tbuckley/cabot-search huggingface dataset:
Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial
Authors: Graham H Jackson, Faith E Davies, Charlotte Pawlyn, David A Cairns, Alina Striha, Corinne Collett, Anna Hockaday, John R Jones, Bhuvan Kishore, Mamta Garg, Cathy D Williams, Kamaraj Karunanithi, Jindriska Lindsay, Matthew W Jenner, Gordon Cook, Nigel H Russell, Martin F Kaiser, Mark T Drayson, Roger G Owen, Walter M Gregory, Gareth J Morgan
Journal: The Lancet Oncology (2018)

Patients with multiple myeloma treated with lenalidomide maintenance therapy have improved progression-free survival, primarily following autologous stem-cell transplantation. A beneficial effect of lenalidomide maintenance therapy on overall survival in this setting has been inconsistent between individual studies. Minimal data are available on the effect of maintenance lenalidomide in more aggressive disease states, such as patients with cytogenetic high-risk disease or patients ineligible for transplantation. We aimed to assess lenalidomide maintenance versus observation in patients with newly diagnosed multiple myeloma, including cytogenetic risk and transplantation status subgroup analyses.
Top Italian public health official faces allegation of failing to disclose pharma links
Authors: Michael Day
Journal: BMJ (2018)

The row over the conflicts of interests of one of Italy’s most senior public health officials has reignited, with fresh claims that he failed to disclose earnings from drug companies.

The country’s leading consumer rights group, Codacons, this week published what it said were all the relations between Walter Ricciardi, head of the National Institute of Health (Istituto Superiore di Sanita, ISS) and the drug industry.1

The group said that Ricciardi should be investigated for activities including the receipt of €4000 (£3600; $4500) for speaking to Pfizer staff in 2017, his involvement in a project sponsored by Pfizer and Janssen-Silage with the medicine faculty of Milan’s Catholic University of the Sacred Heart, a €400 sponsorship payment from GlaxoSmithKline in November 2017, and his role as “scientific director” in an Abbvie project that involved a payment of €58 250 to the Milan …
Clinical Responses and Pharmacokinetics of MCARH171, a Human-Derived Bcma Targeted CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma: Final Results of a Phase I Clinical Trial
Authors: Sham Mailankody, Arnab Ghosh, Mette Staehr, Terence J Purdon, Mikhail Roshal, Elizabeth Halton, Claudia Diamonte, John Pineda, Pavan Anant, Yvette Bernal, Analisa Wills, Neha Korde, Nikoletta Lendvai, Alexander M. Lesokhin, Hani Hassoun, Malin Hultcrantz, Heather J. Landau, Gunjan L. Shah, Michael Scordo, David J. Chung, Oscar B Lahoud, Pallavi Khattar, Carlos Fernandez de Larrea, Qi Gao, Achim Jungbluth, Jae H. Park, Kevin J. Curran, Craig S. Sauter, Maria Lia Palomba, Brigitte Senechal, Xiuyan Wang, Ahmet Dogan, Sergio Giralt, Isabelle Riviere, Ola Landgren, Renier J. Brentjens, Eric L. Smith
Journal: Blood (2018)
Guidelines for the early management of patients with acute myocardial infarction
Authors: Rolf M. Gunnar, Patrick D.V. Bourdillon, Donald W. Dixon, Valentin Fuster, Robert B. Karp, J.Ward Kennedy, Francis J. Klocke, Eugene R. Passamani, Bertram Pitt, Elliot Rapaport, T.Joseph Reeves, Richard O. Russell, Burton E. Sobel, William L. Winters, Charles Fisch, George A. Beller, Roman W. DeSanctis, Harold T. Dodge, J.Ward Kennedy, T.Joseph Reeves, Sylvan Lee Weinberg
Journal: Journal of the American College of Cardiology (1990)
ID3 Promotes Stem Cell Features and Predicts Chemotherapeutic Response of Intrahepatic Cholangiocarcinoma
Authors: Lifeng Huang, Jie Cai, Han Guo, Jinyang Gu, Ying Tong, Bijun Qiu, Chenchen Wang, Meng Li, Lei Xia, Jianjun Zhang, Hailong Wu, Xiaoni Kong, Qiang Xia
Journal: Hepatology (2018)

Cancer stem cells contribute to a high rate of recurrence and chemotherapeutic resistance in many types of cancer, including intrahepatic cholangiocarcinoma (ICC). Inhibitor of differentiation 3 (ID3) has been reported to promote cancer stem cells, but its role in ICC is obscure. In this study, we identified that ID3 is highly expressed in human ICC tissues compared with matched normal tissues and correlates with poor prognosis. Functional studies demonstrate that ID3 is required for stemness maintenance in cholangiocarcinoma both in vitro and in vivo. Consistent with the regulation of cancer stem cell features by ID3, transgenic expression of ID3 enhances chemoresistance of cholangiocarcinoma cells. Moreover, we found that ICC patients with low ID3 levels benefited from postoperative transarterial chemoembolization, whereas patients with high ID3 levels did not, indicating the significance of ID3 in individualized ICC therapy. Mechanistically, ID3 could interact with E47 and block E47 recruitment to the promoter of β‐catenin, which leads to activation of Wnt/β‐catenin signaling. Conclusion: Our results show that ID3 could promote the stemness of ICC by increasing the transcriptional activity of β‐catenin and could serve as a biomarker in predicting ICC patients' response to adjuvant chemotherapeutics.
Telomere Length and Use of Immunosuppressive Medications in Idiopathic Pulmonary Fibrosis
Authors: Chad A. Newton, David Zhang, Justin M. Oldham, Julia Kozlitina, Shwu-Fan Ma, Fernando J. Martinez, Ganesh Raghu, Imre Noth, Christine Kim Garcia
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Immunosuppression was associated with adverse events for patients with idiopathic pulmonary fibrosis (IPF) in the PANTHER-IPF (Evaluating the Effectiveness of Prednisone, Azathioprine and
Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results
Authors: Marta González Vicent, Blanca Molina, Jesús González de Pablo, Ana Castillo, Miguel Ángel Díaz
Journal: American Journal of Hematology (2018)

Ruxolitinib is a promising treatment for steroid refractory graft-vs-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively. Overall response rate (ORR) in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively. Ruxolitinib was associated with an increase in CD4 effector memory (EM), and decrease of CD4 central memory percentage. CD4 regulatory T cells percentage decreased significantly. Patients who achieved complete response to ruxolitinib had higher natural killer (NK) cells before ruxolitinib that patients who did not respond. Also there was an increase of CD4 lymphocytes percentage, with decrease of CD8 and NK cells percentage in responders against non-responders. There were 54%, 18% and 13% of infections caused by virus, bacteria and fungi, respectively. Cumulative incidence of relapse and non-relapse mortality was 19 ± 9%and 28 ± 10%, respectively. Overall survival and disease-free survival rate at 2 years were 62 ± 11% and 58 ± 11%, respectively. Ruxolitinib is a promising treatment for acute and chronic GvHD with a high ORR of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 EM cells and decrease in NK and regulatory T cells. Now, we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis.
Unique role of rheumatology in establishing collaborative relationships in research. Past, present and future of patient engagement
Authors: Maarten de Wit, Adewale Adebajo
Journal: Annals of the Rheumatic Diseases (2018)

The specialty of rheumatology takes care of people with disabling and long-term musculoskeletal conditions. For these patients, good healthcare requires the establishment of a sustainable partnership with healthcare professionals. For over two decades, rheumatology has been a frontrunner in piloting and implementing new kinds of partnerships in scientific research. In this viewpoint paper, we provide evidence for the leading role of rheumatology in developing strategies for engaging patients in research agenda setting, outcome research, developing treatment recommendations, assessing grant applications, conducting patient-centred research and transferring knowledge from research into practice. Experiences and lessons learnt in rheumatology are regularly published and are currently widely adapted and implemented in other specialties and research contexts. Challenges still exist and it is expected that rheumatology, as a leading discipline in this field, may further enhance our knowledge, expertise and understanding of the conditions for relational empowerment and meaningful patient involvement.
A Reciprocal Model of Pain and Substance Use: Transdiagnostic Considerations, Clinical Implications, and Future Directions
Authors: Joseph W. Ditre, Emily L. Zale, Lisa R. LaRowe
Journal: Annual Review of Clinical Psychology (2018)

Pain and substance use are highly prevalent and co-occurring conditions that continue to garner increasing clinical and empirical interest. Although nicotine and tobacco, alcohol, and cannabis each confer acute analgesic effects, frequent or heavy use may contribute to the development and progression of chronic pain, and pain may be heightened during abstinence. Additionally, pain can be a potent motivator of substance self-administration, and it may contribute to escalating use and poorer substance-related treatment outcomes. We integrated converging lines of evidence to propose a reciprocal model in which pain and substance use are hypothesized to interact in the manner of a positive feedback loop, resulting in the exacerbation and maintenance of both conditions over time. Theoretical mechanisms in bidirectional pain-substance use relations are reviewed, including negative reinforcement, social cognitive processes, and allostatic load in overlapping neural circuitry. Finally, candidate transdiagnostic factors are identified, and we conclude with a discussion of clinical implications and future research directions.
Face Mask Use and Persistence of Livestock-associated <i>Staphylococcus aureus</i> Nasal Carriage among Industrial Hog Operation Workers and Household Contacts, USA
Authors: Maya L. Nadimpalli, Jill R. Stewart, Elizabeth Pierce, Nora Pisanic, David C. Love, Devon Hall, Jesper Larsen, Karen C. Carroll, Tsigereda Tekle, Trish M. Perl, Christopher D. Heaney
Journal: Environmental Health Perspectives (2018)

Background: Industrial hog operation (IHO) workers may persistently carry antibiotic-resistant, livestock-associated Staphylococcus aureus in their nasal cavities. It is unclear whether IHO work activities can alter IHO workers' and their household members' exposure to these bacteria. Objective: Our objective was to investigate the relationship of IHO work activities with persistence of antibiotic-resistant, livestock-associated S. aureus nasal carriage among IHO workers and their household members. Methods: At biweekly intervals over 4 months, IHO workers and their household members completed questionnaires and provided nasal swabs that were assessed for S. aureus, multidrug-resistant S. aureus (MDRSA), and livestock-associated markers (tetracycline resistance, scn absence, spa type). We examined the association between transient and habitual IHO work activities and S. aureus nasal carriage outcomes. Results: One hundred one IHO workers and 79 household members completed 1,456 study visits. Face mask use (each 25% increase) was associated with reduced odds of nasal carriage of MDRSA (odds ratio [OR]: 0.65 [95% confidence interval (CI): 0.46, 0.92], tetracycline-resistant S. aureus [OR = 0.74 (95% CI: 0.56, 0.97)], and S. aureus clonal complex (CC) 398/CC9 [OR = 0.77 (95% CI: 0.60, 0.99)]. IHO workers who ever (vs. never) gave pigs injections had higher odds of these outcomes. Among household members, living with an IHO worker who consistently (≥80% of the time) versus sometimes or never used a face mask was associated with reduced odds of carrying scn-negative S. aureus, tetracycline-resistant S. aureus, and S. aureus CC398/CC9 (OR range: 0.12–0.20, all p<0.05), and consistent IHO worker coveralls use was associated with reduced odds of household member MDRSA carriage only. Living with an IHO worker who habitually had contact with ≥4,000 hogs (vs. <4000) was associated with higher odds of household member livestock-associated S. aureus carriage. Conclusions: Consistent face mask use was associated with reduced exposure to antibiotic-resistant, livestock-associated S. aureus among IHO workers and their household members. https://doi.org/10.1289/EHP3453
Tackling the Hospital-Acquired Pneumonia Enrollment Paradox
Authors: Michael Klompas
Journal: JAMA Network Open (2018)

Amy Corneli, PhD; Brian Perry, MPH; Deborah Collyar, BS; John H. Powers III, MD; John J. Farley, MD, MPH; Sara B. Calvert, PharmD; Jonas Santiago, PharmD; Helen K. Donnelly, RN, BSN; Teresa Swezey, PhD; Carrie B. Dombeck, MA; Carisa De Anda, PharmD; Vance G. Fowler Jr, MD; Thomas L. Holland, MD
Systolic blood pressure lower than the heart rate indicates a poor outcome in patients with severe isolated traumatic brain injury: A cross-sectional study
Authors: Jin-Fu Huang, Yu-Chin Tsai, Cheng-Shyuan Rau, Shiun-Yuan Hsu, Peng-Chen Chien, Hsiao-Yun Hsieh, Ching-Hua Hsieh
Journal: International Journal of Surgery (2018)
Facial Feminization Surgery: The Ethics of Gatekeeping in Transgender Health
Authors: Alex Dubov, Liana Fraenkel
Journal: The American Journal of Bioethics (2018)

The lack of access to gender-affirming surgery represents a significant unmet health care need within the transgender community, frequently resulting in depression and self-destructive behavior. While some transgender people may have access to gender reassignment surgery (GRS), an overwhelming majority cannot afford facial feminization surgery (FFS). The former may be covered as a "medical necessity," but FFS is considered "cosmetic" and excluded from insurance coverage. This demarcation between "necessity" and "cosmetic" in transgender health care based on specific body parts is in direct opposition to the scientific community's understanding of gender dysphoria and professional guidelines for transgender health. GRS affects one's ability to function in an intimate relationship, while FFS has the same impact on social interactions an, therefore may have a far greater implication for one's quality of life. FFS is a cost-effective intervention that needs to be covered by insurance policies. The benefits of such coverage far exceed the insignificant costs.
Changes in Coronary Plaque Composition in Patients With Acute Myocardial Infarction Treated With High-Intensity Statin Therapy (IBIS-4)
Authors: Lorenz Räber, Konstantinos C. Koskinas, Kyohei Yamaji, Masanori Taniwaki, Marco Roffi, Lene Holmvang, Hector M. Garcia Garcia, Thomas Zanchin, Rafaela Maldonado, Aris Moschovitis, Giovanni Pedrazzini, Serge Zaugg, Jouke Dijkstra, Christian M. Matter, Patrick W. Serruys, Thomas F. Lüscher, Henning Kelbaek, Alexios Karagiannis, Maria D. Radu, Stephan Windecker
Journal: JACC. Cardiovascular imaging (2018)
First evidence of antitumor activity of ITPP, a novel hypoxia-modifier: Results of a phase Ib trial
Authors: M.A. Schneider, P. Limani, M. Linecker, P. Kron, H. Petrosky, B.C. Pestalozzi, A. Jetter, R. Graf, B. Humar, J.-M. Lehn, P.-A. Clavien
Journal: Annals of Oncology (2018)

Background: Tumor hypoxia promotes the Warburg effect, decreases anti-tumor immune responses and increases malignant behavior, thereby fostering disease progression. The novel anti-hypoxic molecule myo-inositoltrispyrophosphate (ITPP) acts as an allosteric effector of hemoglobin and efficiently counteracts hypoxia. In preclinical models, ITPP normalized tumor-associated vasculature, enhanced chemotherapy efficacy, decreased tumor burden and increased survival. Methods: The present study is a first in-human exploratory, prospective, open-labelled, mono-centric Phase IB study according to a classical 3 + 3 dose escalation scheme in patients with non-resectable hepatopancreatobiliary tumors. The study intervention consists of 9 infusions of ITPP over 3 weeks, followed by administration of conventional chemotherapy. Primary endpoints are the determination of safety and tolerability of ITPP, while secondary endpoints aim at assessing tumor responses via imaging. Results: 29 patients were included between 04/2015 and 07/2018, with 1 patient withdrawn from the study and 28 assessed for the primary endpoints. ITPP administration was safe and well tolerated. Dose limiting toxicity in the form of Hypercalcemia CTCAE grade 4 occured in the highest cohort tested (Cohort 8: 14'500mg/m2). 7 serious adverse events were recorded without relation to ITPP. 48 adverse events occurred, with 30 judged to be possibly or definitively related to ITPP. Hypercalcemia (19x), Hypomagnesemia (5x), Hypophosphatemia (4x) were the most freequently observed treatment emerged toxicities. Of the ITPP-treated patients, 10 had radiological disease stabilization, 4 experienced a decrease in tumor markers. 4 patients had stable disease with subsequent chemotherapy, while 5 benefited from a strong partial response. Conclusions: Administration of ITPP before chemotherapy is safe and well tolerated with acceptable side-effects. Further exploration of ITPP's potential in phase II/III trials is warranted. Clinical trial identification: NCT02528526. Legal entity responsible for the study: Pierre-Alain Clavien. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Microneedle‐Mediated Vaccine Delivery to the Oral Mucosa
Authors: Rachel L. Creighton, Kim A. Woodrow
Journal: Advanced Healthcare Materials (2018)

Abstract The oral mucosa is a minimally invasive and immunologically rich site that is underutilized for vaccination due to physiological and immunological barriers. To develop effective oral mucosal vaccines, key questions regarding vaccine residence time, uptake, adjuvant formulation, dose, and delivery location must be answered. However, currently available dosage forms are insufficient to address all these questions. An ideal oral mucosal vaccine delivery system would improve both residence time and epithelial permeation while enabling efficient delivery of physicochemically diverse vaccine formulations. Microneedles have demonstrated these capabilities for dermal vaccine delivery. Additionally, microneedles enable precise control over delivery properties like depth, uniformity, and dosing, making them an ideal tool to study oral mucosal vaccination. Select studies have demonstrated the feasibility of microneedle‐mediated oral mucosal vaccination, but they have only begun to explore the broad functionality of microneedles. This review describes the physiological and immunological challenges related to oral mucosal vaccine delivery and provides specific examples of how microneedles can be used to address these challenges. It summarizes and compares the few existing oral mucosal microneedle vaccine studies and offers a perspective for the future of the field.
Pulmonary hypertension due to left heart disease
Authors: Jean-Luc Vachiéry, Ryan J. Tedford, Stephan Rosenkranz, Massimiliano Palazzini, Irene Lang, Marco Guazzi, Gerry Coghlan, Irina Chazova, Teresa De Marco
Journal: European Respiratory Journal (2018)

Pulmonary hypertension (PH) is frequent in left heart disease (LHD), as a consequence of the underlying condition. Significant advances have occurred over the past 5 years since the 5th World Symposium on Pulmonary Hypertension in 2013, leading to a better understanding of PH-LHD, challenges and gaps in evidence. PH in heart failure with preserved ejection fraction represents the most complex situation, as it may be misdiagnosed with group 1 PH. Based on the latest evidence, we propose a new haemodynamic definition for PH due to LHD and a three-step pragmatic approach to differential diagnosis. This includes the identification of a specific "left heart" phenotype and a non-invasive probability of PH-LHD. Invasive confirmation of PH-LHD is based on the accurate measurement of pulmonary arterial wedge pressure and, in patients with high probability, provocative testing to clarify the diagnosis. Finally, recent clinical trials did not demonstrate a benefit in treating PH due to LHD with pulmonary arterial hypertension-approved therapies.
Stereotactic Radiofrequency Ablation of Hepatocellular Carcinoma: a Histopathological Study in Explanted Livers
Authors: Reto Bale, Peter Schullian, Gernot Eberle, Daniel Putzer, Heinz Zoller, Stefan Schneeberger, Claudia Manzl, Patrizia Moser, Georg Oberhuber
Journal: Hepatology (2018)

This retrospective study was performed to evaluate the efficacy of three-dimensional (3D)-navigated multiprobe radiofrequency ablation (RFA) with intraprocedural image fusion for treatment of hepatocellular carcinoma (HCC) by histopathological examination. From 2009 to 2018, 97 patients (84 men, 13 women; median age, 60 years; range, 1-71) were transplanted after bridging therapy of 195 HCCs by stereotactic RFA (SRFA). The median interval between the first SRFA and transplantation was 6.8 months (range, 0-71). The rate of residual vital tissue (RVT) could be assessed in 188 of 195 lesions in 96 of 97 patients by histological examination of the explanted livers using hematoxylin and eosin (H&E) and Tdt-mediated UTP nick-end labeling (TUNEL) stains. Histopathological results were compared with the findings of the last computed tomography (CT) imaging before liver transplantation (LT). Median number and size of treated tumors were 1 (range, 1-8) and 2.5 cm (range, 1-8). Complete radiological response was achieved in 186 of 188 nodules (98.9%) and 94 of 96 patients (97.9%) and complete pathological response in the explanted liver specimen in 183 of 188 nodules (97.3%) and 91 of 96 patients (94.8%), respectively. In lesions ≥3 cm, complete tumor cell death was achieved in 50 of 52 nodules (96.2%). Residual tumor did not correlate with tumor size (P = 0.5). Conclusion: Multiprobe SRFA with intraprocedural image fusion represents an efficient, minimally invasive therapy for HCC, even with tumor sizes larger than 3 cm, and without the need of a combination with additional treatments. The results seem to justify the additional efforts related to the stereotactic approach.