tbuckley/cabot-search huggingface dataset:
Abstract 6131: Regadenoson Induces Perfusion Defects of Comparable Extent and Severity as Adenosine: A Quantitative Analysis from the ADVANCE 2 Trial
Authors: John J Mahmarian, Manuel D Cerqueira, Ami E Iskandrian, Timothy M Bateman, Gregory S Thomas, Robert C Hendel, Lemuel A Moye, Ann W Olmsted
Journal: Circulation (2008)

The quantified total and ischemic left ventricular (LV) perfusion defect size (PDS) is an important determinant of subsequent patient outcome. Therefore it is important to determine whether a new stressor agent induces similar perfusion abnormalities as a standard stressor agent such as adenosine. The ADVANCE 2 was a double-blind randomized trial comparing image results in patients undergoing standard adenosine (Ad) SPECT who were then randomized to either a second Ad SPECT (N=260) or SPECT following pharmacologic stress with Regadenoson (Reg) (N=493). All raw data of gated SPECT images (2 sets/patient) were reconstructed and reoriented in a standard fashion. Quantitative SPECT was performed using a previously validated automated program which determined the extent and severity of left ventricular (LV) perfusion defect size (PDS) and the extent of scintigraphic ischemia. PDS severity was defined as mild, moderate or severe based on the relation to normal pixel count activity (&gt;50%, 26–50%, and 0–25%, respectively). Quantification was performed blinded to randomization and image sequence. Baseline perfusion results were similar (p&gt;.05) between patients randomized to Ad vs Reg with respect to total (10.2±14.8 vs 11.5±15.8), ischemic (4.2±7.8 vs 4.6±8.9) and scar (6.0±10.7 vs 6.9±11.3) LV PDS. Results are summarized in the table below. Linear regression analysis showed a close correlation between Ad vs Reg for total (r=0.97, p&lt;.0001) and ischemic (0.94, p&lt;.0001) LV PDS. In this large database, quantitative SPECT analysis demonstrates that Regadenoson induces a comparable extent and severity of perfusion abnormality as induced with standard adenosine stress. This implies that similar prognostic information should be obtainable with Regadenoson stress as observed with adenosine.
Infant nasal nitric oxide over time: natural evolution and impact of respiratory tract infection
Authors: June K. Marthin, Maria C. Philipsen, Susanne Rosthoj, Kim G. Nielsen
Journal: European Respiratory Journal (2018)

Nasal nitric oxide (NO) discriminates between patients with primary ciliary dyskinesia (PCD) and healthy individuals. We report feasibility of measurement and natural evolution of nasal NO and upon the impact of respiratory tract infection (RTI) on nasal NO in healthy infants (HI), followed from birth until age 2 years, with comparison to nasal NO in infant PCD. Tidal-breathing nasal NO measurements were performed at scheduled visits at 2 weeks old and at 4, 8, 12, 18 and 24 months old, with extra visits during RTIs. Historical nasal NO measurements for infant PCD were included for comparison. Altogether, 224 nasal NO measurements were performed in 44 enrolled infants. Median newborn nasal NO was 46 ppb (interquartile range (IQR) 29–69 ppb), increasing at a rate of 5.4% per month up to 283 ppb (IQR 203–389 ppb) at the age of 2 years. RTIs in 27 out of 44 infants temporarily suppressed nasal NO by 79%. Values for nasal NO in seven infants with PCD ranged from 6–80 ppb. The success rate to accept nasal NO sampling was 223 out of 224 measurements (99.6%). Tidal-breathing nasal NO measurement was indeed feasible in infancy and nasal NO in HI increased significantly up to 2 years of age, in opposition to nasal NO in PCD cases, which stayed low past 2 years of age. RTI episodes caused marked, temporary reductions in nasal NO in HI indistinguishable from that in infant PCD, suggesting that nasal NO should be measured in RTI-free intervals.
Molecular profiling to predict outcomes following Y90 radioembolization for metastatic colorectal cancer.
Authors: Petra Prins, Alexandra Gradzka, Alexander Y. Kim, John Marshall, Keith Robert Unger
Journal: Journal of Clinical Oncology (2018)

686 Background: Radioembolizaton with yttrium-90 (Y90) has been shown to decrease progression within the liver in patients with unresectable metastatic colorectal cancer (CRC). Molecular profiling (MP) plays an important role in providing precision based therapy for our patients. The purpose of this study was to evaluate predictive associations between genetic mutations in Y90 treated CRC pts and treatment outcomes. Methods: A retrospective chart review of patients at GUMH was conducted for patients who underwent Y90 radioembolization for metastatic CRC between 2010 and 2017. Inclusion criteria were: Liver metastasis, Y90 treatment and MP. Y90 response of the treated liver lesions was evaluated according to RECIST criteria within 4 months of treatment; non-responders were classified as those with progressive disease (PD) and all others were considered responders. Statistical analysis was performed to reveal any significant associations. Results: Out of 285 CRC records with MP screened, 32 pts adhered to our inclusion criteria. Of these 47% were male and 53% female. The average age at diagnosis was 50.4 yrs. For22 pts (69%) Y90 treatment was combined with chemotherapy. Y90 response data showed response in 50% (n = 16) and PD in 31% (n = 10) of the pts. Six pts did not have Y90 response data. Median OS between groups was not significant but longer for those responders (33 vs 26 m). Next Generation Sequencing revealed pathogenic mutations for APC in 20 pts (63%), KRAS in 12 (38%) and TP53 in 13 pts (41%) none of them showing any significant association with Y90 response data (p &gt; 0.05). OS from date of Y90 was significantly improved in patients with TP53 mutations and KRAS WT. There was no association between differences in MP and OS from date of diagnosis. Conclusions: TP53 and KRAS mutations were predictive of survival but not response following Y90 for metastatic colorectal cancer patients. This hypothesis generating study demonstrates the MP may be helpful in stratifying CRC patients who benefit from radiation therapy. Further study is necessary.
Nanoparticle Tracking Analysis of Urine to Detect Exosomes Can Be Confounded by Albuminuria
Authors: Jonathan Gleadle, Kym McNicholas, Jordan Li, Michael Michael, Darling Rojas-Canales
Journal: Journal of the American Society of Nephrology (2018)

In the article by Lv et al.1 published in the Journal of the American Society of Nephrology, the authors describe enhanced urinary exosomal release in experimental models of acute and chronic renal injury. They also describe increased exosomal release in patients with IgA nephropathy and a correlation between exosomal concentration and proteinuria. These findings are of clear interest, but we have reservations about some of the methodology used to ascertain this observation. They use nanoparticle tracking analysis (NTA) of urine and describe enhanced particle concentration in patients who are proteinuric. We have recently reported similar observations using NTA in 32 patients with varying levels of albuminuria.2 We found that albuminuria confounded particle analysis by NTA, because albumin-containing solutions contain particles of exosome-like size, and such particles can mimic exosomes in standard NTA. Immunodepletion of albumin from proteinuric urine resulted in a substantial reduction in the concentration of particles detected by NTA as did urine purification using iodixanol density gradients. More importantly, NTA measurements of pure albumin solutions yielded a substantial number of particles with a diameter of 105 nm. This reinforces the need for great caution in the interpretation of NTA results in fluids that have significant levels of protein. It also emphasizes the importance of stringent methods of purification, such as density gradients, in exosome analysis as recommended by the International Society for Extracellular Vesicles.3 Disclosures None.
Abstract 12173: A Randomized Controlled Trial Comparing Self-instruction and Traditional Instruction in Training of Bystander Cardiopulmonary Resuscitation
Authors: Ming-Ju Hsieh, Chih-Wei Yang, Hao-Yang Lin, Shu-Hsien Hsu, Wen-Chu Chiang, Jen-Tang Sun, Kah-Meng Chong, Matthew Huei-Ming Ma
Journal: Circulation (2016)

Introduction: Self-instruction of learning cardiopulmonary resuscitation (CPR) saves manpower and may be applied in large-scale public training, but its effect comparing to traditional instruction remains unclear. Hypothesis: In bystander CPR training, self-instruction compared to traditional instruction, has different post-training performances. Methods: In this randomized controlled study, administrative clerks and other non-health care providers were randomly allocated into 2 groups: self-instruction group and traditional instruction group. Both groups watched a 27-minute standardized teaching video. Participants in the self-instruction group then performed a 30-minute hands-on practice on Resusci Anne® QCPR (Laerdal company, Norway) with automated feedback, while participants in the traditional instruction group performed the same duration of practice on manikins with feedback by the instructors aside. Both groups had to receive skill tests before and after practice. Blinded evaluators used checklists to decide whether participants passed the tests by reviewing the videos of the skill tests. Data of skill performance was also collected using SkillReporter® software. The primary outcome was the pass rate. The secondary outcomes were items of individual skill performances. Results: Totally sixty-four participants were randomly allocated. All participants completed the protocol. The baseline characteristics of 2 groups were no different. In the primary outcome, the pass rates were the same between 2 groups (94% vs 94%, p=1.00). In the secondary outcomes, the self-instruction group performed better in mean compression depth (48.4 vs 42.0 mm, p=0.002), mean percentage of full chest recoils (77.7% vs 56.4%, p=0.014) and mean percentage of correct ventilation volume (96.5% vs 75.1%, p=0.013), but performed worse in confirming environmental safety (47% vs 78%, p=0.010) and checking normal breathing (26% vs 97%, p&lt;0.001). Conclusions: Bystander CPR training using self-instruction was no different from traditional instruction in pass rate, and even better in some skill performances, but confirmation of environmental safety and check of normal breathing before starting CPR should be emphasized in self-instruction training.
Single Step Double-walled Nanoencapsulation (SSDN)
Authors: Aharon Azagury, Vera C. Fonseca, Daniel Y. Cho, James Perez-Rogers, Christopher M. Baker, Elaine Steranka, Victoria Goldenshtein, Dominick Calvao, Eric M. Darling, Edith Mathiowitz
Journal: Journal of Controlled Release (2018)
Abstract 12731: Impact of Cardiac Valvular Calcification at Beginning Hemodialysis Therapy on Cardiovascular Outcome in Patients with End-stage Renal Disease
Authors: Yoshihiro Kawamura, Hideki Ishii, Toru Aoyama, Daisuke Kamoi, Takashi Sakakibara, Hiroshi Takahashi, Toyoaki Murohara
Journal: Circulation (2012)

Background:  Cardiac valvular calcification is highly prevalent in patients with end-stage renal disease (ESRD), and its presence may be potentially linked with the increasing risk of systemic atherosclerotic events. We investigated whether the presence of calcified valve at just beginning of hemodialysis (HD) therapy could predict individual cardiovascular (CV) events in ESRD patients.   Methods:  A total of 1785 consecutive ESRD patients were screened by echocardiography at beginning of HD therapy. Calcification was defined as bright echoes >1mm on one or more cusps of the cardiac valve. They were divided into three groups; those without valve calcification (group 0, n=783), those with calcification in a single (aortic or mitral) valve (group 1, n=651) and those with calcification in both valves (group 2, n=351), and were followed up for up to 10 years.   Results:  During follow-up period (median 55months), 687 CV events [358 cardiac events (20.1%), 153 cerebrovascular events (8.6%) and 176 peripheral arterial events (9.9%)] occurred, and 536 patients (30.0%) died including 234 CV death (13.1%). In the group 0, 1 and 2, 10-year event-free rates were 67.6%, 58.6% and 40.9% for cardiac events (p   Conclusion:  The presence of calcified valves at beginning of HD therapy could predict not only cardiac events but also cerebrovascular and peripheral artery events, and might be associated with systemic atherosclerotic events in ESRD patients.
Prevalence and Severity of High Blood Pressure Among Children Based on the 2017 American Academy of Pediatrics Guidelines
Authors: Atul K. Sharma, Daniel L. Metzger, Celia J. Rodd
Journal: JAMA Pediatrics (2018)

Based on the new 2017 blood pressure guidelines, the prevalence of high blood pressure (BP) among adults has increased from 32% to 46%. Based on new norms and diagnostic thresholds that better align with adult definitions, new clinical practice guidelines were also published for children. The American Academy of Pediatrics clinical practice guidelines for the management of elevated BP in children replace the 2004 fourth report from the National Heart, Lung, and Blood Institute.
Community interventions and peer support for active case finding and treatment support for underserved populations with hepatitis C in the UK, Ireland, Romania and Spain as part of the HEPCARE programme
Authors: J. Surey, D. Menezes, A. Story, J.M. Sanchez, O.A. Cristiana, P. Vickerman, W. Cullen, J. Lambert
Journal: Journal of Hepatology (2018)
The impact of EMR modification and a multi-disciplinary care team on the hepatitis C care cascade of a US Federally Qualified Health Center
Authors: L. Magaldi, N. Brown, C. Coleman, M. Dorshimer, J. Kostman, D. Zaret, T.-W. Preston, R. Rivera, M. Reddy, S. Trooskin
Journal: Journal of Hepatology (2018)
Epigenomics
Authors: Kevin C. Wang, Howard Y. Chang
Journal: Circulation Research (2018)

The advent of high-throughput epigenome mapping technologies has ushered in a new era of multiomics where powerful tools can now delineate and record different layers of genomic output. Integrating various components of the epigenome from these multiomics measurements allows the interrogation of cellular heterogeneity in addition to the discovery of molecular connectivity maps between the genome and its functional output. Mapping of chromatin accessibility dynamics and higher-order chromatin structure has enabled new levels of understanding of cell fate decisions, identity, and function in normal development, physiology, and disease. We provide a perspective on the progress of the epigenomics field and applications and anticipate an even greater revolution in our understanding of the human epigenome for years to come.
Abstract 13083: Multi-Center Study of Risk Factor Status on Entry to a Contemporary Phase 2 Cardiac Rehabilitation Program: Temporal Trends
Authors: Pratik B Sandesara, Danny J Eapen, Laurence Sperling, Richard D Salmon, Neil F Gordon
Journal: Circulation (2015)

Introduction: No comprehensive data are available on temporal trends in the percentage of participants who are not at recommended ASCVD risk factor goal levels on entry to a contemporary phase 2 cardiac rehabilitation (CR) program and, therefore, in need of intensified risk factor intervention. The purpose of this study was to determine whether improvements have occurred in recent years in the control of multiple risk factors in patients entering CR. Methods: In this multi-center registry, we compared the percentage of participants not at goal for select risk factors on entry to CR during 2000-2004 versus 2005-2009. Subjects were 26,956 consecutive patients (age=63.8 + 11.5 years; males=69.8%; females=30.2%) who enrolled in a phase 2 CR program at 35 centers in the US between 2000 and 2009 and completed an initial evaluation on program entry. Statistical significance of differences between groups was analyzed using chi-square and unpaired t-tests and statistical significance was established at p &lt; 0.05. Results: Percentages of patients with risk factors not at goal levels on entry to CR for the 2000-2004 (n=10,900) and 2005-2009 (n=16,056) cohorts are shown in Figure 1 (*statistically significant difference) . Compared to the 2000-2004 cohort, the percentage of the 2005-2009 cohort not at goal was lower (p&lt;0.001) for BP (goal &lt;120/80 mmHg) and LDL cholesterol (goal &lt;100 mg/dl), higher (p&lt;0.001) for BMI (goal &lt;25 kg/m 2 ), and not significantly different (p&gt;0.05) for smoking (goal=no smoking), fasting glucose (goal &lt;100 mg/dl) and physical activity (goal ≥150 min/wk). Conclusions: These data indicate that while the control of some risk factors has improved significantly over time, the control of others has remained unchanged or worsened. The data further demonstrate that multiple risk factors are often inadequately controlled on entry to contemporary phase 2 CR programs and serve to emphasize the need for intensive risk factor intervention during CR.
First real-world data on safety and effectiveness of glecaprevir/pibrentasvir for the treatment of patients with chronic hepatitis C virus infection: Data from the German Hepatitis C-Registry
Authors: T. Berg, U. Naumann, A. Stoehr, C. Sick, G. Teuber, W. Schiffelholz, S. Mauss, J. Hettinger, H. Kleine, A. Pangerl, C. Niederau
Journal: Journal of Hepatology (2018)
P337Circulating CD14+CD16- classical monocytes do not associate to a vulnerable plaque phenotype, nor prognosticate secondary events in atherosclerotic patients
Authors: Jal Meeuwsen, J J De Vries, A Van Duijvenvoorde, S M Van De Weg, G J De Borst, G Pasterkamp, I E Hoefer, Sca De Jager
Journal: Cardiovascular Research (2018)
Open Label Phase I Study of Single Agent Oral RG7388 (idasanutlin) in Patients with Polycythemia Vera and Essential Thrombocythemia
Authors: John Mascarenhas, Min Lu, Elizabeth Virtgaym, Heidi Kosiorek, Marina Stal, Lonette Sandy, Alicia Orellana, Lijuan Xia, Marina Kremyanskaya, Bruce Petersen, Amylou Dueck, Ronald Hoffman
Journal: Blood (2017)
India admits to unapproved drug formulations in market
Authors: G. Mudur
Journal: BMJ (2003)

The Indian government has admitted that drug formulations unapproved by India's drug regulatory agency and not evaluated for effectiveness are prescribed and sold across the country.

The unprecedented admission from the health ministry emerged at a court hearing on nimesulide, a controversial non-steroidal anti-inflammatory drug prescribed in India to treat fever and pain ( BMJ 2003;326:70).

A group of lawyers in New Delhi called Social Jurist has filed a public interest lawsuit challenging the use of nimesulide among children. The group had also objected to unapproved combinations of nimesulide and other drugs, prescribed for use in adults, as illegal.

Documents submitted to the court said …
Role of inflammation gene polymorphisms on pain and response to radiotherapy in multiple myeloma patients with painful bone destructions.
Authors: Milda Rudzianskiene, Arturas Inciura, Rolandas Gerbutavicius, Ruta Dambrauskiene, Viktoras Rudzianskas, Elona Juozaityte
Journal: Journal of Clinical Oncology (2016)

8030 Background: Previous researches have demonstrated, that the severity of pain perception and it’s response to analgesia is highly dependent on gene polymorphism encoding for cytokines. We evaluated 12 single nucleotide polymorphisms (SNP) in 6 genes encoding for cytokines in multiple myeloma patients (n = 81) and assessed their influence on pain severity and response to palliative radiotherapy. Methods: Pain intensity was assessed by Visual Analogue Scale. The total dose of opioids was converted to a mean morphine-equivalent dose (mg/day). Pain intensity and dose of analgesics were evaluated before radiotherapy and 4, 12 and 24 weeks after the treatment. Analysis of SNP of genes IL6, IL10, TNFA, IL1A, IL1B, IL1RN was carried out. Multivariable regression was used to assess correlations between severe pain and SNP, adjusting demographic and clinical variables. Results: Severe pain was more prevalent among patients with a Karnofsky index ≥ 60% (OR 5.84; 95% CI 1.49 – 22.87) and patients with GG genotype of IL1RN c.1812G > A polymorphism (OR 2.79; 95% CI 1.05 – 7.46). The analysis revealed that patients with IL1A c.889C > T CC genotype had a better response to radiotherapy after 12 and 24 weeks, compared to patients with TT and CT genotypes (p = 0.013 and p = 0.006 respectively). Patients with IL1B c. 3953C > T CC genotype also demonstrated a better response to radiotherapy after 12 and 24 weeks, compared to patients with TT and CT genotypes (p = 0.002 and p = 0.002 respectively). Patients with IL1RN c.11100T > C CC genotype had a faster response (after 4 weeks) to radiotherapy, compared to patients with TT and CT genotypes (p = 0.023). Conclusions: This study provides preliminary evidence, that genes encoding for particular cytokines play a significant role on pain severity and response to radiotherapy in multiple myeloma patients. Clinical trial information: NCT02024815.
Analyzing the efficacy and safety of immunotherapy in pancreatic ductal adenocarcinoma (PDA): A systematic review and meta-analysis.
Authors: Hani M. Babiker, Umar Zahid, Carol L. Howe, Aaron James Scott, Irbaz Bin Riaz, Cynthia M Elliott, Utkarsh H Acharya, Alejandro Recio Boiles, Emad Elquza, Daruka Mahadevan
Journal: Journal of Clinical Oncology (2018)

512 Background: The tumor microenvironment in PDA is heterogeneous and immunosuppressive given the presence of regulatory T cells and exhausted effector T cells. Despite the upsurge of effective immunotherapeutic agents (IA) in other tumor types, the role in PDA remains unknown. We conducted a meta-analysis of IA in PDA. Methods: Following PRISMA guidelines, we searched PubMed/MEDLINE, Elsevier/Embase, Wiley/Cochrane Library and ClinicalTrials.gov. Articles were selected per the following criteria: (1) Study participants had a diagnosis of PDA; (2) An IA was used in the trial. Titles, abstracts and full text articles were reviewed by 2 independent reviewers; disagreements were resolved by a third. Data extraction and analysis were performed by 3 independent reviewers. Descriptive analysis, mean, median, confidence interval and forest plots were used for statistical analysis. Results: We found 20,792 studies through the database, 16,105 remained after duplicates were removed and 15,889 were excluded due to irrelevance. Strict inclusion criteria were applied to the full text of 216 articles. The most common reason for exclusion were conference abstracts (44%) and ongoing trials (16%). Fifty-four trials (39 metastatic (met), 12 adjuvant (Ad) and 3 neoadjuvant (nAd) met criteria for further analysis. Age range was 27-86 (median 61) and 52.3% were males. IA included cytokine therapy (33%), peptide vaccines (22%), dendritic cell vaccine (13%), oncolytic viruses (9%), CTLA-4 inhibitors (2%) and others. IA in met-PDA had a median overall survival (mOS) of 8.1 months (ms) and a disease control rate (DCR) of 55.4% (95% CI, 51.85-58.95). There was no statistical difference in DCR among IA subtypes (range 49-60%) (p = 0.22). The mOS of Ad-PDA trials was 25 ms (historically comparable to gemcitabine, p = 0.75) and 18 ms for nAd-PDA. The most common Gr1/2 toxicities were skin reactions, fever, and chills and Gr3/4 were cytopenias, diarrhea, and mucositis. One death occurred due to neutropenic sepsis. Conclusions: IA demonstrates modest efficacy in the treatment of met-PDA albeit exhibits a favorable toxicity profile. Many trial results are available only in abstract format and some are ongoing.
Vogt-Koyanagi-Harada Syndrome Induced by Pembrolizumab in a Patient with Non–Small Cell Lung Cancer
Authors: Tomoki Tamura, Etsuko Akimoto, Chiaki Matsumoto, Syunta Mori, Tatuya Nishi, Kennichiro Kudo, Syouichi Kuyama
Journal: Journal of Thoracic Oncology (2018)