tbuckley/cabot-search huggingface dataset:
Outcome of pancreatic cancer patients at Windsor regional cancer program: Single institution experience.
Authors: Akmal Ghafoor
Journal: Journal of Clinical Oncology (2015)

e15294 Background: Pancreatic cancer prognosis remains poor even in those with resectable disease.World wide it is eight leading cause of cancer death in men and ninth in women,As the incidence of pancreatic cancer increases with age, an aging population means that disease burden is expected to rise with time. Thus, there is a clear need for further information regarding the management of pancreatic cancer. Purpose: Determine the current overall survival (OS) of pancreatic patients treated at Windsor Regional Hospital’s Cancer Centre based on stage of disease. Methods: Data were analyzed using Kaplan-Meier and multivariate Cox-regression analyses as appropriate based on a 95% CI or an alpha of 0.05. Results: OS was significant (P < .001) between groups with 3.63 (95% CI, 2.84-4.43), 6.57 (95% CI, 4.06-9.08), and 15.57 (95% CI, 11.79-19.35) months in the metastatic, locally-advanced, and localized disease groups respectively. OS was higher in metastatic-stage patients who received chemotherapy (6.07 months [95% CI, 4.75-7.39]) compared to those who received supportive therapy alone (2.50 months [95% CI, 2.16-2.84]; P < .001). Advanced-stage patients with partial or stable response to chemotherapy had higher OS (10.53 months [95% CI, 6.35-14.72]) in comparison to those with progression (6.33 months [95% CI, 5.79-6.88]) or undocumented response (3.30 months [95% CI, 1.76-4.84]; P < .001). In patients undergoing surgical resection of localized disease, adjuvant therapy increased OS and DFS vs. surgical excision alone after Cox regression analysis adjusting for margin status (P = 0.013; 95% CI, 0.278-0.862). Positive margins reduced OS (HR 2.670; P = 0.001; 95% CI, 1.467-4.860). Conclusions: This single institution analysis demonstrates OS significantly differed based on disease status at diagnosis. Advanced-stage patients with stable or partial response to chemotherapy had increased OS, as did adjuvant treatment surgical patients with localized disease once adjusting for margins.
Abstract P188: Cluster Analysis of Systolic Blood Pressure Trajectories Before and After Initiation of Anti-Hypertensive Therapy
Authors: David R Gagnon, Yuk-Lam Ho, Jacqueline P Honerlaw, J. M Gaziano, Peter W Wilson, Luc Djousse, Kelly Cho
Journal: Circulation (2019)

Background: Responses to new anti-hypertensive therapy (AHT) can differ. Cluster analysis of longitudinal systolic blood pressure (SBP) data allows identification of individuals with similar trajectories, which enables hypothesis generation to potentially explain the observed patterns. We examined electronic health data from U.S. Veterans initiating AHT from 2002-2009. Methods: SBP was tracked for 1 year before and up to 2 years after AHT initiation. Subjects were clustered using a K-means approach with the mean of the squared Euclidean distances as a distance metric and evaluated for the optimal number of clusters. Thin-plate splines were used to display the smoothed trajectories of each group with predicted SBP measures over time. Results: A total of 45,598 subjects contributed 783,852 SBP measurements. Five clusters of subjects with similar trajectories were produced, providing visualization of SBP [Figure 1] prior to initiation, immediately after starting therapy, and after longer treatment duration. For example, Group 1 had the lowest mean age, lowest HDL-C, lowest LDL-C, highest triglycerides, lowest baseline SBP, lowest insulin use, and highest statin use. Conclusions: Trajectory clustering for SBP identifies distinct response groups that differ in response to therapy, laboratory measures, and medication use. Future analyses can examine anti-hypertensive medication use, compliance and genetic factors to identify potential causes for these trajectories. These cluster analyses can provide new analytical approaches related to risk factor diagnosis and treatment.
Similar Effectiveness of Total and 270° Posterior Fundoplication for the Treatment of Gastroesophageal Reflux Disease
Authors: Marco G. Patti
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Abstract 422: CITED4 is Sufficient to Induce Physiologic Cardiac Hypertrophy and Necessary to Protect Against Pathological Hemodynamic Stress
Authors: Carolin Lerchenmueller, Vassilios J Bezzeridis, Colin Platt, Chunyang Xiao, Anthony Rosenzweig
Journal: Circulation Research (2016)

Cardiac hypertrophy is an adaptive response to increased physiologic or pathologic hemodynamic stress. Previous work from our laboratory suggested that the CEBPβ/ CITED4 pathway plays an important role in exercise-induced cardiac hypertrophy. Consistent with this model, our laboratory recently found that inducible cardiac expression of CITED4 in adult mice increases heart weight and cardiomyocyte size with normal systolic function and a gene expression profile consistent with physiologic growth. After ischemia-reperfusion injury (IRI), induced CITED4 mice show significant functional recovery and evidence for decreased adverse remodeling. Next, we sought to investigate the role of CITED4 in the setting of physiologic (forced swimming exercise) and pathological (transverse aortic constriction, TAC) cardiac hypertrophy. Cardiomyocyte-specific CITED4 knockout mice (C4KO) undergoing a three week swimming exercise protocol showed modestly but significantly reduced systolic function when compared to control animals (%FS controls 55.4±1.09 vs. C4KO 51.75±0.86; p=0.025). C4KO mice exposed to TAC demonstrated a more rapid and severe decline in cardiac function after TAC (at 6 weeks post surgery, %FS controls 41.55±2.06 vs. C4KO 32.51±2.67; p=0.024). Both in vitro and in vivo we demonstrate that CITED4 is necessary and sufficient for activation of mTOR signaling. Of note, mTORC1 inhibition by rapamycin abrogated the beneficial effects of CITED4 expression after IRI. Taken together, our data identify CITED4 as a novel regulator of mTOR signaling. Moreover they demonstrate that CITED4 is sufficient for physiologic growth and to protect against adverse remodeling after ischemic injury. CITED4 is also necessary for adaptive responses to pathological biomechanical stress and may represent a novel therapeutic target to mitigate adverse ventricular remodeling.
Accuracy of Transient Elastography Data Combined With APRI in Detection and Staging of Liver Disease in Pediatric Patients With Cystic Fibrosis
Authors: Peter J. Lewindon, Mora V. Puertolas-Lopez, Louise E. Ramm, Charlton Noble, Tamara N. Pereira, Julie A. Wixey, Gunter F. Hartel, Diego A. Calvopina, Daniel H. Leung, Grant A. Ramm
Journal: Clinical Gastroenterology and Hepatology (2019)
FOXO transcription factors at the interface between aging and cancer
Authors: Anne Brunet
Journal: Cancer Research (2007)

SY30-03  Aging is regulated by modifications in single genes and by simple changes in the environment. The signaling pathway connecting insulin, Akt, and FOXO transcription factors provides the most compelling example for a conserved genetic pathway that integrate environmental stimuli to regulate lifespan. FOXO transcription factors (FOXO) promote longevity and tumor suppression, suggesting that these factors may link longevity and cancer prevention. FOXO transcription factors are directly phosphorylated in response to insulin/growth factor signaling by the protein kinase Akt, thereby causing their sequestration in the cytoplasm. In the absence of insulin/growth factors, FOXO factors translocate to the nucleus where they trigger a range of cellular responses, including resistance to oxidative stress, a phenotype highly coupled with lifespan extension. FOXO factors integrate oxidative stress stimuli via phosphorylation and acetylation of a series of novel sites. Oxidative stress stimuli elicit the physical interaction between FOXO and SIRT1 deacetylase, a member of the Sir2 family, which has the remarkable ability to extend longevity in invertebrates. Our recent results indicate that FOXO transcription factors are also regulated in response to nutrient deprivation by AMP-dependent protein kinase (AMPK), a protein kinase activated by the tumor suppressor LKB1. The energy-sensing AMPK directly phosphorylates FOXO transcription factors at six previously unidentified conserved regulatory sites. AMPK phosphorylation enhances FOXO transcriptional activity, leading to the expression of specific target genes involved in stress resistance and changes in energy metabolism. The AMPK-FOXO pathway plays a crucial role in the ability of caloric restriction to extend lifespan in worms. As caloric restriction extends lifespan and delays the onset of cancer cancer, understanding how FOXO translate environmental conditions into changes in gene expression that extend lifespan will be pivotal to identify ways to slow aging and age-dependent diseases.
Abstract P131: Sex Specific Patterns of Heart Rate Variability Following Acute Coronary Syndrome Do Not Drive 2-Year Hospital Readmission Outcomes
Authors: Adrienne Oneil, Anna J Scovelle, C. Barr Taylor, David L Hare, Emma Thomas, Samia Toukhsati, John Oldroyd, Brian Oldenburg
Journal: Circulation (2019)

Introduction: Women experience poorer clinical outcomes after Acute Coronary Syndrome (ACS). While the reason for this differential is unclear, autonomic function -indicative of vagal and sympathetic modulation directed to the sinus node- is a candidate mechanism. Hypothesis: That sex-specific differences in heart rate variability (HRV) in the year following ACS drive all-cause readmission outcomes after 2-years. Methods: 416 ACS patients were enrolled in the ADVENT longitudinal cohort study after admission to a large cardiology hospital (January 2013 to June 2014). At 1 and 12 months following discharge, autonomic functioning was measured by HRV using time and spectral analysis via 3-lead electrocardiogram at the Study Centre. All-cause hospital readmission was collected from an audit of hospital records by medically trained researcher fellows. Hierarchical linear regression analyses were used to determine the extent to which HRV parameters (Standard Deviation of RR, Median RR (millisecond), Low Frequency Power, Very Low Frequency Power), drive sex-specific readmission outcomes (yes/no) over 2-years. Interaction terms (sex x individual HRV parameter) were used to determine the extent to which HRV was a modifier of the main effects model. Results: Women were more likely to be rehospitalized for all cause morbidity over the ensuing 2-years, however this was not statistically significant (Coef: 0.09; 95% CIs: -0.03, 0.21). The inclusion of only one of the HRV parameters (Median RR (ms)) substantially ameliorated the chance of women being readmitted (adj. Coef -0.47, 95% CIs: -1.38, 0.43; ns). Conclusion: Women experience significantly poorer autonomic functioning in the year following ACS, but this does not appear to influence sex-specific all-cause readmission over 2 years in a statistically meaningful way.
Small cell bladder carcinoma: Single institution experience.
Authors: Megan Wheelden, Matthew Kaag, Junjia Zhu, Sheldon L. Holder, Joseph J. Drabick, Jay D. Raman, Leonard Tuanquin, Suzanne Merrill, Joshua Warrick, Monika Joshi
Journal: Journal of Clinical Oncology (2019)

468 Background: Small cell bladder carcinoma (SCBC) is an uncommon neuroendocrine tumor with poor prognosis. Treatment has largely been derived from data for small cell lung carcinoma and typically includes a multimodality approach with chemotherapy (chemo) serving as the backbone along with radical cystectomy (RC), and radiation (RT). Prior studies have demonstrated conflicting results regarding survival benefit. Methods: We performed a retrospective chart review of patients with SCBC between 2003 and 2017. We compared baseline patient characteristics and patient outcomes. OS was measured from time of initial diagnosis to death or last follow-up. Subgroup analyses were performed between patients treated with chemoRT vs. chemoRC using Fisher’s exact test for categorical variables, and nonparametric Wilcoxon Rank-Sum test for quantitative variables. Kaplan-Meier analyses were done on OS and RFS. All tests were two-sided and statistical significance level of 0.05 was used. Results: We identified a total of 31 patients with SCBC; 28 were non-metastatic and 3 were metastatic. Of the non-metastatic, 14 received chemoRT and 4 received chemoRC. The median age was 70; M:F ratio was 17:1. The median RFS in chemoRT patients was 3.05 yrs, and in chemoRC, RFS was not reached (p = 0.18). The median OS in chemoRT and chemoRC were 10.1 and 10.7 yrs respectively (p = 0.38). The overall median OS for SCBC was 2.45 yrs. Conclusions: There were no statistically significant differences in regards to median RFS or OS between the chemoRT and chemoRC patients, but this analysis was limited by the small sample size. However, the median OS in non-metastatic SCBC patients who received treatment with curative intent (chemoRT or chemoRC) was noticeably longer than that of all SCBC patients. This median OS is also longer than anticipated with small cell lung cancer and suggests that SCBC has a different natural history. These findings warrant further investigation.
Does Atelectasis Cause Fever After Surgery? Putting a Damper on Dogma
Authors: Joseph G. Crompton, Peter D. Crompton, Polly Matzinger
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Pulmonary arterial hypertension associated with protein kinase inhibitors: a pharmacovigilance–pharmacodynamic study
Authors: Lucie Cornet, Charles Khouri, Matthieu Roustit, Christophe Guignabert, Marie-Camille Chaumais, Marc Humbert, Bruno Revol, Fabien Despas, David Montani, Jean-Luc Cracowski
Journal: European Respiratory Journal (2019)

The pathophysiology of pulmonary arterial hypertension (PAH) induced by protein kinase inhibitors (PKIs) remains unclear. To gain knowledge into this rare and severe pathology we performed a study combining a pharmacovigilance approach and the pharmacodynamic properties of PKIs.A disproportionality analysis on the World Health Organization pharmacovigilance database VigiBase using the reporting odds ratio (ROR) and 95% confidence interval was first performed. Then, we identified the most relevant cellular targets of interest through a systematic literature review and correlated the pharmacovigilance signals with the affinity for the different PKIs. We further performed a hierarchical cluster analysis to assess patterns of binding affinity.A positive disproportionality signal was found for dasatinib, bosutinib, ponatinib, ruxolitinib and nilotinib. Five non-receptor protein kinases significantly correlate with disproportionality signals: c-Src (r=0.79, p=0.00027), c-Yes (r=0.82, p=0.00015), Lck (r=0.81, p=0.00046) and Lyn (r=0.80, p=0.00036), all belonging to the Src protein kinase family, and TEC (r=0.85, p=0.00006). Kinases of the bone morphogenetic protein signalling pathway also seem to play a role in the pathophysiology of PKI-induced PAH. Interestingly, the dasatinib affinity profile seems to be different from that of other PKIs in the cluster analysis.The study highlights the potential role of the Src protein kinase family and TEC in PAH induced by PKIs. This approach combining pharmacovigilance and pharmacodynamics data allowed us to generate some hypotheses about the pathophysiology of the disease; however, the results have to be confirmed by further studies.
Keynote-365 cohort a: Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Evan Y. Yu, Christophe Massard, Margitta Retz, Ali Tafreshi, Joan Carles Galceran, Peter Hammerer, Peter C.C. Fong, Neal D. Shore, Anthony Joshua, Mark David Linch, Howard Gurney, Emanuela Romano, Marinela Augustin, Josep M. Piulats, Haiyan Wu, Charles Schloss, Christian Heinrich Poehlein, Johann S. De Bono
Journal: Journal of Clinical Oncology (2019)

145 Background: Activity with pembro or olaparib has been observed in mCRPC pts who progressed on 2nd-generation hormonal therapy (HT) and chemotherapy. From KEYNOTE-365 (NCT02861573), a phase 1b/2 umbrella study testing combinations in mCRPC, we report early results from cohort A combining pembro + olaparib. Methods: Pts with mCRPC were eligible if they progressed within 6 months prior to screening determined by either PSA progression or radiologic progression in bone or soft tissue. Pts were docetaxel-pretreated for mCRPC, may have received 1 other chemotherapy, and had ≤2 2nd-generation HT. Pts received pembro 200 mg IV Q3W + olaparib 400 mg orally twice daily. Primary end points: safety and PSA response rate (confirmed PSA decline ≥50%). Key secondary end points: ORR RECIST v1.1 (investigator review), disease control rate (DCR: CR+PR+SD ≥6 mo), time to PSA progression, composite response rate (ORR RECIST v1.1, confirmed PSA response, or confirmed decrease in circulating tumor cell count from ≥5 to &lt;5 cells/7.5 mL blood), rPFS, and OS. Results: Median follow-up was 11 mo. 41 initiated treatment (median age 69 years; PD-L1+ 27%; visceral disease 42%; RECIST-measurable 68%; homologous recombination repair mutation [HRR] 0%). See efficacy in table below. Treatment-related AEs occurred in 39 (95%) pts. Most frequent (≥30%) were anemia (37%), fatigue (34%), and nausea (34%). Grade 3-5 treatment-related AEs were in 21 (51%) pts. There were 2 deaths; only 1 was treatment-related (cause unknown). Conclusions: Combination of pembro + olaparib has activity in pts previously treated with docetaxel and ≤2 2nd-generation HT for mCRPC and who are HRR wild type. Observed safety profile for the combination is consistent with individual profiles of pembro and olaparib. Clinical trial information: NCT02861573. [Table: see text]
Nivolumab in second or third line setting for the treatment of metastatic renal cell carcinoma (mRCC): The real-world experience from Guy’s Hospital.
Authors: Ha Mo Linh Le, Debra Hannah Josephs, Simon Chowdhury, Sarah Maria Rudman, Deborah Enting
Journal: Journal of Clinical Oncology (2019)

624 Background: Nivolumab (Nivo) has been approved by the FDA for patients (pts) with mRCC who have received prior VEGF tyrosine kinase inhibition based on the Checkmate 025 study. However following various new anti-angiogenic therapies licensed over the past decade, optimal sequence of treatments in mRCC remains unknown. Methods: This is a retrospective review of mRCC pts who received nivo at Guy’s Hospital. Pts were divided based on treatment line setting. Clinical characteristics, response rate (RR), progression free survival (PFS), duration on treatment and safety are reported. Results: Between March 2016 and April 2018, 50 pts with mRCC received nivo, 25 as second line (2L) and 25 as third line treatment or beyond (3L+). In 2L setting, median age was 62 years and 68% were male. 76% had a nephrectomy, with a majority of clear cell (cc) histology (92%). 96% of pts had visceral metastases. 88% received pazopanib in the first line setting (1L). Median age for pts in 3L+ was 60 years and 88% were male. 60% had a nephrectomy and 80% had cc histology. 96% had visceral metastases. Pazopanib was given in 72% in 1L. RR was 28% and 16% in 2L and 3L+ respectively. Median duration of treatment was 4.3 months in 2L and 2.2 months in 3L+, with 11 patients (22%) still on treatment. Median follow-up time was 12.4 months in 2L and 9 months in 3L+. Median PFS was 4.8 months and 3.7 months respectively in 2L and 3L+ groups. Median OS was not reached in either group. Adverse events leading to treatment discontinuation occurred in 7 pts (14%). 5 pts experienced grade 3/4 toxicities (colitis, pneumonitis, hepatitis, arthritis and nephritis), with 4 pts in 3L+. Overall 22 pts received subsequent treatments: 8/25 (32%) had cabozantinib (cabo) and 4/25 (16%) were treated with axitinib following nivo given in 2L. For pts who received nivo in the 3L+ setting 7/25 (28%) received cabo and 2/25 (8%) had axitinib as subsequent therapy. Conclusions: Our real world data supports the efficacy and safety of nivo following VEGF inhibition for pts with mRCC. Nivo was associated with a trend towards superior clinical responses in the 2L setting. For the entire cohort no new safety signals were reported.