tbuckley/cabot-search huggingface dataset:
Lower baseline autoantibody levels are associated with immune-related adverse events from immune checkpoint inhibition
Authors: Nilasha Ghosh, Michael Postow, Chengsong Zhu, Deanna Jannat-Khah, Quan-Zhen Li, Greg Vitone, Karmela K Chan, Anne R Bass
Journal: Journal for ImmunoTherapy of Cancer (2022)

Introduction Immune checkpoint inhibitors (ICI) are a novel cancer therapeutic that have been successful in treating advanced malignancies; however, they also cause immune-related adverse events (irAE). Given that some irAE are clinically similar to traditional autoimmune diseases, autoantibodies have been suggested as possible biomarkers of irAE. However, there are very little data on autoantibody investigation prior to ICI. Our aim was to determine if specific baseline autoantibodies were associated with irAE and see if changes in autoantibody concentration corresponded with irAE development. Methods This study used data from an oncologic clinical trial of adaptive dosing combination ICI therapy in patients with advanced melanoma. Plasma was collected at baseline and 6 weeks after ICI initiation and tested in a microarray of 120 autoantigens commonly associated with autoimmune disease, as well as antinuclear antibody (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibody (anti-CCP). Autoantibody concentrations were compared between patients experiencing an organ-specific event versus not. Heatmaps, volcano plots and hierarchical clustering were used to determine autoantibody concentration differences among irAE patient clusters as defined by signal intensity of autoantibodies. Kaplan-Meier curves were created and a log-rank test was performed to assess differences in survival. Results The microarray analysis demonstrated that patients who experienced specific irAE had fewer differentially expressed autoantibodies at baseline than those that did not have those specific irAE, and a greater fold change (FC) in antibody concentration from baseline to 6 weeks corresponded with specific irAE development. However, no autoantibodies were identified as being predictive of specific events. Time to first irAE was less than 6 weeks in 69% of patients, and these patients had less autoantibodies at baseline. Considering ANA, RF and CCP autoantibodies, there were no significant differences between the seropositive and seronegative patients in irAE development, severity, timing or survival. Conclusion Patients with low autoantibody concentrations at baseline as well as a greater FC in autoantibody concentration over 6 weeks developed more distinct organ-specific irAE. This may suggest differences in the balance of cellular immunity and humoral pathways that are relevant in the pathogenesis of irAE, though further investigation is needed.
Scinderin promotes fusion of electron transport chain dysfunctional muscle stem cells with myofibers
Authors: Xun Wang, Spencer D. Shelton, Bogdan Bordieanu, Anderson R. Frank, Yating Yi, Siva Sai Krishna Venigalla, Zhimin Gu, Nicholas P. Lesner, Michael Glogauer, Navdeep S. Chandel, Hu Zhao, Zhiyu Zhao, David G. McFadden, Prashant Mishra
Journal: Nature Aging (2022)

Abstract Muscle stem cells (MuSCs) experience age-associated declines in number and function, accompanied by mitochondrial electron transport chain (ETC) dysfunction and increased reactive oxygen species (ROS). The source of these changes, and how MuSCs respond to mitochondrial dysfunction, are unknown. We report here that in response to mitochondrial ROS, murine MuSCs directly fuse with neighboring myofibers; this phenomenon removes ETC-dysfunctional MuSCs from the stem cell compartment. MuSC–myofiber fusion is dependent on the induction of Scinderin, which promotes formation of actin-dependent protrusions required for membrane fusion. During aging, we find that the declining MuSC population accumulates mutations in the mitochondrial genome but selects against dysfunctional variants. In the absence of clearance by Scinderin, the decline in MuSC numbers during aging is repressed; however, ETC-dysfunctional MuSCs are retained and can regenerate dysfunctional myofibers. We propose a model in which ETC-dysfunctional MuSCs are removed from the stem cell compartment by fusing with differentiated tissue.
Prophylactic Use of Compression Sleeves Reduces the Incidence of Arm Swelling in Women at High Risk of Breast Cancer–Related Lymphedema: A Randomized Controlled Trial
Authors: Vincent S. Paramanandam, Elizabeth Dylke, Gary M. Clark, Anuradha A. Daptardar, Ajeeta M. Kulkarni, Nita S. Nair, Rajendra A. Badwe, Sharon L. Kilbreath
Journal: Journal of Clinical Oncology (2022)

PURPOSE To determine whether prophylactic use of compression sleeves prevents arm swelling in women who had undergone axillary lymph node dissection for breast cancer surgery. METHODS Women (n = 307) were randomly assigned to either a compression or control group. In addition to usual postoperative care, the compression group received two compression sleeves to wear postoperatively until 3 months after completing adjuvant treatments. Arm swelling was determined using bioimpedance spectroscopy (BIS) thresholds and relative arm volume increase (RAVI). Incidence and time free from arm swelling were compared using Kaplan-Meier analyses. Hazard ratios (HRs) were estimated from Cox regression models for BIS and RAVI thresholds independently. In addition, time to documentation of the first minimally important difference (MID) in four scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the breast cancer–specific (BR23) questionnaire was analyzed. RESULTS The HR for developing arm swelling in the compression group relative to the control group was 0.61 (95% CI, 0.43 to 0.85; P = .004) on the basis of BIS and 0.56 (95% CI, 0.33 to 0.96; P = .034) on the basis of RAVI. The estimated cumulative incidence of arm swelling at 1 year was lower in the compression group than the control group on the basis of BIS (42% v 52%) and RAVI (14% v 25%). HRs for time from baseline to the first change of the minimally important difference were not statistically significant for any of the four scales of EORTC QLQ-30 and BR23 questionnaires. CONCLUSION Prophylactic use of compression sleeves compared with the control group reduced and delayed the occurrence of arm swelling in women at high risk for lymphedema in the first year after surgery for breast cancer.
Work and worker health in the post-pandemic world: a public health perspective
Authors: Susan E Peters, Jack T Dennerlein, Gregory R Wagner, Glorian Sorensen
Journal: The Lancet Public Health (2022)

The COVID-19 pandemic has highlighted the importance of work in shaping population health and wellbeing. This Viewpoint applies a multilevel systems framework to assist in understanding the diverse and complex interactions of forces affecting worker health and wellbeing, and how trending changes in employment and working conditions have been accelerated by the pandemic. Government agencies concerned with population health and wellbeing, and economic activity must expand their capacity to monitor, evaluate, and respond to these trends. In addition, integrated enterprise and workplace-based approaches that consider the interactions among these multidimensional drivers will build organisation and worker resilience to navigate the continual changes in work and worker safety, health, and wellbeing in a post-pandemic world.
Rural–Urban Disparities in Cancer Outcomes: Opportunities for Future Research
Authors: Smita Bhatia, Wendy Landier, Electra D Paskett, Katherine B Peters, Janette K Merrill, Jonathan Phillips, Raymond U Osarogiagbon
Journal: JNCI Journal of the National Cancer Institute (2022)

Cancer care disparities among rural populations are increasingly documented and may be worsening, likely because of the impact of rurality on access to state-of-the-art cancer prevention, diagnosis, and treatment services, as well as higher rates of risk factors such as smoking and obesity. In 2018, the American Society of Clinical Oncology undertook an initiative to understand and address factors contributing to rural cancer care disparities. A key pillar of this initiative was to identify knowledge gaps and promote the research needed to understand the magnitude of difference in outcomes in rural vs nonrural settings, the drivers of those differences, and interventions to address them. The purpose of this review is to describe continued knowledge gaps and areas of priority research to address them. We conducted a comprehensive literature review by searching the PubMed (Medline), Embase, Web of Science, and Cochrane Library databases for studies published in English between 1971 and 2021 and restricted to primary reports from populations in the United States and abstracted data to synthesize current evidence and identify continued gaps in knowledge. Our review identified continuing gaps in the literature regarding the underlying causes of rural-urban disparities in cancer outcomes. Rapid advances in cancer care will worsen existing disparities in outcomes for rural patients without directed effort to understand and address barriers to high-quality care in these areas. Research should be prioritized to address ongoing knowledge gaps about the drivers of rurality-based disparities and preventative and corrective interventions.
Genetics of Sudden Cardiac Death
Authors: Connie R. Bezzina, Najim Lahrouchi, Silvia G. Priori
Journal: Circulation Research (2015)

Sudden cardiac death occurs in a broad spectrum of cardiac pathologies and is an important cause of mortality in the general population. Genetic studies conducted during the past 20 years have markedly illuminated the genetic basis of the inherited cardiac disorders associated with sudden cardiac death. Here, we review the genetic basis of sudden cardiac death with a focus on the current knowledge on the genetics of the primary electric disorders caused primarily by mutations in genes encoding ion channels, and the cardiomyopathies, which have been attributed to mutations in genes encoding a broader category of proteins, including those of the sarcomere, the cytoskeleton, and desmosomes. We discuss the challenges currently faced in unraveling genetic factors that predispose to sudden cardiac death in the setting of sequela of coronary artery disease and present the genome-wide association studies conducted in recent years on electrocardiographic parameters, highlighting their potential in uncovering new biological insights into cardiac electric function.
P130: PROVIDING ADEQUATE HEALTHCARE TO PEOPLE WITH HEMOGLOBINOPATHIES DURING THE PANDEMIC (COVID-19)
Authors: S Sophia Delicou, A Aikaterini Xydaki, K Konstantinos Manganas, L Lucia Evliati, C Chrysoula Kalkana, M Michael Diamantidis, A Achilles Manafas, M Marianna Katsatou, L Leonidas Roumpatis, T Theodoros Aforozis
Journal: HemaSphere (2022)

Background: Countries around the world were dealing with an increase in demand for COVID-19 healthcare, which was exacerbated by fear, confusion, and mobility restrictions, all of which impacted the provision of health care for all conditions. Patients with severe diseases, such as hemoglobinopathies, seem to pose additional challenges. Aim-Methods: An anonymous questionnaire was developed and given to 130 patients from four Thalassemia and Sickle Cell Disease Units of the National Health System of Greece Hospitals using stratified random sampling technique. To perform statistical analysis on the questionnaires, the MedCalc 2018 application was used. Results: There were 130 participants (51 % women, 49 % males) with transfusion-dependent thalassemia (84%), transfused sickle cell disease (15%), and other conditions (1%). During the pandemic, patients’ main concern was a lack of blood for transfusions (64 percent). The consistency of scheduled transfusions was not impaired (72 %) during the lock-down, while they were occasionally delayed (21 %) or did not appear at all (7 %). Similarly, when it came to systemic iron chelation therapy, 82 % were consistent, whereas 6 % stopped taking the drug on a regular basis because of worry of not having enough. The pandemic and lockdown had an impact on the annual follow-up of basic disease comorbidities, with 42% postponing the standard cardiac evaluation, 30% postponing magnetic resonance imaging of the liver-heart, and 23% cancelling major assessments or treatments such as biopsies or in vitro fertilisation (IVF) therapeutic interventions. Finally, 6% of scheduled surgeries had to be rescheduled. Conclusion: Patients with hemoglobinopathies received their scheduled transfusions without delay during the pandemic. A small percentage of patients modified their home medications because they were concerned about not being adequate during the pandemic. The significant consequence of the pandemic on our patients was the postponement of scheduled assessments and medical procedures required for chronic complications of their underlying condition. References 1. World Health Organization. (2020). COVID-19: Operational guidance for maintaining essential health services during an outbreak.
Association Between IgE Levels and COVID-19 Mortality
Authors: Yasmine Oprea, Denisa Ferastraoaru
Journal: Journal of Allergy and Clinical Immunology (2022)

Data suggest that individuals with higher absolute eosinophil counts (AEC) have better outcomes of COVID-19 infection. It remains unknown if other molecules of the TH2 immune response, such as immunoglobulin (Ig) E, play a role. We identified patients detected positive for COVID-19 at our institution between March-December 2020, who also had IgE levels measured prior to COVID-19 infection. Mortality rates due to COVID-19 were compared among patients with IgE deficiency (IgE<2.5 kU/L), normal (2.5≥IgE<100 kU/L), high (100≥IgE<1000 kU/L), and very high (IgE≥1000 kU/L) IgE levels. Overall, 320 COVID-19 positive individuals had IgE levels measured prior to infection: 11 (3.4%) were IgE deficient, 144 (45%) had normal IgE, 137 (42.8%) had high IgE, and 28 (8.8%) had very high IgE levels. Overall, the mortality rate due to COVID-19 was 11.6% (37/320). A significantly higher rate and odds of death attributable to COVID-19 were found in IgE deficient patients (3/11, 27.3%) compared to those with normal (15/144, 10.4%, OR=7.09, 95%CI:1.13-44.37, P=.036) and high (13/137, 9.5%, OR=5.69, 95%CI:1.01-32.16, P=.049) IgE levels. A similar mortality rate was found between IgE deficient individuals and those with very high IgE levels (27.3% vs 21.4%, P=.52). In this cohort, the average prior AEC was not associated with COVID-19 mortality in any of the four groups. These data raise the possibility that other molecules of the TH2 pathway may also be involved in COVID-19-asociated mortality. Larger studies are necessary to better define the relationship between IgE, AEC, and COVID-19 outcomes.
Toll-Like Receptor 7 Protects From Atherosclerosis by Constraining “Inflammatory” Macrophage Activation
Authors: Maria Salagianni, Ioanna E. Galani, Anna M. Lundberg, Constantinos H. Davos, Aimilia Varela, Ariana Gavriil, Leo-Pekka Lyytikäinen, Terho Lehtimäki, Fragiska Sigala, Lasse Folkersen, Vassilis Gorgoulis, Sébastien Lenglet, Fabrizio Montecucco, François Mach, Ulf Hedin, Göran K. Hansson, Claudia Monaco, Evangelos Andreakos
Journal: Circulation (2012)

Toll-like receptors (TLRs) have long been considered to be major culprits in the development of atherosclerosis, contributing both to its progression and clinical complications. However, evidence for most TLRs beyond TLR2 and TLR4 is lacking. We used experimental mouse models, human atheroma cultures, and well-established human biobanks to investigate the role of TLR7 in atherosclerosis. We report the unexpected finding that TLR7, a receptor recognizing self-nucleic acid complexes, is protective in atherosclerosis. In Apoe(-/-) mice, functional inactivation of TLR7 resulted in accelerated lesion development, increased stenosis, and enhanced plaque vulnerability as revealed by Doppler ultrasound and/or histopathology. Mechanistically, TLR7 interfered with macrophage proinflammatory responses to TLR2 and TLR4 ligands, reduced monocyte chemoattractant protein-1 production, and prevented expansion of Ly6C(hi) inflammatory monocytes and accumulation of inflammatory M1 macrophages into developing atherosclerotic lesions. In human carotid endarterectomy specimens TLR7 levels were consistently associated with an M2 anti-inflammatory macrophage signature (interleukin [IL]-10, IL-1RA, CD163, scavenger and C-type lectin receptors) and collagen genes, whereas they were inversely related or unrelated to proinflammatory mediators (IL-12/IL-23, interferon beta, interferon gamma, CD40L) and platelet markers. Moreover, in human atheroma cultures, TLR7 activation selectively suppressed the production of key proatherogenic factors such as monocyte chemoattractant protein-1 and tumor necrosis factor without affecting IL-10. These findings provide evidence for a beneficial role of TLR7 in atherosclerosis by constraining inflammatory macrophage activation and cytokine production. This challenges the prevailing concept that all TLRs are pathogenic and supports the exploitation of the TLR7 pathway for therapy.
Survivors Of Severe COVID-19 With Long-Haul Respiratory Symptoms Display Enhanced Activation of Circulating T Cells
Authors: Glenda Canderan, Lyndsey Muehling, Alexandra Kadl, Chintan Ramani, Jeffrey Sturek, Cathy Bonham, Deborah Murphy, Paul Wright, Behnam Keshavarz, Jeffrey Wilson, Sierra Barone, Jonathan Irish, Judith Woodfolk
Journal: Journal of Allergy and Clinical Immunology (2022)
Energetics of the human aorta: the effect of age
Authors: C. Stefanadis, C. Vlachopoulos, L. Diamantopoulos, S. Vaina, D. Tsokoura, J. Dernellis, K. Toutouzas, N. Glatrakos, E. Tsiamis, C. Pitsavos, P. Toutouzas
Journal: Journal of the American College of Cardiology (1998)
Therapeutic endoscopic ultrasound: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review
Authors: Roy L. J. van Wanrooij, Michiel Bronswijk, Rastislav Kunda, Simon M. Everett, Sundeep Lakhtakia, Mihai Rimbas, Tomas Hucl, Abdenor Badaoui, Ryan Law, Paolo Giorgio Arcidiacono, Alberto Larghi, Marc Giovannini, Mouen A. Khashab, Kenneth F. Binmoeller, Marc Barthet, Manuel Pérez-Miranda, Jeanin E. van Hooft, Schalk W. van der Merwe
Journal: Endoscopy (2022)

1: ESGE recommends a prolonged course of a prophylactic broad-spectrum antibiotic in patients with ascites who are undergoing therapeutic endoscopic ultrasound (EUS) procedures.Strong recommendation, low quality evidence. 2: ESGE recommends placement of partially or fully covered self-expandable metal stents during EUS-guided hepaticogastrostomy for biliary drainage in malignant disease.Strong recommendation, moderate quality evidence. 3: ESGE recommends EUS-guided pancreatic duct (PD) drainage should only be performed in high volume expert centers, owing to the complexity of this technique and the high risk of adverse events.Strong recommendation, low quality evidence. 4: ESGE recommends a stepwise approach to EUS-guided PD drainage in patients with favorable anatomy, starting with rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP), followed by antegrade or transmural drainage only when RV-ERP fails or is not feasible.Strong recommendation, low quality evidence. 5: ESGE suggests performing transduodenal EUS-guided gallbladder drainage with a lumen-apposing metal stent (LAMS), rather than using the transgastric route, as this may reduce the risk of stent dysfunction.Weak recommendation, low quality evidence. 6: ESGE recommends using saline instillation for small-bowel distension during EUS-guided gastroenterostomy.Strong recommendation, low quality evidence. 7: ESGE recommends the use of saline instillation with a 19G needle and an electrocautery-enhanced LAMS for EUS-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) procedures.Strong recommendation, low quality evidence. 8: ESGE recommends the use of either 15- or 20-mm LAMSs for EDGE, with a preference for 20-mm LAMSs when considering a same-session ERCP.Strong recommendation, low quality evidence.
Retraction
Authors: Marjolaine Vareille, Elisabeth Kieninger, Marco P. Alves, Brigitte S. Kopf, Alexander Möller, Thomas Geiser, Sebastian L. Johnston, Michael R. Edwards, Nicolas Regamey
Journal: Thorax (2013)

Vareille M, Kieninger E, Alves MP, et al . Impaired type I and type III interferon induction and rhinovirus control in human cystic fibrosis airway epithelial cells. Thorax 2012;67:517-25. This article has been retracted. In our article recently published in Thorax , we described a novel mechanism explaining the increased susceptibility of patients with cystic fibrosis (CF) to rhinovirus infections, namely defective interferon type I and III production by CF airway epithelial cells. In experiments performed after publication of the article we were unable to consistently replicate our findings of deficient interferon type I and III production by CF airway epithelial cells upon rhinovirus infection. In the light of these results, we carried out detailed investigations of the data reported in the above manuscript and regrettably found evidence of deliberate manipulation of experimental data by the first author Dr M. Vareille. This manipulation was accompanied in some instances by absence of original data files. The manipulation/original data absence involved data presented in most, if not all of the figures, thus we wish to fully retract the paper and apologise to the readers of Thorax and to the scientific community for the inconvenience this has caused. We also checked data published by our group in manuscripts on which Dr Vareille was a co-author and found that data published in these manuscripts had not been manipulated. These two manuscripts, whose data and conclusions we stand by are: Edwards MR, Regamey N, Vareille M, et al. Impaired innate interferon induction in severe therapy resistant atopic asthmatic children. Mucosal Immunol 2013;6:797–806. doi: 10.1038/mi.2012.118. and Kieninger E, Vareille M, Kopf BS, et al . Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis. Eur Respir J 2012;39:297–304. doi: 10.1183/09031936.00054511. Dr. Vareille has received a letter from the Secretary General of the University of Bern condemning her scientific misconduct as a severe offence against the rules of scientific integrity. Her current employers have also been informed. All co-authors of the publication including Dr. Vareille concur with the retraction statement.
Clinical Characteristics of Anaphylaxis Cases in an Inner-City Pediatric Emergency Department (E.D.) in Brooklyn Over a 4 Year Period
Authors: Mansi Kothari, Sairaman Nagarajan, Vrinda Kumar, Deeksha Katoch, Sonia Gandhi, Matthew Merola, Rauno Joks, Maria-Anna Vastardi
Journal: Journal of Allergy and Clinical Immunology (2022)
Measurement of hypoxia in the lung in idiopathic pulmonary fibrosis: a matter of control
Authors: Pierre-Simon Bellaye, Guillaume Beltramo, Olivier Burgy, Bertrand Collin, Alexandre Cochet, Philippe Bonniaud
Journal: European Respiratory Journal (2022)

<b>Despite the discouraging results provided by Porter and co-workers, we believe that there is room for improvements, mainly by using better controls, which may ultimately lead to more promising outcomes for the use of hypoxia-focused imaging in IPF patients</b>https://bit.ly/30Ku2AV