tbuckley/cabot-search huggingface dataset:
Real world skeletal related events (SREs) associated with oral treatments in patients with metastatic castration resistant prostate cancer (mCRPC).
Authors: Nicole Engel-Nitz, Ajay S. Behl, Cori Blauer-Peterson, Nancy Ann Dawson
Journal: Journal of Clinical Oncology (2016)

e16537 Background: Abiraterone acetate (ABI) with prednisone and enzalutamide (ENZ) are oral treatments for patients with mCRPC. There is a lack of information on the impact of sequencing of therapies on patients’ real-world outcomes. This study compared SRE events in patients initiated on ABI and ENZ. Methods: A national health claims database was used to conduct a retrospective analysis of patients initiated on ABI or ENZ (index date) from 09/01/2012 to 06/30/2015 with: ≥1 non-diagnostic claim with a prostate cancer diagnosis (ICD-9-CM 185.xx) from 6 months prior to through 30 days after index date; ≥6 month pre-index and ≥3 months post-index health plan enrollment (retaining patients who died). Cohorts (ABI or ENZ) were defined based on the first medication initiated. Follow-up SREs (spinal cord compression, radiation to bone, pathological fracture, bone surgery) were assessed for patients without baseline SREs. Descriptive analyses, Kaplan-Meier curves with log-rank tests, and Cox proportional hazards were used to compare ABI to ENZ cohorts; models adjusted for age, geographic region, and pre-index clinical (comorbidities, bone/ brain metastases, docetaxel). Results: Table 1 summarizes study results. Among ABI (n=1,095) and ENZ (n=421) cohorts, baseline SREs were similar: 82.57% (n=903) and 79.57% (n=335) respectively had no baseline SREs (P=0.192). Follow-up incidence rates for SREs were higher for the ENZ vs. ABI patients (incidence rate ratio 1.27, P=0.044). Adjusted Cox proportional hazards analysis found a higher hazard of SREs for ENZ vs. ABI (HR: 1.34; 95% confidence limits: 1.06, 1.69; P=0.015). Conclusions: Patients with mCRPC who were initiated on ABI first had better SRE outcomes, with those initiated on ENZ having a 34% higher risk of SREs. ABI n=903 ENZ n=335 P-value Baseline Age, mean (SD) 73.02 (9.43) 75.01 (9.37) <0.001 Charlson Comorbidity Index, mean (SD) 5.74 (2.11) 6.15 (2.11) 0.002 Follow-up SREs Events / Person-year 259 / 176.23 105 / 56.42 Incidence rate, per person-yr 1.47 1.86 Incidence rate ratio, ENZ vs. ABI 1.27 0.044 Adjusted hazard ratio, ENZ vs. ABI, [95% LCL, UCL] 1.34 [1.06, 1.69] 0.015
Abstract 13709: Ross Procedure in Adults: Is Reoperation a Real Concern?
Authors: Maria C Escarain, Gerardo E Bozovich, Roberto R Favaloro
Journal: Circulation (2013)

Objectives: The aim is to assess long term results of the Ross procedure in adults and identify predictors of autograft reoperation in the second post-operative decade. Methods: From July 1995 to O...
Targeting the <scp>ICOS</scp>/<scp>ICOS</scp>‐L pathway in a mouse model of established allergic asthma disrupts T follicular helper cell responses and ameliorates disease
Authors: Faith I. Uwadiae, Chloe J. Pyle, Simone A. Walker, Clare M. Lloyd, James A. Harker
Journal: Allergy (2018)

Allergic asthma is characterized by chronic inflammation and remodelling of the airways, associated with dysregulated type 2 immune responses and allergen-specific IgE. T follicular helper cells (TFH ) are crucial in T-dependent B-cell responses and have been implicated in allergic airway disease (AAD). TFH , unlike other CD4+ T cells, are uniquely reliant on continuous ICOS signalling to maintain their phenotype after T-cell priming; therefore, disrupting this signal can impair TFH responses. However, the contribution of TFH to disease during chronic aero-allergen exposure and the therapeutic potential of targeting these cells have not been evaluated.To establish AAD, female BALB/c mice were repeatedly exposed to house dust mite or Alternaria alternata three times a week for up to 5 weeks. To examine the impact of TFH on AAD, mice were allergen exposed for 5 weeks and co-administered anti-ICOS Ligand-targeted antibodies, three times a week for the last 2 weeks.TFH were first observed in the lung-draining lymph nodes and with further exposure were also found locally within the lungs. TFH accumulated with sustained allergen exposure, alongside germinal centre (GC) B cells. Blockade of ICOS signalling after AAD establishment successfully depleted TFH but did not affect the differentiation of other CD4+ T-cell subsets. This reduced GC responses, allergen-specific IgE, inflammation, pulmonary IL-13 and airway hyper-responsiveness.TFH are crucial in the regulation of AAD and the ICOS/ICOS-L pathway could represent a novel therapeutic target in allergic asthma.
Safety of Topical Calcineurin Inhibitors for Hailey-Hailey Disease—Reply
Authors: Christopher T. Haley, Uyen Ngoc Mui, Stephen K. Tyring
Journal: JAMA (2018)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
TCT-714 Association of Statin and Mortality after Transcatheter Aortic Valve Replacement
Authors: Poghni Peri-Okonny, Yangbo Liu, S. Malaisrie, Chetan Huded, Samir Kapadia, Vinod Thourani, John Webb, Thomas McAndrew, Maria Alu, David Cohen, Martin Leon, Suzanne Arnold
Journal: Journal of the American College of Cardiology (2018)
Abstract MP032: Anemia is Associated With Increased Risk of Mortality in Heart Failure With Preserved Ejection Fraction in the US Veteran Population
Authors: Tasnim F Imran, Katherine E Kurgansky, Yash R Patel, Ariela R Orkaby, Robert R McLean, David R Gagnon, Saadia Qazi, Senthil Selvaraj, Yuk-Lam Ho, Kelly Cho, J Michael Gaziano, Luc Djousse, Jacob Joseph
Journal: Circulation (2017)

Background: Anemia is increasingly being identified as a poor prognostic factor in patients with heart failure with reduced ejection fraction. However, few studies, and with small sample sizes, have examined the role of anemia in patients with heart failure with preserved ejection fraction (HFpEF). Thus, the purpose of our study is to examine whether anemia is associated with mortality in a large national cohort of patients with HFpEF. Methods: We identified subjects with HFpEF using a validated algorithm in the national Veterans Affairs patient database from 2002 to 2012. The criteria for HFpEF included: all recorded ejection fractions &gt; 50% and symptoms, signs and treatment for heart failure. Anemia was identified using the International Classification of Diseases (ICD-9) code at the index time of HFpEF diagnosis. All-cause mortality was confirmed from medical death records and Center for Medicare Services data. Using a multivariable Cox proportional hazards model, we examined the association of anemia at the time of HFpEF diagnosis with all-cause mortality. Results: In total, 29,022 HFpEF patients met criteria for HFpEF. Mean age of the participants was 71±12 years; 96% were men, 84% were white, 35% had anemia, 88% had hypertension, 65% had hyperlipidemia and 42% had coronary artery disease at baseline. After a median follow-up of 3.6 years (IQR: 1.7-6.4), 17,269 deaths occurred. After adjusting for age, sex, race, body mass index, coronary artery disease, hypertension, hyperlipidemia, atrial fibrillation, chronic obstructive pulmonary disease, diabetes mellitus, serum sodium, renal function, heart rate and ejection fraction, patients with anemia had higher mortality (HR 1.52, 95% CI 1.47-1.57, p &lt; 0.0001) as compared to those without anemia. Conclusion: Our study suggests that prevalent anemia is associated with an increased risk of all-cause mortality among US veterans with HFpEF. Further studies may shed light on its role as a prognosticator and potential therapeutic target in this population.
A HPV-18 positive NET of the uvula: Diagnosis and course of therapy in a 76 year old male patient.
Authors: Johannes Ehrich
Journal: Journal of Clinical Oncology (2016)

e17505 Background: The high-risk strains -16 and -18 of the human papilloma virus family (HPV) play a decisive role in the carcinogenesis of diverse malignancies. The immunhistochemical proof of Chromogranin-A, Synaptophysin and CD56 classifies neuroendocrine tumors (NET). HPV positive NET may represent an emerging malignant sub entity. Methods: We report about a 76 year old male patient diagnosed with bipulmonary metastases of a HPV-18 positive non-small cell NET of the uvula. Due to progressive odynophagia the patient initially presented in the outpatient department of our ENT clinic in June 2011. Here a highly suspicious lesion of the uvula and the soft palate were found. Based on those findings a tumor resection was performed. Histopathologic findings revealed a HPV-18 positive, basaloid pT1, pN2 (5/21); g3; L1; V0; R0 squamous cell carcinoma. No indicator for a tumor relapse was found in the trimestrial follow-up examinations conducted by our ENT clinic. But in May 2013 a CT chest revealed new bipulmonary nodules of the left upper and lower lobe. Thus the patient was referred to our clinic for thoracic surgery. Here an atypical lung resection of the lung segments II and III was performed. Immunhistochemical staining of the tumor tissue proved positivity for CD56, synaptophysine and chromogranine-A. As the immunhistochemical staining of lung and oropharyngeal tumor tissue was the same, there was as well the proof of HPV-18 in the lung tumor tissue. Results: This patient suffered from a bipulmonary metastasized HPV-18 positive NET of the uvula Conclusions: Aggressive spread, seen in this case, is reported for HPV-18 positive oropharyngeal NETs which might yet represent an inadequate characterized malignant sub entity. An early cooperation between ENT physicians, pathologists and medical oncologists will improve diagnostic and therapy of this disease.
Induction nivolumab or nivolumab/ipilimumab prior to concurrent chemoradiation plus nivolumab in patients with operable stage II/III esophageal/gastroesophageal junction cancer.
Authors: Ronan Joseph Kelly, Russell K. Hales, Richard James Battafarano, K Ranh Voong, Stephen C. Yang, Eun Ji Shin, Chen Hu, Valsamo Anagnostou, Victor E. Velculescu, Josephine Louella Feliciano, Elizabeth Thompson, Kellie Nicole Smith, Cynthia Sears, Drew M. Pardoll, Valerie Rowe, Hanika Rodavia, Ali Imran Amjad, Patrizia Guerrieri, Blair Anderson Jobe, Ali Hussainy Zaidi
Journal: Journal of Clinical Oncology (2018)

TPS4140 Background: Neoadjuvant chemoradiation (cRT) prior to surgical resection in stage II/III esophageal/gastroesophageal junction (EC/GEJ) cancer results in a complete pathologic response rate of approximately 20-25%, in adenocarcinoma subtypes. The appearance of favorable microenvironment features (enhanced tumor lymphocytes, perivascular lymphocytes and tertiary lymphoid structures) after induction therapy in resected EC suggest tumors may respond favorably to immune based therapy and in particular to PD-1 based checkpoint blockade when combined with cRT prior to surgical resection. In addition, pre-clinical models suggest that esophageal radiation significantly increases PD-L1 expression. The Phase III Attraction 2 study has demonstrated activity of nivolumab in a subset of heavily pretreated patients with gastroesophageal cancer. This trial proposes to evaluate the safety/efficacy of induction nivolumab or nivolumab plus ipilimumab prior to concurrent chemoradiation plus nivolumab in operable stage II/III EC. Methods: This is an open-label, single-arm, multicenter clinical study that will enroll 32 patients. Eligible subjects consist of adults with histologically confirmed, resectable stage II/III EC/GEJ located below the carina. Subjects must be newly diagnosed and cannot have received prior treatment. A pre-treatment biopsy is required prior to two cycles of induction nivolumab (arm A) or one cycle of induction nivolumab/ipilimumab (arm B). A repeat research biopsy is performed after the induction phase and prior to initiation of carboplatin/paclitaxel/RT plus nivolumab. Nivolumab 240mg is administered every 2 weeks for 5 cycles in total (two as induction and three with concurrent cRT). An Ivor-Lewis esophagectomy is performed approximately 6-10 weeks post completion of cRT. The primary endpoint is safety. Secondary endpoints include an assessment of the pathological complete response rate, recurrence free survival, overall survival and immunologic correlates. The study was initiated in July 2017 and is ongoing at Johns Hopkins and at the Allegheny Health Network. Clinical trial information: NCT03044613.
Implementing cost transparency in oncology: A qualitative study of barriers, facilitators, and patient preferences.
Authors: Erin Aakhus, Abigail Rosenstein, Steven Joffe, Angela R. Bradbury
Journal: Journal of Clinical Oncology (2017)

6597 Background: As cancer drug prices rise and insurance plans shift toward greater cost sharing, studies link patients’ high out-of-pocket (OOP) costs to non-adherence and early discontinuation of treatment. Meanwhile, few oncologists routinely discuss OOP costs with their patients. Using qualitative methods, we explored barriers and facilitators of cost transparency (i.e., disclosure of financial risks of cancer treatment). Methods: We performed semi-structured interviews with cancer patients (n = 22) and providers (n = 19) at an academic medical center and three affiliated community practices between August, 2015 and May, 2016. Two analysts coded the transcribed interview data using textual thematic methods, and hypotheses were generated employing grounded theory method. Results: We grouped themes that emerged into three major domains: 1) barriers, 2) facilitators, and 3) patient preferences. Patients and providers both expressed a strong aversion to making tradeoffs between financial and physical health outcomes. While patients feared being “profiled” based on their ability to pay, providers feared that cost transparency might threaten the doctor-patient relationship by exposing personal or institutional financial conflicts of interest. Pragmatic barriers included time constraints and difficulty in providing accurate cost estimates. Important facilitators were strong doctor-patient relationships and availability of support staff with financial expertise. We detected substantial heterogeneity in patient preferences. While some patients wanted to discuss costs with their provider, others feared “distracting” providers from their primary roles as health advocates. Conclusions: With implementation of OOP cost transparency, oncology practices will need to consider patient/provider aversion to financial/health tradeoffs, patients’ sensitivity to socioeconomic “profiling,” provider- and practice-level financial incentives, time constraints, accuracy of cost estimates, and variability in patient preferences. Meanwhile, strong provider-patient relationships and availability of support staff will facilitate OOP cost transparency.
Comparison between Canadian and British oncology drug review recommendations and their impact on patient access.
Authors: Matthew K. Smith, Omar Farooq Khan, Steven Yip, Patricia A. Tang
Journal: Journal of Clinical Oncology (2017)

6537 Background: Access and funding for oncology medications in Canada and the United Kingdom are influenced by recommendations released by the pan-Canadian Oncology Drug Review (pCODR) and the National Institute for Health and Care Excellence (NICE), respectively. This study investigated variations between these organizations’ recommendations and the clinical implications these differences had on access to medications. Methods: The pCODR Drug Review and NICE Technology Appraisal Guidance databases were reviewed to identify all oncological drug recommendations made by both agencies between 2008 and 2016. Recommendations were matched and then evaluated according to an algorithm to identify clinically relevant differences that restricted access in one jurisdiction relative to the other. Length of time from drug submission to final recommendation by NICE and pCODR were compared using Wilcoxon rank sum tests, as was the length of time between regional funding approval. Results: Between 2008 and 2016, 31 medication indications were evaluated by both pCODR and NICE. For 12 indications, funding was only supported by one agency. Eight indications were approved by both agencies, but with clinically relevant differences in wording, with each agency making a more restrictive recommendation four times. Average time from submission to recommendation was faster for pCODR than NICE (213.8 days vs. 407.9 days; p &lt; 0.001) but the average time to funding decision (see table) was similar (410.1 days in Canada vs. 407.9 days in the United Kingdom; p = 0.71). Conclusions: Although clinically relevant differences in recommendations do exist between NICE and pCODR, neither agency was consistently more restrictive. pCODR recommendations were made more quickly than NICE, but this did not translate into faster funding approval in Canada. Jurisdictional barriers exist for cancer patients which could be mitigated through harmonization and acceleration of drug review processes. [Table: see text]
Quantitative and qualitative analysis of effect of potential drug target knockdown on soft agar colony formation utilizing Qcount™ automated analysis system.
Authors: Damodaran Chendil, Rama Ranga, Girija Ramankutty, Nure Alam, Sabapathy Sathishkumar, Mohammed A. Akbarsha, Subbiah Thirugnanam, Rohr Jurgen, Mansoor M. Ahmed
Journal: Cancer Research (2004)

2088   The use of complimentary and alternative medicine (CAM) among cancer patients has been increasing which may be due to the limitations of the conventional modalities of treatment for cancer. The therapeutic modalities which originated from India,  viz ., Ayurveda and Siddha, have phytotherapy as the fundamental basis and, therefore, produce little side effects. They are among the most ancient medicinal systems and are still being practiced in India and elsewhere to cure, among other diseases, cancer. Many Siddha practitioners in the southern parts of India prescribe Rasagenthi Lehyam (RGL) as a drug for cancer. RGL, as a formulation, contains 38 different botanicals, many of which have been shown to possess therapeutic efficacy, and 8 inorganic compounds purified and refined in the methods prescribed, all prepared into a paste in palm sugar and hen’s egg base. A preliminary epidemiological survey by the present investigating team revealed that RGL does at least palliate solid tumors. In order to scientifically validate the anticancer activity of RGL on prostate cancer, serial extraction of the methanolic fraction of RGL was done and the various extracts were tested for clonogenic inhibition and induction of apoptosis in prostate cancer cell PC-3.  N -hexane, ethyl acetate and chloroform extracts of RGL showed effective killing effect on PC-3 cells. The IC 50  values of  n -hexane, ethyl acetate and chloroform extracts were 3.84μg/ml, 3.68μg/ml and 75ng/ml, respectively. All the three extracts induced apoptosis in PC-3 cells. Further, all the three extracts of RGL, when combined with radiation, caused enhanced effect on killing of PC-3 cells. Among the three extracts chloroform extract showed the most significant radiation sensitizing effect. Therefore, RGL, either in the original formulation prepared under strict quality control or its chloroform extract, can be a potential CAM for prostate cancer, and also a potential sensitizing agent in the context of radiation therapy for prostate cancer. A more directed study can lead to identification of the active principle(s) in the chloroform extract of RGL for scientifically validated application in prostate cancer therapy
Letter to the Editor Regarding Article, “Alternating Bundle-Branch Block: What Is the Mechanism?”
Authors: Lei Wang, Zhong Yi
Journal: Circulation (2018)

We read with interest the article by Saini et al 1 concerning the alternating bundlebranch block, and we would like to offer some opinions.The ECG was characterized by an alternating left bundle-branch and a right bundle-branch block.This finding indicated an incomplete block.Consequently, we must consider whether the block is intraventricular.Because this patient had a history of non-Hodgkin lymphoma and chemotherapy, it is important to identify the myocardial damage caused by the myocardial infiltration or chemotherapy associated with lymphoma.It would be informative to provide the echocardiography for that patient to determine whether the heart endured any structural changes.The study considered the electrophysiological causes of arrhythmia, but the authors should also consider the real causes behind it.Different etiologies require different treatment strategies.The article does not analyze the ultimate cause of arrhythmia or whether the patient needs a pacemaker for treatment.