tbuckley/cabot-search huggingface dataset:
POS0422 PANNICULITIS AS A MANIFESTATION OF AN AUTOIMMUNE/AUTOINFLAMMATORY DISEASE
Authors: O. Egorova, A. Datsina, A. Potapova
Journal: Annals of the Rheumatic Diseases (2021)

Background: ASIA syndrome or Schonfeld syndrome is an autoimmune/inflammatory condition induced by adjuvants in genetically susceptible individuals with the development of rheumatic diseases (RD), multiple sclerosis, sarcoidosis, and others. Objectives: to characterize the symptoms of panniculitis (Pn) associated with ASIA-syndrome Methods: Within 7 years, ASIA syndrome was diagnosed in 12 women, average age 37.2±7.4, with a referral diagnosis of “Erythema Nodosum” or “Panniculitis”. The duration of the disease was 16.7±3.9 months. In addition to general clinical study, the serum concentration of α-1 antitrypsin, amylase, lipase, ferritin, creatine phosphokinase (CPK), immunological parameters (ANP-Hep2, dsDNA, C3 and C4, CRP, ANCA, Scl-70, antibodies to cardiolipins G and M), computed tomography of the chest organs, pathomorphological and immunohistochemical examination of a biopsy specimen of skin with subcutaneous fat tissue (SFA) from the affected areas. Results: The development of ASIA syndrome was preceded by gluteoplasty using propantriol-1,2,3 (in 4 patients), liposuction (2), biorevitalization with hyaluronic acid (2) and endoprosthetics with breast implants (2), bone metal construction (1) and mesh hernioplasty (1). The clinical picture of Pn was characterized by generalized red-purple painful (VAS pain 55.8±17.3 mm) subcutaneous indurations on the upper limbs and trunk (in 100% of cases), face (16.6%) and lower limbs (33.3%), with ulceration and oily fluid leakage (58.6%). The saucer symptom was recorded in 83.3% of the observed patients. In 66.6% of cases, fever and articular syndrome were observed, in 41.6% – myasthenic syndrome and lymphadenopathy, in 8.3% – xerophthalmia, keratoconjunctivitis dry, xerostomia and recurrent parotitis. In blood tests, leukopenia (up to 2.0x109/l) was identified in 33.3% of patients, a significant increase in the level of creatinine phosphakinase – in 16,6%, a two or more times increase in ESR and CRP – in 100%. All patients demonstrated immunological changes. The morphological picture of the skin and SFA in 75% of cases resembled lobular Pn, in 8.3% – tumor lymphocytes with the immunophenotype of cytotoxic T-lymphocytes: CD3+, CD8+ were detected. The results obtained allowed confirming RD in 8 patients: systemic lupus erythematosus and idiopathic lobular panniculitis in 2 patients (respectively) and 1 in dermatomyositis, systemic scleroderma of Sjogren’s disease, mixed connective tissue disease. One case was diagnosed with sarcoidosis and T-cell lymphoma. In 2 patients after the liposuction procedure the course of Pn was reversible. Conclusion: Diagnosis of Pn associated with ASIA syndrome is a complex task that requires a multidisciplinary approach to verify the diagnosis and treatment tactics. Disclosure of Interests: None declared
Covid 19: How harm reduction advocates and the tobacco industry capitalised on the pandemic to promote nicotine
Authors: Stéphane Horel, Ties Keyzer
Journal: BMJ (2021)

Scientific papers suggesting that smokers are less likely to fall ill with covid-19 are being discredited as links to the tobacco industry are revealed, report <b>Stéphane Horel</b> and <b>Ties Keyzer</b>
Long-term follow-up of subcutaneous versus intravenous bortezomib during induction therapy for newly diagnosed multiple myeloma treated within the GMMG-MM5 Phase III Trial
Authors: Hans Salwender, Ahmet Elmaagacli, Maximilian Merz, Kaya Miah, Axel Benner, Mathias Haenel, Christian Jehn, Elias K. Mai, Uta Bertsch, Igor W. Blau, Christof Scheid, Dirk Hose, Anja Seckinger, Anna Jauch, Marc S. Raab, Steffen P. Luntz, Britta Besemer, Markus Munder, Peter Brossart, Stephan Fuhrmann, Hans-Walter Lindemann, Katja Weisel, Jan Duerig, Hartmut Goldschmidt
Journal: Leukemia (2021)
POS1368 ANTI-IL-1 THERAPIES IN COLCHICINE-RESISTANT OR İNTOLERANT PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER: SINGLE CENTER EXPERIENCE
Authors: M. E. Derin, B. Karakaş, B. Karataş, N. Çabuk Çelik, İ. Yalçin, A. Şahin
Journal: Annals of the Rheumatic Diseases (2021)

Background: Familial Mediterranean Fever (FMF) is a hereditary auto-inflammatory disease characterized by recurrent fever and serosal inflammation (1). The goal of FMF treatment is to prevent the attacks and to minimize subclinical inflammation between attacks The main treatment of FMF is colchicine however anti-interleukin-1 treatments are recommended in colchicine resistant and/or intolerant FMF patients (2). Objectives: The aim of this study is to evaluate the efficacy of anti-interleukin-1 (anti-IL-1) agents in 81 FMF patients with resistant/intolareted to colchicine or complicated with amyloidosis. Methods: Between January 2014 and December 2020, eighty-one patients who were diagnosed as FMF according to the criteria of Tel-Hashomer that following-up at Cumhuriyet University Medical Faculty Rheumatology-Internal Medicine Department were included in to the study. Results: 45 (55.6%) male and 36 (44.4%) female were included in the study. The median age of the patients was 25 years (min:17-max: 60) and the median age at diagnosis was 15 years (min 3-max 46). 44 patients (54.3%) used Anakinra (100 mg/day), and 27 (45.7%) canakinumab (150mg/8month) were used. 49 cases were resistant to colchicine,16 were intolerant to colchicine, 16 (20%) cases were comlicated with amyloidosis. 10 patients had renal transplantation. MEFV gene mutations are shown in Table 1. Median duration of anti-IL-1 agent use was 24 month (min:4-max 52). 9 patients were resistant to anakinra, 18 patients had side effects which anakinra related. After a median follow up 12 months overall clinical response was %95 (frequency of attacks &lt;1/6months). median proteinuria decreased from 3500 mg /day to median 1500 mg /day (p: 0.04) (Table 2). IL-6 treatment was started in 4 patients because of ineffective canakinumab. Five pregnant patients were followed up with anakinra during pregnancy and there were no problems. Conclusion: Anti-interleukin-1 agents are effectively and safely in the treatment of FMF patients. There are still unanswered questions in FMF treatment such as other factors affecting the frequency of attacks, colchicine resistance is not defined precisely and the importance of some mutations. The effect of anti IL-1 agents on FMF patients with amyloidosis is not clearly. According to our experience, these treatments are effective in patients with glomerular filtration rate&gt; 60 ml/min. For answers to these and similar questions, Large and long follow-up studies are needed for long-term effects. References: [1]Özen S, Batu ED, Demir S., Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management. Front Immunol. 2017 Mar 23;8:253. doi: 10.3389/fimmu.2017.00253. eCollection 2017. [2]Seza Özen ve ark. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis. 2016 Apr;75(4):644-51. Disclosure of Interests: None declared
Understanding T cell phenotype for the design of effective chimeric antigen receptor T cell therapies
Authors: Daniela GM Tantalo, Amanda J Oliver, Bianca von Scheidt, Aaron J Harrison, Scott N Mueller, Michael H Kershaw, Clare Y Slaney
Journal: Journal for ImmunoTherapy of Cancer (2021)

Rapid advances in immunotherapy have identified adoptive cell transfer as one of the most promising approaches for the treatment of cancers. Large numbers of cancer reactive T lymphocytes can be generated ex vivo from patient blood by genetic modification to express chimeric antigen receptors (CAR) specific for tumor-associated antigens. CAR T cells can respond strongly against cancer cells, and adoptive transferred CAR T cells can induce dramatic responses against certain types of cancers. The ability of T cells to respond against disease depends on their ability to localize to sites, persist and exert functions, often in an immunosuppressive microenvironment, and these abilities are reflected in their phenotypes. There is currently intense interest in generating CAR T cells possessing the ideal phenotypes to confer optimal antitumor activity. In this article, we review T cell phenotypes for trafficking, persistence and function, and discuss how culture conditions and genetic makeups can be manipulated to achieve the ideal phenotypes for antitumor activities.
Ivacaftor and Airway Inflammation in Preschool Children with Cystic Fibrosis
Authors: Paul McNally, Daryl Butler, Yuliya V. Karpievitch, Barry Linnane, Sarath Ranganathan, Stephen M. Stick, Graham L. Hall, André Schultz
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Ivacaftor and Airway Inflammation in Preschool Children with Cystic Fibrosis." American Journal of Respiratory and Critical Care Medicine, 204(5), pp. 605–608
Treatment of Fanconi Anemia–Associated Head and Neck Cancer: Opportunities to Improve Outcomes
Authors: Rex H. Lee, Hyunseok Kang, Sue S. Yom, Agata Smogorzewska, Daniel E. Johnson, Jennifer R. Grandis
Journal: Clinical Cancer Research (2021)

Abstract Fanconi anemia, the most frequent genetic cause of bone marrow failure, is characterized by an extreme predilection toward multiple malignancies, including a greater than 500-fold incidence of head and neck squamous cell carcinoma (HNSCC) relative to the general population. Fanconi anemia–associated HNSCC and esophageal SCC (FA-HNSCC) often present at advanced stages with poor survival. Surgical resection remains the primary treatment for FA-HNSCC, and there is often great reluctance to administer systemic agents and/or radiotherapy to these patients given their susceptibility to DNA damage. The paucity of FA-HNSCC case reports limits evidence-based management, and such cases have not been analyzed collectively in detail. We present a systematic review of FA-HNSCC treatments reported from 1966 to 2020, defining a cohort of 119 patients with FA-HNSCC including 16 esophageal SCCs (131 total primary tumors), who were treated with surgery, radiotherapy, systemic therapy (including cytotoxic agents, EGFR inhibitors, or immune checkpoint inhibitors), or a combination of modalities. We summarize the clinical responses and regimen-associated toxicities by treatment modality. The collective evidence suggests that when possible, surgical resection with curative intent should remain the primary treatment modality for FA-HNSCC. Radiation can be administered with acceptable toxicity in the majority of cases, including patients who have undergone stem cell transplantation. Although there is little justification for cytotoxic chemotherapy, EGFR inhibitors and tyrosine kinase inhibitors may be both safe and effective. Immunotherapy may also be considered. Most oncologists have little personal experience with FA-HNSCC. This review is intended as a comprehensive resource for clinicians.
Abstract 19355: Tissue Doppler Imaging For Rejection Surveillance in Pediatric Heart Transplant Recipients
Authors: Fatima I Lunze, Kimberlee Gauvreau, Steven D Colan, Elizabeth D Blume, Rex Neal Smith, Antonio Perez-Atayde, Tajinder P Singh
Journal: Circulation (2012)

Conventional echocardiography is not considered reliable for rejection-surveillance in pediatric heart transplant (HT) recipients. Pulse-wave tissue Doppler imaging (TDI) is geometry-independent and more sensitive than conventional imaging to evaluate bi-ventricular function. The purpose of this study was to assess TDI findings during biopsy-proven rejection in pediatric HT recipients and to develop TDI criteria for absence of rejection with high predictive accuracy. Methods: All HT recipients in follow-up at our center were included (N=122, median age at transplant 8.7 yrs, range 2 weeks-22 yrs). We identified all echocardiograms with TDI imaging performed within 24 hrs of an endomyocardial biopsy during 2005-2011. Rejection was defined as ISHLT Grade ≥2R cellular rejection or antibody-mediated rejection. Paired comparisons of TDI velocities were made using each patient’s baseline TDI as control. Results: Overall, 650 biopsy-pairs were identified where there was no rejection by biopsy at baseline (median duration between paired biopsies 4.3 mo, 25th-75th percentile 1-8.7 mo). In 25 of these pairs, the second biopsy demonstrated cellular or antibody mediated rejection. Rejection was associated with 27±17 % decline in LV S’ (P&lt;0.001), 17±25 % decline in RV S’ (P&lt;0.001) and a 16±18 % decline in septal S’ velocity (P&lt;0.001). Using a receiver-operating characteristic curve, &lt;24% decline in LV S’, &lt;15% decline in RV S’ and &lt;12% decline in septal S’ were all individually associated with a negative predictive value (NPV) of 98% for rejection. When all three criteria were met, the NPV was 98.5% (95% CI 96.9%, 99.4%) for rejection. Overall, 83% of biopsy pairs met criteria of 98.5% NPV for rejection. Conclusions: Biopsy-proven rejection in pediatric HT recipients is associated with significant and easily measured changes in ventricular function using TDI echocardiography. Using well-defined TDI criteria to predict absence of rejection, over 80% of planned biopsies may be deferred or avoided at minimal risk to pediatric HT recipients.
Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism
Authors: Diba Borgmann, Elisa Ciglieri, Nasim Biglari, Claus Brandt, Anna Lena Cremer, Heiko Backes, Marc Tittgemeyer, F. Thomas Wunderlich, Jens C. Brüning, Henning Fenselau
Journal: Cell Metabolism (2021)

Sensory neurons relay gut-derived signals to the brain, yet the molecular and functional organization of distinct populations remains unclear. Here, we employed intersectional genetic manipulations to probe the feeding and glucoregulatory function of distinct sensory neurons. We reconstruct the gut innervation patterns of numerous molecularly defined vagal and spinal afferents and identify their downstream brain targets. Bidirectional chemogenetic manipulations, coupled with behavioral and circuit mapping analysis, demonstrated that gut-innervating, glucagon-like peptide 1 receptor (GLP1R)-expressing vagal afferents relay anorexigenic signals to parabrachial nucleus neurons that control meal termination. Moreover, GLP1R vagal afferent activation improves glucose tolerance, and their inhibition elevates blood glucose levels independent of food intake. In contrast, gut-innervating, GPR65-expressing vagal afferent stimulation increases hepatic glucose production and activates parabrachial neurons that control normoglycemia, but they are dispensable for feeding regulation. Thus, distinct gut-innervating sensory neurons differentially control feeding and glucoregulatory neurocircuits and may provide specific targets for metabolic control.
Effect of a Smartphone App on Weight Change and Metabolic Outcomes in Asian Adults With Type 2 Diabetes
Authors: Su Lin Lim, Kai Wen Ong, Jolyn Johal, Chad Yixian Han, Qai Ven Yap, Yiong Huak Chan, Yu Chung Chooi, Zhi Peng Zhang, Cheryl Christine Chandra, Anandan Gerard Thiagarajah, Chin Meng Khoo
Journal: JAMA Network Open (2021)

Lifestyle interventions are effective in diabetes management, with smartphone apps that manage health data and dietary and exercise schedules gaining popularity. However, limited evidence from randomized clinical trials exists regarding the effectiveness of smartphone-based interventions among Asian adults with type 2 diabetes.To compare the effects of a culturally contextualized smartphone-based intervention with usual care on weight and metabolic outcomes.This randomized clinical trial conducted at multiple primary care centers in Singapore included 305 adults with type 2 diabetes and body mass index (BMI) of 23 or greater who had literacy in English and smartphone access. Participants were recruited between October 3, 2017, and September 9, 2019, and were randomly assigned (1:1; stratified by gender, age, and BMI) to intervention (99 participants) or control (105 participants) groups. Participants' data were analyzed using intention-to-treat analysis.Both control and intervention participants received diet and physical activity advice from a dietitian at a baseline face-to-face visit. Intervention participants additionally used a smartphone app to track weight, diet, physical activity, and blood glucose and then communicated with dietitians for 6 months.Primary outcome was change in body weight, while secondary outcomes were changes in hemoglobin A1c (HbA1c), fasting blood glucose, blood pressure, lipids, and diet. Post hoc analyses included glycemic changes in the subgroup with HbA1c levels of 8% or greater and diabetes medication changes.Among the 204 randomized participants (mean [SD] age, 51.2 [9.7] years; 132 [64.7%] men), baseline mean (SD) BMI was 30.6 (4.3). Compared with the control group, intervention participants achieved significantly greater reductions in weight (mean [SD] change, -3.6 [4.7] kg vs -1.2 [3.6] kg) and HbA1c levels (mean [SD] change, -0.7% [1.2] vs -0.3% [1.0]), with a greater proportion having a reduction in diabetes medications (17 participants [23.3%] vs 4 participants [5.4%]) at 6 months. The intervention led to a greater HbA1c reduction among participants with HbA1c levels of 8% or higher (mean [SD] change, -1.8% [1.4] vs -1.0% [1.4]; P = .001). Intergroup differences favoring the intervention were also noted for fasting blood glucose, diastolic blood pressure, and dietary changes.In this study, a smartphone-based lifestyle intervention was more effective in achieving weight and glycemic reductions among Asian adults with type 2 diabetes compared with usual care, supporting the use of apps in lifestyle intervention delivery.anzctr.org.au Identifier: ACTRN12617001112358.
<i>APOE</i> Allele Testing and Alzheimer Disease
Authors: Mu-Hong Chen, Fu-Chi Yang, Chih-Sung Liang
Journal: JAMA (2021)

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
Self-management: diabetes care is getting social
Authors: Erika Frey, Catriona Bonfiglioli, Jane Frawley
Journal: BMJ (2021)

Kar discusses changing the narrative around self-management of chronic diseases and the need to switch focus from professionals to patients.1

We suggest that patients use Facebook and other social media platforms for peer support and to meet their self-management needs. Even from social media’s earliest iterations, patients were supporting each other in the safe environment …
Covid-19: Peru’s official death toll triples to become world’s highest
Authors: Owen Dyer
Journal: BMJ (2021)

Covid-19: Peru's official death toll triples to become world's highest Owen DyerPeru has revised its official death toll in the covid-19 pandemic from 69 342 to 185 380, after a scientific review of medical records ordered by the government.The new figure means that Peru has had 5551 covid deaths per million population, proportionally the worst official toll in the world.Hungary, which before this week had the world's highest official toll per capita, now stands a distant second at 3094 deaths per million.
Phosphorylation and Stabilization of PIN1 by JNK Promote Intrahepatic Cholangiocarcinoma Growth
Authors: Alessio Lepore, Pui Man Choy, Nathan C.W. Lee, Maria Annunziata Carella, Rosy Favicchio, Marco A. Briones‐Orta, Shannon S. Glaser, Gianfranco Alpini, Clive D’Santos, Reuben M. Tooze, Mihaela Lorger, Wing‐Kin Syn, Athanasios Papakyriakou, Georgios Giamas, Concetta Bubici, Salvatore Papa
Journal: Hepatology (2021)

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive type of liver cancer in urgent need of treatment options. Aberrant activation of the c-Jun N-terminal kinase (JNK) pathway is a key feature in ICC and an attractive candidate target for its treatment. However, the mechanisms by which constitutive JNK activation promotes ICC growth, and therefore the key downstream effectors of this pathway, remain unknown for their applicability as therapeutic targets. Our aim was to obtain a better mechanistic understanding of the role of JNK signaling in ICC that could open up therapeutic opportunities.Using loss-of-function and gain-of-function studies in vitro and in vivo, we show that activation of the JNK pathway promotes ICC cell proliferation by affecting the protein stability of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), a key driver of tumorigenesis. PIN1 is highly expressed in ICC primary tumors, and its expression positively correlates with active JNK. Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation. Moreover, pharmacological inhibition of PIN1 through all-trans retinoic acid, a Food and Drug Administration-approved drug, impairs the growth of both cultured and xenografted ICC cells.Our findings implicate the JNK-PIN1 regulatory axis as a functionally important determinant for ICC growth, and provide a rationale for therapeutic targeting of JNK activation through PIN1 inhibition.