tbuckley/cabot-search huggingface dataset:
PTH-046 Double-balloon enteroscopy assisted cyanoacrylate injection therapy of small-bowel varices: international experience from two european centres
Authors: Alberto Murino, Andrea May, Nikolaos Lazaridis, Nikolaos Koukias, Erasmia Vlachou, Katie Planche, David Patch, Edward J Despott
Journal: Endoscopy (2018)

<h3>Introduction</h3> Small bowel varices (SBV) are a rare consequence of portal hypertension and could lead to life-threatening mid-gut bleeding. Radiological intervention (RI) is usually considered first line management (e.g. Trans-jugular intrahepatic portosystemic shunting (TIPS), stenting of occluded mesenteric veins±embolisation of culprit varices). In cases where RI is impossible, management options become very limited. This multicentre case series evaluated the usefulness of double-balloon enteroscopy (DBE) assisted cyanoacrylate injection of SBV. <h3>Methods</h3> Retrospective review of DBE facilitated cyanoacrylate injection of SBV (December 2015 to October 2016). Demographic, clinical, endoscopic and radiological findings, interventions and follow-up data were analysed. <h3>Results</h3> Ten DBEs were performed in 6 patients (4 women, median age: 68.5 years). Five patients had previous surgery (hemi-hepatectomy (n=2); SB resection (n=2); appendicitis with peritonitis (n=1)); one patient had a history of intra-abdominal sepsis in childhood causing portal vein thrombosis and one had cryptogenic thrombosis of the portal and the mesenteric vein. No radiological or surgical options were deemed feasible in any case. SBV were diagnosed at capsule endoscopy and triple phase CT mesenteric angiography. At DBE, a total of 13 nests of SBV were identified and injected with cyanoacrylate glue. There were no haemorrhagic or embolic complications but 1 patient developed an infection of a congenital urachal cyst, which was treated successfully with antibiotics. All patients underwent DBEs via the anterograde route, 2 patients required bi-directional DBE for treatment of both proximal and distal SBV and in total 2 patients required a repeat DBE for further treatment of SBV. At 30 day follow-up post-therapy, only 1 patient had experienced a mild recurrence of mid-gut bleeding treated conservatively. One patient presented with acute gastrointestinal bleeding 7 months later and a repeat DBE with cyanoacrylate injection therapy was successfully performed. One patient was lost to follow-up. The remaining patients had 12 months of follow-up without any recurrent gastrointestinal bleeding. <h3>Conclusion</h3> Cyanoacrylate injection therapy of SBV at DBE appears to be a safe and effective management strategy for this condition when other first-line options are not feasible.
Treating diarrhoea
Authors: S. L Gorbach
Journal: BMJ (1997)

Central tolerance serves to eliminate newly developing T cells that express strongly autoreactive T cell receptors. Although central tolerance is efficient in deleting high avidity autoreactive T cells, some lower avidity autoreactive T cells escape negative selection to cause autoimmune diseases. Although tight allelic exclusion limits thymocytes to expressing a single TCRbeta chain, rearrangement of the TCRalpha chain continues unabated until halted by positive selection, enabling thymocytes to express up to two TCRalpha chains and thus two TCRs. Moreover, it has been postulated that pathogenic low avidity autoreactive CD8 T cells may escape central tolerance through expression of a secondary benign TCR that mediates positive selection. To determine the role of dual TCR expressing CD8 T cells in autoreactivity and autoimmunity, we have compared CD8 T cell autoreactivity against the model autoantigen ovalbumin between T cells capable of expressing two TCRs (TCRalpha<sup>+/+</sup>) versus T cells capable of expressing a single TCR (TCRalpha<sup>+/−</sup>). TCRalpha<sup>+/−</sup> CD8 T cells exhibited reduced proliferative capacity upon OVA stimulation relative to TCRalpha<sup>+/+</sup> CD8 T cells. In addition, a lower frequency of TCRalpha<sup>+/−</sup> CD8 T cell effectors produced IFN-gamma upon activation with OVA compared to TCRalpha<sup>+/+</sup> CD8 T cell effectors. Taken together, we shown that dual TCR expression by CD8 T cells reduces the efficiency of T cell tolerance and may potentiate T cell autoreactivity. We are investigating whether dual TCR-expressing T cells are key to the pathogenesis of autoimmune diabetes in our mouse model system. Our results will provide valuable insight into the escape mechanisms exploited by pathogenic autoreactive CD8 T cells.
Initial Management of Acute Pancreatitis
Authors: Alexander Chaitoff, Adam S. Cifu, Joshua D. Niforatos
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sleep Onset Problems and Subcortical Development in Infants Later Diagnosed With Autism Spectrum Disorder
Authors: Katherine E. MacDuffie, Mark D. Shen, Stephen R. Dager, Martin A. Styner, Sun Hyung Kim, Sarah Paterson, Juhi Pandey, Tanya St. John, Jed T. Elison, Jason J. Wolff, Meghan R. Swanson, Kelly N. Botteron, Lonnie Zwaigenbaum, Joseph Piven, Annette M. Estes
Journal: American Journal of Psychiatry (2020)

Sleep patterns in children with autism spectrum disorder (ASD) appear to diverge from typical development in the second or third year of life. Little is known, however, about the occurrence of sleep problems in infants who later develop ASD and possible effects on early brain development. In a longitudinal neuroimaging study of infants at familial high or low risk for ASD, parent-reported sleep onset problems were examined in relation to subcortical brain volumes in the first 2 years of life.A total of 432 infants were included across three study groups: infants at high risk who developed ASD (N=71), infants at high risk who did not develop ASD (N=234), and infants at low risk (N=127). Sleep onset problem scores (derived from an infant temperament measure) were evaluated in relation to longitudinal high-resolution T1 and T2 structural imaging data acquired at 6, 12, and 24 months of age.Sleep onset problems were more common at 6-12 months among infants who later developed ASD. Infant sleep onset problems were related to hippocampal volume trajectories from 6 to 24 months only for infants at high risk who developed ASD. Brain-sleep relationships were specific to the hippocampus; no significant relationships were found with volume trajectories of other subcortical structures examined (the amygdala, caudate, globus pallidus, putamen, and thalamus).These findings provide initial evidence that sleep onset problems in the first year of life precede ASD diagnosis and are associated with altered neurodevelopmental trajectories in infants at high familial risk who go on to develop ASD. If replicated, these findings could provide new insights into a potential role of sleep difficulties in the development of ASD.
Platelets docking to VWF prevent leaks during leukocyte extravasation by stimulating Tie-2
Authors: Laura J. Braun, Rebekka I. Stegmeyer, Kerstin Schäfer, Stefan Volkery, Silke M. Currie, Birgit Kempe, Astrid F. Nottebaum, Dietmar Vestweber
Journal: Blood (2020)
Solidarity and Community Engagement in Global Health Research
Authors: Bridget Pratt, Phaik Yeong Cheah, Vicki Marsh
Journal: The American Journal of Bioethics (2020)

Community engagement (CE) is gaining prominence in global health research. A number of ethical goals-spanning the instrumental, intrinsic, and transformative-have been ascribed to CE in global health research. This paper draws attention to an additional transformative value that CE is not typically linked to but that seems very relevant: solidarity. Both are concerned with building relationships and connecting parties that are distant from one another. This paper first argues that furthering solidarity should be recognized as another ethical goal for CE in global health research. It contends that, over time, CE can build the bases of solidaristic relationships-moral imagination, recognition, understanding, empathy-between researchers and community members. Applying concepts from existing accounts of solidarity, the paper develops preliminary ideas about who should be engaged and how to advance solidarity. The proposed approach is compared to current CE practice in global health research. Finally, the paper briefly considers how solidaristic CE could affect how global health research is performed.
Differentiation Syndrome with Ivosidenib and Enasidenib Treatment in Patients with Relapsed or Refractory IDH-Mutated AML: A U.S. Food and Drug Administration Systematic Analysis
Authors: Kelly J. Norsworthy, Flora Mulkey, Emma C. Scott, Ashley F. Ward, Donna Przepiorka, Rosane Charlab, Sarah E. Dorff, Albert Deisseroth, Dickran Kazandjian, Rajeshwari Sridhara, Julia A. Beaver, Ann T. Farrell, R. Angelo de Claro, Richard Pazdur
Journal: Clinical Cancer Research (2020)

Differentiation syndrome (DS) is a serious adverse reaction of isocitrate dehydrogenase (IDH) inhibitors ivosidenib and enasidenib in patients with (IDH)1- and IDH2-mutated acute myeloid leukemia (AML), respectively.During FDA review of marketing applications for ivosidenib and enasidenib, data from pivotal trials were queried to identify cases of DS in patients with relapsed or refractory (R/R) AML. One hundred seventy-nine patients with R/R AML received ivosidenib and 214 received enasidenib. Adverse events, labs, and vital signs in the first 90 days of treatment were screened per diagnostic criteria, and narratives were reviewed to adjudicate DS cases.We identified 72 of 179 (40%) potential cases for ivosidenib and 86 of 214 (40%) for enasidenib; 34 of 179 (19%) and 41 of 214 (19%) were adjudicated as DS. Leukocytosis was present in 79% and 61% of cases, respectively. Median (range) time to onset was 20 (1-78) and 19 (1-86) days. Grade ≥ 3 adverse reactions occurred in 68% and 66%; 6% and 5% were fatal. Univariate analyses suggested baseline bone marrow blasts ≥ 48% and peripheral blood blasts ≥ 25% and 15% for ivosidenib and enasidenib, respectively, were associated with increased risk of DS. Complete remission (CR) + CR with partial hematologic recovery rates were lower in patients with versus without DS [ivosidenib 18% (95% confidence interval, 7%-35%) vs. 36% (28%-45%); enasidenib 18% (7%-33%) vs. 25% (18%-32%)].DS is a common and potentially fatal adverse reaction of IDH inhibitors, and use of standardized diagnostic criteria may aid in earlier diagnosis and treatment.See related commentary by Zeidner, p. 4174.
Facioscapulohumeral Muscular Dystrophy—a Tale of Heterogeneity and the Power of Clinical Assessments
Authors: Karine Nguyen, Jérôme D. Robin
Journal: JAMA Network Open (2020)

Lucia Ruggiero, PhD; Fabiano Mele, MASc; Fiore Manganelli, MD; Dario Bruzzese, MD; Giulia Ricci, PhD; Liliana Vercelli, PhD; Monica Govi, MASc; Antonio Vallarola, MASc; Silvia Tripodi, MD; Luisa Villa, MD; Antonio Di Muzio, MD; Marina Scarlato, MD; Elisabetta Bucci, PhD; Giovanni Antonini, MD; Lorenzo Maggi, PhD; Carmelo Rodolico, MD; Giuliano Tomelleri, MD; Massimiliano Filosto, MD; Stefano Previtali, MD; Corrado Angelini, MD; Angela Berardinelli, MD; Elena Pegoraro, MD; Maurizio Moggio, MD; Tiziana Mongini, MD; Gabriele Siciliano, MD; Lucio Santoro, MD; Rossella Tupler, PhD
Treatment of Spinal-Cord Injury
Authors: Thomas B. Ducker
Journal: New England Journal of Medicine (1990)

To have an intact brain and intact sensation and function about the head, neck, and shoulders, yet to lack basic hand skills and locomotion is indeed a tragic disability. If there is also loss of bowel and bladder control, the problem seems overwhelming. Just over 50 years ago, traumatic quadriplegia was lethal in 60 to 80 percent of cases.1 With improved medical and surgical care and effective modern rehabilitation, men and women with spinal injury now usually live. Even the bowel, bladder, and cardiovascular problems that result from spinal injury can be managed. Mortality from spinal injury dropped from 30 . . .
Blocking IL-6 trans-Signaling Prevents High-Fat Diet-Induced Adipose Tissue Macrophage Recruitment but Does Not Improve Insulin Resistance (vol 21, pg 403, 2015)
Authors: Michael J Kraakman, Helene L Kammoun, Tamara L Allen, Virginie Deswaerte, Darren C Henstridge, Emma Estevez, Vance B Matthews, Bronwyn Neill, David A White, Andrew J Murphy, Lone Peijs, Christine Yang, Steve Risis, Clinton R Bruce, Xiao-Jun Du, Alex Bobik, Robert S Lee-Young, Bronwyn A Kingwell, Ajithkumar Vasanthakumar, Wei Shi, Axel Kallies, Graeme I Lancaster, Stefan Rose-John, Mark A Febbraio
Journal: Cell Metabolism (2016)
The application and prospect of CDK4/6 inhibitors in malignant solid tumors
Authors: Qi Du, Xiang Guo, Miao Wang, Yongfu Li, Xiaoyi Sun, Qin Li
Journal: Journal of Hematology & Oncology (2020)

Abstract Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, which block the transition from the G1 to S phase of the cell cycle by interfering with Rb phosphorylation and E2F release, have shown potent antitumor activity and manageable toxicity in HR+/HER2− breast cancer patients. Some clinical trials involving CDK4/6 inhibitors in other tumors have achieved preliminary impressive efficacy. Whether CDK4/6 inhibitors possess great potential as broad-spectrum antitumor drugs and how to maximize their clinical benefits remain uncertain. TCGA database analysis showed that CDK4/6 genes and related genes are widely expressed among various tumors, and high or moderate expression of CDK4/6 genes commonly indicates poor survival. CDK4/6 gene expression is significantly higher in COAD, ESCA, STAD, LIHC, and HNSC, suggesting that CDK4/6 inhibitors could be more efficacious in those tumors. Moreover, network analysis with the STRING database demonstrated that CDK4/6-related proteins were co-expressed or co-occurred with the classical tumor signaling pathways, such as the cell cycle pathway, RAS pathway, PI3K pathway, Myc pathway, and p53 pathway. The extensive antitumor effects of CDK4/6 inhibitors may be achieved by synergizing or antagonizing with other signaling molecule inhibitors, and combination therapy might be the most effective treatment strategy. This article analyzed the feasibility of expanding the application of CDK4/6 inhibitors at the genetic level and further summarized the associated clinical/preclinical studies to collect supportive evidence. This is the first study that presents a theoretical foundation for CDK4/6 inhibitor precision therapy via combined analysis of comprehensive gene information and clinical research results.
Management of early melanoma recurrence despite adjuvant anti-PD-1 antibody therapy☆
Authors: C.N. Owen, A.N. Shoushtari, D. Chauhan, D.J. Palmieri, B. Lee, M.W. Rohaan, J. Mangana, V. Atkinson, F. Zaman, A. Young, C. Hoeller, P. Hersey, R. Dummer, M.A. Khattak, M. Millward, S.P. Patel, A. Haydon, D.B. Johnson, S. Lo, C.U. Blank, S. Sandhu, M.S. Carlino, J.M.G. Larkin, A.M. Menzies, G.V. Long
Journal: Annals of Oncology (2020)
Breast Cancer Screening and Diagnosis
Authors: Therese B. Bevers, Benjamin O. Anderson, Ermelinda Bonaccio, Sandra Buys, Mary B. Daly, Peter J. Dempsey, William B. Farrar, Irving Fleming, Judy E. Garber, Randall E. Harris, Alexandra S. Heerdt, Mark Helvie, John G. Huff, Nazanin Khakpour, Seema A. Khan, Helen Krontiras, Gary Lyman, Elizabeth Rafferty, Sara Shaw, Mary Lou Smith, Theodore N. Tsangaris, Cheryl Williams, Thomas Yankeelov
Journal: Journal of the National Comprehensive Cancer Network (2009)

Women in the United States have a 12.3% estimated lifetime risk for developing breast cancer (i.e., 1 in 8 women). 1 In 2009, an estimated 194,290 cases of invasive breast cancer (192,370 women and 1919 men) and 62,280 cases of female carcinoma in situ of the breast will be diagnosed in the United States, with 40,610 deaths from invasive breast cancer predicted. 2However, mortality from breast cancer has decreased slightly, attributed partly to mammographic screening. 3he NCCN Breast Cancer Screening and Diagnosis Panel designed these practice guidelines to fa-
Danger signals in liver injury and restoration of homeostasis
Authors: Hui Han, Romain Desert, Sukanta Das, Zhuolun Song, Dipti Athavale, Xiaodong Ge, Natalia Nieto
Journal: Journal of Hepatology (2020)

Damage-associated molecular patterns are signalling molecules involved in inflammatory responses and restoration of homeostasis. Chronic release of these molecules can also promote inflammation in the context of liver disease. Herein, we provide a comprehensive summary of the role of damage-associated molecular patterns as danger signals in liver injury. We consider the role of reactive oxygen species and reactive nitrogen species as inducers of damage-associated molecular patterns, as well as how specific damage-associated molecular patterns participate in the pathogenesis of chronic liver diseases such as alcohol-related liver disease, non-alcoholic steatohepatitis, liver fibrosis and liver cancer. In addition, we discuss the role of damage-associated molecular patterns in ischaemia reperfusion injury and liver transplantation and highlight current studies in which blockade of specific damage-associated molecular patterns has proven beneficial in humans and mice.
Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis
Authors: Franco Locatelli, Michael B. Jordan, Carl Allen, Simone Cesaro, Carmelo Rizzari, Anupama Rao, Barbara Degar, Timothy P. Garrington, Julian Sevilla, Maria-Caterina Putti, Franca Fagioli, Martina Ahlmann, Jose-Luis Dapena Diaz, Michael Henry, Fabrizio De Benedetti, Alexei Grom, Genevieve Lapeyre, Philippe Jacqmin, Maria Ballabio, Cristina de Min
Journal: New England Journal of Medicine (2020)

Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality.We investigated the efficacy and safety of emapalumab (a human anti-interferon-γ antibody), administered with dexamethasone, in an open-label, single-group, phase 2-3 study involving patients who had received conventional therapy before enrollment (previously treated patients) and previously untreated patients who were 18 years of age or younger and had primary hemophagocytic lymphohistiocytosis. The patients could enter a long-term follow-up study until 1 year after allogeneic hematopoietic stem-cell transplantation or until 1 year after the last dose of emapalumab, if transplantation was not performed. The planned 8-week treatment period could be shortened or extended if needed according to the timing of transplantation. The primary efficacy end point was the overall response, which was assessed in the previously treated patients according to objective clinical and laboratory criteria.At the cutoff date of July 20, 2017, a total of 34 patients (27 previously treated patients and 7 previously untreated patients) had received emapalumab; 26 patients completed the study. A total of 63% of the previously treated patients and 65% of the patients who received an emapalumab infusion had a response; these percentages were significantly higher than the prespecified null hypothesis of 40% (P = 0.02 and P = 0.005, respectively). In the previously treated group, 70% of the patients were able to proceed to transplantation, as were 65% of the patients who received emapalumab. At the last observation, 74% of the previously treated patients and 71% of the patients who received emapalumab were alive. Emapalumab was not associated with any organ toxicity. Severe infections developed in 10 patients during emapalumab treatment. Emapalumab was discontinued in 1 patient because of disseminated histoplasmosis.Emapalumab was an efficacious targeted therapy for patients with primary hemophagocytic lymphohistiocytosis. (Funded by NovImmune and the European Commission; NI-0501-04 and NI-0501-05 ClinicalTrials.gov numbers, NCT01818492 and NCT02069899.).
Community Empowerment Through Education: The Inherent Foundation of Promoting Solidarity in Global Health Research
Authors: Gregory C. Valentine, Krystle Perez, Elliott Mark Weiss
Journal: The American Journal of Bioethics (2020)

Solidarity is defined as a “…a value/concept [that] acknowledges our equal vulnerability, self-insufficiency, and interdependence” (Pratt et al. 2020). While the authors discuss the importance of s...
Efficacy and safety of endoscopic submucosal dissection in elderly patients with esophageal squamous cell carcinoma.
Authors: In Seub Shin, Byeong Geun Song, Doyeon Kim, Hyuk Lee, Byung-Hoon Min, Jun Haeng Lee, Poong-Lyul Rhee, Jae J. Kim, Yang Won Min
Journal: Journal of Clinical Oncology (2017)

182 Background: Endoscopic submucosal dissection (ESD) has been widely applied to superficial esophageal squamous cell carcinoma (SCC) as a minimally invasive treatment, which has advantages over surgery especially in the elderly who are at high risk of surgery. This study elucidated the efficacy and safety of ESD for superficial esophageal SCC in the elderly. Methods: Between April 2007 and June 2016, a total of 176 patients with superficial esophageal SCC were studied. The short-term outcomes including En bloc resection, complete resection, and curative resection rate and procedure-related complication rates were compared between elderly group ( n = 20, ≥ 75 years of age) and non-elderly group ( n = 156, &lt; 75 years of age). Results: The mean age of elderly group was 76.9 ± 1.5 years and that of non-elderly group was 62.9 ± 6.9 years ( p &lt; 0.001). Sex, past medical history (hypertension and diabetes), body mass index, tumor characteristics (number, location, shape, maximal and circumferential size of tumor and resected specimen, and depth), and presence of stricture prevention did not differ between two groups. En bloc resection (95% vs 93.6%, p &gt; 0.999), complete resection (85% vs 73.1%, p = 0.292), and curative resection rates (75% vs 56.4%, p = 0.149) did not differ significantly between two groups. Procedure time and hospital stay were also similar. Complications of ESD such as stricture (10% vs 12.8%, p &gt; 0.999) and perforation (10% vs 7.7%, p = 0.587) occurred similarly. Conclusions: ESD for superficial esophageal SCC is effective and safe in elderly patients like in non-elderly patients.