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1.
Artigo em Inglês | MEDLINE | ID: mdl-38529674

RESUMO

OBJECTIVE: Deucravacitinib, a tyrosine kinase 2 inhibitor, was assessed in a phase 2 trial in patients with active psoriatic arthritis (PsA). Here, we report effects of deucravacitinib from the patient perspective. METHODS: This phase 2, double-blind trial (NCT03881059) randomized patients with active PsA 1:1:1 to deucravacitinib 6 mg once daily (QD), 12 mg QD, or placebo, for 16 weeks. Key secondary end points were changes from baseline (CFBs) at week 16 in Health Assessment Questionnaire-Disability Index (HAQ-DI) and 36-item Short-Form Health Survey (SF-36) physical component summary (PCS) scores. Additional patient-reported outcomes (PROs) assessed disease impact, including fatigue, pain, and mental health. The mean CFBs in PROs and percentages of patients reporting improvements with minimum clinically important differences (MCIDs) or scores of greater than normal values were also assessed. RESULTS: This study comprised 203 patients (51.2% female; mean ± SD age, 49.8 ± 13.5 years). At week 16, the adjusted mean difference (95% confidence interval) versus placebo in HAQ-DI and SF-36 PCS CFB was significant for each deucravacitinib group (HAQ-DI 6 mg, -0.26 [-0.42 to -0.10], P = 0.0020; HAQ-DI 12 mg, -0.28 [-0.45 to -0.12], P = 0.0008; SF-36 PCS 6 mg, 3.3 [0.9 to 5.7], P = 0.0062; SF-36 PCS 12 mg, 3.5 [1.1 to 5.9], P = 0.0042). MCID at week 16 were reported for all PROs with either dose of deucravacitinib. Improvements of MCID or to normative values were reported by more patients receiving deucravacitinib than placebo. CONCLUSION: Deucravacitinib groups demonstrate significant and clinically meaningful improvements in PROs versus placebo in patients with active PsA, which warrants further study.

2.
Eur J Anaesthesiol ; 41(5): 351-362, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38414426

RESUMO

BACKGROUND: Chronic postsurgical pain (CPSP) is a clinical problem, and large prospective studies are needed to determine its incidence, characteristics, and risk factors. OBJECTIVE: To find predictive factors for CPSP in an international survey. DESIGN: Observational study. SETTING: Multicentre European prospective observational trial. PATIENTS: Patients undergoing breast cancer surgery, sternotomy, endometriosis surgery, or total knee arthroplasty (TKA). METHOD: Standardised questionnaires were completed by the patients at 1, 3, and 7 days, and at 1, 3, and 6 months after surgery, with follow-up via E-mail, telephone, or interview. MAIN OUTCOME MEASURE: The primary goal of NIT-1 was to propose a scoring system to predict those patient likely to have CPSP at 6 months after surgery. RESULTS: A total of 3297 patients were included from 18 hospitals across Europe and 2494 patients were followed-up for 6 months. The mean incidence of CPSP at 6 months was 10.5%, with variations depending on the type of surgery: sternotomy 6.9%, breast surgery 7.4%, TKA 12.9%, endometriosis 16.2%. At 6 months, neuropathic characteristics were frequent for all types of surgery: sternotomy 33.3%, breast surgery 67.6%, TKA 42.4%, endometriosis 41.4%. One-third of patients experienced CPSP at both 3 and 6 months. Pre-operative pain was frequent for TKA (leg pain) and endometriosis (abdomen) and its frequency and intensity were reduced after surgery. Severe CPSP and a neuropathic pain component decreased psychological and functional wellbeing as well as quality of life. No overarching CPSP risk factors were identified. CONCLUSION: Unfortunately, our findings do not offer a new CPSP predictive score. However, we present reliable new data on the incidence, characteristics, and consequences of CPSP from a large European survey. Interesting new data on the time course of CPSP, its neuropathic pain component, and CPSP after endometriosis surgery generate new hypotheses but need to be confirmed by further research. TRIAL REGISTRATION: clinicaltrials.gov ID: NCT03834922.


Assuntos
Neoplasias da Mama , Dor Crônica , Endometriose , Neuralgia , Feminino , Humanos , Dor Crônica/diagnóstico , Dor Crônica/epidemiologia , Dor Crônica/etiologia , Endometriose/complicações , Neuralgia/diagnóstico , Neuralgia/epidemiologia , Neuralgia/etiologia , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Qualidade de Vida , Inquéritos e Questionários , Masculino
3.
J Scleroderma Relat Disord ; 8(2): 120-130, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37287945

RESUMO

Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis. Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months. Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement. Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.

4.
Nutrients ; 15(4)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36839277

RESUMO

Frequent intake of sugar-sweetened beverages (SSBs) is associated with adverse health outcomes such as obesity, type 2 diabetes, and cardiovascular disease. Little is known about when, where, and why U.S. adults consume SSBs. This study, using data from an online survey distributed in 2021, examined the occasions, locations, and reasons for consuming SSBs and the characteristics of the adults who consume them. Nearly 7 of 10 adults reported consuming a SSB (1-6 times) in the past 7 days, and more than a third (38%) reported doing so once or more per day (on average). For comparative purposes, the sample was limited to adults who reported consuming SSBs within the last 7 days. Mealtimes were reported as the most frequent occasion for the intake of SSBs (43%) and SSBs were most often consumed at home (70%). Over half of respondents (56%) reported they consume SSBs because they enjoy the taste. Younger adults (18-34 years old) were more likely to consume SSBs in social settings than older adults (≥50 years old). Hispanic adults were less likely to consume SSBs at the beginning of the day compared to non-Hispanic White adults. Younger (18-34 years old) and middle-aged (35-49 years old) adults were more likely to consume SSBs in restaurants, at work, and in cars than older adults (≥50 years old). Women were less likely to consume SSBs at work than men. Hispanic adults were less likely to consume SSBs in cars than non-Hispanic White adults, while those earning USD 50,000-

Assuntos
Diabetes Mellitus Tipo 2 , Bebidas Adoçadas com Açúcar , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Adolescente , Adulto Jovem , Adulto , Bebidas/efeitos adversos , Inquéritos e Questionários , Obesidade
5.
Arthritis Care Res (Hoboken) ; 74(3): 364-370, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141441

RESUMO

OBJECTIVE: Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high-resolution computed tomography (HRCT) in juvenile SSc. METHODS: The juvenile SSc cohort database was queried for patients enrolled from January 2008 to January 2020 with recorded pulmonary function tests (PFTs) parameters and HRCT to determine the discriminatory properties of PFT parameters, FVC, and DLco in detecting ILD. RESULTS: Eighty-six juvenile SSc patients had both computed tomography imaging and FVC values for direct comparison. Using findings on HRCT as the standard measure of ILD presence, the sensitivity of FVC in detecting ILD in juvenile SSc was only 40%, the specificity was 77%, and area under the curve (AUC) was 0.58. Fifty-eight juvenile SSc patients had both CT imaging and DLco values for comparison. The sensitivity of DLco in detecting ILD was 76%, the specificity was 70%, and AUC was 0.73. CONCLUSION: The performance of PFTs in juvenile SSc to detect underlying ILD was quite limited. Specifically, the FVC, which is one of the main clinical parameters in adult SSc to detect and monitor ILD, would miss ~60% of children who had ILD changes on their accompanying HRCT. The DLco was more sensitive in detecting potential abnormalities on HRCT, but with less specificity than the FVC. These results support the use of HRCT in tandem with PFTs for the screening of ILD in juvenile SSc.


Assuntos
Doenças Pulmonares Intersticiais/complicações , Escleroderma Sistêmico/complicações , Adolescente , Criança , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Masculino , Diagnóstico Ausente , Estudos Prospectivos , Curva ROC , Tomografia Computadorizada por Raios X , Capacidade Vital
6.
Arthritis Care Res (Hoboken) ; 74(10): 1575-1584, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-33787070

RESUMO

OBJECTIVE: To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. METHODS: A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. RESULTS: At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. CONCLUSION: Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.


Assuntos
Doenças Pulmonares Intersticiais , Esclerodermia Difusa , Escleroderma Sistêmico , Úlcera Cutânea , Estudos Transversais , Feminino , Humanos , Masculino , Esclerodermia Difusa/diagnóstico , Esclerodermia Localizada , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/epidemiologia
7.
Rheumatol Ther ; 9(2): 465-480, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34940957

RESUMO

INTRODUCTION: Patients with rheumatoid arthritis (RA) may respond to treatments differently based on their underlying serology and biomarker status, but real-world data comparing treatment responses to abatacept versus other non-TNFi biologic or targeted-synthetic DMARDs by anti-citrullinated protein antibody (ACPA) status remain limited. We assessed the association between ACPA status and response to treatment in patients with RA. METHODS: Adults from CorEvitas' RA Registry were identified who initiated abatacept, rituximab, tocilizumab, or tofacitinib, and had ACPA measured at/prior to treatment initiation and at the 6-month follow-up visit. Three cohorts were included: abatacept/rituximab (2006-2019), abatacept/tocilizumab (2010-2019), and abatacept/tofacitinib (2012-2019). Patient characteristics at initiation were compared by ACPA status (positive [+], anti-cyclic citrullinated peptide-2 [anti-CCP2] ≥ 20 U/ml; negative [-], anti-CCP2 < 20 U/ml). Outcomes over 6 months: changes in Clinical Disease Activity Index (CDAI), modified Health Assessment Questionnaire (mHAQ), patient global assessment (PGA) scores, and proportion of patients achieving a clinical response. Adjusted mean differences and odds ratios were estimated using mixed-effects linear regression models. RESULTS: Overall, 982 abatacept, 246 rituximab, 404 tocilizumab, and 429 tofacitinib initiators were identified. ACPA+ (vs. ACPA-) patients had longer disease duration and more erosive disease. During most time periods adjusted mean changes in CDAI, mHAQ, and PGA scores and the proportion of patients achieving a clinical response were significantly higher for ACPA+ versus ACPA- patients initiating abatacept. Adjusted mean change in PGA score and patient fatigue were significantly higher for ACPA+ versus ACPA- patients initiating rituximab. No significant differences were seen by ACPA status for patients initiating tocilizumab or tofacitinib. CONCLUSIONS: Patients who initiated abatacept or rituximab and were ACPA+ had a greater clinical response at 6-month follow-up post index compared to patients who were ACPA- treated with the same biologic.

8.
Rheumatol Ther ; 8(2): 937-953, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34047953

RESUMO

INTRODUCTION: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with poor prognosis in patients with rheumatoid arthritis (RA). Previous data from randomized controlled trials and clinical practice have shown anti-CCP-positive (+) patients had a better response to treatment with abatacept or tumor necrosis factor inhibitor (TNFi) treatment than those who were anti-CCP negative. This study assessed the association between baseline anti-CCP2 [a surrogate for anti-citrullinated protein antibody (ACPA)] concentration and 6-month treatment responses to abatacept or TNFi in patients with RA. METHODS: This real-world analysis included biologic-experienced patients from CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory CoNditions) who initiated abatacept or TNFi, had prior biologic disease-modifying drug exposure and baseline anti-CCP2 concentration/serostatus and serum samples (baseline and 6 months). Baseline demographics and disease characteristics were compared. Change from baseline at 6 months in Clinical Disease Activity Index (CDAI) score and patient-reported outcomes [PROs: pain, fatigue, patient global assessment (PtGA), modified Health Assessment Questionnaire (mHAQ) score], by baseline anti-CCP2 quartile and binary cut-off (> 10-250 and > 250 U/ml), were evaluated separately in the abatacept and TNFi groups using a linear regression model adjusted for age, sex, CDAI/PROs, comorbidity index, and methotrexate use. RESULTS: Included were 138 abatacept and 137 TNFi initiators who were anti-CCP2+. At baseline, there were significant differences between anti-CCP2 quartiles and mean CDAI, swollen joint count 28, C-reactive protein (CRP), Disease Activity Score 28 (CRP), rheumatoid factor (RF), mHAQ and physician global assessment among abatacept initiators, and in mean RF, mHAQ, and PtGA among TNFi initiators. Among abatacept (but not TNFi) initiators, CDAI numerically improved (p = 0.208) and PROs significantly improved (p < 0.05) with increasing baseline anti-CCP2. CONCLUSIONS: In patients treated with abatacept, not TNFi, higher anti-CCP2 concentrations at baseline were associated with numerically greater improvements in CDAI and significant improvements in PROs after 6 months. CLINICAL TRIAL NUMBER: NCT01625650.


Rheumatoid arthritis (RA) is an autoimmune disease ­ a disease that causes the immune system to attack an individual's own body. A key feature of RA is the presence of proteins called autoantibodies in the blood. While antibodies help protect against external threats such as viruses, autoantibodies mistakenly target an individual's own tissues and organs. One type of autoantibody often found in patients with RA is called anti-cyclic citrullinated peptide (anti-CCP). Studies have shown that patients with RA with anti-CCP antibodies may experience worse physical symptoms, function, disease activity, and outcomes than patients with RA without anti-CCP antibodies. Clinical trials suggest that some drugs may be more effective than others at managing symptoms of RA in patients who have anti-CCP in their blood. It is important to study this further to give doctors a sense of how patients respond to drug therapy in the 'real world', without clinical trial constraints. This study examined real-world patient data to see whether the presence of anti-CCP in patients' blood impacted how their RA symptoms responded to treatment with two different drugs: abatacept or a tumor necrosis factor inhibitor (TNFi). This study found that patients with higher levels of anti-CCP at the start of the study, compared with patients with lower levels of anti-CCP, experienced less disease activity and greater improvement in physical function after 6 months of treatment with abatacept. The study found no relationship between anti-CCP and treatment response after 6 months of treatment with a TNFi.

9.
Hand (N Y) ; 16(3): 362-367, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-31185745

RESUMO

Background: The purpose of this study was to evaluate the demographics and early radiographic treatment outcome of patients with carpometacarpal (CMC) injuries at our institution over a 10-year period. Methods: We conducted a retrospective review of all patients who sustained CMC injuries of the second to fifth digits between 2005 and 2015. We recorded demographic data, mechanisms of and associated injuries, treatment methods, and complications. Injury and intraoperative and postoperative radiographs were evaluated, and the adequacy of reduction was determined on lateral radiographs of the hand using a grading system that we developed. Results: Eighty patients were included in this study. Delivering a blow with a closed fist was the most common mechanism of injury; however, high-energy mechanisms also made up a large percentage of those included. Injuries to the fourth and fifth CMC joints were most common, and these were frequently associated with fractures of the metacarpal bases and distal carpal row. Closed reduction and percutaneous pinning offered a higher percentage of patients with concentric reduction at the time of pin removal. Time to surgery was significantly different between those with concentric reduction and those with residual subluxation. Conclusion: The most common mechanism of CMC injuries was blow with a closed fist; however, these injuries can be associated with high-energy mechanisms. Fractures of the metacarpal base and distal carpal row are commonly seen with these injuries. With early diagnosis, closed reduction and percutaneous pinning achieved concentric radiographic reduction. Delayed diagnosis makes closed reduction difficult and was associated with less favorable radiographic outcome.


Assuntos
Ossos do Carpo , Articulações Carpometacarpais , Fraturas Ósseas , Luxações Articulares , Articulações Carpometacarpais/diagnóstico por imagem , Articulações Carpometacarpais/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Estudos Retrospectivos
10.
J Rheumatol ; 48(6): 852-858, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33060314

RESUMO

OBJECTIVE: Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA-related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis. METHODS: Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population. RESULTS: The analyzed cohort consisted of 1540 patients: 1351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations between all non-HLA GRS and age of SLE diagnosis: P = 0.011 and r2 = 0.175 for GRWS; P = 0.008 and r2 = 0.178 for GRSCS; P = 0.002 and r2 = 0.176 for GRSWS (higher GRS correlated with lower age of diagnosis.) All HLA GRS showed significant positive associations with age of diagnosis: P = 0.049 and r2 = 0.176 for GRCS; P = 0.022 and r2 = 0.176 for GRWS; P = 0.022 and r2 = 0.176 for GRSCS; P = 0.011 and r2 = 0.177 for GRSWS (higher GRS correlated with higher age of diagnosis). CONCLUSION: Our data suggest that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA GRS are associated with age of diagnosis in opposite directions.


Assuntos
Lúpus Eritematoso Sistêmico , Adulto , Idade de Início , Criança , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco
11.
Arterioscler Thromb Vasc Biol ; 40(3): 802-818, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31996019

RESUMO

OBJECTIVE: Kawasaki disease (KD) is the leading cause of acute vasculitis and acquired heart disease in children in developed countries. Notably, KD is more prevalent in males than females. We previously established a key role for IL (interleukin)-1 signaling in KD pathogenesis, but whether this pathway underlies the sex-based difference in susceptibility is unknown. Approach and Results: The role of IL-1 signaling was investigated in the Lactobacillus casei cell wall extract-induced experimental mouse model of KD vasculitis. Five-week-old male and female mice were injected intraperitoneally with PBS, Lactobacillus caseicell wall extract, or a combination of Lactobacillus caseicell wall extract and the IL-1 receptor antagonist Anakinra. Aortitis, coronary arteritis inflammation score and abdominal aorta dilatation, and aneurysm development were assessed. mRNA-seq (messenger RNA sequencing) analysis was performed on abdominal aorta tissue. Publicly available human transcriptomics data from patients with KD was analyzed to identify sex differences and disease-associated genes. Male mice displayed enhanced aortitis and coronary arteritis as well as increased incidence and severity of abdominal aorta dilatation and aneurysm, recapitulating the increased incidence in males that is observed in human KD. Gene expression data from patients with KD and abdominal aorta tissue of Lactobacillus caseicell wall extract-injected mice showed enhanced Il1b expression and IL-1 signaling genes in males. Although the more severe IL-1ß-mediated disease phenotype observed in male mice was ameliorated by Anakinra treatment, the milder disease phenotype in female mice failed to respond. CONCLUSIONS: IL-1ß may play a central role in mediating sex-based differences in KD, with important implications for the use of anti-IL-1ß therapies to treat male and female patients with KD.


Assuntos
Aorta Abdominal/metabolismo , Interleucina-1beta/metabolismo , Síndrome de Linfonodos Mucocutâneos/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Aorta Abdominal/imunologia , Estudos de Casos e Controles , Modelos Animais de Doenças , Resistência a Medicamentos , Feminino , Disparidades nos Níveis de Saúde , Humanos , Incidência , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1beta/genética , Lacticaseibacillus casei , Masculino , Camundongos Endogâmicos C57BL , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/microbiologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Transdução de Sinais
12.
Immunity ; 51(3): 508-521.e6, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31471109

RESUMO

Recent experimental data and clinical, genetic, and transcriptome evidence from patients converge to suggest a key role of interleukin-1ß (IL-1ß) in the pathogenesis of Kawasaki disease (KD). However, the molecular mechanisms involved in the development of cardiovascular lesions during KD vasculitis are still unknown. Here, we investigated intestinal barrier function in KD vasculitis and observed evidence of intestinal permeability and elevated circulating secretory immunoglobulin A (sIgA) in KD patients, as well as elevated sIgA and IgA deposition in vascular tissues in a mouse model of KD vasculitis. Targeting intestinal permeability corrected gut permeability, prevented IgA deposition and ameliorated cardiovascular pathology in the mouse model. Using genetic and pharmacologic inhibition of IL-1ß signaling, we demonstrate that IL-1ß lies upstream of disrupted intestinal barrier function, subsequent IgA vasculitis development, and cardiac inflammation. Targeting mucosal barrier dysfunction and the IL-1ß pathway may also be applicable to other IgA-related diseases, including IgA vasculitis and IgA nephropathy.


Assuntos
Doenças Cardiovasculares/imunologia , Imunoglobulina A/imunologia , Inflamação/imunologia , Intestinos/imunologia , Animais , Modelos Animais de Doenças , Humanos , Interleucina-1beta/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Síndrome de Linfonodos Mucocutâneos/imunologia , Permeabilidade , Transdução de Sinais/imunologia , Vasculite/imunologia
14.
JCI Insight ; 4(3)2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30728329

RESUMO

Kawasaki disease (KD), the leading cause of acquired cardiac disease among children, is often associated with myocarditis that may lead to long-term myocardial dysfunction and fibrosis. Although those myocardial changes develop during the acute phase, they may persist for decades and closely correlate with long-term myocardial sequelae. Using the Lactobacillus casei cell wall extract-induced (LCWE-induced) KD vasculitis murine model, we investigated long-term cardiovascular sequelae, such as myocardial dysfunction, fibrosis, and coronary microvascular lesions following adrenergic stimuli after established KD vasculitis. We found that adrenergic stimulation with isoproterenol following LCWE-induced KD vasculitis in mice was associated with increased risk of cardiac hypertrophy and myocardial fibrosis, diminished ejection fraction, and increased serum levels of brain natriuretic peptide. Myocardial fibrosis resulting from pharmacologic-induced exercise after KD development was IL-1 signaling dependent and was associated with a significant reduction in myocardial capillary CD31 expression, indicative of a rarefied myocardial capillary bed. These observations suggest that adrenergic stimulation after KD vasculitis may lead to cardiac hypertrophy and bridging fibrosis in the myocardium in the LCWE-induced KD vasculitis mouse model and that this process involves IL-1 signaling and diminished microvascular circulation in the myocardium.

15.
J Scleroderma Relat Disord ; 4(1): 49-61, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35382144

RESUMO

Introduction: Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Methods: Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. Results: In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud's and first non-Raynaud's symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). Discussion: The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis.

16.
Arthritis Res Ther ; 20(1): 269, 2018 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-30522501

RESUMO

BACKGROUND: To explore the effect of abatacept treatment on patient-reported outcomes (PROs) in psoriatic arthritis (PsA). METHODS: Patients with PsA were randomised (1:1) to subcutaneous abatacept 125 mg weekly/placebo for 24 weeks with early escape (EE) to open-label abatacept (week 16). Adjusted mean changes from baseline to weeks 16 (all patients) and 24 (non-EE responders) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 (SF-36; physical and mental component summary and domains), Dermatology Life Quality Index and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Subpopulations were analysed by baseline C-reactive protein (CRP) level (> vs ≤ upper limit of normal [ULN]) and prior tumour necrosis factor inhibitor (TNFi) exposure. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCIDs) and ≥ normative values (NVs) in HAQ-DI, SF-36 and FACIT-F (week 16 before EE) were analysed. RESULTS: In total population, numerically higher improvements in most PROs were reported with abatacept (n = 213) versus placebo (n = 211) at both time points (P > 0.05). Higher proportions of abatacept versus placebo patients reported PRO improvements ≥ MCID and ≥ NV at week 16. At week 16, all PRO improvements were numerically greater (P > 0.05) in patients with baseline CRP > ULN versus CRP ≤ ULN (all significant [95% confidence interval] for abatacept vs placebo); improvements in SF-36 component summaries and FACIT-F were greater in TNFi-naïve versus TNFi-exposed patients (abatacept > placebo). Week 24 subgroup data were difficult to interpret due to low patient numbers. CONCLUSIONS: Abatacept treatment improved PROs in patients with PsA versus placebo, with better results in elevated baseline CRP and TNFi-naïve subpopulations. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb); date of registration: 23 May 2013.


Assuntos
Abatacepte/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Metotrexato/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Adulto , Antirreumáticos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Telemed J E Health ; 24(1): 54-60, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28682706

RESUMO

INTRODUCTION: The intent was to evaluate time to match initial investment of a new, statewide correctional system telehealth program based upon cumulative savings by avoidance of transportation and custody-related costs. MATERIALS AND METHODS: The setting was a statewide correctional system where prisoners received medical care through enhanced telemedicine technology supported by newly recruited specialty providers delivered through an open architecture system. The patients were incarcerated persons requiring nonemergent consultations in 10 specialties. A financial model was created to estimate transportation expenses, including vehicular use and custody staff, during the out of prison travel for traditional face-to-face care. Cost savings were then estimated by multiplying transportation expenses by the number of telehealth encounters (avoided cost) and summed cumulatively. Savings were mapped monthly. Private sector specialists were recruited, provided security clearance, trained in the use of the technology, and provided a secure site to provide services. MEASUREMENTS AND MAIN RESULTS: Based on the financial model, 1.2 million dollars in savings, equaling the initial capital investment, were achieved at 32 months. The total number of patient telemedicine encounters increased from 2,365 (±98/month) to 3,748 during the first 32 months of operation (July 2013 through January 2016: ±117/month) with 89% of the established specialties performed by telemedicine technologies. DISCUSSION: It was initially estimated to require 48 months to achieve the investment savings, but savings were achieved in 32 months, demonstrating greater adoption than expected. While finances were quantifiable, enhanced public safety by avoidance of out of prison time is unquantifiable, but judged to be significant.


Assuntos
Programas de Assistência Gerenciada/organização & administração , Prisões/organização & administração , Telemedicina/organização & administração , Humanos , Programas de Assistência Gerenciada/economia , Prisões/economia , Telemedicina/economia , Meios de Transporte/economia , Meios de Transporte/métodos
18.
Prev Chronic Dis ; 14: E126, 2017 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-29215979

RESUMO

We conducted a content analysis of newspaper and television news coverage in Centers for Disease Control and Prevention (CDC) grantee locations from June 2011 through May 2013. After searching 2 databases for news stories related to overweight or obesity, we coded and analyzed stories for valence (how the author/reporter framed overweight and obesity control strategies), descriptors, causes and solutions, and populations mentioned. Of almost 3,000 stories analyzed, most had a neutral or positive valence, depicted overweight and obesity as epidemic, discussed individual causes and environmental solutions most frequently, and mentioned children most often. Earned media can be part of addressing overweight and obesity by emphasizing prevention and by emphasizing both environmental and individual causes and solutions.


Assuntos
Organização do Financiamento , Jornais como Assunto , Obesidade/prevenção & controle , Centers for Disease Control and Prevention, U.S. , Humanos , Estados Unidos
19.
Front Public Health ; 5: 202, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28868272

RESUMO

BACKGROUND: Among medical providers, even though radiological and nuclear events are recognized as credible threats, there is a lack of knowledge and fear about the medical consequences among medical personnel which could significantly affect the treatment of patients injured and/or contaminated in such scenarios. This study was conducted to evaluate the relative knowledge, willingness to respond, and familiarity with nuclear/radiological contamination risks among U.S. and Japanese emergency medical personnel. METHODS: An institutional review board-approved anonymous paper survey was distributed at various medical and disaster conferences and medicine courses in Japan and in the U.S. The surveys were written in Japanese and English and collected information on the following four categories: generalized demographics, willingness to manage, knowledge of disaster systems, and contamination risks. RESULTS: A total of 418 surveys were completed and collected. Demographics showed that physicians and prehospital responders were the prevalent survey responders. The majority of responders, despite self-professed disaster training, were still very uncomfortable with and unaware how to respond to a radiological/nuclear event. CONCLUSION: Despite some educational coverage in courses and a limited number of disaster events, it is concluded that there is a lack of comfort and knowledge regarding nuclear and radiological events among the medical community. It is recommended that considerable development and subsequent distribution is needed to better educate and prepare the medical community for inevitable upcoming radiological/nuclear events.

20.
Hand Clin ; 33(1): 97-106, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27886844

RESUMO

Hand and wrist injuries in martial arts are typically a reflection of the combat nature of this discipline. In striking sports, the axial load mechanism of injury is common and causes fractures and dislocations; in grappling sports, sprain injuries and degenerative changes predominate. There is clear evidence to support that hand protection reduces the risk of hand injury. Traditional training in martial arts on proper technique and target selection in striking sports reduces the risk of hand injury, and is an important component of hand and wrist injury prevention.


Assuntos
Boxe/lesões , Traumatismos da Mão/etiologia , Traumatismos da Mão/prevenção & controle , Artes Marciais/lesões , Traumatismos do Punho/etiologia , Traumatismos do Punho/prevenção & controle , Humanos
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