tbuckley/cabot-search huggingface dataset:
The analytic performance of a TaqMelt PCR assay for the detection of KRAS mutations (codons 12/13 and 61) in formalin-fixed paraffin-embedded tissue (FFPET) samples of colorectal carcinoma (CRC).
Authors: J. Cao, M. Velez, C. Hoeppner, S. Lee, V. H. Brophy, S. Soviero, H. J. Lawrence
Journal: Journal of Clinical Oncology (2011)

e21032 Background: KRAS mutation testing is now mandatory to select patients with metastatic CRC for treatment with anti-EGFR antibodies such as cetuximab and panitumumab. Multiple studies have shown that these agents do not benefit patients with KRAS-mutant CRC, and may even be deleterious. Thus there is a need for a well-validated diagnostic test to detect these mutations. Although current U.S. guidelines recommend testing for codon 12 and 13 mutations, clinical data indicate that codon 61 mutations are also predictive of nonresponsiveness to anti-EGFR antibodies. Recent studies have observed a higher prevalence of codon 61 mutations than previously reported. Methods: We describe the analytic performance of a TaqMelt PCR research assay (cobas KRAS Mutation Test), which is designed to detect 19 mutations in codons 12, 13 and 61. A panel of 187 CRC samples was tested with two different lots of the PCR test and results compared to 2x bidirectional Sanger sequencing. Results: Preliminary discrepant analysis was performed on the thirteen discordant samples (7.0%) using a quantitative deep sequencing method (454 GS-Titanium). Three (1.6%) PCR-pos Sanger-neg samples yielded 454 results that agreed with their Sanger results. Eight (4.3%) of the 11 PCR-pos, Sanger-neg samples and 2 (1.1%) of the 2 PCR-neg, Sanger-pos samples gave 454 results consistent with their respective PCR results. When a panel of six tumor samples, including two near the limit of analytical sensitivity and two with low tumor content, was repeatedly tested by two operators, using different instruments and reagent lots, a correct result was observed for 100% of tests. PCR test results were not affected by repeated freezing and thawing of the DNA sample, or by addition of hemoglobin or triglycerides. Conclusions: These studies show that this PCR test is a robust reproducible assay that 1) detects mutations in codons 12, 13 and 61 of the KRAS gene, 2) requires a small amount of DNA and 3) appears to be more sensitive than bidirectional Sanger sequencing. Test method Sanger MUT WT PCR 85 11 96 MUT 2 89 91 WT 87 100 187
Long-Term Survival with High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation and Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm: A Retrospective Registry Study from the Japan Society for Hematopoietic Cell Transplantation
Authors: Tomohiro Aoki, Ritsuro Suzuki, Yachiyo Kuwatsuka, Shinichi Kako, Katsuya Fujimoto, Jun Taguchi, Tadakazu Kondo, Akiyo Yoshida, Toshiro Ito, Yoshimasa Kamoda, Takahiro Fukuda, Tatsuo Ichinohe, Kengo Takeuchi, Koji Izutsu, Junji Suzumiya
Journal: Blood (2014)
Deregulation of TLR2-JMJD3 Innate Immunity Signaling, Including a Rare TLR2 SNP As a Potential Somatic Mutation, in Myelodysplastic Syndromes (MDS)
Authors: Yue Wei, Rui Chen, Sophie Dimicoli, Carlos E. Bueso-Ramos, Donna S. Neuberg, Sherry A. Pierce, Hui Yang, Yu Jia, Hong Zheng, Zhihong Fang, Martin Nguyen, Michael Fernandez, Sa A. Wang, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2012)
DOC-MEK: A double-blind randomized phase II trial of docetaxel with or without selumetinib (AZD6244; ARRY-142886) in wt <i>BRAF</i> advanced melanoma.
Authors: Avinash Gupta, Sharon Love, Anna Schuh, Linda Collins, Adelyn Thomason, Ruth Asher, Richard Lisle, Michael Churchman, Milensu Shanyinde, Ruth Plummer, Paul D. Nathan, Sarah Danson, Christian H.H Ottensmeier, Paul Lorigan, James M. G. Larkin, Mark R. Middleton
Journal: Journal of Clinical Oncology (2013)

9068 Background: Inhibitors of mutant BRAF have transformed the treatment of melanoma for the 40% of patients whose tumors harbor V600 mutations. ERK1/2 is constitutively active in melanoma cells regardless of mutation status, and plays key roles in cell cycle entry, invasion, angiogenesis and in resistance to apoptosis. Selumetinib is a highly selective allosteric inhibitor of MEK1/2, suppressing pERK levels in melanoma independent of BRAF and NRAS mutation status. In melanoma cells, docetaxel induces mitochondrial dependent apoptosis by activation of Bax. Activation of ERK1/2 results in degradation of the BH3-only protein Bim and phosphorylation of Bad, inhibiting apoptosis. Selumetinib and docetaxel have demonstrated synergy in a variety of xenograft models, including melanoma. Methods: DOC-MEK (NCT01256359) is a randomised, double-blind, placebo-controlled multi-centre study in patients with wild-type BRAF advanced melanoma. Patients were randomised (1:1) to docetaxel with placebo or selumetinib, with stratification for M stage and performance status. Docetaxel was administered intravenously every 3 weeks at a dose of 75mg/m 2 for a maximum 6 cycles. Placebo or selumetinib 75mg was given orally twice per day until disease progression or unacceptable toxicity. Results: Between October 2010 and April 2012 eighty three patients were randomised at 18 sites from 257 patients screened. Progression free survival (PFS) favored combination therapy (HR 0.753, p=0.13), as did response rate (32 vs 14%, p=0.059) and 6 month PFS (40 vs 26%, p=0.19). Patients on docetaxel with selumetinib experienced more rash, diarrhea, febrile neutropenia and edema, but less neuropathy. Overall survival data and outcomes according to tumor NRAS mutation status will be presented. Conclusions: Although PFS and response rates favored docetaxel with selumetinib further interest in the regimen will be dependent on overall survival outcomes and/or the identification of a sub-population that benefit most from this approach. Clinical trial information: NCT01256359.
<i>Notes from the Field</i>: Shigellosis Outbreak Among Men Who Have Sex with Men and Homeless Persons — Oregon, 2015–2016
Authors: Jonas Z. Hines, Taylor Pinsent, Kathleen Rees, Jennifer Vines, Anna Bowen, Jacqueline Hurd, Richard F. Leman, Katrina Hedberg
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In July 2015, Shigella sonnei infections with a specific pulsed-field gel electrophoresis (PFGE) pattern linked to a multistate outbreak were recognized among men who have sex with men (MSM) in the Portland metropolitan area, and an outbreak investigation was initiated. During November 2015, isolates with PFGE patterns indistinguishable from the outbreak strain were identified in cases reported in four women, none of whom had epidemiologic links to other affected persons; however, three reported homelessness. In the ensuing months, additional S. sonnei infections were reported among homeless persons in the Portland area.
Nifedipine for hypertensive emergencies
Authors: R. L. Bloomfield
Journal: JAMA (1997)

To the Editor.  —The article by Dr Grossman and colleagues1regarding recommendations for sublingual nifedipine uses the term pseudoemergency. Unfortunately, this term is not common in the hypertensive literature, and its use suggests that there are primarily 2 clinical situations: true and false hypertensive emergencies. On the other hand, the term urgency suggests that the clinician has thoughtfully assessed the patient's condition and feels that the blood pressure elevation should be classified in a less-than-emergency category.  Moreover, the authors should consider some useful alternatives, such as oral captopril, which are noted in textbooks on hypertension.2,3Another alternative is to use a lower dose of short-acting nifedipine, especially in elderly patients.4  Some of the potential adverse effects of an otherwise effective therapy may be avoidable by a knowledge of the dose-response relationship. This may be true with diuretics, β-blockers, angiotensin-converting enzyme inhibitors, aspirin, digoxin, and calcium channel blockers, as well as
Long-term outcomes of cytoreduction and HIPEC for malignant peritoneal mesothelioma.
Authors: Gleneara Elizabeth Bates, Michael D. Kluger, Zhezhen Jin, John A. Chabot, Joshua Leinwand, Toby Bressler, Michelle Rae, Robert N. Taub, Alain C. Borczuk, Mary Hesdorffer
Journal: Journal of Clinical Oncology (2015)

4111 Background: The prognosis of malignant peritoneal mesothelioma (MPM) has improved over the past decade in patients undergoing operative extirpation and intraperitoneal chemotherapy (IC). This study investigates the largest reported cohort of patients operated on for MPM. Methods: Kaplan-Meier curves and univariate cox proportional hazards model was used to estimate survival and significant treatment and prognosis factors, for 195 patients who underwent cytoreductive surgery and or HIPEC treatment between 1995-2014; patients were not excluded for bicavity disease or for unresectable disease. Results: The median survival time was 3.21 years with (95% CI: 2.38- 5.53), with median follow-up of 3.44 years (SD = 3.4, minimum = 0.014 and maximum = 16.752) years from first operation. The mean age at diagnosis was 54.8 years [HR: 1.027 (95% CI: 1.012-1.042)] with 111 men (57%) and 84 women (43.1), with female gender having favorable survival [HR: 0.442 95% CI: 0.296-0.659)]. Asbestos exposure was reported in 77 patients (39.5%) with n = 80 (41.0%) having no known asbestos exposure and in 38 patients (19.5%) asbestos exposure was not documented. The majority of patients had epithelioid histology (n = 161(82.6%), with the remainder biphasic/sarcomatoid (n = 34, 17.4%), with increased risk of death with non-epithelioid histology [HR: 2.46(95%CI 1.59-3.82)], (P = 0.001). Of the 195 patients who received cytoreductive surgery, 71(36.1%) received 1 HIPEC treatment, while 124 (63.9%) received 2 HIPEC treatments, with completion of protocol having an associated favorable prognosis [HR: 0.161 (95%CI 0.109-0.237)] (p = 0.001). Of those who received a full treatment course of cytoreductive surgery and 2 HIPEC treatments, 66 (33.8% CI: 95%) were still alive at the median follow-up. Conclusions: This large cohort illustrates that long-term survival is possible in MPM, although there is continued significant decline after 3 years from diagnosis. While the treatment of MPM continues to evolve, a comprehensive treatment approach may give the best chance for long-term survival.
The correlation of PD-L1 and microRNA-34a and their clinical implications in human non-small cell lung cancer.
Authors: Ji Hyung Hong, Kang San Roh, Sung-Suk Suh, Sukchan Lee, Jae Ho Byun, Chan-Kwon Jung, Jae Kil Park, Jin Hyoung Kang
Journal: Journal of Clinical Oncology (2016)

e23277 Background: Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, however, its transcriptional regulatory mechanisms are not well understood. Some previous studies suggested that PD-L1 was regulated by microRNA (miR)-34a targeting PD-L1 mRNA in human malignancies. We analyzed the association between the expression of PD-L1 and that of miR -34a as well as CD8 positive tumor infiltrating T lymphocytes (TIL) and tumor suppressor p53 in early stage (I - III) non-small cell lung cancer (NSCLC) tissues. Methods: For 60 samples archived from NSCLC patients, we measured the immunohistochemical stain of PD-L1, CD8, p53 and the mRNA expression of miR-34a by quantitative real-time PCR. Results: Using the cut-off value of 50% of positive PD-L1 cells at any intensity, low PD-L1 expression was observed in 19 (31.7%) patients and high PD-L1 expression in 41 (68.3%). Median number of CD8 positive TIL was 74 (range 0-173). In low PD-L1 expression group, the expression of miR-34a tended to be higher than that in high PD-L1 expression group (2−△△CT, 3.55 vs. 1.53; P = 0.069) and the number of CD8 positive TILs were lower than that in high PD-L1 expression group (65 ± 8.64 vs. 98 ± 10.46, P = 0.05). The expression of p53 was not correlated with that of PD-L1 in NSCLC. Recurrence-free survival (RFS) was longer in NSCLC patients with high PD-L1 expression than in those with low PD-L1 expression (50.2 vs. 27.2 months; 95% confidence interval (CI) 19.75-34.65, 42.08-58.36: P = 0.020). With univariate analysis, statistically significant prognostic factors for RFS were PD-L1 expression (Hazard Ration [HR], 2.76; P = 0.049), TNM stage (HR, 2.72; P = 0.003), lymph node metastasis (HR, 2.71; P = 0.043). In multivariate analysis, TNM stage was the independent prognostic factor for RFS (HR 2.838; P = 0.041), however, PD-L1 could not retain its independency for RFS (HR 2.374; P = 0.094). Conclusions: The expression of PD-L1 showed tendency to be inversely correlated with that of miR-34a and be positive correlation with CD8 positive TILs in NSCLC tissues. Additional larger scaled study is ongoing in expanded cohort.
Health of the Public: The Private-Sector Challenge
Authors: Steven Woloshin
Journal: JAMA (1996)

To the Editor.  —In the excellent article by Mr Showstack and colleagues,1 the authors argue that, from a societal point of view, managed care systems should adopt a population perspective: these systems depend on publicly financed assets (eg, Medicare and Medicaid managed care) and may draw resources away from the traditional systems mandated to provide for the uninsured. The authors also suggest that investment in the health of society is a prudent business strategy to improve community relations and to obviate legislative mandates.  We suggest 2 additional reasons why a managed care system might, for entirely self-interested reasons, reach beyond its enrollees and focus on the health of the population at large. First, the enrollment populations for managed care plans have been noted to be increasingly unstable. When patients change plans frequently, the concept of an enrolled population loses much of its meaning and the health of nonenrollees becomes highly
Місце транзієнтної еластографії в діагностиці неалкогольної жирової хвороби печінки
Authors: Yu.M. Stepanov, V.B. Iagmur, L.M. Shendryk, N.V. Nedzvetskaya
Journal: GASTROENTEROLOGY (2016)

Неалкогольна жирова хвороба печінки включає стеатоз печінки, стеатогепатит та фіброз, що можуть прогресувати до стеатогенного цирозу печінки. З огляду на поширеність цієї патології, погіршення якості життя хворих, зростання смертності від ускладнень зростає інтерес до розробки методів для точної та своєчасної оцінки ступеня жирової дистрофії печінки та прогресування фіброзу. Мета: вивчити діагностичні можливості транзієнтної еластографії у пацієнтів з ідіопатичним підвищенням рівня трансаміназ. Методи. У 52 хворих (20 чоловіків і 32 жінки) з ідіопатичним збільшенням трансаміназ без ознак стеатозу печінки згідно з сонографічним дослідженням визначали контрольований параметр ультразвукового затухання (CAP) і жорсткість печінки (LSM) з використанням апарата FibroScan з М-зондом. Критеріями виключення з дослідження були наявність хронічних вірусних, автоімунних гепатитів та зловживання алкоголем. Результати. 78,8 % пацієнтів мали жирову дистрофію печінки згідно з CAP. При аналізі контрольованого параметра ультразвукового затухання було встановлено, що 63,4 % мали фіброз F0–F1, 29,3 % — F1–F2, а 7,3 % — F3. За показником САР існували вірогідні відмінності між групою з вираженим фіброзом (F3) та групою з мінімальним фіброзом (F0–F1) ((203,0 ± 5,1) проти (243,0 ± 10,1), р &lt; 0,05). При аналізі біохімічних показників були відзначені вірогідні відмінності рівня гамма-глутамілтрансферази у групі з вираженим фіброзом (F3) від показників групи з мінімальним фіброзом (F0–F1) ((40,2 ± 5,7) проти (26,4 ± 3,7), р &lt; 0,05). Отже, у значної частини пацієнтів з ідіопатичним підвищенням рівня трансаміназ чинником запалення є жирова дистрофія печінки, що не виявлялась при рутинному ультразвуковому обстеженні. У групі з більш розвинутим фіброзом спостерігалось зменшення вмісту жиру в печінці та підвищення активності гамма-глутамілтрансферази, що свідчить про посилення холестазу в печінці в даної категорії пацієнтів. Отже, у пацієнтів з ідіопатичним підвищенням трансаміназ навіть за відсутності ознак стеатозу згідно з даними сонографії доцільно проводити визначення CAP апаратом FibroScan, що є більш чутливим у встановленні жирової дистрофії, ніж ультразвукове дослідження.
Investigations of Genetic Risk Factors in MDS and AML Using High- Density 6.0 Affymetrix Arrays
Authors: Bartlomiej P Przychodzen, Anna Malgorzata Jankowska, Sandra P Smieszek, Sanjay Ram Mohan, Ramon V. Tiu, Monika Jasek, Lukasz P Gondek, Jaroslaw P Maciejewski
Journal: Blood (2008)
Alterations in Diets of Patients With Nonceliac Gluten Sensitivity Compared With Healthy Individuals
Authors: Fabiana Zingone, Chiara Bartalini, Monica Siniscalchi, Monica Ruotolo, Cristina Bucci, Ivonne Morra, Paola Iovino, Carolina Ciacci
Journal: Clinical Gastroenterology and Hepatology (2016)
Blood Transfusion After Coronary Artery Bypass Graft Surgery—Reply
Authors: Elliott Bennett-Guerrero
Journal: JAMA (2011)

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
Doctor who worked as locum while on sick leave is struck off
Authors: Clare Dyer
Journal: BMJ (2016)

A registrar in obstetrics and gynaecology has been struck off the UK medical register after he was convicted of fraud for working as a locum while on extended leave and sick leave, without divulging his true circumstances to any of his employers.

Anthony Madu, 47, who qualified in Nigeria, was convicted of six counts of fraud at Newport Crown Court in 2014. He received a 24 month sentence suspended for two years, three months of electronically monitored curfew, and had to complete 150 hours of unpaid work. 

This June, Cardiff Crown Court …
Procalcitonin-Based Guidelines and Lower Respiratory Tract Infections
Authors: Cornelis Stijnis
Journal: JAMA (2010)

To the Editor: In a randomized controlled trial, Dr Schuetz and colleagues studied the effect of a procalcitonin (PCT) algorithm in the antibiotic management of lower respiratory tract infections (LRTIs) in emergency departments of tertiary hospitals. Procalcitonin showed promise in helping to limit antibiotic therapy to those patients who are likely to benefit in inpatient settings where follow-up measurements are accessible and waiting time to obtain blood test results is short. In their discussion, the authors called for more widespread introduction of PCT measurement for milder LRTIs in outpatient physician offices. We think this conclusion is not justified because their study patients were managed in tertiary care settings. By focusing on the sickest patients with LRTI, the PCT test may have had better sensitivity in the study patients than it would have in less ill patients observed in primary care, a form of spectrum bias. Procalcitonin did not perform well in a prior study based in primary care. Despite a recent study showing efficacy and safety of a PCT approach to the restriction of activities of patients with LRTI in primary care, pragmatic evidence that the use of PCT for LRTI management in primary care leads to a reduction in antibiotic use is lacking. Explanatory trials evaluate efficacy in controlled conditions, and pragmatic trials evaluate effectiveness in usual care. How useful a trial is depends not only on the design but also on the similarity between the trial and the clinician’s context. It seems doubtful that introducing a costly test, not readily available as a near-patient test at present, will change physicians’ decision making. Moreover, such use runs a risk of defining a test result as a medical problem. In contrast, other less costly biomarkers, including C-reactive protein (CRP), have shown test characteristics similar to PCT when assessed in an outpatient population, and there is pragmatic evidence of the effectiveness of CRP testing when used at the point of care in a primary care setting. Before widespread use of PCT in primary care can be advocated, pragmatic evidence of the comparative and cost-effectiveness of different point-of-care strategies is needed.
Definitive Management of Primary Bladder Tumors in the Context of Metastatic Disease: Who, How, When, and Why?
Authors: Matthew D. Galsky, Josep Domingo-Domenech, John P. Sfakianos, Bart S. Ferket
Journal: Journal of Clinical Oncology (2016)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 70-year-old man with urothelial cancer of the bladder (UBC) metastatic to the pelvic and retroperitoneal lymph nodes was treated with gemcitabine plus cisplatin, but after two cycles neutropenic sepsis developed, which required a prolonged intensive care unit admission. Upon recovery, repeat imaging studies revealed progressive pelvic and retroperitoneal lymphadenopathy, and the patient enrolled in a clinical trial that evaluated treatment with an anti-PD-L1 antibody. The patient achieved a complete radiographic response to immune checkpoint blockade, which continued for 18 months after initiating therapy ( Fig 1 ). However, at that time, a cystoscopy of his primary tumor and a transurethral resection revealed residual muscle-invasive UBC. The patient asked whether there is any role for definitive local therapy of his primary bladder tumor with radical cystectomy or radiation.
Targeting FLT3-ITD signaling mediates ceramide-dependent mitophagy and attenuates drug resistance in AML
Authors: Mohammed Dany, Salih Gencer, Rose Nganga, Raquela J. Thomas, Natalia Oleinik, Kyla D. Baron, Zdzislaw M. Szulc, Peter Ruvolo, Steven Kornblau, Michael Andreeff, Besim Ogretmen
Journal: Blood (2016)
Being overweight may raise risk of eight more cancers, review finds
Authors: Susan Mayor
Journal: BMJ (2016)

Being overweight is associated with increased risk of eight further cancers, including stomach and liver cancers, in addition to those previously linked with excess weight, a large review has found.1

The International Agency for Research on Cancer (IARC) Working Group reviewed more than 1000 studies investigating cancer risk and excess body weight to update previous findings. Most of the studies …