tbuckley/cabot-search huggingface dataset:
Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer
Authors: Shang-Gin Wu, Jin-Yuan Shih
Journal: Molecular Cancer (2018)

Recent advances in diagnosis and treatment are enabling a more targeted approach to treating lung cancers. Therapy targeting the specific oncogenic driver mutation could inhibit tumor progression and provide a favorable prognosis in clinical practice. Activating mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are a favorable predictive factor for EGFR tyrosine kinase inhibitors (TKIs) treatment. For lung cancer patients with EGFR-exon 19 deletions or an exon 21 Leu858Arg mutation, the standard first-line treatment is first-generation (gefitinib, erlotinib), or second-generation (afatinib) TKIs. EGFR TKIs improve response rates, time to progression, and overall survival. Unfortunately, patients with EGFR mutant lung cancer develop disease progression after a median of 10 to 14 months on EGFR TKI. Different mechanisms of acquired resistance to first-generation and second-generation EGFR TKIs have been reported. Optimal treatment for the various mechanisms of acquired resistance is not yet clearly defined, except for the T790M mutation. Repeated tissue biopsy is important to explore resistance mechanisms, but it has limitations and risks. Liquid biopsy is a valid alternative to tissue re-biopsy. Osimertinib has been approved for patients with T790M-positive NSCLC with acquired resistance to EGFR TKI. For other TKI-resistant mechanisms, combination therapy may be considered. In addition, the use of immunotherapy in lung cancer treatment has evolved rapidly. Understanding and clarifying the biology of the resistance mechanisms of EGFR-mutant NSCLC could guide future drug development, leading to more precise therapy and advances in treatment.
Speech and Survival
Journal: New England Journal of Medicine (1982)

Abstract In Stage T3 carcinoma of the larynx (carcinoma restricted to the vocal cords, causing complete immobility of the cords but not extending to adjacent structures), laryngectomy leads to a three-year survival rate of approximately 60 per cent and the loss of normal speech. Radiation therapy, on the other hand, leads to a lower survival (30 to 40 per cent at three years) but preserves normal or nearly normal speech. We investigated attitudes toward the quantity and quality of life in 37 healthy volunteers, interviewing 12 firefighters and 25 middle and upper management executives to determine their preferences for longevity and voice preservation. We used the principles of expected utility theory to develop a method for sharpening decisions involving tradeoffs between quantity and quality of life. Our analysis indicates that to maintain their voices, approximately 20 per cent of volunteers would choose radiation instead of surgery. These results suggest that treatment choices should be made on the ba...
Concerns Regarding Resource Use and Outcomes in Subsets of Clinicians
Authors: Finlay A. McAlister
Journal: JAMA Internal Medicine (2018)

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
Influence of Diabetes on Trends in Perioperative Cardiovascular Events
Authors: Jonathan D. Newman, Tanya Wilcox, Nathaniel R. Smilowitz, Jeffrey S. Berger
Journal: Diabetes Care (2018)

OBJECTIVE Patients undergoing noncardiac surgery frequently have diabetes mellitus (DM) and an elevated risk of cardiovascular disease. It is unknown whether temporal declines in the frequency of perioperative major adverse cardiovascular and cerebrovascular events (MACCEs) apply to patients with DM. RESEARCH DESIGN AND METHODS Patients ≥45 years of age who underwent noncardiac surgery from January 2004 to December 2013 were identified using the U.S. National Inpatient Sample. DM was identified using ICD-9 diagnosis codes. Perioperative MACCEs (in-hospital all-cause mortality, acute myocardial infarction, or acute ischemic stroke) by DM status were evaluated over time. RESULTS The final study sample consisted of 10,581,621 hospitalizations for major noncardiac surgery; DM was present in ∼23% of surgeries and increased over time (P for trend &amp;lt;0.001). Patients with DM experienced MACCEs in 3.3% of surgeries vs. 2.8% of surgeries for patients without DM (P &amp;lt; 0.001). From 2004 to 2013, the odds of perioperative MACCEs after multivariable adjustment increased by 6% (95% CI 2–9) for DM patients, compared with an 8% decrease (95% CI −10 to −6) for patients without DM (P for interaction &amp;lt;0.001). Trends for individual end points were all less favorable for patients with DM versus those without DM. CONCLUSIONS In an analysis of &amp;gt;10.5 million noncardiac surgeries from a large U.S. hospital admission database, perioperative MACCEs were more common among patients with DM versus those without DM. Perioperative MACCEs increased over time and individual end points were all less favorable for patients with DM. Our findings suggest that a substantial unmet need exists for strategies to reduce the risk of perioperative cardiovascular events among patients with DM.
Routine Assessment and Promotion of Physical Activity in Healthcare Settings: A Scientific Statement From the American Heart Association
Authors: Felipe Lobelo, Deborah Rohm Young, Robert Sallis, Michael D. Garber, Sandra A. Billinger, John Duperly, Adrian Hutber, Russell R. Pate, Randal J. Thomas, Michael E. Widlansky, Michael V. McConnell, Elizabeth A. Joy
Journal: Circulation (2018)

Physical inactivity is one of the most prevalent major health risk factors, with 8 in 10 US adults not meeting aerobic and muscle-strengthening guidelines, and is associated with a high burden of cardiovascular disease. Improving and maintaining recommended levels of physical activity leads to reductions in metabolic, hemodynamic, functional, body composition, and epigenetic risk factors for noncommunicable chronic diseases. Physical activity also has a significant role, in many cases comparable or superior to drug interventions, in the prevention and management of >40 conditions such as diabetes mellitus, cancer, cardiovascular disease, obesity, depression, Alzheimer disease, and arthritis. Whereas most of the modifiable cardiovascular disease risk factors included in the American Heart Association's My Life Check - Life's Simple 7 are evaluated routinely in clinical practice (glucose and lipid profiles, blood pressure, obesity, and smoking), physical activity is typically not assessed. The purpose of this statement is to provide a comprehensive review of the evidence on the feasibility, validity, and effectiveness of assessing and promoting physical activity in healthcare settings for adult patients. It also adds concrete recommendations for healthcare systems, clinical and community care providers, fitness professionals, the technology industry, and other stakeholders in order to catalyze increased adoption of physical activity assessment and promotion in healthcare settings and to contribute to meeting the American Heart Association's 2020 Impact Goals.
What is the greatest achievement of the NHS?
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

When the NHS launched on 5 July 1948 its mastermind Aneurin Bevan told the professionals at its heart “to use your skills and judgment without hindrance.” At the time there were shortages of doctors and nurses, just as there are now. Nevertheless, the NHS has won an admiring audience the world over, and its endurance over 70 years of reform and challenge should be celebrated.

But what is the greatest achievement of the NHS? The one …
Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion
Authors: Rahul Bhatnagar, Emma K. Keenan, Anna J. Morley, Brennan C. Kahan, Andrew E. Stanton, Mohammed Haris, Richard N. Harrison, Rehan A. Mustafa, Lesley J. Bishop, Liju Ahmed, Alex West, Jayne Holme, Matthew Evison, Mohammed Munavvar, Pasupathy Sivasothy, Jurgen Herre, David Cooper, Mark Roberts, Anur Guhan, Clare Hooper, James Walters, Tarek S. Saba, Biswajit Chakrabarti, Samal Gunatilake, Ioannis Psallidas, Steven P. Walker, Anna C. Bibby, Sarah Smith, Louise J. Stadon, Natalie J. Zahan-Evans, Y.C. Gary Lee, John E. Harvey, Najib M. Rahman, Robert F. Miller, Nick A. Maskell
Journal: New England Journal of Medicine (2018)

Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone.Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through the indwelling pleural catheter on an outpatient basis. Talc or placebo was administered on a single-blind basis. Follow-up lasted for 70 days. The primary outcome was successful pleurodesis at day 35 after randomization.The target of 154 patients undergoing randomization was reached after 584 patients were approached. At day 35, a total of 30 of 69 patients (43%) in the talc group had successful pleurodesis, as compared with 16 of 70 (23%) in the placebo group (hazard ratio, 2.20; 95% confidence interval, 1.23 to 3.92; P=0.008). No significant between-group differences in effusion size and complexity, number of inpatient days, mortality, or number of adverse events were identified. No significant excess of blockages of the indwelling pleural catheter was noted in the talc group.Among patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an indwelling catheter alone, with no deleterious effects. (Funded by Becton Dickinson; EudraCT number, 2012-000599-40 .).
Immunotherapy for Pancreatic Cancer: More Than Just a Gut Feeling
Authors: Erick Riquelme, Anirban Maitra, Florencia McAllister
Journal: Cancer Discovery (2018)

Abstract Summary: Development of pancreatic cancer in spontaneous murine models is associated with enrichment of specific strains of gut and intratumoral bacteria that induce a tolerogenic immunosuppressive microenvironment favoring cancer progression and resistance to immunotherapies. Ablation of the microbiome with antibiotics reshapes the tumor microenvironment, inducing T-cell activation, improving immune surveillance, and increasing sensitivity to immunotherapy in established tumors. Cancer Discov; 8(4); 386–8. ©2018 AACR. See related article by Pushalkar et al., p. 403.
Prognostic value of DNA mismatch repair status and KRAS mutations in Korean colorectal cancer patients.
Authors: Soon Woo Hwang, Young-Seok Cho, Kim Kyeong Ok, Jae Myung Cha, Young-Eun Joo
Journal: Journal of Clinical Oncology (2018)

697 Background: The association of DNA mismatch repair (MMR) and KRAS mutation on clinical outcome of patients with colorectal cancer are frequently documented. However, development of more accurate prediction on clinical outcome using combination of both biomarkers remains a worthy area of investigation. The aim of this study was to evaluate the clinical relevance of KRAS mutation and MMR status in Korean patients with colorectal cancer (CRC). Methods: Clinical and pathological information for 1174 patients, who underwent surgery for colorectal cancer in 3 teaching hospitals from 2011 to 2013, were reviewed and recorded. Mutation analysis for exon 2 of KRAS gene was performed by Sanger sequencing. Expression of MMR proteins including MLH1 and MSH2 was evaluated by immunohistochemistry. Results: The overall frequencies of KRAS mutation was 34.9%. Mutations in KRAS codon 12 and codon 13 were detected in 26.7% and 8.2% of patients, respectively. Overall, 90 s (7.7%) tumors that had at least loss of expression for at least one MMR protein were defined as MMR protein deficient (MMR-D), and the remaining tumors were classified as MMR protein intact (MMR-I). According to KRAS mutation and MMR status, CRC was classified to 4 groups: Group 1, KRAS-mutated and MMR-I; Group 2, KRAS-mutated and MMR-D; Group 3, KRAS wild and MMR-I; and Group 4, KRAS wild and MMR-D. We found that patients in Group 4 had the best prognosis, and patients in Group 2 had the worst overall survival. KRAS mutation was independently associated with shorter time to recurrence and poorer overall survival. Conclusions: Combination status of KRAS mutation and MMR provide fundamental genetic signatures affecting tumor behavior, and may be used as a prognostic biomarker for CRC patient. These findings should be validated by further larger prospective study. [Table: see text]
Mesenchymal stem cells encapsulated into biomimetic hydrogel scaffold gradually release CCL2 chemokine in situ preserving cytoarchitecture and promoting functional recovery in spinal cord injury
Authors: S. Papa, I. Vismara, A. Mariani, M. Barilani, S. Rimondo, M. De Paola, N. Panini, E. Erba, E. Mauri, F. Rossi, G. Forloni, L. Lazzari, P. Veglianese
Journal: Journal of Controlled Release (2018)
Clinical utility of Oncotype DX in early stage colon cancer.
Authors: Mohammed Adam Ibrahim Dawod, Jane Sze Yin Sui, Deirdre Kelly, Lynda M. McSorley, Claire Brady, Richard Bambury, Seamus O'Reilly, Emmet J Andrews, Morgan McCourt, Michael O'Riordain, Kevin J. Murray, Brian Waldron, Michael William Bennett, Ken Feeley, Derek Gerard Power
Journal: Journal of Clinical Oncology (2017)

e15076 Background: With the advent of colon cancer screening, patients with early stage colon cancer will be more common in our clinics. The evidence supporting the absolute benefit of chemotherapy in resected Stage II and (to a lesser extent) Stage IIIA disease is poor. Not all patients benefit from chemotherapy and toxicity is a problem. There is a need for validated biomarkers to assess individual patient recurrence risk and discriminate absolute treatment benefit. Several studies have validated the role of the OncotypeDX testing in Stage II/IIIA disease. Our objective is to characterize whether this test impacted oncologists’ decisions in treating patients with Stage II/IIIA in the adjuvant setting. Methods: :The Onco typeDX assay is a multi-gene reverse-transcriptase-polymerase-chain-reaction test that analyses the expression of 12 genes involved in key biologic pathways in colon cancer. Stage II and Stage IIIA colon cancers were studied in affiliated hospitals of our region in southwest Ireland. All data collected is prospective and each colon cancer was assigned a recurrence risk score. Oncologists were blinded to this score and the decision to prescribe adjuvant chemotherapy was recorded. After un-blinding the score, a second decision was recorded and comparisons made. Results: :From August 2015 to September 2016, 70 patients have been recruited with M: F of 2:1. Median age at diagnosis was 65 years. Most patients (80%) had stage II disease, 11 of whom had mismatch repair loss on IHC. OncotypeDX testing has been carried out and reported for 59 patients (85%), MMR intact. Recurrence scores: &lt; 30 in 46 patients (77.9%), 30-40 in 10 patients, and &gt; 40 in 3 patients. The treatment plan was altered in 16 patients (27%), of whom 12 patients (20%) received none or less intense chemotherapy. Conclusions: We have shown that the decision to prescribe adjuvant chemotherapy was changed in 27% of patients. This test has helped to define patients with low scores, where chemotherapy-related toxicity is a concern especially in older patients. Absolute benefit of adjuvant chemotherapy versus the risk of toxicity should be discussed. . Hospital managers may be interested in cost savings due to a reduction in chemotherapy use.
Mutation Profiling of Key Cancer Genes in Primary Breast Cancers and Their Distant Metastases
Authors: Willemijne A.M.E. Schrijver, Pier Selenica, Ju Youn Lee, Charlotte K.Y. Ng, Kathleen A. Burke, Salvatore Piscuoglio, Samuel H. Berman, Jorge S. Reis-Filho, Britta Weigelt, Paul J. van Diest, Cathy B. Moelans
Journal: Cancer Research (2018)

Abstract Although the repertoire of somatic genetic alterations of primary breast cancers has been extensively catalogued, the genetic differences between primary and metastatic tumors have been less studied. In this study, we compared somatic mutations and gene copy number alterations of primary breast cancers and their matched metastases from patients with estrogen receptor (ER)–negative disease. DNA samples obtained from formalin-fixed paraffin-embedded ER-negative/HER2-positive (n = 9) and ER-, progesterone receptor (PR-), HER2-negative (n = 8) primary breast cancers and from paired brain or skin metastases and normal tissue were subjected to a hybridization capture-based massively parallel sequencing assay, targeting 341 key cancer genes. A large subset of nonsynonymous somatic mutations (45%) and gene copy number alterations (55%) was shared between the primary tumors and paired metastases. However, mutations restricted to either a given primary tumor or its metastasis, the acquisition of loss of heterozygosity of the wild-type allele, and clonal shifts of genes affected by somatic mutations, such as TP53 and RB1, were observed in the progression from primary tumors to metastases. No metastasis location-specific alterations were identified, but synchronous metastases showed higher concordance with the paired primary tumor than metachronous metastases. Novel potentially targetable alterations were found in the metastases relative to their matched primary tumors. These data indicate that repertoires of somatic genetic alterations in ER-negative metastatic breast cancers may differ from those of their primary tumors, even by the presence of driver and targetable somatic genetic alterations. Significance: Somatic genetic alterations in ER-negative breast cancer metastases may be distinct from those of their primary tumors, suggesting that for treatment-decision making, genetic analyses of DNA obtained from the metastatic lesion rather than from the primary tumor should be considered. Cancer Res; 78(12); 3112–21. ©2018 AACR.
Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck: role, controversy, and future directions
Authors: R.I. Haddad, M. Posner, R. Hitt, E.E.W. Cohen, J. Schulten, J.-L. Lefebvre, J.B. Vermorken
Journal: Annals of Oncology (2018)

The value of induction chemotherapy (ICT) remains under investigation despite decades of research. New advancements in the field, specifically regarding the induction regimen of choice, have reignited interest in this approach for patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Sufficient evidence has accumulated regarding the benefits and superiority of TPF (docetaxel, cisplatin, and fluorouracil) over the chemotherapy doublet cisplatin and fluorouracil. We therefore sought to collate and interpret the available data and further discuss the considerations for delivering ICT safely and optimally selecting suitable post-ICT regimens.
ASK1/2 signaling promotes inflammation in a mouse model of neutrophilic dermatosis
Authors: Sarang Tartey, Prajwal Gurung, Tejasvi Krishna Dasari, Amanda Burton, Thirumala-Devi Kanneganti
Journal: Journal of Clinical Investigation (2018)

Mice homozygous for the Tyr208Asn amino acid substitution in the carboxy terminus of Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1) (referred to as Ptpn6spin mice) spontaneously develop a severe inflammatory disease resembling neutrophilic dermatosis in humans. Disease in Ptpn6spin mice is characterized by persistent footpad swelling and suppurative inflammation. Recently, in addition to IL-1α and IL-1R signaling, we demonstrated a pivotal role for several kinases such as SYK, RIPK1, and TAK1 in promoting inflammatory disease in Ptpn6spin mice. In order to identify new kinases involved in SHP-1-mediated inflammation, we took a genetic approach and discovered apoptosis signal-regulating kinases 1 and 2 (ASK1 and ASK2) as novel kinases regulating Ptpn6-mediated footpad inflammation. Double deletion of ASK1 and ASK2 abrogated cutaneous inflammatory disease in Ptpn6spin mice. This double deletion further rescued the splenomegaly and lymphomegaly caused by excessive neutrophil infiltration in Ptpn6spin mice. Mechanistically, ASK regulates Ptpn6spin-mediated disease by controlling proinflammatory signaling in the neutrophils. Collectively, the present study identifies SHP-1 and ASK signaling crosstalk as a critical regulator of IL-1α-driven inflammation and opens future avenues for finding novel drug targets to treat neutrophilic dermatosis in humans.
The evolution of the shaman's cultural toolkit
Authors: Aiyana K. Willard, Yo Nakawake, Jonathan Jong
Journal: Behavioral and Brain Sciences (2018)

A complete picture of shamanism's cultural evolution requires an understanding of how the professionalization of shamanism affects the distribution of knowledge within societies. We suggest that limiting knowledge to fewer people could impede the accumulation of functional knowledge within shamanism. On this basis, we make further predictions about how the domain of shamanism could change and collapse.
Opioid prescriptions decreased in US states where marijuana was legally accessible
Authors: Owen Dyer
Journal: BMJ (2018)

American states that permitted legal access to marijuana through medical cannabis laws or legalized its adult recreational use saw falls in opioid prescriptions over a five year period, research has found.

Researchers from the University of Georgia conducted longitudinal analysis of Medicare Part D records from 2010 to 2015. Their findings, published in JAMA Internal Medicine ,1 showed a significant 14.4% average reduction in opioid prescriptions in states that allowed medical marijuana dispensaries. The effect was particularly pronounced in hydrocodone and morphine use.

The average state dispensed 23.08 million daily doses of any opioid each year, approximately half being hydrocodone. Permitting access to …