tbuckley/cabot-search huggingface dataset:
Single-Payer Reform
Authors: David Silverman
Journal: Annals of Internal Medicine (2017)

Letters3 October 2017Single-Payer ReformDavid Silverman, MDDavid Silverman, MDFrom Rotorua Adult Medicine, Rotorua, New Zealand.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0325 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Woolhandler and Himmelstein's commentary (1) with great interest. I am an internist and worked in the United States for 30 years and in New Zealand for 9 years, 8 of which I served as a full-time employee in a public hospital. As a provider, I never had a job or life better than I have had in New Zealand. All hospital-based care is free. The purpose of public health care is to provide medical care, not make money. There is a health care budget, and not everything is available for everyone; however, we have better ...Reference1. Woolhandler S, Himmelstein DU. Single-payer reform: the only way to fulfill the president's pledge of more coverage, better benefits, and lower costs. Ann Intern Med. 2017;166:587-8. [PMID: 28241256]. doi:10.7326/M17-0302 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Rotorua Adult Medicine, Rotorua, New Zealand.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0325. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPhysician Decision Making and Clinical Outcomes With Laboratory Polysomnography or Limited-Channel Sleep Studies for Obstructive Sleep Apnea Ching Li Chai-Coetzer , Nick A. Antic , Garun S. Hamilton , Nigel McArdle , Keith Wong , Brendon J. Yee , Aeneas Yeo , Rajeev Ratnavadivel , Matthew T. Naughton , Teanau Roebuck , Richard Woodman , and R. Doug McEvoy Single-Payer Reform Steffie Woolhandler and David U. Himmelstein Single-Payer Reform Gilead I. Lancaster and Joseph P. Drozda Jr. Metrics 3 October 2017Volume 167, Issue 7Page: 526KeywordsDisclosureHealth careHealth economicsInsurancePrevention, policy, and public healthShoulders ePublished: 3 October 2017 Issue Published: 3 October 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Neural precursor cell–secreted TGF-β2 redirects inflammatory monocyte-derived cells in CNS autoimmunity
Authors: Donatella De Feo, Arianna Merlini, Elena Brambilla, Linda Ottoboni, Cecilia Laterza, Ramesh Menon, Sundararajan Srinivasan, Cinthia Farina, Jose Manuel Garcia Manteiga, Erica Butti, Marco Bacigaluppi, Giancarlo Comi, Melanie Greter, Gianvito Martino
Journal: Journal of Clinical Investigation (2017)

In multiple sclerosis, the pathological interaction between autoreactive Th cells and mononuclear phagocytes in the CNS drives initiation and maintenance of chronic neuroinflammation. Here, we found that intrathecal transplantation of neural stem/precursor cells (NPCs) in mice with experimental autoimmune encephalomyelitis (EAE) impairs the accumulation of inflammatory monocyte-derived cells (MCs) in the CNS, leading to improved clinical outcome. Secretion of IL-23, IL-1, and TNF-α, the cytokines required for terminal differentiation of Th cells, decreased in the CNS of NPC-treated mice, consequently inhibiting the induction of GM-CSF–producing pathogenic Th cells. In vivo and in vitro transcriptome analyses showed that NPC-secreted factors inhibit MC differentiation and activation, favoring the switch toward an antiinflammatory phenotype. Tgfb2–/– NPCs transplanted into EAE mice were ineffective in impairing MC accumulation within the CNS and failed to drive clinical improvement. Moreover, intrathecal delivery of TGF-β2 during the effector phase of EAE ameliorated disease severity. Taken together, these observations identify TGF-β2 as the crucial mediator of NPC immunomodulation. This study provides evidence that intrathecally transplanted NPCs interfere with the CNS-restricted inflammation of EAE by reprogramming infiltrating MCs into antiinflammatory myeloid cells via secretion of TGF-β2.
Not all interventions for burnout cost money: the value of debrief groups
Authors: Sara V Lightowlers, Mareike K Thompson, Susannah L Hunt
Journal: BMJ (2017)

Spurred on by a BMJ Careers article on Balint groups,1 and recognising rising stress in our peers, we started a monthly debrief group for oncology registrars in our centre, facilitated by a medically qualified chaplain (SLH).

Topics have been wide ranging, reflecting all three dimensions of burnout (depersonalisation, exhaustion, and professional inefficacy),2 and have included high stress when …
Spatiotemporal Mapping of Erythroid, Stromal, and Osteogenic Niche Formation to Support Physiologic Red Cell Production in a Three-Dimensional Hollow Fibre Perfusion Bioreactor
Authors: Mark C. Allenby, Asma Tahlawi, Ruth Misener, Susana Brito dos Santos, Athanasios Mantalaris, Nicki Panoskaltsis
Journal: Blood (2016)
Multiscale Modeling of Inflammation-Induced Tumorigenesis Reveals Competing Oncogenic and Oncoprotective Roles for Inflammation
Authors: Yucheng Guo, Qing Nie, Adam L. MacLean, Yanda Li, Jinzhi Lei, Shao Li
Journal: Cancer Research (2017)

Chronic inflammation is a serious risk factor for cancer; however, the routes from inflammation to cancer are poorly understood. On the basis of the processes implicated by frequently mutated genes associated with inflammation and cancer in three organs (stomach, colon, and liver) extracted from the Gene Expression Omnibus, The Cancer Genome Atlas, and Gene Ontology databases, we present a multiscale model of the long-term evolutionary dynamics leading from inflammation to tumorigenesis. The model incorporates cross-talk among interactions on several scales, including responses to DNA damage, gene mutation, cell-cycle behavior, population dynamics, inflammation, and metabolism-immune balance. Model simulations revealed two stages of inflammation-induced tumorigenesis: a precancerous state and tumorigenesis. The precancerous state was mainly caused by mutations in the cell proliferation pathway; the transition from the precancerous to tumorigenic states was induced by mutations in pathways associated with apoptosis, differentiation, and metabolism-immune balance. We identified opposing effects of inflammation on tumorigenesis. Mild inflammation removed cells with DNA damage through DNA damage-induced cell death, whereas severe inflammation accelerated accumulation of mutations and hence promoted tumorigenesis. These results provide insight into the evolutionary dynamics of inflammation-induced tumorigenesis and highlight the combinatorial effects of inflammation and metabolism-immune balance. This approach establishes methods for quantifying cancer risk, for the discovery of driver pathways in inflammation-induced tumorigenesis, and has direct relevance for early detection and prevention and development of new treatment regimes. Cancer Res; 77(22); 6429-41. ©2017 AACR.
Image Gallery: Annular elastolytic giant cell granuloma responding to hydroxychloroquine therapy
Authors: P. Arzpayma, A. Macfarlane
Journal: British Journal of Dermatology (2017)

DEAR EDITOR, A 61-year-old male farmer presented with a 2-year history of a gradually enlarging, mildly pruritic 5Á8 9 7Á5-cm annular plaque on the scalp.Samples for mycological culture grew no fungus and there was no improvement after 4 weeks of terbinafine 250 mg daily.Punch biopsy of the raised border showed elastolysis and a noncaseating granulomatous infiltrate in the upper-to-mid-dermis, with numerous giant cells containing asteroid bodies.A diagnosis of annular elastolytic giant-cell granuloma was made based on the clinical and histopathological findings.The plaque resolved completely after 3 months of hydroxychloroquine 400 mg daily but recurred 3 months after treatment was stopped.
Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non–Small-Cell Lung Cancer
Authors: Koji Haratani, Hidetoshi Hayashi, Yasutaka Chiba, Keita Kudo, Kimio Yonesaka, Ryoji Kato, Hiroyasu Kaneda, Yoshikazu Hasegawa, Kaoru Tanaka, Masayuki Takeda, Kazuhiko Nakagawa
Journal: JAMA Oncology (2017)

Immune-related adverse events (irAEs) have been associated with the efficacy of PD-1 (programmed cell death protein 1) inhibitors in patients with melanoma, but whether such an association exists for non-small-cell lung cancer (NSCLC) has remained unknown.To evaluate the relation of irAEs to nivolumab efficacy in NSCLC.In this study based on landmark and multivariable analyses, a total of 134 patients with advanced or recurrent NSCLC who were treated with nivolumab in the second-line setting or later between December 2015 and August 2016 were identified from a review of medical records from multiple institutions, including a university hospital and community hospitals. Data were updated as of December 31, 2016.The absence or presence of any irAE before the landmark date.Kaplan-Meier curves of progression-free survival (PFS) according to the development of irAEs in 6-week landmark analysis were evaluated with the log-rank test as a preplanned primary objective. Overall survival (OS) was similarly evaluated. Multivariable analysis of both PFS and OS was performed with Cox proportional hazard regression models.In a cohort of 134 patients (median [range] age, 68 [33-85] years; 90 men [67%], 44 women [33%]), irAEs were observed in 69 of the 134 study patients (51%), including 12 patients (9%) with such events of grade 3 or 4, and 24 patients (18%) requiring systemic corticosteroid therapy. In 6-week landmark analysis, median PFS was 9.2 months (95% CI, 4.4 to not reached [NR]) and 4.8 months (95% CI, 3.0 to 7.5) (P = .04) whereas median OS was NR (95% CI, 12.3 to NR) and 11.1 months (95% CI, 9.6 to NR) (P = .01) for patients with or without irAEs, respectively. Multivariable analysis also revealed that irAEs were positively associated with survival outcome, with hazard ratios of 0.525 (95% CI, 0.287 to 0.937; P = .03) for PFS and 0.282 (95% CI, 0.101 to 0.667; P = .003) for OS.Development of irAEs was associated with survival outcome of nivolumab treatment in patients with advanced or recurrent NSCLC. Further studies are needed to confirm our findings.
Biomechanical Regulation of Mesenchymal Stem Cells for Cardiovascular Tissue Engineering
Authors: Kayla Henderson, Andrew D. Sligar, Victoria P. Le, Jason Lee, Aaron B. Baker
Journal: Advanced Healthcare Materials (2017)

Abstract Mesenchymal stem cells (MSCs) are an appealing potential therapy for vascular diseases; however, many challenges remain in their clinical translation. While the use of biochemical, pharmacological, and substrate‐mediated treatments to condition MSCs has been subjected to intense investigation, there has been far less exploration of using these treatments in combination with applied mechanical force for conditioning MSCs toward vascular phenotypes. This review summarizes the current understanding of the use of applied mechanical forces to differentiate MSCs into vascular cells and enhance their therapeutic potential for cardiovascular disease. First recent work on the use of material‐based mechanical cues for differentiation of MSCs into vascular and cardiovascular phenotypes is examined. Then a summary of the studies using mechanical stretch or shear stress in combination with biochemical treatments to enhance vascular phenotypes in MSCs is presented.
Clinically relevant gene sequencing in lung cancer.
Authors: Patricia L. Thompson, Terri Redmond, Christopher Parks, Rabih Bechara
Journal: Journal of Clinical Oncology (2015)

e22048 Background: Individualized cancer treatment is the ultimate goal for clinicians and their patients. We report the results of a commercially available next-generation sequencing assay in advanced lung cancer. Methods: We retrospectively analyzed all the reports of umors sent for next-generation sequencing as part of clinical decision making from a network of tertiary care centers during the year 2013 Results: Approximately 258 of advanced lung cancer patients were seen at all sites. Of these 182 (70.54%) formalin fixed paraffin embedded tissue were sent for genomic testing with 182 yielding results. Overall median age was 57 yrs (range 28-78). Median number of prior chemotherapy lines 2. Lung cancer types: Non-Small cell (NSCLC)/Adenocarcinoma 134(73.62%), Squamous cell 21 (11.54%), Small Cell 11(6.04%), Large Cell 8 (4.40%), Adenosquamous 3 (1.65%), Lung Adenoid Cystic Carcinoma 2 (1.10%), Lung Sarcomatoid Carcinoma 2 (1.10%), Lung Typical Carcinoid 1(0.55%) There were a total of 23 genomic alterations detected ( 21 in adenocarcinoma, 14 in squamous cell, 6 in small cell, 2 in large cell and 2 in adenosquamous . 177 patients had at least 1 genomic alteration, 3 had no alterations and 2 failed test results. Alterations found: Adenocarcinoma 51/134 (38.06%) had KRAS, Squamous Cell 8/21 (40%) had CDKN2A, Small Cell 5/11 (45.45%) had RB1, Large cell 4/2 (50%) had TP53, and Adenosquamous 3/3 had TP53. Of 177 test results 56 (31.64%) had at least 1 FDA approved treatment for patient’s tumor type, 132 (74.58%) with at least 1 FDA approved treatment for another tumor type, 143 (80.79%) with at least 1 “actionable result” (FDA approved treatment to patient’s or another tumor type, 168 (93.78%) with at least 1 clinical trial for a targeted genomic alteration (in clinicaltrial.gov). Conclusions: Next-generation sequencing presents a role in personalized novel treatments in the majority of advanced lung cancer patients tested. We propose that future trials should address the molecular profile of each individual patient.
COLD-PCR protocols to enrich KRAS codon 61 and 146 mutations in heterogeneous tumor samples.
Authors: Davide Nicoli, Federica Torricelli, Enrico Farnetti, Adriana Albini, Bruno Casali
Journal: Journal of Clinical Oncology (2014)

e22125 Background: About 40% of colorectal cancer patients show mutations on codon 12-13 of KRAS but other, less frequent and mutually exclusive mutations, were described. In Italy, treatments with Cetuximab or Panitumumab for metastatic colorectal cancer are granted only for patients with no mutations on RAS genes and analysis of codon 12,13,59,61,117,146 of KRAS and NRAS are requested before the treatment scheduling. Principal limitation of conventional PCR-based methods for mutation analysis is the inability to selectively amplify low percentages of somatic variants in an elevated background of wild-type sequences. CO-amplification at Lower Denaturation temperature PCR (COLD-PCR) is a simple approach of PCR that selectively enriches minority alleles in a mixture of wild-type and mutant sequences. This method requires the definition of a Critical Temperature (Tc) for each Dna sequence, lower than the melting temperature, at which mismatched Dna heteroduplex (WT-mutated alleles) are preferentially denatured, promoting selective amplification of mutant sequences. Minor allele enrichment by COLD-PCR can be performed in association to different methods of variants detection: Sanger Sequencing, HRM analysis, Pyrosequencing Methods: Comparison of theoretical sensitivity achievable after PCR or COLD-PCR amplification was carried out analyzing serial dilution of mutated cell lines DNA into WT DNA (from 50% to 0.25%). To optimize the enrichment of minority alleles we developed a Full COLD-PCR protocol to analyze the Tm-increasing mutation (183 A>C) on KRAS codon 61 and a Fast COLD-PCR protocol to analyze the Tm-reducing mutation (436 G>A) on KRAS codon 146. Critical temperature was defined experimentally. Results: In KRAS codon 61 and 146 analysis, minimum detectable percentage of mutated allele in WT background was about 10% using conventional PCR followed by both Sanger sequencing and HRM. Conversely limit of sensitivity reached 0.5% using both detection methods after COLD-PCR Conclusions: Our experiments proved as COLD-PCR could be a rapid and economic approach, adaptable to investigate other somatic variants, to enrich very low percentages of mutant alleles in very heterogeneous tumor samples.
Safety and pharmacokinetics of the oral iron chelator SP‐420 in β‐thalassemia
Authors: Ali T. Taher, Antoine N. Saliba, Kevin H. Kuo, Patricia J. Giardina, Alan R. Cohen, Ellis J. Neufeld, Yesim Aydinok, Janet L. Kwiatkowski, Brenda I. Jeglinski, Keith Pietropaolo, Gregory Berk, Vip Viprakasit
Journal: American Journal of Hematology (2017)

Our phase I, open-label, multi-center, dose-escalation study evaluated the pharmacokinetics (PK) of SP-420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent β-thalassemia. SP-420 was administered as a single dose of 1.5 (n = 3), 3 (n = 3), 6 (n = 3), 12 (n = 3), and 24 (n = 6) mg/kg or as a twice-daily dose of 9 mg/kg (n = 6) over 14-28 days. There was a near dose-linear increase in the mean plasma SP-420 concentrations and in the mean values for Cmax and AUC0-τ over the dose range evaluated. The median tmax ranged from 0.5 to 2.25 h and was not dose dependent. The study was prematurely terminated by the sponsor due to renal adverse events (AE) including proteinuria, increase in serum creatinine, and one case of Fanconi syndrome. Other adverse effects included hypersensitivity reactions and gastrointestinal disturbances. Based on current dose administration, the renal AE observed outweighed the possible benefits from chelation therapy. However, additional studies assessing efficacy and safety of lower doses or less frequent dosing of SP-420 over longer durations with close monitoring would be necessary to better explain the findings of our study and characterize the safety of the study drug.
Chronic Obstructive Pulmonary Disease Alters Immune Cell Composition and Immune Checkpoint Inhibitor Efficacy in Non–Small Cell Lung Cancer
Authors: Nicholas M. Mark, Julia Kargl, Stephanie E. Busch, Grace H. Y. Yang, Heather E. Metz, Huajia Zhang, Jesse J. Hubbard, Sudhakar N. J. Pipavath, David K. Madtes, A. McGarry Houghton
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality, and the pathogenesis of both involves aberrant immune functioning.
下壁梗塞後心破裂に対するEpi‐Endocardial Patch Repairの一例
Authors: 井出雄二郎, 坂本和久, 仁科健, 榊原裕, 小山忠明, 大野暢久, 池田義, 西村和修, 米田正始
Journal: Circulation (2004)
Normal Reference Laboratory Values
Authors: Alexander Kratz, Maryjane Ferraro, Patrick M. Sluss, Kent B. Lewandrowski
Journal: New England Journal of Medicine (2004)

The following is a table of reference values for adults for laboratory tests commonly ordered at the Massachusetts General Hospital (MGH) and recorded in the Case Records. The table revises the most recently published data (Normal Reference Laboratory Values. N Engl J Med 1998;339:1063-72). Laboratory values are expressed in the units used at the MGH and the units of the Système International d'Unités (SI units). The table is not intended to provide a comprehensive review of reference values, since this information is widely available in standard textbooks. To avoid suggesting an endorsement of commercial products by the hospital or the Journal, . . .
Concurrent chemoradiotherapy of capecitabine with or without oxaliplatin versus cisplatin with fluorouracil for treatment of squamous oesophageal cancer in Chinese patients (CRTCOESC): an interim report of a randomised, open-label, multicentre trial
Authors: Ruinuo Jia, Tanyou Shan, Fuyou Zhou, Anping Zheng, Lixin Wan, Zhiqiao Xu, Guobao Zheng, Xiaoyong Luo, Yingjuan Zheng, Yanhui Cui, Guifang Zhang, Dan Zhou, Jiachun Sun, Guoqiang Kong, Xiaozhi Yuan, Ruina Yang, Jing Ren, Wei Wang, Xinshuai Wang, Shegan Gao
Journal: The Lancet Oncology (2017)
Advances in the management of oesophageal motility disorders in the era of high-resolution manometry: a focus on achalasia syndromes
Authors: Peter J. Kahrilas, Albert J. Bredenoord, Mark Fox, C. Prakash Gyawali, Sabine Roman, André J.P.M. Smout, John E. Pandolfino
Journal: Nature Reviews Gastroenterology & Hepatology (2017)

Abstract High-resolution manometry (HRM) and new analysis algorithms, summarized in the Chicago Classification, have led to a restructured classification of oesophageal motility disorders. This advance has led to increased detection of clinically relevant disorders, in particular achalasia. It has become apparent that the cardinal feature of achalasia — impaired lower oesophageal sphincter (LES) relaxation — can occur in several disease phenotypes: without peristalsis (type I), with pan-oesophageal pressurization (type II), with premature (spastic) distal oesophageal contractions (type III), or with preserved peristalsis (outlet obstruction). Furthermore, no manometric pattern is perfectly sensitive or specific for achalasia caused by a myenteric plexopathy, and there is no biomarker for this pathology. Consequently, physiological testing reveals other syndromes not meeting achalasia criteria that also benefit from therapies formerly reserved for achalasia. These findings have become particularly relevant with the development of a minimally invasive technique for performing a long oesophageal myotomy, the per-oral endoscopic myotomy (POEM). Optimal management is to render treatment in a phenotype-specific manner; that is, POEM calibrated to patient-specific physiology for spastic achalasia and the spastic disorders, and more conservative strategies such as pneumatic dilation for the disorders limited to the LES. This Consensus Statement examines the effect of HRM on our understanding of oesophageal motility disorders, with a focus on the diagnosis, epidemiology and management of achalasia and achalasia-like syndromes.
Intradermal vaccination with hollow microneedles: A comparative study of various protein antigen and adjuvant encapsulated nanoparticles
Authors: Guangsheng Du, Rania M. Hathout, Maha Nasr, M. Reza Nejadnik, Jing Tu, Roman I. Koning, Abraham J. Koster, Bram Slütter, Alexander Kros, Wim Jiskoot, Joke A. Bouwstra, Juha Mönkäre
Journal: Journal of Controlled Release (2017)

In this study, we investigated the potential of intradermal delivery of nanoparticulate vaccines to modulate the immune response of protein antigen using hollow microneedles. Four types of nanoparticles covering a broad range of physiochemical parameters, namely poly (lactic-co-glycolic) (PLGA) nanoparticles, liposomes, mesoporous silica nanoparticles (MSNs) and gelatin nanoparticles (GNPs) were compared. The developed nanoparticles were loaded with a model antigen (ovalbumin (OVA)) with and without an adjuvant (poly(I:C)), followed by the characterization of size, zeta potential, morphology, and loading and release of antigen and adjuvant. An in-house developed hollow-microneedle applicator was used to inject nanoparticle suspensions precisely into murine skin at a depth of about 120 μm. OVA/poly(I:C)-loaded nanoparticles and OVA/poly(I:C) solution elicited similarly strong total IgG and IgG1 responses. However, the co-encapsulation of OVA and poly(I:C) in nanoparticles significantly increased the IgG2a response compared to OVA/poly(I:C) solution. PLGA nanoparticles and liposomes induced stronger IgG2a responses than MSNs and GNPs, correlating with sustained release of the antigen and adjuvant and a smaller nanoparticle size. When examining cellular responses, the highest CD8+ and CD4+ T cell responses were induced by OVA/poly(I:C)-loaded liposomes. In conclusion, the applicator controlled hollow microneedle delivery is an excellent method for intradermal injection of nanoparticle vaccines, allowing selection of optimal nanoparticle formulations for humoral and cellular immune responses.