tbuckley/cabot-search huggingface dataset:
NCCN Guidelines® Insights: Hodgkin Lymphoma, Version 2.2022
Authors: Richard T. Hoppe, Ranjana H. Advani, Weiyun Z. Ai, Richard F. Ambinder, Philippe Armand, Celeste M. Bello, Cecil M. Benitez, Weina Chen, Bouthaina Dabaja, Megan E. Daly, Leo I. Gordon, Neil Hansen, Alex F. Herrera, Ephraim P. Hochberg, Patrick B. Johnston, Mark S. Kaminski, Christopher R. Kelsey, Vaishalee P. Kenkre, Nadia Khan, Ryan C. Lynch, Kami Maddocks, Jonathan McConathy, Monika Metzger, David Morgan, Carolyn Mulroney, Sheeja T. Pullarkat, Rachel Rabinovitch, Karen C. Rosenspire, Stuart Seropian, Randa Tao, Pallawi Torka, Jane N. Winter, Joachim Yahalom, Joanna C. Yang, Jennifer L. Burns, Mallory Campbell, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2022)

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte–predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.
TCTAP A-081 Early Results of Myval Transcatheter Aortic Valve in Severe Bicuspid Aortic Stenosis (Procedural and 30-Day Outcome)
Authors: Ahmed Elkoumy, Osama Soliman, Mahmoud Abdelshafy, Ashok Seth, Francesco Bedogni, Hesham Elzomor, Sreenivas Arramraju Kumar, Maurizio Tespili, Keyur Parikh, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2022)
Effectiveness of COVID-19 mRNA Vaccination in Preventing COVID-19–Associated Hospitalization Among Adults with Previous SARS-CoV-2 Infection — United States, June 2021–February 2022
Authors: Ian D. Plumb, Leora R. Feldstein, Eric Barkley, Alexander B. Posner, Howard S. Bregman, Melissa Briggs Hagen, Jacqueline L. Gerhart
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Previous infection with SARS-CoV-2, the virus that causes COVID-19, has been estimated to confer up to 90% protection against reinfection, although this protection was lower against the Omicron variant compared with that against other SARS-CoV-2 variants (1-3). A test-negative design was used to estimate effectiveness of COVID-19 mRNA vaccines in preventing subsequent COVID-19-associated hospitalization among adults aged ≥18 years with a previous positive nucleic acid amplification test (NAAT) or diagnosis of COVID-19.
Internal Mammary Node Irradiation in Patients With Node-Positive Early Breast Cancer: Fifteen-Year Results From the Danish Breast Cancer Group Internal Mammary Node Study
Authors: Lise B.J. Thorsen, Jens Overgaard, Louise W. Matthiessen, Martin Berg, Lars Stenbygaard, Anders N. Pedersen, Mette H. Nielsen, Marie Overgaard, Birgitte Vrou Offersen
Journal: Journal of Clinical Oncology (2022)

The Danish Breast Cancer Group Internal Mammary Node study demonstrated improved 8-year overall survival (OS) with internal mammary node irradiation (IMNI) in patients with node-positive early breast cancer. Here, we present long-term results from the Danish Breast Cancer Group Internal Mammary Node study cohort.This nationwide, prospective cohort study allocated patients with node-positive early breast cancer to adjuvant radiotherapy with or without IMNI depending on cancer laterality. Patients with right-sided cancer received IMNI. Patients with left-sided cancer were treated without IMNI because of risk of radiation-induced heart disease. Other treatment was independent of laterality. The primary study end point was OS. Secondary end points were distant recurrence and breast cancer mortality. Analyses were by intention to treat.During 2003-2007, 3,089 women were allocated to IMNI (right-sided, n = 1,491) or no IMNI (left-sided, n = 1,598). With a median follow-up of 14.8 years, 589 patients with and 701 patients without IMNI had died. The corresponding 15-year OS rates were 60.1% and 55.4%. The adjusted hazard ratio (HR) for death was 0.86 (95% CI, 0.77 to 0.96; P = .007) in favor of IMNI. The 15-year risk of developing distant recurrence was 35.6% (523 recurrences) and 38.6% (602 recurrences) with vs. without IMNI (adjusted HR, 0.88 [95% CI, 0.79 to 0.99; P = .04]). The 15-year breast cancer mortality with IMNI was 31.7% (467 deaths) compared with 33.9% (537 deaths) without IMNI (adjusted HR, 0.88 [95% CI, 0.78 to 1.00; P = .05]). The distribution of other deaths was similar across groups.In patients with node-positive early breast cancer treated with IMNI or without IMNI depending on breast cancer laterality, IMNI reduced the risk of distant recurrence and death from breast cancer, thereby improving long-term survival.
Usefulness of Noninvasive Management With the Gutter Method for Epidermal Growth Factor Receptor Inhibitor–Induced Paronychia, Pyogenic Granuloma–Like Lesion, and Ingrown Nail
Authors: Ai Agematsu, Masahiro Kamata, Kaoru Namiki, Yukina Yabuuchi, Mayumi Nagata, Yayoi Tada
Journal: JAMA Dermatology (2022)
Platelet‐activating factor acetylhydrolase is a biomarker of severe anaphylaxis in children
Authors: Julia E. M. Upton, Jennifer A. Hoang, Matilde Leon‐Ponte, Yaron Finkelstein, Yue (Jennifer) Du, Khosrow Adeli, Thomas Eiwegger, Eyal Grunebaum, Peter Vadas
Journal: Allergy (2022)

Abstract Background There is limited ability to predict the severity of allergic reactions in children. Data derived predominantly from adults have implicated the platelet‐activating factor pathway as a potential contributor to severe anaphylaxis. In this study, we sought to prospectively assess involvement of key components of the platelet‐activating factor pathway in pediatric patients with anaphylaxis. Methods Forty‐six pediatric patients (&lt;18 years) presenting with acute anaphylaxis were assessed. Anaphylaxis severity was graded and serum anaphylaxis markers were measured acutely and in 36 children who returned for follow‐up &gt;4 weeks after their acute presentation. These markers were compared with pediatric laboratory reference sera. Results Severe anaphylaxis was experienced by 12/46 (26%) and mild‐moderate anaphylaxis in 34/46 (74%) children. Platelet‐activating factor acetylhydrolase (PAF‐AH) activity was inversely associated with severe anaphylaxis: 9/12 children with severe anaphylaxis had reduced PAF‐AH activity as compared with 14/34 with mild‐moderate anaphylaxis ( p &lt; .05). Furthermore, 3/3 children who required intensive care had markedly reduced mean PAF‐AH (nmol/ml/min) (13.73, 95%CI: 7.42–20.03) versus 20/23 who required ward/emergency department care (17.81, 95%CI: 16.80–18.83; p &lt; .05). In children with anaphylaxis, PAF‐AH during acute anaphylaxis was unchanged relative to the child's basal levels (mean, 17.26, 95%CI: 16.10–18.42 vs 17.50, 95%CI: 16.21–18.78, p = .63) and was lower than healthy pediatric controls (mean 19.21; 95%CI:18.21–20.21; p &lt; .05). Conclusion Decreased serum PAF‐AH activity is a biomarker of severe anaphylaxis. Levels of this enzyme do not change from basal levels during acute anaphylaxis. Our results show that PAF‐AH is a biomarker of anaphylaxis severity in children. This key regulatory enzyme may modulate susceptibility to severe anaphylaxis.
Medical devices, smart drug delivery, wearables and technology for the treatment of Diabetes Mellitus
Authors: Daniel A. Domingo-Lopez, Giulia Lattanzi, Lucien H. J. Schreiber, Eimear J. Wallace, Robert Wylie, Janice O'Sullivan, Eimear B. Dolan, Garry P. Duffy
Journal: Advanced Drug Delivery Reviews (2022)

Diabetes mellitus refers to a group of metabolic disorders which affect how the body uses glucose impacting approximately 9% of the population worldwide. This review covers the most recent technological advances envisioned to control and/or reverse Type 1 diabetes mellitus (T1DM), many of which will also prove effective in treating the other forms of diabetes mellitus. Current standard therapy for T1DM involves multiple daily glucose measurements and insulin injections. Advances in glucose monitors, hormone delivery systems, and control algorithms generate more autonomous and personalised treatments through hybrid and fully automated closed-loop systems, which significantly reduce hypo- and hyperglycaemic episodes and their subsequent complications. Bi-hormonal systems that co-deliver glucagon or amylin with insulin aim to reduce hypoglycaemic events or increase time spent in target glycaemic range, respectively. Stimuli responsive materials for the controlled delivery of insulin or glucagon are a promising alternative to glucose monitors and insulin pumps. By their self-regulated mechanism, these "smart" drugs modulate their potency, pharmacokinetics and dosing depending on patients' glucose levels. Islet transplantation is a potential cure for T1DM as it restores endogenous insulin and glucagon production, but its use is not yet widespread due to limited islet sources and risks of chronic immunosuppression. New encapsulation strategies that promote angiogenesis and oxygen delivery while protecting islets from recipients' immune response may overcome current limiting factors.
Erythrocyte-biomimetic nanosystems to improve antitumor effects of paclitaxel on epithelial cancers
Authors: Mingming Song, Shuqi Dong, Xiaofei An, Wenxiang Zhang, Ning Shen, Yanbo Li, Caixia Guo, Chang Liu, Xiao Li, Siyu Chen
Journal: Journal of Controlled Release (2022)
Esophageal remodeling in eosinophilic esophagitis: Relationships to luminal captured biomarkers of inflammation and periostin
Authors: Amanda B. Muir, Steven J. Ackerman, Zhaoxing Pan, Alain Benitez, Cassandra Burger, Jonathan M. Spergel, Glenn T. Furuta, Joshua Rothman, Benjamin J. Wilkins, Michael A. Arnold, Lauren Dolinsky, Milica Grozdanovic, Calies Menard-Katcher
Journal: Journal of Allergy and Clinical Immunology (2022)
Identifying Accessibility Requests for Patients With Disabilities Through an Electronic Health Record–Based Questionnaire
Authors: Varshini Varadaraj, Xinxing Guo, Nicholas S. Reed, Kerry Smith, Michael V. Boland, A. J. Nanayakkara, Bonnielin K. Swenor
Journal: JAMA Network Open (2022)

People with disabilities experience disparities in health care access and outcomes, and inaccessible health care facilities are major barriers to health care access. Methods to collect accessibility request information are needed to improve health care outcomes for patients with disabilities.To evaluate an electronic health record (EHR)-based questionnaire designed to identify accessibility requests for patients with disabilities at an eye clinic.This cross-sectional pilot study implemented an EHR questionnaire and prospectively collected data on accessibility requests at a university-based eye clinic. The study included 55 722 patients making appointments at the Johns Hopkins Wilmer Eye Institute from April 1, 2019, to March 31, 2020.The Wilmer Eye Institute staff were trained to assess accessibility requests of patients making appointments in-person or via telephone using a standardized script and entering patient responses into the EHR. Data were later extracted for analysis and used to determine the proportion of patients making eye appointments who reported a disability accessibility request (physical, sensory, or intellectual) during their clinic visit.Accessibility request data were collected from 250 932 patient encounters. Patients had a mean (SD) age of 61.9 (20.6) years; most were women (146 846 [58.5%]) and were White individuals (162 720 [64.9%]). Of these, 23 510 (9.4%) encounters were associated with an accessibility request. The most reported accessibility request was mobility related (18 857 [7.5%]) (needing a cane, crutches, motorized scooter, walker, wheelchair, stretcher, assistance standing, or transport services), followed by sensory-related (2988 [1.2%]) (visual, hearing, or speech impairment), intellectual (353 [0.1%]), and other (1312 [0.5%]) (assistance with filling forms or service animal) requests. Patients with an accessibility request compared with those without, were older (72.6 vs 60.8 years), less likely to be White individuals (59.7% vs 65.4%), and more likely to be women (62.6% vs 58.1%), receiving Medicare (69.6% vs 41.5%), and have vision impairment (41.3% vs 13.6%) (P < .001 for all).In this cross-sectional study, a substantial proportion of patients making eye appointments reported having accessibility requests as captured using a new EHR-based questionnaire. Such standardization of data collection for disability-related accessibility requests in EHR is scalable, could be expanded to other clinical settings, and has the potential to improve accessibility of health care interactions for patients with disabilities.
We need a new approach to clinical trials in alcohol‐associated hepatitis: Is there a lesson in RECOVERY?
Authors: Michael Ronan Lucey, Mark R. Thursz
Journal: Hepatology (2022)

Dr. Thursz consults for and received grants from Novartis. He consults for Prodigy and Heparagenix. Dr. Lucey is a member of a DSMB for Novartis. He received grants from Pharmasolutions.
TNFR2 blockade of regulatory T cells unleashes an antitumor immune response after hematopoietic stem-cell transplantation
Authors: Audrey Moatti, Anais Debesset, Caroline Pilon, Asma Beldi-Ferchiou, Mathieu Leclerc, Rabah Redjoul, Frederic Charlotte, Nhu Hanh To, Adeline Bak, Yazid Belkacemi, Benoît Laurent Salomon, Fadi Issa, David Michonneau, Sebastien Maury, José Laurent Cohen, Allan Thiolat
Journal: Journal for ImmunoTherapy of Cancer (2022)

Targeting immune checkpoints that inhibit antitumor immune responses has emerged as a powerful new approach to treat cancer. We recently showed that blocking the tumor necrosis factor receptor-type 2 (TNFR2) pathway induces the complete loss of the protective function of regulatory T cells (Tregs) in a model of graft-versus-host disease (GVHD) prevention that relies on Treg-based cell therapy. Here, we tested the possibility of amplifying the antitumor response by targeting TNFR2 in a model of tumor relapse following hematopoietic stem-cell transplantation, a clinical situation for which the need for efficient therapeutic options is still unmet.We developed appropriate experimental conditions that mimic patients that relapsed from their initial hematological malignancy after hematopoietic stem-cell transplantation. This consisted of defining in allogeneic bone marrow transplantation models developed in mice, the maximum number of required tumor cells and T cells to infuse into recipient mice to develop a model of tumor relapse without inducing GVHD. We next evaluated whether anti-TNFR2 treatment could trigger alloreactivity and consequently antitumor immune response. In parallel, we also studied the differential expression of TNFR2 on T cells including Treg from patients in post-transplant leukemia relapse and in patients developing GVHD.Using experimental conditions in which neither donor T cells nor TNFR2-blocking antibody per se have any effect on tumor relapse, we observed that the coadministration of a suboptimal number of T cells and an anti-TNFR2 treatment can trigger alloreactivity and subsequently induce a significant antitumor effect. This was associated with a reduced percentage of activated CD4+ and CD8+ Tregs. Importantly, human Tregs over-expressed TNFR2 relative to conventional T cells in healthy donors and in patients experiencing leukemia relapse or cortico-resistant GVHD after hematopoietic stem cell transplantation.These results highlight TNFR2 as a new target molecule for the development of immunotherapies to treat blood malignancy relapse, used either directly in grafted patients or to enhance donor lymphocyte infusion strategies. More widely, they open the door for new perspectives to amplify antitumor responses against solid cancers by directly targeting Tregs through their TNFR2 expression.
Erratum. COVID-19–Related Multisystem Inflammatory Syndrome in Children Presenting With New-Onset Type 1 Diabetes in Severe Ketoacidosis: A Case Series. Diabetes Care 2022;45:983–989
Authors: Hanan H. Aly, Eman M. Fouda, Alyaa A. Kotby, Sondos M. Magdy, Ahmed R. Rezk, Marwa W.A. Nasef
Journal: Diabetes Care (2022)

In the article cited above, a composition error resulted in incorrect data presentation in Table 2. The following text in the column “Pharmacologic management of multisystem inflammation and coagulopathy” applies to patient nos. 4, 5, and 6: “Bicarbonate for associated AKI in patient 4 only. Methylprednisolone pulse therapy at 30 mg/kg for 3 days with tapering over 3 weeks. Slow infusion of IVIG on 2 g/kg over 2 days. Anakinra (3 mg/kg/day for 5 days) for patients 5 and 6. Furosemide, captopril, and a short course of digoxin. Enoxaparin and low-dose aspirin.” The editors apologize for the error. The online version of the article (https://doi.org/10.2337/dc21-1094) has been updated to correct the error.
Post-Stroke Cognitive Impairment and Dementia
Authors: Natalia S. Rost, Amy Brodtmann, Matthew P. Pase, Susanne J. van Veluw, Alessandro Biffi, Marco Duering, Jason D. Hinman, Martin Dichgans
Journal: Circulation Research (2022)

Poststroke cognitive impairment and dementia (PSCID) is a major source of morbidity and mortality after stroke worldwide. PSCID occurs as a consequence of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Cognitive impairment and dementia manifesting after a clinical stroke is categorized as vascular even in people with comorbid neurodegenerative pathology, which is common in elderly individuals and can contribute to the clinical expression of PSCID. Manifestations of cerebral small vessel disease, such as covert brain infarcts, white matter lesions, microbleeds, and cortical microinfarcts, are also common in patients with stroke and likewise contribute to cognitive outcomes. Although studies of PSCID historically varied in the approach to timing and methods of diagnosis, most of them demonstrate that older age, lower educational status, socioeconomic disparities, premorbid cognitive or functional decline, life-course exposure to vascular risk factors, and a history of prior stroke increase risk of PSCID. Stroke characteristics, in particular stroke severity, lesion volume, lesion location, multiplicity and recurrence, also influence PSCID risk. Understanding the complex interaction between an acute stroke event and preexisting brain pathology remains a priority and will be critical for developing strategies for personalized prediction, prevention, targeted interventions, and rehabilitation. Current challenges in the field relate to a lack of harmonization of definition and classification of PSCID, timing of diagnosis, approaches to neurocognitive assessment, and duration of follow-up after stroke. However, evolving knowledge on pathophysiology, neuroimaging, and biomarkers offers potential for clinical applications and may inform clinical trials. Preventing stroke and PSCID remains a cornerstone of any strategy to achieve optimal brain health. We summarize recent developments in the field and discuss future directions closing with a call for action to systematically include cognitive outcome assessment into any clinical studies of poststroke outcome.
Case 11-2022: An 80-Year-Old Woman with Pancytopenia
Authors: Rebecca K. Leaf, Ranjodh S. Dhami, Nancy S. Chun, Robert Ta
Journal: New England Journal of Medicine (2022)

An 80-year-old woman was admitted with pancytopenia. Five weeks earlier, nausea, vomiting, diarrhea, chills, and fever had developed. CT revealed bilateral pelvic masses; examination of a peripheral-blood smear revealed schistocytes, anisocytosis, and a low platelet count. A diagnostic test was performed, and management decisions were made.
NK cells limit therapeutic vaccine–induced CD8 <sup>+</sup> T cell immunity in a PD-L1–dependent manner
Authors: Mariana O. Diniz, Anna Schurich, Senthil K. Chinnakannan, Marion Duriez, Kerstin A. Stegmann, Jessica Davies, Stephanie Kucykowicz, Kornelija Suveizdyte, Oliver E. Amin, Frances Alcock, Tamsin Cargill, Eleanor Barnes, Mala K. Maini
Journal: Science Translational Medicine (2022)

A better understanding of mechanisms that regulate CD8
Incidence of Electric Scooter–Associated Injuries in Finland From 2019 to 2021
Authors: Aleksi Reito, Elina Öljymäki, Mikko Franssila, Ville M. Mattila
Journal: JAMA Network Open (2022)

of recorded rides was 2 million, indicating a more robust analysis than those reported previously.The main limitation of this study was its retrospective nature.Because e-scooters remain popular and the market continues to grow, further studies are needed to evaluate targeted safety measures on e-scooter use.The incidence reported in our study can be used as a reference value for new interventions.
SARS-CoV-2 infection relaxes peripheral B cell tolerance
Authors: Moriah J. Castleman, Megan M. Stumpf, Nicholas R. Therrien, Mia J. Smith, Kelsey E. Lesteberg, Brent E. Palmer, James P. Maloney, William J. Janssen, Kara J. Mould, J. David Beckham, Roberta Pelanda, Raul M. Torres
Journal: The Journal of Experimental Medicine (2022)

Severe SARS-CoV-2 infection is associated with strong inflammation and autoantibody production against diverse self-antigens, suggesting a system-wide defect in B cell tolerance. BND cells are a B cell subset in healthy individuals harboring autoreactive but anergic B lymphocytes. In vitro evidence suggests inflammatory stimuli can breach peripheral B cell tolerance in this subset. We asked whether SARS-CoV-2–associated inflammation impairs BND cell peripheral tolerance. To address this, PBMCs and plasma were collected from healthy controls, individuals immunized against SARS-CoV-2, or subjects with convalescent or severe SARS-CoV-2 infection. We demonstrate that BND cells from severely infected individuals are significantly activated, display reduced inhibitory receptor expression, and restored BCR signaling, indicative of a breach in anergy during viral infection, supported by increased levels of autoreactive antibodies. The phenotypic and functional BND cell alterations significantly correlate with increased inflammation in severe SARS-CoV-2 infection. Thus, autoreactive BND cells are released from peripheral tolerance with SARS-CoV-2 infection, likely as a consequence of robust systemic inflammation.
Tuning Polymer Hydrophilicity to Regulate Gel Mechanics and Encapsulated Cell Morphology
Authors: Renato S. Navarro, Michelle S. Huang, Julien G. Roth, Kelsea M. Hubka, Chris M. Long, Annika Enejder, Sarah C. Heilshorn
Journal: Advanced Healthcare Materials (2022)

Mechanically tunable hydrogels are attractive platforms for 3D cell culture, as hydrogel stiffness plays an important role in cell behavior. Traditionally, hydrogel stiffness has been controlled through altering either the polymer concentration or the stoichiometry between crosslinker reactive groups. Here, an alternative strategy based upon tuning the hydrophilicity of an elastin-like protein (ELP) is presented. ELPs undergo a phase transition that leads to protein aggregation at increasing temperatures. It is hypothesized that increasing this transition temperature through bioconjugation with azide-containing molecules of increasing hydrophilicity will allow direct control of the resulting gel stiffness by making the crosslinking groups more accessible. These azide-modified ELPs are crosslinked into hydrogels with bicyclononyne-modified hyaluronic acid (HA-BCN) using bioorthogonal, click chemistry, resulting in hydrogels with tunable storage moduli (100-1000 Pa). Human mesenchymal stromal cells (hMSCs), human umbilical vein endothelial cells (HUVECs), and human neural progenitor cells (hNPCs) are all observed to alter their cell morphology when encapsulated within hydrogels of varying stiffness. Taken together, the use of protein hydrophilicity as a lever to tune hydrogel mechanical properties is demonstrated. These hydrogels have tunable moduli over a stiffness range relevant to soft tissues, support the viability of encapsulated cells, and modify cell spreading as a consequence of gel stiffness.