tbuckley/cabot-search huggingface dataset:
Association of Diagnosis Coding With Differences in Risk-Adjusted Short-term Mortality Between Critical Access and Non–Critical Access Hospitals
Authors: Cyrus M. Kosar, Lacey Loomer, Kali S. Thomas, Elizabeth M. White, Orestis A. Panagiotou, Momotazur Rahman
Journal: JAMA (2020)

Critical access hospitals (CAHs) provide care to rural communities. Increasing mortality rates have been reported for CAHs relative to non-CAHs. Because Medicare reimburses CAHs at cost, CAHs may report fewer diagnoses than non-CAHs, which may affect risk-adjusted comparisons of outcomes. To assess serial differences in risk-adjusted mortality rates between CAHs and non-CAHs after accounting for differences in diagnosis coding. Serial cross-sectional study of rural Medicare Fee-for-Service beneficiaries admitted to US CAHs and non-CAHs for pneumonia, heart failure, chronic obstructive pulmonary disease, arrhythmia, urinary tract infection, septicemia, and stroke from 2007 to 2017. The final date of follow-up was December 31, 2017. Admission to a CAH vs non-CAH. Discharge diagnosis count including trends from 2010 to 2011 when Medicare expanded the allowable number of billing codes for hospitalizations, and combined in-hospital and 30-day postdischarge mortality adjusted for demographics, primary diagnosis, preexisting conditions, and with vs without further adjustment for Hierarchical Condition Category (HCC) score to understand the contribution of in-hospital secondary diagnoses. There were 4 094 720 hospitalizations (17% CAH) for 2 850 194 unique Medicare beneficiaries (mean [SD] age, 76.3 [11.7] years; 55.5% women). Patients in CAHs were older (median age, 80.1 vs 76.8 years) and more likely to be female (58% vs 55%). In 2010, the adjusted mean discharge diagnosis count was 7.52 for CAHs vs 8.53 for non-CAHs (difference, -0.99 [95% CI, -1.08 to -0.90]; P < .001). In 2011, the CAH vs non-CAH difference in diagnoses coded increased (P < .001 for interaction between CAH and year) to 9.27 vs 12.23 (difference, -2.96 [95% CI, -3.19 to -2.73]; P < .001). Adjusted mortality rates from the model with HCC were 13.52% for CAHs vs 11.44% for non-CAHs (percentage point difference, 2.08 [95% CI, 1.74 to 2.42]; P < .001) in 2007 and increased to 15.97% vs 12.46% (difference, 3.52 [95% CI, 3.09 to 3.94]; P < .001) in 2017 (P < .001 for interaction). Adjusted mortality rates from the model without HCC were not significantly different between CAHs and non-CAHs in all years except 2007 (12.19% vs 11.74%; difference, 0.45 [95% CI, 0.12 to 0.79]; P = .008) and 2010 (12.71% vs 12.28%; difference, 0.42 [95% CI, 0.07 to 0.77]; P = .02). For rural Medicare beneficiaries hospitalized from 2007 to 2017, CAHs submitted significantly fewer hospital diagnosis codes than non-CAHs, and short-term mortality rates adjusted for preexisting conditions but not in-hospital comorbidity measures were not significantly different by hospital type in most years. The findings suggest that short-term mortality outcomes at CAHs may not differ from those of non-CAHs after accounting for different coding practices for in-hospital comorbidities.
HBV Care Map for Patients Receiving Anti-CD20 Therapy
Authors: Zachary Liederman, Neil Berinstein, Michael Crump, Jessica Hwang, Harry L.A. Janssen, C. Tom Kouroukis, Patricia Leung, Anna Lok, Colina Yim, Andrew D. Zelenetz, Kelvin Chan, Jordan Feld, Lisa K. Hicks
Journal: Blood (2017)
Increased diversity of gut microbiota during active oral immunotherapy in peanut‐allergic adults
Authors: Ziyuan He, VL Gouri Vadali, Rose L. Szabady, Wenming Zhang, Jason M. Norman, Bruce Roberts, Robert Tibshirani, Manisha Desai, R. Sharon Chinthrajah, Stephen J. Galli, Sandra Andorf, Kari C. Nadeau
Journal: Allergy (2020)

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Covid-19: Where are we on immunity and vaccines?
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Where are we on immunity and vaccines?As covid-19 vaccine trials begin to report early results and research papers on immunity shed more light on the situation, Elisabeth Mahase looks at what we know so far Elisabeth Mahase Do the recent vaccine papers tell us anything new?There was a flurry of excitement last month when two new papers published in the Lancet outlined the early findings from two SARS-CoV-2 vaccine trials.The first came from the University of Oxford 1 and reported that, in a phase I/II trial involving just over 1000 healthy adults (543 given the vaccine, 534 given the meningococcal conjugate vaccine as a control), the vaccine candidate induced strong antibody and T cell immune responses (up to day 56).They reported no serious adverse events.The ChAdOx1 nCoV-19 vaccine uses an adenovirus vaccine vector and the genetic sequence for the SARS-CoV-2 spike protein.After the vaccine has been administered the spike protein is produced, which primes the immune system to recognise and attack the virus if the vaccinated person is infected in the future.The researchers, led by Sarah Gilbert, professor of vaccinology, have teamed up with AstraZeneca and have already begun phase III trials in England to determine efficacy, as well as in South Africa and Brazil.A US trial should begin later this year. 2 The second paper came from researchers in China, who tested their non-replicating adenovirus type-5 vectored vaccine (Ad5-nCoV) on 382 participants (who received either a high or low dose, while 126 people received a placebo). 3This vaccine candidate, developed with CanSino Biologics, uses a weakened human common cold virus to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells.The researchers reported that, 28 days after vaccination, 95% of participants (241/253) in the high dose group and 91% (118/129) in the low dose group showed either T cell or antibody immune responses.The team said that, while the proportion of adverse reactions (such as fever, fatigue, or injection site pain) was considerably higher in vaccine recipients than in placebo recipients (72% in the high dose group, 74% in the low dose group, 37% in the placebo group), most adverse reactions were mild or moderate.However, while both papers reported promising preliminary results and have provided some hope that at least one of these vaccines could be effective, we still do not know what level of immune response is needed to protect against the virus.That information is vital to determining whether a vaccine is effective.
Response to: ‘Presence of anti-phospholipid antibodies in COVID-19: a case series study’ by Amezcua-Guerra<i>et al</i>
Authors: Alexis Mathian, Marc Pineton De Chambrun, Alain Combes, Zahir Amoura
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Background</h3> Suspected causative antigens may be unidentified in 30–50% of patients with fibrotic hypersensitivity pneumonitis (f-HP). It is unclear whether antigen identification and avoidance in this setting offer any additional clinical benefit. We hypothesised that antigen identification and avoidance may improve the clinical course of patients with fibrotic disease. <h3>Methods</h3> Patients meeting recent international practice guidance for f-HP diagnosis evaluated at Mayo Clinic Rochester from January 2005 to December 2018 were included. Causative antigen and antigen avoidance were specifically defined and ascertained through review of the medical records. Cox proportional-hazards regression was performed to assess antigen identification and avoidance as predictors of either all-cause mortality or lung transplantation. <h3>Results</h3> 377 patients were included. Of these, suspected causative antigen was identified in 225 (60%). Identification of a suspected antigen (adjusted hazard ratio (HR) 0.69, 95% CI 0.48–0.99; p=0.04) and subsequent antigen avoidance (adjusted HR 0.47, 95% CI 0.31–0.71; p&lt;0.001) were associated with decreased all-cause mortality and transplantation. Both those with suspected antigen identification but nonavoidance and those with unidentifiable antigen had increased risk of all-cause mortality or transplantation (adjusted HR 2.22, 95% CI 1.34–3.69; p=0.002 <i>versus</i> adjusted HR 2.09, 95% CI 1.34–3.26; p=0.001, respectively). Exposure to avian antigen was associated with better outcome compared to other antigen subtypes (adjusted HR 0.63, 95% CI 0.43–0.93; p=0.02). <h3>Conclusion</h3> Our findings suggest that antigen identification and antigen avoidance remain relevant even in patients with fibrotic disease, where both appear to be associated with improved outcomes.
Response to: ‘Correspondence to ‘Gender gap in rheumatology: speaker representation at annual conferences’ by Monga and Liew–gender discrepancies at annual EULAR congresses: towards the gap narrowing’ by Conigliaro<i>et al</i>
Authors: Kanika Monga, Jean Liew
Journal: Annals of the Rheumatic Diseases (2020)

The authors provide data on the gender gap in the European League Against Rheumatism (EULAR) meetings in 2018 and in 2019.Overall, the authors found that female speakers delivered 46% of presentations in 2018, and 44% in 2019-numbers that were similar to our findings for ACR meetings.The authors were able to break down the proportion of female speakers by invited speakers, moderators and selected abstracts.They found that these percentages were close to 50% for selected abstracts and moderators in 2019, a finding which is reassuring.Interestingly, the lowest proportion of female speakers was recorded in the general scientific session during both years.We found there was a higher proportion of female speakers in the clinical than in the basic science presentations at ACR.If the data were available, it would be additionally informative to see what percentage of submitted abstracts by gender were selected for presentation.This would help identify whether the gender gap is driven by number of submissions vs the selection process; this knowledge could eventually help reduce the gap further.Academic publications are used to disseminate scientific knowledge and are a way to measure research productivity.Publications can influence career prospects and visibility for authors.It would be also interesting to look at a country-stratified analysis of speaker gender using the EULAR data.Holman et al noted that countries, like Japan, Germany and Switzerland, which have higher per capita incomes, have fewer women authors representing the Science, Technology, Engineering, Mathematics and Medicine workforce. 3 In summary, these data presented by Conigliaro et al are similar to ours and further support that a gender gap does exist among speakers during annual rheumatology meetings.Even though it has improved over the years, we must remain aware of its presence and continue to work towards equal representations.We are, thus, appreciative of the efforts of the EULAR Task Force on Gender Equity in Academic Rheumatology and look forward to their future outputs.
Abstract A63: Overcoming challenges in health care with machine learning: Innovation from retinoblastoma
Authors: Isabella Janusonis, Tran Truong, Justin Liu, Mei Chen, Brenda Gallie
Journal: Cancer Research (2020)

Abstract Introduction: As retinoblastoma is a rare pediatric cancer (1/17,000 live births) with little evidence to justify treatment choices, we built a cloud-based retinoblastoma-specific electronic health record database for point-of-care data to support clinical and research collaboration and provide a quantitative analysis of prescribed treatments. Methods: Disease-specific Electronic Patient Illustrated Clinical Timeline (DEPICT HEALTH) is online, cloud-based, interactive, with point-of-care timelines and corresponding retinal/tumor drawings, with standardized scoring of tumor number, size, and locations. Results: DEPICT HEALTH records are contributed by the entire care team and used in quantitative treatment analyses. DEPICT HEALTH effectively communicates disease and treatment information to the patients’ circle of care and their parents, independent of language. The Retinoblastoma Activity Index (RAI) quantifies the active tumor (colored yellow) by counting the yellow pixels in the DEPICT HEALTH digital drawings. The drawings represent tumor at every encounter based on the collective opinion of the care team, and the RAI will quantitate tumor response to treatment. Two clinical trials were initiated using DEPICT HEALTH and RAI for eligibility and short- and long-term outcomes. Conclusion: Using RAI to score tumor response provides RECIST (response evaluation criteria in solid tumors) for retinoblastoma research, a standard of measurement that has never before been available. Machine learning methods will ultimately analyze point-of-care data to predict patient outcomes and assist with clinical decision making. DEPICT HEALTH provides an unbiased view of the efficacy of treatments, with potential to allow global point-of-care data to be widely available for research, essentially an “n” of “ALL.” Citation Format: Isabella Janusonis, Tran Truong, Justin Liu, Mei Chen, Brenda Gallie. Overcoming challenges in health care with machine learning: Innovation from retinoblastoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A63.
Complex landscape of alternative splicing in myeloid neoplasms
Authors: Courtney E. Hershberger, Devlin C. Moyer, Vera Adema, Cassandra M. Kerr, Wencke Walter, Stephan Hutter, Manja Meggendorfer, Constance Baer, Wolfgang Kern, Niroshan Nadarajah, Sven Twardziok, Mikkael A. Sekeres, Claudia Haferlach, Torsten Haferlach, Jaroslaw P. Maciejewski, Richard A. Padgett
Journal: Leukemia (2020)
Abstract B47: Overexpression of <i>TLX3</i> or <i>HOXA9</i> in association mutant <i>IL7R</i>α are sufficient to generate T-ALL in vivo
Authors: Gisele O.L. Rodrigues, Julie Hixon, Hila Winer, Wenqing Li, Scott Durum
Journal: Cancer Research (2020)

Abstract Background: Mutations of the IL7Rα chain occur in approximately 10% of pediatric T-cell acute lymphoblastic leukemia cases. While we have shown that mutant IL7Rα is sufficient to transform an immortalized thymocyte cell line, mutation of IL7Rα alone was insufficient to cause transformation of primary T cells, suggesting that additional genetic lesions may be present, contributing to initiate leukemia. Studies addressing the combinations of mutant IL7Rα plus TLX3 or HOXA9 overexpression indicate in vitro grow advantage, suggesting these two genes as potential collaborative candidates. Furthermore, patients with mutated IL7Rα were more likely to have TLX3 or HOXA subgroup leukemia. Objective: We sought to determine whether combination of mutant hIL7Rα plus TLX3 or HOXA9 overexpression is sufficient to generate T-cell leukemia in vivo. Methods: Double-negative thymocytes were isolated from C57BL/6J mice and transduced with retroviral vectors containing mutant hIL7Rα plus TLX3 or HOXA9. The same combinations were tested for the hIL7Rα wild-type. Transduced thymocytes were cultured on the OP9-DL4 bone marrow stromal cell line for 7-13 days and accessed for driver oncogenes expression and then injected into sublethally irradiated Rag-/- mice. Mice were euthanized at onset of clinical signs, and cells were immunophenotyped by flow cytometry. Results: Thymocytes transduced with muthIL7Rα-TLX3 showed overexpression of c-Myc and Pim-1. Nonetheless, there was no difference in the protein level expression for these two proteins in either thymocytes transduced with muthIL-7Rα-HOXA9 or in the control wthIL7Rα-TLX3. Mice injected with either muthIL7Ra-TLX3 or muthIL7Rα-HOXA9 cells, but not the controls (wthIL7Rα-TLX3 or wthIL7Rα-HOXA9), developed leukemia approximately 14 days post injection, characterized by GFP-expressing T-cells in blood, spleen, liver, lymph nodes, and bone marrow. Conclusion: Thymocytes transduced with muthIL7Rα-TLX3 showed c-Myc and Pim-1 upregulation. Cells expressing the combination muthIL7Rα-TLX3 or muthIL7Rα-HOXA9 were sufficient to trigger T-cell leukemia in vivo. Citation Format: Gisele O.L. Rodrigues, Julie Hixon, Hila Winer, Wenqing Li, Scott Durum. Overexpression of TLX3 or HOXA9 in association mutant IL7Rα are sufficient to generate T-ALL in vivo [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B47.
Metastatic Pancreatic Cancer: ASCO Guideline Update
Authors: Davendra P.S. Sohal, Erin B. Kennedy, Pelin Cinar, Thierry Conroy, Mehmet S. Copur, Christopher H. Crane, Ignacio Garrido-Laguna, Michelle W. Lau, Tyler Johnson, Smitha Krishnamurthi, Cassadie Moravek, Eileen M. O’Reilly, Philip A. Philip, Shubham Pant, Manish A. Shah, Vaibhav Sahai, Hope E. Uronis, Neeha Zaidi, Daniel Laheru
Journal: Journal of Clinical Oncology (2020)

PURPOSE The aim of this work was to provide an update to the ASCO guideline on metastatic pancreatic cancer pertaining to recommendations for therapy options after first-line treatment. METHODS ASCO convened an Expert Panel and conducted a systematic review to update guideline recommendations for second-line therapy for metastatic pancreatic cancer. RESULTS One randomized controlled trial of olaparib versus placebo, one report on phase I and II studies of larotrectinib, and one report on phase I and II studies of entrectinib met the inclusion criteria and inform the guideline update. RECOMMENDATIONS New or updated recommendations for germline and somatic testing for microsatellite instability high/mismatch repair deficiency, BRCA mutations, and TRK alterations are provided for all treatment-eligible patients to select patients for recommended therapies, including pembrolizumab, olaparib, larotrectinib, or entrectinib, or potential clinical trials. The Expert Panel continues to endorse the remaining recommendations for second-line chemotherapy, as well as other recommendations related to treatment, follow-up, and palliative care from the 2018 version of this guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .
Tacrolimus Impairs Kupffer Cell Capacity to Control Bacteremia: Why Transplant Recipients Are Susceptible to Infection
Authors: Carsten Deppermann, Moritz Peiseler, Joel Zindel, Lori Zbytnuik, Woo‐Yong Lee, Elisa Pasini, Cristina Baciu, John Matelski, Yun Lee, Deepali Kumar, Atul Humar, Bas Surewaard, Paul Kubes, Mamatha Bhat
Journal: Hepatology (2020)

Kupffer cells (KCs) are the resident intravascular phagocyte population of the liver and critical to the capture and killing of bacteria. Calcineurin/nuclear factor of activated T cells (NFAT) inhibitors (CNIs) such as tacrolimus are used to prevent rejection in solid organ transplant recipients. Although their effect on lymphocytes has been studied extensively, there are limited experimental data about if and how CNIs shape innate immunity, and whether this contributes to the higher rates of infection observed in patients taking CNIs.Here, we investigated the impact of tacrolimus treatment on innate immunity and, more specifically, on the capability of Kupffer cells (KCs) to fight infections. Retrospective analysis of data of >2,700 liver transplant recipients showed that taking calcineurin inhibitors such as tacrolimus significantly increased the likelihood of Staphylococcus aureus infection. Using a mouse model of acute methicillin-resistant S. aureus (MRSA) bacteremia, most bacteria were sequestered in the liver and we found that bacteria were more likely to disseminate and kill the host in tacrolimus-treated mice. Using imaging, we unveiled the mechanism underlying this observation: the reduced capability of KCs to capture, phagocytose, and destroy bacteria in tacrolimus-treated animals. Furthermore, in a gene expression analysis of infected KCs, the triggering receptor expressed on myeloid cells 1 (TREM1) pathway was the one with the most significant down-regulation after tacrolimus treatment. TREM1 inhibition likewise inhibited KC bacteria capture. TREM1 levels on neutrophils as well as the overall neutrophil response after infection were unaffected by tacrolimus treatment.Our results indicate that tacrolimus treatment has a significant impact directly on KCs and on TREM1, thereby compromising their capacity to fend off infections.
FRI0185 DIAGNOSTIC SIGNIFICANCES OF BOTH MICRORNA-146A AND KALLIKREIN-1 IN PATIENTS WITH LUPUS NEPHRITIS
Authors: S. Soliman, A. Higazi, M. Nasr, N. M. Abd El Hamid, H. Kamel, A. Abd El Samie El Sherif
Journal: Annals of the Rheumatic Diseases (2020)

Background: Lupus nephritis (LN) is one of the most critical complications of systemic lupus erythematosus (SLE). Approximately 30–50% of SLE patients develop LN with 5-year survival rate of about 70-80%. Thus, finding reliable non-invasive biomarkers at the early stages of SLE is of great interest (1). Many studies focused on the association between microRNAs and the risk of LN. miRNA-146a (miR-146a) was one of the most promising circulating markers which was suggested recently for early diagnosis of SLE but its diagnostic relevancies regarding LN have not been extensively investigated. Objectives: This study aims to test the expression of miR-146a in patients with LN in relation to Kallikrein-1 as another widely investigated diagnostic marker for LN along with other conventional measures. Methods: One hundred and thirty subjects were enrolled in this study. They were divided into forty six patients with LN, forty four patients with SLE but without nephritis and forty healthy controls. The expression levels of miR-146a in peripheral blood mononuclear cells (PBMCs) were detected via RT-qPCR analysis. Besides, serum Kallikrein-1 levels were determined by ELISA. The diagnostic role of miR-146a and Kallikrein-1 in LN was evaluated by Receiver operating curve (ROC). The impact of miR-146a and Kallikrein-1 on renal disease was compared to albumin creatinine ratio, renal biopsy findings as well as renal SLEDAI. Results: Levels of miR-146a were significantly lower in the plasma of LN patients than both patients of SLE without LN and normal controls (p &lt; 0.05). However, serum levels of Kallikrein-1 were significantly higher in LN patients when compared to SLE patients and normal population (p &lt; 0.05). ROCs were conducted to assess the diagnostic values of both miR-146a and kallikrein-1. They revealed good diagnostic values with AUC of 0.888 and 0.913 respectively. Also, plasma miR-146a was observed to be negatively associated with serum creatinine, proteinuria as well as SLEDAI score (p &lt; 0.01) while serum Kallikrein-1 was positively correlated with them (p &lt; 0.05) and inversely correlated with miR-146a (p &lt; 0.01). Conclusion: The expression levels of miR-146a are reduced in SLE patients with more reduction with LN. Therefore, miR-146a could be considered as potential biomarker for detecting LN either alone or in combination with Kallikrein-1. However, more studies are required. References: [1]Soliman S. And Mohan C. Lupus nephritis Biomarkers.Clin Immunol.2017 Dec; 185: 10-20. Disclosure of Interests: None declared