tbuckley/cabot-search huggingface dataset:
Abstract 18021: Combining Human Induced Pluripotent Stem Cell Derived Cardiac Sheets, CRISPR-Based Genome Editing, and Optical Mapping of Rotors to Study the Short QT Syndrome
Authors: Rami Shinnawi, Naim Shaheen, Assad Shiti, Irit Huber, Gil Arbel, Amira Gepstein, Anke Tijsen, Rainer Schimpf, Martin Borggrefe, Lior Gepstein
Journal: Circulation (2017)

Introduction: The congenital Short QT Syndrome (SQTS) is a familial arrhythmogenic syndrome caused by abnormal ion channel function leading to action-potential duration (APD) shortening, life-threa...
PANCREOX: A randomized phase 3 study of 5FU/LV with or without oxaliplatin for second-line advanced pancreatic cancer (APC) in patients (pts) who have received gemcitabine (GEM)-based chemotherapy (CT).
Authors: Sharlene Gill, Yoo-Joung Ko, M. Christine Cripps, Annie Beaudoin, Sukhbinder K. Dhesy-Thind, Muhammad Zulfiqar, Pawel Zalewski, Thuan Do, Pablo Oscar Cano, Wendy Lam, Scot D. Dowden, Helene Grassin, John Stewart, Malcolm J. Moore
Journal: Journal of Clinical Oncology (2014)

4022 Background: There is no current standard of care for APC after 1st line GEM. The CONKO3 study (ASCO 2008) reported a survival benefit with 2nd line oxaliplatin-5FU (OFF), but has not yet been validated. PANCREOX was initiated to evaluate the benefit of mFOLFOX6 vs infusional 5FU/LV in this setting. Methods: Pts with APC previously treated with GEM and ECOG PS <=2 were eligible. 108 pts were randomized. PFS was the primary endpoint in this Canadian, multicentre, open-label study. Secondary outcomes included OS and quality of life. Pts received mFOLFOX6 or infusional 5FU/LV until progression. Results: Pt characteristics, efficacy and quality of life results are shown in the Table. Duration of 1st line GEM was similar. More pts withdrew due to adverse events (AEs) in the mFOLFOX6 arm (20.4% vs 1.9%) and due to progression in the 5FU/LV arm (74.1% vs 50.0%). No difference was observed in PFS (median 3.1 vs 2.9 mos, p=0.99). OS was inferior in pts assigned to mFOLFOX6 (median 6.1 vs 9.9 mos, p=0.02). Use of post-progression therapy was significantly higher in the 5FU/LV arm (25% vs 6.8%, p<0.05). Increased toxicity was observed with the addition of oxaliplatin in 2nd line APC with grade 3/4 possibly-related AEs occurring in 63% of mFOLFOX6 pts and 11% of 5FU/LV pts. No treatment related deaths. Conclusions: No benefit was observed with the addition of oxaliplatin to infusional 5FU/LV in GEM-treated 2nd line APC. PFS was similar and OS was inferior with mFOLFOX6. Given the proven benefit of FOLFIRINOX in untreated APC (ACCORD 11), these results suggest that the opportunity for use of oxaliplatin-based CT would be primarily in the 1st-line setting. Funding: Sanofi Canada. Clinical trial information: NCT01121848. Variables Statistic mFOLFOX6 n=54 5FU/LV n=54 HR (95% CI) P Age Median (y) 65 67 0.36 Duration of advanced disease Median (mos) 7.9 5.7 0.20 Stage (%) Locally advanced 7.4 5.6 0.70 Metastatic 92.6 94.4 ECOG (%) 0 13.0 18.9 0.22 1 75.9 75.5 2 11.1 5.7 PFS Median (mos) 3.1 2.9 1.00 (0.66-1.53) 0.99 OS Median (mos) 6.1 9.9 1.78 (1.08-2.93) 0.02 ORR (%) 13.2 8.5 0.36 EORTC-QLQ-C30 Time to definite deterioration > 10 pts (days) 65 92 1.47 (0.74-29.4 0.27
Abstract 17382: Pharmacologically Induced Hypothermia With Cannabinoid Receptor Agonist Win55, 212-2 Improves Cardiac Function in a Rat Model of Cardiac Arrest
Authors: Yan Xiao, Nikki Duggal, Qinyue Guo, Jin Yang, Weiping Huang, Zhangle Hu, Jennifer Bradley, Mary Ann Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2017)

Introduction: Cannabinoid receptors (CB) located in the preoptic anterior hypothalamus play a major role in thermoregulation. Our previous work demonstrates that the CB antagonist WIN55, 212-2 (WIN...
Abstract 17765: Distribution And Comparison Of High-sensitivity Troponin-T And Troponin-I In An Elderly Population Cohort - Findings From The AGES-Reykjavik Study
Authors: Tushar Acharya, Thor Aspelund, Gudny Eiriksdottir, Tamara Harris, Lenore J Launer, Vilmundur Gudnason, Andrew E Arai
Journal: Circulation (2017)

Introduction: High-sensitivity cardiac troponins (TnT and TnI) predict adverse cardiovascular outcomes in the general population. However, their utility has not been compared in the same cohort. Hypothesis: We hypothesized that subjects with concordant positive abnormal TnT and TnI would have worse prognosis than subjects with normal TnT and/or TnI. Methods: Using high-sensitivity assays, TnT and TnI were measured in the AGES-Reykjavik community-based prospective study (baseline 2002-2006.) Subjects were followed for a median 10.6 y. Multivariable logistic regression, Kaplan Meier survival, and receiver-operator curve analyses were used to compare their predictive value. Results: In 5406 subjects (median age 76 y, Framingham score 27, 57% females), median TnT and TnI values were 10.7 ng/L and 6.2 ng/L respectively with modest correlation (Pearson’s coefficient 0.5). Subjects with troponin level ≥95th percentile of the study population had higher odds of all-cause death (TnT: 5.97 vs TnI: 3.08); myocardial...
Radiogenomics of hepatocellular carcinoma: Computed tomography biomarker to predict microvascular invasion and clinical outcome.
Authors: Sudeep Banerjee, Michael Kuo
Journal: Journal of Clinical Oncology (2014)

4089 Background: Microvascular invasion (MVI) is an independent predictor of poor outcome following surgical resection or liver transplantation (LT) in hepatocellular carcinoma (HCC); however, MVI currently cannot be adequately determined until after surgery. Methods: We conducted a multicenter evaluation of a computed tomography (CT) biomarker for MVI, termed radiogenomic venous invasion (RVI), in surgical candidates with HCC. RVI is a prospectively-defined imaging surrogate for a 91-gene HCC
The experience of administration of high-dose recombinant interleukin-2 in combination with chemotherapy in the management of disseminated skin melanoma.
Authors: Olga Streltsova, Yauheni Valerievich Baranau, Edvard Javrid, Maxim Barmotska
Journal: Journal of Clinical Oncology (2014)

e20008 Background: Interleukin-2 (Biotech, Russia) is a complete structural and functional analogue of human endogenous interleukin-2 produced from nonpathogenic Saccharomyces cerevisiae. Our retrospective study evaluated the results of the first-line chemoimmunotherapy of 71 patients with disseminated skin melanoma treated with interleukin-2 from 2004 till 2012. Methods: We retrospectively evaluated efficacy and safety of chemotherapy dacarbazine 800 mg/m2, d 1 and cisplatin 20 mg/m2, d 1–4 (control arm, n=31). In the treatment arm chemotherapy was supplement of one of the following immunotherapy regiments: high-dose IL-2 (9 mg/m2, d 1–5) or gradual dose reduction IL-2 (18 mg/m2, d 1; 9 mg/m2, d 2; 4 mg/m2, d 3–4) (n=71). The median follow –up was 10, 0 months. Results: The objective response rate was 33.8 % and 19.4% in the treatment and control arms respectively. Four complete responses were registered in the treatment arm only (5.6%). The median PFS was 5.3 and 3.2 (p=0.04), the median overall survival was 12.4 and 8.4 months (p=0.1) among the patients treated with chemoimmunotherapy and with chemotherapy alone respectively. The blood serum level of lactate dehydrogenase (LDH) exceeding more than 1.5 fold the upper reference value was an unfavourable prognostic factor with no impact of the treatment type (chemotherapy or chemoimmunotherapy) on its efficacy. At the same time, chemoimmunotherapy for disseminated skin melanoma patients with the LDH level not exceeding more than 1.5-fold the upper reference value increased the median PFS up to 6.3 months and the median overall survival up to 14.7 months. All adverse effects were overcome with conventional medications and had not caused cancels of immunotherapy. Conclusions: Our experience confirmed that immunochemotherapy with high-dose interleukin-2 is an effective treatment of disseminated skin melanoma, is satisfactily tolerated and may be beneficial in patients with the LDH level not exceeding more than 1.5-fold the upper reference value.
Effect of Intranasal Ketamine vs Fentanyl on Pain Reduction for Extremity Injuries in Children
Authors: Theresa M. Frey, Todd A. Florin, Michelle Caruso, Nanhua Zhang, Yin Zhang, Matthew R. Mittiga
Journal: JAMA Pediatrics (2018)

Timely analgesia is critical for children with injuries presenting to the emergency department, yet pain control efforts are often inadequate. Intranasal administration of pain medications provides rapid analgesia with minimal discomfort. Opioids are historically used for significant pain from traumatic injuries but have concerning adverse effects. Intranasal ketamine may provide an effective alternative.To determine whether intranasal ketamine is noninferior to intranasal fentanyl for pain reduction in children presenting with acute extremity injuries.The Pain Reduction With Intranasal Medications for Extremity Injuries (PRIME) trial was a double-blind, randomized, active-control, noninferiority trial in a pediatric, tertiary, level 1 trauma center. Participants were children aged 8 to 17 years presenting to the emergency department with moderate to severe pain due to traumatic limb injuries between March 2016 and February 2017. Analyses were intention to treat and began in May 2017.Intranasal ketamine (1.5 mg/kg) or intranasal fentanyl (2 µg/kg).The primary outcome was reduction in visual analog scale pain score 30 minutes after intervention. The noninferiority margin for this outcome was 10.Of 90 children enrolled, 45 (50%) were allocated to ketamine (mean [SD] age, 11.8 [2.6] years; 26 boys [59%]) and 45 (50%) to fentanyl (mean [SD] age, 12.2 [2.3] years; 31 boys [74%]). Thirty minutes after medication, the mean visual analog scale reduction was 30.6 mm (95% CI, 25.4-35.8) for ketamine and 31.9 mm (95% CI, 26.6-37.2) for fentanyl. Ketamine was noninferior to fentanyl for pain reduction based on a 1-sided test of group difference less than the noninferiority margin, as the CIs crossed 0 but did not cross the prespecified noninferiority margin (difference in mean pain reduction between groups, 1.3; 90% CI, -6.2 to 8.7). The risk of adverse events was higher in the ketamine group (relative risk, 2.5; 95% CI, 1.5-4.0), but all events were minor and transient. Rescue analgesia was similar between groups (relative risk, 0.89; 95% CI, 0.5-1.6).Ketamine provides effective analgesia that is noninferior to fentanyl, although participants who received ketamine had an increase in adverse events that were minor and transient. Intranasal ketamine may be an appropriate alternative to intranasal fentanyl for pain associated with acute extremity injuries. Ketamine should be considered for pediatric pain management in the emergency setting, especially when opioids are associated with increased risk.ClinicalTrials.gov Identifier: NCT02778880.
Assessment of efficacy of retroperitoneal neoplasm treatment in children.
Authors: Natalia A. Maksimova, Elena Frantsiyants, Yuliya Yu. Kozel, Maria G. Ilchenko
Journal: Journal of Clinical Oncology (2014)

e21011 Background: In order to assess treatment efficacy, 44 children with retroperitoneal tumor (RT) were examined, 25 of them had neuroblastoma (NB) and 19 – nephroblastoma (N). Methods: Before every chemotherapy (CT) course a complex ultrasonic scanning (US) was performed with “IU 22 PHILIPS” scanner with the use of convex sensors, frequency 2-5 MHz in B-mode, color flow and energy mapping, by a patented system. Activity of integral markers of plasminogen/plasmin (PG/P) system in peripheral blood was studied. The indices were compared with that of the control group including conditionally healthy donor children. There was not any considerable difference in sonographic changes and in P and PG activity indices in blood serum of children with NB and B, so we combined the data. Results: 39 patients (pts) (88,7%) underwent preoperational chemotherapy, 5 (11,3%) underwent tumor removal surgery first. Under considerable and partial effect (n=34) 87%, tumor diminished by 75-90%, tumor borders became more distinct in 15 pts (38,4%), more even in 10 (25,6%), echogenisity of tumor tissue increased in 19 (48,7%). Calcified focus content increased in 16 (69,5%) of 23 pts with NB. Infiltrative lesion and extravasal compression of great and visceral blood vessels decreased in 31 (79,5%), as well as intratumoral blood flow parameters in 20 (51,3%) down to its dying-away in 8 (20,5%). In pts with RT (n=44) PG activity before CT was 1,5±1,2 KE, P 4,0±0,5 КΕ, PG/P 0,4±0,1. Activity indices under CT in pts with considerable and partial clinical effect (n=34) were: PG 3,5±0,6 КΕ, P 0,2±0,02 КΕ, PG/P 17,4±0,2. In pts without clinical effect (n=5) - PG 1,3±0,2 КΕ, P 2,7±0,1 КΕ, PG/P 0,5±0,09. It is revealed that PG/P rate increase up to the norm and more is a favorable prognostic sign. Conclusions: Thus, complex US, analysis of PG and P activity allow to assess therapy efficacy, which assists in choosing further treatment strategy.
More than 10-year follow-up after total en bloc spondylectomy for spinal tumors.
Authors: Satoshi Kato, Hideki Murakami, Satoru Demura, Katsuhito Yoshioka, Hiroyuki Hayashi, Noriaki Yokogawa, Takayoshi Ishii, Takashi Igarashi, Xiang Fang, Hiroyuki Tsuchiya
Journal: Journal of Clinical Oncology (2014)

e21503 Background: Total en bloc spondylectomy (TES) is a surgical procedure designed to achieve complete resection en bloc of an aggressive benign spinal tumor or a malignant spinal tumor. Hitherto, there are many reports of en bloc resection for spinal tumors. However, no studies have evaluated the clinical outcomes with follow-up exceeding 10 years. The purpose of this study was to examine the clinical outcomes of patients surviving for more than 10 years after TES. Methods: We reviewed 82 patients who had undergone TES for spinal tumors in our institute before January 2002 and identified 29 patients (19 with primary tumors and 10 with metastatic tumors) who had survived for more than 10 years (122 to 240 months) after surgery. Fifty-one patients died within 10 years after surgery and 2 others were lost to follow-up. We evaluated the clinical outcomes including patient-based outcomes using a questionnaire. The questionnaire included subjective assessment of the results of surgery and SF-36. Results: The percentage of patients with metastatic tumors who survived for more than 10 years after surgery were 33% with metastases from kidney cancer, and 25% with metastases from thyroid cancer. Four patients with metastatic tumors had no evidence of disease at the time of survey. There were no tumor recurrences in any of the 23 patients who underwent TES as the primary surgery. There was one tumor recurrence in the 6 patients who underwent TES as the revision procedure after the initial surgery in another hospital. About 90% of the patients were satisfied or very satisfied with the results of TES. All the patients indicated that they would have their surgery again if they returned to their pre-surgical status. The SF-36 results demonstrated that the both physical and mental health of patients with primary tumors was equivalent to those of healthy individuals, and the mental health of patients with metastatic tumors was almost similar to those of healthy individuals. Conclusions: This study showed the long-term clinical outcomes after TES to be favorable. TES played an important role in the treatment strategy for spinal tumors including metastases.
Abstract 15699: Risk Factors for Adverse Events in Children With Pulmonary Artery Hypertension Undergoing Cardiac Catheterization
Authors: Danish Vaiyani, Michael S Kelleman, Laura A Downey, Christopher J Petit, Holly Bauser-Heaton
Journal: Circulation (2017)

Introduction: Pulmonary Artery Hypertension (PAH) leads to progressive heart failure with high morbidity and mortality. Cardiac catheterization (CC) is the gold standard for measuring pulmonary vas...
Behavioral and Clinical Characteristics of American Indian/Alaska Native Adults in HIV Care — Medical Monitoring Project, United States, 2011–2015
Authors: Amy R. Baugher, Linda Beer, Heather M. Bradley, Mary E. Evans, Qingwei Luo, R. Luke Shouse
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

The rate of diagnosis of human immunodeficiency virus (HIV) infection among American Indians and Alaska Natives (AI/ANs) in 2016 (10.2 per 100,000 population) was the fourth highest among seven racial/ethnic groups in the United States (1); the number of diagnoses of HIV infection among AI/AN persons increased by 70%, from 143 in 2011 to 243 in 2016 (1). However, little has been published about the sociodemographic, behavioral, and clinical characteristics of AI/AN patients with HIV infection in care because small sample sizes have led to infrequent analysis of AI/AN-specific estimates (2) and because of underestimation of AI/AN race/ethnicity in surveillance and other data sources (3). CDC analyzed data from the Medical Monitoring Project (MMP), a surveillance system that collects information about the experiences and needs of persons with diagnosed HIV infection, collected during 2011-2015 among AI/AN adults receiving HIV medical care. The results indicated that 64% of AI/AN patients with HIV infection in care achieved sustained viral suppression, and 76% achieved viral suppression at their most recent viral load test within the past 12 months, which is below the national HIV prevention goal of 80%, but comparable to or better than some other racial/ethnic groups (4). Based on self-report, 51% of AI/AN patients with HIV infection had incomes at or below the U.S. Department of Health and Human Services' (HHS) annual poverty limit, 27% had symptoms of depression, 78% reported internalized HIV-related stigma, and 20% reported binge drinking in the past 30 days. To improve the health of AI/AN patients with HIV infection, it is important that health care providers, tribal organizations, and state and local health departments consider the sociodemographic and behavioral barriers to AI/AN patients with HIV infection achieving viral suppression and design care plans that seek to eliminate those barriers.
Abstract 17360: Evaluating Expanded Heart Failure Outcomes in Patients With Type 2 Diabetes After an Acute Coronary Syndrome: Insights From the EXAMINE Trial
Authors: Abhinav Sharma, Christopher P Cannon, William B White, Yuyin Liu, Faiez Zannad
Journal: Circulation (2017)

Introduction: Prognostication for heart failure (HF) outcomes remains challenging in patients with type 2 diabetes mellitus (T2DM) post acute coronary syndrome (ACS). This study evaluated both a cl...
Combination therapy with pomalidomide and ruxolitinib in the treatment of myelofibrosis.
Authors: Mirela Andrei, Hemant Singh Sindhu, Jen C. Wang
Journal: Journal of Clinical Oncology (2014)

e18026 Background: Ruxo, has been shown to be effective in alleviating constitutional symptoms in patients with MF. The limitations of ruxo are hematologic toxicities and for those patients with platelet counts less than 50 x 10⁹/L were not considered to use this drug. Pom, with lower toxicity, better tolerability, showed improvement in MF-associated cytopenia. Therefore , we evaluated this combination therapy in patients who presented as severe thrombocytopenia and constitutional symptoms. Methods:Two MF patients, both with platelets counts below 50 x 10⁹/L, and significant constitutional symptoms were studied. Evaluation of constitutional symptoms was graded according to the MF symptoms assessment form . First, Pom (0.5 mg to 1 mg PO qd ) was initiated to improve cytopenia then Ruxo (10mg PO BID) was then added to control the constitutional symptoms. Results: Patient 1 with PMF, platelets 25 x10⁹/L first received Pom. After 3 months of therapy, an increase in platelets counts to 102 x 10⁹/L. Ruxo was then added. His constitutional symptoms were improved without worsening thrombocytopenia (Table). A sustained hematologic response was maintained at 16 weeks with a median platelet counts of 130 x 10⁹/L. Patient 2 with post-PV MF was given pom. Within four weeks, a doubling of platelet counts to 89 x 10⁹/L from a baseline of 41 x 10⁹/L was noted and at six months, his platelet counts normalized to 269 x 10⁹/L. Ruxo was then started and a rapid and improvement in constitutional symptoms was noted (Table). Dual therapy was continued for 6 months, when patient succumbed to heart disease. Conclusions: Our results illustrate the beneficial results of using this combination therapy in MF patients who present with severe thrombocytopenia and significant constitutional symptoms. A further studies involving more patients will be necessary to confirm our preliminary results . Constitutional symptoms – Grade (MFSAF score) Patient 1 Patient 2 Prior ruxo On ruxo Prior ruxo On ruxo Fatigue 9 1 9 2 Early satiety 8 7 7 7 Night sweats 3 1 2 0 Inactivity 9 2 9 3 Weight loss 6 4 5 5 Overall quality of life 8 3 9 3
Abstract 10936: Rgs5 Protects Against Vagal Related Bradycardia and Atrial Tachyarrhythmia
Authors: mu qin
Journal: Circulation (2015)

Background: The regulator of G-protein signaling 5 (Rgs5), functions as regulator of G protein coupled receptor (GPCR) including muscarinic receptors, has potentially effect on atrial muscarinic receptor activated I K,Ach current. Objective: To elucidate the effect of regulator of G-protein signaling 5 (Rgs5) on vagal related bradycardia and atrial tachyarrhythmia (ATA) in mice. Methods and Results: In the present study, the Rgs5 knockout (KO) mice had decreased LF/HF ratio in spectral measures of heart rate variability, and provoked dramatically exaggerated bradycardia and significantly (P &lt;0.05) prolonged sinus nodal recovery time in response to carbachol (0.1mg/kg, IP). However, cardiac transgenic of human Rgs5 (Rgs5TG) appeared to confer autonomic balance in terms of LF/HF ratio (1.01 ± 0.17), and found to be resistant to carbachol induced bradycardia (Fig.A 1-2 ). Compared with those from wild-type (WT) mice, Langendorff perfused hearts from Rgs5KO mice had significantly (P &lt;0.01) abbreviated atrial effective refractory periods (ERP) and increased susceptibility of ATA following administration of acetylcholine (1μM). Whereas Rgs5TG hearts showed significant longer ERP and less ATA inducibility than WT groups (P&gt;0.05). In addition, whole patch clamp analyses of single atrial myocytes revealed that the acetylcholine-regulated potassium current (I Kach ) was stronger in Rgs5KO than in WT mice. In atrial myocytes (n=8) from Rgs5TG mice, we found a smaller amplitude of I K,ACh (P&gt;0.05), but the time of activation and deactivation was shorter than in WT mice (P&lt;0.05)(Fig.B 1-4 ). The expression levels of I KACh subunits Kir3.1 and Kir3.4 were similar among three groups (P&gt;0.05). Conclusion: The results of this study indicate that as a critical regulator of parasympathetic activation in the heart, Rgs5 prevents vagal related bradycardia and ATA through negatively regulating the I Kach current.
The International Society of Nephrology’s International Consortium of Collaborators on Chronic Kidney Disease of Unknown Etiology: report of the working group on approaches to population-level detection strategies and recommendations for a minimum dataset
Authors: Ben Caplin, Chih-Wei Yang, Shuchi Anand, Adeera Levin, Magdalena Madero, Rajiv Saran, Saroj Jayasinghe, Marc De Broe, Karen Yeates, Marcello Tonelli, Kristina Jakobsson, Luisa Strani, Agnese Ruggiero, Jason Glaser, Ekti Martin, Neil Pearce, Eranga Wijewickrama
Journal: Kidney International (2018)