tbuckley/cabot-search huggingface dataset:
Outcomes of percutaneous coronary intervention in ST elevation myocardial infarction in patients with metastatic diseases.
Authors: Achuta Kumar Guddati, Gagan Kumar, Parijat Saurav Joy, Creticus Petrov Marak
Journal: Journal of Clinical Oncology (2015)

e17766 Background: The role of percutaneous coronary intervention (PCI) with stenting in the management of acute ST elevation myocardial infarction (STEMI) has been well demonstrated. However it has not been studied in patients with metastatic cancer since it is an exclusion criterion for most case-controlled studies. Methods: Using the Nationwide Inpatient Sample Database (2000 to 2009), patients > 18 years with metastatic cancer were identified using ICD-9-CM codes. This group was examined whether they underwent PCI with stenting. Statistical comparisons were performed using chi square test and Wilcoxon rank test. In-hospital mortality was examined with multivariate logistic regression model in a propensity matched sample to study whether PCI with stenting was independently associated with better outcomes in this group. Results: There were 10,102,999 estimated adult discharges with metastatic cancer from 2000 to 2009. Of these, 49,515 (0.49%) had a primary diagnosis of STEMI and of these, 7189(14.5%) underwent PCI with stenting. The in-hospital mortality in patients with metastatic disease with STEMI was significantly higher than those without STEMI (16.6% vs 10.3%, p < 0.001). The in-hospital mortality in those receiving PCI with stenting was significantly lower (8.5% vs 18%, p < 0.001). Even after adjusting for age, gender, race, insurance, hospital characteristics and year, those who did not receive stenting had higher odds of mortality (OR 2.26; 95%CI 1.85-2.75). Median LOS in survivors was significantly shorter in those undergoing PCI with stenting (4 days vs. 5 days, p < 0.001). These patients also were discharged to home more often (71.8% vs 42.2%, p < 0.001). Conclusions: Benefits of PCI with stenting for STEMI (decreased in-hospital mortality and decreased LOS) occur similarly in patients with metastatic disease as has been reported for other patient groups. This study shows that seemingly aggressive interventions such as PCI with stenting may still have a role in the care of patients with metastatic disease. Further studies are needed to examine whether such interventions improve the quality of life and contribute to a meaningful prolongation of survival in these patients.
PPM1D Mutations Are Rare in De Novo and Therapy-Related Acute Myeloid Leukemia
Authors: Mutlu Kartal-Kaess, Tilmann Bochtler, Bianca Kraft, Michael Kirsch, Bettina Maier, Friedrich Stoelzel, Brigitte Mohr, Michael Kramer, Christoph Rollig, Christian Thiede, Martin Bornhäuser, Gerhard Ehninger, Carsten Müller-Tidow, Alwin Krämer
Journal: Blood (2018)
Clinicopathologic and genomic characterization of parenchymal brain metastases (BM) in prostate cancer (PCa).
Authors: Jose Mauricio S. C. Mota, Min Yuen Teo, Andrea Knezevic, Richard Martin Bambury, Vaios Hatzoglou, Karen A. Autio, Wassim Abida, Anuradha Gopalan, Samson Fine, Daniel Costin Danila, Dana E. Rathkopf, Susan F. Slovin, Robert J. Young, Victor E. Reuter, Glenn Heller, Howard I. Scher, Michael J. Morris
Journal: Journal of Clinical Oncology (2019)

227 Background: BM are rarely seen with PCa, but the incidence may be increasing with contemporary therapies. We sought to evaluate the clinical phenotypes associated with BM and their outcomes. Methods: The MSKCC institutional clinical database from 01/2001 through 06/2018 was reviewed to identify pts with PCa and (1) secondary malignant neoplasm of the brain / spinal cord per ICD-9 (198.3), (2) radiation treatment plan targeting the brain, (3) craniotomy, or (3) notes containing the terms “brain metastasis”. Medical charts were reviewed to confirm diagnosis (dx) and extract data. The logrank statistic and the Cox proportional hazards model were used to determine correlations with overall survival (OS). Results: Of 575 pts who met search criteria, 43 had BM and prostate adenocarcinoma. At PCa dx, median age was 60 years (range: 44 –77 years) and 51% had metastasis (mets). Median time from PCa dx to BM was 4.2 years. At the time of BM dx, 36 had metastatic castration-resistant PCa (mCRPC), 55% had liver mets and 66% had lung mets. 45% had ≥3 lines of therapy for mCRPC prior to BM dx (abiraterone/enzalutamide: 47%, chemotherapy: 91%). The median OS from BM dx was 5.8 months (Table). 4/10 pts with sequencing data had germline mutations ( ATM, BRCA1, BRIP1, MUTYH). To date, 4 BM were sequenced, and 3 showed PTEN loss. Conclusions: BM associated with a poor prognosis and occurred after prolonged treatment. Presence of liver/lung mets, 3 or more BM, and surgical resection (SR) prognosticate for OS in univariate analysis; SR in multivariate analysis. Further analysis is needed to determine if germline mutations and/or PTEN loss associate with BM. [Table: see text]
Coronary Angiography after Cardiac Arrest — The Right Timing or the Right Patients?
Authors: Benjamin S. Abella, David F. Gaieski
Journal: New England Journal of Medicine (2019)

The treatment of patients who are comatose after out-of-hospital cardiac arrest involves a complex, multidisciplinary approach that includes the use of targeted temperature management, aggressive hemodynamic management, electroencephalographic monitoring, and consideration of coronary angiography.1 However, studies suggest that despite these interventions, 30 to 50% of these patients die before hospital discharge, and a substantial percentage of long-term survivors have neurologic and cardiac sequelae.2,3 Although clinically significant coronary disease is common in patients who have cardiac arrest,4 the selection of patients for coronary angiography remains controversial. The general consensus is that comatose patients who have had cardiac arrest with evidence of . . .
Patient Safety Outcomes under Flexible and Standard Resident Duty-Hour Rules
Authors: Jeffrey H. Silber, Lisa M. Bellini, Judy A. Shea, Sanjay V. Desai, David F. Dinges, Mathias Basner, Orit Even-Shoshan, Alexander S. Hill, Lauren L. Hochman, Joel T. Katz, Richard N. Ross, David M. Shade, Dylan S. Small, Alice L. Sternberg, James Tonascia, Kevin G. Volpp, David A. Asch
Journal: New England Journal of Medicine (2019)

Concern persists that extended shifts in medical residency programs may adversely affect patient safety.We conducted a cluster-randomized noninferiority trial in 63 internal-medicine residency programs during the 2015-2016 academic year. Programs underwent randomization to a group with standard duty hours, as adopted by the Accreditation Council for Graduate Medical Education (ACGME) in July 2011, or to a group with more flexible duty-hour rules that did not specify limits on shift length or mandatory time off between shifts. The primary outcome for each program was the change in unadjusted 30-day mortality from the pretrial year to the trial year, as ascertained from Medicare claims. We hypothesized that the change in 30-day mortality in the flexible programs would not be worse than the change in the standard programs (difference-in-difference analysis) by more than 1 percentage point (noninferiority margin). Secondary outcomes were changes in five other patient safety measures and risk-adjusted outcomes for all measures.The change in 30-day mortality (primary outcome) among the patients in the flexible programs (12.5% in the trial year vs. 12.6% in the pretrial year) was noninferior to that in the standard programs (12.2% in the trial year vs. 12.7% in the pretrial year). The test for noninferiority was significant (P = 0.03), with an estimate of the upper limit of the one-sided 95% confidence interval (0.93%) for a between-group difference in the change in mortality that was less than the prespecified noninferiority margin of 1 percentage point. Differences in changes between the flexible programs and the standard programs in the unadjusted rate of readmission at 7 days, patient safety indicators, and Medicare payments were also below 1 percentage point; the noninferiority criterion was not met for 30-day readmissions or prolonged length of hospital stay. Risk-adjusted measures generally showed similar findings.Allowing program directors flexibility in adjusting duty-hour schedules for trainees did not adversely affect 30-day mortality or several other measured outcomes of patient safety. (Funded by the National Heart, Lung, and Blood Institute and Accreditation Council for Graduate Medical Education; iCOMPARE ClinicalTrials.gov number, NCT02274818.).
Cocultures of human colorectal tumor spheroids with immune cells reveal the therapeutic potential of MICA/B and NKG2A targeting for cancer treatment
Authors: Tristan Courau, Julie Bonnereau, Justine Chicoteau, Hugo Bottois, Romain Remark, Laura Assante Miranda, Antoine Toubert, Mathieu Blery, Thomas Aparicio, Matthieu Allez, Lionel Le Bourhis
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Immunotherapies still fail to benefit colorectal cancer (CRC) patients. Relevant functional assays aimed at studying these failures and the efficacy of cancer immunotherapy in human are scarce. 3D tumor cultures, called tumor organoids or spheroids, represent interesting models to study cancer treatments and could help to challenge these issues. <h3>Methods</h3> We analyzed heterotypic cocultures of human colon tumor-derived spheroids with immune cells to assess the infiltration, activation and function of T and NK cells toward human colorectal tumors in vitro. <h3>Results</h3> We showed that allogeneic T and NK cells rapidly infiltrated cell line-derived spheroids, inducing immune-mediated tumor cell apoptosis and spheroid destruction. NKG2D, a key activator of cytotoxic responses, was engaged on infiltrating cells. We thus assessed the therapeutic potential of an antibody targeting the specific ligands of NKG2D, MICA and MICB, in this system. Anti-MICA/B enhanced immune-dependent destruction of tumor spheroid by driving an increased NK cells infiltration and activation. Interestingly, tumor cells reacted to immune infiltration by upregulating HLA-E, ligand of the inhibitory receptor NKG2A expressed by CD8 and NK cells. NKG2A was increased after anti-MICA/B treatment and, accordingly, combination of anti-MICA/B and anti-NKG2A was synergistic. These observations were ultimately confirmed in a clinical relevant model of coculture between CRC patients-derived spheroids and autologous tumor-infiltrating lymphocytes. <h3>Conclusions</h3> Altogether, we show that tumor spheroids represent a relevant tool to study tumor-lymphocyte interactions on human tissues and revealed the antitumor potential of immunomodulatory antibodies targeting MICA/B and NKG2A.
State variation in Medicare Part D and choice of initial endocrine therapy for breast cancer.
Authors: Liliana E Pezzin, John A. Charlson, Emily McGinley, Purushottam Laud, Joan Marie Neuner, Ann Nattinger
Journal: Journal of Clinical Oncology (2015)

6532 Background: Evidence suggests that drug utilization under Medicare Part D has been uneven, varying significantly by geographic region. We sought to examine the extent to which geographic variation in Part D plan characteristics contribute to the variation in choice of initial hormone therapy agent among women with incident breast cancer. Methods: Two-stage multivariate regression analyses applied to 23840 Medicare beneficiaries with incident breast cancer in 06-07. The first stage determined the effect of state of residence on the probability of having an aromatase inhibitor (AI, as opposed to tamoxifen) as the initial endocrine therapy, controlling for confounders. The second stage provided estimates of state-specific Part D plan characteristics on state variation in choice of initial hormone therapy. Results: There was substantial residual geographic variation in the likelihood of using an AI as the initial endocrine therapy, despite controls for socioeconomic status, breast cancer treatment, and other factors. Regression-adjusted probabilities of starting an AI ranged from 53.4% in Wyoming to 82.4% in New York. Nineteen states (38%) had adjusted probabilities significantly different than the national mean: 13 of those were above, while the remaining six states –WY, MT, MN, IA, NH, AR-- were significantly below the national mean. Results from the second stage revealed that variation in characteristics of Part D plans across states explained over one- third (35%) of the overall state-level variability in initiating endocrine therapy with an AI. A higher number of drug plans with cost sharing above the mean, greater spread in deductible costs and a greater spread in monthly drug premiums were associated with lower adjusted state probabilities of initiating an AI. In contrast, a higher number of drug plans with monthly premiums above the state mean and higher mean cost sharing were both positively associated with likelihood of starting on an AI. Conclusions: This study suggests that variability in use of AIs-- the newer, more effective breast cancer oral therapy-- could be significantly reduced by changing the benefit design underlying states’ Part D plans.
Is the outcome of glioblastoma multiforme treated in the community affected by poor socioeconomic factors?
Authors: Anuradha Avinash Belur, Arun Kumar Arumugam Raajasekar, Bernadine Donahue, Yiwu Huang, Peter Homel, Alan Bennett Astrow, Yiqing Xu
Journal: Journal of Clinical Oncology (2015)

e17563 Background:Studies of health care disparities have suggested patients with poorer socioeconomic status have worse outcomes.Outcome of Glioblastoma Multiforme (GBM) is affected by extent of resection and RPA class.Median survival (MS) in RPA class IV and V who received adjuvant chemoradiation (CRT) was 15 and 10 months. Patients treated outside of a clinical trial may have poor socioeconomic status and shorter survival.We aimed to evaluate the impact of socioeconomic factors (SEF) on the outcome of patients treated in a community cancer center that serves population with diverse socioeconomic backgrounds. Methods: Retrospective analysis of all patients with GBM between 1/2008-5/2014. We selected 6 unfavorable SEFs(1) Medicaid Insurance (2) non-English speaking requiring translation (3) no family at first visit (4) or at last visit (5) need of home health aide (HHA)(6) need of transportation arrangement. Outcomes included MS, completion of concurrent chemoradiation CRT and adjuvant Temozolomide (TMZ) Results: 58 patients (32 M, 26F) with median age of 64 (range 29-85) were identified; 16 patients > 70. 34 (58%) had Medicaid, 22 (37%) were non-English speaking and 10 (17%) required an HHA. The median number of SEFs was 2 (range 0 – 8), and 12 patients (36%) had ≥ 3 SEFs. Fourteen patients (24 %) were RPA class IV and 44 (76 %) were class V and MS were 12 m (95% CI, 10.2 - 13.8) and 11 m (95% CI, 6.9 - 15.1) respectively. 54 (93%) patients completed CRT, 21(36%) completed adjuvant TMZ. In univariate analysis none of the SEFs, except for the presence of HHA, showed adverse effect on any outcome. For those requiring an HHA versus no HHA, the MS was 7m versus 13m (p = 0.035) and the completion rate for CRT was 72 % vs 97% (p = 0.019). The sum score of all the SEFs did not affect any outcome. Conclusions: Despite poor socioeconomic status our patients with GBM had MS comparable to those reported in clinical trials. Neither individual nor aggregate SEFs adversely affected the outcomes except for HHA. The outcome of GBM treated in the community may not be affected by poor SEFs when standard medical and supportive care can be delivered. The necessity of HHA could indicate worse physical function in addition to low income and poor family support.
A Practical Review of Proteasome Pharmacology
Authors: Tiffany A. Thibaudeau, David M. Smith
Journal: Pharmacological Reviews (2019)

The ubiquitin proteasome system (UPS) degrades individual proteins in a highly regulated fashion and is responsible for the degradation of misfolded, damaged, or unneeded cellular proteins. During the past 20 years, investigators have established a critical role for the UPS in essentially every cellular process, including cell cycle progression, transcriptional regulation, genome integrity, apoptosis, immune responses, and neuronal plasticity. At the center of the UPS is the proteasome, a large and complex molecular machine containing a multicatalytic protease complex. When the efficiency of this proteostasis system is perturbed, misfolded and damaged protein aggregates can accumulate to toxic levels and cause neuronal dysfunction, which may underlie many neurodegenerative diseases. In addition, many cancers rely on robust proteasome activity for degrading tumor suppressors and cell cycle checkpoint inhibitors necessary for rapid cell division. Thus, proteasome inhibitors have proven clinically useful to treat some types of cancer, especially multiple myeloma. Numerous cellular processes rely on finely tuned proteasome function, making it a crucial target for future therapeutic intervention in many diseases, including neurodegenerative diseases, cystic fibrosis, atherosclerosis, autoimmune diseases, diabetes, and cancer. In this review, we discuss the structure and function of the proteasome, the mechanisms of action of different proteasome inhibitors, various techniques to evaluate proteasome function in vitro and in vivo, proteasome inhibitors in preclinical and clinical development, and the feasibility for pharmacological activation of the proteasome to potentially treat neurodegenerative disease.
Influenza C virus in pre-school children with respiratory infections: retrospective analysis of data from the national influenza surveillance system in Germany, 2012 to 2014
Authors: Annemarie Fritsch, Brunhilde Schweiger, Barbara Biere
Journal: Eurosurveillance (2019)

IntroductionRecent data on influenza C virus indicate a possible higher clinical impact in specified patient populations than previously thought.AimWe aimed to investigate influenza C virus circulation in Germany.MethodsA total of 1,588 samples from 0 to 4 year-old children presenting as outpatients with influenza-like illness (ILI) or acute respiratory infection were analysed retrospectively. The samples represented a subset of all samples from the German national surveillance system for influenza in this age group in 2012-14. The presence of influenza C virus was investigated by real-time PCR. For positive samples, information on symptoms as well as other respiratory virus co-infections was considered. Retrieved influenza C viral sequences were phylogenetically characterised.ResultsInfluenza C viral RNA was detected in 20 (1.3% of) samples, including 16 during the 2012/13 season. The majority (18/20) of influenza C-positive patients had ILI according to the European Union definition, one patient had pneumonia. Viruses belonged to the C/Sao Paulo and C/Kanagawa lineages. Most (11/20) samples were co-infected with other respiratory viruses.ConclusionOur data are the first on influenza C virus circulation in Germany and notably from a European national surveillance system. The low detection frequency and the identified virus variants confirm earlier observations outside a surveillance system. More virus detections during the 2012/13 season indicate a variable circulation intensity in the different years studied. Influenza C virus can be considered for ILI patients. Future studies addressing its clinical impact, especially in patients with severe disease are needed.
Abstract P368: Impact of Subclinical Hypoglycemia on Mortality: Findings From the Third National Health and Nutrition Examination Survey
Authors: Parag A Chevli, Muhammad I Ahmad, Muhammad A Anees, Elsayed Z Soliman
Journal: Circulation (2019)

Introduction: Hypoglycemia has shown to be associated with increased risk of cardiovascular disease (CVD) events in diabetics. Although, very few studies have investigated incident CVD and all-cause mortality with regard to low fasting plasma glucose (FPG) in the population without diabetes. Methods: This analysis included 8497 participants (mean age=44 years, 53% women, 40% whites), free of CVD and diabetes at baseline, from the Third National Health and Nutrition Examination Survey (NHANES-III). Cox proportional hazards analysis, was used to report hazard ratio (HR) and 95% confidence interval (CI) for association of FPG categories (80-99 mg/dl (reference) &lt;80 mg/dl, 100-125 mg/dl and ≥126 mg/dl) at baseline with CVD and all-cause mortality over the median follow-up of 14 years. Results: There were 570(6.7%) CVD and 2101(24.7%) all-cause deaths over the period of 14 years. Compared to referent category, in a model adjusted for age, sex, race, smoking, physical activity, systolic blood pressure, antihypertensive medications, body mass index and total cholesterol, low FPG was associated with significantly increased risk of CVD and all-cause mortality [HR(95% CI): 1.79(1.04-3.08) and 1.35(1.02-1.78) respectively]. This association was stronger among men than women for CVD mortality [HR(95%CI): 4.29(2.35-7.84) vs. 0.40(0.10-1.65) respectively; interaction p-value=0.0002] and all-cause mortality [HR(95%CI): 1.84(1.23-2.75) vs. 1.08(0.74-1.59), respectively; interaction p-value=0.02]. There was no significant association of impaired and diabetic range FPG with CVD mortality, but diabetic range FPG was significantly associated with increased risk of all-cause mortality [HR(95%CI): 1.25(1.04-1.51)]. Conclusion: This analysis from a large, population-based survey revealed that subclinical hypoglycemia in non-diabetic individuals is a strong risk factor for CVD and all-cause mortality. Although, it is unknown whether avoiding hypoglycemia will reduce this risk.
Abstract P296: Almond Consumption in Cardiovascular Disease: Markov Model and Health Economic Evaluation
Authors: Jifan Wang, Michelle A Lee-Bravatti, Gowri Raman, Esther E Avendano, Elizabeth J Johnson
Journal: Circulation (2019)

Background: Heart disease is the leading cause of death in the United States, with over 630,000 deaths in 2015 and over 140,000 stroke-related deaths in the same year. Our recent meta-analysis found lower LDL levels with almond intake. According to the US Food and Drug Administration, 1.5 oz. of any tree nut intake may reduce the risk of cardiovascular disease (CVD). The objective of this study was to use Markov models to examine the cost-effectiveness of almond consumption in preventing CVD. Methods: Decision trees with Markov models were developed for consuming 1.5 oz. almond per day versus no almond and myocardial infarction (MI) and stroke, respectively. We set 20 cycles for Markov models with a 1-year time frame for each cycle. Half-cycle correction was applied in the models. In the MI model, people who survived after having MI were considered as having chronic heart disease; in the stroke model, any type of stroke was included. Quality-adjusted life years at each stage were used as the effectiveness. We derived the parameters from published literature and public sources. Results: Consuming almonds had more effectiveness although it led to more cost. It was not preferred for either MI or stroke. When setting the willingness-to-pay as $50,000, the annual net monetary benefit (NMB) in the MI model was $954,542 for consuming almonds and $958,482 for not consuming almonds; the NMB in the stroke model was $945,096 and $947,414 for the almond and the non-almond, respectively. Conclusion: Consuming 1.5 oz. almond per day may not be cost-effective enough in terms of preventing MI and stroke. Further studies are required to evaluate the overall effect of almond on CVD.