tbuckley/cabot-search huggingface dataset:
Abstract 19665: Angiographic Predictors of Successful Guide-wire Crossing Through Infrapopliteal Chronic Total Occlusions (CTOs)
Authors: Thejasvi Thiruvoipati, Aaron Strobel, Singh D Gagan, John R Laird, Ehrin J Armstrong
Journal: Circulation (2015)

Background: No current scoring system exists to predict successful guide-wire crossing of infrapopliteal CTOs. Methods: All patients undergoing peripheral endovascular procedures from 2006 to 2014 at University of California, Davis and Denver Veterans Affairs Medical Centers were reviewed. Interventions performed on anterior tibial, peroneal, or posterior tibial artery CTOs were identified. Angiographic analysis was performed to identify stump morphology, presence of bridging collaterals and side branches near the stump, calcification at entry and within the occluded segment, and the length and the diameter of the lesion. Angiographic predictors of successful wire crossing were then identified. Results: 215 cases of infrapopliteal CTOs were performed at the two centers during the study period. Antegrade wire crossing was successful in 151 cases (70%). Failure of antegrade wire crossing was associated with a beaded stump morphology (15% of failure cases vs. 4% of successful cases, p&lt;0.01); presence of severe calcification at the entry point (56% of failure cases vs. 34% of successful cases, p = 0.02); presence of severe calcification in the occluded route (52% of failure cases vs. 33% of successful cases, p = 0.04); an occluded segment longer than 200 mm (51% of failure cases vs. 17% of successful cases, p&lt;0.01); and reference vessel diameter smaller than 2.5 mm (63% of failure cases vs. 37% of successful cases, p&lt;0.01). The presence of bridging collaterals and side branches were not significantly associated with success or failure of antegrade wire crossing (Table). Conclusions: A beaded stump morphology at the proximal cap, presence of severe calcification at the entry site and in the occluded route, longer occluded segment length, and narrower reference vessel diameter are associated with greater failure of antegrade wire crossing for infrapopliteal CTOs. A scoring system will be developed to identify multivariable predictors of antegrade wire crossing.
Using the E-Value to Assess the Potential Effect of Unmeasured Confounding in Observational Studies
Authors: Sebastien Haneuse, Tyler J. VanderWeele, David Arterburn
Journal: JAMA (2019)

This Guide to Statistics and Methods discusses E-value analysis, an alternative approach to sensitivity analyses for unmeasured confounding in observational studies that specifies the degree of unmeasured confounding that would need to be operative to negate observed results in a study.
Evaluation of Combination Tagraxofusp (SL-401) and Hypomethylating Agent (HMA) Therapy for the Treatment of Chronic Myelomonocytic Leukemia (CMML)
Authors: Aishwarya Krishnan, Bing Li, Maria Pagane, Erin McGovern, Zoe Stone-Molloy, Janice Chen, Christopher Brooks, Ross L. Levine, Raajit K. Rampal
Journal: Blood (2018)
Ritumixab in Combination with Adapted-Dose of Ifosfamide and Etoposide As Salvage Treatment in Elderly Refractory/Relapsed Diffuse Large B-Cell Lymphoma Patients Non-Candidate for High Dose Therapy: A Retrospective Study of Lyon Hospital University
Authors: Guillaume Aussedat, Delphine Maucort-Boulch, Philippe Rey, Violaine Safar, Lionel Karlin, Mad-Helenie Elsensohn, Laure Lebras, Clementine Sarkozy, Emmanuel Bachy, Bertrand Favier, Nicolas Vantard, Pierre Sesques, Anne Lazareth, Emmanuelle Ferrant, Dana Ghergus, Gilles Salles, Emmanuelle Nicolas-Virelizier, Herve Ghesquieres
Journal: Blood (2018)
Formula milk studies couldn’t exist without industry
Authors: Stewart Forsyth
Journal: BMJ (2019)

Regarding The BMJ ’s articles on the formula milk industry, it is important to understand that nutrition intervention studies in infants and young children cannot be undertaken without the collaboration of nutrition companies.12 This is because the intervention product needs to meet established nutrition and safety standards, which requires knowledge, expertise, and technology that are not available in even the most prestigious academic …
Bad to the Bone: The Role of the Insulin-Like Growth Factor Axis in Osseous Metastasis
Authors: Guillaume Rieunier, Xiaoning Wu, Valentine M. Macaulay, Adrian V. Lee, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Journal: Clinical Cancer Research (2019)

Abstract Bone metastases are a frequent complication of cancer that are associated with considerable morbidity. Current treatments may temporarily palliate the symptoms of bone metastases but often fail to delay their progression. Bones provide a permissive environment because they are characterized by dynamic turnover, secreting factors required for bone maintenance but also stimulating the establishment and growth of metastases. Insulin-like growth factors (IGF) are the most abundant growth factors in bone and are required for normal skeletal development and function. Via activation of the IGF-1 receptors (IGF-1R) and variant insulin receptors, IGFs promote cancer progression, aggressiveness, and treatment resistance. Of specific relevance to bone biology, IGFs contribute to the homing, dormancy, colonization, and expansion of bone metastases. Furthermore, preclinical evidence suggests that tumor cells can be primed to metastasize to bone by a high IGF-1 environment in the primary tumor, suggesting that bone metastases may reflect IGF dependency. Therapeutic targeting of the IGF axis may therefore provide an effective method for treating bone metastases. Indeed, anti–IGF-1R antibodies, IGF-1R tyrosine kinase inhibitors, and anti–IGF-1/2 antibodies have demonstrated antitumor activity in preclinical models of prostate and breast cancer metastases, either alone or in combination with other agents. Several studies suggest that such treatments can inhibit bone metastases without affecting growth of the primary tumor. Although previous trials of anti–IGF-1R drugs have generated negative results in unselected patients, these considerations suggest that future clinical trials of IGF-targeted agents may be warranted in patients with bone metastases.
Abstract P112: Coronary RevascularizationProcedure Mortality in Coronary Artery Disease Patients With End-Stage Renal Disease: Do Racial Disparities Matter?
Authors: Alexander V Sergeev
Journal: Circulation (2018)

Background: Studies have demonstrated that chronic kidney disease (CKD), especially its last stage - end-stage renal disease (ESRD) - is not only an independent risk factor for coronary artery disease (CAD), but it also worsens survival prognosis in CAD patients. It remains unclear whether racial disparities affect the outcomes of coronary revascularization procedures - coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) - in CAD patients with ESRD (CAD-ESRD). Study Objectives: (1) to investigate comparative effectiveness of CABG and PCI on in-hospital mortality outcomes in CAD-ESRD patients and (2) to investigate racial disparities in the utilization and in-hospital mortality outcomes of CABG and PCI in CAD-ESRD patients. Methods: We conducted a retrospective cohort study of in-hospital mortality in 23,519 CAD-ESRD patients [mean + SD age: 65.4 + 11.6 years; 62.2% (14,626 of 23,519) males] after CABG and PCI during 2007-2011. Patient race was defined as white, black, Asian, or Native American. In-hospital patient death was a binary outcome of interest. Adjusted odds ratios were obtained from multivariable logistic regression (MLR), adjusted for known clinical, demographic, and socio-economic covariates. Results: In the covariate-adjusted MLR analysis, post-PCI in-hospital mortality in CAD-ESRD patients was significantly lower than post-CABG mortality (adjusted OR = 0.47, 95% CI: 0.41-0.53, p&lt;0.001). Post-procedure mortality was associated with emergency room (ER) admission (adjusted OR 1.62, 95% CI: 1.44-1.83, p&lt;0.001), older age (3.2% increase for each year, 95% CI: 2.6-3.8%, p&lt;0.001), and higher severity of co-existing conditions other than ESRD measured by the Elixhauser Comorbidity Index (8.5% increase for each point increase in the modified Elixhauser-Walraven score, 95% CI: 7.5-9.5%, p&lt;0.001). Blacks were more likely to undergo an ER admission (48.4%) than Asians (46.0%), Native Americans (43.2%) or whites (42.4%, p&lt;0.05, with multiple comparison correction). In the adjusted MLR analysis, race was not a statistically significant independent predictor of post-procedure mortality. C-statistic for the MLR was 0.729. Conclusions: Our results suggest that in-hospital post-PCI mortality in CAD-ESRD patients is lower than post-CABG mortality. Racial disparities in ER admissions - a demonstrated predictor of post-procedure mortality in these patients - may reflect the underlying racial disparities in access to and utilization of primary care. Further studies investigating disparities in CAD-ESRD mortality are warranted.
Clinical implications of tumor-intrinsic mechanisms regulating PD-L1
Authors: Alessandro Prestipino, Robert Zeiser
Journal: Science Translational Medicine (2019)

Treatment with immune checkpoint inhibitors targeting programmed death receptor-1 (PD-1) or programmed death ligand-1 (PD-L1) is effective in many cancer types. Tumors harboring specific mutations modulate antitumor immune responses through the PD-1/PD-L1 axis, and this should be taken into account when designing rational combinatory treatments.
Abstract 11676: High-sensitive C-reactive Protein Does Not Predict Early and 1-year Outcomes After Coronary Artery Bypass
Authors: Julia Merkle, Oliver Liakopoulos, Dimitrios Siskos, Elmar Kuhn, Yeong-Hoon Choi, Kathrin Kuhr, Martin Hellmich, Thorsten Wahlers
Journal: Circulation (2017)

Introduction: High-sensitive C-reactive protein (hsCRP) is an inflammtory marker of patients with coronary heart disease but there is still conflicting data on its impact on early and midterm outco...
Abstract 14136: Right Ventricle Speckle Tracking Analysis During Maximal Exercise in Heart Failure Patients: Possible Indicator of Impaired Ventilatory Efficiency Rather Than Overall Exercise Performance?
Authors: Valeria Donghi, Francesco Carbone, Valentina Labate, Greta Generati, Marta Pellegrino, Francesco Bandera, Eleonora Alfonzetti, Marco Guazzi
Journal: Circulation (2015)

Background: Speckle tracking (ST) analysis is a reliable methodology that allow to quantify myocardial functional properties better than traditional echo parameters. Purpose: We considered a heart failure reduced ejection fraction (HFrEF) population with the aim to investigate how a 2D ST analysis on right ventricle at peak exercise could help to stratify different cardiopulmonary exercise testing (CPET) functional phenotypes. Methods: 36 HFrEF patients (mean age 69±12; male 69%; NYHA I-II-III-IV 19-17-25-5 %) underwent a maximal CPET evaluation combined with Echo-Doppler and off-line ST analysis. Study population was divided in two groups according to median value of 2D right ventricle longitudinal strain at peak exercise (Group A RVLG at peak &lt; -16 vs Group B ≥ -16). In all patients we performed rest and peak 2D left atrium (LA LG), left and right ventricle longitudinal (LV LG, RV LG) strain, considering RV free-wall LG strain and RV LG global strain. Results: The table reports main echo and CPET results in the two groups of patients. Despite similar left ventricle function and RVLG at rest, Group B showed nonsignificant differences in exercise performance (peak VO2) but more impaired ventilation (increased VE/VCO2 slope and reduced PetCO2), associated with more advanced RV reserve limitation and lower LA LG strain at peak exercise. Conclusions: In HFrEF patients, a worse RV disease negatively influence the exercise gas exchange phenotype and RV strain analysis performed at peak exercise is of additive value in the identification of patients with impaired ventilatory efficiency.
Abstract 20222: Adolescent Triglyceride to High Density LipoproteinCholesterol Ratio is Associated With Adult Hypertension: The Kangwha Study
Authors: Hyungseon Yeom, Da-Hye Jeon, Yongwoo Jeon, Hyeon Chang Kim, Il Suh
Journal: Circulation (2017)

Introduction: Triglyceride to high density lipoprotein cholesterol (TG/HDL) ratio is known to be associated with hypertension in adults. However, it is unclear whether TG/HDL ratio in adolescents predicts future hypertension. Hypothesis: High TG/HDL ratio in adolescents is associated with incidence of hypertension in young adults. Methods: The Kangwha Study is an ongoing prospective cohort study which tracked blood pressures of first grade elementary school students since 1986. We evaluated 228 participants who completed health examinations both at age 16 and 35 years. Among them, 23 with adolescent hypertension (defined by blood pressure higher than sex and age specific 95th percentiles) were excluded from this analysis. High TG/HDL group was defined as the highest quartile group, and low TG/HDL group was defined as the remaining quartile groups. Adult hypertension was defined as systolic/diastolic blood pressure ≥ 140/90 mmHg or taking antihypertensive medication at age 35 years. Logistic regression ana...
Vactosertib, a TGF-ß Receptor I Kinase/ALK5 Inhibitor, Diminishes Tumor Progression and Bone Disease in a Mouse Model of Multiple Myeloma and Overcomes Resistance to Proteasome Inhibitors
Authors: Byung-Gyu Kim, Sung Hee Choi, George Luo, Olga Sergeeva, Zhenghong Lee, James Driscoll, Marcos de Lima, Rose Beck, Seong-Jin Kim, John Letterio, Ehsan Malek
Journal: Blood (2018)
Abstract 19627: Factors Affecting the Quality of Life Among the Patients With Pulmonary Artery Hypertension
Authors: Jae Hee Kim, Sang Hui Chu, Hyuk Jae Chang
Journal: Circulation (2017)

Introduction: Pulmonary artery hypertension(PAH) is a rare disease leading to right ventricular failure and premature death, if not treated appropriately. The most prevalent symptoms of PAH such as shortness of breath with exertion and fatigue cause limited physical function and may impact on the quality of life (QoL) among patients with PAH. However, no studies have been conducted to measure the QoL of patients with PAH in Korea. The purpose of this study was to determine the factors affecting the QoL of patients with PAH. Methods: Total 138 patients who visited a PAH outpatient clinic in Seoul, Korea from April 5 to May 31, 2017 participated in this study. QoL was measured by Medical Outcomes Survey Short Form-12(SF-12), physical function by the Korean activity scale index (KASI). symptoms by the pulmonary artery hypertension symptom interference scale (PAHSS) and anxiety by State Anxiety Inventory(SAIT). Multiple regression analyses were performed to analyze the relationship between the factors and QoL...
Abstract 12374: Apparent Diffusion Coefficient Predictors of Outcome in Cardiac Arrest Survivors
Authors: Cuhl-Min Ha, Joonghee Kim, Kyuseok Kim, Gil Joon Suh, Woon Yong Kwon, Kyung Su Kim, Jonghwan Shin, Huijai Lee
Journal: Circulation (2015)

Objective: Various methods of quantitative apparent diffusion coefficient (ADC) analysis has been suggested as useful for prognostication of comatose cardiac arrest (CA) patients. We developed a new computerized prognostication method using relative volume of most dominant cluster of low-ADC voxels and tested its performance in multicenter setting. Method: Adult (&gt;15 years) out-of-hospital CA patients from three different facilities with MRI taken after 12 hours after resuscitation were retrospectively analyzed. Patients with unknown long-term prognosis or poor baseline neurologic function were excluded. Average ADCs (mean and median), LADCV (relative volume of low-ADC voxels) and DC-LADCV (relative volume of most dominant cluster of low-ADC voxels) were extracted using different thresholds from 400 to 800х10–6 mm2/s at 10х10–6 mm2/s intervals. Area under the receiver operating characteristic curve (AUROC) and sensitivity for poor outcome (6-month cerebral performance category score &gt; 2) while maintaining 100% specificity were measured. Results: 110 patients were analyzed. Average ADCs showed fair performance with AUROC of 0.822 (95% confidence interval [CI], 0.744-0.900) for mean and 0.799 (95% CI, 0.716-0.882) for median ADC. LADCV showed better performance with higher AUROC (maximum, 0.925) in ADC threshold range from 400 to 690х10–6mm2/s. DC-LADCV showed the best performance with higher AUROC (maximum, 0.955) compared to LADCV in ADC threshold range of 600 to 680х10–6 mm2/s. It had high sensitivity for poor outcome (&gt;80%) in wide threshold range from 400 to 580х10–6 mm2/s with maximum of 89.2%. Interpretation: Computerized quantitative analysis using DC-LADCV showed impressive performance in prognostication of out-of-hospital CA patients in multicenter setting.
Can’t see the wood for the trees: confounders, colliders and causal inference - a clinician’s approach
Authors: Jennifer K Quint, Cosetta Minelli
Journal: Thorax (2019)

See companion article.1 The world cannot revolve and medicine cannot advance using randomised controlled trial (RCT) data alone. Increasing weight is, quite appropriately, being given to observational research. This is both in the context of answering important clinical questions and in the development of guidelines and policy. With that in mind, the quality of these observational studies is paramount, and quality needs to be appreciated at several levels, including methodology, interpretation and data transparency. There are plenty of examples of observational studies and RCTs failing to reach the same conclusions.2–4 Based on multifaculty input from 47 editors of the main respiratory, critical care and sleep journals, in a recent consensus statement in the Annals of the American Thoracic Society , Lederer and colleagues publish guidance on how to control for confounders and report results in observational studies.5 

Investigation of the causal effect of an exposure (eg, risk factor) on a health outcome in observational studies is not straightforward. Despite a very rich epidemiological and statistical literature covering all issues and methods available to address them, this literature can be a difficult read for clinical researchers—and help from a methodologist is not always at hand. By simplifying complex statistical concepts using accessible language and simple graphical displays, articles like the review by Lederer and colleagues play an important role in making clinical researchers aware of the main …
The Mitochondrial Protease, Neurolysin (NLN), Regulates Respiratory Chain Supercomplex Formation and Represents a New Therapeutic Target for AML
Authors: Sara Mirali, Botham Aaron, Veronique Voisin, Yihua Qiu, Fieke W Hoff, Rose Hurren, Marcela Gronda, Yulia Jitkova, G. Wei Xu, Neil MacLean, Xiaoming Wang, Terzah M. Horton, Steven M. Kornblau, Steven M Chan, Gary D Bader, Aaron Schimmer
Journal: Blood (2018)
Mutational landscape by targeted next-generation sequencing in EBV-associated lymphoepithelioma-like cholangiocarcinoma.
Authors: Nai-Jung Chiang, Ming-Huang Chen, Li-Tzong Chen, Shan Yanshen
Journal: Journal of Clinical Oncology (2019)

269 Background: Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare variant of intrahepatic cholangiocarcinoma, which is highly associated with EBV infection and abundant lymphoplasmacytic cell infiltration. However, there’s limited data of genetic background in LELCC. Therefore, we want to explore the mutation profiles of LELCC, as well as copy number variations. Methods: Five patients’ tumor tissues diagnosed as LELCC, with positive EBER expression were retrospectively collected and microscopically dissected. Of them, two patients’ peripheral blood mononuclear cell served as background of germline mutations. Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes for analysis of tumor tissue and blood. PDL1 immunohistochemistry staining with 22C3 antibody pharmDx was applied. Results: All EBV-associated LELCC showed positive expression of PDL1 staining, with combined positive score from 5% to 30%. Both somatic and germline mutations can be detected in LELCC tissue because diffuse infiltration of lymphocytes over tumor. After adjusting for background germline mutation frequency from peripheral blood, only mutations with allele frequency less than or around 10% were considered as somatic mutations. Overall, 10 nonsynonymous somatic mutations were detected in 4 (80%) patients with a range of 1-5 mutations per sample. Mutations were identified including BARD1, EPHA5, MUC16, TNFAIP3, CD19, PTEN, TET1, RECQL4, CD79B, and KDM5A. Copy number changes were rare in this special population. Interesting, one patient who failed to gemcitabine plus cisplatin got partial response after anti-PD1 inhibitor treatment. Conclusions: LELCC is highly correlated with PDL1 expression in tumor and immune cells. It’s necessary to have both tumor tissue and peripheral blood for next-generation sequencing to identify truly somatic mutations in LELCC.
Impact of hospital volume and type on survival in hepatocellular carcinoma: Results from the National Cancer Database.
Authors: Johannes Uhlig, Cortlandt Sellers, Sajid A. Khan, Charles Cha, Hyun S. Kevin Kim
Journal: Journal of Clinical Oncology (2019)

417 Background: To assess the impact of hospital volume and type on survival in patients with hepatocellular carcinoma (HCC). Methods: Patients with histopathological or imaging-based diagnosis of HCC were identified from the 2003-2015 National Cancer Database (NCDB). First-line treatment was stratified as liver transplant, surgical resection, interventional oncology (IO) and chemotherapy. Hospital volume was stratified as high (ranking among top 10% in case numbers) and low volume, separately for each treatment modality. Hospital type was categorized as academic and non-academic. Overall survival was assessed using multivariable Cox proportional hazards models. Results: A total of 63,877 patients were included (transplant n = 10,596, surgical resection n = 11,132, IO n = 12,286, chemotherapy n = 29,863). Of 1,261 hospitals systems which treated HCC, 226 (17.9%) were academic centers and 1,035 (82.1 %) were non-academic centers. Mean number of cases treated annually was higher in academic centers (55.2; 34.6; 40.7; 79.9) versus non-academic centers (10.7; 6.25; 6.6; 11.9 for transplant; surgical resection; IO and chemotherapy; p &lt; 0.001, respectively). Young African American patients and those with private insurance, high income and education were more likely to receive treatment at academic centers. Geographical difference were evident among US regions, with highest proportion of HCC treated at academic centers in New England states (83.6%) and lowest in South Atlantic states (48.6%). Overall survival was superior for academic versus non-academic centers (HR = 0.89, 95% CI: 0.87-0.91, p &lt; 0.001) and high versus low volume centers (HR = 0.79, 95% CI: 0.77-0.81, p &lt; 0.001), after multivariable adjustment for potential confounders. These effects were evident among all HCC treatment modalities. Conclusions: HCC treatment in academic centers shows distinct patterns according to patient demographics and US geography. Among all treatment modalities, both academic setting and hospital volume independently affected HCC outcomes, with highest patient survival observed in high-volume academic centers.