tbuckley/cabot-search huggingface dataset:
Who Decides When a Patient Can’t? Statutes on Alternate Decision Makers
Authors: Erin S. DeMartino, David M. Dudzinski, Cavan K. Doyle, Beau P. Sperry, Sarah E. Gregory, Mark Siegler, Daniel P. Sulmasy, Paul S. Mueller, Daniel B. Kramer
Journal: New England Journal of Medicine (2017)

U.S. states vary in their procedures for appointing and challenging default surrogates, the attributes they require of them, priority ranking of possible decision makers, and dispute resolution — with important implications for clinicians, patients, and public health.
Comorbidity of chronic spontaneous urticaria and autoimmune thyroid diseases: A systematic review
Authors: P. Kolkhir, M. Metz, S. Altrichter, M. Maurer
Journal: Allergy (2017)

Patients with chronic spontaneous urticaria (CSU) are widely held to often have other autoimmune disorders, including autoimmune thyroid disease. Here, we systematically evaluated the literature on the prevalence of thyroid autoimmunity in CSU and vice versa. There is a strong link between CSU and elevated levels of IgG antithyroid autoantibodies (AAbs), with most of a large number of studies reporting rates of ≥10%. Levels of IgG against thyroid peroxidase (TPO) are more often elevated in CSU than those of other IgG antithyroid AAbs (strong evidence). Levels of IgG antithyroid AAbs are more often elevated in adult patients with CSU than in children (strong evidence). Patients with CSU exhibit significantly higher levels of IgG antithyroid AAbs (strong evidence) and IgE-anti-TPO (weak evidence) than controls. Elevated IgG antithyroid AAbs in CSU are linked to the use of glucocorticoids (weak evidence) but not to disease duration or severity/activity, gender, age, or ASST response (inconsistent evidence). Thyroid dysfunction rates are increased in patients with CSU (strong evidence). Hypothyroidism and Hashimoto's thyroiditis are more common than hyperthyroidism and Graves' disease (strong evidence). Thyroid dysfunction is more common in adult patients with CSU than in children (strong evidence) and in female than in male patients with CSU (weak evidence). Urticaria including CSU is more prevalent in patients with thyroid autoimmunity than in controls (weak evidence). CSU can improve in response to treatment with levothyroxine or other thyroid drugs (strong evidence). Pathogenic mechanisms in CSU patients with thyroid autoimmunity may include IgE against autoantigens, immune complexes, and complement.
Plasma Alemtuzumab Levels at End of Treatment Correlate with Response and Response Duration in Patients with CLL Receiving Treatment for Residual Disease.
Authors: William G Wierda, Thomas J Kipps, Michael J Keating, Jennifer R Brown, John G Gribben, Laura Z Rassenti, Andrew W Greaves, Donna Neuberg, Susan M O’Brien
Journal: Blood (2008)
Phase I Study of Fenretinide Delivered Intravenously in Patients with Relapsed or Refractory Hematologic Malignancies: A California Cancer Consortium Trial
Authors: Ann M. Mohrbacher, Allen S. Yang, Susan Groshen, Shivaani Kummar, Martin E. Gutierrez, Min H. Kang, Denice Tsao-Wei, C. Patrick Reynolds, Edward M. Newman, Barry J. Maurer
Journal: Clinical Cancer Research (2017)

Abstract Purpose: A phase I study was conducted to determine the MTD, dose-limiting toxicities (DLT), and pharmacokinetics of fenretinide delivered as an intravenous emulsion in relapsed/refractory hematologic malignancies. Experimental Design: Fenretinide (80–1,810 mg/m2/day) was administered by continuous infusion on days 1 to 5, in 21-day cycles, using an accelerated titration design. Results: Twenty-nine patients, treated with a median of three prior regimens (range, 1–7), were enrolled and received the test drug. Ninety-seven courses were completed. An MTD was reached at 1,280 mg/m2/day for 5 days. Course 1 DLTs included 6 patients with hypertriglyceridemia, 4 of whom were asymptomatic; 2 patients experienced DLT thrombocytopenia (asymptomatic). Of 11 patients with response-evaluable peripheral T-cell lymphomas, two had complete responses [CR, progression-free survival (PFS) 68+ months; unconfirmed CR, PFS 14+ months], two had unconfirmed partial responses (unconfirmed PR, PFS 5 months; unconfirmed PR, PFS 6 months), and five had stable disease (2–12 cycles). One patient with mature B-cell lymphoma had an unconfirmed PR sustained for two cycles. Steady-state plasma levels were approximately 10 mcg/mL (mid-20s μmol/L) at 640 mg/m2/day, approximately 14 mcg/mL (mid-30s μmol/L) at 905 mg/m2/day, and approximately 22 mcg/mL (mid-50s μmol/L) at 1,280 mg/m2/day. Conclusions: Intravenous fenretinide obtained significantly higher plasma levels than a previous capsule formulation, had acceptable toxicities, and evidenced antitumor activity in peripheral T-cell lymphomas. A recommended phase II dosing is 600 mg/m2 on day 1, followed by 1,200 mg/m2 on days 2 to 5, every 21 days. A registration-enabling phase II study in relapsed/refractory PTCL (ClinicalTrials.gov identifier: NCT02495415) is ongoing. Clin Cancer Res; 23(16); 4550–5. ©2017 AACR.
Long noncoding RNA HULC modulates the phosphorylation of YB‐1 through serving as a scaffold of extracellular signal–regulated kinase and YB‐1 to enhance hepatocarcinogenesis
Authors: Dan Li, Xuefeng Liu, Jian Zhou, Jie Hu, Dongdong Zhang, Jing Liu, Yanyan Qiao, Qimin Zhan
Journal: Hepatology (2016)

Dysregulated expression of long noncoding RNAs has been reported in many types of cancers, indicating that it may play a critical role in tumorigenesis. The long noncoding RNA highly up‐regulated in liver cancer (HULC) was first characterized in hepatocellular carcinoma. However, the detailed mechanisms of HULC remain unclear. Here, we demonstrate a novel mechanism by which long noncoding RNA plays oncogenic roles through modulating the phosphorylation status of its interaction protein. First, we validated the markedly increased expression levels of HULC in hepatocellular carcinoma tissues compared to their adjacent noncancerous tissues. Furthermore, up‐regulation of HULC was correlated with grading and overall survival. Meanwhile, HULC could promote cell proliferation, migration, and invasion in vitro and inhibit cisplatin‐induced apoptosis. Moreover, we show that HULC specifically binds to Y‐box binding protein 1 (YB‐1) protein both in vitro and in vivo . YB‐1 is a major component of translationally inactive messenger ribonucleoprotein particles which keeps mRNA in a silent state. Our study further demonstrated that HULC could promote the phosphorylation of YB‐1 protein, which leads to the release of YB‐1 from its bound mRNA. As a consequence, translation of silenced oncogenic mRNAs would be activated, including cyclin D1, cyclin E1, and matrix metalloproteinase 3. In addition, we found that HULC promotes the phosphorylation of YB‐1 protein mainly through extracellular signal–regulated kinase. Conclusion : We demonstrate that HULC promotes the phosphorylation of YB‐1 through the extracellular signal–regulated kinase pathway, in turn regulates the interaction of YB‐1 with certain oncogenic mRNAs, and consequently accelerates the translation of these mRNAs in the process of tumorigenesis. (H epatology 2017;65:1612‐1627)
Copies of Donor Killer Immunoglobulin-like Receptor Genes and Motifs Titrate Natural Killer (NK) Cells' Functional Response to Epstein - Barr Virus Infections and Influence the Risk of Developing Post-Transplant Lymphoproliferative Disease (PTLD) after Allogeneic Hematopoietic Cell Transplantation
Authors: Rehan Mujeeb Faridi, Taylor J Kemp, Poonam Dharmani, Victor A. Lewis, Noureddine Berka, Jan Storek, Faisal M Khan
Journal: Blood (2015)
Cycling to work has substantial health benefits, study finds
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Cycling to work has substantial health benefits, study finds Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
London commissioning group plans to restrict cataract surgery to “exceptional” cases
Authors: Gareth Iacobucci
Journal: BMJ (2017)

NHS patients in part of southeast London may be prevented from having their cataracts removed unless their cases are “exceptional,” under cost cutting proposals from care commissioners.

Greenwich Clinical Commissioning Group is consulting on plans to restrict access to cataract surgery and 12 other surgical procedures as part of efforts to save up to £500 000 (€590 000; $620 000). The CCG also wants to restrict access to routine elective and planned surgery for smokers and obese people to help reduce its financial deficit.

But the plans were condemned by the Royal National Institute for the Blind (RNIB), which warned that they would harm patients.

In its …
Impact of acute hypertension transients on diastolic function in patients with heart failure with preserved ejection fraction
Authors: Candelas Pérez del Villar, Konstantinos Savvatis, Begoña López, Mario Kasner, Pablo Martinez-Legazpi, Raquel Yotti, Arantxa González, Javier Díez, Francisco Fernández-Avilés, Carsten Tschöpe, Javier Bermejo
Journal: Cardiovascular Research (2017)

To address the mechanisms responsible for the increase in LV filling pressures induced by acute hypertension transients in patients with heart failure with preserved ejection fraction (HFpEF).Multiple-beat pressure-volume loops were recorded during inferior vena cava occlusion in 39 HFpEF patients and 20 controls during handgrip and atrial pacing. We measured the contribution of relaxation, elastic recoil, and stiffness to instantaneous diastolic pressure using a novel processing method. Fibrosis was quantified from endomyocardial biopsies. HFpEF patients showed higher diastolic pressures and stiffness constant than controls (P < 0.05 for all). As opposed to controls, all intrinsic global diastolic properties were sensitive to acute changes in systolic pressure in the HFpEF group. In fact, the stiffness constant increased by more than 50% during handgrip in HFpEF patients (P < 0.05), tightly related to changes in systolic pressure (fixed-effect = 0.26 mm Hg per mm Hg [95% CI = 0.15-0.37]; P < 0.0001). Incomplete relaxation contributed to increasing pressure before atrial contraction, but changes in end-diastolic pressure was mostly caused by the increase in stiffness. The degree of pressure-sensitivity of stiffness correlated with myocardial collagen volume and crosslinking (R = 0.40 to 0.82 for all).Acute chamber stiffening is the main mechanism responsible for rising late-diastolic pressures when HFpEF patients undergo hypertension transients. This stiffening behaviour is related to impaired dynamic systolic-diastolic interactions and correlates with matrix remodelling. Ventricular-vascular relationships are a promising target in HFpEF and should be taken into account when assessing diastolic function.
Diagnosis and initial evaluation of patients with gastrointestinal stromal tumor (GIST): An observational study of 1,226 patients.
Authors: Jonathan C. Trent, Margaret von Mehren, Peter W. T. Pisters, Joel Picus, Christopher Hunt Keir, Andrea Magley, C. D. Blanke
Journal: Journal of Clinical Oncology (2012)

10088 Background: The GIST registry (reGISTry) is an observational database designed to determine diagnostic method and evaluation of GIST patients outside of clinical trials. We previously described differences in treatment of patients in community versus academic centers (Pisters, Ann Oncol 2011;22:2523-9). Herein we present distinct differences in the diagnosis and initial evaluation of patients with GIST. Methods: The analysis cutoff date was May 2010. Patient demographics, presenting symptoms, diagnostic methodology, and KIT and PDFGRA mutations were described. For localized tumors, size and mitotic index (MI) were collected. Results: 1226 patients were included in this analysis. Initial diagnosis was most commonly made by surgeons (54.6%) and gastroenterologists (15.7%). Primary management decisions were made at time of diagnosis by medical oncologists (53%) and surgeons (53%) (sum &gt;100% due to ≥1 responses/site). 84% were symptomatic at diagnosis, while 16% were diagnosed incidentally. Diagnostic procedure was performed during surgery (75%) and/or by endoscopy (22%) or interventional radiology (11%) using percutaneous core biopsy or fine needle aspirate. Initial diagnostic imaging was by CT scan (76%), endoscopy (25%), ultrasound (12%), or a combination. Most primary GISTs were located in the stomach (55%) or small intestine (28%). At diagnosis, localized and metastatic disease was seen in 83% and 17% of patients, respectively, with metastases mainly in the liver (62%) and/or peritoneum (36%). KIT immunostaining was performed in 93% of patients, with 98% positive. Mutation analysis was carried out in 8% of cases (57% KIT exon 11 and 12% exon 9 mutations). Of localized primary tumors, 52% were &gt;5 cm in size and 23% had &gt;5 mitoses per 50 high-power fields. Conclusions: We found that initial diagnosis is made by several different modalities. The majority of GIST patients are managed by medical and surgical oncologists. Most patients with localized tumor were at intermediate risk of recurrence and would be considered for adjuvant imatinib therapy.
Interim results of preoperative gemcitabine (gem) plus cisplatin followed by rapid fractionation chemoradiation for resectable pancreatic adenocarcinoma
Authors: G. R. Varadhachary, D. B. Evans, C. Crane, H. Q. Xiong, J. E. Lee, P. W. Pisters, E. K. Abdalla, J. H. Lee, E. P. Tamm, R. A. Wolff
Journal: Journal of Clinical Oncology (2006)

4037 Background: Over 80% of pts who undergo potentially curative pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma develop local or distant recurrence. Chemotherapy and external-beam radiation therapy (EBRT) prior to surgery maximizes the number of pts who receive multimodality therapy and undergo a complete (R0) resection. Methods: Pts with biopsy proven, stage I/II adenocarcinoma of the pancreatic head or uncinate process received systemic therapy with 4 infusions of gem (750 mg/m 2 ) + cisplatin (30 mg/m 2 ) every 2 wks followed by 30 Gy of EBRT (3 Gy/Fx, M-F over 2 wks) and 4 weekly doses of gem (400 mg/m 2 ). Pts underwent complete restaging 4–6 wks after the last dose of gem. Those without disease progression and with acceptable PS underwent surgery. Results: This study has currently enrolled 87 pts over 4 years. Median age is 65 yrs (38–80), most pts (96%) had ECOG-PS (0–1) at study entry. Median CA19–9 is 170. Six pts were excluded from analysis and 4 are currently on treatment. Of the 77 pts who finished chemoradiation, 72 completed restaging (3 await restaging, 2 drop outs). Of these 72 pts, 10 had disease progression, 1 had a decline in PS, and 61 (79 %) went to surgery. 49 of 61 pts (64 %) underwent a successful PD and metastatic or locally advanced disease was found in 12 (15 %). 44 (90 %) of 49 pts underwent R0 resection. Pathologic PR rate (&gt;50 % tumor kill) was 61 %. The predominant toxicity prompting hospitalization during preoperative therapy was biliary stent occlusion (44 %). Gastrointestinal toxicity ≤ grade 3 was common but controllable. Grade 3 and 4 neutropenia was seen in 19 (25 %) and 3 pts (4 %) respectively. Grade 3–4 thrombocytopenia was rare. Median survival for resected pts was ∼ 21 months. Conclusions: This study, builds on our previous gem-based preop chemoradiation program ( ASCO 2002, Abs # 516) producing good local treatment effect and a high R0 resection rate. However, interim analysis suggests that the addition of systemic chemotherapy delivered prior to preoperative chemoradiation does not appear to improve survival. Optimal treatment sequencing of chemoradiation, systemic therapy and surgery needs further refinement. Supported in part by Eli Lilly and Co. [Table: see text]
A Novel TP53 Mutation Associated with TWIST1 and SIP1 Expression in an Aggressive Adrenocortical Carcinoma
Authors: Daniel Bulzico, Davi Coe Torres, Gerson Moura Ferreira, Bruno Ricardo Barreto Pires, Paulo Antônio Silvestre de Faria, Rocio Hassan, Eliana Abdelhay, Mario Vaisman, Leonardo Vieira Neto
Journal: Endocrine Pathology (2017)
H19 promotes cholestatic liver fibrosis by preventing ZEB1‐mediated inhibition of epithelial cell adhesion molecule
Authors: Yongfeng Song, Chune Liu, Xia Liu, Jocelyn Trottier, Michele Beaudoin, Li Zhang, Chad Pope, Guangyong Peng, Olivier Barbier, Xiaobo Zhong, Linheng Li, Li Wang
Journal: Hepatology (2017)

Based on our recent finding that disruption of bile acid (BA) homeostasis in mice results in the induction of hepatic long noncoding RNA H19 expression, we sought to elucidate the role of H19 in cholestatic liver fibrosis. Hepatic overexpression of H19RNA augmented bile duct ligation (BDL)-induced liver fibrosis, which was accompanied by the elevation of serum alanine aminotransferase, aspartate aminotransferase, bilirubin, and BA levels. Multiple genes related to liver fibrosis, inflammation, and biliary hyperplasia were increased in H19-BDL versus null-BDL mice, whereas genes in BA synthesis were decreased. Livers and spleens of H19-BDL mice showed significant enrichment of CD3+γδ+, interleukin-4, and interleukin-17 producing CD4+ and CD8+ immune cell populations. H19 down-regulated hepatic zinc finger E-box-binding homeobox 1 (ZEB1) but up-regulated epithelial cell adhesion molecule (EpCAM) and SRY (sex determining region Y)-box 9 expression. Mechanistically, ZEB1 repressed EpCAM promoter activity and gene transcription. H19RNA impeded ZEB1's inhibitory action by interacting with ZEB1 protein to prevent its binding to the EpCAM promoter. Hepatic overexpression of ZEB1 or knockdown of EpCAM diminished H19-induced fibrosis; the latter was also prevented in H19-/- mice. H19RNA was markedly induced by bile acids in mouse small cholangiocytes and to a lesser extent in mouse large cholangiocytes. The up-regulation of H19RNA and EpCAM correlated positively with the down-regulation of ZEB1 in primary sclerosing cholangitis and primary biliary cirrhosis liver specimens.The activation of hepatic H19RNA promoted cholestatic liver fibrosis in mice through the ZEB1/EpCAM signaling pathway. (Hepatology 2017;66:1183-1196).
Role of CBX4 in the Colorectal Carcinoma Metastasis—Response
Authors: Xin Wang, Tiebang Kang
Journal: Cancer Research (2017)

In our article ([1][1]), we have reported that CBX4 may serve as a tumor suppressor in colorectal carcinoma by recruiting HDAC3 to the RUNX2 promoter to impede RUNX2 expression and that this novel function of CBX4 depends on its interaction with HDAC3, but is independent of its SUMO E3 ligase, its
Novel PIK3CD mutations affecting N-terminal residues of p110δ cause activated PI3Kδ syndrome (APDS) in humans
Authors: Andrew J. Takeda, Yu Zhang, Gillian L. Dornan, Braden D. Siempelkamp, Meredith L. Jenkins, Helen F. Matthews, Joshua J. McElwee, Weimin Bi, Filiz O. Seeborg, Helen C. Su, John E. Burke, Carrie L. Lucas
Journal: Journal of Allergy and Clinical Immunology (2017)
ECDC Round Table Report and ProMed-mail most useful international information sources for the Netherlands Early Warning Committee
Authors: Paul Bijkerk, Annelie A Monnier, Ewout B Fanoy, Katina Kardamanidis, Ingrid HM Friesema, Mirjam J Knol
Journal: Eurosurveillance (2017)

The Netherlands Early Warning Committee (NEWC) aims to identify infectious diseases causing a potential threat to Dutch public health. Threats are assessed and published as (information) alerts for public health experts. To identify threats from abroad, the NEWC screens 10 sources reporting disease outbreaks each week. To identify the sources essential for complete and timely reporting, we retrospectively analysed 178 international alerts published between 31 January 2013 and 30 January 2014. In addition, we asked the four NEWC coordinators about the required time to scan the information sources. We documented the date and source in which the signal was detected. The ECDC Round Table (RT) Report and ProMED-mail were the most complete and timely sources, reporting 140 of 178 (79%) and 121 of 178 (68%) threats respectively. The combination of both sources reported 169 (95%) of all threats in a timely manner. Adding any of the other sources resulted in minor increases in the total threats found, but considerable additional time investment per additional threat. Only three potential relevant threats (2%) would have been missed by only using the ECDC RT Report and ProMed-mail. We concluded that using only the ECDC RT Report and ProMed-mail to identify threats from abroad maintains a sensitive Early Warning System.
Characterization and risk estimate of cancer in patients with primary Sjögren syndrome
Authors: Pilar Brito-Zerón, Belchin Kostov, Guadalupe Fraile, Daniel Caravia-Durán, Brenda Maure, Francisco-Javier Rascón, Mónica Zamora, Arnau Casanovas, Miguel Lopez-Dupla, Mar Ripoll, Blanca Pinilla, Eva Fonseca, Miriam Akasbi, Gloria de la Red, Miguel-Angel Duarte-Millán, Patricia Fanlo, Pablo Guisado-Vasco, Roberto Pérez-Alvarez, Antonio J. Chamorro, César Morcillo, Iratxe Jiménez-Heredia, Isabel Sánchez-Berná, Armando López-Guillermo, Manuel Ramos-Casals
Journal: Journal of Hematology & Oncology (2017)

The purpose of this study is to characterize the risk of cancer in a large cohort of patients with primary Sjögren syndrome (SjS).We had analyzed the development of cancer in 1300 consecutive patients fulfilling the 2002 SjS classification criteria. The baseline clinical and immunological characteristics and systemic activity (ESSDAI scores) were assessed at diagnosis as predictors of cancer using Cox proportional hazards regression analysis adjusted for age at diagnosis and gender. The sex-and age-specific standardized incidence ratios (SIR) of cancer were estimated from 2012 Spanish mortality data.After a mean follow-up of 91 months, 127 (9.8%) patients developed 133 cancers. The most frequent type of cancer was B-cell lymphoma (including 27 MALT and 19 non-MALT B-cell lymphomas). Systemic activity at diagnosis of primary SjS correlated with the risk of hematological neoplasia and cryoglobulins with a high risk of either B-cell or non-B-cell lymphoma subtypes. Patients with cytopenias had a high risk of non-MALT B-cell and non-B-cell cancer, while those with low C3 levels had a high risk of MALT lymphomas and those with monoclonal gammopathy and low C4 levels had a high risk of non-MALT lymphomas. The estimated SIR for solid cancer was 1.13 and 11.02 for hematological cancer. SIRs for specific cancers were 36.17 for multiple myeloma and immunoproliferative diseases, 19.41 for Hodgkin lymphoma, 6.04 for other non-Hodgkin lymphomas, 5.17 for thyroid cancer, 4.81 for cancers of the lip and oral cavity, and 2.53 for stomach cancer.One third of cancers developed by patients with primary SjS are B-cell lymphomas. The prognostic factors identified at SjS diagnosis differed according to the subtype of B-cell lymphoma developed. Primary SjS is also associated with the development of some non-hematological cancers (thyroid, oral cavity, and stomach).