Suchergebnisse

The objective of this study was to evaluate the impact of one abnormal fetus in a twin pregnancy, to compare impact of chorionicity and clinical outcome of intervention and expectant management. Thirty-seven dichorionic (DC) twins and 18 monochorionic (MC) twins complicated with one malformed fetus were evaluated for gestational age, birthweight and perinatal outcome. Six hundred and forty-two twin pregnancies were evaluated in the database. The control groups consisted of 429 DC and 86 MC twins without anomalous fetus. Mean birthweight and gestational age at birth for DC control group were (n= 429; 2137g and 34.71 weeks), DC study group,n= 37; 2117g (p= .338) and 33.97 weeks (p= .311), and DC study group with major malformations,n= 30; 2019g (p= .289) and 33.3 weeks (p= .01), and showed only significance for gestational age. There was no statistical significance between MC control group,n= 86; 2097g and 34.93 weeks, and MC study group,n= 18; 2237g (p= .338), and 34.42 weeks (p= .502). Because of limited data, the preliminary evaluation for expectant management and intervention, and survival of at least one normal fetus showed no impact. We conclude that, although, all DC twin pregnancies have a risk for preterm delivery, DC twins complicated with major malformation of one twin, have a lower mean gestational age at birth. Preliminary results for intervention does not improve fetal outcome for DC and MC twins and needs further evaluation with greater studies of impact or review.

OBJECTIVE There is an unmet need for reliable, validated, and widely-accepted outcome measures for randomized clinical trials in Behçet syndrome (BS). The Outcome Measures in Rheumatology Clinical Trials (OMERACT) BS Working Group, a large, multi-disciplinary group of experts in BS and patients with BS, worked to develop a Core Set of data-driven outcome measures for use in all clinical trials of BS. METHODS The Core Domain Set was developed through a comprehensive, iterative, multi-stage project which included a systematic review, a focus group meeting and qualitative patient interviews, a survey among experts in BS, a Delphi exercise involving both patients and physician-experts in BS, and utilization of the data, insight, and feedback generated by these processes to develop a final Core Domain Set. RESULTS All steps were completed and domains were delineated across the organ systems involved in this disease. Since trials in BS often focus on specific manifestations and not the disease in its entirety, the final proposed Core Set includes 5 domains mandatory for study in all trials in BS (disease activity, new organ involvement, quality of life, adverse events, and death) with additional sub-domains mandatory for study of specific organ-systems. The final Core Set was endorsed at the 2018 OMERACT meeting. CONCLUSION The Core Set of Domains in BS provides the foundation through which the international research community, including clinical investigators, patients, biopharmaceutical industry, and government regulatory bodies can harmonize the study of this complex disease, compare findings across studies, and advance development of effective therapies.

Objective. Periodic fever syndrome (PFS) conditions are characterized by recurrent attacks of fever and localized inflammation. This study examined the diagnostic pathway and treatments at tertiary centers for familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and mevalonate kinase deficiency (MKD)/hyperimmunoglobulinemia D syndrome (HIDS). Methods. PFS specialists at medical centers in the US, the European Union, and the eastern Mediterranean participated in a retrospective chart review, providing de-identified data in an electronic case report form. Patients were treated between 2008 and 2012, with at least 1 year of followup; all had clinical and/or genetically proven disease and were on/eligible for biologic treatment. Results. A total of 134 patients were analyzed: FMF (n549), TRAPS (n547), and MKD/HIDS (n538). Fever was commonly reported as severe across all indications. Other frequently reported severe symptoms were serositis for FMF patients and elevated acute-phase reactants and gastrointestinal upset for TRAPS and MKD/HIDS. A long delay from disease onset to diagnosis was seen within TRAPS and MKD/HIDS (5.8 and 7.1 years, respectively) compared to a 1.8-year delay in FMF patients. An equal proportion of TRAPS patients first received anti-interleukin-1 (anti-IL-1) and anti-tumor necrosis factor (anti-TNF) biologic agents, whereas IL-1 blockade was the main choice for FMF patients resistant to colchicine and MKD/HIDS patients. For TRAPS patients, treatment with anakinra versus anti-TNF treatments as first biologic agent resulted in significantly higher clinical and biochemical responses (P=0.03 and P< 0.01, respectively). No significant differences in responses were observed between biologic agents among other cohorts. Conclusion. Referral patterns and diagnostic delays highlight the need for greater awareness and improved diagnostics for PFS. This real-world treatment assessment supports the need for further refinement of treatment practices.

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. Methods We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. Results The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. Conclusions The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways. ; Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases ; National Human Genome Research Institute of the National Institutes of Health (NIH) ; NIH ; Arthritis Research UK ; German Federal Ministry of Education and Research (BMBF) ; Val A. Browning Charitable Foundation ; Marcus Foundation ; Proyecto de Excelencia of the Andalousian Government (MA-R) ; Swedish Association Against Rheumatism (MA-R) ; Wellcome Trust ; National Institute for Health Research Biomedical Research Unit Funding Scheme ; Manchester Academic Health Sciences Centre (MAHSC) ; SPARKS UK ; Medical Research Council ; UK National Institute for Health Research GOSH Biomedical Research Centre ; Canadian Institutes of Health Research ; Arthritis Society (CIHR) ; Canadian Arthritis Network ; Cincinnati Children's Research Foundation and its Cincinnati Genomic Control Cohort ; USA NIH research programme ; UK Medical Research Council ; Natl Inst Arthrit & Musculoskeletal & Skin Dis, Natl Inst Hlth, US Dept Hlth & Human Serv, Translat Genet & Genom Unit, Bethesda, MD USA ; NHGRI, Natl Inst Hlth, Inflammatory Dis Sect, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA ; Manchester Acad Hlth Sci Ctr, Arthrit Res UK Ctr Genet & Genom, Ctr Musculoskeletal Res, Manchester, Lancs, England ; Wellcome Trust Sanger Inst, Human Genet, Hinxton, England ; Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA ; Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA ; Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany ; Univ Genoa, Dept Pediat, Genoa, Italy ; Giannina Gaslini Inst, Pediat Unit 2, Genoa, Italy ; Hacettepe Univ, Dept Pediat Rheumatol, Ankara, Turkey ; Emory Univ, Sch Med, Dept Pediat & Human Genet, Atlanta, GA 30322 USA ; Childrens Healthcare Atlanta, Atlanta, GA USA ; Cleveland Clin, Dept Pediat, Cleveland, OH 44106 USA ; Univ Utah, Dept Pediat, Salt Lake City, UT USA ; Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA ; Childrens Hosp Montefiore, Bronx, NY USA ; Stanford Univ, Dept Pediat, Stanford, CA 94305 USA ; Hosp Pediat Garrahan, Serv Immunol & Rheumatol, Buenos Aires, DF, Argentina ; Univ Fed Sao Paulo, Dept Pediat, Sao Paulo, Brazil ; Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil ; Univ Toronto, Dept Pediat, Toronto, ON, Canada ; Univ Toronto, Dept Pediat, Toronto, ON, Canada ; Univ Toronto, Inst Med Sci, Toronto, ON, Canada ; Univ Saskatchewan, Dept Pediat, Saskatoon, SK, Canada ; UCL, Inst Child Hlth, London, England ; UCL, Ctr Paediat & Adolescent Rheumatol, London, England ; Univ Barcelona, Hosp Sant Joan Deu, Pediat Rheumatol Unit, Barcelona, Spain ; German Ctr Pediat & Adolescent Rheumatol, Garmisch Partenkirchen, Germany ; Univ Hosp Cal Gustav Carus, Dresden, Germany ; Charite, Dept Rheumatol & Clin Immunol, Berlin, Germany ; German Rheumatism Res Ctr, Epidemiol Unit, Berlin, Germany ; Rhein Westfal TH Aachen, Dept Pediat, Aachen, Germany ; Univ Manchester, Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust, Natl Inst Hlth Res Manchester Musculoskeletal Bio, Manchester, Lancs, England ; Univ Pittsburgh, Dept Med, Pittsburgh, PA USA ; Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA ; Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA ; Cleveland Clin, Dept Pathobiol, Cleveland, OH 44106 USA ; Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA ; Hosp Sick Children, Ctr Appl Gen, Toronto, ON, Canada ; Pfizer Univ Granada Andalusian Govt, Ctr Genom & Oncol Res, Granada, Spain ; Karolinska Inst, Inst Environm Med, Unit Chron Inflammatory Dis, Solna, Sweden ; Interdisciplinary Cluster Appl Genoprote Univ Lie, Liege, Belgium ; Barcelona Inst Sci & Technol, Ctr Gene Regulat, Barcelona, Spain ; Univ Pompeu Fabra UPF, Barcelona, Spain ; Sidra Med & Res Ctr, Doha, Qatar ; Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey ; Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA ; Univ Fed Sao Paulo, Dept Pediat, Sao Paulo, Brazil ; Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases: Z01-AR041198 ; National Human Genome Research Institute of the National Institutes of Health (NIH): Z01-HG200370 ; NIH: R01-AR059049 ; NIH: R01AR061297 ; NIH: R01-AR060893 ; NIH: P30-AR47363 ; NIH: P01-AR48929 ; NIH: AG030653 ; NIH: AG041718 ; NIH: AG005133 ; NIH: U01-DK062420 ; NIH: R01-DK076025 ; Arthritis Research UK: 20385 ; Arthritis Research UK: 20542 ; German Federal Ministry of Education and Research (BMBF): 01ER0813 ; Proyecto de Excelencia of the Andalousian Government (MA-R): CTS-2548 ; Wellcome Trust: 098051 ; Wellcome Trust: 076113/C/04/Z ; Wellcome Trust: 068545/Z/02 ; SPARKS UK: 08ICH09 ; SPARKS UK: 12ICH08 ; Medical Research Council: MR/M004600/1 ; Arthritis Society (CIHR): 82517 ; Canadian Arthritis Network: SRI-IJD-01 ; USA NIH research programme: RP-PG-0310-1002 ; UK Medical Research Council: G0000934 ; Web of Science