tbuckley/cabot-search huggingface dataset:
Response to: ‘Anti-Ku antibodies: important points to consider’ by Mahler <i>et al</i>
Authors: Mariko Ogawa-Momohara, Yoshinao Muro, Masashi Akiyama
Journal: Annals of the Rheumatic Diseases (2019)

Response to: 'Anti-Ku antibodies: important points to consider' by Mahler et al We thank the authors 1 for their interest in our paper 2 and are grateful for the opportunity to respond to the points raised.We agree with the opinion of Mahler et al that 'SLE frequently express many autoantibodies and sera accompanied by mixed HEp-2 IIF pattern were very common'.We adopted the same methods for anti-Ku screening that Spielmann et al 3 used in their study to avoid missing multiple autoantibody-positive cases.The Spielmann group included ANA-positive sera showing several ANA patterns (ICAP nomenclature: AC-1, AC-4 or AC-5) for ELISA analysis.Although Mahler et al noted that 'In our experience, anti-Ku antibodies are frequently found in SLE patients potentially associated with overlap features of a myopathy', of the four anti-Ku antibody-positive myositis patients in their referenced study, only two patients had systemic lupus erythematosus (SLE) overlapping with myositis. 3Given that 33 anti-Ku-positive SLE patients in their study 4 did not have myositis, it seems that SLE and myositis are less likely to overlap.We need to be careful in discussing the frequency of anti-Ku-associated clinical phenotypes.We detected anti-dsDNA and anti-ssDNA antibodies by using two commercial ELISA kits (MBL, Nagoya, Japan).These kits are commonly used in Japan and are covered by health insurance for clinical laboratory tests.As Mahler et al noted that there is variability between anti-dsDNA assays, 1 we need to use immunofluorescence tests with Crithidia luciliae as a substrate for confirmation.
To Cure Sometimes, To Relieve Often, and To Comfort Always<sup>*</sup>
Authors: Rosalyn Stewart, Valerie Gray Hardcastle
Journal: The American Journal of Bioethics (2019)

Since Dr. Kubler-Ross’s seminal publication in 1969, we have seen significant growth in palliative and hospice care. We have also learned that palliative care can decrease medical costs and the tim...
Multiple chronic conditions and intensity of end-of-life care among patients with cancer.
Authors: Cara L. McDermott, Ruth Engelberg, Mohamed Lotfy Sorror, James Sibley, J. Randall Curtis
Journal: Journal of Clinical Oncology (2019)

47 Background: Multiple chronic conditions (MCCs) are associated with increased intensity of end-of-life (EOL) care in many conditions but their effect has not been well explored in patients with cancer. We examined intensity of EOL care and advance care planning (ACP) by patients with cancer and MCCs versus those without MCCs to better understand how MCCs affect EOL healthcare use in this population. Methods: Our sample included patients with cancer in the UW Medicine system who died between 2010-2017. MCCs were defined using the Dartmouth Atlas of Healthcare for the most common categories of severe illness in the last two years of life. These included chronic pulmonary disease, coronary artery disease (CAD), heart failure, severe chronic liver disease, chronic renal disease, dementia, diabetes with end organ damage, or peripheral vascular disease. Patients were categorized as having none or 1+ MCCs. We used a claims-based indicator for the presence of functional limitation. Outcomes included ACP documentation in the electronic health record, death in hospital, and inpatient or ICU admission in the last month of life. We performed logistic regression for all outcomes controlling for confounders defined a priori (age at death, race, sex, marital status, insurance, education, functional limitation). Results: Of 15,092 patients with cancer, 10,596 (70%) had 1+MCCs (range 1-8 MCCs). Common MCCs were pulmonary (25%), CAD (23%), and renal (18%). Those with MCCs were older (median 66 years (range 18-104) vs 63 years (range 18-102)), with more functional limitations (65% vs 43%). Those with 1+ MCC had more ACP documentation (43% vs. 23%) compared to those with no MCCs. Patients with 1+ MCC were more likely to die in hospital (OR 1.86, 95% CI 1.72-2.02) and to have inpatient (OR 2.45, 95% CI 2.20-2.72) or ICU admissions (OR 2.95, 95% CI 2.55-3.42) in their last 30 days versus patients with cancer and no MCCs. Conclusions: Among patients with cancer in a single healthcare system, patients with cancer and MCCs were more likely to have ACP documentation, die in hospital and experience high-intensity hospital-based care at or near EOL. Further research is needed to explore if such high-intensity care is aligned with patient and family goals for care.
Identification and local delivery of vasodilators for the reduction of ureteral contractions
Authors: Christopher X. Lee, Jaime H. Cheah, Christian K. Soule, Huiming Ding, Charles A. Whittaker, Kyle Karhohs, Aurora A. Burds, Kriti S. Subramanyam, Anne E. Carpenter, Brian H. Eisner, Michael J. Cima
Journal: Nature Biomedical Engineering (2019)
Letter to the Editor: Moderate Alcohol Use in Fatty Liver Disease: Don’t Throw the Cabernet Out With the Bathwater
Authors: Paul Gow, Adam G. Testro, Penelope Hey, Marie Sinclair
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To The Editor: We congratulate Aberg et al. for a significant contribution to the literature on the important topic of moderate alcohol use in fatty liver disease (nonalcoholic fatty liver disease; NAFLD).1 Approximately 30% of the population of the Western world has obesity and/or other complications of insulin resistance and metabolic syndrome. Because of the magnitude of this problem worldwide, palatable lifestyle therapies that are affordable, available, and acceptable are necessary to curtail preventable early deaths. Moderate alcohol has the potential to fill this space, although knowledge remains limited. The most common cause of death in patients with NAFLD is cardiovascular disease. Aberg et al.'s article clearly demonstrated that low‐to‐moderate alcohol consumption reduced cardiovascular events by >20% and all‐cause mortality by a similar magnitude. As hepatologists, we are rightly concerned about variables that influence liver outcomes in NAFLD. However, we should be similarly engaged in the discussion of lifestyle interventions that offer extrahepatic benefits, as Aberg et al.'s data suggest that moderate alcohol does. Moderate alcohol drinking in this population does carry some risks, including increasing the risk of hepatocellular and breast cancer, but at the same time reduces the risk of renal‐cell carcinoma and lymphoma. It may also reduce the risk of developing diabetes, stroke, dementia, and cardiovascular disease.2 The net effect is positive, as demonstrated by Aberg et al., with reduced all‐cause mortality. Aberg et al.'s data therefore do not argue against the use of moderate alcohol in this population, but for it. The association between low‐level alcohol consumption, particularly wine, and the development of liver disease itself remains unanswered from Aberg et al.'s data set. In fact, for low‐dose alcohol consumption (0‐9 g/day), there was no significant link between alcohol intake and liver events, and the association for 10‐19 g/day of alcohol and liver events was only noted in nonwine drinkers. In a previous large cohort study, wine consumption up to 10 g/day reduced the risk of hepatic steatosis by 50%.3 A case‐control study examining histology and gene array also found that low‐level alcohol may suppress gene expression involved in the immune response that drives steatohepatitis.4 Given the small numbers of patients in the current study reporting low‐level wine consumption, it was likely underpowered to assess benefit. Furthermore, information on significant confounders, including baseline hepatic fibrosis, diabetic control, and coffee intake, was not available. Further well‐defined studies are required to assess the impact of low‐to‐moderate alcohol consumption on liver disease and cardiovascular outcomes before this can be recommended as a lifestyle intervention. Similarly, alcohol's narrow therapeutic window can be difficult to achieve.
Earlier Steroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Large B Cell Lymphoma
Authors: Max Topp, Tom Van Meerten, Roch Houot, Monique C. Minnema, Noel Milpied, Pieternella J. Lugtenburg, Catherine Thieblemont, Martin Wermke, Kevin Song, Irit Avivi, John Kuruvilla, Ulrich Dührsen, Rachel Chu, Lianqing Zheng, Vicki Plaks, Anne Kerber, Marie Jose' Kersten
Journal: Blood (2019)
Response to Comment on Cho et al. Antidiabetic Medications and Mortality Risk in Individuals With Pancreatic Cancer–Related Diabetes and Postpancreatitis Diabetes: A Nationwide Cohort Study. Diabetes Care 2019;42:1675–1683
Authors: Jaelim Cho, Maxim S. Petrov
Journal: Diabetes Care (2019)

We thank Devouge et al. (1) for their interest in our nationwide cohort study that will contribute meaningfully to the changing field of diabetes of the exocrine pancreas. The authors made a comment about the possibility of including individuals with undetected type 2 diabetes in the cohort of postpancreatitis diabetes mellitus (PPDM) we established (2). The issue of undetected type 2 diabetes is common and ubiquitous. This is because of suboptimal screening for diabetes in general and PPDM in particular. To ensure that this perennial issue does not cripple accuracy of data in the context of pancreatitis, the use of two terms (as appropriate) is advocated: “new-onset diabetes after pancreatitis” (NODAP) and PPDM (3,4). When an individual is confirmed not to have preexisting …
EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression
Authors: Shunli Peng, Rong Wang, Xiaojuan Zhang, Yueyun Ma, Longhui Zhong, Ke Li, Akihiro Nishiyama, Sachiko Arai, Seiji Yano, Wei Wang
Journal: Molecular Cancer (2019)

Abstract Background The ATLANTIC trial reported that higher PD-L1 expression in tumors was involved in a higher objective response in patients with EGFR + /ALK + non-small cell lung cancer (NSCLC), indicating the possibility of anti-PD-1/PD-L1 therapy as a third-line (or later) treatment for advanced NSCLC. Therefore, the determination of status and regulatory mechanisms of PD-L1 in EGFR mutant NSCLC before and after acquired EGFR-TKIs resistance are meaningful. Methods The correlation among PD-L1, c-MET, and HGF was analyzed based on TCGA datasheets and paired NSCLC specimens before and after acquired EGFR-TKI resistance. EGFR-TKI resistant NSCLC cells with three well-known mechanisms, c-MET amplification, hepatocyte growth factor (HGF), and EGFR-T790M , were investigated to determinate PD-L1 expression status and immune escape ability. PD-L1-deleted EGFR-TKIs sensitive and resistant cells were used to evaluate the immune escape ability of tumors in mice xenograft models. Results Positive correlations were found among PD-L1, c-MET, and HGF, based on TCGA datasheets and paired NSCLC specimens. Moreover, the above three resistant mechanisms increased PD-L1 expression and attenuated activation and cytotoxicity of lymphocytes in vitro and in vivo, and downregulation of PD-L1 partially restored the cytotoxicity of lymphocytes. Both MAPK and PI3K pathways were involved in the three types of resistance mechanism-induced PD-L1 overexpression, whereas the NF-kappa B pathway was only involved in T790M -induced PD-L1 expression. Conclusions HGF, MET -amplification, and EGFR-T790M upregulate PD-L1 expression in NSCLC and promote the immune escape of tumor cells through different mechanisms.
Grants for Rare Disease Research
Authors: Feyza Sancar
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Comprehensive Analysis of Single-Cell Chromatin Accessibility and Gene Expression Identifies Intra-Tumor Heterogeneity and Molecular Treatment Responses in Relapsed/Refractory Multiple Myeloma
Authors: Alexandra M Poos, Jan-Philipp Mallm, Stephan M Tirier, Nicola Casiraghi, Hana Susak, Nicola Giesen, Katharina Bauer, Anja Baumann, Lukas John, Isabelle Lander, Jing Xu, Moritz Przybilla, Anja Kunze, Carsten Mueller-Tidow, Benedikt Brors, Oliver Stegle, Hartmut Goldschmidt, Karsten Rippe, Marc S Raab, Niels Weinhold
Journal: Blood (2019)
Resistance to Acalabrutinib in CLL Is Mediated Primarily By BTK Mutations
Authors: Jennifer Woyach, Ying Huang, Kerry Rogers, Seema A. Bhat, Michael R. Grever, Arletta Lozanski, Tzyy-Jye Doong, James S. Blachly, Gerard Lozanski, Dan Jones, John C. Byrd
Journal: Blood (2019)
Abstract 15207: Predicting Tacrolimus Concentrations in Heart Transplant Recipients Using Population Pharmacokinetic Models
Authors: Kimberly Molina, Joseph Rower, Chris Stockmann, Catherine Sherwin
Journal: Circulation (2016)

Background: Tacrolimus (TAC) promotes graft longevity in heart transplant recipients, yet is associated with large inter-patient variability that necessitates frequent drug monitoring. We hypothesi...
Patient-provider communication and decision making in palliative radiotherapy.
Authors: Jie Jane Chen, Claudia Sofia Roldan, Alexandra N. Nichipor, Tracy A. Balboni, Monica Shalini Krishnan, Anna Revette, Lauren Michelle Hertan, Aileen B. Chen
Journal: Journal of Clinical Oncology (2019)

24 Background: Patient-provider communication may impact patient satisfaction and engagement in decision-making. We aimed to understand patient preferences on radiation therapy (RT) discussions and to identify how to better communicate RT information. Methods: We conducted semi-structured interviews with 17 patients receiving palliative RT for lung or bone metastases at a single institution from 9/2016 to 10/2018. Patients’ answers about RT decision-making and communication were transcribed verbatim and analyzed qualitatively. We reviewed patients’ medical records to obtain demographic and clinical data. Results: The median age of patients was 64 years (range: 21-82). Most patients had metastatic cancer at diagnosis (53%) and had received prior palliative chemotherapy (71%) or RT (88%). The most common palliative RT course was 30 Gy in 10 fractions. Themes that impacted patients’ decisions to proceed with RT included trust in physicians (41%), desire to minimize pain or improve quality of life (35%), and a perceived lack of alternatives (35%). Most patients (76%) described the RT decision-making process as straightforward or logical. All patients reported receiving information from a physician on reasons to consider RT, while only 53% recalled discussions on reasons not to consider RT. Nearly all patients (88%) preferred shared patient-provider decision-making regarding cancer treatment; two patients (12%) preferred to be the main decision-maker. When discussing technical aspects of RT, 65% of patients reported that providers shared information on intensity of RT and number of treatments. Although 82% of patients reported that the provider was the sole decision-maker for the intensity of RT or number of treatments, all patients were satisfied and would not have wanted to be more involved in this decision. Conclusions: Trust in physicians, desire to minimize pain, and perceived lack of alternatives impact patients’ decisions to proceed with RT. Patients were more likely to remember physicians discussing reasons for RT as opposed to reasons not to consider RT. Most patients prefer shared decision-making regarding cancer treatment initiation but prefer physicians to make the decisions regarding RT treatment intensity.
GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions
Authors: Danielle M. Gerhard, Santosh Pothula, Rong-Jian Liu, Min Wu, Xiao-Yuan Li, Matthew J. Girgenti, Seth R. Taylor, Catharine H. Duman, Eric Delpire, Marina Picciotto, Eric S. Wohleb, Ronald S. Duman
Journal: Journal of Clinical Investigation (2019)

A single subanesthetic dose of ketamine, an NMDA receptor (NMDAR) antagonist, produces rapid and sustained antidepressant actions in depressed patients, addressing a major unmet need for the treatment of mood disorders. Ketamine produces a rapid increase in extracellular glutamate and synaptic formation in the prefrontal cortex, but the initial cellular trigger that initiates this increase and ketamine's behavioral actions has not been identified. To address this question, we used a combination of viral shRNA and conditional mutation to produce cell-specific knockdown or deletion of a key NMDAR subunit, GluN2B, implicated in the actions of ketamine. The results demonstrated that the antidepressant actions of ketamine were blocked by GluN2B-NMDAR knockdown on GABA (Gad1) interneurons, as well as subtypes expressing somatostatin (Sst) or parvalbumin (Pvalb), but not glutamate principle neurons in the medial prefrontal cortex (mPFC). Further analysis of GABA subtypes showed that cell-specific knockdown or deletion of GluN2B in Sst interneurons blocked or occluded the antidepressant actions of ketamine and revealed sex-specific differences that are associated with excitatory postsynaptic currents on mPFC principle neurons. These findings demonstrate that GluN2B-NMDARs on GABA interneurons are the initial cellular trigger for the rapid antidepressant actions of ketamine and show sex-specific adaptive mechanisms to GluN2B modulation.
Lower Airway Infection in Preschool Children with Cystic Fibrosis: An International Comparison
Authors: Kathryn M. Hulme, Barry Linnane, Paul McNally
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

in this age group is likely underestimated by less interventional methods of microbiological screening (2).It also aligns with the accumulating evidence that increasing prevalence is associated with increasingly aggressive use of antibiotics in this cohort, and we would support the call for further work to explore the clinical implications of fungal airway infection.We are, however, concerned that the data may not represent the full picture of cystic fibrosis airway microbiology in early childhood, most notably for the omission of microbiology results from airway samples obtained during pulmonary exacerbations.We acknowledge that previously reported data from the same group report the sensitivity of oropharyngeal (OP) cultures for the detection of Pseudomonas aeruginosa to be low (23%) when compared against BAL performed at times of clinical stability (3).However, during pulmonary exacerbations, substantially higher sensitivity (76%) is reported for OP cultures compared with BAL for the detection of P. aeruginosa (4), and no benefit has been found for a strategy of bronchoscopic airway sampling over noninvasive sampling to guide treatment of pulmonary exacerbations in young children (5).Although imperfect, noninvasive airway sampling, with reduced exposure to general anesthesia risk and a significantly reduced cost, continues to form a routine part of clinical care in many cystic fibrosis centers worldwide.Sputum induction has also been shown to act as a credible alternative to BAL in symptomatic children (6).In the current study (1), routine treatment of pulmonary exacerbations at one of the two study sites was guided by previous cultures (including OP samples), thereby inferring that OP cultures were considered to reflect lower airway microbiology.Yet the results of noninvasive (OP or other) cultures collected between surveillance bronchoscopies, and in particular during pulmonary exacerbations, are not reported.The omission of microbiological samples collected during symptomatic periods risks potential underreporting of the prevalence of bacterial airway infection, particularly if infection is then cleared after targeted antibiotic therapy.
Expression of the long non-coding RNA TCL6 is associated with clinical outcome in pediatric B-cell acute lymphoblastic leukemia
Authors: Marta Cuadros, Álvaro Andrades, Isabel F. Coira, Carlos Baliñas, María I. Rodríguez, Juan Carlos Álvarez-Pérez, Paola Peinado, Alberto M. Arenas, Daniel J. García, Pilar Jiménez, Mireia Camós, Antonio Jiménez-Velasco, Pedro P. Medina
Journal: Blood Cancer Journal (2019)

The authors would like to thank the Deutsche Jose Carreras Leukamie-Stiftung,
Inocente Inocente Foundation, the Ministry of Economy of Spain (SAF2015-
67919-R), Consejeria de Salud de la Junta de Andalucia (Pl-0245-2017, CS2016-
3), BBVA Foundation, Francisco-Cobos Foundation, Fero Foundation and AECC
Foundation for funding Pedro P. Medinas’s lab. Alvaro Andrades is supported
by an FPU17/00067 PhD fellowship, Alberto M. Arenas is supported by an
FPU17/01258 PhD fellowship, Paola Peinado is supported by a La Caixa
Foundation PhD Fellowship (LCF/BQ/DE15/10360019), Isabel F. Coira was
supported by a PhD FPI-fellowship (BES-2013-064596), Daniel J. Garcia is
supported by a Fundacion Benefica Anticancer Santa Candida y San Francisco
Javier PhD fellowship and Juan Carlos Alvarez-Perez is supported by a Marie
Sklodowska Curie action (H2020-MSCA-IF-2018). The funding agencies had no
role in study design, data collection, and analysis, decision to publish, or
preparation of the manuscript. The authors would also like to thank the
Biobanc de l’Hospital Infantil Sant Joan de Deu per a la Investigacio, integrated in
the Spanish Biobank Network of ISCIII, as well as Asociacion Malaguena para la
Investigacion en Leucemias (AMPILE), for the sample and data procurement.
Potential Medicare Savings on Inhaler Prescriptions Through the Use of Negotiated Prices and a Defined Formulary
Authors: William B. Feldman, Jerry Avorn, Aaron S. Kesselheim
Journal: JAMA Internal Medicine (2019)

This study examines the estimated cost of asthma inhalers for individuals treated under Medicare Part B compared with those treated under the Veterans Affairs Health System, taking into account separate approaches to price negotiation.