Publication date: Available online 7 March 2018
Source:Trends in Cognitive Sciences
Author(s): Kieran C.R. Fox, Brett L. Foster, Aaron Kucyi, Amy L. Daitch, Josef Parvizi
The human default network (DN) plays a critical role in internally directed cognition, behavior, and neuropsychiatric disease. Despite much progress with functional neuroimaging, persistent questions still linger concerning the electrophysiological underpinnings, fast temporal dynamics, and causal importance of the DN. Here, we review how direct intracranial recording and stimulation of the DN provides a unique combination of high spatiotemporal resolution and causal information that speaks directly to many of these outstanding questions. Our synthesis highlights the electrophysiological basis of activation, suppression, and connectivity of the DN, each key areas of debate in the literature. Integrating these unique electrophysiological data with extant neuroimaging findings will help lay the foundation for a mechanistic account of DN function in human behavior and cognition.
http://ift.tt/2HfvFre
Τετάρτη 7 Μαρτίου 2018
Intracranial Electrophysiology of the Human Default Network
Diagnosing diabetes mellitus in patients with porphyria cutanea tarda
Abstract
The prevalence of diabetes mellitus is increased in patients with porphyria cutanea tarda. Different tests are available for diagnosing and screening for type II diabetes mellitus, however choosing the most suitable test is challenging. The pitfalls in the different tests along with the interfering comorbidities and treatments concerning patients with porphyria cutanea tarda complicate diagnosing these patients with diabetes mellitus. HbA1c, fasting glucose, or oral glucose tolerance are the current available tests, with HbA1c as first choice. Measuring HbA1c requires no fasting, however HbA1c can be false low if the patient is treated with phlebotomy or has liver cirrhosis or chronic hepatitis. Instead fasting glucose and oral glucose tolerance tests can be used if the patient is not acutely ill. If either of the tests give a result in the diagnostic range, the test should be repeated if the patient has no clinical symptoms of diabetes. Diagnosing diabetes mellitus is important for the purpose of early intervention, and this review provides the knowledge needed to diagnose this special patient group properly.
http://ift.tt/2G3n0bW
Prognostic value of primary tumour resection in synchronous metastatic colorectal cancer: Individual patient data analysis of first-line randomised trials from the ARCAD database
Publication date: March 2018
Source:European Journal of Cancer, Volume 91
Author(s): K.L. van Rooijen, Q. Shi, K.K.H. Goey, J. Meyers, V. Heinemann, E. Diaz-Rubio, E. Aranda, A. Falcone, E. Green, A. de Gramont, D.J. Sargent, C.J.A. Punt, M. Koopman
Indication for primary tumour resection (PTR) in asymptomatic metastatic colorectal cancer (mCRC) patients is unclear. Previous retrospective analyses suggest a survival benefit for patients who underwent PTR. The aim was to evaluate the prognostic value of PTR in patients with synchronous mCRC by analysis of recent large RCTs including systemic therapy with modern targeted agents.Individual patient data (IPD) of 3423 patients enrolled into 8 randomised controlled trials (RCTs) with first-line systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analysed.The number of patients with unresected synchronous mCRC, resected synchronous mCRC and metachronous mCRC was 710 (21%), 1705 (50%) and 1008 (29%), respectively. Adjusting for age, gender, performance status (PS) and prior chemotherapy, the unresected group had a significantly worse median overall survival (16.4 m) compared with the synchronous resected (22.2 m; hazard ratio [HR] 1.60, 95% CI 1.43–1.78) and metachronous (22.4 m; HR 1.81, 95% CI 1.58–2.07) groups. Similarly, median progression-free survival was significantly worse for the unresected group compared with the synchronous resected (HR 1.31, 95% CI 1.19–1.44) and metachronous (HR 1.47, 95% CI 1.30–1.66) groups. In a multivariate analysis, the observed associations remained significant.This largest IPD analysis of mCRC trials to date demonstrates an improved survival in synchronous mCRC patients after PTR. These results may be subject to bias since reasons for (non)resection were not available. Until results of ongoing RCTs are available, both upfront PTR followed by systemic treatment and upfront systemic treatment are considered appropriate treatment strategies.
http://ift.tt/2FlOgpc
Fast growing melanoma following treatment with vismodegib for locally advanced basal cell carcinomas: report of two cases
Source:European Journal of Cancer, Volume 91
Author(s): Roberta Giuffrida, Karl Kashofer, Emi Dika, Annalisa Patrizi, Carlotta Baraldi, Nicola Di Meo, Iris Zalaudek
http://ift.tt/2D7npqV
Integrative expression quantitative trait locus–based analysis of colorectal cancer identified a functional polymorphism regulating SLC22A5 expression
Source:European Journal of Cancer, Volume 93
Author(s): Danyi Zou, Jiao Lou, Juntao Ke, Shufang Mei, Jiaoyuan Li, Yajie Gong, Yang Yang, Ying Zhu, Jianbo Tian, Jiang Chang, Rong Zhong, Jing Gong, Xiaoping Miao
Multiple single nucleotide polymorphisms (SNPs) have been found to be highly correlated with colorectal cancer (CRC) risk. However, the variants identified thus far only explain a small part of the cases, suggesting the existence of many uncharacterised genetic determinants. In this study, using the multilevel 'omics' data provided in The Cancer Genome Atlas, we systematically performed expression quantitative trait locus (eQTL) analysis for CRC and identified nine SNPs with significant effects on mRNA expression (correlation |r| > 0.3 and FDR < 0.01). Then we conducted a two-stage case–control study consisting of 1528 cases and 1528 controls to examine the associations between candidate SNPs and CRC risk. We found that rs27437 in SLC22A5 was significantly correlated with CRC risk in both stages and the combined study (additive model, OR = 1.31, 95%CI = 1.17–1.47, P = 1.97 × 10−6). eQTL analysis showed that rs27437 GG and GA genotypes were associated with lower expression of SLC22A5 compared with the AA genotype. Dual-luciferase reporter assays confirmed that the G risk allele could decrease the expression of luciferase. SLC22A5 was significantly decreased in CRC tumour tissues compared with adjacent normal tissues, indicating that SLC22A5 may play important roles in CRC, and rs27437 in SLC22A5 might serve as a novel biomarker for early detection and prevention of CRC.
http://ift.tt/2Fla18F
Histamine H4 receptor as a novel therapeutic target for the treatment of Leydig-cell tumours in prepubertal boys
Publication date: March 2018
Source:European Journal of Cancer, Volume 91
Author(s): Adriana María Belén Abiuso, María Luisa Varela, Luis Haro Durand, Marcos Besio Moreno, Alejandra Marcos, Roberto Ponzio, Marco Aurelio Rivarola, Alicia Belgorosky, Omar Pedro Pignataro, Esperanza Berensztein, Carolina Mondillo
Leydig-cell tumours (LCTs) are rare endocrine tumours of the testicular interstitium, with recent increased incidence. Symptoms include precocious puberty in children; and erectile dysfunction, infertility and/or gynaecomastia, in adults. So far, scientific evidence points to aromatase (CYP19) overexpression and excessive oestrogen and insulin-like growth factor (IGF) –1 production as responsible for Leydig-cell tumourigenesis. LCTs are usually benign; however, malignant LCTs respond poorly to chemo/radiotherapy, highlighting the need to identify novel targets for treatment. Herein, we investigated the potential role of the histamine receptor H4 (HRH4) as a therapeutic target for LCTs using R2C rat Leydig tumour cells, a well-documented in vitro model for Leydigioma. Also, we studied for the first time the expression of CYP19, IGF-1R, oestrogen receptor (ER) α, ERβ, androgen receptor (AR) and HRH4 in human prepubertal LCTs versus normal prepubertal testes (NPTs). HRH4 agonist treatment inhibited steroidogenesis and proliferation in R2C cells and also negatively affected their pro-angiogenic capacity in vitro and in vivo, as assessed by evaluating the proliferative activity of human umbilical vein endothelial cells and by means of the quail chorioallantoic membrane assay, respectively. Moreover, E2 and IGF-1 inhibited HRH4 mRNA and protein levels. In human prepubertal LCTs, CYP19, IGF-1R, ERα and ERβ were overexpressed compared with NPTs. In contrast, HRH4 staining was weak in LCTs, but moderate/strong and confined to the interstitium in NPTs. Importantly, HRH4 was absent or barely detectable in seminiferous tubules or germ cells. Overall, our results point to HRH4 as a novel therapeutic target in LCTs.
http://ift.tt/2DalCBc
Hallmarks of cancer: The CRISPR generation
Source:European Journal of Cancer, Volume 93
Author(s): Colette Moses, Benjamin Garcia-Bloj, Alan R. Harvey, Pilar Blancafort
The hallmarks of cancer were proposed as a logical framework to guide research efforts that aim to understand the molecular mechanisms and derive treatments for this highly complex disease. Recent technological advances, including comprehensive sequencing of different cancer subtypes, have illuminated how genetic and epigenetic alterations are associated with specific hallmarks of cancer. However, as these associations are purely descriptive, one particularly exciting development is the emergence of genome editing technologies, which enable rapid generation of precise genetic and epigenetic modifications to assess the consequences of these perturbations on the cancer phenotype. The most recently developed of these tools, the system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), consists of an RNA-guided endonuclease that can be repurposed to edit both genome and epigenome with high specificity, and facilitates the functional interrogation of multiple loci in parallel. This system has the potential to dramatically accelerate progress in cancer research, whether by modelling the genesis and progression of cancer in vitro and in vivo, screening for novel therapeutic targets, conducting functional genomics/epigenomics, or generating targeted cancer therapies. Here, we discuss CRISPR research on each of the ten hallmarks of cancer, outline potential barriers for its clinical implementation and speculate on the advances it may allow in cancer research in the near future.
http://ift.tt/2FjDH66
Current perspective: Osimertinib-induced QT prolongation: new drugs with new side-effects need careful patient monitoring
Source:European Journal of Cancer, Volume 91
Author(s): Mart Schiefer, Lizza E.L. Hendriks, Trang Dinh, Ulrich Lalji, Anne-Marie C. Dingemans
An increasing number of tyrosine kinase inhibitors (TKIs) are available for the treatment of non–small cell lung cancer (NSCLC). QT prolongation is one of the known, but relatively rare, adverse events of several TKIs (e.g. osimertinib, crizotinib, ceritinib). Screening for QT prolongation in (high risk) patients is advised for these TKIs. When a QT prolongation develops, the physician is challenged with the question whether to (permanently) discontinue the TKI. In this perspective, we report on a patient who developed a grade III QT prolongation during osimertinib (a third-generation epidermal growth factor receptor [EGFR]-TKI) treatment. On discontinuation of osimertinib, she developed a symptomatic disease flare, not responding to subsequent systemic treatment. The main aim of this perspective is to describe the management of QT prolongation in stage IV EGFR driver mutation NSCLC patients. We also discuss the ethical question of how to weigh the risk of a disease flare due to therapy cessation against the risk of sudden cardiac death. A family history of sudden death and a prolonged QT interval might indicate a familiar long QT syndrome. We have summarised the current monitoring advice for TKIs used in the treatment of lung cancer and the most common drug–TKI interactions to consider and to optimise TKI treatment in lung cancer patients.
http://ift.tt/2FrEU75
Diversity of brain metastases screening and management in non-small cell lung cancer in Europe: Results of the European Organisation for Research and Treatment of Cancer Lung Cancer Group survey
Publication date: April 2018
Source:European Journal of Cancer, Volume 93
Author(s): Antonin Levy, Corinne Faivre-Finn, Baktiar Hasan, Eleonora De Maio, Anna S. Berghoff, Nicolas Girard, Laurent Greillier, Sylvie Lantuéjoul, Mary O'Brien, Martin Reck, Anne-Marie C. Dingemans, Silvia Novello, Thierry Berghmans, Benjamin Besse, Lizza Hendriks
BackgroundBrain metastases (BM) are frequent in non-small cell lung cancer (NSCLC) patients, but there is a lack of evidence-based management of this patient group. We aimed to capture a snapshot of routine BM management in Europe to identify relevant research questions for future clinical trials.MethodsAn EORTC Lung Cancer Group (LCG) online survey containing questions on NSCLC BM screening and treatment was distributed between 16/02/17 and 15/06/17 to worldwide EORTC LCG members, and through several European scientific societies in the thoracic oncology field.ResultsA total of 462 European physician responses (394 institutions) were analysed (radiation oncologist: 53% [n = 247], pulmonologist: 26% [n = 119], medical oncologist: 18% [n = 84]; 84% with >5 years' experience in NSCLC). Italy (18%, n = 85), Netherlands (15%, n = 68), UK (14%, n = 66), and France (12%, n = 55) contributed most. 393 physicians (85%) screened neurologically asymptomatic patients for BM at diagnosis (52% using magnetic resonance imaging). Most often screened patients were those with a driver mutation (MUT+; 51%, n = 234), stage III (63%, n = 289), and IV (43%, n = 199). 158 physicians (34%) used a prognostic classification to guide initial treatment decisions, and in 50%, lowest prognostic-score threshold to receive treatment differed between MUT+ and non-driver mutation (MUT−) patients. MUT+ patients with >4 BM were more likely to receive stereotactic radiosurgery (SRS) compared with MUT− (27% versus. 21%; p < 0.01). Most physicians (90%) had access to SRS. After single BM surgery, 50% systematically prescribed SRS or WBRT, and 45% only in case of incomplete resection. The preferred treatment in neurologically asymptomatic treatment-naive patients diagnosed with >5 BM was systemic treatment (79%). Of all, 45%/49% physicians stated that all tyrosine kinase inhibitors and immune checkpoint blockers were discontinued (timing varied) during SRS/WBRT, respectively. Drugs most often continued during SRS/WBRT were erlotinib (44%/40%), gefitinib (39%/34%), afatinib (29%/25%), crizotinib (33%/26%) and anti-PD-(L)-1 (28%/22%).ConclusionBM management is highly variable in Europe: screening is not uniform, prognostic classifications are not often used and MUT+ NSCLC patients generally receive more intensive local treatment. Prospective assessment of BM management in MUT+ NSCLC patients is required.
http://ift.tt/2FlNW9Y
Rechallenge with BRAF-directed treatment in metastatic melanoma: A multi-institutional retrospective study
Source:European Journal of Cancer, Volume 91
Author(s): Sara Valpione, Matteo S. Carlino, Johanna Mangana, Meghan J. Mooradian, Grant McArthur, Dirk Schadendorf, Axel Hauschild, Alexander M. Menzies, Ana Arance, Paolo A. Ascierto, AnnaMaria Di Giacomo, Francesco de Rosa, James Larkin, John J. Park, Simone M. Goldinger, Ryan J. Sullivan, Wen Xu, Elisabeth Livingstone, Michael Weichenthal, Rajat Rai, Lydia Gaba, Georgina V. Long, Paul Lorigan
BackgroundMost metastatic melanoma patients treated with BRAF inhibitors (BRAFi) ± MEK inhibitors (MEKi) eventually progress on treatment. Along with acquired resistance due to genetic changes, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse retrospectively outcomes for patients retreated with BRAF-directed therapy.Patients and methodsOne hundred sixteen metastatic melanoma patients who received BRAFi-based therapy and, after a break, were rechallenged with BRAFi ± MEKi at 14 centres in Europe, US and Australia were studied, respectively. Response rate (RR), overall survival (OS) and progression-free survival (PFS) from the start of retreatment were calculated.ResultsThe median duration of treatment was 9.4 months for first BRAFi ± MEKi treatment and 7.7 months for the subsequent treatment (immunotherapy 72%, other 17%, drug holiday 11%) after BRAFi discontinuation. Brain metastases were present in 51 (44%) patients at BRAFi retreatment. The RR to rechallenge with BRAFi ± MEKi was 43%: complete response (CR) 3%, partial response (PR) 39%, stable disease (SD) 24% and progressive disease 30%, 4% missing. Of 83 patients who previously discontinued BRAFi due to disease progression, 31 (37.3%) responded (30 PR and 1 CR) to retreatment. The median OS from retreatment was 9.8 months, and PFS was 5 months. Independent prognostic factors for survival at rechallenge included number of metastatic sites (hazard ratio [HR] = 1.32 for each additional organ with metastases, P < .001), lactic dehydrogenase (HR = 1.37 for each multiple of the upper normal limit, P < .001), while rechallenge with combination BRAFi + MEKi conferred a better OS versus BRAFi alone (HR = 0.5, P = .006).ConclusionRechallenge with BRAFi ± MEKi results in a clinically meaningful benefit and should be considered for selected patients.
http://ift.tt/2Fqhsap
High-risk soft tissue sarcomas treated with perioperative chemotherapy: Improving prognostic classification in a randomised clinical trial
Source:European Journal of Cancer, Volume 93
Author(s): Sandro Pasquali, Chiara Colombo, Sara Pizzamiglio, Paolo Verderio, Dario Callegaro, Silvia Stacchiotti, Javier Martin Broto, Antonio Lopez-Pousa, Stefano Ferrari, Andres Poveda, Antonino De Paoli, Vittorio Quagliuolo, Josefina Cruz Jurado, Alessandro Comandone, Giovanni Grignani, Rita De Sanctis, Elena Palassini, Antonio Llomboart-Bosch, Angelo Paolo Dei Tos, Paolo G. Casali, Piero Picci, Alessandro Gronchi
BackgroundPatients with extremity and trunk wall soft tissue sarcoma (STS) with high malignancy grade and size >5 cm are at high-risk of death. This risk varies depending also on other patient and tumour features, including histologic subtype. This study investigated whether a prognostic nomogram can improve risk assessment of these patients.MethodsData from high-risk STS patients enrolled in a randomised controlled trial investigating different perioperative chemotherapy regimens were analysed. Ten-year probability of overall survival (OS) and incidence of distant metastasis (DM) were computed using the prognostic nomogram Sarculator (pr-OS and inc-DM, respectively). Tumour response according to RECIST and Choi criteria was also investigated.FindingsVariation in pr-OS and inc-DM were observed and patients stratified in three prognostic groups. The 10-year OS in the low, intermediate, and high pr-OS categories were 0·42 (95%CI 0·32–0·52), 0·63 (95%CI 0·53–0·72), and 0·78 (95%CI 0·68–0·85), respectively. Patients in the intermediate (HR 0·51, P = 0·002) and high (HR 0·28, P < 0·001) pr-OS categories were at statistically significant lower risk of death compared with those in the low pr-OS category. Higher rate of Choi partial tumour responses were detected in intermediate pr-OS category. Tumour response according to Choi but not to RECIST criteria stratified patient survival of pr-OS categories, particularly for patients with intermediate to low pr-OS. Analyses conducted for 10-year inc-DM were consistent with results for pr-OS for prognostic value of Sarculator predictions and Choi tumour response.InterpretationSarculator identifies variations in outcomes of high-risk STS treated with perioperative chemotherapy and improve prognostic classification, which is also associated with different patterns of tumour response, an outcome that further stratifies survival particularly for patients predicted at higher risk. Future trials investigating neoadjuvant chemotherapy should consider prognostic tool for selecting patients to be enrolled.Trial registration numberEuropean Union Drug Regulating Authorities Clinical Trials No. 2004-003979-36.
http://ift.tt/2Fo4bmU
Blood classification and blood response criteria in mycosis fungoides and Sézary syndrome using flow cytometry: recommendations from the EORTC cutaneous lymphoma task force
Source:European Journal of Cancer, Volume 93
Author(s): Julia J. Scarisbrick, Emmilia Hodak, Martine Bagot, Rene Stranzenbach, Rudolf Stadler, Pablo L. Ortiz-Romero, Evangelia Papadavid, Felicity Evison, Robert Knobler, Pietro Quaglino, Maarten H. Vermeer
Our current mycosis fungoides (MF) and Sézary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sézary counts but results from our EORTC survey confirm these are rarely performed in patch/plaque/tumour MF, and there is a trend towards using flow cytometry to measure blood-class. Accurately assigning blood-class effects overall stage and the 'global response' used to measure treatment responses in MF/SS and hence impacts management. The EORTC Cutaneous Lymphoma Task Force Committee have reviewed the literature and held a Workshop (June 2017) to agree a definition of blood-class according to flow cytometry.No large study comparing blood-class as defined by Sézary count with flow cytometry has been performed in MF/SS. The definition of blood-class by flow cytometry varies between publications. Low-level blood involvement occurs in patch/plaque/tumour much less than erythroderma (p < 0.001). The prognostic relevance of blood involvement (B1 or B2) in patch/plaque/tumour is not known. Studies have not shown a statistically worse difference in prognosis in erythrodermic MF patients with low-level blood involvement (IIIB) versus those without (IIIA), but Sezary patients who by definition have a leukaemic blood picture (staged IVA1 or higher) have a worse prognosis.For consistency flow, definition for blood-class must be an objective measurement. We propose absolute counts of either CD4+CD7-or CD4+CD26-where B0<250/μL, B1 = 250/μl–<1000/μL and B2≥1000/μL plus a T-cell blood clone. Fluctuations between B0 and B1 should not be considered in the treatment response criteria until further prognostic information is known.
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A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumab reference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: Final safety, immunogenicity and survival results
Source:European Journal of Cancer, Volume 93
Author(s): X. Pivot, I. Bondarenko, Z. Nowecki, M. Dvorkin, E. Trishkina, J.-H. Ahn, S.-A. Im, T. Sarosiek, S. Chatterjee, M.Z. Wojtukiewicz, Y. Shparyk, V. Moiseyenko, M. Bello, V. Semiglazov, Y. Lee, J. Lim
BackgroundThe equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment.Patients and methodsPatients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide). Patients then underwent surgery, followed by 10 cycles of adjuvant SB3 or TRZ as randomised. End-points included safety, immunogenicity, event-free survival (EFS) and overall survival through the adjuvant period.ResultsOf 875 patients randomised, 764 (SB3, n = 380; TRZ, n = 384) completed the study. The median follow-up duration was 437 days in the SB3 group and 438 days in the TRZ group. The incidence of treatment-emergent adverse events was comparable between groups (SB3, 97.5%; TRZ, 96.1%) during the overall study period. Up to the end of study, the overall incidence of antidrug antibody was low in both treatment groups (3 patients each). EFS was comparable between groups with a hazard ratio (SB3/TRZ) of 0.94 (95% confidence interval, 0.59–1.51) and EFS rates at 12 months of 93.7% for SB3 and 93.4% for TRZ.ConclusionsFinal safety, immunogenicity and survival results of this study further support the biosimilarity established between SB3 and TRZ.Trial registrationClinicalTrials.gov (NCT02149524); EudraCT (2013-004172-35).
http://ift.tt/2Fmq1Hy
Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma
Source:European Journal of Cancer, Volume 93
Author(s): Tarec Christoffer El-Galaly, Chan Yoon Cheah, Mette Dahl Bendtsen, Grzegorz S. Nowakowski, Roopesh Kansara, Kerry J. Savage, Joseph M. Connors, Laurie H. Sehn, Neta Goldschmidt, Adir Shaulov, Umar Farooq, Brian K. Link, Andrés J.M. Ferreri, Teresa Calimeri, Caterina Cecchetti, Eldad J. Dann, Carrie A. Thompson, Tsofia Inbar, Matthew J. Maurer, Inger Lise Gade, Maja Bech Juul, Jakob W. Hansen, Staffan Holmberg, Thomas S. Larsen, Sabrina Cordua, N. George Mikhaeel, Martin Hutchings, John F. Seymour, Michael Roost Clausen, Daniel Smith, Stephen Opat, Michael Gilbertson, Gita Thanarajasingam, Diego Villa
PurposeSecondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited.MethodsPatients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records.ResultsIn total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15–25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0–1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0–1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36–80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9).ConclusionsIn this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.
http://ift.tt/2Da8lZq
Time interval between neoadjuvant chemoradiotherapy and surgery for oesophageal or junctional cancer: A nationwide study
Source:European Journal of Cancer, Volume 91
Author(s): L.R. van der Werf, J.L. Dikken, E.M. van der Willik, M.I. van Berge Henegouwen, G.A.P. Nieuwenhuijzen, B.P.L. Wijnhoven
IntroductionThe optimal time between end of neoadjuvant chemoradiotherapy (nCRT) and oesophagectomy is unknown. The aim of this study was to assess the association between this interval and pathologic complete response rate (pCR), morbidity and 30-day/in-hospital mortality.MethodsPatients with oesophageal cancer treated with nCRT and surgery between 2011 and 2016 were selected from a national database: the Dutch Upper Gastrointestinal Cancer Audit (DUCA). The interval between end of nCRT and surgery was divided into six periods: 0–5 weeks (n = 157;A), 6–7 weeks (n = 878;B), 8–9 weeks (n = 972;C), 10–12 weeks (n = 720;D), 13–14 weeks (n = 195;E) and 15 or more weeks (n = 180;F). The association between these interval groups and outcomes was investigated using univariable and multivariable analysis with group C (8–9 weeks) as reference.ResultsIn total, 3102 patients were included. The pCR rate for the groups A to F was 31%, 28%, 26%, 31%, 40% and 37%, respectively. A longer interval was associated with a higher probability of pCR (≥10 weeks for adenocarcinoma: odds ratio [95% confidence interval]: 1.35 [1.00–1.83], 1.95 [1.24–3.07], 1.64 [0.99–2.71] and ≥13 weeks for squamous cell carcinoma: 2.86 [1.23–6.65], 2.67 [1.29–5.55]. Patients operated ≥10 weeks after nCRT had the same probability for intraoperative/postoperative complications. Patients from groups D and F had a higher 30-day/in-hospital mortality (1.80 [1.08–3.00], 3.19 [1.66–6.14]).ConclusionAn interval of ≥10 weeks for adenocarcinoma and ≥13 weeks for squamous cell carcinoma between nCRT and oesophagectomy was associated with a higher probability of having a pCR. Longer intervals were not associated with intraoperative/postoperative complications. The 30-day/in-hospital mortality was higher in patients with extended intervals (10–12 and ≥15 weeks); however, this might have been due to residual confounding.
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Heterogeneity of mismatch repair defect in colorectal cancer and its implications in clinical practice
Source:European Journal of Cancer
Author(s): Gaelle Tachon, Eric Frouin, Lucie Karayan-Tapon, Marie-Luce Auriault, Julie Godet, Valerie Moulin, Qing Wang, David Tougeron
http://ift.tt/2Fpvw4a
Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals FGFR1 amplifications and tumour genomic alterations burden as prognostic biomarkers of survival
Source:European Journal of Cancer, Volume 91
Author(s): C. Dubot, V. Bernard, M.P. Sablin, S. Vacher, W. Chemlali, A. Schnitzler, G. Pierron, K. Ait Rais, N. Bessoltane, E. Jeannot, J. Klijanienko, O. Mariani, T. Jouffroy, V. Calugaru, C. Hoffmann, M. Lesnik, N. Badois, F. Berger, C. Le Tourneau, M. Kamal, I. Bieche
BackgroundWe aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value.Patients and methodsWe retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis. Univariate and multivariate analyses were performed to assess the prognostic value of altered genes.ResultsA median of 2 (range: 0–10) genomic alterations per sample was observed. Most frequently altered genes involved the cell cycle pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway (PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1 amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications (p = 0.003), correlated with shorter overall survival (OS). The number of genomic alterations was significantly higher in the HPV-negative population (p = 0.029) and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1 amplification status remained statistically significant in the multivariate analysis.ConclusionThese results suggest that genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour genomic alterations burden are prognostic biomarkers and might be therapeutic targets for patients with HNSCC.
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When and how to use carboplatin in metastatic castration-resistant prostate cancer?
Source:European Journal of Cancer, Volume 92
Author(s): A. Omlin, S. Gillessen
http://ift.tt/2Fqix27
Paediatric dysgerminoma: Results of three consecutive French germ cell tumours clinical studies (TGM-85/90/95) with late effects study
Source:European Journal of Cancer, Volume 91
Author(s): Gwénaëlle Duhil de Bénazé, Hélène Pacquement, Cécile Faure-Conter, Catherine Patte, Daniel Orbach, Nadège Corradini, Claire Berger, Hélène Sudour-Bonnange, Cécile Vérité, Hélène Martelli, Brice Fresneau
MethodsFrench patients (≤18years) treated for dysgerminoma between 1985 and 2005 in TGM-85, 90, 95 protocols were included. Treatment was based on primary unilateral oophorectomy followed by prophylactic lymph node irradiation (1985–1998) or a wait-and-see strategy (1998–2005) for localised completely resected tumours (pS1) or by platinum-based chemotherapy for advanced diseases.ResultsForty-eight patients (median age 12.8 years) were included. Six patients had gonadal dysgenesis. Two had bilateral dysgerminoma. Twenty-eight patients had loco-regional dissemination, seven with para-aortic lymph nodes. None had distant metastases. Primary surgery was performed in 47/48 patients. Among the 15 patients with pS1 tumour: seven did not receive adjuvant treatment, six had lymph node irradiation and two received chemotherapy. Among the 32 patients with advanced tumour, 31 received cisplatinum-based (n = 25) or carboplatin-based (n = 8) regimen with lymph node irradiation for one of them and one did not receive adjuvant treatment. With a median follow-up of 14 years, all patients are alive in complete remission. Five events occurred: 2 contralateral dysgerminomas, 1 peritoneal relapse and 2 second neoplasms (teratoma and melanoma). Bilateral oophorectomy was necessary for 12 patients. Desire of pregnancy was expressed for 17/36 patients with unilateral oophorectomy, which succeeded in 13 cases (5 medically assisted). 2/17 had ovarian failure. The renal function was normal in 24/25 evaluated patients treated with platinum, ifosfamide or irradiation. The hearing function was evaluated on 17/36 patients treated with platinum: 12 Brock grade-0, 3 brock grade-1 and 2 grade-4.ConclusionDysgerminoma has an excellent prognosis even in advanced cases with conservative surgery and platinum-based chemotherapy. However the disease and/or treatment resulted in a high rate of bilateral oophorectomies and a significant impact on future fertility.
http://ift.tt/2FlOg8G
The future of blood-based biomarkers for the early detection of breast cancer
Source:European Journal of Cancer, Volume 92
Author(s): Sau Yeen Loke, Ann Siew Gek Lee
Breast cancer (BC) is the most frequently diagnosed cancer and the most common cause of cancer-related mortality among women worldwide. Despite the extensive use of mammography as the gold standard for BC screening, the occurrences of false-positive and false-negative mammograms, as well as overdiagnosis, remain a concern in breast oncology. Thus, there is a need to identify reliable biomarkers from an easily accessible source that could generate cost-effective assays feasible for routine screening. Blood-based biomarkers may offer an alternative non-invasive strategy to improve cancer screening. Although none of the currently used blood-based biomarkers are sensitive enough for the early detection of BC, a plethora of significant findings pertaining to the development of screening tools using blood-based biomarkers have emerged in recent years. Promising candidate biomarkers such as proteins, autoantibodies, miRNAs, nucleic acid methylation, metabolites and lipids have shown great potential for detecting BC, including detection at the pre-invasive and early stages of the disease. Nevertheless, blood-based biomarkers for BC screening are still at the early phases of development, and various clinical and preclinical issues need to be addressed before these biomarkers can be used clinically. This review summarises the latest discoveries for harnessing blood-based biomarkers as novel BC screening tools, as well as discusses the limitations and challenges that need to be overcome before the translation of their use from the bench to the bedside.
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Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease
Source:European Journal of Cancer, Volume 91
Author(s): François-Xavier Danlos, Anne-Laure Voisin, Valérie Dyevre, Jean-Marie Michot, Emilie Routier, Laurent Taillade, Stéphane Champiat, Sandrine Aspeslagh, Julien Haroche, Laurence Albiges, Christophe Massard, Nicolas Girard, Stéphane Dalle, Benjamin Besse, Salim Laghouati, Jean-Charles Soria, Christine Mateus, Caroline Robert, Emilie Lanoy, Aurélien Marabelle, Olivier Lambotte
ObjectivePatients with autoimmune or inflammatory disease (AID) are susceptible to immune-related adverse events (irAEs) when treated with immune check-point inhibitors (ICIs). We decided to analyse the safety and effectiveness of anti-PD-1 antibodies in AID patients and look for an association between the presence of pre-existing AID and the clinical outcome.MethodsIn a prospective study of the REISAMIC registry of grade ≥2 irAEs occurring in ICI-treated patients, we studied the associations between pre-existing AID on one hand and irAE-free survival, overall survival and best objective response rate on the other.ResultsWe identified 45 patients with 53 AIDs in REISAMIC. The cancer diagnoses included melanoma (n = 36), non–small-cell lung cancer (n = 6) and others (n = 3). The most frequent pre-existing AIDs were vitiligo (n = 17), psoriasis (n = 12), thyroiditis (n = 7), Sjögren syndrome (n = 4) and rheumatoid arthritis (n = 2). Twenty patients (44.4%) presented with at least one irAE: eleven of these were associated with a pre-existing AID ('AID flare'). Treatment with anti-PD-1 antibodies was maintained in 15 of the 20 patients with an irAE. The IrAE-free survival time was significantly shorter in AID patients (median: 5.4 months) than in AID-free patients (median: 13 months, p = 2.1 × 10−4). The AID and AID-free groups did not differ significantly with regard to the overall survival time and objective response rate (p = 0.38 and 0.098, respectively).ConclusionIn patients treated with anti-PD-1 antibody, pre-existing AID was associated with a significantly increased risk of irAEs. Our results indicate that cancer treatments with anti-PD-1 antibodies are just as effective in AID patients as they are in AID-free patients.
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PICCA study: panitumumab in combination with cisplatin/gemcitabine chemotherapy in KRAS wild-type patients with biliary cancer—a randomised biomarker-driven clinical phase II AIO study
Source:European Journal of Cancer, Volume 92
Author(s): Arndt Vogel, Stefan Kasper, Michael Bitzer, Andreas Block, Marianne Sinn, Henning Schulze-Bergkamen, Markus Moehler, Nicole Pfarr, Volker Endris, Benjamin Goeppert, Kirsten Merx, Elisabeth Schnoy, Jens T. Siveke, Patrick Michl, Dirk Waldschmidt, Jan Kuhlmann, Michael Geissler, Christoph Kahl, Ralph Evenkamp, Torben Schmidt, Alexander Kuhlmann, Wilko Weichert, Stefan Kubicka
BackgroundCombination chemotherapy has shown benefit in the treatment of biliary cancer and further improvements might be achieved by the addition of a biological agent. We report here the effect of chemotherapy with the monoclonal EGFR antibody panitumumab as therapy for KRAS wild-type biliary cancer.Patients and methodsPatients with advanced biliary tract cancer were randomised (2:1) to receive cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and day 8/q3w with (arm A) or without panitumumab (arm B; 9 mg/kg BW, i.v q3w). The primary end-point was the evaluation of progression-free survival (PFS) at 6 months. Secondary end-points included objective response rate (ORR), overall survival (OS), and toxicity. In addition, a post hoc assessment of genetic alterations was performed. Finally, we performed a meta-analysis of trials with chemotherapy with and without EGFR antibodies.ResultsSixty-two patients were randomised in arm A and 28 patients in arm B. Patients received 7 treatment cycles in median (1–35) with a median treatment duration of 4.7 months (141 days, 8–765). PFS rate at 6 months was 54% in patients treated with cisplatin/gemcitabine and panitumumab but was 73% in patients treated with cisplatin/gemcitabine without antibody, respectively. Secondary end-points were an ORR of 45% in treatment arm A compared with 39% receiving treatment B and a median OS of 12.8 months (arm A) and of 20.1 months (arm B), respectively. In contrast to the p53-status, genetic alterations in IDH1/2 were linked to a high response after chemotherapy and prolonged survival. In accordance with our results, the meta-analysis of 12 trials did not reveal a survival advantage for patients treated with EGFR antibodies compared with chemotherapy alone.ConclusionsPanitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer. Genetic profiling should be included in CCA trials to identify and validate predictive and prognostic biomarkers.Clinical Trials NumberThe trial was registered with NCT01320254.
http://ift.tt/2FsEM7i
Acidic pH weakens the bonding effectiveness of silane contained in universal adhesives
Publication date: Available online 7 March 2018
Source:Dental Materials
Author(s): Chenmin Yao, Jian Yu, Yake Wang, Chuliang Tang, Cui Huang
ObjectivesSome silane-containing universal adhesives were introduced that a separate ceramic primer was unnecessary to glass-ceramic bonding because of incorporated silane. We aimed to investigate the effectiveness of silane in universal adhesives with acidic media.MethodsA functional γ-methacryloxypropyltrimethoxysilane (γ-MPTS) was used, and its pH value was adjusted to 2.7 by adding hydrochloric acid (HCl) or 10-methacryloxydecyl phosphate (MDP). The prepared acidic silane solutions after 2h or 10d storage were characterized by Fourier transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Micro-shear bond strength (μSBS) was used to evaluate the bonding performance of glass ceramics. Two silane-containing and two silane-free universal adhesives were included. Field-emission scanning electron microscopy fractography analysis was also performed.ResultsFTIR, 1H and 13C NMR revealed that the hydrolysis of γ-MPTS and the self-condensation reaction of silanol groups occurred over time under acidic conditions (HCl or MDP solution). This reaction formed the siloxane oligomers. For glass-ceramic bonding, the μSBS of acidic silane after 10 d storage was lower than that of silane stored for 2h storage (p<0.05), although the difference among the μSBS of the four universal adhesives were nonsignificant (p>0.05). Additionally, cohesive failure was the main fracture pattern of universal adhesive bonding.SignificanceThe effectiveness of silane contained in low pH universal adhesives can be weakened by dehydration self-condensation and consequently became unstable. For the enhancement of glass-ceramic bonding efficiency with universal adhesives, a separate ceramic primer was recommended.
Graphical abstract
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Freshly-mixed and setting calcium-silicate cements stimulate human dental pulp cells
Publication date: Available online 7 March 2018
Source:Dental Materials
Author(s): Mariano S. Pedano, Xin Li, Shuchen Li, Zeyi Sun, Stevan M. Cokic, Eveline Putzeys, Kumiko Yoshihara, Yashuhiro Yoshida, Zhi Chen, Kirsten Van Landuyt, Bart Van Meerbeek
ObjectivesTo evaluate the effect of the eluates from 3 freshly-mixed and setting hydraulic calcium-silicate cements (hCSCs) on human dental pulp cells (HDPCs) and to examine the effect of a newly developed hCSC containing phosphopullulan (PPL) on HDPCs.MethodsHuman dental pulp cells, previously characterized as mesenchymal stem cells, were used. To collect the eluates, disks occupying the whole surface of a 12-well plate were prepared using an experimental hCSC containing phosphopullulan (GC), Nex-Cem MTA (GC), Biodentine (Septodont) or a zinc-oxide (ZnO) eugenol cement (material-related negative control). Immediately after preparing the disks (non-set), 3ml of Dulbecco's Modified Eagle Medium (DMEM) with 10% fetal bovine serum (FBS) were added. The medium was left in contact with the disks for 24h before being collected. Four different dilutions were prepared (100%, 50%, 25% and 10%) and cell-cytotoxicity, cell-proliferation, cell-migration and odontogenic differentiation were tested. The cell-cytotoxicity and cell-proliferation assays were performed by XTT-colorimetric assay at different time points. The cell-migration ability was tested with the wound-healing assay and the odontogenic differentiation capacity of hCSCs on HDPCs was tested with RT-PCR.ResultsConsidering all experimental data together, the eluates from 3 freshly-mixed and setting hCSCs appeared not cytotoxic toward HDPCs. Moreover, all three cements stimulated proliferation, migration and odontogenic differentiation of HDPCs.SignificanceThe use of freshly-mixed and setting hCSCs is an appropriate approach to test the effect of the materials on human dental pulp cells. The experimental material containing PPL is non-cytotoxic and positively stimulates HDPCs.
Graphical abstract
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The effect of ultraviolet induced fluorescence on visually perceived tooth color under normal light conditions
Source:Dental Materials
Author(s): Sascha Hein, Jaap J. ten Bosch
ObjectiveRestorative and prosthetic materials should provide an appearance similar to natural teeth under all light conditions, including UV-rich environments and daylight. Various studies claim that UV-induced fluorescence makes teeth whiter and brighter in daylight. The aim of this paper is to determine experimentally the significance of tooth fluorescence in natural sunlight on perceived tooth color.MethodsA total of 35 extracted, hydrated teeth without restorations or endodontic treatments were evaluated in an experimental setup. A UV/VIS spectrometer using a reflectance/backscattering probe was used to collect the reflected spectrum. Unfiltered and filtered sunlight was used for irradiation of the samples so as to use the combined ultraviolet and visible spectrum (UV/VIS) and the visible spectrum (VIS) exclusively. Color coordinates for each group were measured using the CIE L*a*b* 1976 system, averaged, and compared.ResultsThe average color difference between both groups (UV/VIS and UV) was ΔE* 0.527. The average tooth color for the VIS group was L*VIS 72.21, a*VIS −2.42, and b*VIS 22.35, and for the UV/VIS group was L*UV/VIS 72.00, a*UV/VIS −2.47, and b*UV/VIS 22.44.SignificanceUV induced fluorescence from sunlight does not make teeth whiter and brighter.
http://ift.tt/2Hg6Vit
Malignant atrophic papulosis with motor aphasia and intestinal perforation: A case report and review of published works
Abstract
Malignant atrophic papulosis (MAP) is a rare type of obliterating vasculopathy that can present as pure cutaneous lesions or a systemic entity affecting multiple organs. Systemic disease, such as gastrointestinal or central nervous system involvement, may predispose the patients to poorer or even fatal outcomes. We present a 30-year-old female patient with systemic manifestation of MAP 10 days after delivery of a full-term pregnancy who subsequently developed motor aphasia and intestinal perforation. The patient was administrated empirical treatment with an antiplatelet, anticoagulant, methylprednisolone sodium succinate and alprostadil. Antibiotics were administrated due to intestinal perforation and secondary sepsis. Despite all treatment, the patient died a week later. We summarized all the previous reports of MAP based on thorough review of previous published work. Overall, this is the first patient with MAP combined with motor aphasia and intestinal perforation and may provide insights for future studies on the treatment of this disease.
http://ift.tt/2oS7Yyj
New evaluated radioxenon decay data and its implications in nuclear explosion monitoring
Source:Journal of Environmental Radioactivity
Author(s): Monica Galan, Martin Kalinowski, Abdelhakim Gheddou, Kassoum Yamba
This work presents the last updated evaluations of the nuclear and decay data of the four radioxenon isotopes of interest for the Comprehensive Nuclear-Test-Ban Treaty (CTBT): Xe-131 m, Xe-133, Xe-133 m and Xe-135. This includes the most recent measured values on the half-lives, gamma emission probabilities (Pγ) and internal conversion coefficients (ICC). The evaluation procedure has been made within the Decay Data Evaluation Project (DDEP) framework and using the latest available versions of nuclear and atomic data evaluation software tools and compilations. The consistency of the evaluations was confirmed by the very close result between the total available energy calculated with the present evaluated data and the tabulated Q-value. The article also analyzes the implications on the variation of the activity ratio calculations from radioxenon monitoring facilities depending on the nuclear database of reference.
http://ift.tt/2FDw7Cm
Radionuclide distribution in soil and undecayed vegetative litter samples in a riparian system at the Savannah River Site, SC
Source:Journal of Environmental Radioactivity
Author(s): Chieh-Ming Wu, Olorunfemi Adetona, Luke Naeher, Brian J. Viner, Tim Jannik, Allan Hepworth, Eric Doman, Teresa Eddy
The aim of this study is to comprehensively investigate radionuclide concentrations in surface soil and un-decayed vegetative litter along four stream systems (i.e. Fourmile Branch, Lower Three Runs, Pen Branch, and Steel Creek) at the Savannah River Site (SRS), Aiken, South Carolina. Soil and litter samples from systematically spaced 12 pairs (contaminated or uncontaminated) of plots along the four streams were analyzed for 16 distinct radionuclide activities. Lower radionuclide concentrations were observed in soil and litter samples collected along Pen Branch compared to the other 3 streams. The anthropogenic radionuclide with the highest activity was 137Cs in soil (10.6–916.9 Bq/kg) and litter (8.0–222.3 Bq/kg), while the naturally occurring radionuclides possessing the highest concentration in the samples were 40K (33.5–153.7 Bq/kg and 23.1–56.0 Bq/kg in soil and litter respectively) and 226Ra (55.6–159.9 Bq/kg and 30.2–101.8 Bq/kg in soil and litter respectively). A significant difference (p < 0.05) of radionuclide concentrations between paired-plots across four streams was observed for 241Am, 137Cs, 238Pu, 239Pu, and 226Ra in both contaminated and non-contaminated samples. 137Cs and uranium isotopes had the highest litter-to-soil correlation in contaminated (rho = 0.70) and uncontaminated plots (rho = 0.31–0.41), respectively. 90Sr was the only radionuclide with higher radioactive concentrations in litter (12.65–37.56 Bq/kg) compared to soil (1.61–4.79 Bq/kg). The result indicates that 1) historical discharges of anthropogenic 137Cs was the most important contributor of radiation contamination in the riparian environment at SRS, 2) 90Sr was the only radionuclide with higher concentration in litter than in soil, and 3) no apparent pattern in deposition density in soil or litter along downstream was observed for the radionuclides measured in this study.
http://ift.tt/2HgtqnL
Radiocesium contamination of the moss Hypnum plumaeforme caused by the Fukushima Dai-ichi Nuclear Power Plant accident
Source:Journal of Environmental Radioactivity
Author(s): Emiko Oguri, Hironori Deguchi
We investigated 134Cs and 137Cs activity concentrations in the common Japanese moss species Hypnum plumaeforme collected from 32 sites within ca. 100 km radius of the Fukushima Dai-ichi Nuclear Power Plant. A total of 32 samples of H. plumaeforme were collected during the field surveys from November 2013 to September 2014. The maximum radiocesium activity concentrations in H. plumaeforme were 60.9 ± 1.8 kBq kg−1 for 134Cs and 123 ± 2.3 kBq kg−1 for 137Cs. The mean value for the 134Cs/137Cs was 1.17 ± 0.05, and the mean Tag value was 0.09 ± 0.13. Positive correlations were obtained between total 134Cs + 137Cs activity concentrations in H. plumaeforme and the air dose rate with a correlation coefficient (r) of 0.55 (P = 0.001), and between 137Cs activity concentration in H. plumaeforme and 137Cs deposition density on soil with r of 0.55 (P = 0.001). These results suggest that the perennial moss species H. plumaeforme could be more suitable and useful as a qualitative indicator for the radiocesium pollution compared to vascular plants spreading over the lowlands including human habitation in Fukushima Prefecture.
http://ift.tt/2FBV7tK
Challenges and complexities in remediation of uranium contaminated soils: A review
Source:Journal of Environmental Radioactivity
Author(s): Rajendran Selvakumar, Govindarajan Ramadoss, Mridula P. Menon, Karuppuli Rajendran, Palanisami Thavamani, Ravi Naidu, Mallavarapu Megharaj
Uranium contamination of soil has been a major concern with respect to its toxicity, accumulation in the food chain and persistence in the environment. Owing to these problems, remediation of uranium-contaminated soils has been investigated by various techniques. This review focuses on the challenges and complexities associated with the remediation of uranium-contaminated soil at field level. Therefore, laboratory studies have been excluded from this review. Challenges faced during remediation of uranium-contaminated soil using various techniques such as microbial/phyto/chemical/material based strategies have been discussed with suitable examples. Various factors that have a major influence on uranium decontamination process in soil such as soil type, uranium speciation, the presence of coexisting ions and organics, etc., have been highlighted. This review brings out the significance of the integrated role of various factors which determine the efficiency of the uranium decontamination process.
http://ift.tt/2Hg1OPs
The marine kd and water/sediment interaction problem
Source:Journal of Environmental Radioactivity
Author(s): R. Periáñez, I. Brovchenko, K.T. Jung, K.O. Kim, V. Maderich
The behavior of marine distribution coefficients is analyzed with the help of numerical experiments and analytical solutions of equations describing kinetic models for uptake/release of radionuclides. The difficulties in measuring true kd in a marine environment perturbed by an external radionuclide source are highlighted. Differences between suspended matter and bed sediment kd are analyzed. The performances of different kinetic models (1-step/2step; single-layer/multi-layer) are studied in model/model and model/experiment comparisons. Implications for the use of models to assess radioactive contamination after an emergency are given; as well as recommendations when kd data are compiled in order to create a useful database.
http://ift.tt/2FBqx3C
Surgical Site Identification with Personal Digital Device: A Prospective Pilot Study
Publication date: Available online 7 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Leon Chen, Adam M. Parsons, Alexander B. Aria, Ana M. Ciurea, Anisha B. Patel, Christopher Chan, John R. Griffin, Tri H. Nguyen, Michael R. Migden
BackgroundVarious means to facilitate accurate biopsy site identification have been proposed.ObjectiveTo determine the accuracy of biopsy site identification using photos taken with a patient's digital device by a dermatologist versus professional medical photography.MethodsPhotographs of circled biopsy sites were taken with personal digital devices by the principal investigator (PI). Another set of photographs were taken by a professional photographer. Secondary photographs were taken of the biopsy site location pointed to by the staff and PI based on the personal digital device image and professional medical photography, respectively. Based on secondary photographs, two independent dermatologists determined if the skin biopsy locations pointed out by the staff were consistent with the ones pointed out by PI.ResultsPer Dermatologist A, the staff correctly identified all 53/53 biopsy sites. Per Dermatologist B, the staff were correct on 51/53 observations. Dermatologist C, the final arbiter, concurred with Dermatologist A in the two cases that Dermatologist B was not certain of the biopsy site location.LimitationsThe mean interval from initial biopsy to re-identification of the site was 36.2 days.ConclusionUtilizing patients' personal digital devices is a cost-effective, HIPAA compliant, and readily available means to identify skin biopsy sites.
Teaser
Many novel means of biopsy site identification have been proposed., This is a pilot study comparing the accuracy of biopsy site identification with personal digital device photography to professional medical photography., Personal digital device photography is a cost-effective, HIPPA complaint, and readily available means to accurately identify biopsy sites.http://ift.tt/2G9ckJb
Pathologist Characteristics Associated with Accuracy and Reproducibility of Melanocytic Skin Lesion Interpretation
Publication date: Available online 7 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): David E. Elder, Mike Piepkorn, Raymond L. Barnhill, Gary M. Longton, Heidi D. Nelson, Stevan R. Knezevich, Margaret S. Pepe, Patricia A. Carney, Linda J. Titus, Tracy Onega, Anna N.A. Tosteson, Martin A. Weinstock, Joann G. Elmore
BackgroundDiagnostic interpretations of melanocytic skin lesions vary widely among pathologists, yet the underlying reasons remain unclear.ObjectiveIdentify pathologist characteristics associated with rates of accuracy and reproducibility.MethodsPathologists independently interpreted the same set of biopsies of melanocytic lesions on two occasions. Diagnoses were categorized into one of five classes according to the MPATH-Dx© system. Reproducibility was determined by pathologists' concordance of diagnoses across two occasions. Accuracy was defined by concordance with a consensus reference standard. Associations of pathologist characteristics with reproducibility and accuracy were assessed individually and in multivariable logistic regression models.ResultsRates of diagnostic reproducibility and accuracy were highest among pathologists with board certification and/or fellowship training in dermatopathology, and those with ≥5 years of experience. In addition, accuracy was high among pathologists with higher caseload composition and volume of melanocytic lesions.LimitationsData gathered in a test set situation using a classification tool not currently in clinical use.ConclusionDiagnoses are more accurate among pathologists with specialty training and those with more experience interpreting melanocytic lesions. These findings support the practice of referring difficult cases to more experienced pathologists to improve diagnostic accuracy, although the impact on patient outcomes of these referrals requires additional research.
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Transluminal Approach with Bubble-Seeded Histotripsy for Cancer Treatment with Ultrasonic Mechanical Effects
Publication date: Available online 7 March 2018
Source:Ultrasound in Medicine & Biology
Author(s): Reiko Ashida, Ken-ichi Kawabata, Takashi Maruoka, Kazuhiro Yamanaka, Hideki Yoshikawa, Tatsuya Ioka, Kazuhiro Katayama, Sachiko Tanaka
Bubble-seeded histotripsy (BSH) is a newly developed ultrasound-based mechanical fractionation technique using locally injected phase change nanodroplets (PCNDs) as sensitizers. The PCNDs are a kind of microbubble precursor compressed into submicron-size in droplets form, which were designed for local administration and will expand into microbubbles under ultrasound exposure. Previously, we reported that a combination of PCNDs injection and pulsed high-intensity focused ultrasound (pHIFU) with an acoustic intensity as low as about 3 kW/cm2 at 1.1 MHz, which is similar to the acoustic intensity of currently available HIFU coagulation therapy, was enough to induce tissue fractionation after significant antitumor effects in an in vivo study. Toward therapeutic application of BSH to deep-seated tissues such as the pancreas, the transluminal approach, using endoscopic ultrasound was thought to be ideal. Therefore, for a preliminary examination, we developed a new transducer with a small aperture (20- × 20-mm square) and long focal length (35 mm), operating at 2.1 MHz that could be attached to an EUS-mimicking probe. With the newly developed transducer and locally injected PCNDs, predictable tissue mechanical fractionation was observed in both ex vivo and in vivo studies at acoustic intensities that were too low to induce any significant bioeffects (around 4 kW/cm2) without using PCNDs. For in situ monitoring of the treatment site during a procedure, the degree of attenuation of microbubble motions after exposing the microbubbles to pHIFU was monitored, using ultrafast echographic imaging. Microbubble movements were observed to be largest at 25–30 s after pHIFU exposure. On the contrary, after 40 s, the movement of microbubbles decreased to the same level as at the start of the procedure, suggesting that an overdose of pHIFU exposure causes coagulation attributable to the thermal effect caused by absorption of the energy. Those results were promising for expanding the application of BSH for a transluminal approach, using a small transducer under real-time monitoring.
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Microbiological and immunological characteristics of a lethal pulmonary Aspergillus niger infection in a non-neutropenic patient
Publication date: Available online 7 March 2018
Source:Medical Mycology Case Reports
Author(s): Jessica D. Workum, Suzanne W. de Jong, Mark S. Gresnigt, Katharina L. Becker, Peter Pickkers, Frank L. van de Veerdonk, Yvonne F. Heijdra, Eva Kolwijck
Invasive pulmonary aspergillosis is increasingly described in non-neutropenic patients, such as patients with COPD receiving corticosteroids and the critically ill. Here, we present a case of a lethal pulmonary Aspergillus niger infection in a COPD patient. Immunological tests showed an impaired innate and adaptive immune response to Aspergillus. A history of COPD, unresponsiveness to antibiotics and especially a suggestive CT-scan should trigger the clinician to consider diseases caused by Aspergillus.
http://ift.tt/2D9CMPw
A-101, a Proprietary Topical Formulation of High-Concentration Hydrogen Peroxide Solution: A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study of the Dose–Response Profile in Subjects With Seborrheic Keratosis of the Face
BACKGROUND Seborrheic keratosis (SK) is a common benign skin tumor, yet no topical treatments are approved in the United States. OBJECTIVE To evaluate the proprietary, stabilized, high-concentration hydrogen peroxide–based topical solution A-101 (32.5% and 40% concentrations) for treatment of facial SK lesions. MATERIALS AND METHODS In this multicenter, double-blind, vehicle-controlled study, eligible subjects were randomly assigned to receive up to 2 treatments of A-101 40%, A-101 32.5%, or vehicle solution applied to a single facial SK lesion. The primary efficacy assessment was the Physician's Lesion Assessment (PLA), a validated 4-ordinal scale. RESULTS The primary end point, the mean reduction in PLA grade from baseline to Day 106 was 1.7 for A-101 40%, 1.4 for A-101 32.5%, and 0.1 for vehicle (phttp://ift.tt/2oXBFNH
Repair of Defects of the Central Forehead With a Modified Banner Transposition Flap
No abstract availablehttp://ift.tt/2IcDY8s
Histologic Status of Squamous Cell Carcinoma In Situ After Diagnostic Biopsy in Immunocompetent and Immunosuppressed Patients
BACKGROUND The histologic status of squamous cell carcinoma in situ (SCC-IS) after diagnostic biopsy has not been well described or compared between immunocompetent and immunosuppressed patients. Expression of immunohistochemical (IHC) markers of aggressive SCC has not been compared between SCC-IS that clears or becomes invasive after biopsy. OBJECTIVE To determine the histologic status of SCC-IS after diagnostic biopsy in these populations. METHODS Retrospective analysis of 129 patients with SCC-IS treated with excision and 55 patients treated with Mohs surgery. Histologic features of SCC in excised tissue after biopsy were recorded. Known SCC markers were evaluated using IHC. RESULTS Invasive SCC was found in 3% to 16% of residual SCC-IS depending on surgical treatment modality. The history of skin cancer increased the odds of having invasive SCC in SCC-IS excisions (odds ratio 7.1, phttp://ift.tt/2oYrAQL
Pulsed-Dye Laser Treatment of a Nonhealing Chronic Wound That Developed After Incision and Drainage of a Hidradenitis Suppurativa Abscess
No abstract availablehttp://ift.tt/2IcDnne
Histologic Accuracy of Mohs Micrographic Surgery
BACKGROUND Mohs micrographic surgery enables the surgeon to maximize tumor removal while minimizing the amount of tissue being removed using advanced mapping techniques combined with microscopy. Interpretation of frozen section slides is vital to the success of Mohs micrographic surgery. OBJECTIVE Evaluate and confirm the congruence of frozen section slide interpretation between fellowship-trained Mohs surgeons and dermatopathologists. METHODS Retrospective cohort concordance study spanning 10 years (n = 1,720 cases). RESULTS The concordance rate for frozen slide interpretation between fellowship-trained Mohs surgeons and dermatopathologists in this study was 99.5%. CONCLUSION This study demonstrates agreement between the interpretation of histologic frozen section slides when evaluated by fellowship-trained Mohs surgeons and dermatopathologists.http://ift.tt/2oXGGpO
Intraoperative Immunostaining for Cytokeratin-7 During Mohs Micrographic Surgery Demonstrates Low Local Recurrence Rates in Extramammary Paget's Disease
BACKGROUND Extramammary Paget's disease (EMPD) is a rare intraepithelial malignancy with high recurrence rates following standard surgical treatments, ranging from 22% to 60% in large retrospective reviews. OBJECTIVE To evaluate the local recurrence rate of Mohs micrographic surgery (MMS) supplemented with intraoperative immunohistochemistry for cytokeratin-7 (MMS + CK-7) for primary and recurrent EMPD. MATERIALS AND METHODS Retrospective, multi-center, cross-sectional study of patients treated using MMS + CK-7. Demographic, clinicopathologic, treatment, and follow-up data were obtained by chart review. RESULTS The observed local recurrence rate for MMS + CK-7 is 3.3% (2/61 tumors) with a mean follow-up of 43.5 months (1–120 months). Local recurrence occurred in 2.3% (1/43) of primary tumors and 5.6% (1/18) of recurrent tumors. Kaplan–Meier 5-year tumor-free rates are 94.6% overall, 97.1% for primary tumors, and 80.0% for recurrent tumors. The Kaplan–Meier 5-year tumor-free rates for all EMPD tumors treated with MMS + CK-7 versus a historical cohort of MMS alone are 94.6% versus 72.0% (p = .012). CONCLUSION MMS + CK-7 is an effective treatment for EMPD, demonstrating improved outcomes compared with historical controls.http://ift.tt/2oXGC9y
Management of Incompletely Excised Skin Tumors: Our Experience
BACKGROUND Current British Association of Dermatologists guidelines recommend that Mohs micrographic surgery should be considered for incompletely excised basal cell carcinomas and squamous cell carcinomas. Units that perform Mohs surgery are limited. In Teesside, the skin cancer multidisciplinary team discusses all incompletely excised skin tumors, considers all treatment options, provides recommendations, and initiates the agreed management plan. OBJECTIVE To assess the outcome and appropriateness of local surgical macroexcision for incompletely excised skin tumors. METHODS The authors performed a retrospective analysis of the local skin multidisciplinary team notes from July 2010 to July 2012 identifying all incompletely excised skin cancers. A total of 46 basal cell carcinomas and 27 squamous cell carcinomas were incompletely excised. Case note and pathology report review was used to identify the recommended management option and subsequent outcome. RESULTS Fifty-four of the 73 incompletely excised tumor identified underwent further surgical excision locally. Fifty-one of 54 patients (94.4%) had successful completion of excision with a single procedure. The remaining 3 patients' required further surgery, performed locally, to completely excise their tumor. Average follow-up was 35 months with 1 (1.9%) recurrence. CONCLUSION In the authors' region, local surgical management of incompletely excised skin tumors has yielded results comparable to Mohs surgery. Mohs surgery remains a viable option in specific cases.http://ift.tt/2p0Wisi
Successful Treatment of Actinic Granuloma With Pulsed-Dye Laser and Fractionated Carbon Dioxide Laser
No abstract availablehttp://ift.tt/2IcmBF4
Residual Squamous Cell Carcinoma After Shave Biopsy in Solid Organ Transplant Recipients
BACKGROUND After histopathological confirmation of a biopsy sample, cutaneous squamous cell carcinoma (cSCC) is often treated surgically; yet, residual tumor within the excision sample is not always found. The prevalence of residual cSCC after shave biopsy in solid organ transplant recipients (SOTRs) is unknown. OBJECTIVE Determine the prevalence of residual cSCC after shave biopsy in SOTRs. METHODS A retrospective case-controlled review was performed from a single center. Data were collected for 117 SOTRs and 117 age-matched nonimmunosuppressed controls diagnosed with shave biopsy–proven cSCC who underwent subsequent wide local excision from January 2004 to December 2016. Multivariable conditional logistic regression was used to determine variables associated with residual tumor in the combined population. Univariate logistic regression was used to investigate if transplant-related variables were associated with residual tumor in the SOTR group. RESULTS Of the 117 SOTRs, 57 (48.7%) had residual tumor within the excisional specimen. Of the 117 controls, 31 (26.5%) had residual tumor within the excisional specimen. Solid organ transplant recipients have 2.59 times greater odds of having residual cSCC after shave biopsy (95% confidence interval: 1.29–5.22, p = .0076). CONCLUSION Solid organ transplant recipients have a higher prevalence of residual cSCC after shave biopsy when compared with nonimmunosuppressed controls and should be prioritized for margin-controlled surgery.http://ift.tt/2oUDjzM
Cutaneous Metastases of Melanoma Affecting Exclusively Skin Graft Donor and Receiving Sites: A Novel Clinical Presentation
No abstract availablehttp://ift.tt/2IcDizW
Clinical Benefits of Preoperative Conventional Fluorescence Diagnosis in Surgical Treatment of Extramammary Paget Disease
BACKGROUND In extramammary Paget disease (EMPD), initial margins of surgical excision are difficult to determine preoperatively. Fluorescence diagnosis (FD) may have utility as a noninvasive method for delineating tumor boundaries. OBJECTIVE The relationship between FD-delineated borders and results of multiple scouting biopsies (MSBs) in EMPD was investigated, evaluating the potential clinical role of FD. MATERIALS AND METHODS A cohort of 21 patients was studied, looking for consistencies between FD and MSB results. Initial surgical margins were determined by FD or FD plus MSB. All margins were subjected to frozen section analysis. RESULTS Paget cells were identified in 88 of 117 (71.8%) biopsies obtained from FD borders. When used preoperatively with MSB in 9 patients, 96.4% of margins proved negative at initial resection stage. Using a 6-mm margin beyond FD borders in another 9 patients, 86.7% of margins were negative at initial stage. The maximum distance of excision beyond FD border was 12 mm. CONCLUSION Fluorescence diagnosis borders (identified visually) correlated well with MSB histopathology. Fluorescence diagnosis is a useful method to delineate initial margins for surgical resection of EMPD.http://ift.tt/2p2t7Wb
Simple Mohs Reconstruction in a Blistering Disorder Patient
No abstract availablehttp://ift.tt/2I9W2jK
Commentary on Restoration of Visual Loss With Retrobulbar Hyaluronidase Injection After Hyaluronic Acid Filler
No abstract availablehttp://ift.tt/2I83wng
Safety and Efficacy of a Noninvasive 1,060-nm Diode Laser for Fat Reduction of the Flanks
BACKGROUND Preliminary reports indicate a hyperthermic diode laser treatment could be a safe and effective method for noninvasive fat reduction using the 1,060-nm wavelength. This wavelength penetrates the skin to heat subcutaneous adipocytes causing cellular disruption, leaving extracellular lipids, and cellular debris to be evacuated naturally by the body. OBJECTIVE To evaluate the safety and effectiveness of this modality for noninvasive fat reduction of the flanks. MATERIALS AND METHODS Forty-nine subjects received single laser treatment to 1 flank. Ultrasound images were taken at baseline, follow-up at 6 and 12 weeks after treatment. High-resolution photographs were taken at baseline and 12 weeks after treatment and then evaluated by independent reviewers. Adverse events recorded at all visits. Subjects completed a satisfaction questionnaire at the conclusion of the trial. RESULTS Ultrasound images showed statistically significant (phttp://ift.tt/2p2sZ99
Dermoscopy in Facilitating the Recognition of Poikiloderma of Civatte
No abstract availablehttp://ift.tt/2IazyPx
Microneedling: A Review and Practical Guide
BACKGROUND Microneedling is a relatively new treatment option in dermatology and has been touted for a broad range of applications including skin rejuvenation, acne scarring, rhytides, surgical scars, dyschromia, melasma, enlarged pores, and transdermal drug delivery. The significant increase in minimally invasive procedures that has been reported over the past several years suggest that microneedling may occupy a specific niche for patients who desire measurable clinical results from treatments with little to no recovery. OBJECTIVE To review the published medical literature relating to microneedling in dermatology and provide a practical guide for its use in clinical practice. MATERIALS AND METHODS A thorough literature search of microneedling in dermatology using PubMed was conducted, and all references pertaining to skin scarring and rejuvenation were reviewed. Based on the information presented in these publications and the authors' clinical experience, a microneedling technique is outlined for clinical practice. Pretreatment recommendations, intraoperative technique and treatment end points, and postoperative considerations are outlined. RESULTS Microneedling produces substantial clinical improvement of scars, striae, and rhytides with expedient recovery and limited side effects. Controlled dermal wounding and stimulation of the wound healing cascade enhances collagen production and is likely responsible for the clinical results obtained. CONCLUSION Microneedling is a safe, minimally invasive, and effective esthetic treatment for several different dermatologic conditions including acne and other scars, rhytides, and striae. Given its expedient post-treatment recovery, limited side effect profile, and significant clinical results, microneedling is a valuable alternative to more invasive procedures such as laser skin resurfacing and deep chemical peeling.http://ift.tt/2oXG2Zq
Psychometric properties of the INICO-FEAPS scale in a Danish sample with autism spectrum disorders
Source:Research in Developmental Disabilities, Volume 75
Author(s): Ane Knüppel, Helle Jakobsen, Marlene Briciet Lauritsen, Gry Kjærsdam Telléus
BackgroundThere is a need to evaluate subjective perspectives of outcomes, such as quality of life (QoL), in individuals with autism spectrum disorders (ASD), but to date, there is no specific instrument available to assess this population. While the INICO-FEAPS scale is customized for studying QoL in adolescents and adults with intellectual and/or developmental disabilities, this scale has not been previously evaluated in an ASD population.AimsTo examine the usability of the INICO-FEAPS scale in a Danish population of adolescents and adults with ASD.MethodsIn a nationwide survey, 875 adolescents and adults with ASD and 1573 parents completed the INICO-FEAPS scale. Internal consistency was evaluated through several indices. Confirmatory factor analysis (CFA) was conducted to investigate the fit of the model with eight correlated first-order factors, and convergent validity was explored comparing the results of different QoL measures through correlation analysis.ResultsInternal consistency was adequate for the indices applied, and the CFA model tested indicated an acceptable fit to the data. Generally, comparisons of results of different QoL measures resulted in moderate to high correlations.ConclusionOverall, it was concluded that due to the psychometric properties found, the INICO-FEAPS scale is applicable for use in ASD populations.
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Editorial Board
Source:Research in Developmental Disabilities, Volume 75
http://ift.tt/2FmL88p
How common are challenging behaviours amongst individuals with Fragile X Syndrome? A systematic review
Source:Research in Developmental Disabilities
Author(s): Rebecca Lyndsey Hardiman, Peter McGill
Fragile X Syndrome (FXS) appears to be associated with an increased risk for engaging in challenging behaviour, particularly self-injury, relative to those with mixed aetiology learning disabilities. Such behavioural issues are reported to be of high concern for those providing support. As such, this systematic review aimed to gain further epidemiological data regarding challenging behaviours in individuals with FXS, including: self-injurious behaviour (SIB), hand-biting as a specific topography of SIB, aggression and property destruction. Twenty eight manuscripts were identified which reported the prevalence of a relevant topography of behaviour, with widely varying prevalence estimates. Weighted averages of the prevalence of behaviours were calculated across studies. Comparison of proportions revealed significant gender differences and differences in the prevalence of types of behaviour. It is hoped that this comprehensive overview of data on this clinically significant topic will help to inform and drive future investigation to understand and provide effective intervention for the benefit of those with FXS.
http://ift.tt/2FmPd0j
Single-case synthesis tools II: Comparing quantitative outcome measures
Source:Research in Developmental Disabilities
Author(s): Kathleen N. Zimmerman, James E. Pustejovsky, Jennifer R. Ledford, Erin E. Barton, Katherine E. Severini, Blair P. Lloyd
Varying methods for evaluating the outcomes of single case research designs (SCD) are currently used in reviews and meta-analyses of interventions. Quantitative effect size measures are often presented alongside visual analysis conclusions. Six measures across two classes—overlap measures (percentage non-overlapping data, improvement rate difference, and Tau) and parametric within-case effect sizes (standardized mean difference and log response ratio [increasing and decreasing])—were compared to determine if choice of synthesis method within and across classes impacts conclusions regarding effectiveness. The effectiveness of sensory-based interventions (SBI), a commonly used class of treatments for young children, was evaluated. Separately from evaluations of rigor and quality, authors evaluated behavior change between baseline and SBI conditions. SBI were unlikely to result in positive behavior change across all measures except IRD. However, subgroup analyses resulted in variable conclusions, indicating that the choice of measures for SCD meta-analyses can impact conclusions. Suggestions for using the log response ratio in SCD meta-analyses and considerations for understanding variability in SCD meta-analysis conclusions are discussed.
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Systematic review of measurement property evidence for eight financial management instruments in populations with acquired cognitive impairment
Publication date: Available online 7 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Lisa Engel, Adora Chui, Dorcas E. Beaton, Robin E. Green, Deirdre R. Dawson
ObjectiveTo critically appraise the measurement property evidence (i.e., psychometric) for eight observation-based financial management assessment instruments.Data sourcesSeven databases were searched in May 2015.Study SelectionTwo reviewers used an independent decision-agreement process to select studies of measurement property evidence relevant to populations with adulthood acquired cognitive impairment, appraise the quality of the evidence, and extract data. Twenty-one articles were selected.Data extractionThis review used the COnsensus-based Standards for the selection of health Measurement Instruments review (COSMIN) guidelines and four-point tool to appraise evidence. After appraising the methodological quality, adequacy of results and volume of evidence per instrument were synthesized. Measurement property evidence with high risk of bias was excluded from the synthesis.Data synthesisVolume of measurement property evidence per instrument is low; most instruments had one to three included studies. Many included studies had poor methodological quality per measurement property evidence area examined. Six of the eight instruments reviewed had supporting construct validity/hypothesis-testing evidence of fair methodological quality. There is a dearth of acceptable quality content validity, reliability, and responsiveness evidence for all eight instruments.ConclusionsRehabilitation practitioners assess financial management functions in adults with acquired cognitive impairments. However, there is limited published evidence to support using any of the reviewed instruments. Practitioners should exercise caution when interpreting results of these instruments. This review highlights the importance of appraising the quality of measurement property evidence prior to examining the adequacy of the results and synthesizing the evidence.
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Functional Electrical Stimulation-A new therapeutic approach to enhance exercise intensity in Chronic Obstructive Pulmonary Disease patients : a randomised controlled cross-over trial.
Publication date: Available online 7 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Clément Medrinal, Guillaume Prieur, Yann Combret, Aurora Robledo Quesada, David Debeaumont, Tristan Bonnevie, Francis Edouard Gravier, Elise Dupuis Lozeron, Jean Quieffin, Olivier Contal, Bouchra Lamia
ObjectiveTo evaluate the effect of quadriceps Functional Electrical Stimulation (FES)-Cycling on exertional VO2 compared with Placebo FES-cycling in patients with COPD.DesignA randomised, single-blind, placebo-controlled, cross-over trialSettingPulmonary Rehabilitation DepartmentParticipants23 consecutive patients with COPD GOLD stage 2, 3 or 4 (mean FEV1 : 1.4±0.4 L (50.3% pred)) who had recently begun a respiratory rehabilitation program.InterventionTwo consecutive 30-minute sessions were carried out at a constant load with active and placebo FES-Cycling.Main outcome measuresThe primary outcome was mean VO2 during the 30-minute exercise session. The secondary outcomes were respiratory gas exchange and hemodynamic parameters averaged over the 30-minute endurance session. Lactate values, dyspnea and perceived muscle fatigue were evaluated at the end of the sessions.ResultsFES-Cycling increased the physiological response more than the placebo, with a greater VO2 achieved of 36.6 (95% CI 8.9-64.3) mL/min (p=0.01). There was also a greater increase in lactate after FES-Cycling (+1.5 (95% CI 0.05 to 2.9) mmol/L; p=0.01). FES-Cycling did not change dyspnoea or muscle fatigue compared with the placebo condition.ConclusionFES-Cycling effectively increased exercise intensity in patients with COPD. Further studies should evaluate longer-term FES-Cycling rehabilitation programs.
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Cannabis Use in Individuals with Spinal Cord Injury or Moderate to Severe Traumatic Brain Injury in Colorado
Publication date: Available online 7 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Lenore Hawley, Jessica M. Ketchum, Clare Morey, Kathleen Collins Pharm.D., Susan Charlifue
ObjectiveTo describe the prevalence of cannabis use in an adult sample with spinal cord injury (SCI) or traumatic brain injury (TBI) in Colorado, and to describe the self-reported reasons and side effects of cannabis use in this sample.DesignMixed methods observational study, using focus group data and telephone surveySettingCommunityParticipantsColorado adults who have sustained SCI or moderate to severe TBI and have received services through the rehabilitation hospital conducting the study.InterventionsNone; Measures: SurveyResultsFocus group participants identified issues that were then included in the survey development. Seventy percent of the 116 surveyed reported cannabis use pre-injury (67% SCI, 74% TBI) with 48% reporting use after injury (53% SCI, 45% TBI). Overall, the most common reason for use was recreational (67%), followed by reducing stress/anxiety (62.5%), and improving sleep (59%). Among the respondents with SCI, the most common reasons for use were to reduce spasticity (70%), recreation (63%), and to improve sleep (63%). Among those with TBI, reasons endorsed were recreational (72%), reducing stress/anxiety (62%), and improving sleep (55%). Smoking was the most common method of use.ConclusionsA majority of this sample report using cannabis prior to injury, and approximately half report using cannabis post-injury. Both groups report recreational use, while the group with SCI also highly endorses using cannabis to address chronic medical conditions. Clinicians should be aware of the high prevalence of cannabis use in these populations and the impact such use may have on the individual's medical management. Further research in this area is needed.
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Immune-Mediated Inner Ear Disease: Diagnostic and therapeutic approaches
Publication date: Available online 7 March 2018
Source:Acta Otorrinolaringológica Española
Author(s): José Ferreira Penêda, Nuno Barros Lima, Francisco Monteiro, Joana Vilela Silva, Rita Gama, Artur Condé
IntroductionImmune Mediated Inner Ear Disease (IMIED) is a rare form of sensorineural bilateral hearing loss, usually progressing in weeks to months and responsive to immunosuppressive treatment. Despite recent advances, there is no consensus on diagnosis and optimal treatment.MethodsA review of articles on IMIED from the last 10 years was conducted using PubMed® database.ResultsIMIED is a rare disease, mostly affecting middle aged women. It may be a primary ear disease or secondary to autoimmune systemic disease. A dual immune response (both cellular and humoral) seems to be involved. Cochlin may be the inner ear protein targeted in this disease. Distinction from other (core common) forms of neurosensory hearing loss is a challenge. Physical examination is mandatory for exclusion of other causes of hearing loss; audiometry identifies characteristic hearing curves. Laboratory and imaging studies are controversial since no diagnostic marker is available.ConclusionDespite recent research, IMIED diagnosis remains exclusive. Steroids are the mainstay treatment; other therapies need further investigation. For refractory cases, cochlear implantation is an option and with good relative outcome.
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Editorial Board
Source:Behavioural Brain Research, Volume 344
http://ift.tt/2Dap0vT
Design, synthesis and biological evaluation of anti-pancreatic cancer activity of plinabulin derivatives based on the co-crystal structure
Publication date: Available online 7 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Zhangyu Fu, Yingwei Hou, Cunpeng Ji, Mingxu Ma, Zhenhua Tian, Mengyan Deng, Lili Zhong, Yanyan Chu, Wenbao Li
Based on the co-crystal structures of tubulin with plinabulin and Compound 1 (a derivative of plinabulin), a total of 18 novel plinabulin derivatives were designed and synthesized. Their biological activities were evaluated against human pancreatic cancer BxPC-3 cell lines. Two novel Compounds 13d and 13e exhibited potent activities with IC50 at 1.56 and 1.72 nM, respectively. The tubulin polymerization assay indicated that these derivatives could inhibit microtubule polymerization. Furthermore, the interaction between tubulin and these compounds were elucidated by molecular docking. The binding modes of Compounds 13d and 13e were similar to the co-crystal structure of Compound 1. H-π interaction was observed between the aromatic hydrogen of thiophene moiety with Phe20, which could enhance their binding affinities.
Graphical abstract
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Diagnostic accuracy of radiology (CT, X-ray, US) for predicting difficult intubation in adults: A meta-analysis
The aim of this study was to evaluate the overall accuracy of radiological measurements in prediction of difficult airway and compare the diagnostic value between the radiological measurements and the modified Mallampati score through a meta-analysis of published studies.
http://ift.tt/2tnh62K
Obstructive sleep apnea as a risk factor associated with difficult airway management - A narrative review
The association between obstructive sleep apnea (OSA) and difficult airway had been studied in various clinical trials but the relationship between the two conditions has not been clearly established. The objective of this narrative review is to determine if OSA is a risk factor associated with difficult airway.
http://ift.tt/2oS2wvo
Serratus plane block in thoracoscopic sympathectomy surgery
Video-assisted thoracic surgery (VATS), a minimally invasive procedure, has allowed less impairment of pulmonary function compared with thoracotomy. Besides that, there have been reports of significant acute and chronic pain following it [1].
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Ultrasound guided distal adductor canal block provides effective postoperative analgesia in lower leg surgery
In order to provide adequate postoperative analgesia in patients undergoing lower extremity surgeries, blockage of both lumbar and sacral plexus originating nerves are required as part of multimodal analgesia regimens. Block of the sciatic nerve from the popliteal region is a frequently used regional anesthesia/analgesia technique in lower leg surgery. Additionally, saphenous nerve block at the adductor canal level or femoral nerve block may also be included. Runge et al. reported that local anesthetic injected at the distal of the adductor canal around the femoral artery spread both proximally to the saphenous nerve and distally to the popliteal area, around the sciatic nerve in a cadaver model [1].
http://ift.tt/2oQW33M
Can lateral decubitus cause uvular necrosis after general anesthesia?
Uvular necrosis or ulceration is a rare cause of post-operative sore throat after endotracheal intubation (40%) or Laryngeal Mask Airway (7–12%) insertion. Till date, only 17 cases of uvular necrosis have been reported. According to literature, overzealous suctioning, upper GI endoscopy, bronchoscopy via nasal approach, long-term intubation and trans-esophageal echocardiography can cause uvular necrosis (2, 3). Patients present with post-operative severe pain and swollen, elongated, erythematous uvula with odynophagia and dysphagia which require urgent attention and treatment.
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Epidural management for obstetric patient with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) undergoing emergent cesarean section
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare, autosomal dominant disorder that results from mutations of the NOTCH 3 gene on chromosome 19. The resultant dysfunctional NOTCH 3 protein leads to impaired cerebrovascular autoregulation. CADASIL is characterized by recurrent subcortical ischemic infarcts that can lead to migraine, with or without aura; cognitive problems; seizures; psychiatric symptoms; dementia; walking difficulties; and urinary incontinence [1].
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Efficacy of ultrasound imaging for differential diagnosis of cervical swelling after brachial plexus block for shoulder arthroscopy
Various complications associated with peripheral brachial plexus nerve block have been reported, such as pneumothorax, hemodynamic collapse, and hematoma leading to airway obstruction [1]. Here, we report the successful use of ultrasound imaging in the differential diagnosis of cervical swelling after brachial plexus block for shoulder arthroscopy.
http://ift.tt/2tqla2m
Supraglottic airway for upper gastrointestinal endoscopy in children: A review of 10years' experience
Children undergoing diagnostic EGD require deep sedation or general anesthesia [1] [2]. The anesthesiologist may choose to protect the airway with an endotracheal tube, or use sedation using a variety or combinations of sedatives and analgesics, while relying on the patient's native airway, and without airway protection [2] [3]. There can, in these instances, however, be serious cardiorespiratory complications; specifically, apnea, hypoventilation and oxygen desaturation; and hypercarbia from periods of apnea during deep sedation go unmeasured.
http://ift.tt/2tq7ZhV