tbuckley/cabot-search huggingface dataset:
Are mental health tribunals only a nominal challenge?
Authors: Paul Gosney, Paul Lomax, Aileen O’Brien
Journal: BMJ (2017)

We read with interest Wise’s article regarding the rise in detentions under the Mental Health Act (MHA), outlining the obvious human rights concerns.1

What happens to people detained under the MHA once they enter hospital is rarely discussed. Their legal rights are protected by the Mental Health Review Tribunal system.

We examined the outcomes of patients …
TCTAP A-120 A 4-year City Based Multicenter Trial to Improve the Ratio of Ambulance Use in Patients After ST Elevation Myocardial Infarction
Authors: Cheng Chung Hung, Wei-Chun Huang, Cheng-Hung Chiang, Feng Yu Kuo, Chin-Chang Cheng, Guang-Yuan Mar, Yi-Jyan Liou, Hsiao-Hsing Wang, Li-Shuang Yan, Chun-Peng Liu
Journal: Journal of the American College of Cardiology (2017)
Sex Hormones and Hair Loss in Men From the General Population of Northeastern Germany
Authors: Hanna Kische, Andreas Arnold, Stefan Gross, Henri Wallaschofski, Henry Völzke, Matthias Nauck, Robin Haring
Journal: JAMA Dermatology (2017)

time of ED or UCC presentation or treatment for severe sunburn.This is particularly important for patients with sunburns from indoor tanning whose reliance on tanning often mirrors other addictive behaviors. 3lthough our data are derived from 2 large hospitals and affiliated UCCs over a 15-year period, our study is limited by its retrospective nature and common geography in Massachusetts.Future studies should assess patient characteristics for utilization of EDs and UCCs for sunburn treatment on a national scale.Despite these limits, it is clear that ED and UCC utilization for sunburn treatment is a largely avoidable phenomenon that leads to considerable costs.Our study demonstrates possible areas for interventions to reduce disease burden and streamline care.
Axillary node staging for microinvasive breast cancer: Is it justified?
Authors: J. M. Lyons, M. Stempel, K. J. Van Zee, H. S. Cody
Journal: Journal of Clinical Oncology (2011)

7 Background: DCIS with microinvasion (DCISM) is a lesion for which prognosis may be intermediate between that of DCIS and invasive breast cancer, but for which the role of axillary lymph node staging remains controversial. Here we report clinical characteristics and outcome in 112 patients with DCISM, with a particular focus on the role of sentinel lymph node (SLN) biopsy. Methods: From our prospective database we retrospectively identified 112 patients with a diagnosis of DCISM who had undergone SLN biopsy between 1996 and 2004 at Memorial Sloan-Kettering Cancer Center. Median follow up was 6 years. Results: We found positive SLN in 12% (14/112) of all patients, macrometastases in 2.7% (3/112) and micrometastases in 10% (11/112). We performed axillary dissection (ALND) in all patients with macrometastases (3/3), finding additional positive nodes in 66% (2/3), and in 27% of those with micrometastases (3/11), finding no additional positive nodes. Among patients with negative SLN (38% of whom received systemic therapy), there were 5 loco-regional recurrences (1 in the ipsilateral axilla, and 4 in the ipsilateral breast, all DCIS) and 4 contralateral second primary breast cancers. Among patients with positive SLN (86% of whom received systemic adjuvant therapy), there were no loco-regional or distant recurrences. Conclusions: Positive SLN were present in 12% of our patients with DCISM, none of whom experienced recurrence at 6 years’ follow up. SLN biopsy may be justified for DCISM, but is clearly most beneficial to identify a very small subset of DCISM patients (2.7%, with SLN macrometastases) who could benefit from systemic adjuvant therapy. Our data imply that between 125 and 250 SLN biopsy procedures would be required to avoid breast cancer mortality in 1 patient, and do not support the routine use of ALND for SLN-positive patients. We recommend a critical reappraisal of routine SLN biopsy for DCISM.
Nodal stage of surgically resected non-small cell carcinoma of the lung and its effect on recurrence pattern and survival.
Authors: Satvik Ramakrishna, John M. Varlotto, Malcolm M. DeCamp, Nengliang Yao, Abram Recht, John Charles Flickinger, Adin-Cristian Andrei, Jennifer Toth, Michael F Reed, Allan Lipton, Kristen Higgins, Xiyu Zheng, Julia Allison Shelkey, Laura Nyshel Medford-Davis, Christopher Ryan Kelsey
Journal: Journal of Clinical Oncology (2014)

7552 Background: Current NCCN guidelines recommend post-operative radiotherapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2-involvement. We investigated the relationship between nodal-stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods: A multi-institutional database of consecutive patients undergoing R0resection for Stages I-IIIA NSCLC from 1998-2009 was used. Patients receiving any radiation therapy before relapse were excluded. Variables analyzed were age, sex, surgical procedure, extent of lymph node sampling, histology, LVI, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Cumulative incidence rates were calculated for LR and DR as first sites of failure and Kaplan-Meier estimates for OS. Competing-risk analysis was used to compare times to recurrence events. Multivariate Cox modeling was used to analyze OS. Results: 1,288, 210 and 78 patients were identified with N0, N1, and N2 involvement respectively. 161 patients received chemotherapy. Median follow-up was 28.7 months. Patients with N1 or N2 nodal stage had similar rates of LR as patients with N0 disease, but were both at significantly increased risk for DR (N1, HR = 1.77, p = 0.0012; N2, HR = 2.27, p <0.001) and death (N1, HR = 1.464, p =0.0004; N2, HR = 2.32, p <0.0001). LR was associated with squamous histology, visceral pleural involvement, tumor size and segmentectomy in the Cox model. Conclusions: The risk of LR did not vary substantially in relation to N-stage in our population, though DR did. Although the number of patients with N2 disease was small, these findings call into question the NCCN guidelines. Prospective studies of PORT after R0 resection are needed. N-stage Cumulative Incidence rates (%) Kaplan-Meier estimates (%) Local recurrence Distant recurrence Overall survival 3-year 5-year 3-year 5-year 3-year 5-year N0 13 15 15 17 66 50 N1 19 22 30 38 50 32 N2 16 18 37 42 32 26
Role of CBX4 in the Colorectal Carcinoma Metastasis—Letter
Authors: Valentina Sancisi, Alessia Ciarrocchi
Journal: Cancer Research (2017)

The study by Wang and colleagues showed that CBX4 suppresses colon cancer metastasis by repressing the expression of RUNX2. They also demonstrated that CBX4 recruits HDAC3 on the RUNX2 promoter, leading to inhibition of its expression (1).RUNX2 is a transcription factor, important for skeletal morphogenesis and for its function in promoting progression and metastasization of different types of epithelial tumors. As for many other transcription factors, RUNX2 is finely regulated, controlled at multiple levels and through multiple signaling pathways. Unfortunately, the molecular mechanisms governing RUNX2 expression in cancer are still largely undefined. In this regard, the data by Wang and colleagues are relevant and represent a step forward. However, in our opinion, the authors missed addressing some major aspects, with the risk of providing only a narrowed and incomplete overview of the way CBX4 and HDAC3 cooperates in the regulation of RUNX2.Two major RUNX2 isoforms have been described, derived from two distinct promoters, isoform-I transcribed by the proximal P2 promoter and isoform-II transcribed by the distal P1 promoter. Isoform-I is the major RUNX2 variant expressed in epithelial cancer (2, 3), including the HCT116 cell line used by Wang and colleagues in their work (Fig. 1). The expression of isoform-II is confined to skeletal cells and is barely detectable in tumor cells (4). Furthermore, we recently described a novel intragenic enhancer that cooperates with the P2 promoter in controlling RUNX2 isoform-I expression. We showed that this enhancer contains HDACi-responsive elements and that HCT116 was the only model in which HDAC inhibition resulted in RUNX2 upregulation (5).In their work, Wang and colleagues did not acknowledge the existence of two RUNX2 promoters, nor the existence of active enhancers that could interfere with the regulation of RUNX2. The authors limited their investigation to explore the way CBX4 and HDAC3 interact with and regulate the P1 promoter, which is likely the less active element in RUNX2 regulation in colon cancer.Indeed, based on their observations, alteration of CBX4 and/or HDAC3 induces relevant changes in RUNX2 mRNA levels, while the activity of the P1 promoter in the same settings is significantly but only marginally affected. In our opinion, these evidences support the hypothesis that additional regulatory elements are involved in this mechanism.The complex interaction of multiple regulatory elements, including alternative promoters and enhancers, needs to be taken into consideration in searching for mechanisms that control RUNX2 expression in cancer.See the Response, p. 2550No potential conflicts of interest were disclosed.A. Ciarrocchi is supported by Associazione Italiana Ricerca sul Cancro (AIRC IG15862) and by the Italian Ministry of Health (GR-2011-02350937).
B-Cell Maturation Antigen (BCMA)-Specific Chimeric Antigen Receptor T Cells (CART-BCMA) for Multiple Myeloma (MM): Initial Safety and Efficacy from a Phase I Study
Authors: Adam D. Cohen, Alfred L. Garfall, Edward A Stadtmauer, Simon Francis Lacey, Eric Lancaster, Dan T. Vogl, Karen Dengel, David E Ambrose, Fang Chen, Gabriela Plesa, Irina Kulikovskaya, Vanessa E Gonzalez, Minnal Gupta, Regina M Young, Tenesia Carey, Regina Ferthio, Brendan M. Weiss, Celeste Richardson, Randi E. Isaacs, J. Joseph Melenhorst, Bruce L. Levine, Carl H June, Michael C. Milone
Journal: Blood (2016)
Synergistic Anti-Tumor Efficacy of BET Inhibitors JQ1 and Otx-015 in Combination with Dasatinib in Preclinical Models of T-Cell Lymphomas
Authors: Sara Rizzitano, Alessandra Cavanè, Marco Piazzoni, Antonio Vendramin, Silvia Gimondi, Giulia Biancon, Sofia Cannara Malan, Anna Dodero, Paolo Corradini, Cristiana Carniti
Journal: Blood (2016)
Analysis of <i>TERT</i> promoter mutations in pediatric melanoma.
Authors: Armita Bahrami, John Easton, Heather Mulder, Seungjae Lee, Raymond Barnhill, Alberto S. Pappo
Journal: Journal of Clinical Oncology (2014)

9023 Background: Melanoma is rare in children and adolescents and is divided into a conventional adult-type (CM), a small-cell type, and Spitzoid melanoma/ atypical Spitz tumor (AST). ASTs are a group of melanocytic neoplasms with characteristic morphologic features that often affect patients in the first 2 decades, commonly spread to regional lymph nodes, but rarely metastasize to distant sites. Histological criteria are unreliable at predicting the rare subset of AST that disseminates and to date, genomic changes associated with an aggressive clinical behavior have not been identified. Whole genome sequencing has revealed that most adult melanomas have TERT promoter activating mutations that lead to increased telomerase activity. We investigated the frequency of TERT promoter mutations in pediatric CM and AST and its correlation with clinical outcome. Methods: Genomic DNA was extracted from 12 microns of FFPE sections from 15 CM (all in adolescents) and from 26 AST in 25 patients (18 children; 7 adolescents). A portion of the TERT promoter (HG19 coordinates, chr5: 1295151-1295347) was amplified by PCR using conventional methods. The resulting amplicon was Sanger sequenced and analyzed for the presence of heterozygous or homozygous alterations within the amplified region. Results: 12 of 15 CM had one of the two most frequently described UV associated TERT single nucleotide variants (SNVs) (6 SNVs at position 1295228; 6 SNVs at position 1295250), and 2 were marked as indeterminate. An additional CM had a dinucleotide CC->TT variant at positions 1295242/243. At last follow-up (mean, 30 months), 9 patients had died of disease and 3 were alive with disease. Only 2 of 26 AST samples carried a TERT promoter mutation (SNV 1295228) and both patients developed widespread metastasis and died of disease. None of the remaining patients with AST developed extranodal disease spread and all were alive without disease at a mean of 17 months. Conclusions: TERT promoter UV-signature mutations correlate with aggressive clinical behavior in pediatric patients with melanocytic neoplasms. The findings support a pathogenic role for UV light in pediatric melanoma progression.
Phenotypic spectrum of autosomal recessive congenital ichthyosis due to <i>PNPLA1</i> mutation
Authors: L.M. Boyden, B.G. Craiglow, R.H. Hu, J. Zhou, J. Browning, L. Eichenfield, Y.L. Lim, M. Luu, L.M. Randolph, M. Ginarte, L. Fachal, L. Rodriguez-Pazos, A. Vega, D. Kramer, G. Yosipovitch, H. Vahidnezhad, L. Youssefian, J. Uitto, R.P. Lifton, A.S. Paller, L.M. Milstone, K.A. Choate
Journal: British Journal of Dermatology (2017)
ASP2215, a novel FLT3/AXL inhibitor: Preclinical evaluation in combination with cytarabine and anthracycline in acute myeloid leukemia (AML).
Authors: Yoko Ueno, Naoki Kaneko, Rika Saito, Yutaka Kondoh, Itsuro Shimada, Masamichi Mori, Sadao Kuromitsu
Journal: Journal of Clinical Oncology (2014)

7071 Background: Patients with AML harboring internal tandem duplication (ITD) of FLT3 have a poor prognosis following the current chemotherapeutic treatment of cytarabine (AraC) and anthracycline (daunorubicin, DNR or idarubicin, IDR). ASP2215 is a novel small molecule FLT3/AXL inhibitor in a clinical trial. Methods: Cell cycle distribution and apoptosis induction in MV4-11 AML cells, which harbor FLT3-ITD, treated with ASP2215, AraC, and DNR were evaluated via flow cytometry and Western blot. Antitumor efficacy was evaluated in MV4-11 xenografted mice administered with oral daily ASP2215 starting either a week prior to or concomitantly with, intraperitoneal AraC for 5 days, and intravenous DNR or IDR for 3 days. The pharmacokinetics in xenografted mice were also investigated. Results: ASP2215 treatment resulted in an increase in the proportion of MV4-11 cells in the G1 phase of the cell cycle at 24 h, and then the concentration-dependent induction of apoptosis, as determined by the increase in annexin V-positive cells and intracellular PARP cleavage. ASP2215 enhanced AraC- or DNR-induced apoptosis regardless of the treatment schedule. In mice xenografted with MV4-11 cells, the simultaneous administration of ASP2215, AraC, and DNR induced tumor regression, including complete remission. In contrast, combination chemotherapy (AraC and DNR) only induced tumor growth inhibition. Further, treatment of ASP2215 for a week followed by combination with DNR and AraC also induced tumor regression with a final tumor volume similar to that of simultaneous combination therapy. No obvious influence of toxicities on body weight, behavior, or diarrhea was noted for treatment of ASP2215. Concentrations of ASP2215, AraC, and DNR in plasma and tumor were not influenced by their use in combination therapy. ASP2215 also enhanced the antitumor efficacy of AraC plus IDR in the same model. Conclusions: ASP2215 in combination with AraC and either DNR or IDR induced superior antitumor efficacy compared to combination chemotherapy, regardless of dosing schedule. These findings support the development of ASP2215 in combination with chemotherapy for the potential treatment of AML.
A STAT3- and p63-dependent transcriptional network to define a lethal basal subset of human bladder cancers.
Authors: Colin P.N. Dinney, Woonyoung Choi, Sima P. Porten, Beat Roth, Tiewei Cheng, Daniel Levi Willis, Mai Ngoc-Ahn Tran, I-Ling C. Lee, Jolanta E. Bondaruk, Tadeusz Majewski, Shizhen Zhang, Shanna M. Pretzsch, Keith A. Baggerly, Arlene O. Siefker-Radtke, Bogdan Czerniak, David James McConkey
Journal: Journal of Clinical Oncology (2013)

4538 Background: Muscle-invasive bladder cancers (MIBCs) are a heterogeneous group of tumors that display widely variable clinical outcomes and responses to conventional chemotherapy. Methods: We used whole genome mRNA expression profiling and unsupervised hierarchical cluster analyses on a cohort of 73 flash frozen primary tumors to identify 3 distinct subsets of muscle-invasive bladder cancer (MIBC). We confirmed the existence of these 3 subsets in a second cohort of 57 formalin-fixed, paraffin-embedded (FFPE) MIBCs and in 2 other public datasets. Analysis of primary tumors and mechanistic studies in human bladder cancer cell lines identified tumors that respond to FGFR inhibitors or chemotherapy. Results: The first subset was driven by an active "basal" EGFR-STAT3-p63 transcriptional network, and was associated with poor clinical outcomes. High miR-200c expression stratified the survival of these basal tumors. The second subset was characterized by active p53 pathway activation, and tumors and cell lines with these features were resistant to cis-platinum based chemotherapy. The third subset expressed "luminal" markers and active estrogen receptor (ER) and PPARγ signaling, and luminal cell lines were sensitive to fibroblast growth factor receptor (FGFR) inhibition. Conclusions: Molecular subtyping of MIBCs can be used to identify lethal cancers and enrich for tumors that will respond to FGFR inhibitors or conventional chemotherapy.
Factors Contributing to the Weekend Effect
Authors: Nick Black
Journal: JAMA (2017)

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TCTAP A-003 First-in-human Evaluation of a Novel Poly-L-lactide Based Sirolimus-eluting Bioresorbable Vascular Scaffold for the Treatment of De Novo Native Coronary Artery Lesions: MeRes-1 Trial
Authors: Ashok Seth, Manjunath Cholenahally Nanjappa, Ajaykumar Umakant Mahajan, Viveka Kumar, Parvin Kumar Goel, Praveen Chandra, G.S. Wander, Vinay K. Bahl, Mathew Samuel Kalarickal, Ajitkumar Velaparambil Kumaran, Upendra Kaul, P.C. Rath, Vijay Kumar Trehan, Anil Mishra, Gaurav Ganeshwala, A George Koshy
Journal: Journal of the American College of Cardiology (2017)
In HIV/HCV co-infected patients T regulatory and myeloid-derived suppressor cells persist after successful treatment with directly acting antivirals
Authors: Nicola Tumino, Rita Casetti, Gabriele Fabbri, Eleonora Cimini, Antonella Romanelli, Federica Turchi, Olindo Forini, Veronica Bordoni, Andrea Antinori, Adriana Ammassari, Alessandra Sacchi, Chiara Agrati
Journal: Journal of Hepatology (2017)
Re: Zhihua Lu, Guiting Lin, Amanda Reed-Maldonado, Chunxi Wang, Yung-Chin Lee, Tom F. Lue. Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile Function: A Systematic Review and Meta-analysis. Eur Urol 2017;71:223–33
Authors: Claude Schulman, Ronald Virag, Francesco Montorsi
Journal: European Urology (2016)
Reply
Authors: Mattias Ekstedt, Hannes Hagström, Patrik Nasr, Mats Fredrikson, Per Stal, Stergios Kechagias, Rolf Hultcrantz
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. We thank Veeral Ajmera, Norah Terrault, and Peter Bacchetti for their comments on our study.1 In their letter to the editor they challenge our conclusion that the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease‐specific mortality. We agree with the authors in their discussion on hazard ratios, P values, and confidence intervals. In our study there was a trend toward increased mortality in patients with high NAS (5‐8) and low fibrosis stage (0‐2) with a hazard ratio of 1.41 (95% confidence interval 0.97‐2.06, P = 0.07). In clinical studies this type of result is always difficult to interpret as the lack of statistical significance could be a type II error. In a much larger study this trend could reach statistical significance, but it could as easily show that there is no increased mortality whatsoever. Also, it is possible that the potential increase in risk in this group is due to patients with fibrosis stages 1 and 2 being included and not due to the NAS in itself. The highly increased risk of hepatocellular carcinoma in this subset of patients is interesting but must be interpreted cautiously as it is based on five patients. Our conclusion is supported by other recent publications. In the study by Angulo and coworkers, NAS was not an independent predictor for overall mortality in NAFLD patients.2 This is in line with the systematic review and meta‐analysis of paired biopsy studies published by Singh and coworkers, where there was no association between baseline severity of necroinflammation and risk of progressive fibrosis.3 With all this taken into account, we argue that NAS is not only imperfect as a predictor of mortality but probably also insignificant and that fibrosis stage is the most robust marker for prediction of overall mortality in NAFLD. What we need are larger clinical relevant cohort studies of NAFLD patients with liver histology to finally resolve what histopathological patterns actually predict outcome.