tbuckley/cabot-search huggingface dataset:
Closed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma
Authors: Swati Gupta, Leena McCann, Yvonne G. Y. Chan, Edwin W. Lai, Wei Wei, Pok Fai Wong, James W. Smithy, Jodi Weidler, Brian Rhees, Michael Bates, Harriet M. Kluger, David L. Rimm
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> In melanoma, there is no companion diagnostic test to predict response to programmed cell death 1 (PD-1) axis immune checkpoint inhibitor (ICI) therapy. In the adjuvant setting, only one in five patients may benefit from ICI, so a biomarker is needed to select those that may or may not benefit. Here, we test a new 4-gene multiplex immunotherapy panel with research use only (RUO) prototype mRNA expression profile on the GeneXpert closed system using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) for association with clinical benefit after treatment with ICI therapy in metastatic melanoma patients. <h3>Methods</h3> Pretreatment formalin-fixed paraffin-embedded (FFPE) tissue sections from melanoma patients treated with anti-PD-1 therapy (pembrolizumab, nivolumab, or ipilimumab plus nivolumab) between 2011 and 17 were selected from the Yale Pathology archives. FFPE sections were macrodissected to enrich for tumor for quantitative assessment of <i>CD274 (PD-L1), PDCD1LG2 (PD-L2), CD8A,</i> and <i>IRF1</i> by RT-qPCR multiplex mRNA panel. Multiplex panel transcript levels were correlated with clinical benefit (complete response [CR], partial response [PR], stable disease [SD]); disease outcomes (progression-free survival [PFS] and overall survival [OS]); and protein levels assessed by quantitative immunofluorescence (QIF). <h3>Results</h3> Transcript levels were significantly higher in responders (CR/PR/SD) than in nonresponders (PD) for <i>CD8A</i> (<i>p</i> = 0.0001) and <i>IRF1</i> (<i>p</i> = 0.0019). PFS was strongly associated with high <i>CD274</i> (<i>p</i> = 0.0046), <i>PDCD1LG2</i> (<i>p</i> = 0.0039), <i>CD8A</i> (<i>p</i> = 0.0002), and <i>IRF1</i> (<i>p</i> = 0.0030) mRNA expression. Similar associations were observed for OS with high <i>CD274</i> (<i>p</i> = 0.0004), <i>CD8A</i> (<i>p</i> = 0.0030), and <i>IRF1</i> (<i>p</i> = 0.0096) mRNA expression. Multivariate analyses revealed significant PFS and OS associations with immunotherapy panel markers independent of baseline variables. Exploratory analyses revealed a novel significant association of high combined <i>CD274</i> &amp; <i>PDCD1LG2 (L1/L2</i>) transcript expression with PFS (<i>p</i> &lt; 0.0001) and OS (<i>p</i> = 0.0011), which remained significant at a multivariate level for both PFS (HR = 0.31) and OS (HR = 0.39). <h3>Conclusions</h3> Individual immunotherapy panel markers <i>CD274, PDCD1LG2, CD8A</i>, <i>IRF1</i> and a combined <i>L1/L2</i> mRNA levels show promising associations with melanoma immunotherapy outcome. The turnaround time of the test (2 h) and easy standardization of the platform makes this an attractive approach for further study in the search for predictive biomarkers for ICI.
Would You Refer This Patient With Cancer to a Palliative Care Specialist?
Authors: Eileen E. Reynolds, Mary K. Buss, Benjamin L. Schlechter
Journal: Annals of Internal Medicine (2019)

Letters17 September 2019Would You Refer This Patient With Cancer to a Palliative Care Specialist?Eileen E. Reynolds, MD, Mary K. Buss, MD, MPH, and Benjamin L. Schlechter, MDEileen E. Reynolds, MDBeth Israel Deaconess Medical Center, Boston, Massachusetts (E.E.R., M.K.B., B.L.S.)Search for more papers by this author, Mary K. Buss, MD, MPHBeth Israel Deaconess Medical Center, Boston, Massachusetts (E.E.R., M.K.B., B.L.S.)Search for more papers by this author, and Benjamin L. Schlechter, MDBeth Israel Deaconess Medical Center, Boston, Massachusetts (E.E.R., M.K.B., B.L.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0374 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree that a population management approach could be applied to help identify patients with palliative care needs. The American Society of Clinical Oncology guideline essentially endorses the integration of palliative care for patients with advanced cancer—independent of their physical, psychosocial, or spiritual symptom burden—as a means of engaging such care earlier in these patients' disease course. Patients in the primary care setting often have multiple medical conditions and a less-certain prognosis and illness trajectory, which makes prospectively defining those with palliative care needs more challenging. We endorse efforts to use risk stratification tools. Author, Article, and Disclosure InformationAffiliations: Beth Israel Deaconess Medical Center, Boston, Massachusetts (E.E.R., M.K.B., B.L.S.)Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-0361. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoWould You Refer This Patient With Cancer to a Palliative Care Specialist? Eileen E. Reynolds , Mary K. Buss , Benjamin L. Schlechter , and Anjala Tess Would You Refer This Patient With Cancer to a Palliative Care Specialist? Phil Di Sorbo Metrics 17 September 2019Volume 171, Issue 6Page: 448KeywordsConflicts of interestDisclosureMedical conditionsPalliative carePatients ePublished: 17 September 2019 Issue Published: 17 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Selective inhibition of low-affinity memory CD8+ T cells by corticosteroids
Authors: Akihiro Tokunaga, Daisuke Sugiyama, Yuka Maeda, Allison Betof Warner, Katherine S. Panageas, Sachiko Ito, Yosuke Togashi, Chika Sakai, Jedd D. Wolchok, Hiroyoshi Nishikawa
Journal: The Journal of Experimental Medicine (2019)

Patients treated with immune checkpoint blockade (ICB) sometimes experience immune-related adverse events (irAEs), requiring immuno-suppressive drugs such as corticosteroids despite the possibility that immunosuppression may impair the antitumor effects of ICB. Here, we address the dilemma of using corticosteroids for the treatment of irAEs induced by ICB. ICB augments neoantigen-specific CD8+ T cell responses, resulting in tumor regression. In our model, simultaneous, but not late, administration of corticosteroids impaired antitumor responses with reduction of CD8+ T cell proliferation. Secondary challenge using tumors with/without the neoantigen showed selective progression in tumors lacking the neoantigen when corticosteroids were administered. Corticosteroids decreased low- but not high-affinity memory T cells by suppressing fatty acid metabolism essential for memory T cells. In a small cohort of human melanoma patients, overall survival was shorter after treatment with CTLA-4 blockade in patients who received early corticosteroids or had low tumor mutation burden. Together, low-affinity memory T cells are dominantly suppressed by corticosteroids, necessitating careful and thoughtful corticosteroid use.
Association of Early Palliative Care Use With Survival and Place of Death Among Patients With Advanced Lung Cancer Receiving Care in the Veterans Health Administration
Authors: Donald R. Sullivan, Benjamin Chan, Jodi A. Lapidus, Linda Ganzini, Lissi Hansen, Patricia A. Carney, Erik K. Fromme, Miguel Marino, Sara E. Golden, Kelly C. Vranas, Christopher G. Slatore
Journal: JAMA Oncology (2019)

<h3>Importance</h3> Palliative care is a patient-centered approach associated with improvements in quality of life; however, results regarding its association with a survival benefit have been mixed, which may be a factor in its underuse. <h3>Objective</h3> To assess whether early palliative care is associated with a survival benefit among patients with advanced lung cancer. <h3>Design, Setting, and Participants</h3> This retrospective population-based cohort study was conducted among patients with lung cancer who were diagnosed with cancer between January 1, 2007, and December 31, 2013, with follow-up until January 23, 2017. Participants comprised 23 154 patients with advanced lung cancer (stage IIIB and stage IV) who received care in the Veterans Affairs health care system. Data were analyzed from February 15, 2019, to April 28, 2019. <h3>Exposure</h3> Palliative care defined as a specialist-delivered palliative care encounter received after lung cancer diagnosis. <h3>Main Outcomes and Measures</h3> The primary outcome was survival. The association between palliative care and place of death was also examined. Propensity score and time-varying covariate methods were used to calculate Cox proportional hazards and to perform regression modeling. <h3>Results</h3> Of the 23 154 patients enrolled in the study, 57% received palliative care. The mean (SD) age of participants was 68 (9.5) years, and 98% of participants were men. An examination of the timing of palliative care receipt relative to cancer diagnosis found that palliative care received 0 to 30 days after diagnosis was associated with decreases in survival (adjusted hazard ratio [aHR], 2.13; 95% CI, 1.97-2.30), palliative care received 31 to 365 days after diagnosis was associated with increases in survival (aHR, 0.47; 95% CI, 0.45-0.49), and palliative care received more than 365 days after diagnosis was associated with no difference in survival (aHR, 1.00; 95% CI, 0.94-1.07) compared with nonreceipt of palliative care. Receipt of palliative care was also associated with a reduced risk of death in an acute care setting (adjusted odds ratio, 0.57; 95% CI, 0.52-0.64) compared with nonreceipt of palliative care. <h3>Conclusions and Relevance</h3> The results suggest that palliative care was associated with a survival benefit among patients with advanced lung cancer. Palliative care should be considered a complementary approach to disease-modifying therapy in patients with advanced lung cancer.
Efficacy of the CCR5 Antagonist Maraviroc in Reducing Early, Ritonavir-Induced Atherogenesis and Advanced Plaque Progression in Mice
Authors: SabrinaCipriani, DanielaFrancisci, AndreaMencarelli, BarbaraRenga, ElisabettaSchiaroli, ClaudioD’Amore, FrancoBaldelli, StefanoFiorucci
Journal: Circulation (2013)

Background—CCR5 plays an important role in atherosclerosis and ischemic cardiovascular diseases, as well as in HIV replication and diffusion. HIV infection is characterized by a high burden of cardiovascular diseases, particularly in subjects exposed to ritonavir-boosted protease inhibitors. Maraviroc, a CCR5 antagonist antiretroviral drug, might provide benefit for patients with M-tropic HIV infections at high risk for cardiovascular diseases. Methods and Results—Exposure to maraviroc limits the evolution and associated systemic inflammation of ritonavir-induced atherosclerotic in ApoE−/− mice and inhibits plaques development in a late model of atherosclerosis in which dyslipidemia plays the main pathogenic role. In ritonavir-treated mice, maraviroc reduced plaque areas and macrophage infiltration; downregulated the local expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and interleukin-17A; and reduced tumor necrosis factor-α and RANT...
Combination of Omacetaxine Mepesuccinate (homoharringtonine) and Sorafenib As an Effective Regimen for Acute Myeloid Leukemia (AML) Carrying FLT3-ITD
Authors: Garret Mk Leung, Chunxiao Zhang, Alan Wl To, Stephen Sy Lam, Yok Lam Kwong, Anskar Leung
Journal: Blood (2017)
How many lymph nodes may serve as a guideline for a sufficient extended lymph node dissection during radical prostatectomy?
Authors: G. Pomara, G. Campo, C. Milesi, P. Casale, F. Francesca
Journal: Journal of Clinical Oncology (2009)

e16102 Background: Recent data suggest that extended lymph node (LN) dissection at radical prostatectomy (RP) may be necessary to detect occult positive lymph nodes, and that extended dissection may also have a positive impact on disease progression and long-term disease-free survival. However, evaluation of lymphadenectomy to be complete and sufficient as judged by the number of removed lymph nodes is sometimes difficult. Some authors reported that approximately 20 pelvic lymph nodes may serve as a guideline for a sufficient extended lymph node dissection during RP. The purposes of this study were 1) to assess the reproducibility of this number (20 LN) in experienced hands; 2) to evaluate the effect of the number of LNs removed on lymph node metastasis. Materials and Methods: Data from 293 consecutives patients undergone to RP with extended lymphadenectomy were prospectively analyzed [median age 66 (35–79), median PSA 7.98 ng/ml (2.5–35)]. The number of lymph nodes extracted and the number of patients with positive lymph nodes detected were analyzed and compared. Moreover we distinguished and analyzed RPs data of most experienced surgeon: 124 patients [median age 65aa (44–79), median PSA 6.7(2.5–19)]. Results: Analyzing all the population, the median number of removed lymph nodes was 15 (1–39). Analyzing only the most experienced surgeon results, the median number of removed lymph nodes was 20 (range 6–39). The effect of the number of LNs removed on lymph node metastasis is shown in the Table . Conclusions: Compared to limited lymph node dissection (&lt; 10 removed LNs), extended pelvic lymphadenectomy appears to identify men with positive lymph nodes more frequently. Although very experienced surgeons remove approximately 20 pelvic lymph nodes (comparable to the literature), our results seem to underline that 15 removed LNs are sufficient as a guideline for an extended lymph node dissection during RP. [Table: see text] No significant financial relationships to disclose.
Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis
Authors: Laura M Nic Lochlainn, Brechje de Gier, Nicoline van der Maas, Peter M Strebel, Tracey Goodman, Rob S van Binnendijk, Hester E de Melker, Susan J M Hahné
Journal: The Lancet Infectious Diseases (2019)

Measles is an important cause of death in children, despite the availability of safe and cost-saving measles-containing vaccines (MCVs). The first MCV dose (MCV1) is recommended at 9 months of age in countries with ongoing measles transmission, and at 12 months in countries with low risk of measles. To assess whether bringing forward the age of MCV1 is beneficial, we did a systematic review and meta-analysis of the benefits and risks of MCV1 in infants younger than 9 months.
Disentangling the Association of Screen Time With Developmental Outcomes and Well-being
Authors: Janis Whitlock, Philipp K. Masur
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Discovery, Validation, and Application of Novel Methylated DNA Markers for Detection of Esophageal Cancer in Plasma
Authors: Yi Qin, Chung W. Wu, William R. Taylor, Tarek Sawas, Kelli N. Burger, Douglas W. Mahoney, Zhifu Sun, Tracy C. Yab, Graham P. Lidgard, Hatim T. Allawi, Navtej S. Buttar, Thomas C. Smyrk, Prasad G. Iyer, David A. Katzka, David A. Ahlquist, John B. Kisiel
Journal: Clinical Cancer Research (2019)

The burden of esophageal cancer continues to rise, and noninvasive screening tools are needed. Methylated DNA markers (MDM) assayed from plasma show promise in detection of other cancers. For esophageal cancer detection, we aimed to discover and validate MDMs in tissue, and determine their feasibility when assayed from plasma.
Adenosine Primes the Opening of Mitochondrial ATP-Sensitive Potassium Channels
Authors: ToshiakiSato, NorihitoSasaki, BrianO’Rourke, EduardoMarbán
Journal: Circulation (2000)

Background—Adenosine can initiate ischemic preconditioning, and mitochondrial ATP-sensitive potassium (KATP) channels have emerged as the likely effectors. We sought to determine the mechanistic interactions between these 2 observations. Methods and Results—The mitochondrial flavoprotein oxidation induced by diazoxide (100 μmol/L) was used to quantify mitochondrial KATP channel activity in intact rabbit ventricular myocytes. Adenosine (100 μmol/L) increased mitochondrial KATP channel activity and abbreviated the latency to mitochondrial KATP channel opening. These potentiating effects were entirely prevented by the adenosine receptor antagonist 8-(p-sulfophenyl)-theophylline (100 μmol/L) or by the protein kinase C inhibitor polymyxin B (50 μmol/L). The effects of adenosine and diazoxide reflected mitochondrial KATP channel activation, because they could be blocked by the mitochondrial KATP channel blocker 5-hydroxydecanoate (500 μmol/L). In a cellular model of simulated ischemia, adenosine mitigated cell ...
Evidence-Based Treatment for Mixed Urinary Incontinence
Authors: Ingrid E. Nygaard
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Transactions of the American Surgical Association.
Journal: JAMA (1894)

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
Recombinant annexin A6 promotes membrane repair and protects against muscle injury
Authors: Alexis R. Demonbreun, Katherine S. Fallon, Claire C. Oosterbaan, Elena Bogdanovic, James L. Warner, Jordan J. Sell, Patrick G. Page, Mattia Quattrocelli, David Y. Barefield, Elizabeth M. McNally
Journal: Journal of Clinical Investigation (2019)

Membrane repair is essential to cell survival. In skeletal muscle, injury often associates with plasma membrane disruption. Additionally, muscular dystrophy is linked to mutations in genes that produce fragile membranes or reduce membrane repair. Methods to enhance repair and reduce susceptibility to injury could benefit muscle in both acute and chronic injury settings. Annexins are a family of membrane-associated Ca2+-binding proteins implicated in repair, and annexin A6 was previously identified as a genetic modifier of muscle injury and disease. Annexin A6 forms the repair cap over the site of membrane disruption. To elucidate how annexins facilitate repair, we visualized annexin cap formation during injury. We found that annexin cap size positively correlated with increasing Ca2+ concentrations. We also found that annexin overexpression promoted external blebs enriched in Ca2+ and correlated with a reduction of intracellular Ca2+ at the injury site. Annexin A6 overexpression reduced membrane injury, consistent with enhanced repair. Treatment with recombinant annexin A6 protected against acute muscle injury in vitro and in vivo. Moreover, administration of recombinant annexin A6 in a model of muscular dystrophy reduced serum creatinine kinase, a biomarker of disease. These data identify annexins as mediators of membrane-associated Ca2+ release during membrane repair and annexin A6 as a therapeutic target to enhance membrane repair capacity.