tbuckley/cabot-search huggingface dataset:
Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies
Authors: Luis Sordo, Gregorio Barrio, Maria J Bravo, B Iciar Indave, Louisa Degenhardt, Lucas Wiessing, Marica Ferri, Roberto Pastor-Barriuso
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment. <b>Design</b>&nbsp;Systematic review and meta-analysis. <b>Data sources</b>&nbsp;Medline, Embase, PsycINFO, and LILACS to September 2016. <b>Study selection</b>&nbsp;Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine. <b>Data extraction and synthesis</b>&nbsp;Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis. <b>Results</b>&nbsp;There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment. <b>Conclusions</b>&nbsp;Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are potentially important, but further research must be conducted to properly account for potential confounding and selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in and out of each treatment.
Histological Parameters and “In Vitro” Cultures Identify Different Subsets of Myelofibrosis with Myeloid Metaplasia (MMM).
Authors: Federica Servida, Claudia Vener, Viviana Tubazio, Umberto Gianelli, Paola Rafaniello Raviele, Alessia Moro, Antonella Anastasia, Giorgio Lambertenghi Deliliers, Davide Soligo
Journal: Blood (2005)
Journey of particulate pollution in body is mapped in study
Authors: Nigel Hawkes
Journal: BMJ (2017)

Tiny inhaled particles such as those emitted by diesel engines can find their way from the lungs into the bloodstream, a novel experimental approach has shown.1

Using nanoparticles made of gold, scientists from Scotland and the Netherlands traced the particles’ movement within the body after they were inhaled by volunteers. The particles can be detected in the blood within 15 minutes and in urine within 24 hours, and they were still detectable in some volunteers three months later.

Gold was used because it is impossible to detect actual diesel particulates, which are five to 10 times smaller than a human hair and consist of carbon. In a separate experiment, 12 volunteers who were about to undergo an operation …
Assessment of preoperative liver function based on indocyanine green clearance
Authors: Takashi Kokudo, Kiyoshi Hasegawa, Norihiro Kokudo
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the article by Kagawa et al. which identified the responsible transporter for indocyanine green (ICG) clearance, i.e., organic anion transporting polypeptide 1B3 (OATP1B3, gene symbol SLOC1B3), and congratulate the authors for their excellent work.1 Through genetic analysis of 4 patients exhibiting extremely high ICG retention rates at 15 minutes (ICG‐R15) without liver cirrhosis or cholestasis, the authors found that all patients had homozygous insertion of a 6.5‐kbp‐long interspersed element (L1) retrotransposon in intron 5 of SLOC1B3 that induced exon skipping and a premature stop codon. ICG‐R15 has been widely used as a routine guideline in Eastern countries for making appropriate surgical decisions in hepatocellular carcinoma patients, and recent evidence suggests that ICG‐R15 is applicable to Western populations for evaluating preoperative liver function.2 Although a constitutional ICG excretory defect caused by the complete lack of OATP1B3 is relatively easy to diagnose in a clinical setting, important issues need to be elucidated for clinicians concerning whether SLCO1B3 genetic polymorphisms and/or heterozygous L1 insertion affect ICG‐R15. Indeed, several single nucleotide polymorphisms are reportedly associated with reduced OATP1B3 activity.4 Therefore, evaluating the relationship between OATP1B3 function and ICG‐R15 value is important for avoiding erroneous underestimation of hepatocellular carcinoma patients' liver function. Combining ICG‐R15 with other laboratory variables, such as serum albumin (albumin indocyanine green evaluation grade), may also be a way to improve its accuracy.3 The present study revealed that ICG‐R15 is determined not only by the patient's liver function but also by OATP1B3 activity. Future study of the effects of OATP1B3 genetic haplotype variation on ICG‐R15 value is essential for improving the accuracy of this widely used liver function test.
P12.19 Does early adjuvant radiotherapy improve outcomes in atypical meningioma?
Authors: S. Pant, R. Tonse
Journal: Neuro-Oncology (2017)

Introduction: The role of early adjuvant radiotherapy (RT) in patients with atypical meningioma is controversial This single institution study sought to assess the improvement in survival with early post-operative adjuvant RT in patients with atypical meningioma compared to salvage RT delivery at recurrence/progression. METHODS: Patients with a histological diagnosis of atypical meningioma as per World Health Organization (WHO) 2007 classification were identified through an electronic search of the institutional prospective neuro-oncology database. Patients had been treated with fractionated RT either after first surgery (early adjuvant RT group) or at recurrence/progression (salvage RT group) following a second surgical resection. Results: Electronic search of the database identified a total of 86 patients with WHO grade II (atypical) meningioma. The median age of the study cohort was 51 years (range 13-79 years). Fifty-one (59%) patients received early adjuvant RT, while 35 (41%) patients were observed after first surgery. Six of 51 (12%) patients receiving early adjuvant RT recurred/progressed compared to 33 of 35 (94%) patients who were observed following first surgery. Thirty one of 33 patients who recurred/progressed following observation underwent re-excision, while 2 patients directly received salvage RT without a second surgical resection. Three of 33 patients with recurrence/progression did not undergo any irradiation leaving 30 patients receiving salvage RT at recurrence/progression. Post-RT recurrence/progression was seen in 6 of 51 (11.7%) patients at a median of 47 months in early adjuvant RT group versus 12 of 30 (40%) patients in salvage RT group at a median of 25 months (p=0.003). There was a significant difference in progression free survival (PFS) between the two groups calculated from RT till further progression or last follow-up. The 3-year and 5-year PFS of patients in the early adjuvant RT group was 85% and 69% as compared to 49% and 28% in the salvage RT group (p<0.001). At the time of last follow-up, 17 patients had died (6 of 51 in the early adjuvant RT group, 11 of 30 in the salvage RT group). There was no significant difference in overall survival between the two groups calculated from date of first diagnosis. Conclusions: Early adjuvant RT significantly improves PFS in patients with atypical meningioma compared to observation (after initial surgical resection) and salvage RT at recurrence/progression. I would like to apply for WFNO travel grant for members of less developed countries and have already registered for EANO membership.
Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion
Authors: Katherine S. Virgo, Ethan Basch, D. Andrew Loblaw, Thomas K. Oliver, R. Bryan Rumble, Michael A. Carducci, Luke Nordquist, Mary-Ellen Taplin, Eric Winquist, Eric A. Singer
Journal: Journal of Clinical Oncology (2017)

Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies. However, guidelines have neither addressed second-line hormonal therapy for nonmetastatic CRPC nor provided specific guidance with regard to the chemotherapy-naïve population. Recent Data Six phase III randomized controlled trials and expert consensus opinion inform this PCO. Provisional Clinical Opinion For men with CRPC, a castrate state should be maintained indefinitely. Second-line hormonal therapy (eg, antiandrogens, CYP17 inhibitors) may be considered in patients with nonmetastatic CRPC at high risk for metastatic disease (rapid prostate-specific antigen doubling time or velocity) but otherwise is not suggested. In patients with radiographic evidence of metastases and minimal symptoms, enzalutamide or abiraterone plus prednisone should be offered after discussion with patients about potential harms, benefits, costs, and patient preferences. Radium-223 and sipuleucel-T also are options. No evidence provides guidance about the optimal order of hormonal therapies for CRPC beyond second-line treatment. Prostate-specific antigen testing every 4 to 6 months is reasonable for men without metastases. Routine radiographic restaging generally is not suggested but can be considered for patients at risk for metastases or who exhibit symptoms or other evidence of progression. Additional information is available at www.asco.org/genitourinary-cancer-guidelines and www.asco.org/guidelineswiki .
Emergence of new recombinant noroviruses GII.p16-GII.4 and GII.p16-GII.2, France, winter 2016 to 2017
Authors: Maxime Bidalot, Lucie Théry, Jérôme Kaplon, Alexis De Rougemont, Katia Ambert-Balay
Journal: Eurosurveillance (2017)

An early increase in outbreaks of norovirus gastroenteritis characterised at the French National Reference Centre occurred this winter season. They were concurrent with an unusual pattern of circulating strains, with three predominant genotypes: the re-emergent variant GII.P4 2009-GII.4 2012 found in 28% of norovirus outbreaks and two new emergent recombinant strains GII.P16-GII.4 2012 and GII.P16-GII.2 never before observed in France, found in 24% and 14% of norovirus outbreaks, respectively.
A Pediatric-Inspired Regimen Containing Multiple Doses of Intravenous Pegylated Asparaginase Appears Safe and Effective in Newly Diagnosed Adult Patients with Ph-Negative Acute Lymphoblastic Leukemia in Adults up to Age 60: Results of a Multi-Center Phase II Clinical Trial
Authors: Jae H. Park, Ellen K. Ritchie, Arati V. Rao, Sean Devlin, Meier Hsu, Talal T Khawaja, Bridget A O'Donnell, Maria I Cazacu, Diane M Stopka, Martin S. Tallman, Dan Douer
Journal: Blood (2016)
P08.57 Distinct mechanism-of-action of dianhydrogalactitol (VAL-083) overcomes chemoresistance in glioblastoma
Authors: B. Zhai, A. Gobielewska, A. Steino, J. A. Bacha, D. M. Brown, S. Niclou, M. Daugaard
Journal: Neuro-Oncology (2017)

Standard treatments for glioblastoma (GBM) include surgery, radiation and chemotherapy with temozolomide (TMZ). Nearly all tumors recur and 5-year survival is less than 3%, largely due to chemoresistance. Cancer cells utilize DNA damage repair pathways to overcome cytotoxicity of chemotherapy. GBM tumors expressing O6-methylguanine-DNA-methyltransferase (MGMT) are resistant to TMZ and nitrosourea, and deficient DNA mismatch repair (MMR) confers resistance to TMZ and platinum agents. Alterations in p53, particularly gain-of-function mutations, are correlated with increased MGMT and poor prognoses in GBM. Second line anti-angiogenic treatment with bevacizumab has been implicated in increased chemoresistance and has not improved overall survival. Thus, refractory GBM is a significant clinical challenge and novel therapeutic strategies to overcome chemoresistance are essential. VAL-083 is a bi-functional alkylating agent that readily crosses the blood-brain barrier and has shown activity against GBM in prior NCI-sponsored clinical trials. A Phase I/II clinical trial studying VAL-083 in recurrent GBM, after TMZ and bevacizumab failure, suggested the potential of VAL-083 to offer a clinically meaningful survival benefit. The mechanism-of-action of VAL-083 differs from other alkylating agents, including TMZ and nitrosoureas, inducing interstrand cross-links at guanine-N7 causing DNA double-strand breaks and cancer cell death. VAL-083 activity is independent of MGMT and p53 status and it is active against TMZ-resistant GBM cancer stem cells. Recent findings that VAL-083 leads to irreversible S/G2-phase cell cycle arrest, propose synergy with S-phase specific chemotherapeutics, including topoisomerase and PARP inhibitors. VAL-083 persistently activates the homologous recombination (HR) DNA repair pathway and its potency is increased in HR-impaired cancer cells, suggesting increased VAL-083 cytotoxicity in HR-impaired tumors. Further, hypoxic cancer cells downregulate HR, proposing increased VAL-083 potency in hypoxic tumors. Bevacizumab increases intratumor hypoxia, presumably impairing HR, proposing VAL-083 as a treatment option in HR-deficient or hypoxic cancers following, or as part of combination with, bevacizumab. Here, we investigated cytotoxicity and DNA damage response of VAL-083 combinations by crystal violet, western blot and flow cytometry in a range of cancer cells, and MMR-related chemoresistance using lentiviral MLH1 and MSH2 vectors. The potency of VAL-083 in GBM was investigated under hypoxia either in vitro or in vivo as part of a combination treatment with bevacizumab. Our results demonstrate a distinct anti-cancer mechanism for VAL-083, enabling i) ability to overcome resistance to TMZ, platinum agents, and nitrosoureas, ii) increased potency in cancers with impaired HR, and iii) synergy with topoisomerase and PARP inhibitors.
Functional Analyses of V-Atpase Mutations in Follicular Lymphoma
Authors: Fangyang Wang, Damian Gatica, Zhang Xiao Ying, Luke F. Peterson, Denzil Bernard, Kamlai Saiya-Cork, Shaomeng Wang, Alfred Chang, Mark S Kaminski, Tycel Phillips, Daniel Klionsky, Sami N. Malek
Journal: Blood (2016)
Predictors of hepatitis B vaccination status in healthcare workers in Belgrade, Serbia, December 2015
Authors: Darija Kisic-Tepavcevic, Milena Kanazir, Tatjana Gazibara, Gorica Maric, Natasa Makismovic, Goranka Loncarevic, Tatjana Pekmezovic
Journal: Eurosurveillance (2017)

Despite the availability of a safe and effective vaccine since 1982, overall coverage of hepatitis B vaccination among healthcare workers (HCWs) has not reached a satisfactory level in many countries worldwide. The aim of this study was to estimate the prevalence of hepatitis B vaccination, and to assess the predictors of hepatitis B vaccination status among HCWs in Serbia. Of 380 randomly selected HCWs, 352 (92.6%) were included in the study. The prevalence of hepatitis B vaccination acceptance was 66.2%. The exploratory factor analyses using the vaccination-refusal scale showed that items clustered under ‘threat of disease’ explained the highest proportion (30.4%) of variance among those declining vaccination. The factor analyses model of the potential reasons for receiving the hepatitis B vaccine showed that ‘social influence’ had the highest contribution (47.5%) in explaining variance among those vaccinated. In the multivariate adjusted model the following variables were independent predictors of hepatitis B vaccination status: occupation, duration of work experience, exposure to blood in the previous year, and total hepatitis B-related knowledge score. Our results highlight the need for well-planned national policies, possibly including mandatory hepatitis B immunisation, in the Serbian healthcare environment.
P11.10 Atypical teratoid/rhabdoid tumor in the internal auditory canal
Authors: H. Oka
Journal: Neuro-Oncology (2017)

OBJECTIVE: The case of a thirteen-year-old woman showing an atypical teratoid/rhabdoid tumor (AT/RT) primarily occurred in the internal auditory canal was presented. Results: There was a delay in diagnosing AT/RT because of the first histological diagnosis of benign neurofibroma. If we had changed the surgical approach to one which was middle cranial fossa-based or translabyrinthine in the second or third operation, we might have reached an earlier final diagnosis. Although we faced a dilemma about whether to sacrifice facial nerve function for dissection of the tumor, we should have considered the possibility of malignancy at an earlier stage. CONCLUSION: This is a case report of AT/RT in the internal auditory canal presenting with progressive hearing loss as the initial symptom. Although no previous reports of AT/RT primarily occurring in the internal auditory canal are existent, this rare form of the disease should be considered in future evaluations as a differential diagnosis for internal auditory canal tumor.
Over-expressed long noncoding RNA HOXA11-AS promotes cell cycle progression and metastasis in gastric cancer
Authors: Zhili Liu, Zhenyao Chen, Ruihua Fan, Bin Jiang, Xin Chen, Qinnan Chen, Fengqi Nie, Kaihua Lu, Ming Sun
Journal: Molecular Cancer (2017)

Long noncoding RNAs (lncRNAs) have emerged as critical regulators in a variety of human cancers, including gastric cancer (GC). However, the function and mechanisms responsible for these molecules in GC are not fully understood. In our previous study, we found that GC associated lncRNA HOXA11-AS is significantly upregulated in GC tissues. Over-expressed HOXA11-AS promotes GC cells proliferation and invasion through scaffolding the chromatin modification factors PRC2, LSD1 and DNMT1.HOXA11-AS expression levels in GC cells was detected by quantitative real-time PCR (qPCR). HOXA11-AS siRNAs and overexpression vector were transfected into GC cells to down-regulate or up-regulate HOXA11-AS expression. In vitro and in vivo assays were performed to investigate the functional role of HOXA11-AS in GC cells cell cycle progression, invasion and metastasis. RIP and ChIP assays were used to determine the mechanism of HOXA11-AS's regulation of underlying targets.We found that knockdown of HOXA11-AS induced GC cells G0/G1 phase arrest and suppressed GC cells migration, invasion and metastasis in vivo. Moreover, mechanistic investigation showed that HOXA11-AS could interact with WDR5 and promote β-catenin transcription, bind with EZH2 and repress P21 transcription, and induce KLF2 mRNA degradation via interacting with STAU1.Taken together, these findings show that HOXA11-AS not only could promote GC cells migration and invasion in vitro, but also promotes GC cells metastasis in vivo, at least in part, by regulating β-catenin and KLF2.
P09.12 Durable remission with tumor treating fields as adjuvant treatment for glioblastoma relapse in a patient with Grad IV hematotoxicity during initial temozolomide radiochemotherapy
Authors: C. Hirt, C. Vorbau, M. Kirsch, D. Ranft, H. W. S. Schroeder, F. Dombrowski, J. Baldauf
Journal: Neuro-Oncology (2017)

We report on a 53 years old female patient who was diagnosed with a left temporal tumor with significant perifocal edema in August 2015. A microsurgical, neuronavigation-guided gross total resection was performed and glioblastoma was diagnosed histologically. On immunohistochemistry, staining for IDH1-mutations was negative. Methylation analysis revealed a methylated MGMT promotor. One month after resection, the patient started a radiochemotherapy with temozolomide (TMZ) 75mg/m2 per day and radiation fractions of 1.8 Gy with a planned dose of 50.4 Gy and a boost of the tumor region up to a total dose of 60.4 Gy. After 4 weeks the radiochemotherapy was interrupted because of pancytopenia with grade 4 thrombocytopenia (minimal platelets 4000/µl) and grade 3 leukopenia (minimal WBC 1170/µl). The patient was transfused with 8 units of platelets and 6 units of packed erythrocytes. After an interruption of one month WBC were above 2000/µl and platelets above 20000/ml, hence radiation therapy was resumed without concomitant TMZ. On a follow-up MRI in February 2016 a tumor relapse was detected. A second resection of the left temporal tumor was performed and because of a persisting thrombocytopenia with platelets below 100 000/µl, we offered the patient an adjuvant treatment with tumor treating fields (TTF) alone. TTF started in May 2016 and was well tolerated. Except from minor skin reactions, which were managed with ointments, the patient denied any adverse reactions. The latest MRI from September 2016 showed an ongoing remission, and at the most recent clinical follow-up in November 2016 there was no sign of neurological impairment. Hence, the second remission lasts now as long as the first remission, but with a much better toxicity profile of TTF compared to the initial radiochemotherapy. TTF therapy alone might therefore represent an alternative treatment option for patients with relapsed glioblastoma for whom chemotherapy is contraindicated.