tbuckley/cabot-search huggingface dataset:
Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses
Authors: Srdan Verstovsek, Jason Gotlib, Ruben A. Mesa, Alessandro M. Vannucchi, Jean-Jacques Kiladjian, Francisco Cervantes, Claire N. Harrison, Ronald Paquette, William Sun, Ahmad Naim, Peter Langmuir, Tuochuan Dong, Prashanth Gopalakrishna, Vikas Gupta
Journal: Journal of Hematology & Oncology (2017)

Myelofibrosis (MF) is associated with a variety of burdensome symptoms and reduced survival compared with age-/sex-matched controls. This analysis evaluated the long-term survival benefit with ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, in patients with intermediate-2 (int-2) or high-risk MF. This was an exploratory analysis of 5-year data pooled from the phase 3 COMFORT-I and -II trials. In both trials, patients could cross over to ruxolitinib from the control group (COMFORT-I, placebo; COMFORT-II, best available therapy). All continuing patients in the control groups crossed over to ruxolitinib by the 3-year follow-up. Overall survival (OS; a secondary endpoint in both trials) was evaluated using pooled intent-to-treat data from patients randomized to ruxolitinib or the control groups. OS was also evaluated in subgroups stratified by baseline anemia and transfusion status at week 24. A total of 528 patients were included in this analysis; 301 were originally randomized to ruxolitinib (COMFORT-I, n = 155; COMFORT-II, n = 146) and 227 to control (n = 154 and n = 73, respectively). The risk of death was reduced by 30% among patients randomized to ruxolitinib compared with patients in the control group (median OS, 5.3 vs 3.8 years, respectively; hazard ratio [HR], 0.70 [95% CI, 0.54–0.91]; P = 0.0065). After correcting for crossover using a rank-preserving structural failure time (RPSFT) method, the OS advantage was more pronounced for patients who were originally randomized to ruxolitinib compared with patients who crossed over from control to ruxolitinib (median OS, 5.3 vs 2.3 years; HR [ruxolitinib vs RPSFT], 0.35 [95% CI, 0.23–0.59]). An analysis of OS censoring patients at the time of crossover also demonstrated that ruxolitinib prolonged OS compared with control (median OS, 5.3 vs 2.4 years; HR [ruxolitinib vs censored at crossover], 0.53 [95% CI, 0.36–0.78]; P = 0.0013). The survival benefit with ruxolitinib was observed irrespective of baseline anemia status or transfusion requirements at week 24. These findings support ruxolitinib treatment for patients with int-2 or high-risk MF, regardless of anemia or transfusion status. Further analyses will be important for exploring ruxolitinib earlier in the disease course to assess the effect on the natural history of MF. ClinicalTrials.gov identifiers, NCT00952289 and NCT00934544 .
Publication of Cancer Chemotherapy Screening Data
Authors: Ralph K. Barclay, Arthur Furst, Alfred Gellhorn, Michael B. Shimkin
Journal: JNCI Journal of the National Cancer Institute (1956)

Journal Article Publication of Cancer Chemotherapy Screening Data Get access Ralph K. Barclay, Ralph K. Barclay Sloan-Kettering Institute for Cancer Research410 East 68th Street, New York 21, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Arthur Furst, Arthur Furst Department of Pharmacology and Therapeutics Stanford University School of MedicineSan Francisco 15, California Search for other works by this author on: Oxford Academic PubMed Google Scholar Alfred Gellhorn, Alfred Gellhorn College of Physicians and Surgeons620 W. 168th Street New York 32, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael B. Shimkin Michael B. Shimkin National Cancer InstituteBethesda 14, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 16, Issue 6, June 1956, Page 1507, https://doi.org/10.1093/jnci/16.6.1507 Published: 01 June 1956
Calcium Signaling and Transcriptional Regulation in Cardiomyocytes
Authors: Matthias Dewenter, Albert von der Lieth, Hugo A. Katus, Johannes Backs
Journal: Circulation Research (2017)

Calcium (Ca2+) is a universal regulator of various cellular functions. In cardiomyocytes, Ca2+ is the central element of excitation-contraction coupling, but also impacts diverse signaling cascades and influences the regulation of gene expression, referred to as excitation-transcription coupling. Disturbances in cellular Ca2+-handling and alterations in Ca2+-dependent gene expression patterns are pivotal characteristics of failing cardiomyocytes, with several excitation-transcription coupling pathways shown to be critically involved in structural and functional remodeling processes. Thus, targeting Ca2+-dependent transcriptional pathways might offer broad therapeutic potential. In this article, we (1) review cytosolic and nuclear Ca2+ dynamics in cardiomyocytes with respect to their impact on Ca2+-dependent signaling, (2) give an overview on Ca2+-dependent transcriptional pathways in cardiomyocytes, and (3) discuss implications of excitation-transcription coupling in the diseased heart.
The Dangers of Polypharmacy in Elderly Patients
Authors: Jacques Turgeon, Veronique Michaud, Lauren Steffen
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
Improving future studies in chronic pancreatitis: a paradigm shift in our understanding?
Authors: Andrew D Hopper, Jennifer A Campbell
Journal: Gut (2017)

We read with interest the study by de la Iglesia-Garcia et al 1 The authors present a detailed, well-conducted meta-analysis of the efficacy of pancreatic enzyme replacement therapy (PERT) in patients with chronic pancreatitis (CP) who also have evidence of exocrine pancreatic insufficiency (EPI). Using level 1 evidence studies, the primary endpoint of fat absorption is shown to increase with PERT, with additional improvements shown in GI symptoms and quality of life. The authors should be commended for their work clarifying the beneficial use of PERT in this group of patients, but they and the preceding commentary by Windsor2 highlight the heterogenicity of the criteria used to diagnose CP and the greater need for a clear consensus to help target and guide dosing of PERT. Although a recent consensus to produce a mechanistic definition for …
Viral Hepatitis in a Group of Boston Hospitals
Authors: George F. Grady, Thomas G. Chalmers
Journal: New England Journal of Medicine (1965)

REVIEW of the records of 1675 patients with hepatitis hospitalized in Boston from 1951 through 1962 revealed that two thirds had acquired the disease without having been recently exposed to conventionally recognized sources, such as transfusions or jaundiced persons.1 It was postulated that many of them might have contracted hepatitis from more obscure but potential exposures, such as dental procaine injections,2 ingestion of raw shellfish3 and even contact with the ubiquitous household cockroach.4 It was also recognized that the original investigations that have implicated such activities as hepatitis risks might never have been undertaken if some unusual contamination had not . . .
Phase I/IIa trial of chemoradiotherapy plus autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma: Association between complete resection and delayed-type hypersensitivity response.
Authors: Eiichi Ishikawa, Yoshihiro Muragaki, Tetsuya Yamamoto, Takashi Maruyama, Koji Tsuboi, Koichi Hashimoto, Youji Uemae, Takeshi Ishihara, Masahid Matsuda, Masao Matsutani, Katsuyuki Karasawa, Yoichi Nakazato, Tatsuya Abe, Tadao Ohno, Akira Matsumura
Journal: Journal of Clinical Oncology (2014)

e13029 Background: We report a prospective phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with Temozolomide (TMZ) , followed by autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed glioblastoma multiforme (GBM). Methods: Twenty-four patients (aged 16-75 years; Karnofsky performance scale score 60% or more before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy of FRT with daily concurrent TMZ. After a 4-week interval, the patients received three AFTV injections and the first course of TMZ maintenance chemotherapy for 5 days, followed by multiple courses of TMZ for 5 days in each 28-day cycle. Results: This treatment regimen was well toleratedby all patients. The percent of patients with progression-free survival (PFS) ≥24 months was 33%. The median PFS, median overall survival (OS), and the actuarial 2-year survival rate of the 24 patients were 8.2 months, 22.2 months, and 47%, respectively. The median PFS in patients with a delayed-type hypersensitivity (DTH) response after the third AFTV injection (DTH-2) of 10 mm or larger surpassed the follow-up period (29.5 months), which was significantly longer than in patients with a smaller DTH-2 response. Moreover, total resection of the tumor was associated with high DTH response. Conclusions: The treatment regimen resulted in favorable PFS and OS for newly diagnosed GBM patients. Total resection may enhance DTH response after vaccination. Clinical trial information: UMIN000001426.
Nivolumab in previously treated patients with metastatic squamous NSCLC: Results of a European single-arm, phase 2 trial (CheckMate 171) including patients aged ≥70 years and with poor performance status
Authors: S. Popat, A. Ardizzoni, T. Ciuleanu, M. Cobo Dols, K. Laktionov, M. Szilasi, R. Califano, E. Carcereny Costa, R. Griffiths, L. Paz-Ares, C. Szczylik, J. Corral, D. Isla, J. Jassem, W. Appel, J. Van Meerbeeck, J. Wolf, J. Jiang, L.R. Molife, E. Felip Font
Journal: Annals of Oncology (2017)
Prevalence of germline TP53 p.R337H mutation in Brazilian young breast cancer patients.
Authors: Fernanda Paschoal Fortes, Renata Tonhosolo, Rima Jbili, Karina Miranda Santiago, Kelvin Andrade, Amanda Franca Nobrega, Maria Isabel Isabel Achatz
Journal: Journal of Clinical Oncology (2017)

e13101 Background: Germline TP53 mutations are associated with Li-Fraumeni syndrome (LFS), a disease that predisposes carriers to a wide variety of early onset tumors. Pre-menopausal breast cancer is the most frequent tumor found in carriers. In Southern and Southeastern Brazil, a germline TP53 mutation in exon 10, p.R337H, was diagnosed in 0,3% of the population due to a founder effect, a prevalence that is substantially higher than other LFS mutations. Methods: In this study we investigated the prevalence of the p.R337H TP53 germline mutation in 287 young female breast cancer patients (diagnosed before the age of 40) at A. C. Camargo Cancer Center, Sao Paulo, Brazil. DNA was extracted from saliva and Sanger sequencing of exon 10 was performed. All patients were consented. Results: The p.R337H TP53 mutation was present in 1.74% (5/287). Family history of cancer was present in three cases although it did not fulfill LFS clinical criteria. Conclusions: The identification of germline p.R337H mutation in this cohort strengthen the role of TP53 mutations in the early onset of breast cancer in pre-menopausal cancer in Brazil.
Ribonuclease and Thymonucleodepolymerase
Authors: Jesse P. Greenstein, Wendell V. Jenrette
Journal: JNCI Journal of the National Cancer Institute (1941)

Ribonuclease and Thymonucleodepolymerase Get access Jesse P. Greenstein, Jesse P. Greenstein research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Wendell V. Jenrette Wendell V. Jenrette junior physiologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 3, December 1941, Pages 301–303, https://doi.org/10.1093/jnci/2.3.301 Published: 01 December 1941
Sensitivity of TargetSelector in clinical experience in ctDNA profiling of NSCLC 2000 cases.
Authors: Veena M. Singh, Anthony J. Daher, Jeffery J. Chen, Lyle Arnold, Cecile Rose T. Vibat
Journal: Journal of Clinical Oncology (2017)

e23033 Background: Targeted cancer therapy relies on identifying specific DNA mutations from a patient’s tumor. Tyrosine kinase inhibitors (TKIs) tend to be effective for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations, of which exon 19 deletions (Del19) and L858R are most common. Acquired resistance to TKI therapy is associated with a T790M mutation. Standard biomarker analyses may not reflect tumor heterogeneity; they entail tissue biopsies often with surgical complications. To address these limitations, Biocept developed a minimally invasive method to characterize cancer biomarkers in blood. Biocept's proprietary TargetSelector assays selectively amplify relevant mutations from circulating tumor DNA (ctDNA). Clinical validations demonstrated high concordances between molecular tests in blood vs tissue. As further validation, EGFR mutation detection frequencies were compared to US averages (mycancergenome.org). Here we analyze 2000 blood samples received at Biocept from 1Mar 2016 to 4Jan 2017 from late stage NSCLC patients. Methods: Blood was collected in Biocept OncoCEE BCT validated to preserve DNA ≤ 8 days. TargetSelector was used to detect ctDNA L858R, Del19 and T790M.EGFR allele copy numbers for wild type and each mutant were calculated. The prevalence of each mutation was compared to US averages. Results: Del19, L858R, and T790M mutations were detected in 12.9%, 8.5%, and 9.9% of the analyzed blood samples, respectively. This is concordant with US averages, which are 10% for each mutation. Median copy numbers/ml of blood were 30 for Del19 (range: 1 – 91974), 15 for L858R (range: 1 – 91200), and 10 for T790M (range: 1 – 137360). The median wild type EGFR copy number detected/ml blood was 2304 (range: 8 – 2498725). In ~80% of T790M cases, ≥ 1 concomitant activating mutation was detected. Conclusions: Biocept's TargetSelector detects EGFR mutations (Del19, L585R, and T790M) at a very high level of sensitivity down to 1 mutant copy/ml in advanced NSCLC patients at frequencies consistent with cited US rates. Moreover, the underlying activating mutation was detected in ~80% of T790M cases.
Advanced chondrosarcomas: Role of chemotherapy and survival.
Authors: Binh Bui Nguyen, Angela Cioffi, Sophie Piperno-Neumann, Loic Chaigneau, François Bertucci, Nicolas Penel, Florence Duffaud, Axel Le Cesne, Antoine Italiano
Journal: Journal of Clinical Oncology (2012)

10023 Background: There are no data about the role of chemotherapy in patients with advanced chondrosarcomas. Methods: From 2000 to 2011, 98 patients with a confirmed diagnosis of advanced chondrosarcomas were referred to one of the 8 participating institutions, and their medical records reviewed. Results: Median age was 46 years (range 16-82). The most frequent histological subtype was conventional chondrosarcoma (n=60, 61%). 83 patients (85%) had metastatic disease ( lung n=71, bone n=23, liver n=6) and 15 patients (15%) had locoregional unresectable disease. 30 patients (31%) had ≥ 2 metastatic sites. 63 patients (64%) received 1 st -line combination agent chemotherapy. 70 patients (71%) received a 1 st -line anthracycline-containing regimen (doxorubicin + cisplatin +/- ifosfamide: n=30, doxorubicin or pegylated liposomal doxorubicin: n=18, doxorubicin + ifosfamide +/- dacarbazine: n=16, others= 6). RECIST objective response was observed in 14 patients (14%), all but two treated with anthracyclines. 30 patients (31%) had stable disease &gt; 6 months. Median progression-free survival (PFS) and overall survival (OS) were 5.3 months (95% CI: 2.8-7.7) and 19 months (95% CI: 14-24) respectively. Performance status (PS) ≥ 2 was the sole factor significantly associated with OS. Conclusions: Chemotherapy is associated with a 6-month non-progression rate of about 45% in patients with advanced chondrosarcoma. Best supportive care should be considered in patients with poor PS. These data should be used as a reference for response and outcome in the assessment of investigational drugs in advanced chondrosarcoma.
Phase <scp>III</scp> Randomized Study of <scp>SB</scp>5, an Adalimumab Biosimilar, Versus Reference Adalimumab in Patients With Moderate‐to‐Severe Rheumatoid Arthritis
Authors: Michael E. Weinblatt, Asta Baranauskaite, Jaroslaw Niebrzydowski, Eva Dokoupilova, Agnieszka Zielinska, Janusz Jaworski, Artur Racewicz, Margarita Pileckyte, Krystyna Jedrychowicz‐Rosiak, Soo Yeon Cheong, Jeehoon Ghil
Journal: Arthritis & Rheumatology (2017)

Objective SB 5 is a biosimilar agent for adalimumab ( ADA ). The aim of this study was to evaluate the efficacy, pharmacokinetics ( PK ), safety, and immunogenicity of SB 5 in comparison with reference ADA in patients with rheumatoid arthritis ( RA ). Methods In this phase III , randomized, double‐blind, parallel‐group study, patients with moderately to severely active RA despite treatment with methotrexate were randomized 1:1 to receive SB 5 or reference ADA at a dosage of 40 mg subcutaneously every other week. The primary efficacy end point was the response rate based on the American College of Rheumatology 20% improvement criteria ( ACR 20) at week 24 in the per‐protocol set (completer analysis). Additional end points included efficacy, PK , safety, and immunogenicity assessments. Results Of the 544 patients randomized to receive a study drug, the full analysis set comprised 542 patients (269 in the SB 5 group, 273 in the reference ADA group) and the per‐protocol set comprised 476 patients (239 receiving SB 5, 237 receiving reference ADA ). The ACR 20 response rate at week 24 in the per‐protocol set was equivalent between those receiving SB 5 and those receiving reference ADA (72.4% and 72.2%, respectively); the difference in the ACR 20 response rate (0.1%, [95% confidence interval −7.83%, 8.13%]) was within the predefined equivalence margin (±15%). Similar results were seen in the full analysis set (missing data being considered a nonresponse). The SB 5 and reference ADA treatment groups were comparable across other end points, including the ACR 50% and ACR 70% improvement response rates, Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate, PK data, incidence of treatment‐emergent adverse events, and the antidrug antibody response. Subgroup analyses showed that the efficacy and safety of SB 5 and reference ADA were comparable regardless of antidrug antibody status. Conclusion The ACR 20 response rate at week 24 was equivalent between patients treated with the biosimilar agent SB 5 and those treated with reference ADA . SB 5 and reference ADA were both well tolerated, with comparable safety profiles, in patients with RA .
Clinical utility of routine surveillance CT/MRI imaging in patients with localized soft tissue sarcoma (STS) following curative resection.
Authors: Chiew Woon Lim, Mohamad Farid Rin Harunal Rashid, Wei Lin Goh, Sze Huey Tan, Steven Bak Siew Wong, Lai Peng Chan, Tiffany Priyanthi Hennedige, Sathiyamoorthy Selvarajan, Kesavan Sittampalam, Jonathan Yi Hui Teh, Francis Kuok Choon Chin, Mann Hong Tan, Khee Chee Soo, Melissa Ching Ching Teo, Richard Hong Hui Quek
Journal: Journal of Clinical Oncology (2017)

11069 Background: Guidelines recommend routine surveillance imaging in patients (pts) following curative resection of STS. However the benefit of such an approach is unclear. We sought to evaluate the utility of a surveillance imaging strategy in pts with localized STS treated with curative intent. Methods: Pts with localized non-indolent STS, seen between 2010 – 2016, who had undergone surgery with R0/R1 surgical margins were included. Epidemiology, treatment and relapse data were collected as was the mode of detection. We defined optimal surveillance as CT/ MRI performed at least 6-mthly following surgery; suboptimal surveillance was defined as CT/ MRI imaging performed less frequently than 6mthly. Results: Of 294 pts included, 31% (n = 92) vs 34% (n = 100) vs 35% (n = 102) had optimal, suboptimal and no routine CT/MRI surveillance imaging respectively. At a median follow-up of 27mths (range 0-79), 36% (n = 105) experienced a relapse; 43% (n = 45) local and 57% (n = 60) had metastatic relapse. More relapses were noted in the optimal surveillance group, 57% (n = 52) vs 28% (n = 28) and 25% (n = 25) in the suboptimal and no surveillance groups respectively (p &lt; 0.001). Within each cohort, relapses detected directly by routine surveillance imaging vs outside of surveillance imaging were as follows: 35% (n = 32) / 22% (n = 20) in the optimal, 17% (n = 17) / 11% (n = 11) in the suboptimal and 0 / 25% (n = 25) in the no surveillance arms respectively. Comparing the 3 strategies, the proportion of pts who then went on to receive curative resection/ metastacectomy was not significantly different, 38% (n = 20), 57% (n = 16) and 32% (n = 8) of relapses, in the optimal vs suboptimal vs no surveillance cohorts respectively (p = 0.1). Notably, routine surveillance imaging directly leading to curative resection occurred only in 15% (n = 14) of pts in the optimal and 9% (n = 9) in the suboptimal surveillance groups. Conclusions: While an intensive routine CT/MRI surveillance imaging strategy detected more recurrences, the impact it has on subsequent resection is less certain. Optimal frequency of surveillance imaging remains unclear.
Recurrent Benzodiazepine Withdrawal Catatonia in an Older Adult
Authors: Lindsay G. Lebin, Joseph M. Cerimele
Journal: American Journal of Psychiatry (2017)

diagnosed prevalence rates differ by a factor of approximately 40 for personality disorders, compared with a factor of 1.3 for major depression.We caution that our contrasts rely on patients' reports of diagnoses, which may be imperfect proxies of true assessment results.Also, the lion's share of research on pediatric personality disorders has targeted borderline personality disorder, but we could not evaluate the underdiagnosis of borderline personality disorder because it was not surveyed in the NESARC university subsample.With those caveats in mind, we conclude that practitioners are not assessing or treating personality disorders prior to adulthood, despite a clear need for early intervention.Given the data supporting the concurrent and prognostic importance of personality disorder diagnoses in youths, clinicians arguably should assess them.