tbuckley/cabot-search huggingface dataset:
Measuring vs Estimating LDL-C Levels in a Clinical Trial of Bempedoic Acid—Reply
Authors: Anne Carol Goldberg, Jeffrey C. Hanselman, P. Barton Duell
Journal: JAMA (2020)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Induction (Ind) plus concurrent (Con) chemotherapy with high-dose (74 Gy) 3-dimensional (3-D) thoracic radiotherapy (TRT) in stage III non-small cell lung cancer (NSCLC): Preliminary report of Cancer and Leukemia Group B (CALGB) 30105
Authors: A. W. Blackstock, M. A. Socinski, J. Bogart, L. Gu, X. Wang, M. Green, E. E. Vokes
Journal: Journal of Clinical Oncology (2006)

7042 Background: Combined chemoradiotherapy is the standard of care in stage III NSCLC. At standard TRT doses, local failures remain problematic and strategies exploiting the dose-response aspect of TRT are warranted. 3-D TRT allows escalation of TRT dose with acceptable toxicity (Socinski et al, J Clin Oncol 22:4341, 2004) and may enhance survival by improving loco-regional control. Methods: This is a two-arm randomized phase II trial evaluating 74 Gy with Con chemotherapy: Arm A- 2 cycles of Ind carboplatin (C) (AUC 6) and paclitaxel (P) (225 mg/m 2 ) followed by weekly Con C (AUC 2/wk) and P (45 mg/m 2 ) and 74 Gy; Arm B- 2 cycles of Ind C (AUC 5) and gemcitabine (G) (1000 mg/m 2 d1,8) followed by Con G (35 mg/m 2 twice weekly) and 74 Gy. The primary endpoint was a survival rate of ≥50% at 18 months after treatment initiation or med survival time (MST) of ≥18 mos. Results: 69 pts were entered (43 Arm A, 26 Arm B)- med age 61 yrs (39–77), 77% male, PS 0:1 42%:58%, stage IIIA:B 52%:48%. Ind therapy on both arms was well tolerated with no pts experiencing disease progression. ARM A- Overall response rate (RR) to all therapy was 61.9%. Gr 3–4 toxicities during Con therapy were anemia (15%), neutropenia (26%), esophagitis (9%), fatigue (9%), neuropathy (3%) and pulmonary (12%). There was 1 (3%) Gr 5 cardiac event. With med follow-up of 16.4 mos, the med progression-free survival (PFS) is 15.2 mos. The MST is not mature enough to estimate as only 15 deaths have occurred. ARM B- Closed early due to 3 (13%) Gr 5 pulmonary events. Overall RR to all therapy was 66.6%. Gr 3–4 toxicities during Con therapy were anemia (13%), fatigue (35%), esophagitis (35%), hemoptysis (4%), pulmonary (26% plus the 3 Gr 5 events). With med follow-up of 22 mos, the med PFS is 7.7 mos and the MST is 13.9 mos. There was a correlation between Gr 3–5 pulmonary toxicity and V 20 ≥ 38% (p&lt;0.05). Conclusions: 1) High dose 3-D TRT is feasible within CALGB, 2) the details of TRT (V 20 ) are important with regard to toxicity, 3) the survival of pts on Arm A appears promising. [Table: see text]
Moving Toward the Implementation of Precision Medicine Needs Highly Discriminatory, Validated, Inexpensive, and Easy-to-Use Prediction Models
Authors: Vincenzo Trischitta, Massimiliano Copetti
Journal: Diabetes Care (2020)

Diabetes is one of the most challenging global health problems, affecting more than 400 million people (1). Although 10% of current global health care spending is devoted to diabetes (1), patients with diabetes remain at high risk of morbidity and mortality (2) mainly due to cardiovascular disease (3). This extremely heavy burden is likely to increase in the coming decades, especially considering the epidemic nature of the most common form, type 2 diabetes (4). It is, therefore, mandatory to address vigorously the negative impact of type 2 diabetes on vascular health and life expectancy. To this end, the availability of well-performing risk prediction models capable of identifying high-risk patients to be targeted with the most aggressive and most burdensome prevention strategies would play a pivotal role.

The study of Aminian et al. (5), published in this issue of Diabetes Care , presents several models (called Individualized Diabetes Complications [IDC] Risk Scores) able to estimate in obese patients with type 2 diabetes the risk of mortality and of long-term vascular complications, including coronary artery events, heart failure, and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Twenty-six baseline variables as potential predictors were modeled by time-to-event regression and random forest machine learning, an ensemble of survival regression trees grown on bootstrap resampling of the observations. The left-out data were then used to predict the error rate and, after permutation, to estimate the importance of a given predictor. In addition to the time-dependent area under the receiver operating characteristic curve (AUROC) and the calibration plot, a recently described index of prediction accuracy, which combines discrimination and calibration in a single value, was also used (6).

A total of 13,722 patients from the Cleveland Clinic database were analyzed retrospectively (i.e., 2,287 who underwent metabolic surgery and 11,435 propensity-matched nonsurgical individuals, …
A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase
Authors: Song Sun, Jochen Weile, Marta Verby, Yingzhou Wu, Yang Wang, Atina G. Cote, Iosifina Fotiadou, Julia Kitaygorodsky, Marc Vidal, Jasper Rine, Pavel Ješina, Viktor Kožich, Frederick P. Roth
Journal: Genome Medicine (2020)

For the majority of rare clinical missense variants, pathogenicity status cannot currently be classified. Classical homocystinuria, characterized by elevated homocysteine in plasma and urine, is caused by variants in the cystathionine beta-synthase (CBS) gene, most of which are rare. With early detection, existing therapies are highly effective.Damaging CBS variants can be detected based on their failure to restore growth in yeast cells lacking the yeast ortholog CYS4. This assay has only been applied reactively, after first observing a variant in patients. Using saturation codon-mutagenesis, en masse growth selection, and sequencing, we generated a comprehensive, proactive map of CBS missense variant function.Our CBS variant effect map far exceeds the performance of computational predictors of disease variants. Map scores correlated strongly with both disease severity (Spearman's ϱ = 0.9) and human clinical response to vitamin B6 (ϱ = 0.93).We demonstrate that highly multiplexed cell-based assays can yield proactive maps of variant function and patient response to therapy, even for rare variants not previously seen in the clinic.
MUSIC THERAPY IN PATIENTS WITH HYPERTENSION AND EARLY POST-INFARCTION ANGINA: 17-YEAR EXPERIENCE OF THE MUSIC STUDY
Authors: Predrag Mitrovic, Aleksandra Paladin, Mina Radovanovic, Nebojsa Radovanovic, Ida Subotic, Milica Vukicevic
Journal: Journal of the American College of Cardiology (2020)
Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients.
Authors: Andreas D. Hartkopf, Malgorzata Banys, Gerhard Gebauer, Natalia Krawczyk, Markus Hahn, Hans Neubauer, Markus Wallwiener, Florin-Andrei Taran, Diethelm Wallwiener, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2012)

e21003 Background: An imbalance between cell proliferation and programmed cell death leads to tumor growth. Although most cytostatic agents used in systemic therapy of breast cancer induce an apoptosis in tumor cells leading to their destruction, a high ratio of apoptotic cells in primary breast cancer is correlated with poor prognosis. The purpose of this study was to investigate the incidence and prognostic significance of apoptotic disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer (PBC) patients. Methods: PBC patients who underwent primary surgery (PS) or were treated with neoadjuvant chemotherapy (NACT) between 01/2003 and 12/2007 were included into this prospective study. BM aspirates were analyzed by immunocytochemistry (M30 antibody) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. Patients without DTC in the BM were excluded from the study. Survival data were evaluated after a median follow up of 44 months. Results: BM aspirates of 383 PBC patients were analyzed. DTC were M30 positive in 82 of 298 (27%) patients who underwent PS and 41 of 85 (48%) patients treated with NACT. After NACT, the incidence of apoptotic cells in patients with complete/partial remission as compared to patients with stable/progressive disease was 63%/53% vs. 31%/0% (p=0.034). In the NACT group, M30-positive patients suffered less likely of a relapse than those without apoptotic DTC (7% vs. 23% of the events, p = 0.049). Inversely, overall survival in the PS group was significantly shorter in M30-positive as compared to M30-negative patients (75 months, 95% CI: 68-81 months vs. 84 months, 95% CI: 81-86 months; p = 0.008). Conclusions: Apoptotic DTC can be detected in breast cancer patients before and after systemic treatment. The presence of apoptotic DTC in BM of breast cancer patients can reflect the effects of neoadjuvant treatment. Spontaneous and chemotherapy-induced apoptosis may have different prognostic implications.
Intensity-modulated radiation therapy for head and neck cancer of unknown primary
Authors: M. L. Klem, S. L. Wolden, M. J. Zelefsky, Y. B. Su, B. Singh, D. Kraus, A. Shaha, J. Shah, D. G. Pfister, N. Lee
Journal: Journal of Clinical Oncology (2006)

5565 Background: Unknown primary head and neck cancers often require comprehensive mucosal and bilateral neck irradiation. With conventional techniques, significant toxicity can develop. Intensity modulated radiation therapy (IMRT) has the potential to minimize toxicity. Methods: From 2000–2005, 21 patients received IMRT for unknown primary head and neck cancer at our center. Median age was 57. Clinical stages were: TxN1: 43%; TxN2b:38%; TxN2c:5%; TxN3:14%. Five patients received IMRT with primary intent and 16 as postoperative therapy. Fourteen received concurrent chemotherapy, most with cisplatin (100mg/m 2 /cycle) or carboplatin (70mg/m 2 )/ 5FU (600mg/m 2 ) every 3 weeks for 2–3 cycles. Seven received IMRT alone. Median dose was 66 Gy. PEG tube was placed in 13 patients. Toxicities were evaluated. Regional progression free survival (RPFS), distant metastases free survival (DMFS) and overall survival (OS) were calculated with Kaplan Meier curves. Results: Grade 1 and 2 xerostomia was seen in 57% and 43%. Salivary function improved with time. By 6 months, no patient had greater than grade 1 xerostomia. Grade 1, 2, and 3 acute skin toxicity and mucositis were seen in 67%, 29%, 5% and in 33%, 52%, 14%, respectively. PEG tube was required in 72% who had combined modality and 43% with IMRT alone. Of the 13 with PEG tubes, only 3 required PEG support at the time of last follow up. For those who had PEG removed, median time with PEG was 3.8 months from the end of RT. Two patients treated with combined modality and 1 treated with IMRT alone developed esophageal strictures, but all had improvement or resolution with dilation. Two patients had persistent disease after RT and 1 had late regional failure at 39 months. Two patients developed distant metastases and died. With a median follow up of 14.3 months (5.4–73.4), 2 year RPFS, DMFS, and OS were 88.9%, 89.4%, and 84.0%. Conclusions: Preliminary analysis of IMRT for unknown primary head and neck cancer shows acceptable toxicity and encouraging efficacy. Xerostomia was a common acute complication but patients had marked improvement by 6 months. Esophageal strictures were seen but effectively treated with dilation. Techniques to limit esophageal dose may help further minimize this complication. No significant financial relationships to disclose.
Benefits of a centralized cancer control program on outcomes: Evaluation of wait times for diagnosis and management of advanced non-small cell lung cancer (NSCLC).
Authors: Krista Noonan, Janessa J. Laskin, King Mong Tong, Katherine Ramsden, Yongliang Zhai, Cheryl Ho
Journal: Journal of Clinical Oncology (2013)

e19039 Background: Canada has a national cancer registry that tracks patterns across the population; British Columbia (BC) has the lowest lung cancer mortality in the country. The BC Cancer Agency (BCCA) operates five regional cancer centres and community outreach sites that deliver cancer care using evidence-based standards and guidelines established by the BCCA. The province is 945,000 km 2 ; the population is distributed 85% urban and 15% rural. We hypothesize that adherence to provincial cancer control programs results in equitable services in all geographic locations. Methods: A retrospective population-based review of stage IIIb/IV NSCLC patients (pts) diagnosed from Jan 2008 to Dec 2010 referred to the BCCA was done. Pt characteristics and time intervals between diagnosis, referral, oncology consultation and palliative therapy were extracted. The Kruskal-Wallis test was used to compare wait times (WT). The Kaplan-Meier method and log rank test was used for OS. Results: 1,431 pts were identified. Median time from diagnosis (DX) to referral (RF) was similar across all geographic regions (11-13 days). Median time from RF to oncology consultation ranged from 7-16 d. Table 1 describes medical oncology (MO) WT to chemotherapy (CT) and radiation oncology (RO) WT to radiotherapy (RT). Conclusions: While WT varied between key events in the pts’ lung cancer trajectory by geographic location, the overall survival from diagnosis was similar in all groups. Provision of provincially mandated guidelines and care conferred equitable outcomes in advanced NSCLC across BC. [Table: see text]
Cancer-Causing Substances in Food, Drugs, and Cosmetics
Authors: William J. Curran
Journal: New England Journal of Medicine (1988)

EVERY calling, every profession, every common activity of people develops its maxims, its short-hand messages, imparting to later generations the hard-earned lessons of the past. These maxims are often designed to save time that would be wasted, or to avoid risks or dangers that our elders underwent to their peril. Legal systems, filled as they are with historical documentation and adherence to precedent, are replete with pithy maxims that every new law student learns by rote.One of the most frequently cited maxims of the ancient common law is the de minimis rule, which is used to avoid the pointless . . .
19O A phase Ib trial of CFI-402257 in combination with weekly paclitaxel in patients with advanced HER2-negative (HER2-) breast cancer (aBC)
Authors: P. Bedard, M. Mates, K.A. Gelmon, J. Hilton, D. Tu, I. Li, L. Rastgou, N. Drummond-Ivars, J. Edwards, D. Warr, C. Lohrisch, X. Song, A. Srikanthan, A. Robinson, L. Hagerman, L.K. Seymour, M. Rushton, D.W. Cescon
Journal: Annals of Oncology (2020)
Long-course targeted therapy with bevacizumab to predict better survival in patients with advanced colorectal cancer.
Authors: Yanhong Deng, Yuting Tang, Jian Xiao, Jiayu Ling, Yue Cai, Huabin Hu, Yan Zhang, Yiheng Lin, Dianke Chen
Journal: Journal of Clinical Oncology (2013)

e14704 Background: Bevacizumab has been the standard treatment in first-line treatment of advanced colorectal cancer. This study explored whether the short-course and long-course use of bevacizumab could influence overall survival (OS). Methods: A total of 74 patients with advanced colorectal cancer who had received at least one cycle of bevacizumab-based regimens were included. The primary endpoint was OS defined as from the date of first diagnosis of advanced colorectal cancer to death. Results: The P value among the median OS of initiating bevacizumab in first-line group (n = 47), in the second-line group (n = 18), and the third-or more-line group (n = 9) was not reached statistically significance(P = 0.349). In the first-line initiating bevacizumab group, the irinotecan arm showed a trend of better activity than the oxaliplatin arm, but the significance was not reached(P = 0.128). For patients in the first-line initiating bevacizumab group who had received at least four courses of bevacizumab (n = 36), the median PFS and OS was 11 m and 29m respectively and for those receiving less than four courses of bevacizumab (n = 10), it was 3.9 m (P = 0.005) and 13m (P=0.003) respectively. Conclusions: The delayed use of bevacizumab has no negative effect on the OS of patients with advanced colorectal cancer. Long-Course targeted therapy with bevacizumab favors better survival in patients with advanced colorectal cancer.
REGIONAL FAST-SENC CIRCUMFERNTIAL STRAIN ASSESSES CARDIOTOXICITY RISK BEFORE INITIATING CANCER THERAPY: THE PREFECT STUDY
Authors: Henning Steen, Moritz Montenbruck, Blaz Gerzak, Arne Kristian Schwarz, Sebastian Kelle, Sorin Giusca, Grigorios Korosoglou, Susan Dent, Daniel Lenihan
Journal: Journal of the American College of Cardiology (2020)
DIAGNOSTIC DELAY AND CHARACTERIZATION OF THE CLINICAL PRODROME IN AL AMYLOIDOSIS RELATED CARDIOMYOPATHY AMONG 1,173 PATIENTS DIAGNOSED BETWEEN 2001-2018
Authors: Laura Hester, Dina Gifkins, Kevin Bellew, Jessica Vermeulen, Jordan Schecter, John T. Strony, Brendan Weiss
Journal: Journal of the American College of Cardiology (2020)
Nonhuman Primate Spumavirus Infections Among Persons With Occupational Exposure—United States, 1996
Journal: JAMA (1997)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
DEVELOPMENT OF SEX-STRATIFIED PREDICTION SCORES FOR RECURRENT VENOUS THROMBOEMBOLISM: A DANISH NATIONWIDE COHORT STUDY
Authors: Ida Ehlers Albertsen, Mette Søgaard, Samuel Goldhaber, Gregory Piazza, Flemming Skjøth, Thure Filskov Overvad, Torben Bjerregaard Larsen, Peter Brønnum Nielsen
Journal: Journal of the American College of Cardiology (2020)
TEMPORAL TRENDS ON THE PREVALENCE AND OUTCOMES OF PATIENTS REQUIRING ISOLATED AORTIC VALVE SURGERY OVER 17-YEARS: A STATEWIDE COHORT STUDY
Authors: Yeu-Yao (Kevin) Cheng, David Brieger, Vincent Chow, Leonard Kritharides, Austin Chin Chwan Ng
Journal: Journal of the American College of Cardiology (2020)
CircLONP2 enhances colorectal carcinoma invasion and metastasis through modulating the maturation and exosomal dissemination of microRNA-17
Authors: Kai Han, Feng-Wei Wang, Chen-Hui Cao, Han Ling, Jie-Wei Chen, Ri-Xin Chen, Zi-Hao Feng, Jie Luo, Xiao-Han Jin, Jin-Ling Duan, Shu-Man Li, Ning-Fang Ma, Jing-Ping Yun, Xin-Yuan Guan, Zhi-Zhong Pan, Ping Lan, Rui-Hua Xu, Dan Xie
Journal: Molecular Cancer (2020)

Abstract Background Metastasis causes the vast majority of colorectal carcinoma (CRC)-related deaths. However, little is known about the specific traits and underlying mechanisms of metastasis-initiating cells in primary CRC. And whether or not circular RNAs (circRNAs) take part in this particular event remain not adequately stated yet. Methods A screening method based on Transwell assay was first applied to build CRC subgroups with different metastatic potential. High throughput RNA sequencing was used to find out novel metastatic drivers in CRC metastasis-initiating step. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of circRNAs in CRC metastasis. Results A circRNA consisting of exon 8–11 of LONP2, termed as circLONP2, was upregulated in metastasis-initiating CRC subgroups. Aberrant higher expression of circLONP2 was observed in primary CRC tissues with established metastasis, and along the invasive margin in metastatic site. High expression of circLONP2 predicted unfavorable overall survival. Functional studies revealed that circLONP2 could enhance the invasiveness of CRC cells in vitro, and targeting circLONP2 through anti-sense oligonucleotide (ASO) dramatically reduced the penetrance of metastasis to foreign organs in vivo . Mechanically, circLONP2 directly interacted with and promoted the processing of primary microRNA-17 (pri-miR-17), through recruiting DiGeorge syndrome critical region gene 8 (DGCR8) and Drosha complex in DDX1-dependent manner. Meanwhile, upregulated mature miR-17-5p could be assembled into exosomes and internalized by neighboring cells to enhance their aggressiveness. Conclusions Our data indicate that circLONP2 acts as key metastasis-initiating molecule during CRC progression through modulating the intracellular maturation and intercellular transfer of miR-17, resulting in dissemination of metastasis-initiating ability in primary site and acceleration of metastasis formation in foreign organs. circLONP2 could serve as an effective prognostic predictor and/or novel anti-metastasis therapeutic target in CRC treatment.