tbuckley/cabot-search huggingface dataset:
Transforming the National Surgical Quality Improvement Program to the Delivery of Precision Medicine to Improve the Value of Surgical Care
Authors: John A. Spertus, Amir A. Ghaferi
Journal: JAMA Surgery (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 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
Malignancies and ustekinumab: an analysis of the U.S. Food and Drug Administration Adverse Event Reporting System and the European Union Drug Regulating Authorities Pharmacovigilance database
Authors: A.G. Florek, B. Nardone, S. Thareja, G. Tran, F.J. Giles, D.P. West
Journal: British Journal of Dermatology (2017)

Ustekinumab is a fully human monoclonal antibody that targets the common p40 subunit shared by interleukins (IL)-12 and IL-23, approved in the United States and in Europe on September 2009, for treatment of moderate to severe psoriasis and on September 2016 for moderately to severely active Crohn's disease1. Pre-marketing studies supported an acceptable risk-to-benefit profile2-4.

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Pediatric Gliomas: Current Concepts on Diagnosis, Biology, and Clinical Management
Authors: Dominik Sturm, Stefan M. Pfister, David T.W. Jones
Journal: Journal of Clinical Oncology (2017)

Gliomas are the most common CNS tumors in children and adolescents, and they show an extremely broad range of clinical behavior. The majority of pediatric gliomas present as benign, slow-growing lesions classified as grade I or II by the WHO classification of CNS tumors. These pediatric low-grade gliomas (LGGs) are fundamentally different from IDH-mutant LGGs occurring in adults, because they rarely undergo malignant transformation and show excellent overall survival under current treatment strategies. However, a significant fraction of gliomas develop over a short period of time and progress rapidly and are therefore classified as WHO grade III or IV high-grade gliomas (HGGs). Despite all therapeutic efforts, they remain largely incurable, with the most aggressive forms being lethal within months. Thus, the intentions of neurosurgeons, pediatric oncologists, and radiotherapists to improve care for pediatric patients with glioma range from increasing quality of life and preventing long-term sequelae in what is often a chronic, but rarely life-threatening disease (LGG), to uncovering effective treatment options to prolong patient survival in an almost universally fatal setting (HGG). The last decade has seen unprecedented progress in understanding the molecular biology underlying pediatric gliomas, fueling hopes to achieve both goals. Large-scale collaborative studies around the globe have cataloged genomic and epigenomic alterations in gliomas across ages, grades, and histologies. These studies have revealed biologic subgroups characterized by distinct molecular, pathologic, and clinical features, with clear relevance for patient management. In this review, we summarize hallmark discoveries that have expanded our knowledge in pediatric LGGs and HGGs, explain their role in tumor biology, and convey our current concepts on how these findings may be translated into novel therapeutic approaches.
A feasibility study of the Nativis Voyager system in patients with recurrent glioblastoma multiforme (GBM): Interim results of first-in-human study.
Authors: Garni Barkhoudarian
Journal: Journal of Clinical Oncology (2017)

e13506 Background: The Nativis Voyager® ulRFE™ system, a non-invasive investigational device, was studied in a first-in-human feasibility study to assess if it is a safe and feasible treatment for recurrent glioblastoma multiforme (GBM). The anti-mitotic therapy delivers ultra-low radio frequency energy ( ulRFE) profiles produced by changes in molecular electrostatic surface potential to the brain. The interim results of the first stage of a 2-stage study are presented here. Methods: In this prospective, multi-center trial, patients with GBM, following recurrence after receiving standard-of-care chemotherapy and/or radiotherapy were considered for the study. Patients were treated with Voyager alone or with Voyager plus concurrent chemotherapy or Avastin at the discretion of the investigator. Safety was assessed by incidence of any adverse events associated with the investigational therapy. Tumor progression at 8 weeks (2 cycles) was assessed by radiological response by local site. Patients were followed at least every 8 weeks during treatment and every 4 months thereafter. Results: Fourteen patients were enrolled and treated at four clinical sites across the United States. Eleven subjects were followed per protocol. Three subjects withdrew consent prior to the first radiological assessment (day 28) for reasons not associated with the study or investigational therapy, and were not included in the analysis. The local sites reported a partial response in the first 2 months of treatment in 2 of the 11 subjects. These subjects were Avastin-naïve. Two were reported to be progression free after 6 cycles (24 weeks) of treatment. No serious adverse events associated with the investigational therapy were reported. Conclusions: The Nativis Voyager appears to be feasible and safe for the treatment of recurrent GBM. Given that therapy is delivered non-invasively, and no serious adverse events attributed to the investigational therapy were reported, further prospective study in an expanded study of the investigational device is warranted. Clinical trial information: NCT02296580.
La prise en charge endoscopique des affections biliopancréatiques chez l'enfant est-elle possible?
Authors: M Barthet, M El Farisi, B Madougou, M Gasmi, A Desjeux, JC Grimaud
Journal: Endoscopy (2006)

Le traitement endoscopique des pseudokystes pancréatiques (PK) et de la lithiase cholédocienne compliquée est un traitement de première intention chez l'adulte. Toutefois, chez l'enfant, pour des raisons essentiellement techniques de dimension des endoscopes, sa faisabilité n'est pas complètement admise.
A phase 1 study to evaluate infraradical mastectomy for operable breast cancer.
Authors: Michel Coibion, Eric Lifrange, Veronique Jossa, Eugene Mutijima, Andre Crevecoeur, Fabrice Olivier, Julien Di Bella, Guy Heinrich Maria Jerusalem
Journal: Journal of Clinical Oncology (2016)

e12527 Background: Surgical procedures have become less aggressive in breast cancer. However, some patients remain candidates for modified radical mastectomy (MRM). We evaluated if infraradical mastectomy which preserves the skin and fat tissues surrounding the breast is safe. The ultimate goal is to use this new surgical technique in patients who are candidates for breast reconstruction because improved esthetic results are expected. Methods: Patients were recruited in 2 specialized breast clinics. We performed enucleation by a cold knife of the mammary gland after a water-assisted dissection of the periglandular space by a dedicated tool. In a second step we removed the peripheral fat tissue which surrounded the gland and additional skin as done in a MRM. Fat tissue removed in the second step underwent a careful pathological examination (10 biopsies) in order to evaluate residual invasive or in situ breast cancer and atypical hyperplasia. We evaluated also the % of tissue and skin removed in the second step which could be left in the future if the procedure is declared safe. Results: A total of 29 patients (43 to 80 years old) were prospectively recruited from 2-11/2015. Tumor characteristics: pTis: 3%, pT1: 48%, pT2: 41%, pT3: 7%. The pathological analysis of the periglandular tissue removed in the second step revealed (% of specimens): 0% of invasive carcinoma, 1% of focal DCIS and 0% of atypical hyperplasia. On average the weight of an infraradical mastectomy was 36% lower compared to the weight of a MRM. Skin resection was reduced by 48% with infraradial mastectomy. Conclusions: Preliminary results are promising. Our phase 1 trial suggests that the procedure is safe from an oncological point of view. The quantity of periglandular tissue left after infraradical mastectomy is high. We are now recruiting a second cohort of 30 patients in order to confirm this outcome. Presurgical selection criteria on mammography have been modified to avoid residual DCIS left after surgery. Thereafter a randomized multicenter trial (compared to MRM) is planned in order to validate definitively this new surgical technique (including also evaluation of the expected improved esthetical result after reconstructive surgery). Clinical trial information: 80M0594.
Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced cancer: Safety data from 1300 patients enrolled in the phase 1b JAVELIN Solid Tumor trial.
Authors: Karen Kelly, Christopher Ryan Heery, Manish R. Patel, Jeffrey R. Infante, Nicholas Iannotti, Joseph W. Leach, Ding Wang, Jason Claud Chandler, Hendrik-Tobias Arkenau, Matthew H. Taylor, Michael S. Gordon, Deborah Jean Lee Wong, Howard Safran, Howard Kaufman, Ulrich Keilholz, Marcis Bajars, Anja von Heydebreck, Isabell Speit, Jean-Marie Cuillerot, James L. Gulley
Journal: Journal of Clinical Oncology (2016)

3055 Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody showing preliminary efficacy in multiple tumor types. We report updated safety data of single-agent avelumab in patients (pts) with locally advanced or metastatic (LA/M) solid tumors from a phase 1b trial (NCT01772004). Methods: Pts from 16 different expansion cohorts (including NSCLC, gastric, ovarian, urothelial, mesothelioma, and breast), all unselected for PD-L1 expression, received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Treatment-emergent adverse events (AEs) were graded by NCI-CTCAE v4.0. Results: As of Nov 5, 2015, 1,300 pts received avelumab and were followed for ≥ 4 wks. Median age was 63 y (range 20-91), ECOG PS was 0 (37.7%), 1 (62.1%), or 2-3 (0.2%), and median number of prior lines of anticancer therapy was 2 (range 1-13). Median duration of treatment with avelumab and number of administrations were 11.5 wks (range 2-104) and 5 infusions (range 1-50), respectively. Treatment-related (TR) AEs occurred in 813 pts (62.5%), and the most common ( ≥ 5%) were fatigue (n = 212, 16.3%), infusion-related reaction (IRR; n = 209, 16.1%), nausea (n = 108, 8.3%), chills (n = 102, 7.8%), diarrhea (n = 79, 6.1%), and pyrexia (n = 72, 5.5%). Grade ≥ 3 TRAEs occurred in 124 pts (9.5%). The most frequent ( ≥ 0.5%) grade ≥ 3 TRAEs were GGT elevation (n = 9, 0.7%), IRR (n = 9, 0.7%), fatigue (n = 8, 0.6%), lipase elevation (n = 8, 0.6%), anemia (n = 7, 0.5%), and dyspnea (n = 6, 0.5%). Potential immune-related (ir) TRAEs were reported for 93 pts (7.2%); the most frequent ( ≥ 1.0%) were hypothyroidism (n = 45; 3.5%) and pneumonitis (n = 13; 1.0%). TRAEs resulted in permanent discontinuation for 79 pts (6.1%): 25 (1.9%) due to an IRR and 14 (1.1%) due to a potential irTRAE. TRAEs were considered the primary cause of death by the investigator for 5 pts (0.4%): radiation pneumonitis (1), pneumonitis (1), autoimmune hepatitis/liver failure (2), and respiratory distress/sepsis (1). Conclusions: Single-agent avelumab showed an acceptable safety profile in a heavily pretreated population and large dataset of pts with LA/M malignancies. Additional analyses and phase 3 trials are ongoing. *Proposed INN. Clinical trial information: NCT01772004.
Broad, hybrid capture-based next generation sequencing identified actionable genomic alterations in HER2-negative breast cancer.
Authors: Helei Hou, Dong Liu, Na Zhou, Jinping Zhang, Chuantao Zhang, Mei Sun, Xiaoping Zhang, Zhe Wang, Xiaonan Yang, Zhuokun Li, Zhaoyang Qian, Renhua Wu, Hongmei Zhu, Rongjiao Wang, Xin Liu, Xiaochun Zhang
Journal: Journal of Clinical Oncology (2016)

e12544 Background: Molecular profiling has revealed that breast cancer could at least be classified into 4 principle subtypes by status of estrogen receptor, progesterone receptor, and HER2. About 20% of all breast cancer patients harbored HER2 amplification and could benefit from anti-HER2 therapy. In this study, we set out to determine the frequency of potentially actionable genomic alterations via broad, hybrid capture-based next generation sequencing (NGS) in HER2 negative breast cancer tissues. Methods: 47 cases of HER2 negative combined with 14 cases of HER2 positive breast cancers previously determined by FISH testing were enrolled and all the patients signed the informed consent before assay. 7708 exons of 508 tumor related genes and 78 introns of 19 frequently rearranged genes were assessed for base substitutions, indels, copy number alterations, and gene fusions. The average median sequencing depth was about 400×. Results: 19 of 47 HER2 negative breast cancers harbored at least one genomic alteration linked to potential treatment options. The most common actionable alterations were in PIK3CA (n = 7, mTOR inhibitors), BRCA1/2 (n = 6, PARP inhibitors), EGFR (n = 4, EGFR TKIs), PTEN (n = 3, mTOR inhibitors), FGFR1/2/3 (n = 3, FGFR inhibitors). It’s also worth noting that only 12 of 14 (85.7%) HER2 positive breast cancers previously confirmed by FISH were identified with HER2 amplification via NGS and 1 (BRCA1) additional actionable alteration was found in these cases. Conclusions: Our results implied that 40.4% of HER2 negative breast cancers could be targeted with approved drugs or investigational agents in clinical trials. High throughput NGS testing could guide personalized therapy of breast cancer, especially suitable for those HER2 negative patients.
Sex-Based Disparities in Venous Thromboembolism Sociodemographics and Outcomes: A National Inpatient Sample (NIS)-Based Analysis
Authors: Ariela L. Marshall, Adam C Bartley, Aneel A. Ashrani, Wilson I Gonsalves, Prashant Kapoor, Shahrukh K. Hashmi, Mustaqeem A. Siddiqui, Urshila Durani, Ronald S. Go
Journal: Blood (2016)
Reply to Dr. Mosca
Authors: J.  Ahmad, E.  Siqueira, J.  Martin, A.  Slivka
Journal: Endoscopy (2003)

We read Dr. Mosca’s comments with interest, and would reply as follows. We agree that there may have been a selection bias due to the prospective nature of data collection in the Diamond stent group, compared with the retrospective review in the Wallstent group. This limitation of the study was detailed in the text.
Pediatric Migraine Prevention—First, Do No Harm
Authors: Amy A. Gelfand, William Qubty, Peter J. Goadsby
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Development of a population pharmacokinetic (PPK) model of intravenous (IV) trastuzumab in patients with a variety of solid tumors to support dosing and treatment recommendations.
Authors: Whitney Paige Kirschbrown, Angelica Linnea Quartino, Hanbin Li, Ranvir Mangat, D Russell Wada, Amit Garg, Jin Y Jin, Bert L. Lum
Journal: Journal of Clinical Oncology (2017)

2525 Background: The aim of this analysis was to develop a PPK model for IV trastuzumab (Herceptin), to assess the impact of patient covariates on PK, and perform simulations to support dosing recommendations. Methods: Serum trastuzumab concentration data (26,040 samples) from 1582 patients with metastatic breast cancer (MBC), early breast cancer (EBC), advanced gastric cancer (AGC) or other tumor types, and 6 healthy volunteers in 18 Phase I, II, and III trials were analyzed using nonlinear mixed-effects modeling (NONMEM). Monte Carlo simulations were performed using the NONMEM PK parameter estimates (with variability) to inform dosing recommendations. Results: A two-compartment model with parallel linear and nonlinear elimination best described the data. Significant covariates (P &lt; 0.001) influencing linear CL were baseline weight, SGOT, albumin, primary tumor type, and presence of liver metastases. MBC had similar PK parameters as EBC, with lower distributions of C min,ss in MBC explained by covariates. The higher linear CL in AGC patients resulted in a 30.5% lower C min,ss . Simulations for drug washout indicated that 95% of patients with breast cancer (BC) reach trastuzumab concentrations &lt; 1 µg/mL (~97% washout) at ≤7 months. Simulations also indicated that a missed dose of trastuzumab in BC or AGC patients of ≤1 week did not result in a long PK under-exposure (i.e. the trastuzumab concentration is within 15% of C min,ss by 3 weeks) but a missed dose of &gt; 1 week took approximately 6 weeks to get back within the steady-state exposure range. Conclusions: Trastuzumab PK was well described by a two-compartment model with parallel linear and nonlinear eliminationacross cancer types, disease status, and regimens. No dose adjustment is required based on any of the identified patient covariates (e.g. weight, tumor type). Simulations using the PPK model informed the prescribing information for Herceptin; trastuzumab has a 7-month serum washout period during which patients should avoid an anthracycline-based therapy, pregnancy, or breastfeeding. A re-loading dose is required if a maintenance dose is missed by &gt; 1 week to maintain serum concentrations.
Neoadjuvant metronomic chemotherapy in triple-negative breast cancer (TNBC) (NCT00542191): Updated results from a phase II trial.
Authors: Jessica R. Hildebrand, Rachel Elizabeth Raab, Mahvish Muzaffar, Paul R. Walker
Journal: Journal of Clinical Oncology (2016)

e12502 Background: TNBC lacks effective targeted therapies, limiting treatment to cytotoxic chemotherapy alone. One third of patients with TNBC achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (Cortazar Lancet 2014). Carboplatin has been reported to further improve response (von Minckwitz Lancet 2014). It has been reported that patients who attain pCR have improved survival. We sought to determine the benefit of neoadjuvant metronomic chemotherapy utilizing doxorubicin with cyclophosphamide followed by paclitaxel with carboplatin in women with TNBC. Methods: Patients with TNBC > / = 2 cm were eligible. Treatment consisted of weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. Patients received standard surgery and radiation therapy as indicated. The primary endpoint was pCR, secondary endpoints were 5 year survival and toxicities. Results: Between July 2006 and March 2014, 21 patients with TNBC were enrolled, 18 were eligible for analysis and 3 patients died before completing treatment. 1 patient died from pulmonary embolism, 1 from neutropenic sepsis, 1 from non-neutropenic sepsis. Patient characteristics: 5 patients had clinical T4 disease, 12 had clinical node positive disease, 71.4% stage II, 28.6% stage III. The rate of pCR was 47.6%(p = 0.031). 5 patients (27.8%) achieved a partial response, 1 patient (5.5%) maintained stable disease and 2 patients (11%) progressed on treatment. 5 year survival was 58.4%. pCR was significantly associated with survival (p = 0.009). 90% at 5 years for those who achieved pCR versus 12.5% for those who did not. Hematologic toxicities were not uncommon. 62% of patients experienced G3 or 4 neutropenia, 24% experienced febrile neutropenia. 17% experienced anemia. 12 patients discontinued treatment early due to treatment related toxicities. Conclusions: Neoadjuvant metronomic chemotherapy with weekly doxorubicin plus oral cyclophosphamide followed by weekly paclitaxel plus carboplatin is an effective regimen for achieving a pCR in patients with TNBC. Those patients who achieve a pCR have improved survival. Clinical trial information: NCT00542191.
Construction and Pre-Clinical Evaluation of a New Anti-CD19 Chimeric Antigen Receptor
Authors: Anne Marijn Kramer, Sara Ghorashian, Gordon Weng-Kit Cheung, Winston Vetharoy, Dale Moulding, Leila Mekkaoui, Shimobi Onuoha, Persis J Amrolia, Martin A Pule
Journal: Blood (2016)
Modifiable behavioral factors as causes of death [1] (multiple letters)
Authors: George Anstadt, Afschin Gandjour, Joaquin Barnoya, Stanton A. Glantz, M. Nawal Lutfiyya, Eric Henley, Steven N. Blair, Michael J. LaMonte, Milton Z. Nichaman, Ali H. Mokdad, James S. Marks, Donna F. Stroup
Journal: JAMA (2004)