tbuckley/cabot-search huggingface dataset:
Surgical Management of Advanced Kidney Cancer: The Role of Cytoreductive Nephrectomy and Lymphadenectomy
Authors: Hiten D. Patel, Jose A. Karam, Mohamad E. Allaf
Journal: Journal of Clinical Oncology (2018)

Despite the evolution of systemic therapy from the immunotherapy to targeted therapy eras, surgical management remains a mainstay of treatment of patients with locally advanced, lymph node-positive, and distant metastatic renal cell carcinoma. Balancing patient and disease characteristics with the potential morbidity of surgery has gained increasing attention to better define the role of cytoreductive nephrectomy and lymphadenectomy. In this review, we critically evaluate the literature for the potential therapeutic role of cytoreductive nephrectomy and lymphadenectomy in advanced kidney cancer, highlighting current evidence, limitations, and best-management practices. Although retrospective data supported a similar survival benefit for cytoreductive nephrectomy in the targeted therapy era as it did for the initial immunotherapy era (1992 to 2006), level 1 evidence from the randomized Clinical Trial to Assess the Importance of Nephrectomy (CARMENA) demonstrated no benefit for intermediate- and poor-risk patients in the setting of sunitinib therapy. Level 1 evidence among a favorable-risk subset is still awaited from the trial Targeted Therapy With or Without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery (TARIBO). Another trial, Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME), has compared upfront cytoreductive nephrectomy prior to targeted therapy with the initial initiation of targeted therapy followed by deferred cytoreductive nephrectomy. Lymphadenectomy is yet another controversial but less well-defined management option for patients with kidney cancer. The role of lymphadenectomy has been studied in both the localized and advanced settings over the past few decades, with a strong suggestion of no therapeutic benefit for patients with cT1-2N0M0 and cM1 disease, and with uncertain benefit in patients with high-risk disease (ie, locally advanced or cN1M0), leading to weak statements among clinical guidelines.
Ixazomib-Lenalidomide-Dexamethasone (IRd) Consolidation Following Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Large Multi-Center Phase II Trial
Authors: Ravi Vij, Nitya Nathwani, Thomas G. Martin, Mark A. Fiala, Abhinav Deol, Francis K. Buadi, Jonathan L Kaufman, Craig C Hofmeister, Tara Gregory, Jesus G. Berdeja, Ajai Chari, Ashley E. Rosko
Journal: Blood (2018)
Maintenance with Carfilzomib Following Carfilzomib, Cyclophosphamide and Dexamethasone at First Relapse or Primary Refractory Multiple Myeloma (MM) on the Phase 2 Muk Five Study: Effect on Minimal Residual Disease
Authors: Kwee Yong, Samantha Hinsley, Ruth M De Tute, Debbie Sherratt, Sarah R Brown, Louise Flanagan, Catherine Williams, Jamie Cavenagh, Martin Kaiser, Neil K Rabin, Karthik Ramasamy, Mamta Garg, Holger W. Auner, Gareth Morgan, Faith E. Davies, Roger G. Owen
Journal: Blood (2018)
EBNA1-targeted inhibitors: Novel approaches for the treatment of Epstein-Barr virus-associated cancers
Authors: Lijun Jiang, Chen Xie, Hong Lok Lung, Kwok Wai Lo, Ga-Lai Law, Nai-Ki Mak, Ka-Leung Wong
Journal: Theranostics (2018)

Epstein-Barr virus (EBV) infects more than 90% of humans worldwide and establishes lifelong latent infection in the hosts. It is closely associated with endemic forms of a wide range of human cancers and directly contributes to the formation of some. Despite its critical role in cancer development, no EBV- or EBV latent protein-targeted therapy is available. The EBV-encoded latent protein, Epstein-Barr nuclear antigen 1 (EBNA1), is expressed in all EBV-associated tumors and acts as the only latent protein in some of these tumors. This versatile protein functions in the maintenance, replication, and segregation of the EBV genome and can therefore serve as an attractive therapeutic target to treat EBV-associated cancers. In the last decades, efforts have been made for designing specific EBNA1 inhibitors to decrease EBNA1 expression or interfere with EBNA1-dependent functions. In this review, we will briefly introduce the salient features of EBNA1, summarize its functional domains, and focus on the recent developments in the identification and design of EBNA1 inhibitors related to various EBNA1 domains as well as discuss their comparative merits.
Real-World Comparisons of Cardiovascular Events between Different Tyrosine Kinase Inhibitors Among Patients with Chronic Myeloid Leukemia
Authors: Moshe Yair Levy, Lin Xie, Yuexi Wang, Frank Neumann, Shouryadeep Srivastava, Daniel Naranjo, Qisu Zhang, Mehul Dalal
Journal: Blood (2018)
MAGE-A3 Promotes Chemotherapy Resistance and Proliferation in Multiple Myeloma through Regulation of BIM and p21Cip1
Authors: Hearn Jay Cho, Anna Huo-Chang Mei, Kaity Tung, Jessie Han, Deepak Perumal, Jonathan J Keats, Daniel Auclair, Ajai Chari, Sundar Jagannath, Samir Parekh, Alessandro Lagana
Journal: Blood (2018)
A Transcriptomic Method to Determine Airway Immune Dysfunction in T2-High and T2-Low Asthma
Authors: Michael C. Peters, Lando Ringel, Nathan Dyjack, Rachelle Herrin, Prescott G. Woodruff, Cydney Rios, Brian O’Connor, John V. Fahy, Max A. Seibold
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Type 2 (T2) inflammation drives airway dysfunction in many patients with asthma; yet, we lack a comprehensive understanding of the airway immune cell types and networks that sustain this inflammation. Moreover, defects in the airway immune system in patients with asthma without T2 inflammation are not established.
Natural killer cells in lung transplantation
Authors: Daniel R Calabrese, Lewis L Lanier, John R Greenland
Journal: Thorax (2018)

Natural killer (NK) cells are innate lymphoid cells that have been increasingly recognised as important in lung allograft tolerance and immune defence. These cells evolved to recognise alterations in self through a diverse set of germline-encoded activating and inhibitory receptors and display a broad range of effector functions that play important roles in responding to infections, malignancies and allogeneic tissue. Here, we review NK cells, their diverse receptors and the mechanisms through which NK cells are postulated to mediate important lung transplant clinical outcomes. NK cells can promote tolerance, such as through the depletion of donor antigen-presenting cells. Alternatively, these cells can drive rejection through cytotoxic effects on allograft tissue recognised as 'non-self' or 'stressed', via killer cell immunoglobulin-like receptor (KIR) or NKG2D receptor ligation, respectively. NK cells likely mediate complement-independent antibody-mediated rejection of allografts though CD16A Fc receptor-dependent activation induced by graft-specific antibodies. Finally, NK cells play an important role in response to infections, particularly by mediating cytomegalovirus infection through the CD94/NKG2C receptor. Despite these sometimes-conflicting effects on allograft function, enumeration of NK cells may have an important role in diagnosing allograft dysfunction. While the effects of immunosuppression agents on NK cells may currently be largely unintentional, further understanding of NK cell biology in lung allograft recipients may allow these cells to serve as biomarkers of graft injury and as therapeutic targets.
Rural Residence and Poverty Are Independent Risk Factors for Chronic Obstructive Pulmonary Disease in the United States
Authors: Sarath Raju, Corinne A. Keet, Laura M. Paulin, Elizabeth C. Matsui, Roger D. Peng, Nadia N. Hansel, Meredith C. McCormack
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

In developing countries, poor and rural areas have a high burden of chronic obstructive pulmonary disease (COPD), and environmental pollutants and indoor burning of biomass have been implicated as potential causal exposures. Less is known about the prevalence of COPD in the United States with respect to urban-rural distribution, poverty, and factors that uniquely contribute to COPD among never-smokers.To understand the impact of urban-rural status, poverty, and other community factors on COPD prevalence nationwide and among never-smokers.We studied a nationally representative sample of adults in the National Health Interview Survey 2012-2015, with data linkage between neighborhood data from the U.S. Census's American Community Survey and the National Center for Health Statistics Urban-Rural Classification Scheme. The main outcome was COPD prevalence.The prevalence of COPD in poor, rural areas was almost twice that in the overall population (15.4% vs. 8.4%). In adjusted models, rural residence (odds ratio [OR], 1.23; P < 0.001) and census-level poverty (OR, 1.12; P = 0.012) were both associated with COPD prevalence, as were indicators of household wealth. Among never-smokers, rural residence was also associated with COPD (OR, 1.34; P < 0.001), as was neighborhood use of coal for heating (OR, 1.09; P < 0.001).In a nationally representative sample, rural residence and poverty were risk factors for COPD, even among never-smokers. The use of coal for heating was also a risk factor for COPD among never-smokers. Future disparities research to elucidate contributors to COPD development in poor and rural areas, including assessments of heating sources and environmental pollutants, is needed.
Cancer Risk Estimates for Study of Multiple-Gene Testing After Diagnosis of Breast Cancer
Authors: Steven A. Narod
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Mechanisms of Connexin-Related Lymphedema
Authors: Jorge A. Castorena-Gonzalez, Scott D. Zawieja, Min Li, R. Sathish Srinivasan, Alexander M. Simon, Cor de Wit, Roger de la Torre, Luis A. Martinez-Lemus, Grant W. Hennig, Michael J. Davis
Journal: Circulation Research (2018)

Rationale: Mutations in GJC2 and GJA1 , encoding Cxs (connexins) 47 and 43, respectively, are linked to lymphedema, but the underlying mechanisms are unknown. Because efficient lymph transport relies on the coordinated contractions of lymphatic muscle cells (LMCs) and their electrical coupling through Cxs, Cx-related lymphedema is proposed to result from dyssynchronous contractions of lymphatic vessels. Objective: To determine which Cx isoforms in LMCs and lymphatic endothelial cells are required for the entrainment of lymphatic contraction waves and efficient lymph transport. Methods and Results: We developed novel methods to quantify the spatiotemporal entrainment of lymphatic contraction waves and used optogenetic techniques to analyze calcium signaling within and between the LMC and the lymphatic endothelial cell layers. Genetic deletion of the major lymphatic endothelial cell Cxs (Cx43, Cx47, or Cx37) revealed that none were necessary for the synchronization of the global calcium events that triggered propagating contraction waves. We identified Cx45 in human and mouse LMCs as the critical Cx mediating the conduction of pacemaking signals and entrained contractions. Smooth muscle–specific Cx45 deficiency resulted in 10- to 18-fold reduction in conduction speed, partial-to-severe loss of contractile coordination, and impaired lymph pump function ex vivo and in vivo. Cx45 deficiency resulted in profound inhibition of lymph transport in vivo, but only under an imposed gravitational load. Conclusions: Our results (1) identify Cx45 as the Cx isoform mediating the entrainment of the contraction waves in LMCs; (2) show that major endothelial Cxs are dispensable for the entrainment of contractions; (3) reveal a lack of coupling between lymphatic endothelial cells and LMCs, in contrast to arterioles; (4) point to lymphatic valve defects, rather than contraction dyssynchrony, as the mechanism underlying GJC2 - or GJA1 -related lymphedema; and (5) show that a gravitational load exacerbates lymphatic contractile defects in the intact mouse hindlimb, which is likely critical for the development of lymphedema in the adult mouse.
Smoldering Myeloma Presenting with Renal Histopathology of Monoclonal Gammopathy of Renal Significance: Adding to the Complexity
Authors: Andreas Kousios, Neill Duncan, Rawya Charif, Candice Roufosse
Journal: Journal of the American Society of Nephrology (2018)

Sethi et al.1 provide a comprehensive review of monoclonal Ig (MIg)–associated renal diseases and elucidate monoclonal gammopathy of renal significance (MGRS). In MGRS, the clonal plasma cell or B cell proliferation is too small to meet the criteria of multiple myeloma (MM) or symptomatic lymphoma, and thus, it does not warrant immediate hematologic treatment. This new term has fulfilled a clinical need to distinguish monoclonal gammopathy of undetermined significance from MGRS and paved the way for an onconephrologic approach using clone-directed therapies in thoroughly assessed patients with MGRS with the objective to preserve renal function.2,3 MGRS caused by plasma cells is defined as <10% bone marrow plasma cells (BMPCs), <3 g/dl of M protein, and the presence of renal lesions without any other myeloma-defining events.1 As with MGRS, patients with smoldering myeloma (SMM) are asymptomatic but have higher MIg levels and BMPCs. In 2014, the International Myeloma Working Group (IMWG) updated the diagnostic criteria of MM to include BMPCs>60% and serum free light chain ratio >100 as myeloma-defining events. Thus, the revised definition of SMM is an intermediate stage between monoclonal gammopathy of undetermined significance and MM with BMPCs of 10%–60% and/or serum MIg >3g/dl.4 The standard of care in SMM is observation until progression to MM or enrolment in a clinical trial. For patients with SMM who have MGRS renal lesions, guidance is lacking. The IMWG recommends that MGRS renal lesions should not be regarded as myeloma-defining events leading to MM diagnosis. With patients with SMM excluded from the MGRS group and not warranting immediate myeloma-type management, a clinicopathologic gap is created. In our center, during 2006–2017, we identified 163 of 4374 (3.7%) native biopsies with MIg-associated lesions. After exclusion of MM, lymphoma, and Light-chain (AL) amyloidosis, 40 patients had an MGRS-type renal lesion. Of these patients, 30 had a bone marrow biopsy. Eight of 30 (27%) patients had SMM (BMPCs=10%–60%). Therefore, the number of patients falling in this clinicopathologic gap is quite substantial in our experience. SMM with MGRS-type lesions is not uncommon, and the best therapeutic approach remains to be defined. Although it is reasonable to adopt treatment strategies similar to MGRS, we believe that SMM of renal significance merits more attention in the MIg-associated renal diseases nomenclature. This will increase awareness for renal screening in SMM and improve study design when evaluating new approaches to the full spectrum of MIg-associated diseases. Disclosures None.
Poorly Differentiated Primary Carcinoma of the Middle Ear on 18F-FDG PET/CT
Authors: John S. Nemer, Meng-Chieh P. Hsieh, Diane Chen, Kathleen M. O'Toole, Randy Yeh
Journal: Clinical Nuclear Medicine (2018)

Primary carcinoma of the middle ear is extremely rare. A 41-year-old woman with a history of skull base osteomyelitis and chronic suppurative right otitis media presented with 1 month of right-sided facial droop, tearing, and headaches. Initial head CT revealed bony destruction and soft tissue opacification involving the right middle ear. Surgical biopsy yielded poorly differentiated carcinoma. Subsequent F-FDG PET/CT and MRI scans demonstrated FDG-avid soft tissue in the right middle ear with associated heterogeneously enhancing soft tissue on MRI.
Creatine kinase pathway inhibition alters GSK3 and WNT signaling in EVI1-positive AML
Authors: Lina Benajiba, Gabriela Alexe, Angela Su, Emmanuel Raffoux, Jean Soulier, Michael T. Hemann, Olivier Hermine, Raphael Itzykson, Kimberly Stegmaier, Alexandre Puissant
Journal: Leukemia (2018)
Quantitative sensory testing in patients with sensitive skin
Authors: F. Huet, A. Dion, A. Batardière, A.S. Nedelec, F. Le Caër, P. Bourgeois, E. Brenaut, L. Misery
Journal: British Journal of Dermatology (2018)

Sensitive skin is defined as unpleasant sensation, such as itch, pain or burning, in response to stimuli that would not normally cause these symptoms. It does not include patients with skin diseases such as eczema, which can cause these symptoms. Sensitive skin is claimed to affect 50% of women and 30% of men in Europe, and impairs their quality of life. It can be measured using a questionnaire, the Sensitive Scale. It is not clear whether these symptoms are due to changes in the skin's blood supply, a defect in the skin barrier or due to changes in the nerve supply to the epidermis (outermost layer of skin). The authors, based in Brittany, France, quantified heat‐pain threshold, a measure of touch sensitivity, in 21 individuals with Sensitive Skin Syndrome (having a Sensitive Scale score greater than 50) and 21 control subjects (Sensitive Scale score less than 20). The authors also quantified the degree of neuropathic (nerve‐related) pain in both groups using two questionnaires. They found a significantly reduced heat‐pain threshold and higher neuropathic pain scores in the individuals with sensitive skin, compared with controls. They conclude that these findings support the idea that sensitive skin is linked with abnormal function of the nerve endings in the skin. Conventionally, sensitive skin has been treated with moisturisers but the authors suggest that at least the more severely affected individuals may require a different approach to treatment.
Socio-Demographic Features and Societal Perspective of Relapse and/or Refractory Multiple Myeloma (RRMM) Patients in Spain: An Interim Analysis of Charismma Study
Authors: Enrique M. Ocio, Laura Rosinol, Marta Grande, Ana Ruiz-Zorrilla, Alonso Fernandez, Carmen Montoto
Journal: Blood (2018)
Trends in incidence of cutaneous malignant melanoma in Canada: 1992-2010 versus 2011-2015
Authors: Feras M. Ghazawi, Michelle Le, Nebras Alghazawi, Elham Rahme, Linda Moreau, Elena Netchiporouk, Andrei Zubarev, Osama Roshdy, Steven J. Glassman, Denis Sasseville, Ivan V. Litvinov
Journal: Journal of the American Academy of Dermatology (2018)
Comparison of Reperfusion Times in Patients Transferred for Primary Angioplasty for ST-Elevation Myocardial Infarction: Prior to and After Instituting a Regional MI Alert Protocol
Authors: Michael A Rossi, Michael J Durkin, J Patrick Kleaveland, Richard S. MacKenzie, DO Bruce Feldman, Frank Penatar, Deborah Neff, Jo A Wells, Vincent Tallarico, MA Tamara Masiado, Thomas Wasser
Journal: Circulation (2005)
Abstract 20591: High-Sensitivity Cardiac Troponin After Cardiac Stress Test - A Meta-Analysis
Authors: Eslam Samaha, Audrey Avila, Mohammad A Helwani, Arbi Ben Abdallah, Allan S Jaffe, Mitchell G Scott, Peter Nagele
Journal: Circulation (2017)

Introduction: Rising patterns of high-sensitivity cardiac troponin (hscTn) do not only occur during acute coronary syndrome, but also following cardiovascular stress. To improve our understanding a...
Sacubitril/Valsartan Averts Adverse Post-Infarction Ventricular Remodeling and Preserves Systolic Function in Rabbits
Authors: Juan Torrado, Chad Cain, Adolfo G. Mauro, Francisco Romeo, Ramzi Ockaili, Vinh Q. Chau, John A. Nestler, Teja Devarakonda, Siddhartha Ghosh, Anindita Das, Fadi N. Salloum
Journal: Journal of the American College of Cardiology (2018)
Abstract MP039: Relationship between Nontraditional and Standard Markers of Glycemia
Authors: Stephen P Juraschek, Michael W Steffes, Elizabeth Selvin
Journal: Circulation (2012)

Background: Glycated albumin, fructosamine, and 1,5-anhydroglucitol (1,5-AG) may be utilized to monitor glycemic control when standard markers are unavailable. However, their fasting glucose- and HbA1c-equivalents have not been characterized in a general population. Methods: We compared glycated albumin, fructosamine, 1,5-AG, HbA1c, and fasting glucose in 1,719 participants (mean age = 71yr) in a cross-sectional subsample of the Atherosclerosis Risk in Communities (ARIC) Study. We modeled the relationship between the markers with generalized linear equations, using R2 and F-statistics. We also used the Area Under the Curve (AUC) to evaluate the ability of nontraditional markers to identify people with diabetes defined by HbA1c ≥6.5%, fasting glucose≥126 mg/dL, or self-report. Results: Median fasting glucose and HbA1c were 103 mg/dL and 5.6%, respectively; 25% (n=423) of the study population reported a diabetes diagnosis. Glycated albumin, fructosamine, and 1,5-AG were more strongly associated with HbA1c (r = 0.51, 0.43, and -0.25, respectively) vs. fasting glucose (r = 0.38, 0.34, and -0.15, respectively). Models generally performed better (higher R2) in diabetic subjects (Figure). Glycated albumin was superior to fasting glucose for identification of diabetes defined by HbA1c (AUC, 0.87 vs. 0.83) or by self-report (AUC, 0.84 vs. 0.81). Conclusion: Nontraditional glycemic markers can identify people with diabetes when whole blood required for HbA1c is not available. Glycated albumin was superior to fasting glucose in identifying persons with diabetes. The models identified in this study enable comparison of these markers to HbA1c and fasting glucose on a common scale, which could be useful clinically. Figure. Scatter plots of nontraditional serum glycemic markers vs. hemoglobin A1c (%) or fasting glucose (mg/dL) overlaid with a Lowess curve (dash) and best fit model (line). Also presented are formulae for the best model in a subset of the population with diagnosed diabetes (data points and fit not shown).
Re: A Prospective Randomised Placebo-controlled Study of the Impact of Dutasteride/Tamsulosin Combination Therapy on Sexual Function Domains in Sexually Active Men with Lower Urinary Tract Symptoms (LUTS) Secondary to Benign Prostatic Hyperplasia (BPH)
Authors: Ignacio Moncada, Pramod Krishnappa
Journal: European Urology (2018)
Bronchoalveolar lavage Aspergillus Galactomannan lateral flow assay versus Aspergillus-specific lateral flow device test for diagnosis of invasive pulmonary Aspergillosis in patients with hematological malignancies
Authors: Jeffrey D. Jenks, Sanjay R. Mehta, Randy Taplitz, Nancy Law, Sharon L. Reed, Martin Hoenigl
Journal: Journal of Infection (2018)