tbuckley/cabot-search huggingface dataset:
Association of Early Physical Therapy With Long-term Opioid Use Among Opioid-Naive Patients With Musculoskeletal Pain
Authors: Eric Sun, Jasmin Moshfegh, Chris A. Rishel, Chad E. Cook, Adam P. Goode, Steven Z. George
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Nonpharmacologic methods of reducing the risk of new chronic opioid use among patients with musculoskeletal pain are important given the burden of the opioid epidemic in the United States. <h3>Objective</h3> To determine the association between early physical therapy and subsequent opioid use in patients with new musculoskeletal pain diagnosis. <h3>Design, Setting, and Participants</h3> This cross-sectional analysis of health care insurance claims data between January 1, 2007, and December 31, 2015, included privately insured patients who presented with musculoskeletal pain to an outpatient physician office or an emergency department at various US facilities from January 1, 2008, to December 31, 2014. The sample comprised 88 985 opioid-naive patients aged 18 to 64 years with a new diagnosis of musculoskeletal shoulder, neck, knee, or low back pain. The data set (obtained from the IBM MarketScan Commercial database) included person-level<i>International Classification of Diseases, Ninth Revision</i>or<i>Tenth Revision</i>diagnosis codes,<i>Current Procedural Terminology</i>codes, and date of service as well as pharmaceutical information (National Drug Code, generic name, dose, and number of days supplied). Early physical therapy was defined as at least 1 session received within 90 days of the index date, the earliest date a relevant diagnosis was provided. Data analysis was conducted from March 1, 2018, to May 18, 2018. <h3>Main Outcomes and Measures</h3> Opioid use between 91 and 365 days after the index date. <h3>Results</h3> Of the 88 985 patients included, 51 351 (57.7%) were male and 37 634 (42.3%) were female with a mean (SD) age of 46 (11.0) years. Among these patients, 26 096 (29.3%) received early physical therapy. After adjusting for potential confounders, early physical therapy was associated with a statistically significant reduction in the incidence of any opioid use between 91 and 365 days after the index date for patients with shoulder pain (odds ratio [OR], 0.85; 95% CI, 0.77-0.95;<i>P</i> = .003), neck pain (OR, 0.92; 95% CI, 0.85-0.99;<i>P</i> = .03), knee pain (OR, 0.84; 95% CI, 0.77-0.91;<i>P</i> &lt; .001), and low back pain (OR, 0.93; 95% CI, 0.88-0.98;<i>P</i> = .004). For patients who did use opioids, early physical therapy was associated with an approximately 10% statistically significant reduction in the amount of opioid use, measured in oral morphine milligram equivalents, for shoulder pain (−9.7%; 95% CI, −18.5% to −0.8%;<i>P</i> = .03), knee pain (−10.3%; 95% CI, −17.8% to −2.7%;<i>P</i> = .007), and low back pain (−5.1%; 95% CI, −10.2% to 0.0%;<i>P</i> = .046), but not for neck pain (−3.8%; 95% CI, −10.8% to 3.3%;<i>P</i> = .30). <h3>Conclusions and Relevance</h3> Early physical therapy appears to be associated with subsequent reductions in longer-term opioid use and lower-intensity opioid use for all of the musculoskeletal pain regions examined.
Improved survival for children and young adolescents with acute myeloid leukemia: a Dutch study on incidence, survival and mortality
Authors: A. M. J. Reedijk, K. Klein, J. W. W. Coebergh, L. C. Kremer, A. G. Dinmohamed, V. de Haas, A. B. Versluijs, G. J. Ossenkoppele, H. B. Beverloo, R. Pieters, C. M. Zwaan, G. J. L. Kaspers, H. E. Karim-Kos
Journal: Leukemia (2018)
Using a multiplexed immunofluorescence assay to detect immunosuppressive cells and their mechanisms in the pancreatic tumor microenvironment
Authors: A. Juncker-Jensen, J. Fang, R. Padmanabhan, E. Parnell, J. Kuo, Q. Au, E. Leones, F. Sahafi, M. Nagy, N. Hoe, J. William
Journal: Annals of Oncology (2018)

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an excessive amount of desmoplastic stroma seeded with inflammatory cells and it is one of the most aggressive forms of cancer with no current specific therapies. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME), and in most solid cancers increased TAM infiltration is associated with a poor prognosis. TAMs can be described as classically activated M1 types with pro-inflammatory antitumor functions, versus alternatively activated M2 types with immunosuppressive pro-tumor functions. The immunosuppressive functions of M2 TAMs can be exerted through release of cytokines and growth factors as well as via direct recruitment of T regulatory cells (Tregs), a subset of lymphocytes responsible for immune tolerance of the system to the tumor. While the differentiation from M1 to M2 in PDAC has been shown to be associated with a worse prognosis, little is known about PDAC TAM polarization and its potential correlation to Treg recruitment. Methods: For this study we have used MultiOmyx™, a multiplexed immunofluorescence (IF) assay allowing up to 60 protein biomarkers to be interrogated from a single FFPE section. The MultiOmyx™ assay utilizes a pair of directly conjugated Cyanine dye-labeled (Cy3, Cy5) antibodies per round of staining. Each round of staining is imaged and followed by novel dye inactivation chemistry, enabling repeated rounds of staining and deactivation. Results: Using the pan macrophage marker CD68 in combination with either M1 marker HLA-DR or M2 marker CD163 we confirmed the presence of M1 and M2 TAM populations in 9 stage IIB PDAC FFPE samples and found a positive significant correlation (Pearson's correlation p < 0.05) between the presence of M2 TAMs and Tregs, but not between M1 TAMs and Tregs. Moreover, in a spatial nearest neighbor analysis we found M2 type TAMS to be in closer proximity to Tregs compared to M1 type TAMs. Conclusions: We demonstrate a positive significant correlation between the presence of, as well as the distance between, M2 TAMs and Tregs in the TME of PDAC, suggesting a possible pathway in which TAM polarization plays an immunosuppressive function by recruiting Tregs. Legal entity responsible for the study: NeoGenomics. Funding: NeoGenomics. Disclosure: A. Juncker-Jensen, J. Fang, R. Padmanabhan, E. Parnell, J. Kuo, Q. Au, E. Leones, F. Sahafi, M. Nagy, N. Hoe, J. William: Employed by NeoGenomics.
NHS safety culture needs radical change, says CQC
Authors: Jacqui Wise
Journal: BMJ (2018)

The safety culture of the NHS must transform radically to reduce “never events” that continue to happen despite the efforts of frontline staff, a report from the Care Quality Commission (CQC) has said.1

The regulator’s report calls for a new training programme to ensure that all members of the NHS workforce have a shared understanding of their role in patient safety from the moment they start their first job in healthcare and throughout their careers.

Other recommendations are for the National Patient Safety Alert Committee to oversee a standardised patient safety alert system that aligns the processes and outputs of all bodies and for teams to issue alerts to make sure that they set out clear and effective actions that providers must take on safety critical issues.

Provisional data show that 468 incidents classed as “never events” occurred in England from 1 April 2017 to 31 March 2018—serious incidents that are regarded as …
Relation between post‐myocardial infarct remodelling and gelatinase activity in patients enrolled in the TIPTOP trial
Authors: Giampaolo Cerisano, Piergiovanni Buonamici, Angela Migliorini, Alberto Santini, Rossella Marcucci, Anna Maria Gori, Matteo Becatti, Chiara Zocchi, Martina Berteotti, Renato Valenti
Journal: European Journal of Heart Failure (2018)
A Phase 2 Study of Carfilzomib, Lenalidomide, and Dexamethasone with Lenalidomide Maintenance (KRd-r) in Newly Diagnosed Multiple Myeloma (NDMM): Sustained Long Term Deep Remissions and Prolonged Progression-Free Duration Regardless of Age or Cytogenetic Risk after 5 Years of Follow up
Authors: Dickran Kazandjian, Neha Korde, Sham Mailankody, Yong Zhang, Jennifer Hsu, Elizabeth Hill, Candis Morrison, Sneha Divakarla, Mary L. Kwok, Elisabet E. Manasanch, Manisha Bhutani, Nishant Tageja, Pallavi Galera, Alina Dulau-Florea, Dalia Salem, Esther Gonzalez, Liza Lindenberg, Irina Maric, Katherine R. Calvo, Raul C. Braylan, Constance Yuan, Wyndham H. Wilson, Peter Choyke, Maryalice Stetler-Stevenson, Seth M. Steinberg, William Figg, Mark Roschewski, Ola Landgren
Journal: Blood (2018)
Immunogenomic Exploration of the Acute Myeloid Leukemia Microenvironment Identifies Determinants of T-Cell Fitness
Authors: Lauren K. Brady, David Soong, Evan F. Lind, Yoko Kosaka, Adam J. Lamble, Michael Schaffer, Brendan P. Hodkinson, Clare Lefave, Ted Laderas, Shannon K. McWeeney, Homer Adams, Yann Abraham, Pegah Safabakhsh, Jeffrey W. Tyner, Brian J. Druker, Fei Huang
Journal: Blood (2018)
Community-Based Approach to Trauma and Violence
Authors: Danby Kang, Mamta Swaroop
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Spatiotemporal Control Strategies for Bone Formation through Tissue Engineering and Regenerative Medicine Approaches
Authors: Kristopher A. White, Ronke M. Olabisi
Journal: Advanced Healthcare Materials (2018)

Abstract Global increases in life expectancy drive increasing demands for bone regeneration. The gold standard for surgical bone repair is autografting, which enjoys excellent clinical outcomes; however, it possesses significant drawbacks including donor site morbidity and limited availability. Although collagen sponges delivered with bone morphogenetic protein, type 2 (BMP2) are a common alternative or supplement, they do not efficiently retain BMP2, necessitating extremely high doses to elicit bone formation. Hence, reports of BMP2 complications are rising, including cancer promotion and ectopic bone formation, the latter inducing complications such as breathing difficulties and neurologic impairments. Thus, efforts to exert spatial control over bone formation are increasing. Several tissue engineering approaches have demonstrated the potential for targeted and controlled bone formation. These approaches include biomaterial scaffolds derived from synthetic sources, e.g., calcium phosphates or polymers; natural sources, e.g., bone or seashell; and immobilized biofactors, e.g., BMP2. Although BMP2 is the only protein clinically approved for use in a surgical device, there are several proteins, small molecules, and growth factors that show promise in tissue engineering applications. This review profiles the tissue engineering advances in achieving control over the location and onset of bone formation (spatiotemporal control) toward avoiding the complications associated with BMP2.
THU0619 The frequency of exon-10 mutations in mefv gene in “probable” diagnosed fmf patients according to tel hashomer criteria
Authors: F. Cosan, S. Arda, O.M. Gedar Totuk
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Familial Mediterranean Fever (FMF) is characterised with recurrent inflammatory attacks with serosal inflammation. The clinical findings of FMF is seen in a large spectrum. Tel Hashomer criteria are widely used for classifying FMF. According this criteria set FMF is classified as 'definite' and 'probable' disease. <h3>Objectives</h3> We aimed in this study to investigate the frequency of exon-10 MEFV mutations in 'probable' FMF patients according to Tel Hashomer criteria. <h3>Methods</h3> The study group consisted of 117 patients (79 male, 38 female, median age:31±11,<sup>12–69</sup> which is classified as 'probable' FMF according to Tel-Hashomer criteria. The 12 frequently seen mutations in Turkey analysed in all blood samples and comparised with the previous reported 'definite' FMF data from Turkey. <h3>Results</h3> We found in probable FMF group single mutation in 36 patients (%30,8), two mutations in 56 patients (%47,9), 3 mutations in 5 patients (%4,3) and no mutations in 20 patients (%17,1). The distrubition of exon 10 mutations showed single exon-10 mutation in 46 patients (%39,3) and two exon-10 mutations only in 23 patients (%19,7). The detailed distrubition of MEFV mutations in 'probable' FMF group is shown in table 1. <h3>Conclusions</h3> We found decreased frequency of exon 10 mutations in the MEFV gene in "probable FMF' group according to Tel-Hashomer criteria in comparison previous reported MEFV mutations data. The distribution of non-exon 10 mutations were similar in the definite FMF group. It is needed more clinical studies with large patient group for the clinical significance of non-exon 10 mutations in "probable" FMF patients. <h3>Reference</h3> [1] Cosan F, Ustek D, Oku B, Duymaz-Tozkir J, Cakiris A, Abaci N, Ocal L, Aral O, Gül A. Association of familial Mediterranean fever-related MEFV variations with ankylosing spondylitis. Arthritis Rheum2010Nov;62(11):3232–6. doi:10.1002/art.27683 <h3>Disclosure of Interest</h3> None declared
PRE-surgical Metformin In Uterine Malignancy (PREMIUM): a Multi-Center, Randomized Double-Blind, Placebo-Controlled Phase III Trial
Authors: Sarah J. Kitson, Zoe Maskell, Vanitha N. Sivalingam, Jennifer L. Allen, Saad Ali, Sean Burns, Kyle Gilmour, Rahamatulla Latheef, Richard J. Slade, Philip W. Pemberton, Joseph Shaw, W. David Ryder, Henry C. Kitchener, Emma J. Crosbie
Journal: Clinical Cancer Research (2018)

Endometrioid endometrial cancer is strongly associated with obesity and insulin resistance. Metformin, an insulin sensitizer, reduces endometrial tumor growth in vitro. Presurgical window studies allow rapid in vivo assessment of antitumor activity. Previous window studies found metformin reduced endometrial cancer proliferation but these lacked methodological rigor. PREMIUM measured the anti-proliferative effect of metformin in vivo using a robust window study design.Patients and Methods: A multicenter, double-blind, placebo-controlled trial randomized women with atypical hyperplasia or endometrioid endometrial cancer to receive metformin (850 mg daily for 3 days, and twice daily thereafter) or placebo for 1 to 5 weeks until surgery. The primary outcome was posttreatment IHC expression of Ki-67. Secondary outcomes investigated the effect of metformin on markers of the PI3K-Akt-mTOR and insulin signaling pathways and obesity.Eighty-eight women received metformin (n = 45) or placebo (n = 43) and completed treatment. There was no overall difference in posttreatment Ki-67 between the metformin and placebo arms, in an ANCOVA analysis adjusting for baseline Ki-67 expression (mean difference -0.57%; 95% CI, -7.57%-6.42%; P = 0.87). Metformin did not affect expression of markers of the PI3K-Akt-mTOR or insulin signaling pathways, and did not result in weight loss.Short-term treatment with standard diabetic doses of metformin does not reduce tumor proliferation in women with endometrioid endometrial cancer awaiting hysterectomy. This study does not support a biological effect of metformin in endometrial cancer and casts doubt on its potential application in the primary and adjuvant treatment settings.
Coordinately Targeting Cell-Cycle Checkpoint Functions in Integrated Models of Pancreatic Cancer
Authors: Sejin Chung, Paris Vail, Agnieszka K. Witkiewicz, Erik S. Knudsen
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Cancer cells often have deficiencies in cell-cycle control mechanisms and could be dependent on specific cell-cycle checkpoints to maintain viability. Because of the documented role of KRAS in driving replication stress, we targeted the checkpoint governing DNA replication using CHK1 kinase inhibitors in pancreatic ductal adenocarcinoma (PDAC) models and examined mechanisms of resistance. Experimental Design: Single-agent efficacy of CHK1 inhibition was investigated in established and primary PDAC lines. Drug screening was performed to identify cooperative agents. In vitro and in vivo studies were employed to interrogate combination treatment efficacy and mechanisms of resistance. Results: Many PDAC models evade single-agent inhibition through mechanisms that allow S-phase progression with CHK1 inhibited. Gene expression analysis revealed FOXM1 as a potential marker of CHK1 sensitivity and defined a form of pancreatic cancer with poor prognosis. Drug screen analysis identified WEE1 as a cooperative agent with CHK1 and was effective in cell culture. In vivo experiments validated the combination efficacy; however, resistance could evolve. Resistance was due to selection of a stable subclone from the original PDX tumor, which harbored high baseline replication stress. In vitro analysis revealed that gemcitabine could eliminate viability in the resistant models. The triplet regimen of gemcitabine, CHK1, and WEE1 inhibition provided strong disease control in all xenograft models interrogated. Conclusions: These results demonstrate the therapeutic resiliency of pancreatic cancer and indicate that coordinately targeting cell-cycle checkpoints in concert with chemotherapy could be particularly efficacious.
PI3Kδ inhibition modulates regulatory and effector T-cell differentiation and function in chronic lymphocytic leukemia
Authors: Bola S. Hanna, Philipp M. Roessner, Annika Scheffold, Billy M. C. Jebaraj, Yasmin Demerdash, Selcen Öztürk, Peter Lichter, Stephan Stilgenbauer, Martina Seiffert
Journal: Leukemia (2018)
Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update
Authors: Anton Vonk Noordegraaf, Kelly Marie Chin, François Haddad, Paul M. Hassoun, Anna R. Hemnes, Susan Roberta Hopkins, Steven Mark Kawut, David Langleben, Joost Lumens, Robert Naeije
Journal: European Respiratory Journal (2018)

The function of the right ventricle determines the fate of patients with pulmonary hypertension. Since right heart failure is the consequence of increased afterload, a full physiological description of the cardiopulmonary unit consisting of both the right ventricle and pulmonary vascular system is required to interpret clinical data correctly. Here, we provide such a description of the unit and its components, including the functional interactions between the right ventricle and its load. This physiological description is used to provide a framework for the interpretation of right heart catheterisation data as well as imaging data of the right ventricle obtained by echocardiography or magnetic resonance imaging. Finally, an update is provided on the latest insights in the pathobiology of right ventricular failure, including key pathways of molecular adaptation of the pressure overloaded right ventricle. Based on these outcomes, future directions for research are proposed.
AKT/mTORC2 Inhibition Activates FOXO1 Function in CLL Cells Reducing B-Cell Receptor-Mediated Survival
Authors: Emilio Cosimo, Anuradha Tarafdar, Michael W. Moles, Ailsa K. Holroyd, Natasha Malik, Mark A. Catherwood, Jodie Hay, Karen M. Dunn, Alan M. Macdonald, Sylvie M. Guichard, Declan O'Rourke, Michael T. Leach, Owen J. Sansom, Sabina C. Cosulich, Alison M. McCaig, Alison M. Michie
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To determine whether inhibition of mTOR kinase-mediated signaling represents a valid therapeutic approach for chronic lymphocytic leukemia (CLL). Experimental Design: Stratification of mTOR activity was carried out in patients with primary CLL samples and an aggressive CLL-like mouse model. The potency of dual mTOR inhibitor AZD8055 to induce apoptosis in primary CLL cells was assessed in the presence/absence of B-cell receptor (BCR) ligation. Furthermore, we addressed the molecular and functional impact of dual mTOR inhibition in combination with BTK inhibitor ibrutinib. Results: Differential regulation of basal mTORC1 activity was observed in poor prognostic CLL samples, with elevated p4EBP1T37/46 and decreased p70S6 kinase activity, suggesting that dual mTORC1/2 inhibitors may exhibit improved response in poor prognostic CLL compared with rapalogs. AZD8055 treatment of primary CLL cells significantly reduced CLL survival in vitro compared with rapamycin, preferentially targeting poor prognostic subsets and overcoming BCR-mediated survival advantages. Furthermore, AZD8055, and clinical analog AZD2014, significantly reduced CLL tumor load in mice. AKT substrate FOXO1, while overexpressed in CLL cells of poor prognostic patients in LN biopsies, peripheral CLL cells, and mouse-derived CLL-like cells, appeared to be inactive. AZD8055 treatment partially reversed FOXO1 inactivation downstream of BCR crosslinking, significantly inhibiting FOXO1T24 phosphorylation in an mTORC2-AKT–dependent manner, to promote FOXO1 nuclear localization, activity, and FOXO1-mediated gene regulation. FOXO1 activity was further significantly enhanced on combining AZD8055 with ibrutinib. Conclusions: Our studies demonstrate that dual mTOR inhibitors show promise as future CLL therapies, particularly in combination with ibrutinib.
The prognostic value of troponin T and N‐terminal pro B‐type natriuretic peptide, alone and in combination, in heart failure patients with and without diabetes
Authors: Rasmus Rørth, Pardeep S. Jhund, Søren L. Kristensen, Akshay S. Desai, Lars Køber, Jean L. Rouleau, Scott D. Solomon, Karl Swedberg, Michael R. Zile, Milton Packer, John J.V. McMurray
Journal: European Journal of Heart Failure (2018)

We examined the prognostic importance of N-terminal pro B-type natriuretic peptide (NT-proBNP) and troponin T (TnT) in heart failure patients with and without diabetes.We measured NT-proBNP and TnT in the biomarker substudy of the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Of 1907 patients, 759 (40%) had diabetes. Median TnT in patients with diabetes was 18 (interquartile range 11-27) ng/L and 13 (9-21) ng/L in those without (P < 0.001). The TnT frequency-distribution curve was shifted to the right in patients with diabetes, compared to those without diabetes. By contrast, NT-proBNP did not differ between patients with and without diabetes. Diabetes and each biomarker were predictive of worse outcomes. Thus, patients with diabetes, an elevated TnT and a NT-proBNP level in the highest tertile (9% of all patients) had an absolute risk of cardiovascular death or heart failure hospitalization of 265 per 1000 person-years, compared to a rate of 42 per 1000 person-years in those without diabetes, a TnT < 18 ng/L and a NT-proBNP in the lowest tertile (16% of all patients). TnT remained an independent predictor of adverse outcomes in multivariable analyses including NT-proBNP.TnT is elevated to a greater extent in heart failure patients with diabetes compared to those without (whereas NT-proBNP is not). TnT and NT-proBNP are additive in predicting risk and when combined help identify diabetes patients at extremely high absolute risk.