tbuckley/cabot-search huggingface dataset:
Evaluation of Cockcroft-Gault (CG) and abbreviated modified diet in renal disease (MDRD) formulae in dosing of cancer drugs other than carboplatin
Authors: S. A. Jennings, M. L. de Lemos, A. Levin, N. Murray
Journal: Journal of Clinical Oncology (2007)

2522 Background: Glomerular filtration rate (GFR) is often used to determine initial dosing of renally-excreted cancer drugs. Estimated GFR (eGFR) can be calculated using serum creatinine (SrCr) -based formulae such as CG and MDRD. MDRD is more accurate in non-cancer patients, does not require patient weight, and is reported automatically by all laboratories in British Columbia (BC). We previously showed that CG and MDRD have similar accuracy for carboplatin dosing in patients with gynecological malignancies. We now examine dosing of all renally-excreted cancer drugs in the general cancer population. Since this setting does not include routine measurement of GFR, we report the concordance of eGFR derived from CG and MDRD. Methods: Patient data were collected retrospectively at the BC Cancer Agency. The primary outcome was concordance of eGFR derived from CG and MDRD, using the method of Bland and Altman. A difference of ≥ 30% was assumed to be clinically significant because this difference would usually lead to dose adjustment based on reclassification of renal function. The secondary outcome was the proportion of patients who would have received a different initial dose due to difference in eGFR. Each patient’s dose was determined from dose adjustment tables stated in specific treatment protocols. Results: 313 patients were evaluated: 40% male, median 56y, 67.5kg, 166cm, SrCr 74micromol/L. Median eGFR derived from CG and MDRD were 86.8mL/min and 87.6mL/min, respectively. A difference of ≥ 30% in eGFR was found in 17.9% (56/313) of patients. 8.6% (27/313) of patients would have received a different dose due to difference in eGFR; of these, 67% (18/27) would have received a higher dose. Conclusions: There is good concordance of eGFR derived from CG and MDRD for most cancer patients, with less than 10% of patients expected to receive a different initial dose of chemotherapy. MDRD may be a reasonable alternative to CG for dosing of any renally-excreted cancer drug. No significant financial relationships to disclose.
Insulin Pumps Could Be Hacked
Authors: Rebecca Voelker
Journal: JAMA (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 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
Preoperative chemoradiation with nimotuzumab and capecitabine in patients with locally advanced rectal cancer: A phase II study.
Authors: Yuan Zhu, Luying Liu, Jialing Luo, Dechuan Li, Yuping Zhu
Journal: Journal of Clinical Oncology (2012)

e14049 Background: To evaluate the efficacy and safety of preoperative chemoradiation with Nimotuzumab(a humanized monoclonal antibody that targets and binds to the epidermal growth factor receptor)and capecitabine in the patients with locally advanced rectal cancer. Methods: Twelve patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50 Gy/25 fractions. Concurrent therapy consisted of Nimotuzumab 400 mg/m 2 ,1 week before radiotherapy, and then Nimotuzumab 400 mg/m 2 /week for 5 weeks, and capecitabine 1,650 mg/m 2 /day for 5 days a week (weekdays only) from the first day during radiotherapy. Three weeks after the end of chemoradiation, 1 cycle chemotherapy with oxaliplatin and capecitabine(XELOX) was performed. Oxaliplatin 130mg/m 2 , Day1 and capecitabine 1000 mg/m 2 , bid, from Day 1 to Day 14. Postoperative chemotherapy after surgery followed by preoperative CRT was in all patients, The same dosage of XELOX was started within 3 to 4 weeks after surgery, repeated every 3 weeks for 6 cycles. Total mesorectal excision was performed within 6 ~ 8 weeks. The pathologic response was evaluated as study endpoint, and an additional KRAS mutation analysis was performed. Results: In total, 9 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 33.3% (3/9), and 3 patients (33.3%) showed near total regression of tumor. Grade 3 toxicities was diarrhea (2/12, 16.7 %), No grade 4 toxicity was observed. KRAS mutations were found in 2 of 12 patients (16.7%) who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with Nimotuzumab and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.
Lomeguatrib, a O6-Methylguanine-DNA-Methyltransferase (MGMT) Inhibitor, Induces DNA Damage Induced Apoptosis By Targeting Double-Strand DNA Repair in Multiple Myeloma
Authors: Dilara Akcora Yildiz, Tulin Ozkan, Yunus Yukselten, Nezaket Turkel Sesli, Seyma Ozkanca, Mehmet Gunduz, Mehmet Ozen, Meral Beksac, Asuman Sunguroglu
Journal: Blood (2016)
Breaking the Cycle of Burnout and Bias in Resident Physicians
Authors: Vineet M. Arora, Anita Blanchard
Journal: JAMA Network Open (2019)

Liselotte Dyrbye, MD, MHPE; Jeph Herrin, PhD; Colin P. West, MD, PhD; Natalie M. Wittlin, MS; John F. Dovidio, PhD; Rachel Hardeman, PhD; Sara Emily Burke, PhD; Sean Phelan, PhD, MPH; Ivuoma Ngozi Onyeador, MA, PhD; Brooke Cunningham, MD, PhD; Michelle van Ryn, PhD, MPH
m6A mRNA methylation regulates human β-cell biology in physiological states and in type 2 diabetes
Authors: Dario F. De Jesus, Zijie Zhang, Sevim Kahraman, Natalie K. Brown, Mengjie Chen, Jiang Hu, Manoj K. Gupta, Chuan He, Rohit N. Kulkarni
Journal: Nature Metabolism (2019)
Randomised Trial of Adjuvant Radiotherapy Following Radical Prostatectomy Versus Radical Prostatectomy Alone in Prostate Cancer Patients with Positive Margins or Extracapsular Extension
Authors: Greetta Hackman, Kimmo Taari, Teuvo L. Tammela, Mika Matikainen, Mauri Kouri, Timo Joensuu, Tiina Luukkaala, Arto Salonen, Taina Isotalo, Anssi Pétas, Niilo Hendolin, Peter J. Boström, Sirpa Aaltomaa, Kari Lehtoranta, Pekka Hellström, Jarno Riikonen, Merja Korpela, Heikki Minn, Pirkko-Liisa Kellokumpu-Lehtinen, Eero Pukkala, Akseli Hemminki
Journal: European Urology (2019)
WHO tobacco report: smoking cessation services must be stepped up
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Progress is being made in the fight against tobacco, but some countries are still not doing enough to help people quit smoking, according to the World Health Organization.1

In its 2019 global tobacco epidemic report, WHO said that only 23 countries have implemented cessation support policies at the best practice level, making this the most under-implemented recommended measure in terms of number of countries offering full coverage.

It added that …
A Phase I/II Study of Reduced Dose FCR (FCR-lite) in Combination with Lenalidomide Followed By Lenalidomide Maintenance (FCR2) for Initial Therapy of CLL: Final Results and Long-Term Follow-up
Authors: Anthony R. Mato, Andre Goy, Tatyana A Feldman, Joanna Rhodes, Lori A. Leslie, Mary Mrkulic, Sabrina Kdiry, Kara Yannotti, Marisa Valentinetti, Stephen J. Schuster, Jakub Svoboda, Kenneth Foon, Alan P Skarbnik
Journal: Blood (2017)
Coexistence of multiple escape mechanisms in a BRAF<sup>V600E</sup>-mutated cutaneous melanoma treated with vemurafenib.
Authors: Olivier Michielin, Emanuela Romano, Solange Peters, Alexandra Paillusson, Johann Weber, Katia Muehlethaler, Keith Harshman, Daniel E Speiser, Sylvain Pradervand, Donata Rimoldi
Journal: Journal of Clinical Oncology (2013)

9014 Background: Mechanisms of acquired resistance to vemurafenib are the subject of intense research. Here we report, for the first time, two coexisting yet mutually exclusive mechanisms of escape in a melanoma patient who presented an excellent clinical response following reintroduction of vemurafenib. Methods: To investigate the mechanisms of resistance to vemurafenib, we performed whole-exome sequencing using the Illumina technology of a pre-treatment paraffin-embedded lymph node metastasis (Pre) and of two progressing subcutaneous snap-frozen metastases of the right arm (PV1 and PV2). The tumor samples, along with germline controls, were sequenced at high coverage (mean range 268x-356x). Results: We identified 107 exonic somatic Single Nucleotide Variants (SNVs) in Pre, 139 SNVs in PV1, and 127 SNVs in PV2, generating a set of 202 different SNVs, 82 of which were common to all 3 samples. The non-synonymous to synonymous ratios were higher for PV1 (1.82) than for PV2 (1.46), and lower for Pre (1.31). C&gt;T transitions, largely predominated in the samples, indicating light-induced damage. Two independent NRAS escape mutations (Q61K and Q61R) where observed in PV1, whereas appearance of a BRAF splice variant (lack of exon 4-10) was present in PV2. Most importantly, these 2 escape mechanisms were mutually exclusive, i.e. no BRAF splice variant was observed by PCR in PV1 and no NRAS mutation found in PV2. Conclusions: Our results clearly demonstrate that multiple molecular escape mechanisms can be both coexistent and mutually exclusive. These findings have clinical implications: firstly, local treatment of isolated progressing lesions and continuation of vemurafenib could be supported by the fact that the resistance mechanisms are not necessarily shared. This approach is currently being tested within clinical trials with preliminary results that seem to support this hypothesis. Secondly, the coexistence of divergent escapes within the same patient strongly argues that single biopsy analysis at progression might not reflect the molecular complexity of tumor progression, and therefore might not be sufficient to guide selection of second-line optimal combination therapy.
Natural Polymer‐Based Hydrogels with Enhanced Mechanical Performances: Preparation, Structure, and Property
Authors: Ziting Bao, Caihong Xian, Qijuan Yuan, Guiting Liu, Jun Wu
Journal: Advanced Healthcare Materials (2019)

Abstract Hydrogels based on natural polymers have bright application prospects in biomedical fields due to their outstanding biocompatibility and biodegradability. However, the poor mechanical performances of pure natural polymer‐based hydrogels greatly limit their application prospects. Recently, a variety of strategies has been applied to prepare natural polymer‐based hydrogels with enhanced mechanical properties, which generally exhibit stiffening, strengthening, and stretchable behaviors. This article summarizes the recent progress of natural polymer‐based hydrogels with enhanced mechanical properties. From a structure point of view, four kinds of hydrogel are reviewed; double network hydrogels, nanocomposite hydrogels, click chemistry‐based hydrogels, and supramolecular hydrogels. For each typical hydrogel, its preparation, structure, and mechanical performance are introduced in detail. At the end of this article, the current challenges and future prospects of hydrogels based on natural polymers are discussed and it is pointed out that 3D printing may offer a new platform for the development of natural polymer‐based hydrogels.
New warning signs on the road: 5-hydroxymethylcytosine-based liquid biopsy for the early detection of hepatocellular carcinoma
Authors: Maria Arechederra
Journal: Gut (2019)

Hepatocellular carcinoma (HCC) ranks as the sixth most common neoplasm and the third leading cause of cancer-related death.1 As with many other cancers, HCC detected at an early stage has a better prognosis than the advanced-stage disease, in part due to the relative efficacy of local treatments compared with systemic therapies.1 At present, the serological determination of alpha-fetoprotein (AFP) levels is the only liquid biopsy test used for the detection and surveillance of HCC. However, it has demonstrated serious limitations and most patients are diagnosed in an advanced stage, when current treatments have little effectiveness. Moreover, although patients in early and intermediate stages might benefit from potentially curative treatments, there is a high rate of recurrence.2 Therefore, since the only chance to offer effective treatment is the early detection, there is an urgent need to develop non-invasive and precise methods for early HCC diagnosis and recurrence monitoring.

In this regard, the focus of several recent studies has concentrated on the identification of specific genetic and epigenetic tumour alterations in plasma cell-free DNA (cfDNA). Among the circulating cfDNA, DNA released by the tumour to the peripheral blood has been shown not only to contain the same mutations as the primary tumour cells but also the same epigenetic patterns.3 The most extensively studied epigenetic feature for blood-based cancer biomarker development is DNA methylation, especially the 5-methylcytosine (5-mC) modification at the 5'-cytosine-phosphate-guanine-3' (CpG) dinucleotides. Importantly, DNA methylation patterns are usually tissue- and cancer-type specific. However, in spite …
Feasibility analysis of mutational status of advanced colorectal cancer patients and correlation to disease progression.
Authors: Daniel Grissom, Mark Wade, John R. Weis, Kenneth M. Boucher, Sunil Sharma
Journal: Journal of Clinical Oncology (2012)

e14177 Background: Mutational Analyses are being increasingly performed on colorectal cancer patients. More efforts are needed to correlate this data to clinical outcomes such as disease prognosis, metastasis, and tumor responsiveness to chemotherapy or targeted therapy. We assessed the mutational status of patients diagnosed with colorectal cancer in the GI oncology clinics of Huntsman Cancer Institute. Methods: We examined 46 patients diagnosed with colorectal cancer that had molecular profiling performed. To determine effectiveness of mutation analysis we compared the time to progression (TTP) of patients in correlation to KRAS or BRAF, PIK3CA and PTEN status. KRAS, BRAF and PIK3CA testing was performed by direct sequence analysis on genomic DNA isolated from a formalin-fixed paraffin-embedded tumor sample. Testing utilized custom primers designed to flank, amplify and sequence codons 12 and 13 in exon 2 and codon 61 in exon 3 of the KRAS gene, codons 464-469 of exon 11 and codon 600 of exon 15 in the BRAF gene located at 7q34, and codons 539-546 of exon 9 and codons 1043-1049 of exon 20 in the PIK3CA gene located at 3q26.3. PTEN expression was determined by immunohistochemistry. H-score of ≤10 was considered PTEN Low. Results: Of the patients reviewed there were 26 male, 20 female with a median age of 59 (23-81). 43 patients had metastatic disease and 3 patients had localized disease. Mutations found were 48% KRAS, 6% BRAF, 13% PIK3CA, 46% PTEN Low, 13% KRAS + PIK3CA, and 28% KRAS/BRAF + PTEN Low. In patients with KRAS/BRAF wild type (n=14), median TTP from diagnosis to starting first chemotherapy for metastatic disease was 365 days as compared to KRAS/BRAF mutant (n=21) of 182 days (p=0.008). This study could not detect any correlation between dual alterations in RAS with PI3 kinase pathway and TTP probably as a function of lower sample sizes. Conclusions: Our data supports association of KRAS and BRAF mutational status to TTP rates in colorectal cancer patients. Substantial numbers of patients have alterations in the PI3-Kinase pathway in combination with the RAS pathway. Continued testing of molecular mutational status is needed in order to improve these predictive models.
EGFR/K-ras mutations in lung adenocarcinoma and atypical adenomatous hyperplasia (AAH)
Authors: S. Matsumoto, T. Takuwa, N. Kondo, Y. Okumura, K. Fukuoka, T. Nakano, S. Hasegawa, F. Tanaka
Journal: Journal of Clinical Oncology (2007)

21074 Background: Mutations in the epidermal growth factor receptor (EGFR) gene and k-ras gene are found in 10–30% of non-small cell lung cancer, and are useful to predict the efficacy of EGFR-tyrosine kinase inhibitors. Such mutations are also onco- developmentally important especially in lung adenocarcinoma, but the exact incidences of such mutations in adenocarcinoma/AAH and surrounding normal lung. Methods: A total of 45 consecutive patients with lung adenocarcinoma and/or AAH (18 females; mean age, 65 years) who received thoracotomy from August 2005 through December 2006. In each case, EGFR/k-ras mutations were examined in specimens cut from adenocarcinoma/AAH and normal lung; in the present study, pure bronchioalveolar carcinoma (BAC) was reviewed separately from adenocarcinoma. Results: As 12 (27%) of all 45 patients had multiple adenocarcinoma/BAC/AAH lesions, mutations were examined in 59 lesions (41 adenocarcinomas, 7 BACs, 11 AAHs) and 45 normal lung tissues. EGFR and k-ras mutations were documented in 37% (15/41) and 2% (1/41) of adenocarcinomas, and no EGFR/k-ras mutation was documented in any BAC, AAH, or normal lung tissue. Next, clinical characteristics of patients were compared between patients with solitary adenocarcionma/BAC/AAH lesion and those with multiple lesions; non-smoker were more frequently documented in multiple-lesions group (42%) than in solitary-lesion group (15%), and there was no significant difference in other characteristics such as sex and age. Conclusions: EGFR mutation was not documented in non-invasive (BAC) or pre-neoplastic (AAH) lesion in this series, which may suggest that EGFR mutation play a critical role in the development of invasive adenocarcinoma. No significant financial relationships to disclose.
Cisplatin and docetaxel plus concurrent three-dimensional (3D) conformal radiotherapy in unresectable stage III A/B NSCLC
Authors: L. Arcangeli, B. Orlandini, M. Torre, C. Carbonini, A. Sbarufatti, E. Vattemi
Journal: Journal of Clinical Oncology (2009)

e18503 Background: Concurrent chemoradiation is standard of care for most patients with unresectable stage III A/B NSCLC but no standard chemotherapy regimen/schedule has been established. We conducted an experience to evaluate the efficacy and toxicity of a combination consisting of weekly docetaxel/cisplatin and radiotherapy in patients with unresectable stage III A/B NSCLC. Methods: Unresectable stage III A/B NSCLC pts with a good performance status (ECOG PS 0–1) were eligible. Patients with stage IIIB were chemonaive, while patients with stage IIIA were inoperable after a first line platinum-based chemotherapy. Treatment consisted of docetaxel 25 mg/m2 IV infusion followed by cisplatin 25 mg/m2 IV infusion was administered weekly during concurrent thoracic radiotherapy. Concurrent 3D-conformal RT thoracic radiation consisted of 45 Gy (1.8 Gy fractions 5 days/wk for first five weeks. Results: From 2006/01 to 2008/04, 16 pts were enrolled and all were evaluable for toxicity and response. Pt. characteristics: median age- 68 years (54–77), 80% males. Nine pts had stage IIIA (56%) and 7 patients had stage IIIB (44%).Histology subtypes included epidermoid (25%) and adenocarcinoma (75%). Radiologic response was seen in 11 patients (68%). Four patients had a stable disease (25%). Disease progression has occurred in 1 pt. Six patients undergone surgery after chemo-radiotherapy (37%). Four patients (25%) underwent a radical resection without residual mediastinal malignant disease. Toxicity was mild. Conclusions: Weekly docetaxel/cisplatin with concurrent 3D-conformal RT thoracic radiation plus is a well-tolerated out-patient regimen. and is feasible by multi-physicians collaboration group. No significant financial relationships to disclose.
Benefits of Supplemental Ultrasonography With Mammography—Reply
Authors: Janie M. Lee, Robert Smith, Karla Kerlikowske
Journal: JAMA Internal Medicine (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 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
Portable normothermic ex-vivo lung perfusion, ventilation, and functional assessment with the Organ Care System on donor lung use for transplantation from extended-criteria donors (EXPAND): a single-arm, pivotal trial
Authors: Gabriel Loor, Gregor Warnecke, Mauricio A Villavicencio, Michael A Smith, Jasleen Kukreja, Abbas Ardehali, Matthew Hartwig, Mani A Daneshmand, Marshall I Hertz, Stephen Huddleston, Axel Haverich, Joren C Madsen, Dirk Van Raemdonck
Journal: The Lancet Respiratory Medicine (2019)