tbuckley/cabot-search huggingface dataset:
Myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T): Mayo-Moffitt collaborative study of 158 patients
Authors: Abhishek A. Mangaonkar, Terra L. Lasho, Rhett P. Ketterling, Kaaren K. Reichard, Naseema Gangat, Aref Al-Kali, Kebede H. Begna, Animesh Pardanani, Najla H. Al Ali, Chetasi Talati, David Sallman, Eric Padron, Mrinal M. Patnaik, Ayalew Tefferi, Rami Komrokji
Journal: Blood Cancer Journal (2022)

Abstract The current World Health Organization (WHO) classification of myeloid malignancies includes myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) as a distinct entity. Previous literature on predictors of survival was based on the provisional category of refractory anemia with ring sideroblast and thrombocytosis (RARS-T), which was not subject to MDS/MPN-RS-T exclusionary criteria such as PB blast% ≥1, BM blast% ≥5 or cytogenetic abnormalities such as t(3;3)(q21.2;q26.2), inv(3)(q21.23q26.2) or isolated del(5q). We examined overall (OS) and leukemia-free (LFS) survival and its predictors, among 158 patients with WHO-defined MDS/MPN-RS-T. In univariate analysis, age ≥70 years ( P = 0.006), hemoglobin (Hb) ≤10 g/dL ( P = 0.03) and abnormal karyotype (excluding -Y, P = 0.008) were associated with shortened OS, which was otherwise not affected by either ASXL1 ( P = 0.7), SF3B1 (P = 0.4 ) or JAK2 V617F (P = 0.7 ) mutations; in multivariable analysis, Hb ≤ 10 g/dL ( P = 0.03) and abnormal karyotype ( P = 0.001) remained significant, and thus allowed the development of an operational survival model with low (0 risk factors, median OS 10.5 years), intermediate (1 risk factor, median OS 4.8 years) and high risk (2 risk factors, median OS 1.4 years) categories ( P = 0.0009). Comparison of MDS/MPN-RS-T ( n = 158) and MDS/MPN-U with BM RS ≥ 15% (MDS/MPN-U-RS; n = 25) did not reveal significant differences in frequency of thrombosis, OS, or LFS, although SF3B1 mutation frequency was higher in the former (93% versus 59%; P = 0.0005). These data suggest limited survival impact for molecular abnormalities and the morphological distinction between MDS/MPN-RS-T and MDS/MPN-U-RS.
Interim PET-CT Scan in Advanced Hodgkin’s Lymphoma
Authors: Hugo J A Adams, Thomas C Kwee
Journal: New England Journal of Medicine (2016)

To the Editor: Johnson et al. (June 23 issue) 1 report that their trial included 172 patients with advanced-stage Hodgkin's lymphoma who switched from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) because of positive results on interim positron-emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG).Among these patients, the 3-year progression-free survival rate was 67.5% and the overall survival rate was 87.8%.These patients had more therapy-related adverse events than did patients who had negative results on interim FDG-PET and continued to receive ABVD chemotherapy.Unfortunately, the benefit of early intensification with BEACOPP in patients who had positive results on interim FDG-PET cannot be assessed because, as in other recent nonrandomized studies of chemotherapy intensification, the trial design did not include a randomized comparison between continuation of standard ABVD chemotherapy and intensified BEACOPP chemotherapy and because of futile comparisons with historical cohorts in trials in which the methods and results were not homogeneous. 2 Remarkably, the German Hodgkin Study Group HD15 trial 3 showed that 191 patients who continued to have positive findings on FDG-PET after six to eight cycles of BEACOPP had a good 4-year progression-free survival rate of 86.2% after they received additional treatment with radiation therapy.Comparable results were observed in studies that included patients who had earlystage or advanced-stage Hodgkin's lymphoma and received ABVD. 4,5 These findings show that radiation therapy can successfully eradicate persistent FDG-avid lesions after first-line therapy and that early intensification of chemotherapy may not be warranted in these patients.
Deaths
Journal: JAMA (1933)

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
Classified Advertising
Journal: JAMA (1994)

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
Cirrhosis Quality Collaborative
Authors: Michael L. Volk, Christina Clarke, Sumeet K. Asrani, Saira Khaderi, Meena B. Bansal, Elliot B. Tapper, Chanda Ho, Raymond T. Chung, John Lake, Nicholas Lim, Brett E. Fortune, Ray Kim, Deepti Dronamraju, Fasiha Kanwal
Journal: Clinical Gastroenterology and Hepatology (2022)
Combination therapy targeting Erk1/2 and CDK4/6i in relapsed refractory multiple myeloma
Authors: Sophia Adamia, Shruti Bhatt, Kenneth Wen, Zuzana Chyra, Geoffrey G. Fell, Yu-Tzu Tai, Marisa S. Pioso, Ivane Abiatari, Anthony Letai, David M. Dorfman, Teru Hideshima, Kenneth C. Anderson
Journal: Leukemia (2022)

Oncogenic activated RAS mutations have been detected in 50% of de novo and 70% of relapsed multiple myeloma (MM) patients. Translocation t(11;14) involving IgH/CCDN1 and overexpression of cyclin-Ds are early events in MM pathogenesis, enhancing uncontrolled MM cell growth. We hypothesized that targeting both RAS/MAPK pathway molecules including Erk1/2 along with cyclin-Ds enhances MM cytotoxicity and minimizes side effects. Recent studies have demonstrated the high potency of Erk1/2 and CDK4/6 inhibitors in metastatic relapsed cancers, and here we tested anti-MM effects of the Erk1/2 + CDK4/6 inhibitor combination. Our studies showed strong synergistic (IC < 0.5) cytotoxicity of Erk1/2i + CDK4/6i in MM-cells. Erk1/2i + CDK4/6i treatment in a dose-dependent manner arrested MM-cells in the G0/G1 phase and activated mitochondrial apoptotic signaling. Our studies showed that Erk1/2i + CDK4/6i treatment-induced inhibition of key target molecules in Erk1/2 and CDK4/6 signaling, such as c-myc, p-RSK, p-S6, p-RB, and E2F1, suggesting on-target activity of these inhibitors. We identified Erk1/2i + CDK4/6i treatment associated five-gene signature which includes SNRPB and SLC25A5; these genes are involved in RNA processing and mitochondrial metabolism, respectively. Overall, our studies provide the preclinical framework for Erk1/2i + CDK4/6i combination clinical trials to target Ras+CDK pathways to improve patient outcome in MM.
Correction
Journal: BMJ (1927)

JUm CHRONIC URl1iCARIA."J. B. S." writes: " Pruritus " shoIld( again examine the urine or his patient for sug1ar, wvith a specimeni of high specflic gravity.Nota large amount of sugar, bit a small amotiit-saty, 3 per 1,000- for which the " Char test" is the best.Treat thie patient as a potential diabetic, perhiaps by lheredity.Cutt off starch and snurar anzl give liquor amimnonii acetatis to act oni the skin.Conisider also occupationi.
National Diabetes Month — November 2019
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

November is National Diabetes Month. In the United States, 30 million adults aged ≥18 years are living with diabetes and 84 million with prediabetes (1). Among persons aged ≥65 years, one in four is estimated to have diabetes, and one in two has prediabetes (1). Persons with prediabetes are at risk for developing type 2 diabetes, heart disease, and stroke (2). However, type 2 diabetes can be prevented or delayed through a structured lifestyle change program that promotes weight loss, healthy eating, and increased physical activity (2). A report on diabetes among Medicare beneficiaries is included in this issue of MMWR (3).
Accuracy in recorded diagnoses
Authors: S. F. Jencks
Journal: JAMA (1992)

Although making accurate diagnoses is a critical clinical skill, putting accurate diagnoses on the face sheet of a medical record does not have the same priority for most physicians. Even those who see recording a correct principal diagnosis as an important part of good clinical thinking are unlikely to be perfectionists regarding additional diagnoses because it is hard to see that they will have any effect on patient care. See also p 2197. In the last few years, however, major journals have published a growing number of articles in which recorded additional diagnoses play an important part in analysis, either to establish a clinical point or to assess additional diagnoses as a measure of clinical severity of illness. Investigators seek to secure information from additional diagnoses, which would otherwise require costly manual abstraction, about the occurrence of adverse events and the risk of outcomes such as death. In addition, hospital
Static mucus impairs bacterial clearance and allows chronic infection with<i>Pseudomonas aeruginosa</i>in the cystic fibrosis rat
Authors: Alexander G. Henderson, Joy M. Davis, Johnathan D. Keith, Morgan E. Green, Ashley M. Oden, Steven M. Rowe, Susan E. Birket
Journal: European Respiratory Journal (2022)

Cystic fibrosis airway disease is characterised by chronic Pseudomonas aeruginosa infection. Successful eradication strategies have been hampered by a poor understanding of the mechanisms underlying conversion to chronicity. The cystic fibrosis transmembrane conductance receptor (CFTR)-knockout (KO) rat harbours a progressive defect in mucociliary transport and viscosity. KO rats were infected before and after the appearance of the mucus defect, using a clinical mucoid-isolate of P. aeruginosa embedded in agarose beads. Young KO rats that were exposed to bacteria before the development of mucociliary transport defects resolved the infection and subsequent tissue damage. However, older KO rats that were infected in the presence of hyperviscous and static mucus were unable to eradicate bacteria, but instead had bacterial persistence through 28 days post-infection that was accompanied by airway mucus occlusion and lingering inflammation. Normal rats responded to infection with increased mucociliary transport to supernormal rates, which reduced the severity of a second bacterial exposure. We conclude that the aberrant mucus present in the CF airway permits persistence of P. aeruginosa in the lung.
Where are the women ‘Heroes and Pillars of Rheumatology’?
Authors: Nicola Dalbeth, Tuhina Neogi
Journal: Annals of the Rheumatic Diseases (2022)

We have enjoyed reading the 'Heroes and Pillars of Rheumatology' section of Ann Rheum Dis which was introduced in 2018 to highlight 'persons or scientific innovations of the past that were pivotal in advancing our discipline'.1 While we acknowledge the recognition of Dr Barbara Ansell CBE, FRCP, FRCS, FRCPCH in the June 2019 issue,2 we note that the remaining 14 'Heroes' profiled to date3 have been men. We recognise that, historically, opportunities for women in medicine were limited. However, there are many women who have made ground-breaking contributions to the field of rheumatology. Examples of past Heroes include:
18F-Fluciclovine Uptake in Intramuscular Injecting Site of Antiandrogen
Authors: Te-Chun Hsieh, Yu-Chin Wu, Chia-Hung Kao, Kuo-Yang Yen, Shung-Shung Sun
Journal: Clinical Nuclear Medicine (2022)

Abstract 18 F-fluciclovine, a radiolabeled amino acid analog, has been approved by US Food and Drug Administration for detecting lesions of biochemical recurrence of prostate adenocarcinoma with PET/CT. However, it is not specific for prostate cancer and has been found to be present in variety of malignant and benign etiologies. We herein present an interesting case of the incidental finding of increasing uptake of 18 F-fluciclovine related to intramuscular injection of antiandrogen.
Unsupervised Cluster Analysis of Nasal Cytokines During RV Infection Identifies Distinct Immunophenotypes in Both Children and Adults with Allergic Asthma
Authors: Lyndsey Muehling, Peter Heymann, Holly Carper, Deborah Murphy, Joshua Kennedy, Stephen Early, Mauel Soto-Quiros, Lydiana Avila, Lisa Workman, Thomas Platts-Mills, Judith Woodfolk
Journal: Journal of Allergy and Clinical Immunology (2022)
The Single Cell Transcriptomic and Epigenomic Map of the Innate Immune Response to Vaccination in Lymph Nodes
Authors: Madeleine Scott, Audrey Lee, Florian Wimmers, Prabhu Arunachalam, Christopher Fox, Mark Tomai, Purvesh Khatri, Bali Pulendran
Journal: Journal of Allergy and Clinical Immunology (2022)
P109: CLINICAL CATEGORIZATION OF CHILDREN WITH SICKLE CELL DISEASE USING SEVERITY SCORE AT A TERTIARY CARE CENTER
Authors: L Dipty Jain, K Swaroop
Journal: HemaSphere (2022)

Introduction and Aim: India has been identified as having the second largest number of births with sickle cell anaemia(SCA) in the world after Africa and exhibits wide clinical diversity (1). We therefore introduced a scoring system to evaluate the severity of SCA in India children using simple clinico-laboratory parameter. Objective and work plan: The main aim is to see if Indian score is different from international scores -tweel et al.,(2) In India, the disease is largely undocumented. Thus, there is an urgent need to document the features of Indian disease so that locally appropriate models of care may be evolved across other countries too. We used cluster analysis of clinical parameters like avascular necrosis,stroke, hepatic or splenic sequestration, acute chest syndrome, vaso-occlusive crisis, number of blood transfusions with combined clinical and laboratory parameters of internationally validated score. The idea is to clinically categorise the children based on expert opinion into mild,moderate and severe using several clinical parameters and to match this with a validated international scoring system. The total severity score of 173 patients ranging from 0 to 70 with mean ± standard deviation of 27.69 ± 24.51. Approximately 63.7% had mild disease, 13.2% moderate disease, and 35.7% severe disease, according to our severity score grading system. Comparison of international score with our score was done with a matching of 64.9%. Some minor modifications was done in a validated score due to local factors and clinical diversity.Present samples cohort (171) was divided randomly into two groups; Discovery group (N=100) and Validation group (N=71). Validation was done with overall matching of 81.5% after including parameters which was not present in an international score as per Indian patients. Score matching increased from 65% to 82% All weightings demonstrated a significant difference between the scores of mild, moderate, and severely affected patients, as classified by a subjective rating or with an existing index (P < 0.01). Conclusion: Routine evaluation of disease severity in children with SCA will help to prospectively identify children at higher risk for a turbulent clinical course who may need more active management and monitoring. Assessment of patients objectively after any type of intervention like counselling, treatment(pre and post hydroxyurea) can be done by score. References 1. Hockham et al, The spatial epidemiology of sickle-cell anemia in india, Sci Rep. 2018;10.1038 2. W.van den Tweel et al, Develepment and validation of pediatric severity index for sickle cell patients, Am.J.hematology.85 (2010);746–751
Evaluation of cytosine base editing and adenine base editing as a potential treatment for alpha-1 antitrypsin deficiency
Authors: Michael S. Packer, Vivek Chowdhary, Genesis Lung, Lo-I Cheng, Yvonne Aratyn-Schaus, Dominique Leboeuf, Sarah Smith, Aalok Shah, Delai Chen, Marina Zieger, Brian J. Cafferty, Bo Yan, Giuseppe Ciaramella, Francine M. Gregoire, Christian Mueller
Journal: Molecular Therapy (2022)

Alpha-1 antitrypsin deficiency (AATD) is a rare autosomal codominant disease caused by mutations within the SERPINA1 gene. The most prevalent variant in patients is PiZ SERPINA1, containing a single G > A transition mutation. PiZ alpha-1 antitrypsin (AAT) is prone to misfolding, leading to the accumulation of toxic aggregates within hepatocytes. In addition, the abnormally low level of AAT secreted into circulation provides insufficient inhibition of neutrophil elastase within the lungs, eventually causing emphysema. Cytosine and adenine base editors enable the programmable conversion of C⋅G to T⋅A and A⋅T to G⋅C base pairs, respectively. In this study, two different base editing approaches were developed: use of a cytosine base editor to install a compensatory mutation (p.Met374Ile) and use of an adenine base editor to mediate the correction of the pathogenic PiZ mutation. After treatment with lipid nanoparticles formulated with base editing reagents, PiZ-transgenic mice exhibited durable editing of SERPINA1 in the liver, increased serum AAT, and improved liver histology. These results indicate that base editing has the potential to address both lung and liver disease in AATD.
HERA: a new era for health emergency preparedness in Europe?
Authors: Simone Villa, Remko van Leeuwen, Claire Craig Gray, Marianne van der Sande, Flemming Konradsen, Günter Fröschl, David Gisselsson Nord, Clarissa Prazeres da Costa, Oriana Ramirez-Rubio, Ibrahim Abubakar, Till Bärnighausen, Núria Casamitjana, Astrid Berner-Rodoreda, Frank Cobelens, Antoni Plasència, Mario Raviglione
Journal: The Lancet (2021)
Predictors and microbiology of respiratory and bloodstream bacterial infection in patients with COVID-19: author's response
Authors: Bradley J. Langford, Miranda So, Valerie Leung, Sumit Raybardhan, Jennifer Lo, Tiffany Kan, Felicia Leung, Nick Daneman, Derek R. MacFadden, Jean-Paul R. Soucy
Journal: Clinical Microbiology and Infection (2022)
Contribution of Necroptosis to Myofiber Death in Idiopathic Inflammatory Myopathies
Authors: Qing‐Lin Peng, Ya‐Mei Zhang, Yan‐Chun Liu, Lin Liang, Wen‐Li Li, Xiao‐Lan Tian, Lu Zhang, Hong‐Xia Yang, Xin Lu, Guo‐Chun Wang
Journal: Arthritis & Rheumatology (2022)

Objective Myofiber necrosis is a significant pathologic characteristic of idiopathic inflammatory myopathies (IIMs), and its molecular mechanism is largely unknown. Necroptosis is a recently identified form of regulated necrotic cell death, and its activation might have crucial biologic consequences. The aim of the present study was to investigate the role of necroptosis in IIM muscle damage. Methods Western blot and immunohistochemistry analyses were performed to examine the expression of receptor‐interacting protein 3 (RIP‐3) and mixed‐lineage kinase domain–like (MLKL) proteins in 26 IIM patients and 4 healthy controls, as well as necroptosis‐related damage–associated molecular pattern molecules. Tumor necrosis factor (TNF) was used to stimulate cultured C2C12 myoblasts, and the involvement of necroptosis in cell death of C2C12 cells was studied in vitro. Results The expression of RIP‐3 and MLKL proteins and their phosphorylated forms was significantly increased in the muscle tissue of IIM patients compared to that of healthy controls. The expression levels of RIP‐3 and MLKL proteins were associated with the severity of muscle damage in patients with IIM. Significant colocalization of MLKL with high mobility group box chromosomal protein 1 in necrotizing myofibers was observed in muscle biopsy tissue from patients with IIM. Stimulation of C2C12 myoblasts with TNF and a pan‐caspase inhibitor, Z‐VAD, resulted in the overactivation of necroptosis and significantly increased necrotic cell death. Strategies involving either inhibition of necroptosis with necrostatin‐1 or knockdown of MLKL expression successfully prevented necroptosis‐induced cell death of C2C12 cells. Conclusion These findings demonstrate that overactivated necroptosis contributes to muscle damage in IIMs and suggest that necroptosis inhibitors could represent a new therapeutic target in the treatment of IIMs.
New Zealand Rheumatism Association: Annual Report, 1960
Journal: Annals of the Rheumatic Diseases (1961)

believe that the study of the main antigens and anti- bodies which participate in the process is most promising.Changes in the antigenic structure of human protein in the affected organisms are essential for diagnosis, as is partly apparent when examining the antigenic properties of human serum.In typical cases of rheumatic fever and rheumatoid arthritis, we separated electrophoretically homogeneous fractions of the serum proteins and used them for the immunization of rabbits in order to obtain appropriate antisera.Antisera for single fractions were studied in cross- experiments with sera of patients with rheumatic fever, rheumatoid arthritis, lupus erythematosus, scleroderma, and other collagen and non-collagen diseases, as well as with sera of perfectly healthy individuals.Various immunological processes were worked out and used for this purpose as well as certain physicochemical methods, such as di-electrical measurements, immuno- electrophoresis in gel and on paper, gel-precipitation, etc.
Host Biochemical Defense Mechanisms Against Prooxidants
Authors: I. Cotgreave
Journal: The Annual Review of Pharmacology and Toxicology (1988)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More