tbuckley/cabot-search huggingface dataset:
Association of adverse events and tumor response in melanoma patients treated with tremelimumab.
Authors: D. Pavlov, M. A. Marshall
Journal: Journal of Clinical Oncology (2010)

e13104 Background: Several analyses of data from trials of anti-CTLA4 mAbs have suggested a relationship between antitumor activity and certain AEs. Such associations are confounded by the fact that responding patients receive more doses of drug and have longer follow- up. An analysis was done using data from 2 pivotal tremelimumab melanoma studies to determine whether certain AEs in the first treatment cycle (90 days) predict response to tremelimumab. This time period was chosen in order to decrease the difference in follow up time between responders and nonresponders. Methods: Tremelimumab was administered at 15 mg/kg Q90days in studies A3671008 and A3671009. Adverse events were reported for 90 days post last dose or until start of new therapy. RECIST responders were determined by independent radiological review for A3671008 and by sponsor using investigator measurements for A3671009. The following AE categories were analyzed: diarrhea/colitis, all grades and grade ≥3; endocrine events, rash, and pruritus. Results: 37 of 325 treated pts in A3671009 and 16 of 246 treated pts in A3671008 achieved response. All responders and 67% of nonresponders remained on study at least 80 days. Most tumor responders received ≥4 doses and were on study for ≥1 year. Most nonresponders received only a single dose. Rash but not pruritus was more frequent in the first cycle in responders compared to nonresponders. Rates of diarrhea and of severe diarrhea in the first cycle were similar in responders and nonresponders. None of the responders reported endocrine events in the first cycle. Conclusions: Endocrine and GI AEs occurring in the first cycle did not predict response. The higher incidence of endocrine and GI events AEs reported on study in pts with tumor response is due to the greater number of doses received and longer time on study. Responders were more likely than nonresponders to report rash, but not pruritus, in the first cycle; however, about half of the responders did not experience rash in the first cycle, so appearance of rash should not be used to decide whether to continue therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer
CD8 T-Cell Infiltration in Extravascular Tissues of Patients With Human Immunodeficiency Virus Infection. Interleukin-15 Upmodulates Costimulatory Pathways Involved in the Antigen-Presenting Cells–T-Cell Interaction
Authors: Carlo Agostini, Renato Zambello, Monica Facco, Alessandra Perin, Francesco Piazza, Marta Siviero, Umberto Basso, Michela Bortolin, Livio Trentin, Gianpietro Semenzato
Journal: Blood (1999)
Suicidality and aggression during antidepressant treatment: authors misinterpreted earlier paper from the FDA
Authors: Marc Stone
Journal: BMJ (2016)

Sharma and colleagues essentially duplicate, with more limited data, many of the analyses presented in our 2009 paper but seem not to have read our paper very carefully.1 2 They write, “The FDA did not consider the limitations of the trials that we identified and introduced some of their own—for example, by …
Effects of High Energy Shock Wave Exposure on Renal Function during Extracorporeal Shock Wave Lithotripsy for Kidney Stones
Authors: T. Kishimoto, M. Senju, T. Sugimoto, K. Yamamoto, W. Sakamoto, M. Iimori, T. Kanasawa, S. Wada, M. Maekawa
Journal: European Urology (1990)
Incidence of ovarian cancer in <i>BRCA</i>-negative hereditary breast cancer families
Authors: N. Kauff, T. Cigler, K. Hurley, H. Huang, H. Rapaport, E. Wadsworth, M. Robson, L. Norton, R. Barakat, K. Offit
Journal: Journal of Clinical Oncology (2004)

9534 Background: Mutations in BRCA1 and BRCA2 account for the majority of hereditary breast/ovarian cancer (HBOC) and half of hereditary breast cancer (HBC). Sequence analysis, however, is known to be incompletely sensitive for detecting BRCA mutations associated with HBOC/HBC. Because of this, many centers recommend consideration of ovarian cancer risk-reduction strategies in BRCA-negative individuals with a strong family history of breast cancer. Limited data is available regarding the actual risk of ovarian cancer in these individuals. Methods: Pedigrees from all women who underwent BRCA mutation testing at the Clinical Genetics Service at MSKCC from 8/1/96 through 7/31/02 and consented to prospective follow-up were reviewed. 285 individuals who 1) had no deleterious BRCA mutation on either founder mutation testing or full sequencing; and 2) whose family history included ≥ 3 breast cancers in a single lineage with one being diagnosed at ≤50 were identified and sent a structured questionnaire asking about occurrence of new cancer. Number of cancers expected was calculated from the SEER database for 1975–2000 and the Connecticut Tumor Registry Study of Multiple Primary Cancers. Observed versus expected cancers were compared using the Exact Poisson Test. Results: 171 (60%) individuals returned a questionnaire. At baseline, 77% had a personal history of breast cancer and a mean of 4.2 breast cancers in the kindred. 22 kindreds also had ≥1 individual with ovarian cancer. During a mean 3.6 years follow-up, a single fallopian tube cancer was reported in an individual with a BRCA1 variant of uncertain significance. When the 11 patients with such variants were excluded, 8 breast, 4 non-melanoma skin, and one each of lymphoma, CML, uterine sarcoma and thyroid cancer were reported during 567 women years of follow-up. Breast cancer was seen significantly more than expected (8 vs 3.9 cases; p = 0.045). No ovarian cancers were observed vs 0.25 expected (p=0.78). Conclusions: Individuals from HBC kindreds without a demonstrable BRCA mutation did not have an increased risk of ovarian cancer. If confirmed, these findings may have important implications for cancer screening in such kindreds. No significant financial relationships to disclose.
The composition and differentiation potential of the duodenal intraepithelial innate lymphocyte compartment is altered in coeliac disease
Authors: Frederike Schmitz, Yvonne Kooy-Winkelaar, Anna-Sophia Wiekmeijer, Martijn H Brugman, M Luisa Mearin, Chris Mulder, Susana Chuva de Sousa Lopes, Christine L Mummery, Frank JT Staal, Jeroen van Bergen, Frits Koning
Journal: Gut (2015)

<h3>Objective</h3> Coeliac disease (CD), a gluten-induced enteropathy, alters the composition and function of duodenal intraepithelial T cells. The intestine also harbours four types of CD3-negative intraepithelial lymphocytes (IELs) with largely unknown function: CD56<sup>−</sup>CD127<sup>−</sup>, CD56<sup>−</sup>CD127<sup>+</sup>, CD56<sup>+</sup>CD127<sup>−</sup> and CD56<sup>+</sup>CD127<sup>+</sup>. Here we aimed to gain insight into the potential function of these innate IELs in health and disease. <h3>Design</h3> We determined the phenotypes, relative abundance and differentiation potential of these innate IEL subsets in duodenal biopsies from controls and patients with CD or patients with refractory CD type II (RCDII). <h3>Results</h3> Hierarchical clustering analysis of the expression of 15 natural killer and T cell surface markers showed that innate IELs differed markedly from innate peripheral blood lymphocytes and divided innate IEL subsets into two main branches: a CD127<sup>−</sup> branch expressing high levels of interleukin (IL) 2/15Rβ but no IL-21R, and a CD127<sup>+</sup> branch with the opposite phenotype. While CD was characterised by the contraction of all four innate IEL subsets, a selective expansion of CD56<sup>−</sup>CD127<sup>−</sup> and CD56<sup>−</sup>CD127<sup>+</sup> innate IEL was detected in RCDII. In vitro, in the presence of IL-15, CD56<sup>−</sup>CD127<sup>−</sup> IEL from controls and patients with CD, but not from patients with RCDII, differentiated into functional natural killer and T cells, the latter largely dependent on notch-signalling. Furthermore, compared with non-coeliac controls, CD56<sup>−</sup>CD127<sup>−</sup> IEL from patients with CD expressed more intracellular CD3ε and CD3γ and gave more pronounced T cell differentiation. <h3>Conclusions</h3> Thus, we demonstrate previously unappreciated diversity and plasticity of the innate IEL compartment and its loss of differentiation potential in patients with RCDII.
Results of a randomized study of the JAK inhibitor ruxolitinib (INC424) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) or post-essential thrombocythemia-myelofibrosis (PET-MF).
Authors: C. N. Harrison, J. Kiladjian, H. K. Al-Ali, H. Gisslinger, R. J. Waltzman, V. Stalbovskaya, M. McQuitty, D. S. Hunter, R. S. Levy, F. Cervantes, A. M. Vannucchi, T. Barbui, G. Barosi
Journal: Journal of Clinical Oncology (2011)

LBA6501 Background: MF, a myeloproliferative neoplasm characterized by dysregulation of the JAK pathway, is associated with splenomegaly, constitutional symptoms and reduced lifespan. Ruxolitinib is a potent and selective JAK1 and JAK2 inhibitor. Methods: COMFORT-II, a randomized (2:1) phase III study, compared the efficacy and safety of ruxolitinib PO BID with BAT (other agents or no therapy) in adults with intermediate-2 or high-risk (Cervantes et al, Blood 2009) PMF, PPV-MF or PET-MF and palpable splenomegaly. The primary endpoint was the proportion of patients (pts), stratified by baseline risk category, achieving ≥ 35% reduction in spleen volume at week (wk) 48 determined by MRI or CT. The key secondary endpoint was the proportion achieving ≥ 35% reduction in spleen volume at wk 24. Results: 219 pts were randomized: 146 to ruxolitinib and 73 to BAT. Both arms included 49% high- and 51% intermediate-2 risk pts. The wk 48 response rate was 28.5% vs 0% (ruxolitinib vs BAT, P &lt; .0001). The wk 24 response rate was 31.9% vs 0% (ruxolitinib vs BAT, P &lt; .0001). Median duration of response to ruxolitinib was 48 wks. The most common (&gt; 20%) adverse events (AEs) of any grade were (ruxolitinib vs BAT) thrombocytopenia (44.5% vs 9.6%), anemia (40.4% vs 12.3%), diarrhea (24.0% vs 11.0%), and peripheral edema (21.9% vs 26.0%). Grade 3-4 AEs occurring in ≥ 5% of pts in the ruxolitinib arm were: anemia (11%) and thrombocytopenia (7.5%). The most frequent grade 3-4 AEs in the BAT arm were anemia, thrombocytopenia, pneumonia and dyspnea (each 4.1%). Seven deaths occurred on treatment or within 28 days after end of treatment: 4 (2.7%) ruxolitinib and 3 (4.1%) BAT. Disposition of discontinuations were (ruxolitinib vs BAT) 8.2% vs 5.5% due to AEs and 1.4% vs 12.3% due to withdrawn consent. Conclusions: The COMFORT-II study demonstrates that ruxolitinib provides marked and sustained clinical benefit in spleen size and an acceptable safety profile relative to BAT, extends the positive results of COMFORT-I which compared ruxolitinib with placebo, and may result in a new standard of care for a large number of patients with MF.
Gene Mutations and Treatment Outcome in CLL Patients Treated with Chlorambucil (Chl) or Ofatumumab-Chl (O-Chl): Results from the Phase III Study COMPLEMENT1 (OMB110911)
Authors: Eugen Tausch, Christina Galler, Richard Schlenk, Peter Hillmen, Fritz Offner, Ann Janssens, K Govindbabu, Jiri Mayer, Sebastian Grosicki, Panagiotis Panagiotidis, Daniel Mertens, Astrid McKeown, Ira Gupta, Hartmut Döhner, Stephan Stilgenbauer
Journal: Blood (2014)
Increased Risk of Brain Tumors in Children Exposed to Barbiturates&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: E Gold, L Gordis, J Tonascia, M Szklo
Journal: JNCI Journal of the National Cancer Institute (1978)

The possible etiologic role of barbiturates in the development of brain tumors in children was examined. Interviews were conducted with mothers of children with brain tumors and results compared with those from interviews with mothers of normal children and mothers of children with other cancers. Mothers of children with brain tumors more frequently reported having used barbiturates during their pregnancy with the index child than did mothers of normal children or mothers of children with other cancers. In addition, more children with brain tumors were reported to have used barbiturates than were normal children or children with other malignant diseases, with most of such uses appearing to be unrelated to symptoms resulting from the brain tumor itself. The results suggested that barbiturates may play an etiologic role, and it is estimated that as many as 8% of brain tumors in children may be attributable to use of barbiturates either by the child or prenatally by the mother.
Violent crime arrest rates of White House Case subjects and matched control subjects
Authors: D Shore, C R Filson, D S Rae
Journal: American Journal of Psychiatry (1990)

White House Case subjects typically are schizophrenic patients who have been psychotically preoccupied with a prominent political figure. The authors report the arrest rates for murder, aggravated assault, other assault, and robbery among 192 male White House Case subjects 20-59 years old who were discharged from civil commitments in the early 1970s. These rates were compared with those for the same crimes in a random matched sample of arrested subjects and with the general population arrest rates. When rates were covaried for prior violent crime arrests, White House Case subjects with prior arrests had a significantly higher rate of total posthospitalization violent crime arrests than the matched control sample.
Efficacy and toxicity of sorafenib monotherapy in patients with advanced soft tissue sarcoma failing anthracycline-based chemotherapy.
Authors: A. Bertuzzi, E. M. Stroppa, S. Secondino, P. Pedrazzoli, P. Zucali, V. Quagliuolo, A. Comandone, U. Basso, H. J. Soto Parra, A. Santoro
Journal: Journal of Clinical Oncology (2010)

10025 Background: Sorafenib, an orally administered inhibitor of RAF-family serine/threonine kinases andtyrosine kinase receptors, has demonstrated promising results in the treatment of refractory advanced solid tumors, including soft tissue sarcoma (STS), in terms of disease control and toxicity profile. We performed a multicenter phase II study aimed to evaluate the efficacy and safety of sorafenib in patients with advanced STS progressing after anthracycline-based chemotherapy. Methods: Patients with recurrent STS failing at least one line of chemotherapy and no relevant comorbidities were eligible for the study and received sorafenib 400 mg bid until progression or major toxicity. Patients who received the study drug for at least 4 weeks were considered evaluable for statistical analysis. Endpoints of the study were progression-free survival (PFS), overall survival (OS) and the proportion of patients achieving response (RECIST criteria). Toxicity was graded according to the NCI Common Toxicity Criteria V3.0. Results: Sixty-one patients received the study drug and were evaluable for response and toxicity. Most frequent pathologic subtypes were leiomyosarcoma and lyposarcoma. About half of patients received sorafenib as third or subsequent line of treatment. Six-months PFS and OS were 32% and 67%, respectively. Partial response lasting at least one month was in 9/61 pts (15%). Most frequently reported adverse events were fatigue, weight loss, diarrhea, hand-foot syndrome (HFS) and alopecia. Grade 3-4 toxicities included HFS in 8%, fatigue in 8%, diarrhea in 7%. Conclusions: Sorafenib is associated with antitumor activity and acceptable toxicity profile in patients with antracycline-refractory STS. Survival analysis of additional 30 leiomyosarcoma patients treated with sorafenib is ongoing. No significant financial relationships to disclose.
TLR9 Priming Promotes Proliferation Of Mesenchymal Stem Cells and Restores The Immunosuppressive Activity Impaired By TLR4 Priming: Potential Involvement Of Non-Canonical NF-Kb Signaling
Authors: Bruno B. Sangiorgi, Vitor Leão, Josiane Lilian dos Santos Schiavinato, Maristela Delgado Orellana, Marco A. Zago, Dimas T Covas, Rodrigo Alexandre Panepucci, Eduardo M. Rego
Journal: Blood (2013)
Abstract 13065: Trends, Predictors and Outcomes in Heart Failure Patients undergoing Palliative Care
Authors: Navdeep Gupta, Muhammed Shahreyar, Vijayadershan Muppidi, Nunzio Gaglianello, Mary A Papp, Michael P Cinquegrani
Journal: Circulation (2014)

Background: Palliative care improves quality of life and potentially survival in advanced heart failure patients but is underutilized. Current trends in palliative care in heart failure patients in real world practice are not known. Methods: We analyzed patients in the Nationwide Inpatient Sample (NIS) between 2002-2011 with primary discharge diagnosis of heart failure. Among these patients we analyzed the co-diagnosis of palliative care. Primary outcomes of interest were yearly trends in palliative care utilization during the study period. Secondary outcomes of interest were clinical characteristics and outcomes in those undergoing palliative care. Results: Out of 10,475,928 discharges with primary diagnosis of heart failure 88,595(0.8%)patients had co-diagnosis of palliative care. We saw a steady increase in palliative care utilization from 0.2% to 2.4% from 2002 to 2011(p<0.001)(Figure). In prior to admission variables Age, female sex, malignancy, weight loss and liver disease while during index admiss...
Highly efficient gene transfer into cord blood nonobese diabetic/severe combined immunodeficiency repopulating cells by oncoretroviral vector particles pseudotyped with the feline endogenous retrovirus (RD114) envelope protein
Authors: Patrick F. Kelly, Jody Vandergriff, Amit Nathwani, Arthur W. Nienhuis, Elio F. Vanin
Journal: Blood (2000)
Race bias in the diagnosis and disposition of violent adolescents
Authors: D O Lewis, S S Shanok, R J Cohen, M Kligfeld, G Frisone
Journal: American Journal of Psychiatry (1980)

The authors compared psychiatric symptoms, violent behaviors, and medical histories of an entire one-year sample of adolescents from the same community who were sent either to the correctional school or the only state hospital adolescent psychiatric unit serving the area. The initial hypothesis that the incarcerated group would be equally disturbed but more violent than the hospitalized group was contradicted. Violence as well as severe psychiatric symptomatology was equally prominent in the two groups. The most powerful variables distinguishing the groups were race, accidents, and injuries (especially head injury), and sex. The medical and social implications of the findings are discussed.
First-line temozolomide (TEM) combined with bevacizumab (BEV) in metastatic melanoma (MM): A multicenter phase II trial (SAKK 50/07).
Authors: R. Dummer, O. Michielin, B. Seifert, A. F. Ochsenbein, R. Cathomas, M. R. Schlaeppi, M. Simcock, S. Gillessen, S. M. Goldinger, R. von Moos
Journal: Journal of Clinical Oncology (2010)

8521 Background: Single agent DTIC is current standard therapy for MM. Oral TEM has shown equal efficacy in phase III trials with median progression free survival (PFS) of 2.1 months and response rates of 5%-20%. BEV has an inhibitory effect on the proliferation of melanoma cells and sprouting endothelial cells. Combining this angiogenesis inhibitor with a cytotoxic agent may provide additional clinical benefit in MM. Methods: Primary endpoint: disease stabilisation rate (CR, PR or SD) at week 12 (DSR12) considered uninteresting if ≤ 20% and promising if ≥ 35%. Based on Simon's two stage optimal design (5% significance level, 80% power), 62 patients required. Secondary endpoints: best overall response, response duration (RD), PFS, overall survival (OS) and adverse events (AE). Eligibility: stage IV MM, ECOG PS 0-2 and previously untreated metastatic disease. One cycle consisted of TEM at 150 mg/m2 days 1-7 po and BEV at 10 mg/kg day 1 over 30 min iv every 2 weeks until progression or unacceptable toxicity. Response assessed every 6 weeks by RECIST. Results: From 01/08 until 04/09, 40 males and 22 females, median age 59 years (29-84), stage IV (M1a:4, M1b:12, M1c:46) were enrolled. Median follow-up is 14.1 months (1.7-20.7). Unreviewed DSR12 was 58% (CR:1, PR:11, SD:24) and reviewed 52% (PR:10, SD:22). Confirmed, independently reviewed overall response rate was 16.1% (CR:1, PR:9). Median RD, PFS and OS was 5.0 (95% CI: 4.1-6.2), 4.2 (95% CI: 3.4-5.5) and 9.3 (95% CI: 8.2- 12.3) months respectively. Hematologic CTCAE v3.0 grade 3/4 AEs were thrombocytopenia (9.7%) and neutropenia (6.5%). Non-hematological AEs grade 3 were hypertension (11.3%), fatigue (8.0%), hemorrhage (4.8%), nausea (4.8%) and vomiting (3.2%). Response (chi-squared p = 0.02) and OS (14.8 vs. 9.2 months; p = 0.02) where higher in the BRAF V600E wild-type patients compared to mutated. Conclusions: The primary endpoint was met (DSR12 ≥ 18 patients) showing promising activity in this high-risk population with PFS 4.2 months. Response and OS were significantly higher in BRAF wild type patients. TEM/BEV has a low toxicity profile. A confirmatory phase III trial is required. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Cepahlon, Essex Pharma, Genta, Merck, Novartis, Roche, sanofi-aventis, Schering-Plough, Temodal, Transgene Essex Pharma, Roche AstraZeneca, Bayer, Cepahlon, Merck, Novartis, Roche, Transgene
Resource Effective Strategies to Prevent and Treat Cardiovascular Disease
Authors: J.D. Schwalm, Martin McKee, Mark D. Huffman, Salim Yusuf
Journal: Circulation (2016)

Cardiovascular disease (CVD) is the leading cause of global deaths, with the majority occurring in low- and middle-income countries. The primary and secondary prevention of CVD is suboptimal throughout the world, but the evidence–practice gaps are much more pronounced in low- and middle-income countries. Barriers at the patient, healthcare provider, and health system level prevent the implementation of optimal primary and secondary prevention. Identification of the particular barriers that exist in resource-constrained settings is necessary to inform effective strategies to reduce the identified evidence–practice gaps. Furthermore, targeting modifiable factors that contribute most significantly to the global burden of CVD, including tobacco use, hypertension, and secondary prevention for CVD, will lead to the biggest gains in mortality reduction. We review a select number of novel, resource-efficient strategies to reduce premature mortality from CVD, including (1) effective measures for tobacco control, (2) implementation of simplified screening and management algorithms for those with or at risk of CVD, (3) increasing the availability and affordability of simplified and cost-effective treatment regimens including combination CVD preventive drug therapy, and (4) simplified delivery of healthcare through task-sharing (nonphysician health workers) and optimizing self-management (treatment supporters). Developing and deploying systems of care that address barriers related to the above will lead to substantial reductions in CVD and related mortality.