tbuckley/cabot-search huggingface dataset:
Disordered development of gut microbiome interferes with the establishment of the gut ecosystem during early childhood with atopic dermatitis
Authors: Min-Jung Lee, Yoon Mee Park, Byunghyun Kim, in Hwan Tae, Nam-Eun Kim, Marina Pranata, Taewon Kim, Sungho Won, Nam Joo Kang, Yun Kyung Lee, Dong-Woo Lee, Myung Hee Nam, Soo-Jong Hong, Bong-Soo Kim
Journal: Gut Microbes (2022)

The gut microbiome influences the development of allergic diseases during early childhood. However, there is a lack of comprehensive understanding of microbiome-host crosstalk. Here, we analyzed the influence of gut microbiome dynamics in early childhood on atopic dermatitis (AD) and the potential interactions between host and microbiome that control this homeostasis. We analyzed the gut microbiome in 346 fecal samples (6–36 months; 112 non-AD, 110 mild AD, and 124 moderate to severe AD) from the Longitudinal Cohort for Childhood Origin of Asthma and Allergic Disease birth cohort. The microbiome-host interactions were analyzed in animal and in vitro cell assays. Although the gut microbiome maturated with age in both AD and non-AD groups, its development was disordered in the AD group. Disordered colonization of short-chain fatty acids (SCFA) producers along with age led to abnormal SCFA production and increased IgE levels. A butyrate deficiency and downregulation of GPR109A and PPAR-γ genes were detected in AD-induced mice. Insufficient butyrate decreases the oxygen consumption rate of host cells, which can release oxygen to the gut and perturb the gut microbiome. The disordered gut microbiome development could aggravate balanced microbiome-host interactions, including immune responses during early childhood with AD.
Treatment strategies for unruptured pancreaticoduodenal artery aneurysms associated with celiac artery occlusion
Authors: Koji Kubota, Akira Shimizu, Tsuyoshi Notake, Kiyotaka Hosoda, Atushi Kamachi, Takamune Goto, Hidenori Tomida, Shiori Yamazaki
Journal: International Journal of Surgery (2022)
Intervening on the storage time of RBC units and its effects on adverse recipient outcomes using real-world data
Authors: Peter Bruun-Rasmussen, Per Kragh Andersen, Karina Banasik, Søren Brunak, Pär Ingemar Johansson
Journal: Blood (2022)

Randomized controlled trials (RCTs) have found no evidence that the storage time of transfused red blood cell (RBC) units affects recipient survival. However, inherent difficulties in conducting RBC transfusion RCTs have prompted critique of their design, analyses, and interpretation. Here, we address these issues by emulating hypothetical randomized trials using large real-world data to further clarify the adverse effects of storage time. We estimated the comparative effect of transfusing exclusively older vs fresher RBC units on the primary outcome of death, and the secondary composite end point of thromboembolic events, or death, using inverse probability weighting. Thresholds were defined as 1, 2, 3, and 4 weeks of storage. A large Danish blood transfusion database from the period 2008 to 2018 comprising >900 000 transfusion events defined the observational data. A total of 89 799 patients receiving >340 000 RBC transfusions during 28 days of follow-up met the eligibility criteria. Treatment with RBC units exclusively fresher than 1, 2, 3, and 4 weeks of storage was found to decrease the 28-day recipient mortality with 2.44 percentage points (pp) (0.86 pp, 4.02 pp), 1.93 pp (0.85 pp, 3.02 pp), 1.06 pp (-0.20 pp, 2.33 pp), and -0.26 pp (-1.78 pp, 1.25 pp) compared with transfusing exclusively older RBC units, respectively. The 28-day risk differences for the composite end point were similar. This study suggests that transfusing exclusively older RBC units stored for >1 or 2 weeks increases the 28-day recipient mortality and risk of thromboembolism or death compared with transfusing fresher RBC units.
Author Correction: Stem cell architecture drives myelodysplastic syndrome progression and predicts response to venetoclax-based therapy
Authors: Irene Ganan-Gomez, Hui Yang, Feiyang Ma, Guillermo Montalban-Bravo, Natthakan Thongon, Valentina Marchica, Guillaume Richard-Carpentier, Kelly Chien, Ganiraju Manyam, Feng Wang, Ana Alfonso, Shuaitong Chen, Caleb Class, Rashmi Kanagal-Shamanna, Justin P. Ingram, Yamini Ogoti, Ashley Rose, Sanam Loghavi, Pamela Lockyer, Benedetta Cambo, Muharrem Muftuoglu, Sarah Schneider, Vera Adema, Michael McLellan, John Garza, Matteo Marchesini, Nicola Giuliani, Matteo Pellegrini, Jing Wang, Jason Walker, Ziyi Li, Koichi Takahashi, Joel D. Leverson, Carlos Bueso-Ramos, Michael Andreeff, Karen Clise-Dwyer, Guillermo Garcia-Manero, Simona Colla
Journal: Nature Medicine (2022)
Association of Influenza Vaccination With Cardiovascular Risk
Authors: Bahar Behrouzi, Deepak L. Bhatt, Christopher P. Cannon, Orly Vardeny, Douglas S. Lee, Scott D. Solomon, Jacob A. Udell
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Influenza infection is associated with increased cardiovascular hospitalization and mortality. Our prior systematic review and meta-analysis hypothesized that influenza vaccination was associated with a lower risk of cardiovascular events. <h3>Objective</h3> To evaluate, via an updated meta-analysis, if seasonal influenza vaccination is associated with a lower risk of fatal and nonfatal cardiovascular events and assess whether the newest cardiovascular outcome trial results are consistent with prior findings. <h3>Data Sources</h3> A previously published meta-analysis of randomized controlled trials (RCTs) and a large 2021 cardiovascular outcome trial. <h3>Study Selection</h3> Studies with RCTs published between 2000 and 2021 that randomized participants to either influenza vaccine or placebo/control. Eligible participants were inpatients and outpatients recruited for international multicenter RCTs and randomized to receive either influenza vaccine or placebo/control. <h3>Data Extraction and Synthesis</h3> PRISMA guidelines were followed in the extraction of study details, and risk of bias was assessed using the Cochrane Collaboration tool. Trial quality was evaluated using Cochrane criteria. Data were analyzed January 2020 and December 2021. <h3>Main Outcomes and Measures</h3> Random-effects Mantel-Haenszel risk ratios (RRs) and 95% CIs were derived for a composite of major adverse cardiovascular events and cardiovascular mortality within 12 months of follow-up. Where available, analyses were stratified by patients with and without recent acute coronary syndrome (ACS) within 1 year of randomization. <h3>Results</h3> Six published RCTs comprising a total of 9001 patients were included (mean age, 65.5 years; 42.5% women; 52.3% with a cardiac history). Overall, influenza vaccine was associated with a lower risk of composite cardiovascular events (3.6% vs 5.4%; RR, 0.66; 95% CI, 0.53-0.83;<i>P</i> &lt; .001). A treatment interaction was detected between patients with recent ACS (RR, 0.55; 95% CI, 0.41-0.75) and without recent ACS (RR, 1.00; 95% CI, 0.68-1.47) (<i>P</i>for interaction = .02). For cardiovascular mortality, a treatment interaction was also detected between patients with recent ACS (RR, 0.44; 95% CI, 0.23-0.85) and without recent ACS (RR, 1.45; 95% CI, 0.84-2.50) (<i>P</i>for interaction = .006), while 1.7% of vaccine recipients died of cardiovascular causes compared with 2.5% of placebo or control recipients (RR, 0.74; 95% CI, 0.42-1.30;<i>P</i> = .29). <h3>Conclusions and Relevance</h3> In this study, receipt of influenza vaccination was associated with a 34% lower risk of major adverse cardiovascular events, and individuals with recent ACS had a 45% lower risk. Given influenza poses a threat to population health during the COVID-19 pandemic, it is integral to counsel high-risk patients on the cardiovascular benefits of influenza vaccination.
Machine learning algorithms as early diagnostic tools for pancreatic fistula following pancreaticoduodenectomy and guide drain removal: A retrospective cohort study
Authors: Ziyun Shen, Haoda Chen, Weishen Wang, Wei Xu, Yiran Zhou, Yuanchi Weng, Zhiwei Xu, Xiaxing Deng, Chenghong Peng, Xiongxiong Lu, Baiyong Shen
Journal: International Journal of Surgery (2022)
Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies
Authors: Yuting Lu, Xiangliang Yuan, Miao Wang, Zhihao He, Hongzhong Li, Ji Wang, Qin Li
Journal: Journal of Hematology & Oncology (2022)

The gut microbiota have long been recognized to play a key role in human health and disease. Currently, several lines of evidence from preclinical to clinical research have gradually established that the gut microbiota can modulate antitumor immunity and affect the efficacy of cancer immunotherapies, especially immune checkpoint inhibitors (ICIs). Deciphering the underlying mechanisms reveals that the gut microbiota reprogram the immunity of the tumor microenvironment (TME) by engaging innate and/or adaptive immune cells. Notably, one of the primary modes by which the gut microbiota modulate antitumor immunity is by means of metabolites, which are small molecules that could spread from their initial location of the gut and impact local and systemic antitumor immune response to promote ICI efficiency. Mechanistic exploration provides novel insights for developing rational microbiota-based therapeutic strategies by manipulating gut microbiota, such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites, to augment the efficacy of ICI and advance the age utilization of microbiota precision medicine.
Hepatic hemangioma with Kasalbach Merritt syndrome in a specialized hospital in the north of Mexico
Authors: Vicente Alejandro Carrillo-Acosta, Vicente Carrillo-Maciel, Alma Leticia Acosta-Saludado, Felix Guillermo Estrada-Alonso, Samuel Ramos-Linaje, Jorge Garza-Sanchez, Yolanda Jaramillo-Rodriguez, Veronica Rodriguez-Carrillo, Oscar Chapa-Azuela
Journal: International Journal of Surgery (2022)
Vascular Aging After COVID-19: A Story of Lasting Injury or Prolonged Healing?
Authors: Leili Behrooz, Jennifer E. Ho, Naomi M. Hamburg
Journal: Circulation Research (2022)

ascular injury characterizes acute coronavirus disease 2019 (COVID-19) contributing to thrombotic, myocardial, and pulmonary complications. 1 More than 450 million people worldwide have survived acute COVID-19 with many suffering from persistent symptoms; 2 thus understanding the long-term cardiovascular implications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a critical public health problem.A recent study from the US Department of Veterans Affairs reported an increased risk of multiple cardiovascular disease events associated with prior COVID-19 even among individuals with mild disease. 3ersistent cardiovascular symptoms are frequently reported in individuals with postacute sequelae of severe acute respiratory syndrome coronavirus 2 (PASC) and are an integral portion of the multi-billion dollar National Institutes of Health-funded RECOVER study (Researching COVID to Enhance Recovery; recovercovid.org). 4The study by Zanoli et al 5 in this issue of Circulation Research provides early information about arterial aging following acute COVID-19 as a potential contributor to long-term cardiovascular symptoms and risk.
Annals Story Slam - Three-Finger Salute to the COVID-19 Pandemic
Authors: Marguerite Ahmar Sein Ohn-Saith
Journal: Annals of Internal Medicine (2022)

Web Exclusives29 April 2022Annals Story Slam - Three-Finger Salute to the COVID-19 PandemicFREEMarguerite Ahmar Sein Ohn-Saith, MBBSMarguerite Ahmar Sein Ohn-Saith, MBBSPortage, Michigan (M.A.O.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W22-0010 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Three-Finger Salute to the COVID-19 Pandemic "Three-Finger Salute to the COVID-19 Pandemic," by Dr. Marguerite Ahmar Sein Ohn-Saith (Duration 5:33)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Author, Article, and Disclosure InformationAuthors: Marguerite Ahmar Sein Ohn-Saith, MBBSAffiliations: Portage, Michigan (M.A.O.)Corresponding Author: Marguerite Ahmar Sein Ohn-Saith, MBBS; e-mail, drmsaith@gmail.com.This article was published at Annals.org on 29 April 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 2022Volume 175, Issue 6 Page: SS1 ePublished: 29 April 2022 Issue Published: June 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.Loading ...
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Journal: JAMA Network Open (2022)

Lori Uscher-Pines, PhD; Colleen McCullough, MPA; Michael S. Dworsky, PhD; Jessica Sousa, MSQ; Zachary Predmore, PhD; Kristin Ray, MD; Anthony Magit, MD; Chris Rivanis, BA; Carlos Lerner, MD; Joy Iwakoshi, MBA; Steven Barkley, MD; James P. Marcin, MD; Troy McGuire, MD; Michael-Anne Browne, MD; Craig Swanson, MD; John Patrick Cleary, MD; Erin Kelly, MPH; Katie Layton, BA; Lucy Schulson, MD
Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial
Authors: Charlotte Duch Lynggaard, Christian Grønhøj, Siri B. Jensen, Robin Christensen, Lena Specht, Elo Andersen, Tobias T. Andersen, Urszula M. Ciochon, Gulla S. Rathje, Adam E. Hansen, Helene Stampe, Anne Fischer-Nielsen, Christian von Buchwald
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections into the submandibular glands. Experimental Design: An investigator-initiated, randomized, single-center, placebo-controlled trial. Previous patients with oropharyngeal squamous cell carcinoma with radiation-induced xerostomia were randomly (1:1) allocated to receive a 2.8 million ASCs/cm3 injection or placebo in both submandibular glands and followed for a minimum of 2 years. The primary endpoint was number of serious adverse events (SAE). Secondary endpoints included whole saliva flow rates and xerostomia-related symptoms. Data analysis was based on the intention-to-treat population using repeated measures mixed-effects linear models. Results: Thirty-three patients were randomized; 30 patients were treated (ASC group, n = 15; placebo group, n = 15). Long-term safety data were collected from all 30 patients. During follow-up, 6 of 15 (40%) of the ASC-treated patients versus 5 of 15 (33%) of the placebo patients experienced an SAE; no SAEs appeared to be treatment related. Unstimulated whole saliva flow rate increased to 0.20 and 0.16 mL/minute in the ASC and placebo group, respectively, yielding a 0.05 mL/minute (95% confidence interval: 0.00–0.10; P = 0.051) difference between groups. Patient-reported xerostomia symptoms diminished according to a decreased xerostomia questionnaire summary score of 35.0 and 45.1, respectively [−10.1 (−18.1 to −2.2); P = 0.013]. Three of the visual analog scale xerostomia measures indicated clinical benefit following use of ASC. Conclusions: Our data show that ASC therapy is safe with a clinically relevant effect on xerostomia-related symptoms. Confirmation in larger randomized controlled trials is warranted.
Ninety-day mortality following lung cancer surgery: outcomes from the English national clinical outcomes audit
Authors: Helen Morgan, David Baldwin, Richard Hubbard, Neal Navani, Doug West, Emma Louise O'Dowd
Journal: Thorax (2022)

Accurately explaining perioperative mortality and risk to patients is an essential part of shared decision making. In the case of lung cancer surgery, the currently available multivariable mortality prediction tools perform poorly, and could mislead patients. Using data from 2004 to 2012, this group has previously produced data tables for 90-day postoperative mortality, to be used as a communication aid in the consenting process. Using National Lung Cancer Clinical Outcomes audit data from 2017 to 2018, we have produced updated early mortality tables, to reflect current thoracic surgery practice.
Preoperative future liver remnant (FLR) augmentation with special focus on local tumor control and in-situ immunization for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LC)
Authors: Oleksandr Korshak, Olga Sokolova, Alla Kubashko, Andriy Zylenko, Vlad Kropelnytsckyi, Maria Stassiuk, Natalia Kostyleva, Ivan Mazanovych, Oleksandr Ostapyshen, Oleksandr Hrinenko
Journal: International Journal of Surgery (2022)
Two <i>SERPINC1</i> variants affecting N-glycosylation of Asn224 cause severe thrombophilia not detected by functional assays
Authors: Maria Eugenia de la Morena-Barrio, Pierre Suchon, Eva Marie Jacobsen, Nina Iversen, Antonia Miñano, Belén de la Morena-Barrio, Carlos Bravo-Pérez, Jose Padilla, Rosa Cifuentes, Susana Asenjo, Jean François Deleuze, David Alexandre Trégouët, Maria Luisa Lozano, Vicente Vicente, Per Morten Sandset, Pierre Emmanuel Morange, Javier Corral
Journal: Blood (2022)

Abstract Antithrombin deficiency, the most severe congenital thrombophilia, might be underestimated, as some pathogenic variants are not detected by routine functional methods. We have identified 2 new SERPINC1 variants, p.Glu227Lys and p.Asn224His, in 4 unrelated thrombophilic patients with early and recurrent thrombosis that had normal antithrombin activity. In one case, the mutation was identified by whole genome sequencing, while in the 3 remaining cases, the mutation was identified by sequencing SERPINC1 based on a single functional positive finding supporting deficiency. The 2 variants shared a common functional defect, an impaired or null N-glycosylation of Asn224 according to a eukaryotic expression model. Carriers had normal anti-FXa or anti-FIIa activities but impaired anti-FVIIa activity and a detectable loss of inhibitory function when incubating the plasma for 1 hour at 41°C. Moreover, the β glycoform of the variants, lacking 2 N-glycans, had reduced secretion, increased heparin affinity, no inhibitory activity, and a potential dominant–negative effect. These results explain the increased thrombin generation observed in carriers. Mutation experiments reflected the role that Lysine residues close to the N-glycosylation sequon have in impairing the efficacy of N-glycosylation. Our study shows new elements involved in the regulation of N-glycosylation, a key posttranslational modification that, according to our results, affects folding, secretion, and function, providing new evidence of the pathogenic consequence of an incorrect N-glycosylation of antithrombin. This study supports that antithrombin deficiency is underestimated and encourages the development of new functional and genetic tests to diagnose this severe thrombophilia.
Real-World Evidence — Where Are We Now?
Authors: John Concato, Jacqueline Corrigan-Curay
Journal: New England Journal of Medicine (2022)

Interview with Kushal Kadakia on the 21st Century Cures Act, Cures 2.0, and lessons from Covid-19 for medical product development. (11:29)Download Notwithstanding ongoing confusion over the concepts of "real-world data" and "real-world evidence" in 2022, more than 5 years after the passage of the 21st Century Cures Act, the FDA continues to evaluate such data and evidence as it considers regulatory decisions.
Local anesthetics elicit immune-dependent anticancer effects
Authors: Lucillia Bezu, Alejandra Wu Chuang, Allan Sauvat, Juliette Humeau, Wei Xie, Giulia Cerrato, Peng Liu, Liwei Zhao, Shuai Zhang, Julie Le Naour, Jonathan Pol, Peter van Endert, Oliver Kepp, Fabrice Barlesi, Guido Kroemer
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Retrospective clinical trials reported a reduced local relapse rate, as well as improved overall survival after injection of local anesthetics during cancer surgery. Here, we investigated the anticancer effects of six local anesthetics used in clinical practice. Results In vitro , local anesthetics induced signs of cancer cell stress including inhibition of oxidative phosphorylation, and induction of autophagy as well as endoplasmic reticulum (ER) stress characterized by the splicing of X-box binding protein 1 (XBP1s) mRNA, cleavage of activating transcription factor 6 (ATF6), phosphorylation of eIF2α and subsequent upregulation of activating transcription factor 4 (ATF4). Both eIF2α phosphorylation and autophagy required the ER stress-relevant eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3, best known as PERK). Local anesthetics also activated two hallmarks of immunogenic cell death, namely, the release of ATP and high-mobility group box 1 protein (HMGB1), yet failed to cause the translocation of calreticulin (CALR) from the ER to the plasma membrane. In vivo , locally injected anesthetics decreased tumor growth and improved survival in several models of tumors established in immunocompetent mice. Systemic immunotherapy with PD-1 blockade or intratumoral injection of recombinant CALR protein, increased the antitumor effects of local anesthetics. Local anesthetics failed to induce antitumor effects in immunodeficient mice or against cancers unable to activate ER stress or autophagy due to the knockout of EIF2AK3/PERK or ATG5, respectively. Uncoupling agents that inhibit oxidative phosphorylation and induce autophagy and ER stress mimicked the immune-dependent antitumor effects of local anesthetics. Conclusion Altogether, these results indicate that local anesthetics induce a therapeutically relevant pattern of immunogenic stress responses in cancer cells.
The Vacinómetro® initiative: an eleven-year monitorization of influenza vaccination coverage rates among risk groups in Portugal
Authors: F. Froes, A. Morais, V. Hespanhol, R. Nogueira, J.S. Carlos, N. Jacinto, M. Martins, C. Gomes, C.R. Cordeiro
Journal: Pulmonology (2022)

Annual vaccination is fundamental for individual and group protection against seasonal influenza infection. International and Portuguese healthcare organizations have established influenza vaccination coverage rate (VCR) targets for risk groups, namely 75% in people ≥ 65 years old. The Vacinómetro® initiative has been monitoring influenza VCR among target risk groups in Portugal since 2009,: Group 1, ≥ 65 years old; Group 2, patients with chronic conditions; Group 3, healthcare workers in direct contact with patients; and Group 4, 60-64 years old. Besides VCR, social-demographic and health-related variables have been evaluated. During the study period (2009/2010 – 2019/2020), the VCR increased in the 4 target risk groups: from 58.6% to 76.0% in Group 1 (reaching the WHO target); 33.3% to 72.0% in Group 2; 25.0% to 58.9% in Group 3; and 36.6% to 42.8% in Group 4. "Physician recommendation" was the main driver for vaccination whereas "lack of habit" was the main barrier to vaccination. Vacinómetro® data demonstrate that free-of-charge vaccination has a positive impact on VCR. The observed positive trends in influenza VCR demonstrate that public health measures implemented in Portugal to facilitate access to influenza vaccine result in increased vaccine uptake. Strategies to promote population literacy and the physician's awareness should be continued and reinforced. Free-of-charge vaccination criteria extended to more risk groups would also contribute to higher influenza VCR in Portugal.