tbuckley/cabot-search huggingface dataset:
Defects in mucosal immunity and nasopharyngeal dysbiosis in HSC-transplanted SCID patients with IL2RG/JAK3 deficiency
Authors: Pedro Goncalves, Jean-Marc Doisne, Toshiki Eri, Bruno Charbit, Vincent Bondet, Celine Posseme, Alba Llibre, Armanda Casrouge, Christelle Lenoir, Bénédicte Neven, Darragh Duffy, Alain Fischer, James P. Di Santo
Journal: Blood (2022)

Both innate and adaptive lymphocytes have critical roles in mucosal defense that contain commensal microbial communities and protect against pathogen invasion. Here we characterize mucosal immunity in patients with severe combined immunodeficiency (SCID) receiving hematopoietic stem cell transplantation (HSCT) with or without myeloablation. We confirmed that pretransplant conditioning had an impact on innate (natural killer and innate lymphoid cells) and adaptive (B and T cells) lymphocyte reconstitution in these patients with SCID and now show that this further extends to generation of T helper 2 and type 2 cytotoxic T cells. Using an integrated approach to assess nasopharyngeal immunity, we identified a local mucosal defect in type 2 cytokines, mucus production, and a selective local immunoglobulin A (IgA) deficiency in HSCT-treated SCID patients with genetic defects in IL2RG/GC or JAK3. These patients have a reduction in IgA-coated nasopharyngeal bacteria and exhibit microbial dysbiosis with increased pathobiont carriage. Interestingly, intravenous immunoglobulin replacement therapy can partially normalize nasopharyngeal immunoglobulin profiles and restore microbial communities in GC/JAK3 patients. Together, our results suggest a potential nonredundant role for type 2 immunity and/or of local IgA antibody production in the maintenance of nasopharyngeal microbial homeostasis and mucosal barrier function.
Iridocyclitis
Authors: J. H. Doggart
Journal: BMJ (1936)

Although these last twenty years have seen important advances in our knowledge concerning the aetiology of iridocyclitis, ophthalmologists are feeling more bewildered than ever at the problem of causation.Their perplexity is natural.Many of the most striking observations have been of a negative kind, sweeping away barriers which were formerly supposed to define various clinical types, or undermining the validity of long-established diagnostic criteria. Tuberculous InfectionLet us consider for a moment the tubercle bacillus, which on the European mainland is often held responsible for 50 per cent.or more of the cases of iridocyclitis, although the average English-speaking ophthalmologist blames it in less than 5 per cent.It has, of course, been recognized for a long time that the ordinary tuberculin diagnostic test was open to the objection that some focus of tubercle was present in almost every person, so as to destroy the significance of a positive reaction.Most people, however, were ready to be convinced by the therapeutic test.When a patient suffering from irido- cyclitis of doubtful origin unresponsive to other kinds of treatment derived obvious benefit from a course of tuberculin, he was usually credited with a tuberculous aetiology.No such conclusion is justified if we are to take into consideration the recent researches of Almroth Wright.This authority believes, on experimental evi- dence, that tuberculin may augment the immunity to other organisms-for example, staphylococci.As for the clinical appearances of tuberculous iridocyclitis, Finnoff reminds us that the classical chronic form characterized by nodules on the iris and " mutton fat " k.p. is by no means the only possible variety.He points out that many cases begin violently, presenting signs indistinguishable from those that occur in other kinds of iridocyclitis.
Genomic characterization and identification of actionable variants in patients with locally advanced or metastatic urothelial carcinoma (mUC).
Authors: Carlos Stecca, Shamini Selvarajah, Di Maria Jiang, Osama Abdeljalil, Tong Zhang, Philippe L. Bedard, Aaron Richard Hansen, Nazanin Fallah-Rad, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2022)

562 Background: Next generation sequencing (NGS)-based molecular profiling has been widely used across various tumor types including genitourinary malignancies to better understand and potentially predict tumor behavior. The goal of this study was to determine the feasibility of using NGS to characterize mUC and to identify potentially actionable variants. Methods: Patients with locally advanced or metastatic urothelial carcinoma (mUC) treated at the Princess Margaret Cancer Center were prospectively recruited for the OCTANE study, which collects archival tumor samples to provide genomic characterization through NGS with a custom hybridization capture DNA-based panel (555 genes) or a targeted DNA/RNA amplicon panel (Oncomine Comprehensive Assay v3, 161 driver gene panel). Variants were annotated using a somatic variant scheme [PMID: 25880439] or the oncoKB database. Comprehensive clinical information including patient, disease and treatment characteristics was collected using electronic patient records. Kaplan-Meier and cox regression were used for survival analysis. Results: Of the 73 patients, median age was 65 (23-83), majority were men (69%), most had lower tract disease (80%) and 41% had de novo metastatic disease. NGS was deemed feasible, based on availability of tumor samples, and performed in 67 (92%) patients. Overall, 61 (91%) had at least one oncogenic variant, including 34 (56%) with a potentially "druggable" target. The most frequent genomic alterations found were TP53 (44%), FGFR (18%), TERT (18%), ARID1A (18%) and PIK3CA (16%), all classified as "pathogenic/likely pathogenic". Only 2 patients received targeted treatment, one as part of clinical trial and one as standard of care. mOS was numerically longer among patients with genomic mutations compared to the ones without: 55 vs 31 months (HR: 0.87, CI 95% 0.3-2.4; p:0.7). No specific mutation was shown to significantly impact survival (table). Conclusions: Use of NGS technology in characterizing the genomic profile of patients with locally advanced or metastatic UC was feasible in most cases. Oncogenic variants were detected in the majority of patients, and more than half of them harbored a potentially "druggable" target, which may lead to future therapeutic advances.[Table: see text]
Ionic Liquid‐Mediated Transdermal Delivery of Thrombosis‐Detecting Nanosensors
Authors: Ahmet Bekdemir, Eden E. L. Tanner, Jesse Kirkpatrick, Ava P. Soleimany, Samir Mitragotri, Sangeeta N. Bhatia
Journal: Advanced Healthcare Materials (2022)

Abstract Blood clotting disorders such as pulmonary embolism are associated with high morbidity and mortality. A large portion of thrombotic events occur postoperative and after hospital discharge. Therefore, easily applicable, noninvasive, and long‐term monitoring of thrombosis occurrence is critical for urgent clinical intervention. Here, the use is proposed of ionic liquids as a skin transport facilitator to deliver thrombin‐sensitive nanosensors that enable prolonged monitoring of pulmonary embolism. Co‐formulation of nanosensors with choline and geranic acid (CAGE) ionic liquids demonstrates significant transdermal diffusion into the dermis of the skin and provides sustained release into the blood throughout 72 h. Upon reaching the systemic circulation, the nanosensors release reporter molecules into the urine by responding to activation of the clotting cascade and retain a diagnostic power for 24 h in an acute pulmonary embolism mouse model. These results demonstrate a proof‐of‐concept disease monitoring system that can be topically applied by patients and potentially reduce mortality and high cost of hospitalization.
Chidamide plus prednisone, etoposide, and thalidomide for untreated angioimmunoblastic T‐cell lymphoma in a Chinese population: A multicenter phase <scp>II</scp> trial
Authors: Yawen Wang, Mingzhi Zhang, Wei Song, Qingqing Cai, Liling Zhang, Xiuhua Sun, Liqun Zou, Huilai Zhang, Lili Wang, Hongwei Xue
Journal: American Journal of Hematology (2022)

Angioimmunoblastic T-cell lymphoma (AITL) is a common type of peripheral T-cell lymphoma (PTCL) with a poor prognosis, and an effective first-line therapy is lacking. Chidamide is a selective histone deacetylase inhibitor and has been approved by the China Food and Drug Administration for relapsed or refractory PTCL. We conducted a multicenter phase II clinical trial combining chidamide with prednisone, etoposide, and thalidomide (CPET regimen) for a total of eight cycles in untreated AITL patients in China. The primary objectives were the overall response rate (ORR) and complete remission (CR) rate after eight cycles of the CPET regimen. The secondary endpoints were progression-free survival (PFS) and safety. Of the 71 enrolled patients, 51 completed the eight cycles of the CPET regimen. The ORR and CR of the 51 patients were 90.2 and 54.9%, respectively. After a median follow-up of 11.4 months (95% confidence interval [CI], 9.9-17.0), the median PFS of the 51 patients was 42.6 months (95% CI, 27.7-not reached) and the median overall survival (OS) was not reached. The 2-year PFS rate and OS rate were 66.5 and 82.2%, respectively. Sixty-eight patients received at least one cycle of CPET regimen and were included as the safety assessment population. The most common grade 3/4 adverse event was neutropenia (n = 22, 32.3%). Twelve patients showed treatment-related infections and recovered from antibiotic therapy; the other adverse events were mostly mild and reversible. The oral CPET regimen is an effective, tolerable, and economical choice for untreated AITL in a Chinese population. This trial was registered in www.clinicaltrials.gov as NCT03273452.
Current Cigarette Smoking Among Adults — United States, 2005–2015
Authors: Ahmed Jamal, Brian A. King, Linda J. Neff, Jennifer Whitmill, Stephen D. Babb, Corinne M. Graffunder
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Tobacco use is the leading cause of preventable disease and death in the United States, and cigarettes are the most commonly used tobacco product among U.S. adults (1,2). To assess progress toward achieving the Healthy People 2020 target of reducing the proportion of U.S. adults who smoke cigarettes to ≤12.0% (objective TU1.1),* CDC assessed the most recent national estimates of cigarette smoking prevalence among adults aged ≥18 years using data from the 2015 National Health Interview Survey (NHIS). The proportion of U.S. adults who smoke cigarettes declined from 20.9% in 2005 to 15.1% in 2015, and the proportion of daily smokers declined from 16.9% to 11.4%. However, disparities in cigarette smoking persist. In 2015, prevalence of cigarette smoking was higher among adults who were male; were aged 25-44 years; were American Indian/Alaska Native; had a General Education Development certificate (GED); lived below the federal poverty level; lived in the Midwest; were insured through Medicaid or were uninsured; had a disability/limitation; were lesbian, gay, or bisexual; or who had serious psychological distress. Proven population-based interventions, including tobacco price increases, comprehensive smoke-free laws, anti-tobacco mass media campaigns, and barrier-free access to tobacco cessation counseling and medications, are critical to reducing cigarette smoking and smoking-related disease and death among U.S. adults, particularly among subpopulations with the highest smoking prevalences (3).
Bioactive glass nanoparticles inhibit osteoclast differentiation and osteoporotic bone loss by activating lncRNA NRON expression in the extracellular vesicles derived from bone marrow mesenchymal stem cells
Authors: Zhengyu Yang, Xiaodong Liu, Fujian Zhao, Mengyu Yao, Zefeng Lin, Zhen Yang, Cong Liu, Yuwei Liu, Xiaofeng Chen, Chang Du
Journal: Biomaterials (2022)
Long-term outcomes of polycythemia vera patients treated with ropeginterferon Alfa-2b
Authors: Jean-Jacques Kiladjian, Christoph Klade, Pencho Georgiev, Dorota Krochmalczyk, Liana Gercheva-Kyuchukova, Miklos Egyed, Petr Dulicek, Arpad Illes, Halyna Pylypenko, Lylia Sivcheva, Jiří Mayer, Vera Yablokova, Kurt Krejcy, Victoria Empson, Hans C. Hasselbalch, Robert Kralovics, Heinz Gisslinger, Jean-Jacques Kiladjian, Pencho Georgiev, Dorota Krochmalczyk, Liana Gercheva-Kyuchukova, Miklos Egyed, Petr Dulicek, Arpad Illes, Halyna Pylypenko, Lylia Sivcheva, Jiří Mayer, Vera Yablokova, Heinz Gisslinger
Journal: Leukemia (2022)

Interferon alfa not only restores normal blood cell counts in patients with polycythemia vera (PV) but can diminish the mutant JAK2V617F allele burden [1][2][3].After discontinuing long-term interferon therapy, hematologic responses may persist [4,5], which is more likely in patients achieving JAK2V617F allele burden <10% before stopping treatment [6].Allele burden declines gradually during interferon treatment [7]; however, no data from large, prospective, clinical studies of long-term treatment with pegylated alfa interferons are available.Results from 3 years' treatment in the phase 3, open-label, randomized clinical trial PROUD-PV and its phase 3b extension trial CONTINUATION-PV [8] led to regulatory approval of ropeginterferon alfa-2b (BESREMi®), a novel, monopegylated interferon alfa-2b with an extended administration interval of 2-4 weeks, in the European Union.The compound was subsequently approved by the US FDA for first-line treatment of PV.Here we report hematologic and molecular responses and safety results after 5 years' treatment in PROUD-PV and CONTINUATION-PV, which compared the efficacy and safety of ropeginterferon alfa-2b with hydroxyurea in the first year, and with best available treatment (BAT) thereafter.Study design and methods were published previously [8]; selection criteria, dosing and endpoints are described in the supplement (Supplementary Tables 1-3 and Supplementary Fig. 1).JAK2V617F-positive patients with PV who were hydroxyurea naïve or hydroxyurea pre-treated for <3 years without complete response, resistance or intolerance were randomized 1:1 (stratified by age, history of thromboembolic events and hydroxyurea pretreatment) in PROUD-PV to receive ropeginterferon alfa-2b or hydroxyurea for 12 months.Dosing increased until blood counts
Association of Residual Cancer Burden After Neoadjuvant Therapy and Event-Free Survival in Breast Cancer
Authors: Xiaomei Huang, Zaiyi Liu
Journal: JAMA Oncology (2022)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
Safety and efficacy of nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma: results from the phase 3b/4 CheckMate 920 trial
Authors: Scott S Tykodi, Lucio N Gordan, Robert S Alter, Edward Arrowsmith, Michael R Harrison, Ivor Percent, Rakesh Singal, Peter Van Veldhuizen, Daniel J George, Thomas Hutson, Joshua Zhang, Jesus Zoco, Jennifer L Johansen, Arash Rezazadeh Kalebasty
Journal: Journal for ImmunoTherapy of Cancer (2022)

CheckMate 920 (NCT02982954) is a multicohort, phase 3b/4 clinical trial of nivolumab plus ipilimumab treatment in predominantly US community-based patients with previously untreated advanced renal cell carcinoma (RCC) and clinical features mostly excluded from phase 3 trials. We report safety and efficacy results from the advanced non-clear cell RCC (nccRCC) cohort of CheckMate 920.Patients with previously untreated advanced/metastatic nccRCC, Karnofsky performance status ≥70%, and any International Metastatic Renal Cell Carcinoma Database Consortium risk received up to four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks followed by nivolumab 480 mg every 4 weeks for ≤2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥3 immune-mediated adverse events (AEs) within 100 days of last dose of study drug. Key secondary endpoints included objective response rate (ORR), progression-free survival (PFS; both investigator-assessed), time to response (TTR), and duration of response (DOR), all using RECIST V.1.1. Overall survival (OS) was exploratory.Fifty-two patients with nccRCC (unclassified histology, 42.3%; papillary, 34.6%; chromophobe, 13.5%; translocation-associated, 3.8%; collecting duct, 3.8%; renal medullary, 1.9%) received treatment. With 24.1 months minimum study follow-up, median duration of therapy (range) was 3.5 (0.0-25.8) months for nivolumab and 2.1 (0.0-3.9) months for ipilimumab. Median (range) number of doses received was 4.5 (1-28) for nivolumab and 4.0 (1-4) for ipilimumab. Grade 3-4 immune-mediated AEs were diarrhea/colitis (7.7%), rash (5.8%), nephritis and renal dysfunction (3.8%), hepatitis (1.9%), adrenal insufficiency (1.9%), and hypophysitis (1.9%). No grade 5 immune-mediated AEs occurred. ORR (n=46) was 19.6% (95% CI 9.4 to 33.9). Two patients achieved complete response (papillary, n=1; unclassified, n=1), seven achieved partial response (papillary, n=4; unclassified, n=3), and 17 had stable disease. Median TTR was 2.8 (range 2.1-14.8) months. Median DOR was not reached (range 0.0+-27.8+); eight of nine responders remain without reported progression. Median PFS (n=52) was 3.7 (95% CI 2.7 to 4.6) months. Median OS (n=52) was 21.2 (95% CI 16.6 to not estimable) months.Nivolumab plus ipilimumab for previously untreated advanced nccRCC showed no new safety signals and encouraging antitumor activity.NCT02982954.
EULAR points to consider for minimal reporting requirements in synovial tissue research in rheumatology
Authors: Aurélie Najm, Félicie Costantino, Stefano Alivernini, Alessia Alunno, Elettra Bianchi, Jacqueline Bignall, Brendan Boyce, Juan D Cañete, Francesco Carubbi, Patrick Durez, João Eurico Fonseca, Søren Andreas Just, Raquel Largo, Antonio Manzo, Mark Maybury, Esperanza Naredo, Carl Orr, Costantino Pitzalis, Felice Rivellese, Vasco C Romão, Jef van Rompay, Sander W Tas, Douglas J Veale, Maria-Antonietta D'Agostino, Andrew Filer
Journal: Annals of the Rheumatic Diseases (2022)

Background Synovial tissue research has become widely developed in several rheumatology centres, however, large discrepancies exist in the way synovial tissue is handled and, more specifically, how data pertaining to biopsy procedure, quality check and experimental results are reported in the literature. This heterogeneity hampers the progress of research in this rapidly expanding field. In that context, under the umbrella of European Alliance of Associations for Rheumatology, we aimed at proposing points to consider (PtC) for minimal reporting requirements in synovial tissue research. Methods Twenty-five members from 10 countries across Europe and USA met virtually to define the key areas needing evaluation and formulating the research questions to inform a systematic literature review (SLR). The results were presented during a second virtual meeting where PtC were formulated and agreed. Results Study design, biopsy procedures, tissue handling, tissue quality control and tissue outcomes (imaging, DNA/RNA analysis and disaggregation) were identified as important aspects for the quality of synovial tissue research. The SLR interrogated four databases, retrieved 7654 abstracts and included 26 manuscripts. Three OPs and nine PtC were formulated covering the following areas: description of biopsy procedure, overarching clinical design, patient characteristics, tissue handling and processing, quality control, histopathology, transcriptomic analyses and single-cell technologies. Conclusions These PtC provide guidance on how research involving synovial tissue should be reported to ensure a better evaluation of results by readers, reviewers and the broader scientific community. We anticipate that these PtC will enable the field to progress in a robust and transparent manner over the coming years.
Human genetics of SARS-CoV-2 infection and critical COVID-19
Authors: Trine H. Mogensen
Journal: Clinical Microbiology and Infection (2022)

BackgroundDuring the past 2 years, studies on patients with SARS-CoV-2 infection have revealed rare inborn errors of immunity (IEIs) in type interferon (IFN) pathways underlying critical COVID-19 pneumonia. This has provided insights into pathophysiological mechanisms and immune signaling circuits regulating antiviral responses to SARS-CoV-2 and governing the susceptibility to and outcome of SARS-CoV-2 infection in humans.ObjectivesIn this review, the current knowledge on IEIs underlying critical COVID-19 is presented, and the clinical implications of these findings for individualized prophylaxis and treatment are outlined.SourcesThe review is based on a broad literature search, including primarily studies on whole-exome sequencing, and to a lesser extent genome-wide association studies, of patients with critical COVID-19, as well as retrospective descriptive studies of the SARS-CoV-2 disease course in individuals with known IEIs.ContentThe review describes the discovery of monogenic IEI in 9 genetic loci related to the production or responses to type I IFN in patients with critical COVID-19 pneumonia and the surprising finding of phenocopies of these, represented by neutralizing autoantibodies to type IFN in a significant proportion of patients with critical pneumonia, particularly in elderly men, and further enriched in patients with lethal disease course. Moreover insights gained from studies on SARS-CoV-2 infection, disease course, and outcome in patients with known IEI is presented. Finally, some hypotheses for a possible genetic basis of autoimmune, inflammatory, and long-term complications of SARS-CoV-2 infection are presented and discussed.ImplicationsUncovering IEIs underlying critical COVID-19 or other severe SARS-CoV-2 disease manifestations provides valuable insights into the basic principles of antiviral immune responses and pathophysiology related to SARS-CoV-2 infection. Such knowledge has important clinical implications for identification of susceptible individuals and for diagnosis, prophylaxis, and treatment of patients to reduce disease burden and improve preparedness against viral pandemics with known or emerging viruses in the future.
A commentary on “Recurrent appendicitis following successful drainage of appendicular abscess in adult without interval appendectomy during COVID-19. Prospective cohort study” (Int J Surg 2022;97:106200)
Authors: Hon-Yi Shi, Po-Huang Lee, I-Ting Tsai, Nan-Han Lu, Chong-Chi Chiu
Journal: International Journal of Surgery (2022)