tbuckley/cabot-search huggingface dataset:
Immunologic memory to SARS-CoV-2 in convalescent COVID-19 patients at 1 year postinfection
Authors: Hongyan Hou, Yandi Zhang, Guoxing Tang, Ying Luo, Wei Liu, Chang Cheng, Yuhuan Jiang, Zhigang Xiong, Shiji Wu, Ziyong Sun, Shabei Xu, Xionglin Fan, Feng Wang
Journal: Journal of Allergy and Clinical Immunology (2021)

Understanding the complexities of immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to gain insights into the durability of protective immunity against reinfection.We sought to evaluate the immune memory to SARS-CoV-2 in convalescent patients with longer follow-up time.SARS-CoV-2-specific humoral and cellular responses were assessed in convalescent patients with coronavirus disease 2019 (COVID-19) at 1 year postinfection.A total of 78 convalescent patients with COVID-19 (26 moderate, 43 severe, and 9 critical) were recruited after 1 year of recovery. The positive rates of both anti-receptor-binding domain and antinucleocapsid antibodies were 100%, whereas we did not observe a statistical difference in antibody levels among different severity groups. Accordingly, the prevalence of neutralizing antibodies (nAbs) reached 93.59% in convalescent patients. Although nAb titers displayed an increasing trend in convalescent patients with increased severity, the difference failed to achieve statistical significance. Notably, there was a significant correlation between nAb titers and anti-receptor-binding domain levels. Interestingly, SARS-CoV-2-specific T cells could be robustly maintained in convalescent patients, and their number was positively correlated with both nAb titers and anti-receptor-binding domain levels. Amplified SARS-CoV-2-specific CD4+ T cells mainly produced a single cytokine, accompanying with increased expression of exhaustion markers including PD-1, Tim-3, TIGIT, CTLA-4, and CD39, while the proportion of multifunctional cells was low.Robust SARS-CoV-2-specific humoral and cellular responses are maintained in convalescent patients with COVID-19 at 1 year postinfection. However, the dysfunction of SARS-CoV-2-specific CD4+ T cells supports the notion that vaccination is needed in convalescent patients for preventing reinfection.
P14.90 Survival outcomes and prognostic factors in glioblastoma patients treated with radiotherapy plus concomitant and adjuvant temozolomide - real-world study
Authors: M J Sousa, J Magalhães, R Basto, C Costa, A Pego, G Sousa
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumour in adults. The current standard of care for newly diagnosed GBM is maximal surgical resection, followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ). This study aimed to evaluate the survival outcomes and identify predictors of survival among these patients. MATERIAL AND METHODS We performed a single-centre retrospective analysis of GBM patients treated with radiotherapy plus concomitant and adjuvant TMZ from 2013 to 2020. The analyses of progression-free survival (PFS) and overall survival (OS), each one evaluated starting from initial diagnosis, were performed. Survival curves were estimated with the Kaplan- Meier method and compared using the log-rank test. RESULTS Fifty-eight patients were identified. The median age was 61 years (range 18- 80), 51 (88%) patients were in ECOG-PS 0–1, 6 (10%) patients had isocitrate dehydrogenase (IDH) mutation and 53 (91%) of patients had undergone debulking surgery. At a median follow-up of 21 months, median OS was 12.8 months (95% confidence interval [CI] 9.7–15.9), whereas median PFS was 9.5 months (95% CI 8.5–10.5). The 1-year survival rate was 42% and the 2-year survival rate was 10%. Grade 3 or 4 hematologic toxicity occurred in 11 (19%) patients. Twenty-five (42%) patients completed at least 6 cycles of TMZ monotherapy with statistically significant differences between this sub-group and those who weren’t able to continue TMZ monotherapy [median OS 19.3 months (95% CI 14.4–24.2) vs 10.6 months (95% CI 7.8–13.4) p&amp;lt;0.001]. ECOG-PS = 0 [median OS 16.7 months (95% CI 13.4–20.0, p=0.001)] and patients under 65 years of age [median OS 15.6 months (95% CI 12.3–18.9, p=0.02) were associated with significantly better median OS. CONCLUSION The current standard of care treatment for GBM remains poor. An important factor predictor of survival is the completion of the 6 maintenance cycles of TMZ. At baseline, ECOG PS and the patient’s age could be used to define patient prognosis.
SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3
Authors: Ann R Falsey, Robert W Frenck, Edward E Walsh, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, Ruth Bailey, Kena A Swanson, Xia Xu, Kenneth Koury, Warren Kalina, David Cooper, Jing Zou, Xuping Xie, Hongjie Xia, Özlem Türeci, Eleni Lagkadinou, Kristin R Tompkins, Pei-Yong Shi, Kathrin U Jansen, Uğur Şahin, Philip R Dormitzer, William C Gruber
Journal: New England Journal of Medicine (2021)

Immune Response to a Third Dose of BNT162b2 A third dose of the BNT162b2 vaccine was administered to 23 volunteers 8 to 9 months after the second dose, and the immune response was assessed. Local r...
PKM2 promotes neutrophil activation and cerebral thromboinflammation: therapeutic implications for ischemic stroke
Authors: Nirav Dhanesha, Rakesh B. Patel, Prakash Doddapattar, Madankumar Ghatge, Gagan D. Flora, Manish Jain, Daniel Thedens, Heena Olalde, Mariia Kumskova, Enrique C. Leira, Anil K. Chauhan
Journal: Blood (2021)

There is a critical need for cerebro-protective interventions to improve the suboptimal outcomes of patients with ischemic stroke who have been treated with reperfusion strategies. We found that nuclear pyruvate kinase muscle 2 (PKM2), a modulator of systemic inflammation, was upregulated in neutrophils after the onset of ischemic stroke in both humans and mice. Therefore, we determined the role of PKM2 in stroke pathogenesis by using murine models with preexisting comorbidities. We generated novel myeloid cell-specific PKM2-/- mice on wild-type (PKM2fl/flLysMCre+) and hyperlipidemic background (PKM2fl/flLysMCre+Apoe-/-). Controls were littermate PKM2fl/flLysMCre- or PKM2fl/flLysMCre-Apoe-/- mice. Genetic deletion of PKM2 in myeloid cells limited inflammatory response in peripheral neutrophils and reduced neutrophil extracellular traps after cerebral ischemia and reperfusion, suggesting that PKM2 promotes neutrophil hyperactivation in the setting of stroke. In the filament and autologous clot and recombinant tissue plasminogen activator stroke models, irrespective of sex, deletion of PKM2 in myeloid cells in either wild-type or hyperlipidemic mice reduced infarcts and enhanced long-term sensorimotor recovery. Laser speckle imaging revealed improved regional cerebral blood flow in myeloid cell-specific PKM2-deficient mice that was concomitant with reduced post-ischemic cerebral thrombo-inflammation (intracerebral fibrinogen, platelet [CD41+] deposition, neutrophil infiltration, and inflammatory cytokines). Mechanistically, PKM2 regulates post-ischemic inflammation in peripheral neutrophils by promoting STAT3 phosphorylation. To enhance the translational significance, we inhibited PKM2 nuclear translocation using a small molecule and found significantly reduced neutrophil hyperactivation and improved short-term and long-term functional outcomes after stroke. Collectively, these findings identify PKM2 as a novel therapeutic target to improve brain salvage and recovery after reperfusion.
Tattoo you?
Authors: James C. H. Hardwick
Journal: Endoscopy (2021)

Tattoos are all the rage. Once the exclusive territory of sailors, there are now nearly twenty television programs devoted to tattoos and it almost seems as if no self-respecting professional sportsman would be seen without one. The placement of tattoos endoscopically in the colon has been described for over 50 years. With the rise of laparoscopic resection for colorectal cancer, surgeons have increasingly recommended the preoperative placement of a tattoo to enable them to swiftly and accurately locate colorectal tumors and prevent the inadvertent resection of the wrong segment or inadequate resection margins. In a meta-analysis, tattoo placement lowered the risk of location errors from 16% to 10% [1].
Automated lung sound analysis using the LungPass platform: a sensitive and specific tool for identifying lower respiratory tract involvement in COVID-19
Authors: Elena A. Lapteva, Olga N. Kharevich, Victoria V. Khatsko, Natalia A. Voronova, Maksim V. Chamko, Irina V. Bezruchko, Elena I. Katibnikova, Elena I. Loban, Mostafa M. Mouawie, Helena Binetskaya, Sergey Aleshkevich, Aleksey Karankevich, Vitaly Dubinetski, Jørgen Vestbo, Alexander G. Mathioudakis
Journal: European Respiratory Journal (2021)

Lower respiratory tract (LRT) involvement, observed in about 20% of patients suffering from coronavirus disease 2019 (COVID-19), is associated with a more severe clinical course, adverse outcomes and long-term sequelae [1, 2]. By pointing out people at risk of deterioration, early identification of LRT involvement could facilitate targeted and timely administration of treatments that could alter short- and long-term disease outcomes [3]. While imaging represents the gold standard diagnostic test for LRT involvement, it is associated with a potentially avoidable radiation burden and may not be easily accessible in some treatment settings, such as primary care [4]. Alternatively, oxygen desaturation appears to be a specific, but not sensitive marker, since ground glass changes or consolidation are often observed in the absence of hypoxia [5–7]. The sensitivity of chest auscultation in identifying LRT involvement has been evaluated in limited populations and varies [8, 9], possibly to some extent due to variable skill among the assessors. Automated lung sound analysis using the #LungPass platform is a sensitive and specific tool for identifying lower respiratory tract involvement in COVID-19 <https://bit.ly/3tyAgOD>
U.S. Food and Drug Administration Reasoning in Approval Decisions When Efficacy Evidence Is Borderline, 2013–2018
Authors: Perrine Janiaud, Telba Irony, Estelle Russek-Cohen, Steven N. Goodman
Journal: Annals of Internal Medicine (2021)

The U.S. Food and Drug Administration (FDA) has substantial flexibility in its approval criteria in the context of life-threatening disease and unmet therapeutic need.To understand the FDA's evidentiary standards when flexible criteria are employed.Case series.Applications submitted between 2013 and 2018 that went through multiple review cycles because the evidence for clinical efficacy was initially deemed insufficient.Information was obtained from the approval package (available on Drugs@FDA), including advisory committee minutes, FDA reviews, and complete response letters.Of 912 applications reviewed, 117 went through multiple review cycles; only 22 of these faced additional review primarily because of issues related to clinical efficacy. Concerns about the end point, the clinical meaningfulness of the observed effect, and inconsistent results were common bases for initial rejection. In 7 of the 22 cases, the approval did not require new evidence but rather new interpretations of the original evidence. No FDA decisions cited reasoning used in previous decisions.The conclusions rely on the authors' interpretation of the FDA statements and on a series of "close calls."The FDA has no mechanism to find or tradition to cite similar cases when weighing evidence for approvals, resulting in standalone, bespoke decisions. These decisions show highly variable criteria for "substantial evidence" when flexible evidential criteria are used, highlighted by the recent approval of aducanumab. A precedential tradition and suitable information system are required for the FDA to improve institutional memory and build upon past decisions. These would increase the FDA's decisional transparency, consistency, and predictability, which are critical to preserving the FDA's most valuable asset, the public's trust.U.S. Food and Drug Administration.
Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial
Authors: Lucia Del Mastro, Mauro Mansutti, Giancarlo Bisagni, Riccardo Ponzone, Antonio Durando, Laura Amaducci, Enrico Campadelli, Francesco Cognetti, Antonio Frassoldati, Andrea Michelotti, Silvia Mura, Ylenia Urracci, Giovanni Sanna, Stefania Gori, Sabino De Placido, Ornella Garrone, Alessandra Fabi, Carla Barone, Stefano Tamberi, Claudia Bighin, Fabio Puglisi, Gabriella Moretti, Grazia Arpino, Alberto Ballestrero, Francesca Poggio, Matteo Lambertini, Filippo Montemurro, Paolo Bruzzi
Journal: The Lancet Oncology (2021)
Disparities in Physician Compensation by Gender in Ontario, Canada
Authors: Mitch Steffler, Nadine Chami, Samantha Hill, Gail Beck, Stephen C. Cooper, Robert Dinniwell, Sarah Newbery, Sarah Simkin, Brittany Chang-Kit, James G. Wright, Jasmin Kantarevic, Sharada Weir
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Men and women should earn equal pay for equal work. An examination of the magnitude of pay disparities could inform strategies for remediation. <h3>Objective</h3> To examine gender-based differences in pay within a large, comprehensive physician population practicing within a variety of payment systems. <h3>Design, Setting, and Participants</h3> This cross-sectional study used data from the Ontario Health Insurance Plan (OHIP) in the 2017 to 2018 fiscal year to estimate differences in gross payments between men and women physicians in Ontario, Canada. Pay gaps were calculated annually and daily. Regression analyses were used to control for observable practice characteristics that could account for individual differences in daily pay. In Canada's largest province, Ontario, medical services are predominantly provided by self-employed physicians who bill the province's single payer, OHIP. All physicians who submitted claims to OHIP were included. Data were analyzed from January 2020 to July 2021. <h3>Exposures</h3> Physician gender, obtained from the OHIP Corporate Provider Database. Gender is recorded as male or female. <h3>Main Outcomes and Measures</h3> Gross clinical payments were tabulated for individual physicians on a daily and annual basis in conjunction with each physician's practice characteristics, setting, and specialty. <h3>Results</h3> A total of 31 481 physicians were included in the study sample (12 604 [40.0%] women; 18 877 [60.0%] men; mean [SD] time since graduation, 23.3 [13.6] years), representing 99% of active physicians in Ontario. The unadjusted differences in clinical payments between male and female physicians were 32.8% (95% CI, 30.8%-34.6%) annually and 22.5% (95% CI, 21.2%-23.8%) daily. After accounting for practice characteristics, region, and specialty, the overall daily payment gap was 13.5% (95% CI, 12.3%-14.8%). The pay gap persisted with differing magnitudes when examined by specialty (ranging from 6.6% to 37.6%), practice setting (8.3% to 17.2%), payment model (13.4% to 22.8% for family medicine; 8.0% to 11.6% for other specialties), and rurality (8.0% to 16.5%). <h3>Conclusions and Relevance</h3> This cross-sectional study examined differences in magnitude of annual and daily payment gaps and between unadjusted and adjusted gaps. Comparing the gaps for different specialties, geography, and payment systems illustrated the complexity of the issue by showing that the pay gap varied for physicians in different practice settings. As such, multiple directed interventions will be necessary to ensure that all physicians are paid equally for equal work, regardless of gender.
Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment
Authors: James P. Howard, Frances A. Wood, Judith A. Finegold, Alexandra N. Nowbar, David M. Thompson, Ahran D. Arnold, Christopher A. Rajkumar, Susan Connolly, Jaimini Cegla, Chris Stride, Peter Sever, Christine Norton, Simon A.M. Thom, Matthew J. Shun-Shin, Darrel P. Francis
Journal: Journal of the American College of Cardiology (2021)

Most people who begin statins abandon them, most commonly because of side effects.The purpose of this study was to assess daily symptom scores on statin, placebo, and no treatment in participants who had abandoned statins.Participants received 12 1-month medication bottles, 4 containing atorvastatin 20 mg, 4 placebo, and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the "nocebo" ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo.A total of 60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% CI: 4.7-11.3) in no-tablet months. It was higher in statin months (16.3; 95% CI: 13.0-19.6; P < 0.001), but also in placebo months (15.4; 95% CI: 12.1-18.7; P < 0.001), with no difference between the 2 (P = 0.388). The corresponding nocebo ratio was 0.90. In the individual-patient daily data, neither symptom intensity on starting (OR: 1.02; 95% CI: 0.98-1.06; P = 0.28) nor extent of symptom relief on stopping (OR: 1.01; 95% CI: 0.98-1.05; P = 0.48) distinguished between statin and placebo. Stopping was no more frequent for statin than placebo (P = 0.173), and subsequent symptom relief was similar between statin and placebo. At 6 months after the trial, 30 of 60 (50%) participants were back taking statins.The majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo. (Self-Assessment Method for Statin Side-effects Or Nocebo [SAMSON]; NCT02668016).
Poziotinib for Patients With <i>HER2</i> Exon 20 Mutant Non–Small-Cell Lung Cancer: Results From a Phase II Trial
Authors: Yasir Y. Elamin, Jacqulyne P. Robichaux, Brett W. Carter, Mehmet Altan, Don L. Gibbons, Frank V. Fossella, Vincent K. Lam, Anisha B. Patel, Marcelo V. Negrao, Xiuning Le, Frank E. Mott, Jianjun Zhang, Lei Feng, George Blumenschein, Anne S. Tsao, John V. Heymach
Journal: Journal of Clinical Oncology (2021)

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with HER2 exon 20 mutant advanced NSCLC in a single-arm, open-label, phase II study. PATIENTS AND METHODS Patients with advanced HER2 exon 20 mutant NSCLC were enrolled to receive poziotinib at a dose of 16 mg/d for 28-day cycles. The primary end point was objective response rate per RECIST version 1.1. Confirmatory scans were performed at least 28 days from initial radiologic response. RESULTS Thirty patients received poziotinib treatment. At baseline, 90% of patients received prior platinum-based chemotherapy and 53% had two lines or more prior systemic therapies. As of data cutoff on March 1, 2021, the confirmed objective response rate was 27% (95% CI, 12 to 46). Responses were observed across HER2 exon 20 mutation subtypes. The median duration of response was 5.0 months (95% CI, 4.0 to not estimable). The median progression-free survival was 5.5 months (95% CI, 4.0 to 7.0). The median overall survival was 15 months (95% CI, 9.0 to not estimable). The most common grade 3 treatment-related adverse events were skin rash (47%) and diarrhea (20%). There was one possible treatment-related death because of pneumonitis. CONCLUSION Poziotinib showed promising antitumor activity in patients with HER2 exon 20 mutant NSCLC including patients who had previously received platinum-based chemotherapy.
A Cre-driven allele-conditioning line to interrogate CD4+ conventional T cells
Authors: Lawrence P Andrews, Kate M Vignali, Andrea L Szymczak-Workman, Amanda R Burton, Erin A Brunazzi, Shin Foong Ngiow, Akihito Harusato, Arlene H Sharpe, E John Wherry, Ichiro Taniuchi, Creg J Workman, Dario A A Vignali
Journal: Immunity (2021)
Factors and Challenges in Understanding SARS-CoV-2 RNA Levels, Symptoms, and Transmissibility—Reply
Authors: Erin Chung, James P. Hughes, Helen Y. Chu
Journal: JAMA Pediatrics (2021)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 2024 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 Pediatrics journal