tbuckley/cabot-search huggingface dataset:
Vein of Galen Malformation
Authors: Laura Stone McGuire, Demetrios Nikas
Journal: New England Journal of Medicine (2020)

A neonate born at 37 weeks of gestation had respiratory distress 3 hours after birth. A chest radiograph and an echocardiogram showed signs of cardiac failure. Cranial ultrasonography and magnetic resonance imaging revealed a large vein of Galen malformation.
Aetiology and pathogenesis of hidradenitis suppurativa
Authors: K. Wolk, O. Join‐Lambert, R. Sabat
Journal: British Journal of Dermatology (2020)

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Patients develop inflamed nodules and abscesses and, at later stages of disease, epithelialized tunnels and scars in skinfolds of axillary, inguinal, gluteal and perianal areas. Quality of life is affected due to severe pain, purulent secretion, restricted mobility and systemic involvement. Genetics and lifestyle factors including smoking and obesity contribute to the development of HS. These factors lead to microbiome alteration, subclinical inflammation around the terminal hair follicles, and infundibular hyperkeratosis, resulting in plugging and rupture of the follicles. Cell‐damage‐associated molecules and propagating bacteria trigger inflammation and lead to massive immune cell infiltration that clinically manifests as inflamed nodules and abscesses. The immune system plays a key role also in the progression and chronification of skin alterations. Innate proinflammatory cytokines (e.g. interleukin‐1β and tumour necrosis factor‐α), mediators of activated T helper (Th)1 and Th17 cells (e.g. interleukin‐17 and interferon‐γ), and effector mechanisms of neutrophilic granulocytes, macrophages and plasma cells are involved. Simultaneously, skin lesions contain anti‐inflammatory mediators (e.g. interleukin‐10) and show limited activity of Th22 and regulatory T cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction and scarring. Chronic inflammation in patients with HS is also frequently detected in organs other than the skin, as indicated by their comorbidities. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. This scholarly review focuses on the causes and pathogenetic mechanisms of HS and the potential therapeutic value of this knowledge.
Macrophage membrane functionalized biomimetic nanoparticles for targeted anti-atherosclerosis applications
Authors: Yi Wang, Kang Zhang, Tianhan Li, Ali Maruf, Xian Qin, Li Luo, Yuan Zhong, Juhui Qiu, Sean McGinty, Giuseppe Pontrelli, Xiaoling Liao, Wei Wu, Guixue Wang
Journal: Theranostics (2020)

Atherosclerosis (AS), the underlying cause of most cardiovascular events, is one of the most common causes of human morbidity and mortality worldwide due to the lack of an efficient strategy for targeted therapy. In this work, we aimed to develop an ideal biomimetic nanoparticle for targeted AS therapy. Methods: Based on macrophage "homing" into atherosclerotic lesions and cell membrane coating nanotechnology, biomimetic nanoparticles (MM/RAPNPs) were fabricated with a macrophage membrane (MM) coating on the surface of rapamycin-loaded poly (lactic-co-glycolic acid) copolymer (PLGA) nanoparticles (RAPNPs). Subsequently, the physical properties of the MM/RAPNPs were characterized. The biocompatibility and biological functions of MM/RAPNPs were determined in vitro. Finally, in AS mouse models, the targeting characteristics, therapeutic efficacy and safety of the MM/RAPNPs were examined. Results: The advanced MM/RAPNPs demonstrated good biocompatibility. Due to the MM coating, the nanoparticles effectively inhibited the phagocytosis by macrophages and targeted activated endothelial cells in vitro. In addition, MM-coated nanoparticles effectively targeted and accumulated in atherosclerotic lesions in vivo. After a 4-week treatment program, MM/RAPNPs were shown to significantly delay the progression of AS. Furthermore, MM/RAPNPs displayed favorable safety performance after long-term administration. Conclusion: These results demonstrate that MM/RAPNPs could efficiently and safely inhibit the progression of AS. These biomimetic nanoparticles may be potential drug delivery systems for safe and effective anti-AS applications.
Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen
Authors: Xiaoling Xie, Yuxing Hu, Tong Ye, Yiran Chen, Lijuan Zhou, Feng Li, Xiaobo Xi, Shuang Wang, Yanjie He, Xiaoyong Gao, Wei Wei, Guanghui Ma, Yuhua Li
Journal: Nature Biomedical Engineering (2020)
Heritable Human Genome Editing
Authors: Eli Y. Adashi, I. Glenn Cohen
Journal: JAMA (2020)

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
Compliance with every 12-week zoledronic acid dosing guidelines for bone metastasis in breast cancer patients.
Authors: Monika Kumar, Pallavi Dev, Radhika Kainthla
Journal: Journal of Clinical Oncology (2020)

81 Background: Bisphosphonates, including zoledronic acid (Zometa), decrease skeletal-related events in breast cancer patients with bone metastasis but are also associated with side effects and utilization costs. Data from a randomized trial supporting 12-week versus 4-week dosing of Zometa was released in July 2016 and officially published in January 2017. We examined the practice pattern of Zometa dosing over time in our practice to determine compliance and develop interventions for improvement. Methods: We conducted a retrospective chart review on all breast cancer patients treated at Parkland Health and Hospital System oncology clinic to identify patients who were initiated on Zometa for bone metastasis between June 2015 and September 2019. The initially prescribed dosing frequencies were assessed for time periods before and after the Zometa dosing data was made available. The prescribing patterns were also compared between teaching and non-teaching clinics. An educational review of the guidelines was presented to providers in all clinics in March 2020 to improve compliance. Results: In the year prior to July 2016, of the 27 patients who started Zometa, only 1 (4%) was on every 12-week dosing. In the six months after release of the data, 29% (6/21 patients) were placed on 12-week Zometa dosing. Between January 2019 and September 2019, 52% of patients were started on the recommended 12-week dosing interval. These patterns were consistent between teaching and non-teaching clinics. Conclusions: We found that the variability in Zometa prescribing patterns persisted despite updated national guidelines and multiple studies supporting 12-week dosing intervals. In addition to educational interventions, we plan to implement electronic interventions to improve rates of compliance with the goal of 80% adherence by September 2020. Improved adherence will likely lead to a reduction in potential complications from treatment as well as infusion costs (estimated $482.81 saved per patient annually).
Racial differences in hospitalizations associated with COVID-19 in patients with cancer.
Authors: Chintan Pandya, Sishemo Mwesigwa, David W. Dougherty
Journal: Journal of Clinical Oncology (2020)

122 Background: Reports concerning possible racial disparities in Covid-19 illness severity and health consequences for U.S. minority population have been emerging. Similar data for patients with cancer diagnosis have been scant. We aimed to evaluate the effect of race on primary outcome of hospitalization in patients with cancer who tested positive for Covid-19. Methods: Retrospective observational quality of care study of electronic health records for patients with cancer who tested positive for Covid-19 between March 1 and June 10, 2020 and had at least one visit in the past 1-year at the cancer center. Demographics, non-cancer comorbidities, cancer type and treatment were captured. Primary outcome of hospitalization and secondary outcome of emergency department (ED) visits were assessed from index event up to 30 days after index event, which is laboratory-confirmed diagnosis of Covid-19. Logistic regression analysis was performed to evaluate the association of race with outcomes after adjusting for confounding factors. Results: 557 patients tested positive for Covid-19 and had at least one visit at the cancer institute in past one year. Of the total positive patients, 325 (58%) were females, 79 (14%) were blacks, and 225 (40%) had 2 or more comorbidities. The most common cancers were gastrointestinal (N=105) and other cancers (N=194); 47 had any systemic cancer treatment in the past 30 days before Covid-19 test. 56 patients had ED visit out of which 26% were blacks (p=0.002) and 96 had inpatient hospital visit out of which blacks were 19% (p=0.13). The mean length of hospital stay (LOS) was 7.86±11.6 days. On multivariate analysis, after controlling for demographics, comorbidities, and cancer variables, black race was independently associated with higher odds of hospitalization (Odds Ratio=2.19, confidence interval=1.2 to 3.8). Conclusions: In a large cohort of patients with cancer who tested positive for Covid-19, while 14% were blacks, they contributed to 17% hospitalizations and 26% ED visits associated with Covid-19. Black race was independently associated with higher odds of hospitalization due to Covid-19 than white race, after adjusting for confounding factors.
Evaluating risk characteristics for patients who die within 30 days of hospitalization.
Authors: Christine Kurian, Jennifer Hong, Andrea McSweeney, Laetitia N'Dri, Karen Walsh, Adam Binder
Journal: Journal of Clinical Oncology (2020)

161 Background: Advanced cancer patients often receive aggressive end of life care despite questionable benefit. As a result, there are ongoing efforts to improve end of life care and coordinate palliative care supportive services. This study is an expansion of a previous study performed examining descriptive data in a population of oncology patients who died within 30 days of admission. Here, we compare patients who died within 30 days of admission against those who survived to evaluate differences in patient characteristics and healthcare utilization. Methods: Adult oncology patients who were admitted from 10/1/2018-3/30/2019 at an academic medical center were evaluated. Two groups of patients were studied–oncology patients who died within thirty days of admission and those who survived. The patients were selected using ICD-10 codes, EMR systems support, and manual chart review. Additionally, we examined demographic (i.e. gender, ethnicity, cancer diagnosis) and clinical characteristics (i.e. level of care, code status, previous palliative care consult, palliative care consult in the hospital, nutrition status, clinical trial status, advance care planning, hospice enrollment). Statistical analysis included chi-squared and ANOVA tests, and logistic regression models. Results: A total of 267 patients were included in the analysis. For all patients in the study, 38% had a change in code status during their admission. 26% of patients had palliative care involvement and 23% were known to palliative care prior to admission. Twenty three percent spent the duration of their admission in the ICU for their end of life care. Significant mortality-level variation was found compared to overall mean number of admissions for the past 6 months (ANOVA F=25.3, p&lt;0.0001). We conducted a logistic regression and adjusted for ethnicity, number of admits in the last 6 months, and length of stay to identify the outcome of patients who died within 30 days of admission vs. those who did not. Factors associated with increased odds of mortality included the number of admits in the last 6 months (OR 1.753, 95% CI: 1.397-2.200). Length of stay did not increase one’s odds for mortality (OR 0.989, 95% CI: 0.965-1.014). Conclusions: Low utilization of palliative care and advanced care planning was seen widely in both populations. Previous hospitalization in the last 6 months was a predictor of mortality in this patient population.
Better treatment at what cost? A study of myeloma spending.
Authors: Rohini Naipaul, Elena Mow, Rebecca Mercer, Lyndee Yeung, Scott Gavura, C. Tom Kouroukis
Journal: Journal of Clinical Oncology (2020)

60 Background: Multiple myeloma represents less than 1.5% of new cancer cases in Canada. Currently, the estimated median overall survival is at least 5-6 years, primarily driven by therapeutic advances over the past decade. As treatment protocols routinely use doublet and triplet combinations, there are increasing concerns about the ability of health systems to afford growing costs of treatment. To inform system planning in Ontario, we examined trends in costs and utilization of myeloma drugs funded by Ontario’s New Drug Funding Program (NDFP) and the Ontario Drug Benefit program (ODB). Methods: NDFP primarily funds IV cancer drugs while ODB funds take-home cancer drugs (THCD). Treatment volumes and government costs, including drug costs and pharmacy fees where applicable, were obtained from ODB and NDFP claims data. Based on the available data, trends were examined from the 2010/11 to the second quarter of the 2019/20 fiscal year. Results: A total of 7 myeloma drugs (3-IV cancer drugs, 4-THCD) were examined. Over 9 years (2010/11 - 2018/19), spending on publicly-funded myeloma drugs increased by 303% while treatment volumes increased by 116%. Between 2014/15 and 2018/19, bortezomib spending decreased by 72%, largely due to generic pricing policies, while lenalidomide spending increased by 158%, likely due to new indications. By 2018/19, these 7 drugs accounted for 17% of the total cancer drug costs under Ontario's publicly funded programs. NDFP spending on IV cancer drugs by the second quarter of 2019/20 has surpassed the annual expenditures in 2018/19 due to the addition of daratumumab. Conclusions: Since 2010/11, growth in Ontario's public expenditures on myeloma drugs has outpaced savings from pricing policies and this growth is mainly driven by the high cost of the novel agents.
SLC14A1 prevents oncometabolite accumulation and recruits HDAC1 to transrepress oncometabolite genes in urothelial carcinoma
Authors: Ti-Chun Chan, Wen-Jeng Wu, Wei-Ming Li, Meng-Shin Shiao, Yow-Ling Shiue, Chien-Feng Li
Journal: Theranostics (2020)

Urothelial carcinoma (UC), including upper tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC), is a common malignant disease in developed countries. Oncogenic metabolic lesions have been associated with UC development. Methods: Using data mining, a series of studies were performed to study the involvement of SLC14A1 in UC specimens, animal models and UC-derived cell lines. Results: In two cohorts of UTUC (n = 340) and UBUC (n = 295), the SLC14A1 protein level was an independent prognostic factor. Epigenetic silencing contributed to SLC14A1 downregulation in UCs. Total and membranous SLC14A1 played tumor suppressive roles through the inhibition of cell proliferation and metastasis in distinct UC-derived cells and animal models. Functional SLC14A1 prevented the accumulation of arginine and urea, enhanced mitochondrial fusion and aerobic respiration, inhibited glycolysis by altering the expression levels of several related proteins and sensitized arginine-deprivation treatment in ASS1-deficient UC-derived cells. In vitro and in vivo, SLC14A1 inhibited the mTOR signaling pathway and subsequently tumorigenesis, supported by reduced arginine concentrations in vitro. Nuclear SLC14A1 transrepressed HK2 and DEGS1 genes via recruitment of HDAC1 and/or SIN3A to maintain metabolic homeostasis and thereafter impeded tumorigenesis. Conclusion: Clinical associations, animal models and in vitro indications provide solid evidence that the SLC14A1 gene is a novel tumor suppressor in UCs. Total and membranous SLC14A1 prevents urea and arginine accumulation via the mTOR signaling pathway. Nuclear SLC14A1 recruits HDAC1 to transrepress oncometabolite genes.
Lung Clearance Index to Track Acute Respiratory Events in School-Age Children with Cystic Fibrosis
Authors: Lucy Perrem, Sanja Stanojevic, Michelle Shaw, Renee Jensen, Nancy McDonald, Sarah M. Isaac, Miriam Davis, Charles Clem, Julia Guido, Sylvia Jara, Lisa France, Melinda Solomon, Hartmut Grasemann, Valerie Waters, Neil Sweezey, Don B. Sanders, Stephanie D. Davis, Felix Ratjen
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: The lung clearance index (LCI) is responsive to acute respiratory events in preschool children with cystic fibrosis (CF), but its utility to identify and manage these events in school-age children with CF is not well defined.Objectives: To describe changes in LCI with acute respiratory events in school-age children with CF.Methods: In a multisite prospective observational study, the LCI and FEV1 were measured quarterly and during acute respiratory events. Linear regression was used to compare relative changes in LCI and FEV1% predicted at acute respiratory events. Logistic regression was used to compare the odds of a significant worsening in LCI and FEV1% predicted at acute respiratory events. Generalized estimating equation models were used to account for repeated events in the same subject.Measurements and Main Results: A total of 98 children with CF were followed for 2 years. There were 265 acute respiratory events. Relative to a stable baseline measure, LCI (+8.9%; 95% confidence interval, 6.5 to 11.3) and FEV1% predicted (-6.6%; 95% confidence interval, -8.3 to -5.0) worsened with acute respiratory events. A greater proportion of events had a worsening in LCI compared with a decline in FEV1% predicted (41.7% vs. 30.0%; P = 0.012); 53.9% of events were associated with worsening in LCI or FEV1. Neither LCI nor FEV1 recovered to baseline values at the next follow-up visit.Conclusions: In school-age children with CF, the LCI is a sensitive measure to assess lung function worsening with acute respiratory events and incomplete recovery at follow-up. In combination, the LCI and FEV1 capture a higher proportion of events with functional impairment.
STAT1 Gain of Function, Type 1 Diabetes, and Reversal with JAK Inhibition
Authors: Natalia S. Chaimowitz, Sophia J. Ebenezer, I. Celine Hanson, Mark Anderson, Lisa R. Forbes
Journal: New England Journal of Medicine (2020)

similar to an RT-qPCR cycle-threshold (Ct) value of 40.3 (Fig. S10D andS10E).In blinded testing at an external laboratory at the University of Washington, we tested 202 SARS-CoV-2-positive and 200 SARS-CoV-2-negative nasopharyngeal swab samples obtained from patients.These samples were prepared by adding 50 μl of swab specimens obtained from patients with Covid-19 to a clean swab, in accordance with the recommendation of the Food and Drug Administration for simulating whole swabs for regulatory applications (see the Methods section in the Supplementary Appendix).This testing showed that STOPCovid.v2had a sensitivity of 93.1% and a specificity of 98.5% (Fig. 1B and 1C, Fig. S11A, andTable 1).STOP-Covid.v2 false negative samples had RT-qPCR Ct values greater than 37. Positive samples were detected in 15 to 45 minutes.Finally, we used fresh, dry, anterior nasal swabs (collected according to the recommendations of the CDC) to validate STOPCovid.v2,and we correctly identified 5 positive samples (Ct values, 19 to 36) and 10 negative samples (Fig. S11B through S11E).A detailed protocol for STOPCovid.
Development and Validation of a Next-Generation Sequencing–Based Multigene Assay to Predict the Prognosis of Estrogen Receptor–Positive, HER2-Negative Breast Cancer
Authors: Han-Byoel Lee, Sae Byul Lee, Minsu Kim, Sunyoung Kwon, Jeonghee Jo, Jinkyoung Kim, Hee Jin Lee, Han-Suk Ryu, Jong Won Lee, Chungyeul Kim, Jaehwan Jeong, Hyoki Kim, Dong-Young Noh, In-Ae Park, Sei-Hyun Ahn, Sun Kim, Sungroh Yoon, Aeree Kim, Wonshik Han
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Multigene assays provide useful prognostic information regarding hormone receptor (HR)-positive breast cancer. Next-generation sequencing (NGS)-based platforms have numerous advantages including reproducibility and adaptability in local laboratories. This study aimed to develop and validate an NGS-based multigene assay to predict the distant recurrence risk. Experimental Design: In total, 179 genes including 30 reference genes highly correlated with the 21-gene recurrence score (RS) algorithm were selected from public databases. Targeted RNA-sequencing was performed using 250 and 93 archived breast cancer samples with a known RS in the training and verification sets, respectively, to develop the algorithm and NGS–Prognostic Score (NGS-PS). The assay was validated in 413 independent samples with long-term follow-up data on distant metastasis. Results: In the verification set, the NGS-PS and 21-gene RS displayed 91.4% concurrence (85/93 samples). In the validation cohort of 413 samples, area under the receiver operating characteristic curve plotted using NGS-PS values classified for distant recurrence was 0.76. The best NGS-PS cut-off value predicting distant metastasis was 20. Furthermore, 269 and 144 patients were classified as low- and high-risk patients in accordance with the cut-off. Five- and 10-year estimates of distant metastasis–free survival (DMFS) for low- versus high-risk groups were 97.0% versus 77.8% and 93.2% versus 64.4%, respectively. The age-related HR for distant recurrence without chemotherapy was 9.73 (95% CI, 3.59–26.40) and 3.19 (95% CI, 1.40–7.29) for patients aged ≤50 and &amp;gt;50 years, respectively. Conclusions: The newly developed and validated NGS-based multigene assay can predict the distant recurrence risk in ER-positive, HER2-negative breast cancer.
Mitigating Postintensive Care Syndrome Among Patients And Caregivers via a Dyadic Intervention
Authors: David Y. Hwang
Journal: JAMA Network Open (2020)

Ana-Maria Vranceanu, PhD; Sarah Bannon, PhD; Ryan Mace, PhD; Ethan Lester, PhD; Emma Meyers, PhD; Melissa Gates, BA; Paula Popok, BA; Ann Lin, BS; Danielle Salgueiro, RN; Tara Tehan, RN; Eric Macklin, PhD; Jonathan Rosand, MD