tbuckley/cabot-search huggingface dataset:
Pericarditis as a Marker of Occult Cancer and a Prognostic Factor for Cancer Mortality
Authors: Kirstine Kobberøe Søgaard, Dóra Körmendiné Farkas, Vera Ehrenstein, Krishnan Bhaskaran, Hans Erik Bøtker, Henrik Toft Sørensen
Journal: Circulation (2017)

Pericarditis may be a serious complication of malignancy. Its significance as a first symptom of occult cancer and as a prognostic factor for cancer survival is unknown.Using Danish medical databases, we conducted a nationwide cohort study of all patients with a first-time diagnosis of pericarditis during 1994 to 2013. We excluded patients with previous cancer and followed up the remaining patients for subsequent cancer diagnosis until November 30, 2013. We calculated risks and standardized incidence ratios of cancer for patients with pericarditis compared with the general population. We assessed whether pericarditis predicts cancer survival by the Kaplan-Meier method and Cox regression using a matched comparison cohort of cancer patients without pericarditis.Among 13 759 patients with acute pericarditis, 1550 subsequently were diagnosed with cancer during follow-up. The overall cancer standardized incidence ratio was 1.5 (95% confidence interval [CI], 1.4-1.5), driven predominantly by increased rates of lung, kidney, and bladder cancer, lymphoma, leukemia, and unspecified metastatic cancer. The <3-month cancer risk among patients with pericarditis was 2.7%, and the standardized incidence ratio was 12.4 (95% CI, 11.2-13.7). The 3- to <12-month standardized incidence ratio of cancer was 1.5 (95% CI, 1.2-1.7), subsequently decreasing to 1.1 (95% CI, 1.0-1.2). Three-month survival after the cancer diagnosis was 80% and 86% among those with and without pericarditis, respectively, and the hazard ratio was 1.5 (95% CI, 1.3-1.8). One-year survival was 65% and 70%, respectively, corresponding to a 3- to <12-month hazard ratio of 1.3 (95% CI, 1.1-1.5).Pericarditis may be a marker of occult cancer and augurs increased mortality after a cancer diagnosis.
Pathologic complete response and changes related to T-infiltrating lymphocytes and regulatory T cells in tissue and peripheral blood after neoadjuvant chemotherapy in breast carcinoma.
Authors: Luis De La Cruz-Merino, Antonio Barco Sanchez, Fernan Henao Carrasco, Jose Ibanez Martinez, Esteban Nogales, Ana Vallejo BenÃƒÂtez, Javier Brugal Molina, V. Sanchez Margalet, M. Lobo Acosta, A. Nieto Garcia
Journal: Journal of Clinical Oncology (2013)

e22073 Background: Some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings in the neoadjuvant setting. In this context, tumor infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in tissue specimens and in peripheral blood are being tested as two emerging prognostic and predictive factors. We designed a protocol to analyze specifically TILs before, during and after neoadjuvant chemotherapy (CT) in breast cancer in blood and tissue, and their eventual relation with pathological complete response. Methods: From March 2011 to January 2013, 48 patients (18 HER2+/ 30 HER2-) with T2-4 N0-3 breast carcinoma treated with neoadjuvant chemotherapy in the Breast Cancer Unit of the Hospital Universitario Virgen Macarena (Seville, Spain) were included in the study protocol. CD3+, CD8+, CD8-16-56+ and Foxp3+ cell infiltrates were detected by immunohistochemistry before and after the end of neoadjuvant chemotherapy in tissue specimens. Blood samples were collected in EDTA-K3 tubes before every cycle of CT to determine the immunophenotype and regulatory cell profile. Cell populations were determined by flow cytometry analysis of whole blood. Results: By January 2013, 35 patients (11 HER2+/ 24 HER2-) were operated. Pathological complete responses (pCR) or near pCR (grade 4/5 Myller and Payne) were attained in 13 patients. pCR was achieved in 63.63% (7 of 11) of tumors overexpressing HER2, but in only a 25% (6 of 24) of HER2-negative tumors. Overall Tregs diminished in the pCR and non pCR groups. Disappearance of Tregs (Black grading system) was more frequent in the pCR group (69.23 vs 54.54%) and HER2+ population (63.63 vs 58.53%), although differences were not statistically significant. CD8+ infiltrates remain stable during treatment. Conclusions: Neoadjuvant CT decreases Tregs immunosuppressive infiltrates with no changes in CD8+ cytotoxic lymphocytes. Changes observed in lymphocytic infiltrates during neoadjuvant treatment indicate that Tregs may represent an interesting therapeutic target in breast carcinoma.
Evolocumab Added to Statins to Reduce Progression of Coronary Atherosclerosis—Reply
Authors: Laura Kann, Lisa C. Barrios
Journal: JAMA (2017)

Sexual orientation is defined by sexual attraction, sexual identity, and sex of sexual contacts. The national YRBS currently measures sexual identity and sex of sexual contacts and, consistent with National Academy of Medicine (formerly the Institute of Medicine) recommendations,1 each construct is measured separately. Sexual orientation typically develops during adolescence and may progress in such a way that sexual identity and sex of sexual contacts may not be concordant. This dissonance between sexual identity and sex of sexual contacts is well documented1- 3 and, as national YRBS data demonstrate,4 is not uncommon among youth. Consequently, we defined sexual minority students as those whose sexual identity was gay, lesbian, or bisexual or those who had sexual contact with only the same sex or with both sexes.
New molecular breast cancer classification with adjuvant therapy in our population
Authors: E. Richardet, B Mascheroni, I Magri, L Perelli, M Cortés
Journal: Journal of Clinical Oncology (2009)

e11624 Background: The molecular classification (Perou) helped to identify new groups of patients with different biological behaviors. A retrospective, descriptive, comparative trial with adjuvant chemotherapy treatment was conducted. Objectives: Analyze the natural history of the subgroups of patients, frequency, site of relapse and Disease-free survival (DFS). Materials and Methods: 200 Medical charts of patients with breast cancer were analyzed from 1997 to 2007, who had received adjuvant treatment without Trastuzumab. The 92, 5 % of Luminal A, 91 % of Luminal B y C, the 75.9 % of Her2 (+) and the 69.2 % of Triple Negative (TN) had received adjuvant therapy with FAC, while 30% of the last two groups were treated with taxanes and anthracyclines. We evaluated the site of the first relapse after adjuvant treatment in relation to the new molecular classification. Log-rank test was used to compare the rates of Disease-free survival (DFS). Results: Frequency: Luminal A (86, 42%) Luminal B y C (65, 33%) Her2 + (33, 17%) TN: (16, 8%) The locoregional relapse in the TN group was 36.4% (P = 0.003), the average of bone relapses were 64.5% on the four groups without statically significance compared to other groups. The CNS had a greater trend in TN groups (16.7%) and Her2+ (13.6%), compared to Luminal Type A-B (0 % y 8.3 %). Disease-free survival (DFS): Luminal A 65.0 ± 5.0 months Luminal B y C 50.3 ± 4.3 months HER2 42.9 ± 5.5 months TN 31.1 ± 7.3 months In the analysis of type A luminal subgroup, a prolonged disease free time was showed when compared with the others subgroups, of major statistical significance Log rank (p = 0.002). Conclusions: Her2 negative and TN tumors have less DFS and a higher locoregional and CNS relapse. No significant financial relationships to disclose.
IL-10-Engineered Human CD4+ Tr1 Cells Eliminate Myeloid Leukemia in an HLA Class I-Dependent Mechanism
Authors: Grazia Locafaro, Grazia Andolfi, Fabio Russo, Luca Cesana, Antonello Spinelli, Barbara Camisa, Fabio Ciceri, Angelo Lombardo, Attilio Bondanza, Maria Grazia Roncarolo, Silvia Gregori
Journal: Molecular Therapy (2017)

T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4+ T cells into T regulatory type 1 (Tr1)-like (CD4IL-10) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models. In the present study, we show that CD4IL-10 cells mediate anti-leukemic effects in vitro and in vivo in a human leukocyte antigen (HLA) class I-dependent but antigen-independent manner. The cytotoxicity mediated by CD4IL-10 cells is granzyme B (GzB) dependent, is specific for CD13+ target cells, and requires CD54 and CD112 expression on primary leukemic target blasts. CD4IL-10 cells adoptively transferred in humanized mouse models directly mediate anti-tumor and anti-leukemic effects. In addition, when co-transferred with peripheral blood mononuclear cells (PBMCs), CD4IL-10 cells contribute to the GvL activity but suppress xenoGvHD mediated by the PBMCs. These findings provide for the first time a strong rationale for CD4IL-10 cell immunotherapy to prevent GvHD and promote GvL in allo-HSCT for myeloid malignancies. T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4+ T cells into T regulatory type 1 (Tr1)-like (CD4IL-10) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models. In the present study, we show that CD4IL-10 cells mediate anti-leukemic effects in vitro and in vivo in a human leukocyte antigen (HLA) class I-dependent but antigen-independent manner. The cytotoxicity mediated by CD4IL-10 cells is granzyme B (GzB) dependent, is specific for CD13+ target cells, and requires CD54 and CD112 expression on primary leukemic target blasts. CD4IL-10 cells adoptively transferred in humanized mouse models directly mediate anti-tumor and anti-leukemic effects. In addition, when co-transferred with peripheral blood mononuclear cells (PBMCs), CD4IL-10 cells contribute to the GvL activity but suppress xenoGvHD mediated by the PBMCs. These findings provide for the first time a strong rationale for CD4IL-10 cell immunotherapy to prevent GvHD and promote GvL in allo-HSCT for myeloid malignancies.
Effects of an Intervention to Reduce Hospitalizations From Nursing Homes
Authors: Robert L. Kane, Peter Huckfeldt, Ruth Tappen, Gabriella Engstrom, Carolina Rojido, David Newman, Zhiyou Yang, Joseph G. Ouslander
Journal: JAMA Internal Medicine (2017)

Medicare payment initiatives are spurring efforts to reduce potentially avoidable hospitalizations.To determine whether training and support for implementation of a nursing home (NH) quality improvement program (Interventions to Reduce Acute Care Transfers [INTERACT]) reduced hospital admissions and emergency department (ED) visits.This analysis compared changes in hospitalization and ED visit rates between the preintervention and postintervention periods for NHs randomly assigned to receive training and implementation support on INTERACT to changes in control NHs. The analysis focused on 85 NHs (36 717 NH residents) that reported no use of INTERACT during the preintervention period.The study team provided training and support for implementing INTERACT, which included tools that help NH staff identify and evaluate acute changes in NH resident condition and document communication between physicians; care paths to avoid hospitalization when safe and feasible; and advance care planning and quality improvement tools.All-cause hospitalizations, hospitalizations considered potentially avoidable, 30-day hospital readmissions, and ED visits without admission. All-cause hospitalization rates were calculated for all resident-days, high-risk days (0-30 days after NH admission), and lower-risk days (≥31 days after NH admission).We found that of 85 NHs, those that received implementation training and support exhibited statistically nonsignificant reductions in hospitalization rates compared with control NHs (net difference, -0.13 per 1000 resident-days; P = .25), hospitalizations during the first 30 days after NH admission (net difference, -0.37 per 1000 resident-days; P = .48), hospitalizations during periods more than 30 days after NH admission (net difference, -0.09 per 1000 resident-days; P = .39), 30-day readmission rates (net change in rate among hospital discharges, -0.01; P = .36), and ED visits without admission (net difference, 0.02 per 1000 resident-days; P = .83). Intervention NHs exhibited a reduction in potentially avoidable hospitalizations overall (net difference, -0.18 per 1000 resident-days, P = .01); however, this effect was not robust to a Bonferroni correction for multiple comparisons.Training and support for INTERACT implementation as carried out in this study had no effect on hospitalization or ED visit rates in the overall population of residents in participating NHs. The results have several important implications for implementing quality improvement initiatives in NHs.clinicaltrials.gov Identifier: NCT02177058.
Prognostic Impact of Circulating Tumor Cells for Breast Cancer Patients Treated in the Neoadjuvant "Geparquattro" Trial
Authors: Sabine Riethdorf, Volkmar Müller, Sibylle Loibl, Valentina Nekljudova, Karsten Weber, Jens Huober, Tanja Fehm, Iris Schrader, Jörn Hilfrich, Frank Holms, Hans Tesch, Christian Schem, Gunter von Minckwitz, Michael Untch, Klaus Pantel
Journal: Clinical Cancer Research (2017)

Purpose: This study aimed to evaluate the prognostic impact of circulating tumor cells (CTC) detected in patients with operable or locally advanced breast cancer before and after neoadjuvant therapy (NT) within the clinical trial GeparQuattro.Experimental Design: Data on CTCs enumerated with the CellSearch system were available for 213 and 207 patients before and after NT, respectively. Associations of CTCs with disease-free survival (DFS) and overall survival (OS) were analyzed by nonparametric Kaplan-Meier estimates and parametric Cox regression.Results: After a median follow-up of 67.1 months, the detection of ≥1 CTC/7.5 mL and ≥2 CTCs/7.5 mL before NT was associated with reduced DFS (P = 0.031 and P < 0.0001, respectively) and OS (P = 0.0057 and P < 0.0001, respectively), whereas CTCs detected after NT did not correlate with DFS or OS. In parametric univariate and multivariate Cox models, ≥1 CTC/7.5 mL, ≥2 CTCs/7.5 mL, and absolute CTC numbers before NT revealed to be independent prognostic parameters of DFS and OS. CTC-negative patients with pathologic complete response (pCR) exhibited the best prognosis, whereas those with CTCs and less tumor response were at high risk of tumor relapse. In HER2 (ERBB2)-positive and triple-negative patients, ≥2 CTCs/7.5 mL detected before NT also were significantly associated with worse DFS and OS.Conclusions: Detection of CTCs before NT is an independent prognostic factor of impaired clinical outcome, and combined with pCR, it could be helpful to stratify breast cancer patients for therapeutic interventions. Clin Cancer Res; 23(18); 5384-93. ©2017 AACR.
Evaluation of clinical and histological criteria and outcome in management of hereditary non-polyposis colorectal carcinoma (HNPCC).
Authors: Elena Tsvetkova, Phillip Williams, Eva Tomiak, Laura Bourns, Timothy R. Asmis, Jean Alfred Maroun, Fawas Halwani
Journal: Journal of Clinical Oncology (2015)

e14552 Background: Lynch syndrome, or HNPCC, is the most common inherited colorectal carcinoma (CRC) syndrome accounting for 2-5% of all cases. Pathologists initiate IHC testing based on patient age and defined histological criteria. This study aimed to evaluate the efficiency of these criteria and their clinical outcome. Methods: All CRC cases diagnosed at The Ottawa Hospital (TOH) from January 2012-July 2013 reviewed. Cases with MMR deficiency were reviewed for Genetics referral rates, treatment, and outcomes. Results: Of 480 cases of CRC, 90 (19%) cases had IHC performed for MMR status with 45 (9%) cases having intact MMR gene expression (MSS) and 45 (9%) deficient (39 MLH1, 4 MSH2, 1 MSH6 and 1 PMS2) (MSI). MLH1 deficient tumors analyzed for BRAF mutation; 9/39 (23%) were negative. 16/90 (18%) patients had strong family history of HNPCC-associated malignancies (8 MSS, 8 MSI); 15 (17%) had personal history of multiple HNPCC-associated cancers (5 MSS, 10 MSI). 31 patients treated with adjuvant chemotherapy (20 MSS, 11 MSI); 15 patients referred for genetic counseling. 3 germline pathogenic mutations identified (1 each in MLH1, MSH2 and PMS2) with 4 cases pending and 2 inconclusive. Histological criteria that were informative are: right colon cancer (82% vs 44%, p = 0.0004), intraepithelial lymphocytes (IEL) (67% vs 31%, p = 0.007), high histologic grade (60% vs 22%, p = 0.0003) and any amount of mucinous differentiation (60% vs 27%, (p = 0.0014). Criteria without statistical significance were mucinous carcinoma ( > 70%), Crohn’s-like lymphoid aggregate (CLLA), stage and tumor size. Conclusions: MSI-H colon cancers are biologically distinctive in their behaviour and outcome. Testing for MSI-H and BRAF-methylation by IHC shows correlation with genetic testing. At TOH incidence of MSI-H with current detection is 0.6% of total CRC cases. Standardization of histological criteria will increase detection rate. We recommend testing on any CRC that fulfils any of the following criterions: age < 70 years, right colon, IEL, high grade or mucinous differentiation. Using this strategy, 62% of total CRC cases need to be tested with a positive predictive value of 57% and negative predictive value of 92%.
Effects of physical condition and body composition on cancer risk in a nationwide cohort of 31,158 men from Finland.
Authors: Jorma Tauno Juhani Sormunen, Melina Arnold, Isabelle Soerjomataram, Eero Pukkala
Journal: Journal of Clinical Oncology (2017)

1565 Background: Regular physical activity seems to protect men from colorectal cancer and possibly also from prostate cancer. In the case of other cancers the evidence is adding up, and physical activity seems to have a small protective effect to its incidence. The aim of this study was to analyse the effects of physical condition (PC) in early adulthood on cancer incidence later in life. Methods: We collected data on general health, anthropometry and PC for 31,158 Finnish men born in 1958 from the time of their military service between the ages of 17 and 30 years. Using linkage with the Finnish Cancer Registry, all men were followed-up for cancer incidence up to 2014. Results: Overweight and obesity (body mass index (BMI) ≥ 25 kg/m 2 ) were associated with an increased overall cancer risk [hazard ratio (HR): 1.08, 95% confidence interval (CI): 0.89-1.30] when compared to those with BMI &lt; 25 kg/m 2 . Those with normal weight but bad PC had an increased risk of all cancers combined as compared to those with normal weight and good PC (HR 1.18, 95% CI: 1.01-1.38), which further increased in those who were also overweight (HR 1.30, 95% CI: 1.01-1.69). We noticed an increased overall cancer risk in men in who entered service with minor health problems (HR 1.46, 95% CI 1.19-1.80), when compared to those that were completely healthy. This was especially observed for advanced prostate cancer (HR: 3.35, 95% CI: 1.14-9.90). Increased HRs, yet statistically insignificant, were also seen for colorectal and other obesity-related cancers. Conclusions: Good PC at young age seems to protect men from cancer later in life. Early adulthood obesity, when combined with bad PC, seems to further increase cancer risk.
Harnessing Genomic Biobanks to Understand Obesity in Cardiometabolic Disease
Authors: Christopher J. O’Donnell
Journal: JAMA Cardiology (2017)

Donald M. Lyall, PhD; Carlos Celis-Morales, PhD; Joey Ward, BSc; Stamatina Iliodromiti, MD; Jana J. Anderson, PhD; Jason M. R. Gill, PhD; Daniel J. Smith, PhD; Uduakobong Efanga Ntuk, PhD, MSc; Daniel F. Mackay, PhD; Michael V. Holmes, MD, PhD; Naveed Sattar, MD, PhD; Jill P. Pell, MD
The impact of frailty on intensive care unit outcomes: a systematic review and meta-analysis
Authors: John Muscedere, Braden Waters, Aditya Varambally, Sean M. Bagshaw, J. Gordon Boyd, David Maslove, Stephanie Sibley, Kenneth Rockwood
Journal: Intensive Care Medicine (2017)

Functional status and chronic health status are important baseline characteristics of critically ill patients. The assessment of frailty on admission to the intensive care unit (ICU) may provide objective, prognostic information on baseline health. To determine the impact of frailty on the outcome of critically ill patients, we performed a systematic review and meta-analysis comparing clinical outcomes in frail and non-frail patients admitted to ICU. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PubMed, CINAHL, and Clinicaltrials.gov. All study designs with the exception of narrative reviews, case reports, and editorials were included. Included studies assessed frailty in patients greater than 18 years of age admitted to an ICU and compared outcomes between fit and frail patients. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were hospital and long-term mortality. We also determined the prevalence of frailty, the impact on other patient-centered outcomes such as discharge disposition, and health service utilization such as length of stay. Ten observational studies enrolling a total of 3030 patients (927 frail and 2103 fit patients) were included. The overall quality of studies was moderate. Frailty was associated with higher hospital mortality [relative risk (RR) 1.71; 95% CI 1.43, 2.05; p < 0.00001; I 2 = 32%] and long-term mortality (RR 1.53; 95% CI 1.40, 1.68; p < 0.00001; I 2 = 0%). The pooled prevalence of frailty was 30% (95% CI 29–32%). Frail patients were less likely to be discharged home than fit patients (RR 0.59; 95% CI 0.49, 0.71; p < 0.00001; I 2 = 12%). Frailty is common in patients admitted to ICU and is associated with worsened outcomes. Identification of this previously unrecognized and vulnerable ICU population should act as the impetus for investigating and implementing appropriate care plans for critically ill frail patients. Registration: PROSPERO (ID: CRD42016053910).