Showing papers by "Medical University of South Carolina published in 2021"
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
TL;DR: In this article, a provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination and found that delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions.
Abstract: Background Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. Objective To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. Methods A provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination. Results From December 2020 to February 2021, we recorded 414 cutaneous reactions to mRNA COVID-19 vaccines from Moderna (83%) and Pfizer (17%). Delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. Forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less common reactions included pernio/chilblains, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. Limitations Registry analysis does not measure incidence. Morphologic misclassification is possible. Conclusions We report a spectrum of cutaneous reactions after mRNA COVID-19 vaccines. We observed some dermatologic reactions to Moderna and Pfizer vaccines that mimicked SARS-CoV-2 infection itself, such as pernio/chilblains. Most patients with first-dose reactions did not have a second-dose reaction and serious adverse events did not develop in any of the patients in the registry after the first or second dose. Our data support that cutaneous reactions to COVID-19 vaccination are generally minor and self-limited, and should not discourage vaccination.
546 citations
Centers for Disease Control and Prevention1, United States Public Health Service2, Harvard University3, New York University4, University of Colorado Denver5, University of Texas at Dallas6, Nationwide Children's Hospital7, Johns Hopkins University8, Yale University9, Westchester Medical Center10, Rutgers University11, University of Alabama at Birmingham12, Children's Mercy Hospital13, University of Miami14, University of North Carolina at Chapel Hill15, Baylor College of Medicine16, University of Mississippi17, Vanderbilt University18, SUNY Downstate Medical Center19, California State University, Long Beach20, University of Minnesota21, Saint Barnabas Medical Center22, University of Arkansas for Medical Sciences23, Children's Hospital Oakland Research Institute24, Boston Children's Hospital25, University of Washington26, Central Michigan University27, Icahn School of Medicine at Mount Sinai28, University of Iowa29, Indiana University30, Emory University31, Medical University of South Carolina32, University of Pennsylvania33, Northwestern University34
TL;DR: In this article, the authors compared clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19) at 66 US hospitals in 31 states.
Abstract: Importance Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, Design, and Participants Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase–polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure SARS-CoV-2. Main Outcomes and Measures Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7,P Conclusions and Relevance This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.
493 citations
University of Siena1, University of Göttingen2, UCL Institute of Neurology3, City College of New York4, National Institutes of Health5, Brown University6, University of Toronto7, Università Campus Bio-Medico8, Beth Israel Deaconess Medical Center9, Medical University of South Carolina10, Cincinnati Children's Hospital Medical Center11, Aristotle University of Thessaloniki12, Aalto University13, Paris 12 Val de Marne University14, Vita-Salute San Raffaele University15, University of Trento16, Ludwig Maximilian University of Munich17, Harvard University18, Duke University19, University of Messina20, Copenhagen University Hospital21, Fukushima Medical University22, Ben-Gurion University of the Negev23, University of Tübingen24
TL;DR: New operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.
387 citations
TL;DR: In this paper, the authors summarize current knowledge of long noncoding RNAs subcellular localization, factors controlling their localization, emerging themes, including the role of lncRNA isoforms and the involvement of LncRNAs in phase separation bodies, and the implications of LNCRNA localization on their function and on cellular behavior.
Abstract: Subcellular localization of RNAs has gained attention in recent years as a prevalent phenomenon that influences numerous cellular processes. This is also evident for the large and relatively novel class of long noncoding RNAs (lncRNAs). Because lncRNAs are defined as RNA transcripts >200 nucleotides that do not encode protein, they are themselves the functional units, making their subcellular localization critical to their function. The discovery of tens of thousands of lncRNAs and the cumulative evidence involving them in almost every cellular activity render assessment of their subcellular localization essential to fully understanding their biology. In this review, we summarize current knowledge of lncRNA subcellular localization, factors controlling their localization, emerging themes, including the role of lncRNA isoforms and the involvement of lncRNAs in phase separation bodies, and the implications of lncRNA localization on their function and on cellular behavior. We also discuss gaps in the current knowledge as well as opportunities that these provide for novel avenues of investigation.
375 citations
University of Utah1, University of Colorado Denver2, Oregon Health & Science University3, Harvard University4, University of California, San Diego5, University of Texas Health Science Center at Houston6, Medical College of Wisconsin7, Medical University of South Carolina8, Northwestern University9, Emory University10, University of Pennsylvania11, University of São Paulo12, Sun Yat-sen University13, Ghent University14, Karolinska Institutet15, University of Chicago16, Rush University Medical Center17, University of Barcelona18, University of California, Los Angeles19, Vanderbilt University20, University of Arizona21, University of Kansas22, Université de Montréal23, University of Auckland24, Rutgers University25, University of Amsterdam26, Columbia University27, Eastern Virginia Medical School28, University of New South Wales29, Katholieke Universiteit Leuven30, Guy's Hospital31, Stanford University32, University of British Columbia33, Mayo Clinic34, Johns Hopkins University35, Korea University36, Uniformed Services University of the Health Sciences37, Jikei University School of Medicine38, University of Washington39, University of Siena40, University of East Anglia41, University of Adelaide42, Pusan National University43, University of Calgary44, University of Cincinnati45, University of North Carolina at Chapel Hill46, Cleveland Clinic47, University of Winnipeg48, Chulalongkorn University49, Cornell University50, National University of Singapore51, University of Alabama at Birmingham52, University of Alberta53, Capital Medical University54
TL;DR: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in the understanding and treatment of rhinologic disease.
Abstract: I. Executive summary BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. Methods ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. Conclusion This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.
299 citations
TL;DR: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks.
Abstract: Importance Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. Objective To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. Design, setting, and participants Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). Interventions Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. Main outcomes and measures The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. Results Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P Conclusions and relevance Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. Trial registration ClinicalTrials.gov Identifier: NCT03611582.
290 citations
TL;DR: A randomized, double-blind, randomized, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) was conducted to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma as discussed by the authors.
Abstract: Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Results from a phase 3, double-blind, randomized, placebo-controlled trial demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder.
288 citations
Free University of Berlin1, Hospital Kuala Lumpur2, Cleveland Clinic3, Mater Dei Hospital4, Kantonsspital St. Gallen5, University of Zurich6, Medical University of Vienna7, Montreal Children's Hospital8, University of Cincinnati9, University of Southern Denmark10, Technische Universität München11, Opole University12, Federal University of Paraná13, University of Southampton14, Federal University of São Paulo15, New York University16, University of Debrecen17, Istanbul University18, Pompeu Fabra University19, University of Coimbra20, Vrije Universiteit Brussel21, Bethel University22, Laval University23, Hiroshima University24, Medical University of South Carolina25, Hannover Medical School26, Rappaport Faculty of Medicine27, Koç University28, Mahidol University29, University of Helsinki30, Royal Free Hospital31, Fraunhofer Society32, National and Kapodistrian University of Athens33, University of Groningen34, Nippon Medical School35, University of Milan36, Universidad Nacional de Asunción37, Johns Hopkins University38, Hacettepe University39, University of Paris40, University of Mainz41, University of Perugia42, University of Toronto43, University of Copenhagen44, Aarhus University Hospital45, Peking University46
TL;DR: This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS) on 3 December 2020 as mentioned in this paper, with the participation of 64 delegates of 50 national and international societies and from 31 countries.
Abstract: This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
223 citations
Harvard University1, Johns Hopkins University2, University of Texas at Dallas3, University of North Carolina at Chapel Hill4, Westchester Medical Center5, New York University6, University of Mississippi7, University of Miami8, University of Colorado Denver9, Boston Children's Hospital10, Indiana University – Purdue University Indianapolis11, University of Washington12, University of Pennsylvania13, Saint Barnabas Medical Center14, University of Texas Health Science Center at Houston15, University of Arkansas for Medical Sciences16, Mayo Clinic17, University of Cincinnati18, Centers for Disease Control and Prevention19, Vanderbilt University20, Yale University21, Nationwide Children's Hospital22, University of Alabama at Birmingham23, Children's Mercy Hospital24, SUNY Downstate Medical Center25, Baylor College of Medicine26, Emory University27, California State University, Long Beach28, Rutgers University29, University of California, San Francisco30, Washington University in St. Louis31, University of Minnesota32, University of Iowa33, Medical University of South Carolina34, Northwestern University35, University of Michigan36
TL;DR: In this article, the authors investigated the range and severity of neurologic involvement among children and adolescents associated with COVID-19 and found that patients with involvement were more likely to have underlying neurologic disorders (81 of 365 [22] compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]).
Abstract: Importance Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants Case series of patients (age Exposures Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barre syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19–related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.
220 citations
University of California, San Francisco1, Oslo University Hospital2, Cleveland Clinic3, St. Vincent's Health System4, University of Toronto5, University of São Paulo6, Medical University of South Carolina7, University of Gothenburg8, Duke University9, University of Washington10, University of Pennsylvania11, Papworth Hospital12, Inova Fairfax Hospital13, Erasmus University Rotterdam14, University Medical Center Groningen15, Columbia University16
TL;DR: The International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates as mentioned in this paper.
Abstract: Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.
Fred Hutchinson Cancer Research Center1, Stanford University2, University of Cincinnati3, Vanderbilt University Medical Center4, Vanderbilt University5, Harvard University6, Broad Institute7, University of Lausanne8, University of Hawaii9, University of Colorado Denver10, Thomas Jefferson University11, Mayo Clinic12, Loyola University Medical Center13, Houston Methodist Hospital14, Emory University15, Beth Israel Deaconess Medical Center16, University of Florida17, McGill University Health Centre18, University of California, San Diego19, Case Western Reserve University20, St. Elizabeth Healthcare21, Icahn School of Medicine at Mount Sinai22, University of Kentucky23, Brown University24, Tufts Medical Center25, University of Michigan26, Henry Ford Health System27, Intermountain Healthcare28, George Washington University29, Cleveland Clinic30, Duke University31, Montefiore Medical Center32, Columbia University33, University of Connecticut34, Mount Auburn Hospital35, University of Kansas36, University of California, San Francisco37, Baylor College of Medicine38, Cancer Treatment Centers of America39, Ohio State University40, Penn State Cancer Institute41, University of Texas Health Science Center at San Antonio42, Loma Linda University43, University of California, Davis44, Medical University of South Carolina45, University of North Carolina at Chapel Hill46, Rutgers University47, Washington University in St. Louis48, LSU Health Sciences Center New Orleans49, University of Miami50
TL;DR: In this article, the authors analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.
Medical University of South Carolina1, University of California, San Francisco2, Centers for Disease Control and Prevention3, Johns Hopkins University4, University of Texas Health Science Center at San Antonio5, University of Zimbabwe6, Case Western Reserve University7, University of the Witwatersrand8, University of Cape Town9, United States Department of Health and Human Services10, University of Nebraska Medical Center11
TL;DR: In this paper, Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis.
Abstract: Background Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. Methods In an ope...
Vanderbilt University Medical Center1, Medical University of South Carolina2, Brigham and Women's Hospital3, Montreal Heart Institute4, Integris Baptist Medical Center5, Ochsner Medical Center6, University of California, San Diego7, East Carolina University8, University of Kansas9, Louisiana State University10, Providence Hospital11
TL;DR: The GUIDE-HF trial as discussed by the authors was designed to evaluate whether haemodynamic-guided management using remote pulmonary artery pressure monitoring could reduce heart failure events and mortality in patients with heart failure across the spectrum of symptom severity.
University Hospitals of Cleveland1, University of California, San Francisco2, University of Miami3, University College London Hospitals NHS Foundation Trust4, Medical College of Wisconsin5, Medical University of South Carolina6, Washington University in St. Louis7, Manchester Academic Health Science Centre8, Northside Hospital9, University of Bologna10, Humanitas University11
TL;DR: Loncastuximab tesirine is a CD19-directed antibody-drug conjugate with encouraging phase 1 single-agent antitumour activity and acceptable safety in non-Hodgkin lymphoma as discussed by the authors.
Abstract: Summary Background Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who do not respond to or who have progressive disease after salvage therapies have a poor prognosis. Loncastuximab tesirine is a CD19-directed antibody–drug conjugate with encouraging phase 1 single-agent antitumour activity and acceptable safety in non-Hodgkin lymphoma. We aimed to evaluate the antitumour activity and safety of loncastuximab tesirine in patients with relapsed or refractory DLBCL. Methods We did a multicentre (28 hospital sites in the USA, UK, Italy, and Switzerland), open-label, single-arm, phase 2 trial (LOTIS-2) in patients aged 18 years or older with relapsed or refractory DLBCL after two or more multiagent systemic treatments, who had measurable disease and Eastern Cooperative Oncology Group performance status 0–2. Eligible patients received loncastuximab tesirine intravenously on day 1 of each 21-day cycle, at 150 μg/kg for two cycles, then 75 μg/kg thereafter, for up to 1 year or until disease relapse or progression, unacceptable toxicity, death, major protocol deviation, pregnancy, or patient, investigator, or sponsor decision. The primary endpoint was overall response rate assessed by central review. Primary antitumour activity and safety analyses were done in the as-treated population (patients who received at least one dose of loncastuximab tesirine), when all responding patients had at least 6 months of follow-up after initial documented response. Enrolment is complete. This trial is registered with ClinicalTrials.gov , NCT03589469 . Findings Between Aug 1, 2018, and Sept 24, 2019, 184 patients were assessed for eligibility and 145 (79%) were enrolled and received at least one dose of loncastuximab tesirine, including patients with high-risk characteristics for poor prognosis, such as double-hit, triple-hit, transformed, or primary refractory DLBCL. 70 of 145 patients had complete or partial response (overall response rate 48·3% [95% CI 39·9–56·7]); 35 had complete response and 35 had partial response. The most common grade 3 or higher treatment-emergent adverse events were neutropenia (37 [26%] of 145 patients), thrombocytopenia (26 [18%]), and increased gamma-glutamyltransferase (24 [17%]). Serious adverse events were reported in 57 (39%) of 145 patients. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. Interpretation Loncastuximab tesirine has substantial single-agent antitumour activity and produces durable responses with an acceptable safety profile, potentially offering a new therapeutic option for heavily pretreated patients with relapsed or refractory DLBCL. Funding ADC Therapeutics.
Case Western Reserve University1, Johns Hopkins University2, John Radcliffe Hospital3, Washington University in St. Louis4, University of Maryland, Baltimore5, Billings Clinic6, Rosalind Franklin University of Medicine and Science7, Universidade Federal de Minas Gerais8, University of Sydney9, Autonomous University of Madrid10, Mayo Clinic11, Tel Aviv Sourasky Medical Center12, Cleveland Clinic13, Northwestern University14, Seoul National University15, Harvard University16, The Commonwealth Medical College17, Fundación Favaloro18, Boston Children's Hospital19, Medical University of South Carolina20, University of Texas Southwestern Medical Center21, Erasmus University Rotterdam22
TL;DR: In a survey conducted by the Autoimmune Encephalitis Alliance Clinicians Network as mentioned in this paper, the authors evaluated available evidence for each step in autoimmune encephalitis management and provided expert opinion when evidence is lacking.
Abstract: The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.
TL;DR: In this paper, the authors used two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, and found that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and precapillary arterioles.
Abstract: The majority of the brain's vasculature is composed of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, we find that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and precapillary arterioles. This slow vasoconstriction was inhibited by the clinically used vasodilator fasudil, a Rho-kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and slower to dilate towards baseline following optogenetically induced vasoconstriction. Optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux selectively in capillaries lacking pericyte contact. These data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain.
Ohio State University1, University of Bern2, Children's Hospital of Eastern Ontario3, University of Ottawa4, Johns Hopkins University5, University of Padua6, University of California, Los Angeles7, University of Sydney8, University of New South Wales9, Victor Chang Cardiac Research Institute10, Medical University of South Carolina11, University of Amsterdam12, University College London13, Royal Melbourne Hospital14, University of North Carolina at Chapel Hill15, Utrecht University16, National Institutes of Health17, Imperial College London18, National Health Service19
TL;DR: In this paper, each of the cardiomyopathies, classically categorized as hypertrophic Cardiomyopathy (HC), dilated CPM (DCM), arrhythmogenic right ventricular (RAV) cardiopathy and arrhythmic right ventric cardiogenesis (RVC), has a signature signature.
Abstract: Background: Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature ...
University of Florida1, Emory University2, Cedars-Sinai Medical Center3, University of Alabama at Birmingham4, Harvard University5, University of Wisconsin-Madison6, Mayo Clinic7, United States Department of the Army8, University of Pittsburgh9, Medical University of South Carolina10, University of Pennsylvania11
TL;DR: These Society for Vascular Surgery Practice Guidelines are applicable to the use of TEVAR for descending thoracic aortic aneurysm (TAA) as well as for other rarer pathologic processes of the DTA.
University of Glasgow1, Rancho Los Amigos National Rehabilitation Center2, University of Texas System3, University of California, Los Angeles4, Emory University5, National Health Service6, Spectrum Health7, Duke University8, Harvard University9, Medical University of South Carolina10, University of Sheffield11, Cornell University12, University of East London13, MGH Institute of Health Professions14
TL;DR: In this article, a randomized, randomized, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation pairing with sham stimulation (control group), and the primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy.
University Hospitals of North Midlands NHS Trust1, Goethe University Frankfurt2, University College London3, University of Tübingen4, Ludwig Maximilian University of Munich5, University of Augsburg6, Katholieke Universiteit Leuven7, Leibniz Institute for Neurobiology8, Ghent University Hospital9, University of Sheffield10, Leiden University11, Medical University of South Carolina12, University of Potsdam13, Dresden University of Technology14, Utah State University15, Oslo University Hospital16, University of Oslo17, Otto-von-Guericke University Magdeburg18, University of Milan19, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico20, Vienna University of Technology21, Università Campus Bio-Medico22, Complutense University of Madrid23, Queen Mary University of London24, Babasaheb Bhimrao Ambedkar University25, University of Würzburg26, Harvard University27, Maastricht University28, University of Liège29, Peking Union Medical College30, University of Leeds31, Medical University of Vienna32, University of California, Irvine33, University of Brasília34, Mersin University35, Vrije Universiteit Brussel36, City College of New York37, Erasmus University Rotterdam38, University of Bern39, Heidelberg University40, University of Düsseldorf41, University of Minnesota42, University of California, San Diego43, University of Göttingen44, University of Greifswald45, University of Pittsburgh46, Logan College of Chiropractic47, University of Padua48, University of Oklahoma Health Sciences Center49, University Hospital Bonn50, German Sport University Cologne51, McMaster University52, Greifswald University Hospital53, University of Ostrava54
TL;DR: In this paper, a review of transcutaneous vagus nerve stimulation (tVNS) literature is presented, and a set of minimal reporting items are proposed to guide future tVNS studies.
Abstract: Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.
TL;DR: This is the first, prospective, multicenter study of robotic bronchoscopy in patients with PPLs, and successful lesion localization was achieved in 96.2% of cases, with an adverse event rate comparable with conventional bronchoscopic procedures.
TL;DR: The UNTOUCHED trial was designed to evaluate the IAS rate in a more typical, contemporary ICD patient population implanted with the S-ICD using standardized programming and enhanced discrimination algorithms and demonstrates high efficacy and safety despite the relatively high incidence of comorbidities.
Abstract: Background: The subcutaneous (S) implantable cardioverter-defibrillator (ICD) is safe and effective for sudden cardiac death prevention. However, patients in previous S-ICD studies had fewer comorb...
TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus as a source of infection for other animals.
Abstract: Background: Percutaneous closure of the left atrial appendage (LAA) is an alternative to chronic oral anticoagulation to reduce stroke risk in patients with nonvalvular atrial fibrillation. The Amu...
TL;DR: The clinical and genetic diagnosis of the inherited cardiomyopathies are discussed, with the aim of better defining the epidemiology of these diseases.
Abstract: In the absence of contemporary, population-based epidemiological studies, estimates of the incidence and prevalence of the inherited cardiomyopathies have been derived from screening studies, most often of young adult populations, to assess cardiovascular risk or to detect the presence of disease in athletes or military recruits. The global estimates for hypertrophic cardiomyopathy (1/500 individuals), dilated cardiomyopathy (1/250) and arrhythmogenic right ventricular cardiomyopathy (1/5,000) are probably conservative given that only individuals who fulfil diagnostic criteria would have been included. This caveat is highly relevant because a substantial minority or even a majority of individuals who carry disease-causing genetic variants and are at risk of disease complications have incomplete and/or late-onset disease expression. The genetic literature on cardiomyopathy, which is often focused on the identification of genetic variants, has been biased in favour of pedigrees with higher penetrance. In clinical practice, an abnormal electrocardiogram with normal or non-diagnostic imaging results is a common finding for the sarcomere variants that cause hypertrophic cardiomyopathy, the titin and sarcomere variants that cause dilated cardiomyopathy and the desmosomal variants that cause either arrhythmogenic right ventricular cardiomyopathy or dilated cardiomyopathy. Therefore, defining the genetic epidemiology is also challenging given the overlapping phenotypes, incomplete and age-related expression, and highly variable penetrance even within individual families carrying the same genetic variant.
TL;DR: Fewer than 1 in 20 eligible adults received LCS nationally, and uptake varied widely across states, so LCS rates were not aligned with lung cancer burden across states.
Abstract: BACKGROUND Annual lung cancer screening (LCS) with low-dose chest computed tomography in older current and former smokers (ie, eligible adults) has been recommended since 2013. Uptake has been slow and variable across the United States. We estimated the LCS rate and growth at the national and state level between 2016 and 2018. METHODS The American College of Radiology's Lung Cancer Screening Registry was used to capture screening events. Population-based surveys, the US Census, and cancer registry data were used to estimate the number of eligible adults and lung cancer mortality (ie, burden). Lung cancer screening rates (SRs) in eligible adults and screening rate ratios with 95% confidence intervals (CI) were used to measure changes by state and year. RESULTS Nationally, the SR was steady between 2016 (3.3%, 95% CI = 3.3% to 3.7%) and 2017 (3.4%, 95% CI = 3.4% to 3.9%), increasing to 5.0% (95% CI = 5.0% to 5.7%) in 2018 (2018 vs 2016 SR ratio = 1.52, 95% CI = 1.51 to 1.62). In 2018, several southern states with a high lung-cancer burden (eg, Mississippi, West Virginia, and Arkansas) had relatively low SRs (<4%) among eligible adults, whereas several northeastern states with lower lung cancer burden (eg, Massachusetts, Vermont, and New Hampshire) had the highest SRs (12.8%-15.2%). The exception was Kentucky, which had the nation's highest lung cancer mortality rate and one of the highest SRs (13.7%). CONCLUSIONS Fewer than 1 in 20 eligible adults received LCS nationally, and uptake varied widely across states. LCS rates were not aligned with lung cancer burden across states, except for Kentucky, which has supported comprehensive efforts to implement LCS.
TL;DR: In this article, the authors evaluated the efficacy and safety of endovascular renal denervation in patients with hypertension resistant to three or more antihypertensive medications including a diuretic.
TL;DR: A culturally-informed Adverse Childhood Experiences (ACEs) model is presented, or "C-ACE", to understand the pervasive and deleterious mental health impact of racism on Black youth.
Abstract: The high prevalence and psychological impact of childhood exposure to potentially traumatic events (PTE) is a major public health concern in the United States. Considerable evidence has demonstrated the significant racial disparities that exist with respect to PTE exposure, indicating that Black youth are particularly burdened by these harmful experiences. Racism may serve a unique role in explaining why Black youth are disproportionately exposed to PTEs, and why mental health disparities are more likely to occur following such experiences. Despite clear evidence acknowledging racism as a major life stressor for Black youth, theoretical models of early childhood adversity have largely neglected the multifaceted influence of racism on mental health outcomes. Inspired by bourgeoning literature highlighting the potentially traumatic nature of racism-related experiences for Black youth, we present a culturally-informed Adverse Childhood Experiences (ACEs) model, or “C-ACE”, to understand the pervasive and deleterious mental health impact of racism on Black youth. This model extends the ACE framework by noting the significance of racism as an ACE exposure risk factor, a distinct ACE category, and a determinant of post-ACE mental health outcomes among Black youth. The model acknowledges and supports the advancement of ACEs research that takes a culturally informed approach to understanding the intergenerational and multilevel impact of racism on the mental health of Black youth. Future research utilizing the proposed C-ACE model is essential for informing clinical and public health initiatives centered on reducing the mental health impact of racism-related experiences and health disparities in the United States.
University of Texas at Dallas1, University of California, Los Angeles2, National Institute on Drug Abuse3, University of California, San Francisco4, University of Texas Health Science Center at Houston5, University of Minnesota6, Medical University of South Carolina7, Duke University8, National University of Singapore9, Texas Tech University10, Columbia University11
TL;DR: In this article, the use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied and a multisite, double-blind, two-stage, placebo-contr...
Abstract: Background The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. Methods We conducted this multisite, double-blind, two-stage, placebo-contr...