] 0.86, 95% confidence interval [CI], 0.77–0.97) and severe ROP or ROP requiring intervention (RR 0.58, 95% CI, 0.45–0.74) but increased mortality (RR 1.15, 95% CI, 1.04–1.29). Aggressive parenteral nutrition reduced the risk of any stage ROP but not severe ROP. Supplementation of vitamin A, E, or inositol and breast milk feeding were beneficial but only in observational studies. Use of transfusion guidelines, erythropoietin, and antifungal agents were not beneficial.LIMITATIONS:Results of observational studies were not replicated in randomized trials. Interventions were heterogeneous across studies.CONCLUSIONS:At the present time, there are no safe interventions supported with high quality evidence to prevent severe ROP.

AbstractTraining and credentialing for robotic surgery in otolaryngology ‐ head and neck surgery is currently not standardized, but rather relies heavily on industry guidance. This manuscript represents a comprehensive review of this increasingly important topic and outlines clear recommendations to better standardize the practice. The recommendations provided can be used as a reference by individuals and institutions alike, and are expected to evolve over time. © 2016 Wiley Periodicals, Inc. Head Neck 38: E151–E158,

Deletion of the long arm of chromosome 20 (20q‐) is a frequent finding in bone marrow karyotypes, mainly associated with myeloid neoplasms (MNs). Its clinical significance in the setting of normal bone marrow morphology is unclear. We described the clinical characteristics, cytogenetic findings, and outcome of 102 such patients seen at our institution from 2000‐2014. Their median age was 66 years. The indication for bone marrow biopsy was either unexplained cytopenias (48%) or hematologic cancer staging/reevaluation (52%). In 88 (86%) patients, 20q‐ was an isolated finding. Thirty‐nine (38%) patients previously received chemotherapy and 88 (86%) had cytopenias at the time of 20q‐ finding. After a median of 35 months, 12 (13%) patients developed MNs: 10 myelodysplastic syndromes, one acute myeloid leukemia and one myeloproliferative neoplasm. None of 14 patients with normal blood counts, but 7 of 35 (20%) with mild cytopenias, and 5 of 53 (9%) with moderate/severe cytopenias developed MNs. We did not find an association between the number of metaphases with 20q‐ and the development of MN. The incidental finding of 20q‐ in the bone marrow generally does not portend an early stage MN. Particularly, those without cytopenias at the time of diagnosis may have a good prognosis. Am. J. Hematol. 91:556–559, 2016. © 2016 Wiley Periodicals, Inc.

Purpose This trial assessed the efficacy and safety of docetaxel monotherapy or docetaxel in combination with ramucirumab (vascular endothelial growth factor receptor 2 antibody) or icrucumab (vascular endothelial growth factor receptor 1 antibody) after progression during or within 12 months of platinum-based regimens for patients with locally advanced or metastatic urothelial carcinoma. Patients and Methods Patients were randomly assigned (1:1:1) to receive docetaxel 75 mg/m2 intravenously (IV) on day 1 of a 3-week cycle (arm A), docetaxel 75 mg/m2 IV plus ramucirumab 10 mg/kg IV on day 1 of a 3-week cycle (arm B), or docetaxel 75 mg/m2 IV on day 1 plus icrucumab 12 mg/kg IV on days 1 and 8 of a 3-week cycle (arm C). Treatment continued until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS). Results A total of 140 patients were randomly assigned and treated in arms A (n = 45), B (n = 46), or C (n = 49). PFS was significantly longer in arm B compared with arm A (median, 5.4 months; 95% CI, 3.1 to 6.9 months v 2.8 months; 95% CI, 1.9 to 3.6 months; stratified hazard ratio, 0.389; 95% CI, 0.235 to 0.643; P = .0002). Arm C did not experience improved PFS compared with arm A (1.6 months; 95% CI, 1.4 to 2.9; stratified hazard ratio, 0.863; 95% CI, 0.550 to 1.357; P = .5053). The most common grade 3 or worse adverse events (arms A, B, and C) were neutropenia (36%, 33%, and 39%), fatigue (13%, 30%, and 20%), febrile neutropenia (13%, 17%, and 6.1%), and anemia (6.7%, 13%, and 14%, respectively). Conclusion The addition of ramucirumab to docetaxel met the prespecified efficacy end point for prolonging PFS in patients with locally advanced or metastatic urothelial carcinoma receiving second-line treatment and warrants further investigation in the phase III setting.

Abstract: Cellular blue nevomelanocytic lesions (CBNLs) frequently pose diagnostic problems to pathologists, and their biological potential may be difficult to establish. In this study, the authors have analyzed the clinical, histological, and outcome data of 37 cellular blue nevomelanocytic lesions and the molecular characteristics of 4 lesions. The cohort of cases comprised 8 cellular blue nevi (CBNs), 17 atypical cellular blue nevi (ACBNs), and 12 blue-nevus–like melanomas (BNLMs) with a mean follow-up of 5 years. The average age at diagnosis was 25.9 years for patients with ACBN, versus 30.4 years for CBN, and 44.6 years for BNLM. Both CBN and ACBN occurred most frequently on the trunk or extremities, whereas BNLM primarily involved the scalp. Histologically, CBN and ACBN were characterized by a mean diameter of <1 cm, absence of necrosis, low mitotic rate (mean: 1–2 mitotic figures/mm2), little or no infiltrative properties, and usually low-grade cytologic atypia. In contrast, BNLM had a mean diameter of 1.6 cm, necrosis, tissue infiltration, greater mitotic activity (mean: 6 mitotic figures/mm2), and high-grade cytologic atypia. ACBNs often were larger, more densely cellular, exhibited higher mitotic counts, and were cytologically more atypical than CBN. Seven CBN cases with follow-up had a benign clinical course (average follow-up of 4.7 years). Among 6 patients with ACBN who underwent sentinel lymph node (SLN) biopsy, 3 were positive, and a single additional case had 1 positive non-SLN (this patient did not have a SLN biopsy performed). All 14 cases of ACBN with follow-up were alive and without recurrence with mean follow-up of 5 years. Of the 9 melanoma cases with follow-up, 3 patients with SLN and non-SLN involvement died from their disease (average follow-up of 4.8 years). Array comparative genomic hybridization was performed on 2 ACBNs and 1 BNLM: One of the 2 ACBNs showed chromosomal aberrations and 1 BNLM showed multiple chromosomal gains and losses. Multiplex polymerase chain reaction was performed on 1 ACBN, and no mutations were found. From these results, the authors conclude that ACBN occupy an intermediate position within the spectrum of CBN and BNLM, yet many lesions cannot be reliably distinguished from either CBN or BNLM because of overlapping histologic features. However, in general, ACBNs seem to aggregate more closely with CBN in terms of clinical, histological, molecular profile (limited data), and biological behavior.

Background.Noninvasive prenatal screening (NIPS) is revolutionizing prenatal screening as a result of its increased sensitivity, specificity. NIPS analyzes cell-free fetal DNA (cffDNA) circulating in maternal plasma to detect fetal chromosome abnormalities. However, cffDNA originates from apoptotic placental trophoblast; therefore cffDNA is not always representative of the fetus. Although the published data for NIPS testing states that the current technique ensures high sensitivity and specificity for aneuploidy detection, false positives are possible due to isolated placental mosaicism, vanishing twin or cotwin demise, and maternal chromosome abnormalities or malignancy.Results.We report a case of false negative cell-free DNA (cfDNA) screening due to fetoplacental mosaicism. An infant male with negative cfDNA screening result was born with multiple congenital abnormalities. Postnatal chromosome and FISH studies on a blood specimen revealed trisomy 13 in 20/20 metaphases and 100% interphase nuclei, respectively. FISH analysis on tissues collected after delivery revealed extraembryonic mosaicism.Conclusions.Extraembryonic tissue mosaicism is likely responsible for the false negative cfDNA screening result. This case illustrates that a negative result does not rule out the possibility of a fetus affected with a trisomy, as cffDNA is derived from the placenta and therefore may not accurately represent the fetal genetic information.