tbuckley/cabot-search huggingface dataset:
Possible mechanisms of serotonin and aprepitant actions in chemotherapy induced nausea and vomiting (CINV): Insights into the mechanisms of serotonin and aprepitant actions in CINV—According to recent multi-institutional double-blind randomized clinical research on the AC regimen.
Authors: Michiko Tsuneizumi, Mitsue Saito, Hideaki Ogata, Goro Kutomi, Keiko Hosoya, Yuko Kawai, Joe Matsuoka
Journal: Journal of Clinical Oncology (2017)

6587 Background: One of our interests has been whether palonosetron(P) would be superior to granisetron(G) when administering triplet antiemetic therapy for the prevention of CINV, since a prior trial demonstrated P to be superior to G for controlling CINV induced by highly emetogenic chemotherapy (HEC) in doublet therapy. In this study(TTT; trial for antiemetic therapy), we assessed the efficacies of P and G for use as triplet antiemetic therapy for AC, by monitoring CINV, focusing complete response (CR; no vomiting and no rescue medicine) in the delayed phase. The primary endpoint of TTT was a CR during the delayed phase with 5-HT3ra plus dexamethasone and aprepitant administration for AC. The purpose of gaining insights into the possible mechanism of action of aprepitant and P was to obtain ideas for the next strategy against CINV. Methods: Between 2012 and 2015, 491 breast cancer receiving AC were recruited from 11 institutions, and randomly assigned to either single-dose P(0.75mg) or G(40μg/kg) prior to AC on day 1, both with dexamethasone (9.9 mg) and aprepitant (125mg) on day 1 followed by additional doses (80mg) on days 2 and 3. Age, institution and habitual alcohol intake were used as stratification factors. The primary endpoint was a CR. Results: All 491 patients were included in efficacy analyses: 246 patients in the group P and 245 in the group G. The difference in CR during the delayed phase, i.e. 24 hrs after the administration of AC, did not reach statistical significance, however, there was a remarkable difference between 48 and 72 hrs in the day-to-day analysis(p &lt; 0.02). Conclusions: P showed better efficacy in controlling CINV between 48 to 72 hours after AC, than G as triplet antiemetic therapy for AC. We can reasonably speculate that the influence of serotonin has two peaks (0-24 hrs and 48-72 hrs). For controlling CINV in the delayed phase, not only an NK1 receptor antagonist but also administering a 5-HT3ra with long life should be considered until 72 hrs after HEC. Clinical trial information: UMIN 000007882.
Postmortem Incidence of Acute Surgical- and Trauma-Associated Pathologic Conditions in Prison Inmates in Miami Dade County, Florida
Authors: Alexander Busko, Hahn Soe-Lin, Cecily Barber, Rishi Rattan, Roderick King, Tanya L. Zakrison
Journal: JAMA Surgery (2018)

Postmortem Incidence of Acute Surgical-and Trauma-Associated Pathologic Conditions in Prison Inmates in Miami Dade County, FloridaAccording to the Bureau of Justice Statistics, more than 2.2 million adults were incarcerated in the United States as of 2015, 1 representing 0.7% of the total population.The United States has the highest rate and number of incarcerated persons in the world. 2 To date, no national statistics on surgical outcomes have been reported for the actively incarcerated prison population in the United States, to our knowledge.Florida has the third-largest incarcerated population in the country. 2 Incarcerated individuals represent a vulnerable patient population, in particular with regards to medical care. 3 We hypothesized that surgical access would be affected in this population and sought to quantify the postmortem incidence of acute surgical-and trauma-associated pathologic conditions of inmates in Miami Dade County, Florida.Methods | From January 1, 2008, to December 31, 2014, we reviewed all medical examiner reports for any inmate who was incarcerated and died in Miami Dade County, Florida.Demographic data were recorded and comorbid medical conditions reviewed.Rates of surgical intervention were recorded.All primary causes of death determined by the medical examiner were analyzed and mortality associated with acute surgical-or trauma-specific pathologic conditions quantified.Statistical analysis was conducted from January 15, 2015, to June 30,
The fibrinogen/CRP ratio as a novel prognostic parameter for pancreatic cancer patients.
Authors: Thomas Winder, Michael Stotz, Alexander Rheinhard Siebenhuener, Konstantin Schlick, Teresa Magnes, Panagiotis Samaras, Joanna Szkandera, Pierre-Alain Clavien, Daniel Neureiter, Richard Greil, Bernhard C. Pestalozzi, Armin Gerger, Alexander Egle, Martin Pichler
Journal: Journal of Clinical Oncology (2016)

e15701 Background: Inflammatory and coagulative processes influence cancer initiation and progression. Fibrinogen and C-reactive protein (CRP) are markers of the systemic inflammatory response as well as important mediators of complex intracellular signaling activated by interleukins with a crosstalk to STAT3- and NF-κB. Despite their similarities, they represent different inflammation drivers in terms of underlying pathophysiological triggers, genetic background and cellular as well as molecular effects. The aim of this study was to investigate the fibrinogen/CRP as a novel prognostic parameter in patients with pancreatic cancer. Methods: Six hundred and twelve consecutive patients with pancreatic adenocarcinoma from an international tri-center study (Austria and Switzerland) had routine measurements of fibrinogen/CRP levels. Their clinical outcome was related to their fibrinogen/CPR ratio. An optimal cut-off value was calculated by ROC analysis, and the prognostic impact of this variable on survival was evaluated using Kaplan-Meier curves, multivariate Cox proportional models and Harrel´s concordance index. Results: A low fibrinogen/CRP ratio (cut off value: 125) represented a poor prognostic factor for clinical outcome (p < 0.001) in patients with pancreatic cancer. The hazard ratio (and 95% confidence interval) for risk of death in the group of low fibrinogen/CRP ratio was 1.47 (1.21 – 1.79, p < 0.001), which holds true in a multivariate analysis including gender, age, tumor stage, grading and levels of CA19-9. Conclusions: For the first time, the fibrinogen/CRP ratio is described as a novel prognostic variable in patients with pancreatic cancer. This marker might be helpful in patients risk assessment and more personalized risk stratification of patients in clinical trials.
IMiDs prime myeloma cells for daratumumab-mediated cytotoxicity through loss of Ikaros and Aiolos
Authors: Pasquale L. Fedele, Simon N. Willis, Yang Liao, Michael S. Low, Jai Rautela, David H. Segal, Jia-Nan Gong, Nicholas D. Huntington, Wei Shi, David C. S. Huang, George Grigoriadis, Julie Tellier, Stephen L. Nutt
Journal: Blood (2018)
Abstract 11969: Post Myocardial Infarction Hearts Exhibit Larger Calcium Sparks which are Not Modified by Flecainide
Authors: Markus B Sikkel, Mit Shah, Thomas Desplantez, Thomas P Collins, Peter O'Gara, Sian E Harding, Alexander R Lyon, Kenneth T MacLeod
Journal: Circulation (2011)

A proportion of arrhythmias which occur following MI and ischemic cardiomyopathy may result from increased sarcoplasmic reticulum (SR) Ca2+ leak. In the CAST trial flecainide was assessed for its ability to reduce post-MI arrhythmias but in fact increased arrhythmias and mortality. Recent evidence has shown flecainide to be effective in the therapy of some forms of triggered arrhythmia, in part through reduction in Ca2+ spark amplitude. We set out to assess whether flecainide had a specific effect on post MI cardiomyocytes that might help explain the lack of benefit seen in CAST. Confocal microscopy of isolated intact rat ventricular cardiomyocytes treated with 30nM isoprenaline (ISO) was used to assess sparks in the presence (FLEC) or absence (CTRL) of 5µM flecainide loaded for 5 mins (n=733 sparks from 52 cells). Cells were isolated either from rats with MI induced approximately 4-8 weeks earlier (MI) or age matched controls (AMC). This gave four main conditions for spark measurement - AMC-CTRL, AMC-FLE...
TCT-454 Myocardial Fibrosis Imaging by Speckle Tracking Echocardiography Improves Risk Stratification in Severe Aortic Stenosis After Transcatheter Aortic Valve Replacement
Authors: Ahmad Manshad, Mohamad Hemu, Fatima Ballout, Fareed Moses Collado, Clifford Kavinsky
Journal: Journal of the American College of Cardiology (2018)
Does total breastfeeding time influence the clinicopathologic characteristics and prognosis in breast cancer patients?
Authors: Sebnem Yaman, Sercan Aksoy, Mehmet Ali Nahit Sendur, Zafer Arik, Nuriye Ozdemir, Nurullah Zengin, Kadri Altundag
Journal: Journal of Clinical Oncology (2012)

e11033 Background: Several studies suggest that total breastfeeding time reduces breast cancer risk although the underlying mechanism is unclear. However the total breast feeding is not well studied as a prognostic factor in patients with cancer. We aimed to investigate the possible prognostic role of total breastfeeding time (TBT) in breast cancer patients both on relation with tumor characteristics and also on prognosis. Methods: We retrospectively evaluated 1673 breast cancer patients who followed up between 2004 and 2010 in our clinic. The total breastfeeding time was obtained by summing the breastfeeding time for each child. The total breastfeeding time was categorized as: 1-The total breastfeeding time between 0-12 months; 2-Total breastfeeding time more than 12 months. Results: The median total breastfeeding time of this population was 12 months. 1011(60.4%) of these have total breastfeeding time between 0-12 months and 662 (%39.6) of them have total breastfeeding time more than 12 months. T, N, M stages were similar in both groups. Total breastfeeding time was not correlated with any of clinical parameters including lymphovascular invasion, extracapsulary invasion, estrogen receptor, progesterone receptor, HER2 2 status, perineural invasion. There was a positive correlation found between total breastfeeding time and BMI (r=1.24; P&lt;0.001).TBT (≥12 months) has poor disease free survival (DSF) time (116 vs. 75 months; p=0.002) and 3-years overall survival rate (98% vs 95.2%; p=0.049). Conclusions: In our study; total breastfeeding time was not found to be correlated with any of the clinico-pathological parameters. However, disease free survival and overall survival were statistically shorter in patients whose total breastfeeding time was more than 12 months.
Effect of fish oil supplementation in pregnancy on bone, lean, and fat mass at six years: randomised clinical trial
Authors: Rebecca Kofod Vinding, Jakob Stokholm, Astrid Sevelsted, Tobias Sejersen, Bo L Chawes, Klaus Bønnelykke, Jonathan Thorsen, Laura D Howe, Martin Krakauer, Hans Bisgaard
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To examine the effect of supplementation with n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) in pregnancy on anthropometry and body composition in offspring. <h3>Design</h3> Double blinded, randomised controlled trial. <h3>Setting</h3> Copenhagen Prospective Studies on Asthma in Childhood<sub>2010</sub> cohort. <h3>Participants</h3> 736 pregnant women and their offspring. <h3>Intervention</h3> n-3 LCPUFA (fish oil) or control (olive oil) daily from pregnancy week 24 until one week after birth. <h3>Main outcome measures</h3> Height/length, weight, head, and waist measurements and body composition from dual energy <i>x</i> ray absorptiometry (all pre-specified secondary endpoints of the n-3 LCPUFA trial; the primary outcome for the trial was persistent wheeze/asthma). <h3>Results</h3> The mean body mass index (BMI) z score was increased between age 0 and 6 years in the fish oil supplementation group compared with the control group (0.14 (95% confidence interval 0.04 to 0.23); P=0.006). At 6 years, supplementation was associated with a higher BMI z score (0.19 (0.06 to 0.32); P=0.004), a higher weight/height (3.48 (0.38 to 6.57) g/cm; P=0.03), and a larger waist circumference (0.6 (0.0 to 1.2) cm; P=0.04) but not a higher proportion of obese children, using International Obesity Task Force grades. The dual energy <i>x</i> ray absorptiometry scan at age 6 years showed a higher total mass (395.4 (86.6 to 704.3) g; P=0.01) in the supplementation versus the control group, explained by a higher lean mass (280.7 (98.9 to 462.4) g; P=0.002), a higher bone mineral content (10.3 (2.3 to 18.1) g; P=0.01), and a non-significantly higher fat mass (116.3 (−92.9 to 325.5) g; P=0.28), but no differences were seen in total body fat or lean mass percentage. <h3>Conclusion</h3> Fish oil supplementation from the 24th week of pregnancy led to a higher BMI in the offspring from 0 to 6 years of age but not an increased risk of obesity at age 6. The body composition at age 6 years in children given fish oil supplementation was characterised by a proportional increase in lean, bone, and fat mass suggesting a general growth stimulating effect of n-3 LCPUFA. <h3>Trial registration</h3> Clinicaltrials.gov NCT00798226
Abstract 18364: Barriers to Community CPR Training in High-risk Neighborhoods- Lessons Learned From the Hands-only CPR Program
Authors: Ashish R Panchal, Marina Del Rios, Jennifer Waxler, Debra Heard, Comilla Sasson
Journal: Circulation (2015)

Background: Improving the performance of bystander CPR in high-risk communities is essential for decreasing disparities in cardiac arrest survival. In this study, we identified the barriers to community CPR training in high-risk neighborhoods as part of the multi-centered trial of the Hands-Only™ CPR Program - a novel intervention targeting neighborhoods with high incidence of cardiac arrest and low bystander CPR rates. Methods: The Hands-Only CPR program was implemented in high-risk neighborhoods in Tampa, FL, Columbus, OH and Chicago, IL. Participants underwent group-based Hands-Only CPR training (1 hour) with a CPR Anytime kit, which includes a DVD and manikin. A $10 gift card incentive was offered to participants who used the kits to train family and friends and returned data at 2 weeks. Study coordinators identified barriers and facilitators to recruitment, training and follow-up. Results: In 20 weeks, 815 participants were recruited (Tampa, n=580; Columbus, n=165; Chicago, n=70). Participant demographics differed by site. Participants in Columbus and Chicago were predominantly Black (81% and 88%, respectively) whereas in Tampa they were White (42%) and Hispanic (38%). Annual income was &lt; $30,000 for 45% of participants. Recruitment was challenging even with participants receiving a $10 incentive, CPR Anytime kit, and meal with training. This may be related to CPR training being a low priority compared to other needs (i.e work, child care, neighborhood safety). Communication challenges with the community was cited as another barrier leading to low return response rate of 11%. Highest response rates occurred in Columbus (33%) where community liaisons lived in the neighborhood and interacted with residents daily. Participants did feel comfortable training others using the CPR Anytime kits (P&lt;0.001) The average number of family and friends trained was 4.1 (range: 1 to 15) individuals per respondent. Conclusion: The Hands-Only CPR program facilitates training in high-risk neighborhoods and minority populations through a train the trainer model. The biggest challenges faced by the sites were recruiting participants and response rates on family and friends trained. Future research will need to assess methods to improve outreach to this population.
Overview of pancreatic neuroendocrine tumor management and survival in the Netherlands.
Authors: Cansu Guney Genc, Casper H.J. van Eijck, Els J.M. Nieveen van Dijkum
Journal: Journal of Clinical Oncology (2016)

e15660 Background: Pancreatic neuroendocrine tumors (pNETs) are classified as rare diseases with a prevalence of 2/100.000. As a result of improved recognition and imaging incidence rises over the past decades. To develop optimal treatment strategies more insight in the prognosis and treatment outcomes is needed. Methods: From a retrospective national database of pNET patients an overall overview is made using descriptive and statistical analyses. Results: Between 2008 – 2013 638 patients with pNET were diagnosed in the Netherlands. With a mean age of 60.9 years at diagnosis median follow-up was 25.7 months and 261 patients died. Metastasis in lymph nodes were seen in 156 (25.4%) cases, distant metastasis in 235 (38.3%). Survival of patients with distant metastasis was worse (p = < 0.001), with decreasing influence at advanced tumor stage (T1-2 p < 0.001, T3 p = 0.019, T4 p = 0.11). 5 year cumulative survival without distant metastasis was 79%, significantly higher compared to patients with distant metastasis (27%, p < 0.001). Resection for metastatic disease showed better 5 year survival (87%) compared to systemic treatment (28%, p = 0.004). Without surgery these patients had better survival with systemic treatment (28%) in contrast to no treatment (15%, p = 0.015); independent of tumor stage (T1-2 vs T3-4, p < 0.001). Although the former is also true for patients without distant metastasis (p = 0.015), T1-2 showed better survival (87%) compared to T3-4 (28%, p = 0.004) in this group. Independent of metastatic status survival was better for grade 1 or 2 tumors compared to grade 3 (both p < 0.001). Nodal status in did not have an influence on survival, neither when separated for distant metastasis, tumor stage or tumor grade (all p > 0.05). Conclusions: Distant metastasis, tumor stage and tumor grade seem to have effect on survival. Nodal status, however, does not. contribution of distant metastasis to poor survival is reduced with advanced tumor stage. In the presence of distant metastasis, resection and systemic treatment show better survival.
A low dose and individualized regimen for palliative treatment of head and neck squamous cell cancer.
Authors: Rohit Bishnoi, Jeffery A Bennett, David Reisman
Journal: Journal of Clinical Oncology (2016)

e17501 Background: Inoperable or metastatic HNSCC is known to have poor prognosis. Regimens TPF (Taxol, Platin and FU) or PFE (Platin, FU and EGFR inhibitors) are among first line therapies. Due to toxicities, these regimens are not the most suitable for palliative treatment where quality of life is very important. The principle axiom of chemotherapy has been that the highest tolerated is the preferred regimen (with acceptable grade 3 and 4 toxicities) and high toxicity limits the number of cycles given. Methods: This is a retrospective study of 15 patients with HNSCC where treatment goal was palliative. Of 15 patients, 8 got TPF while 7 got PFE. Total 129 cycles were given with median of 9 cycles (range 3 to 14). These patients were started on very low doses of chemo and then slowly titrated up based on tolerance and response. Unexpectedly we noted very good response with lower doses and maximal doses were not needed. Median dose for Cis-platin was 40 mg/m2; paclitaxel was used at median dose of 80/mg/m2 and 5-FU was used at 360 mg/m2/day for 5 days. Cetuximab was used at recommended dose. Rarely cetuximab was replaced with Panitumumab at a median dose of 3.5 mg/kg. Results: At initial follow up (mean - 64 days, 3 Cycles), we achieved 100% disease control and 80% overall response rates. Good response of 60% disease control rate and 60% overall response rate was maintained till late (mean-217 days, 9 cycles). After stopping chemo after > 9 cycles, 4 patients were still disease free after almost 1 year post-chemo. 3 patients had pathologic complete response even though they had some residual disease radiologically. Average tumor volume reduction was about ~53%, ~69% and ~73% after 3(n = 15), 6(n = 13) and 9(n = 8) cycles respectively. Median progression free survival (PFS) was 10.03 months and overall survival of 15.77 months. Only grade 3 hematologic toxicity noted was neutropenia in 3 (20%) patients. 1 (6.67%) patient each had grade 3 nausea, vomiting and stomatitis. Conclusions: This small study suggests that lower doses and more cycles can be an option with similar or better results as noted. Due to low toxicity it is better tolerated especially in palliative intent. Moreover, these results call in question the axiom that higher doses are more effective.
Premedication for Neonates Requiring Nonemergency Intubation
Authors: Frank Fideler, Christian Grasshoff
Journal: JAMA (2018)

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Abstract 16112: Could Cardiac Re-Synchronization via His Bundle Pacing Reduce Arrhythmic Risk?
Authors: Jonathan Logue, Pugazhendhi Vijayaraman, Behzad Pavri
Journal: Circulation (2017)

Introduction: For patients with LBBB or frequent RV pacing and cardiomyopathy, His bundle pacing (HBP) recruits the left bundle branch and narrows the QRS complex. The effects of HBP on repolariz...
Accuracy and precision of transcutaneous carbon dioxide monitoring: a systematic review and meta-analysis
Authors: Aaron Conway, Elizabeth Tipton, Wei-Hong Liu, Zachary Conway, Kathleen Soalheira, Joanna Sutherland, James Fingleton
Journal: Thorax (2018)

Background Transcutaneous carbon dioxide (TcCO 2 ) monitoring is a non-invasive alternative to arterial blood sampling. The aim of this review was to determine the accuracy and precision of TcCO 2 measurements. Methods Medline and EMBASE (2000–2016) were searched for studies that reported on a measurement of PaCO 2 that coincided with a measurement of TcCO 2 . Study selection and quality assessment (using the revised Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2)) were performed independently. The Grading Quality of Evidence and Strength of Recommendation approach was used to summarise the strength of the body of evidence. Pooled estimates of the mean bias between TcCO 2 and PaCO 2 and limits of agreement with outer 95% CIs (termed population limits of agreement) were calculated. Results The mean bias was −0.1 mm Hg and the population limits of agreement were −15 to 15 mm Hg for 7021 paired measurements taken from 2817 participants in 73 studies, which was outside of the clinically acceptable range (7.5 mm Hg). The lowest PaCO 2 reported in the studies was 18 mm Hg and the highest was 103 mm Hg. The major sources of inconsistency were sensor location and temperature. The population limits of agreement were within the clinically acceptable range across 3974 paired measurements from 1786 participants in 44 studies that applied the sensor to the earlobe using the TOSCA and Sentec devices (−6 to 6 mm Hg). Conclusion There are substantial differences between TcCO 2 and PaCO 2 depending on the context in which this technology is used. TcCO 2 sensors should preferentially be applied to the earlobe and users should consider setting the temperature of the sensor higher than 42°C when monitoring at other sites. Systematic review registration number PROSPERO; CRD42017057450.