tbuckley/cabot-search huggingface dataset:
Abstract 18748: What is the Resilience of Out-of-hospital Cardiac Arrest Patients Who Do Not Receive Bystander Resuscitation?
Authors: Brian E Grunau, Frank X Scheuermeyer, Robert Stenstrom, Sarah Pennington, Ron Straight, David Barbic, Jim Christenson
Journal: Circulation (2015)

Background: Many patients with witnessed out-of-hospital cardiac arrest (OHCA) will not have CPR attempted until emergency medical services (EMS) personnel arrive. The potential for favourable outcomes in patients with increasing no-flow durations is unclear. While some extra-corporeal CPR programs have excluded patients without bystander CPR, others have treated these patients provided short durations to EMS arrival. We sought to describe the outcomes of patients with increasing no-flow durations to determine the potential viability of these patients. Methods: This study examined consecutive non-traumatic OHCA’s collected by a prospective registry in British Columbia (2007 and 2011). We included adult patients with bystander-witnessed OHCA but no attempt at bystander chest compressions. The primary variable of interest was the duration from the bystander 9-1-1 call to the time of CPR commencement by EMS. The primary endpoint was survival at hospital discharge. Multivariable logistic regression, with adjustment for sex, age, public location of arrest, and initial shockable rhythm, was used to assess the association of time to CPR and survival to hospital discharge. Results: Of 6571 EMS-treated OHCA’s, 1062 were included. The median age was 73 (IQR 58-82), 69% were male, and 35% had initial shockable rhythms. Overall survival was 13%. The median time to CPR commencement was 8.5 minutes (IQR 6.9 - 10.5). Time to CPR was independently associated with survival to hospital discharge (adjusted OR 0.85 per minute increase; 95% CI 0.78-0.92). Among survivors, the 90th percentile of time from 9-1-1 call to CPR was 10.3 minutes. Conclusion: In adult OHCA patients, no-flow durations were negatively correlated with outcome, however survival was observed with prolonged durations without CPR extending to 16 minutes. Patients with witnessed OHCA and no bystander CPR include survivors and aggressive resuscitation strategies are warranted.
A combined local treatment with anti-PD-1 antibody and bone marrow derived dendritic cells after x-ray irradiation to subcutaneous melanoma in a murine model.
Authors: Yuzi Wang, Lue Sun, Xiaokang Li, Koji Tsuboi
Journal: Journal of Clinical Oncology (2017)

e14541 Background: In situ dying and just died tumor cells after irradiation give danger signals and release tumor-specific antigens which are supposed to be incorporated into dendritic cells (DCs), and sequentially rendering T-cells activated and proliferated. However, it has been clarified that activated T-cells are killed by PD-L1 ligands on tumor cells which bind to PD-1 receptors on T-cells, consequently suppressing systemic cellular immunological response. To improve local control and prevent metastases after localized radiotherapy, we examined whether the combination of anti-PD-1 antibody and bone marrow derived DCs (BM-DCs) can enhance both the local and systemic antitumor immunoreactions after localized X-ray irradiation in a murine melanoma model. Methods: BM-DCs were induced by using GM-CSF and IL-4 from bone marrow cells taken from the femur and tibia of C57BL/6 mice. Syngeneic B16 melanoma cells implanted subcutaneously at the left thighs of C57BL/6 mice were irradiated with X-ray (8 Gy) 5 days after inoculation. After 1, 3, 5, 7 days from irradiation, induced DCs were injected directly to the tumor site, similarly, after 1, 3, 5 days from irradiation, anti-PD-1 antibody were injected intraperitoneally. To examine the systemic immunoreaction, B16 cells were also inoculated to the right side 4 days after the left side inoculation, and treated with the same protocols only on the left side. The size of tumors was monitored and survival analyses were performed. Results: The induced DCs showed the ability to incorporate antigens and to prime and proliferate T-cells in vitro. The combination treatment of anti-PD-1 antibody, BM-DCs and X-ray irradiation showed a significant delay of tumor growth compared to single or double combination treatments in vivo. In addition, this triple combination treatment significantly inhibited the tumor growth on the other side compared to other treatments. Conclusions: DCs and anti-PD-1 antibody significantly enhanced the antitumor effect of X-ray irradiation and prolonged the survival time. This combination also can induce a strong systemic antitumor immunoreaction which could treat metastatic tumors.
Abstract 13263: Risk of Heart Failure in Children and Young Adults Born Preterm- A National Cohort Study
Authors: Hanna Carr, Sven Cnattingius, Jonas F Ludvigsson, Anna-Karin E Bonamy
Journal: Circulation (2015)

Introduction: An increasing number of infants survive preterm birth. Previous studies have found that preterm birth is associated with increased risks of hypertension, stroke and cardiovascular mortality later in life. We hypothesized that preterm birth would be associated with an increased risk of later heart failure. Aim: To investigate the association between preterm birth and incident heart failure children and young adults without previous ischemic heart disease. Material and Methods: This registry-based cohort included 2.5 million individuals born in Sweden between 1987 and 2010. Subjects were followed from one year of age to end of study in December 2011. Event definition was a diagnosis of or death from heart failure in the Swedish National Patient Register or Cause of Death Register. We used Cox proportional hazards regression to estimate the association between preterm birth (categorized as extremely preterm, &lt;28 weeks of gestation; very preterm, &lt;28-31 weeks of gestation; and moderately preterm, 32-36 weeks of gestation) and heart failure. Results: During 29.2 million years of follow-up time we found 373 cases of heart failure (1.3/100 000 person-years). Preterm birth was associated with an increased risk of heart failure across all categories of prematurity, also after exclusion of children with major malformations and adjustment for birth weight, maternal and paternal cardiovascular disease, and other potential confounders. Risk elevation was most pronounced in subjects born &lt;28 weeks, with an adjusted hazard ratio of 19.5 (95% CI, 7.89-48.23). Corresponding hazard ratios for very and moderately preterm birth were 3.11 (1.12-8.62) and 1.76 (1.10-2.81), compared to subjects born at term. Conclusions: This study found a strong association between preterm birth and risk of incident heart failure in children and young adults. Risk elevation was inversely related to gestational age at birth. Although the absolute risk of heart failure is low at this young age, our findings may indicate a future health problem among the new generations of survivors after preterm birth.
Effect of heterogeneity of HER2 expression on brain metastases of breast cancer.
Authors: Mari Hosonaga, Yoshimi Arima, Eiji Sugihara, Norio Kohno, Hideyuki Saya
Journal: Journal of Clinical Oncology (2012)

635 Background: HER2-overexpressing or triple-negative [ER(-)/PR(-)/HER2(-)] breast cancers are associated with increased risk of brain metastases. The mechanisms leading to metastasis in each subtype are not well known. Methods: We introduced the wild-type HER2 gene into MDA-MB-231-luc-D3H2LN (231-Luc) cells, which are triple-negative breast cancer cells, and established HER2-expressing (63.2%) cells as 231-Luc-HER2 cells. We investigated the tumor formation following orthotopic inoculation and brain metastasis following intracardiac injection into nude mice. Metastasis was detected by bioluminescence imaging and confirmed in H&amp;E staining and immunohistochemistry of vimentin and HER2 expressions. Flow cytometry analysis was used to detect the proportion of CD44+/CD24- cells, a maker for stem-like breast cancer cells. Results: 231-Luc-HER2 cells formed larger tumors in orthotopic xenograft models compared to 231-Luc cells, however, no significant difference was observed in proliferation in vitro. Neither 231-Luc-HER2 nor 231-Luc metastasized in the brain from the breast after orthotopic inoculation. After intracardiac injections of the 231-Luc-HER2 cells, brain metastasis developed (7/13 mice, 53.8%). Immunohistochemical analysis revealed that most metastasized cells expressed HER2, although we had injected a mixture of HER2-positive and HER2-negative cancer cells. Interestingly, administering Lapatinib, a dual EGFR and HER2 tyrosine kinase inhibitor, effectively prevented HER2-positive cells to colonize the brain. However, the HER2-negative 231-Luc-HER2 cells developed into brain metastases. In fact, the 231-Luc cells, which are HER2-negative, also metastasized in the brain (10/16 mice, 62.5%). Flow cytometry analysis of the 231-Luc-HER2 cells showed that HER2-positive cells decreased the population of CD44+/CD24- (HER2+/CD44+/CD24-: 86.8% and HER2-/CD44+/CD24-: 96.3%). Conclusions: The mechanism of brain metastases of HER2-positive breast cancer cells is different from that of HER2-negative breast cancer cells. It is therefore important to consider an additional therapeutic approach when dealing with HER2-negative cells in tumors having the heterogeneity of HER2 expression.
Prevalence of Aging, Dementia, and Multimorbidity in Older Adults With Down Syndrome
Authors: Eleonore Bayen, Katherine L. Possin, Yingjia Chen, Laurent Cleret de Langavant, Kristine Yaffe
Journal: JAMA Neurology (2018)

<h3>Importance</h3> As the life expectancy of people with Down syndrome (DS) has markedly increased over the past decades, older adults with DS may be experiencing a higher incidence of aging conditions. In addition to longevity, the amyloid precursor protein gene located on chromosome 21 places individuals with DS at a high risk for developing Alzheimer disease. Yet, few studies have determined prevalence of dementia and comorbidities among older people with DS. <h3>Objective</h3> To determine the prevalence of dementia and aging-related comorbidities in older adult individuals with DS. <h3>Design, Setting, and Participants</h3> Cross-sectional analysis of 2015 California Medicare claims data. We examined 1 year of cross-sectional Medicare claims data that included 100% of Californian Medicare beneficiaries enrolled in both Medicare Part A and B in 2015. Of these 3 001 977 Californian Medicare beneficiaries 45 years or older, 878 individuals were identified as having a diagnosis of DS. Data were analyzed between April 2017 and February 2018. <h3>Main Outcomes and Measures</h3> The frequency of DS dementia was assessed across different age categories. The number and frequency of 27 comorbidities were compared among individuals with DS with and without dementia and by age and sex groups. <h3>Results</h3> A total of 353 DS individuals (40%) were identified as having dementia diagnoses (mean, 58.7 years; 173 women [49%]) and 525 without dementia diagnoses (mean, 55.9 years; 250 women [48%]). The frequency of DS dementia among those 65 years or older rose to 49%. The mean number of comorbidities per individual increased with age in general. Comorbid conditions were more numerous among those with dementia compared with those with DS without dementia (mean, 3.4 vs 2.5, respectively), especially among those younger than 65 years. In particular, 4 treatable conditions, hypothyroidism, epilepsy, anemia, and weight loss, were much more frequent in DS dementia. <h3>Conclusions and Relevance</h3> Older Medicare beneficiaries in California with DS, especially those with dementia, have a high level of multimorbidity including several treatable conditions. While DS follow-up has long been confined to the pediatric sphere, we found that longevity in individuals with DS will necessitate complex adult and geriatric care. More evidenced-based and standardized follow-up could support better long-term comorbidity management and dementia care among aging adults with DS.
Sirolimus for Secondary Prevention of Skin Cancer in Kidney Transplant Recipients: 5-Year Results
Authors: Jacques Dantal, Emmanuel Morelon, Lionel Rostaing, Eric Goffin, Anabelle Brocard, Isabelle Tromme, Nilufer Broeders, Véronique del Marmol, Valérie Chatelet, Anne Dompmartin, Michèle Kessler, Andreas Serra, Günther F.L. Hofbauer, Nassim Kamar, Claire Pouteil-Noble, Jean Kanitakis, Adeline Roux, Evelyne Decullier, Sylvie Euvrard
Journal: Journal of Clinical Oncology (2018)

Purpose Transplant recipients who develop cutaneous squamous cell carcinomas are at high risk for multiple subsequent skin cancers. Sirolimus has been shown to reduce the occurrence of secondary skin cancers, but no study included a follow-up exceeding 2 years. We extended at 5 years the TUMORAPA randomized trial of sirolimus-based immunosuppressive regimen versus calcineurin inhibitor–based immunosuppression. Methods Kidney transplant recipients receiving calcineurin inhibitors who had at least one cutaneous squamous cell carcinoma were randomly assigned to receive sirolimus as a substitute for calcineurin inhibitors (n = 64) or to maintain their initial treatment (n = 56). The primary end point was survival free of squamous cell carcinoma at 5 years. Secondary end points included the occurrence of other skin cancers, renal function, patient and graft survival, and treatment tolerance. Results Survival free of cutaneous squamous cell carcinoma was significantly longer in the sirolimus group than in the calcineurin inhibitor group ( P = .007). In the sirolimus group, the number of patients with new skin cancers was significantly lower compared with the calcineurin inhibitor group: 22% versus 59% for squamous cell carcinomas ( P &lt; .001), 34% versus 66% for other skin cancers ( P &lt; .001), and 20% versus 37.5% for basal cell carcinomas ( P &lt; .05). Kidney graft function, patients, and graft survival were similar in both groups. In the sirolimus group, the mean number of serious adverse effects per patient decreased from 1.16 during the first 2 years, to 0.83 between years 2 and 5. Conclusion In kidney transplant recipients with previous cutaneous squamous cell carcinomas, the antitumoral effect of conversion from calcineurin inhibitors to sirolimus was maintained at 5 years, and sirolimus tolerance was satisfactory.
Trends in the use of breast-conserving surgery and adjuvant radiation therapy in patients with DCIS: A U.S. population-based analysis from 1996 to 2007.
Authors: Jennifer Nishimura, Audrey Choi, Sharon Kim, Julian Kim
Journal: Journal of Clinical Oncology (2012)

1031 Background: The treatment for patients with DCIS remains controversial. Current guidelines based upon best available evidence suggest that breast conserving surgery (BCS) followed by adjuvant radiation therapy (RT) result in acceptable local control and breast cancer specific survival. The purpose of this study was to analyze trends in patterns of care as well as identify factors associated with surgery type and use of adjuvant radiation therapy in a select cohort of patients enrolled into the SEER database. Methods: The study included females 18 years and older with focal DCIS and known tumor size of 5 cm or less diagnosed between 1996 and 2007. The Cochran-Armitage trend test was applied to identify trends in the use of BCS and RT over time. Multivariate logistic regression analyses were used to determine factors associated with receiving BCS vs. mastectomy and BCS plus RT vs. BCS alone. Cox proportional hazard model was used to determine associations with breast cancer-specific mortality. Results: Of the 34,233 women with DCIS, 76.59% were treated with BCS. 66.36% of BCS patients received adjuvant RT over the study period. The proportion of women receiving BCS increased from 71.5% in 1996 to 76.9% in 2007 (p&lt;0.0001). Additionally, the proportion of women who underwent BCS and received adjuvant radiation therapy over the same time period increased from 55.3% to 69.7% (p&lt;0.0001). Multivariate analysis demonstrated that year of diagnosis, race, marital status, geographic region, tumor size, tumor grade and comedo necrosis all were significantly associated with the use of adjuvant radiation therapy, but age was not. Cox proportional hazards models did not associate either surgery type or use of adjuvant radiation in patients undergoing BCS with breast cancer-specific mortality. Conclusions: Based upon reporting within the SEER database, the proportion of DCIS patients undergoing BCS and the BCS patients receiving adjuvant radiation increased over the study time period. Surgery type and use of adjuvant radiation therapy in patients with BCS was not associated with decreased risk of breast-cancer specific death in this cohort.
Antihypertensive Treatment and Change in Blood Pressure Are Associated With the Progression of White Matter Lesion Volumes
Authors: OphéliaGodin, ChristopheTzourio, PaulineMaillard, BernardMazoyer, CaroleDufouil
Journal: Circulation (2011)

Background—Blood pressure (BP) is recognized as a major risk factor for white matter lesions (WMLs), but longitudinal data are scarce, and there is insufficient evidence for the benefit of antihypertensive therapy on WML progression. We studied the relationship between BP change and WML volume progression over time in a sample of 1319 elderly individuals who had 2 cerebral magnetic resonance imaging examinations 4 years apart. We also examined the impact of antihypertensive treatment on WML progression. Methods and Results—Subjects were participants from the Three-City (3C)–Dijon Magnetic Resonance Imaging Study, a prospective population-based cohort of elderly ≥65 years of age. WML volumes and their progression were estimated with the use of a fully automatic procedure. We performed ANCOVA models first to assess the association between BP change and WML progression and second to estimate the relation between antihypertensive treatment and WML load progression. Baseline and change in BP were significant p...
Risk of Breast Implant–Associated Anaplastic Large Cell Lymphoma—Reply
Authors: Daphne de Jong, Mintsje de Boer, Flora E. van Leeuwen
Journal: JAMA Oncology (2018)

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Radiosensitivity Is an Acquired Vulnerability of PARPi-Resistant BRCA1-Deficient Tumors
Authors: Marco Barazas, Alessia Gasparini, Yike Huang, Asli Küçükosmanoğlu, Stefano Annunziato, Peter Bouwman, Wendy Sol, Ariena Kersbergen, Natalie Proost, Renske de Korte-Grimmerink, Marieke van de Ven, Jos Jonkers, Gerben R. Borst, Sven Rottenberg
Journal: Cancer Research (2018)

Abstract The defect in homologous recombination (HR) found in BRCA1-associated cancers can be therapeutically exploited by treatment with DNA-damaging agents and PARP inhibitors. We and others previously reported that BRCA1-deficient tumors are initially hypersensitive to the inhibition of topoisomerase I/II and PARP, but acquire drug resistance through restoration of HR activity by the loss of end-resection antagonists of the 53BP1/RIF1/REV7/Shieldin/CST pathway. Here, we identify radiotherapy as an acquired vulnerability of 53BP1;BRCA1-deficient cells in vitro and in vivo. In contrast to the radioresistance caused by HR restoration through BRCA1 reconstitution, HR restoration by 53BP1 pathway inactivation further increases radiosensitivity. This highlights the relevance of this pathway for the repair of radiotherapy-induced damage. Moreover, our data show that BRCA1-mutated tumors that acquire drug resistance due to BRCA1-independent HR restoration can be targeted by radiotherapy. Significance: These findings uncover radiosensitivity as a novel, therapeutically viable vulnerability of BRCA1-deficient mouse mammary cells that have acquired drug resistance due to the loss of the 53BP1 pathway.
The overlap between bronchiectasis and chronic airway diseases: state of the art and future directions
Authors: Eva Polverino, Katerina Dimakou, John Hurst, Miguel-Angel Martinez-Garcia, Marc Miravitlles, Pierluigi Paggiaro, Michal Shteinberg, Stefano Aliberti, James D. Chalmers
Journal: European Respiratory Journal (2018)

Bronchiectasis is a clinical and radiological diagnosis associated with cough, sputum production and recurrent respiratory infections. The clinical presentation inevitably overlaps with other respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD). In addition, 4–72% of patients with severe COPD are found to have radiological bronchiectasis on computed tomography, with similar frequencies (20–30%) now being reported in cohorts with severe or uncontrolled asthma. Co-diagnosis of bronchiectasis with another airway disease is associated with increased lung inflammation, frequent exacerbations, worse lung function and higher mortality. In addition, many patients with all three disorders have chronic rhinosinusitis and upper airway disease, resulting in a complex “mixed airway” phenotype. The management of asthma, bronchiectasis, COPD and upper airway diseases has traditionally been outlined in separate guidelines for each individual disorder. Recognition that the majority of patients have one or more overlapping pathologies requires that we re-evaluate how we treat airway disease. The concept of treatable traits promotes a holistic, pathophysiology-based approach to treatment rather than a syndromic approach and may be more appropriate for patients with overlapping features. Here, we review the current clinical definition, diagnosis, management and future directions for the overlap between bronchiectasis and other airway diseases.