tbuckley/cabot-search huggingface dataset:
Abstract MP078: Are Patients With Less Activation at Greater Risk of Declines in Health-related Quality of Life After Hospitalization for an Acute Coronary Syndrome?
Authors: Nathaniel A Erskine, Barbara Gandek, Molly E Waring, Darleen M Lessard, Catarina I Kiefe, Robert J Goldberg
Journal: Circulation (2017)

Background: Patient activation comprises the knowledge, skills, and confidence for self-care, and may lead to better health outcomes. Hypothesis: We hypothesized that less-activated survivors of a hospitalization for an acute coronary syndrome (ACS) would be more likely to experience declines in health-related quality of life than more activated patients. Methods: We studiedpatients from 6 medical centers in central Massachusetts and Georgia who had been hospitalized for an ACS between 2011 and 2013. At 1 month after hospital discharge, patients completed the 6-item Patient Activation Measure and at 1, 3, and 6 months after discharge generic physical (SF-36 PCS), generic mental (SF-36 MCS), and disease-specific (SAQ - Seattle Angina Questionnaire) health-related quality of life (QOL) scales. Four categories of 1-month activation levels were defined. Multinomial logistic regression estimated odds ratios were calculated for clinically meaningful changes in QOL, with patients in the highest level of activation serving as the referent group, adjusting for sociodemographic and clinical confounders. Results: Patients (n=1,042) were on average 62 years old, 34% were female, and 87% were non-Hispanic white; 10% and 29% of patients were in the lowest and highest levels of activation, respectively. Higher proportions of patients in the least activated group vs. the most activated group tended to experience clinically meaningful declines in QOL, for all scales and both follow-up periods (Table). Least activated patients had significantly higher adjusted odds of experiencing clinically meaningful declines in MCS and SAQ scores from 1 to 6 months after hospital discharge, but not PCS scores, with a similar pattern observed between 1 and 3 months after hospital discharge. Conclusions: Following hospitalization for an ACS, patients with low activation may be more likely to have declines in mental and disease-specific health-related QOL than highly activated patients, identifying a group at high risk of poor outcomes.
Medizinische Welt, Stuttgart
Journal: JAMA (1966)

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GOBLET: A phase 1/2 multiple-indication biomarker, safety, and efficacy study in advanced or metastatic gastrointestinal cancers exploring treatment combinations with pelareorep and atezolizumab.
Authors: Dirk Arnold, Maike Collienne, Grey A Wilkinson, Houra Loghmani, Thomas Charles Heineman
Journal: Journal of Clinical Oncology (2022)

TPS216 Background: Checkpoint blockade therapy only benefits a small subset of GI cancer patients (approximately 4%) with microsatellite instability-high (MSI-H) tumors, which are characterized as immunologically ‘hot’ (Bonneville et al., 2017). Most GI cancers, however, have microsatellite stable (MSS) tumors, which have an immunologically “cold” phenotype with fewer genetic mutations, reduced immune cell infiltration, and downregulated immune checkpoint proteins. These attributes make MSS tumors resistant to conventional immunotherapy including checkpoint blockade therapy (Ooki et al., 2021). Pelareorep is a naturally occurring, non-genetically modified reovirus. Upon intravenous administration, pelareorep selectively kills tumor cells and promotes several immunologic effects that prime tumors to respond to checkpoint blockade. These include the stimulation of tumor-directed innate and adaptive immune responses, increased T cell infiltration, expansion of new T cell clones, and increased PD-L1 expression in tumors (Samson et al., 2018, Manso et al. 2021 AACR). Given its expected synergy with checkpoint blockade, as well as its encouraging efficacy in prior GI cancer studies (Mahalingam et al. 2020), the GOBLET study is designed to evaluate pelareorep plus atezolizumab in multiple GI cancer indications. Methods: GOBLET is an open-label, non-randomized, multiple-cohort, phase 1/2 study in patients with advanced or metastatic GI cancers. This study employs a Simon two-stage design. Stage 1 comprises four treatment groups: Cohort 1 – First-line pancreatic cancer treated with pelareorep plus atezolizumab and chemotherapy (gemcitabine and nab-paclitaxel) (N = 12); Cohort 2 – First-line MSI-H colorectal cancer (CRC) treated with pelareorep plus atezolizumab (N = 19); Cohort 3 – Third-line CRC treated with pelareorep plus atezolizumab and chemotherapy (trifluridine/tipiracil) (N = 14); and Cohort 4 – Second-line or later squamous cell carcinoma of the anal canal treated with pelareorep plus atezolizumab (N = 10). The first 3-6 patients enrolled into the chemotherapy-containing cohorts (Cohorts 1 and 3) comprise a safety run-in that must be successfully concluded prior to enrolling additional patients into these cohorts. The primary objectives are safety and efficacy based on objective response rate (ORR) at week 16. Any cohort showing a promising ORR in Stage 1, based on pre-specified criteria, may be advanced to Stage 2 and enroll additional patients. Clinical trial information: 2020-003996-16.
Maternal and early life exposures and their potential to influence development of the microbiome
Authors: Erin E. Bolte, David Moorshead, Kjersti M. Aagaard
Journal: Genome Medicine (2022)

Abstract At the dawn of the twentieth century, the medical care of mothers and children was largely relegated to family members and informally trained birth attendants. As the industrial era progressed, early and key public health observations among women and children linked the persistence of adverse health outcomes to poverty and poor nutrition. In the time hence, numerous studies connecting genetics (“nature”) to public health and epidemiologic data on the role of the environment (“nurture”) have yielded insights into the importance of early life exposures in relation to the occurrence of common diseases, such as diabetes, allergic and atopic disease, cardiovascular disease, and obesity. As a result of these parallel efforts in science, medicine, and public health, the developing brain, immune system, and metabolic physiology are now recognized as being particularly vulnerable to poor nutrition and stressful environments from the start of pregnancy to 3 years of age. In particular, compelling evidence arising from a diverse array of studies across mammalian lineages suggest that modifications to our metagenome and/or microbiome occur following certain environmental exposures during pregnancy and lactation, which in turn render risk of childhood and adult diseases. In this review, we will consider the evidence suggesting that development of the offspring microbiome may be vulnerable to maternal exposures, including an analysis of the data regarding the presence or absence of a low-biomass intrauterine microbiome.
Corrigenda
Authors: Daniel Jackson, William Busse, Alkis Togias, James Gern, Mathew Altman
Journal: Journal of Allergy and Clinical Immunology (2020)

corticosteroids on COVID-19 outcomes.This is highlighted by preliminary findings in a recent study demonstrating the efficacy of dexamethasone in reducing mortality in critically ill patients with COVID-19, but showing no benefit in those not requiring respiratory support. 4Furthermore, our study 5 demonstrated a ''dose-response,'' with greater degrees of respiratory allergy being associated with larger reductions in angiotensin-converting enzyme 2 gene expression in the nasal epithelium, and the impact of suppressing type 2 inflammation in these individuals is not currently known.Thus, we agree that strategies targeting the upper airway for the prevention and/or treatment of COVID-19 are of significant interest.Studies with nasal/inhaled corticosteroids as postexposure prophylaxis for very early stages of the disease (prehospitalization) may be worth considering.Furthermore, various additional approaches are available for consideration, including topical therapy with intranasal antivirals, immune stimulants, and/or vaccines.
Risk of Cardiometabolic Risk Factors in Women With and Without a History of Breast Cancer: The Pathways Heart Study
Authors: Marilyn L. Kwan, Richard K. Cheng, Carlos Iribarren, Romain Neugebauer, Jamal S. Rana, Mai Nguyen-Huynh, Zaixing Shi, Cecile A. Laurent, Valerie S. Lee, Janise M. Roh, Hanjie Shen, Eileen Rillamas-Sun, Margarita Santiago-Torres, Dawn L. Hershman, Lawrence H. Kushi, Heather Greenlee
Journal: Journal of Clinical Oncology (2022)

The incidence of cardiometabolic risk factors in breast cancer (BC) survivors has not been well described. Thus, we compared risk of hypertension, diabetes, and dyslipidemia in women with and without BC.Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California (KPNC) were identified and matched 1:5 to noncancer controls on birth year, race, and ethnicity. Cumulative incidence rates of hypertension, diabetes, and dyslipidemia were estimated with competing risk of overall death. Subdistribution hazard ratios (sHRs) were estimated by Fine and Gray regression, adjusted for cardiovascular disease-related risk factors, and stratified by treatment and body mass index (BMI).A total of 14,942 BC cases and 74,702 matched controls were identified with mean age 61.2 years and 65% non-Hispanic White. Compared with controls, BC cases had higher cumulative incidence rates of hypertension (10.9% v 8.9%) and diabetes (2.1% v 1.7%) after 2 years, with higher diabetes incidence persisting after 10 years (9.3% v 8.8%). In multivariable models, cases had higher risk of diabetes (sHR, 1.16; 95% CI, 1.07 to 1.26) versus controls. Cases treated with chemotherapy (sHR, 1.23; 95% CI, 1.11 to 1.38), left-sided radiation (sHR, 1.29; 95% CI, 1.13 to 1.48), or endocrine therapy (sHR, 1.23; 95% CI, 1.12 to 1.34) continued to have higher diabetes risk. Hypertension risk was higher for cases receiving left-sided radiation (sHR, 1.11; 95% CI, 1.02 to 1.21) or endocrine therapy (sHR, 1.10; 95% CI, 1.03 to 1.16). Normal-weight (BMI < 24.9 kg/m2) cases had higher risks overall and within treatment subgroups versus controls.BC survivors at KPNC experienced elevated risks of diabetes and hypertension compared with women without BC depending on treatments received and BMI. Future studies should examine strategies for cardiometabolic risk factor prevention in BC survivors.
Comprehensive genomic profiling (CGP)-informed personalized molecular residual disease (MRD) detection: An exploratory analysis from the PREDATOR study of metastatic colorectal cancer (mCRC) patients undergoing surgical resection.
Authors: Halla Nimeiri, Amanda Young, Russell Madison, Alexander D. Fine, Ole Gjoerup, Fotios Loupakis, Matteo Fassan, Sara Lonardi, Shruti Sharma, Hsin-Ta Wu, Alexey Aleshin, Elise Renkonen, Priti Hegde
Journal: Journal of Clinical Oncology (2022)

187 Background: Detection of MRD following metastatic liver resection in advanced CRC patients is associated with poor prognosis with high rate of relapse. Nevertheless, there is currently no standard of care to guide further therapy after curative intent surgery. MRD detection has the promise to be implemented into standard of care and guide treatment decision making. Here we establish feasibility of MRD detection using Foundation Medicine’s novel tissue-informed personalized monitoring assay, FoundationOne Tracker (F1T), in mCRC patients undergoing surgical resection with curative intent. Methods: Tissue-based CGP was performed retrospectively on a cohort of 72 patients from the PREDATOR trial. Trackable patient-specific single nucleotide variants were selected using a novel computational approach negating the need for buffy coat sequencing to filter germline variants. Personalized multiplex PCR was used to detect and evaluate prognostic value of ctDNA from plasma collected at MRD timepoint post-surgery (median 27 days, range 8-99.5). Median follow-up of patients in the overall population was 10.7 months (range: 0.9-53.8 months). Survival analyses were performed using the Kaplan-Meier Estimator and Cox regression. Results: Post-surgical F1T analysis was successful on 96% of cases (69/72). CGP analysis revealed at least one driver mutation in 57% of samples (41/72) including KRAS/NRAS (46%) and BRAF mutations (3%). MRD was detected in 45% (31/69) of patients, of which 94% (29/31) had progressed at the time of the data cut. Median progression -free survival (PFS) was 3.2 months (2.1-7.1) in ctDNA-positive vs 28 months (20.9-NA) in ctDNA-negative population (HR 5, CI 2.7-9.3, p&lt;0.001). Median overall survival (OS) was 31.6 months in ctDNA-positive vs not reached in ctDNA-negative group (HR 27, CI 3.6-205, p&lt;0.001). Conclusions: CGP-informed post-operative MRD detection is a strong prognostic biomarker and correlates with survival outcomes in patients with resected mCRC. F1T is a novel and convenient technological approach to MRD detection utilizing highly validated FMI testing to reveal potentially targetable mutations and inform personalized ctDNA monitoring. These results demonstrate the ability of F1T to accurately detect MRD in mCRC patients following surgical resection, without the need for germline sequencing.
COVID-19: learning from experience
Authors: None The Lancet
Journal: The Lancet (2020)

Over the past 2 weeks, the coronavirus disease 2019 (COVID-19) pandemic has marched relentlessly westward. On March 13, WHO said that Europe was now the centre of the pandemic. A few days later, deaths in Italy surpassed those in China. Iran and Spain had also reported over 1000 deaths as of March 23, and many other European countries and the USA reported increasing numbers of cases, heralding an imminent wave of fatalities. Following the sweep of COVID-19 is a series of dramatic containment measures that reflect the scale of the threat posed by the pandemic.
Data Set Error in: Pharmacogenetic Association of the NPPA T2238C Genetic Variant With Cardiovascular Disease Outcomes in Patients With Hypertension
Authors: Jonathan Purnell, David Flum
Journal: JAMA (2009)

sure to classify risk of decline is developed, it could be used to triage bariatric surgery in patients with diabetes.Until such time, however, we believe that our proposal is a more rational, ethical, and pragmatic approach to the broader use of surgery for the remission of diabetes, while acknowledging that this is a debate that will evolve with evidence over time.
Prospective, Observational Study to Assess the Safety of Rituximab(R) in Combination with Chemotherapy in Patients with Previously-Untreated or Relapsed or Refractory B Cell-Lineage Chronic Lymphocytic Leukaemia (B-CLL): Final Results
Authors: Pilar Giraldo, Andres Lopez, Eduardo Rios, Felix Carbonell, Javier Lopez, Angel Ramírez, Alicia Rodriguez, Marta Gomez, Ricardo Garcia, Patricia Baltasar, Maria Duran, Raul Perez, Maria Garcia, José Antonio Márquez, Javier De la Serna
Journal: Blood (2014)
Enhanced expression of cytokine-induced neutrophil chemoattractant in rat hepatic allografts during acute rejection
Authors: Y Yamaguchi
Journal: Hepatology (1997)

The kinetics of messenger RNA (mRNA) and protein levels of cytokine-induced neutrophil chemoattractant (CINC) in rat hepatic allografts during acute rejection were investigated. Infiltrating cells were identified by double immunostaining with anti-CINC and anti-macrophage monoclonal antibodies, ED1 and ED2. The serum CINC concentration in untreated hepatic allograft recipients increased significantly at a constant rate over time after transplantation. No significant increases in serum CINC concentrations were observed in hepatic isografts or allografts treated with the immunosuppressant FK506. The number of neutrophils in untreated hepatic allografts increased significantly at a constant rate. Conversely, neutrophil accumulation in isografts or allografts treated with FK506 was much less than in untreated hepaticallografts. Immunostaining revealed that in the portal areas, mononuclear cells infiltrating untreated allograft liver were mainly positive for CINC and that CINC+ cells represented a subpopulation (∼ 25%) of the ED1+ cells. On the other hand, in the sinusoidal areas CINC+ cells were scattered and mainly positive for ED2. Levels of CINC mRNA in liver tissues taken from untreated hepatic allografts increased after transplantation, peaked on day 5, and decreased thereafter. Hepatic allografts treated with FK506 or isografts showed much lower levels of CINC mRNA than untreated allografts. Allogeneic mixed lymphocyte reactions induced CINC production. The cellular source of CINC was mononuclear cells. CINC production in mixed lymphocyte reactions was inhibited in the presence of anti-tumor necrosis factor α (TNF-α) antibody. These results suggest that enhanced expression of CINC mRNA and prominent accumulation of neutrophils in the liver grafts are characteristic features of the immune response during acute rejection.
Optimizing Thromboembolism Prophylaxis for the Contemporary Age of Multiple Myeloma
Authors: Muhamed Baljevic, Douglas W. Sborov, Ming Y. Lim, Jens Hillengass, Thomas Martin, Jorge J. Castillo, Michael B. Streiff, Shaji K. Kumar, Natalie S. Callander
Journal: Journal of the National Comprehensive Cancer Network (2022)

Venous thromboembolism (VTE) is a major complication in all patients with cancer. Compared with the general population, patients with multiple myeloma (MM) have a 9-fold increase in VTE risk, likely because of their malignancy, its treatments, and other additional patient-related factors. In MM, thromboembolism events tend to occur within 6 months of treatment initiation, regardless of treatment regimen; however, the use of immunomodulatory agents such as thalidomide or lenalidomide, especially in combination with dexamethasone or multiagent chemotherapy, is known to create a significant risk for VTE. Currently, official recommendations for VTE prophylaxis in MM outlined in various national guidelines or multidisciplinary society panels are based on expert opinion, because data from randomized controlled trials are scarce. Large studies which have mainly focused on the efficacy of thromboprophylaxis in patients with cancer at higher risk for VTE either had a very low representation of patients with MM, or excluded them all together, limiting our ability to draw evidence-based conclusions on how to effectively protect MM population from VTE. In this brief perspective, we highlight some of the greatest challenges that have hampered the field concerning the availability of high-quality clinical trial data for the formulation of best VTE prophylaxis strategies in patients with newly diagnosed MM, as well as the rationale for the latest updates in the NCCN Guidelines on this topic.
ABSTRACTS
Journal: Circulation (1961)

Histologic studies were made of the kidneys obtained at necropsy from 17 patients with cyanotic congenital heart disease and one patient with primary pulmonary hypertension.The le- sions were similar and consisted of hypercellularity and intereapillary deposition of eosino- philic material, particularly in the axial stalk of the mesangium; many gloineruli were congested and enlarged, the basement membranes were altered and a few hilar arterioles were dilated.The histologic pattern was rather characteristic, and was not found in patients with cyanotic heart disease or in other primary cardiac or renal disease processes.No correlation was ap- parent between the severity of the disease process and the degree of arterial oxygen desaturation.The pathogenesis of the glomerular lesions re- mains obscure, since there were no associated autopsy, clinical, or laboratory findings that were helpful in determining the etiology of these changes.
Intravenous use of dimethylsulfoxide to improve outcome of acute myocardial ischemia in a porcine model Dennis W. Dunning, George Eyster, Kevin L. Kelco, Echo Hansen, Earl T. Hawkins, Shirley Siew, Lynn Cronin, William W. O'Neill. William Beaumont Hospital, Royal Oak, MI, Michigan State University - College of Veterinary Medicine, East Lansing, MI
Journal: Journal of the American College of Cardiology (2001)
Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder
Authors: Meryem Grabski, Amy McAndrew, Will Lawn, Beth Marsh, Laura Raymen, Tobias Stevens, Lorna Hardy, Fiona Warren, Michael Bloomfield, Anya Borissova, Emily Maschauer, Rupert Broomby, Robert Price, Rachel Coathup, David Gilhooly, Edward Palmer, Richard Gordon-Williams, Robert Hill, Jen Harris, O. Merve Mollaahmetoglu, H. Valerie Curran, Brigitta Brandner, Anne Lingford-Hughes, Celia J.A. Morgan
Journal: American Journal of Psychiatry (2022)

Objective: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. Methods: In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. Results: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. Conclusions: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.