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1.
N Engl J Med ; 383(24): 2333-2344, 2020 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-33085857

RESUMEN

BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Receptores de Interleucina-6/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Boston , COVID-19/mortalidad , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Intubación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Terapia Respiratoria , Insuficiencia del Tratamiento , Adulto Joven
2.
J Rheumatol ; 50(5): 684-689, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36521924

RESUMEN

OBJECTIVE: To determine if the degree of baseline fibromyalgia (FM) symptoms in patients with rheumatoid arthritis (RA), as indicated by the Fibromyalgia Survey Questionnaire (FSQ) score, predicts RA disease activity after initiation or change of a disease-modifying antirheumatic drug (DMARD). METHODS: One hundred ninety-two participants with active RA were followed for 12 weeks after initiation or change of DMARD therapy. Participants completed the FSQ at the initial visit. The Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) was measured at baseline and follow-up to assess RA disease activity. We evaluated the association between baseline FSQ score and follow-up DAS28-CRP. As a secondary analysis, we examined the relationship between the 2 components of the FSQ, the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), with follow-up DAS28-CRP. Multiple linear regression analyses were performed, adjusting for clinical and demographic variables. RESULTS: In multiple linear regression models, FSQ score was independently associated with elevated DAS28-CRP scores 12 weeks after DMARD initiation (B = 0.04, P = 0.01). In secondary analyses, the WPI was significantly associated with increased follow-up DAS28-CRP scores (B = 0.08, P = 0.001), whereas the SSS was not (B = -0.03, P = 0.43). CONCLUSION: Higher levels of FM symptoms weakly predicted worse disease activity after treatment. The primary factor that informed the FSQ's prediction of disease activity was the spatial extent of pain, as measured by the WPI.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Fibromialgia , Humanos , Fibromialgia/diagnóstico , Índice de Severidad de la Enfermedad , Artritis Reumatoide/tratamiento farmacológico , Dolor/complicaciones , Proteína C-Reactiva , Encuestas y Cuestionarios , Antirreumáticos/uso terapéutico
3.
Rheumatology (Oxford) ; 61(4): 1556-1562, 2022 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-34293092

RESUMEN

OBJECTIVES: Over one-third of patients with RA exhibit evidence of fibromyalgianess, which is associated with higher rates of disability and inadequate responsiveness to RA treatment. Patients with RA often remain on glucocorticoids long-term, despite the known risk of dose-dependent morbidity. We undertook this study to examine the relationship between fibromyalgianess and glucocorticoid persistence among RA patients. METHODS: We followed participants with active RA on oral prednisone for ∼3 months after initiating a new DMARD. Fibromyalgianess was measured using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key FM features often superimposed upon RA. Severity of fibromyalgianess was stratified as follows: FSQ <8 low, FSQ 8-10 moderate and FSQ >10 high/very high. The association between baseline fibromyalgianess and glucocorticoid persistence, defined as prednisone use at 3-month follow-up visit after DMARD initiation, was assessed using multiple logistic regression adjusted for baseline demographics, RA duration, serostatus and inflammatory activity assessed using swollen joint count and CRP. RESULTS: Of the 97 participants on prednisone at baseline, 65% were still taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent glucocorticoid use, compared with 84% of participants with high or very high fibromyalgianess. After adjustment for non-inflammatory factors and inflammatory activity, participants with high/very high baseline fibromyalgianess were more likely to be taking prednisone at follow-up relative to those with low fibromyalgianess [odds ratio 4.99 (95% CI 1.20, 20.73)]. CONCLUSION: High fibromyalgianess is associated with persistent glucocorticoid use, independent of inflammatory activity.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Fibromialgia , Antirreumáticos/uso terapéutico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Fibromialgia/complicaciones , Fibromialgia/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Humanos , Prednisona/uso terapéutico
4.
Clin Exp Rheumatol ; 40(9): 1754-1761, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35084303

RESUMEN

OBJECTIVES: Many studies have found that moderate alcohol consumption is associated with lower risks of mortality and myocardial infarction (MI). Our aim was to examine the potential effects of alcohol on all-cause mortality and MI in rheumatoid arthritis (RA), a risk factor condition. METHODS: A cohort study (1995-2017) was conducted using medical records of RA patients from The Health Improvement Network in the United Kingdom (UK). Alcohol exposure was divided into non-drinkers, mild (1-7 UK units/week), moderate (8-14 UK units/week), moderate-high (15-21 UK units/week), and high (>21 UK units/week) consumption levels. We calculated hazard ratios (HRs) for the relation of alcohol consumption to all-cause mortality and MI, adjusting for covariates. RESULTS: Of 30,320 RA patients, 5,994 deaths and 1,098 MI cases occurred over 236,188 person-years. Mild-to-moderate alcohol use was associated with lower all-cause mortality in RA patients, including those taking methotrexate. The multivariable HRs (95% CI) for mortality by alcohol use category were non-drinkers 1.0, mild 0.80 (0.75-0.85), moderate 0.74 (0.67-0.82), moderate-high 0.84 (0.72-0.98), and high 0.99 (0.86-1.15). Mild, moderate-high, and high levels of alcohol use were associated with lower risk of MI among RA patients. The HRs MI risk by alcohol use category were non-drinkers 1.0, mild 0.81 (0.70-0.94), moderate 0.84 (0.68-1.04), moderate-high 0.51 (0.35-0.74), and high 0.59 (0.42-0.84). CONCLUSIONS: These findings suggest that mild-to-moderate alcohol use is associated with a lower mortality risk and overall alcohol use is associated with a lower MI risk in RA patients, similar to the general population.


Asunto(s)
Artritis Reumatoide , Infarto del Miocardio , Consumo de Bebidas Alcohólicas/efectos adversos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Estudios de Cohortes , Humanos , Metotrexato , Factores de Riesgo
5.
J Allergy Clin Immunol ; 147(1): 368-382, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32485263

RESUMEN

BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated fibrotic disorder that has been linked to CD4+ cytotoxic T lymphocytes (CD4+CTLs). The effector phenotype of CD4+CTLs and the relevance of both CD8+ cytotoxic T lymphocytes (CD8+CTLs) and apoptotic cell death remain undefined in IgG4-RD. OBJECTIVE: We sought to define CD4+CTL heterogeneity, characterize the CD8+CTL response in the blood and in lesions, and determine whether enhanced apoptosis may contribute to the pathogenesis of IgG4-RD. METHODS: Blood analyses were undertaken using flow cytometry, cell sorting, transcriptomic analyses at the population and single-cell levels, and next-generation sequencing for the TCR repertoire. Tissues were interrogated using multicolor immunofluorescence. Results were correlated with clinical data. RESULTS: We establish that among circulating CD4+CTLs in IgG4-RD, CD27loCD28loCD57hi cells are the dominant effector subset, exhibit marked clonal expansion, and differentially express genes relevant to cytotoxicity, activation, and enhanced metabolism. We also observed prominent infiltration of granzyme A-expressing CD8+CTLs in disease tissues and clonal expansion in the blood of effector/memory CD8+ T cells with an activated and cytotoxic phenotype. Tissue studies revealed an abundance of cells undergoing apoptotic cell death disproportionately involving nonimmune, nonendothelial cells of mesenchymal origin. Apoptotic cells showed significant upregulation of HLA-DR. CONCLUSIONS: CD4+CTLs and CD8+CTLs may induce apoptotic cell death in tissues of patients with IgG4-RD with preferential targeting of nonendothelial, nonimmune cells of mesenchymal origin.


Asunto(s)
Antígenos CD/inmunología , Apoptosis/inmunología , Linfocitos T CD4-Positivos/inmunología , Enfermedad Relacionada con Inmunoglobulina G4/inmunología , Células Madre Mesenquimatosas/inmunología , Linfocitos T Citotóxicos/inmunología , Adulto , Linfocitos T CD4-Positivos/patología , Femenino , Fibrosis , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/patología , Masculino , Células Madre Mesenquimatosas/patología , Linfocitos T Citotóxicos/patología
7.
Rheumatology (Oxford) ; 59(7): 1505-1513, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31628482

RESUMEN

OBJECTIVES: 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity. METHODS: We conducted a randomized double-blind placebo-controlled 12 week trial of lovastatin vs placebo in 64 RA patients with mild clinical disease activity but an elevated CRP. The primary efficacy end point was the reduction in mean log CRP. Secondary end points included disease activity, RF and anti-CCP antibody titres. Mechanistic end points included levels of serum cytokines. Safety was assessed; hepatic and muscle toxicities were of particular interest. RESULTS: Baseline features were similar between groups. No significant difference in mean log CRP reduction between the two groups was observed, and disease activity did not change from baseline in either treatment group. Mechanistic analyses did not reveal significant changes in any biomarkers. A post hoc analysis of subjects not using biologic therapy demonstrated a significantly greater proportion achieving ⩾20% reduction in CRP from baseline in the lovastatin group compared with placebo (P-value = 0.007). No difference was observed in subjects receiving biologics. Lovastatin was well tolerated with no serious safety concerns. CONCLUSION: This study showed no anti-inflammatory or clinical effects on RA disease activity after 12 weeks of treatment with lovastatin. Lovastatin had a modest effect on CRP in subjects not using biologics, suggesting statins may be anti-inflammatory in selected patients. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00302952.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Proteína C-Reactiva/inmunología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lovastatina/uso terapéutico , Adulto , Anticuerpos Antiproteína Citrulinada/inmunología , Artritis Reumatoide/inmunología , Artritis Reumatoide/fisiopatología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factor Reumatoide/inmunología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
8.
J Clin Rheumatol ; 25(5): 232-236, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30035754

RESUMEN

BACKGROUND: The aims of this study were to define changes in catastrophizing that occur with initiation of a new disease-modifying antirheumatic drug (DMARD) and to examine the relationship between changes in Clinical Disease Activity Index (CDAI) and changes in catastrophizing. METHODS: Participants in an ongoing multisite, observational study completed the Pain Catastrophizing Scale (PCS) before and 12 weeks after DMARD initiation. We used multivariable linear regression models to examine the association between changes in CDAI as the exposure and change in pain catastrophizing as the outcome. We also assessed the relationship between changes in each component of CDAI and change in PCS, using multivariable linear regression models. RESULTS: Among the 165 rheumatoid arthritis patients with data on CDAI at both time points, CDAI decreased from 22 to 11.5 on a 76-point scale (p < 0.0001) after 12 weeks. Pain intensity decreased from a median of 5 to 3 on a 10-point numeric rating scale (p < 0.0001), and catastrophizing decreased, from 16.0 to 12.0 on the 52-point PCS (p = 0.0005). Among the 163 with complete data for the regression analysis, changes in CDAI were positively correlated with changes in catastrophizing (standardized ß = 0.19, p = 0.01). Of the components of the CDAI, change in assessor global score was most strongly associated with changes in catastrophizing (standardized ß = 0.24, p = 0.003). CONCLUSIONS: Pain catastrophizing decreases, in conjunction with disease activity, after initiation of a new DMARD. These findings provide support for catastrophizing as a dynamic construct that can be altered with treatment directed at decreasing inflammatory disease activity and pain.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/psicología , Catastrofización , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Índice de Severidad de la Enfermedad
10.
Clin Exp Rheumatol ; 35 Suppl 106(4): 106-113, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27908301

RESUMEN

OBJECTIVES: To assess the utility of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) in detecting and monitoring pulmonary hypertension (PH) in systemic sclerosis (SSc). METHODS: PHAROS is a multicenter prospective cohort of SSc patients at high risk for developing pulmonary arterial hypertension (SSc-AR-PAH) or with a definitive diagnosis of SSc-PH. We evaluated 1) the sensitivity and specificity of BNP≥64 and NT-proBNP≥210 pg/mL for the detection of SSc-PAH and/ or SSc-PH in the SSc-AR-PAH population; 2) baseline and longitudinal BNP and NT-proBNP levels as predictors of progression to SSc-PAH and/or SSc-PH; 3) baseline BNP≥180, NT-proBNP≥553 pg/mL, and longitudinal changes in BNP and NT-proBNP as predictors of mortality in SSc-PH diagnosed patients. RESULTS: 172 SSc-PH and 157 SSc-AR- PAH patients had natriuretic peptide levels available. Median BNP and NT-proBNP were significantly higher in the SSc-PH versus SSc-AR-PAH group. The sensitivity and specificity for SSc-PAH detection using baseline BNP≥64 pg/mL was 71% and 59%; and for NT-proBNP≥210 pg/mL, 73% and 78%. NT-proBNP showed stronger correlations with haemodynamic indicators of right ventricular dysfunction than BNP. Baseline creatinine, RVSP > 40 mmHg, and FVC%:DLco% ratio ≥1.8 were associated with progression from SSc-AR-PAH to SSc-PH but no association with individual or combined baseline BNP and NT-proBNP levels was observed. Baseline and follow-up BNP or NT-proBNP levels were not predictive of death, however, a composite BNP/NT-proBNP group predicted mortality (HR 3.81 (2.08-6.99), p<.0001). CONCLUSIONS: NT-proBNP may be more useful than BNP in the detection and monitoring of PAH in SSc patients, but additional studies are necessary.


Asunto(s)
Hipertensión Pulmonar/diagnóstico , Péptido Natriurético Encefálico/sangre , Esclerodermia Sistémica/complicaciones , Anciano , Progresión de la Enfermedad , Femenino , Hemodinámica , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Estudios Prospectivos , Sistema de Registros , Esclerodermia Sistémica/sangre
12.
Curr Opin Rheumatol ; 27(3): 216-24, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25760281

RESUMEN

PURPOSE OF REVIEW: Osteoporosis is a skeletal disorder in which bone strength is decreased leading to an increased risk of fracture. In line with advances in knowledge of bone biology, the past several years have held major therapeutic advances in osteoporosis treatment. In this article, we review the current approaches to osteoporosis treatment with a focus on issues of interest to the practicing rheumatologist. RECENT FINDINGS: In addition to the bisphosphonates, the introduction of denosumab, teriparatide and selective oestrogen-receptor modulators, as well as the development of new therapeutic agents (romosozumab and odanacatib) has opened the door to new approaches, including individualization of treatment in different clinical circumstances based on patient comorbidities and preference; combination therapy to optimize treatment effect; and consideration of goal-based treatment. Postmarketing surveillance of bisphosphonates has revealed several safety concerns including osteonecrosis of the jaw and atypical femoral fractures. Bisphosphonate drug holidays should be considered in patients on bisphosphonate therapy because prolonged treatment may be associated with adverse events. SUMMARY: Substantial progress has been made in the past several years in the understanding and modification of osteoporosis management. Many conditions encountered by rheumatologists are associated with bone loss; therefore, the rheumatologist needs to be aware of the current approaches in osteoporosis management.


Asunto(s)
Difosfonatos/uso terapéutico , Osteoporosis/tratamiento farmacológico , Conservadores de la Densidad Ósea/uso terapéutico , Humanos , Resultado del Tratamiento
13.
Curr Rheumatol Rep ; 16(11): 455, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25240684

RESUMEN

The high prevalence of osteoporotic fractures and their major effect on morbidity and mortality emphasizes the critical need to optimize bone health care. Patients presenting with fragility fractures are at high risk of subsequent fracture, but treatment rates have remained low for these patients. Recently developed fracture liaison services have successfully increased osteoporosis treatment, with improved patient outcomes. We review factors contributing to the treatment gap in osteoporosis, the function of fracture liaison services in reducing this gap, and lessons learned from the literature on effective formats, key elements, and suggestions for managing challenges in implementation of a fracture liaison service.


Asunto(s)
Osteoporosis/terapia , Fracturas Osteoporóticas/prevención & control , Servicios Preventivos de Salud/organización & administración , Humanos , Osteoporosis/complicaciones , Osteoporosis/diagnóstico , Fracturas Osteoporóticas/etiología
14.
ACR Open Rheumatol ; 6(3): 139-144, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38155482

RESUMEN

OBJECTIVE: Feedback from fellows-in-training (FITs) is important for faculty development and to enrich clinical teaching. We sought to evaluate the effectiveness of traditional online evaluations and a novel compiled verbal feedback mechanism. METHODS: An annual feedback system was implemented in our rheumatology division in which FITs provided verbal feedback on all faculty to a facilitator who compiled, deidentified, and shared the feedback with individual faculty members. FITs also completed standard online annual evaluations of faculty. FITs and faculty completed surveys assessing the perceived effectiveness and confidentiality of each feedback mechanism. RESULTS: Thirteen of 15 eligible faculty and all 4 eligible FITs completed both surveys. Responses by FITs and faculty regarding the quality of online evaluations were generally unfavorable or neutral. Faculty responses regarding compiled verbal feedback were more favorable in all questions and significantly more favorable with respect to the feedback's ability to explain strengths (54% favorable for online evaluations vs 100% for compiled verbal feedback), the feedback's specificity (0% vs 54%), and the feedback's actionable nature (15% vs 62%). All FITs' responses regarding quality of compiled verbal feedback were favorable. FITs had concerns regarding confidentiality with both online evaluations (0% favorable) and compiled verbal feedback (25% favorable), though FITs had less concern for future faculty interactions with compiled verbal feedback (100% favorable) than with online evaluations (0% favorable). CONCLUSION: Compiled verbal feedback by FITs produced more actionable and effective feedback for faculty, with less concerns regarding future faculty interactions compared with traditional online evaluations. Further study of this method across different programs and institutions is warranted.

15.
J Endocr Soc ; 8(5): bvae050, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38550278

RESUMEN

Context: Addressing vitamin D deficiency (VDD) is important for fracture secondary prevention. Objectives: To explore the function of a fracture liaison service (FLS) to address VDD. Design Setting and Patients: An observational study of patients admitted to the Massachusetts General Hospital with fractures between January 1, 2016, and October 31, 2023, cared for by the FLS. Intervention: Ergocalciferol 50 000 international units (50ku-D2) oral daily for 3 to 7 days. Main Outcomes Measures: VDD prevalence. Efficacy of inpatient daily 50ku-D2 in raising serum 25-hydroxyvitamin D (25OHD) levels. Results: Of the 2951 consecutive patients, 724 (24.53%) had VDD (defined by 25OHD ≤ 19 ng/mL). Men (252/897, or 28.09%) were more likely than women (472/2054, or 22.98%) to have VDD (P = .003). VDD was seen in 41.79% (117/280), 24.41% (332/1360), and 20.98% (275/1311) of patients of aged ≤59, 60 to 79, and ≥80 years, respectively (P < .00001). Of the 1303 patients with hip fractures, 327 (25.09%) had VDD, which was associated with a longer length of stay (8.37 ± 7.35 vs 7.23 ± 4.78 days, P = .009) and higher trend of 30-day-readmission rate (13.63% vs 18.35%, P = .037). In a cohort of 32 patients with complete data, each dose of 50ku-D2 increased serum 25OHD by 3.62 ± 2.35 ng/mL without affecting serum calcium or creatinine levels. Conclusion: VDD was seen in nearly 25% of Massachusetts General Hospital FLS patients and more prevalent in male and younger patients. VDD was associated with longer length of stay and higher 30-day-readmission risk in patients with hip fracture. Daily 50ku-D2 appeared to be a practical way to quickly replete vitamin D in the inpatient setting.

16.
J Am Heart Assoc ; 13(9): e030387, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38686879

RESUMEN

BACKGROUND: Coronary microvascular dysfunction as measured by myocardial flow reserve (MFR) is associated with increased cardiovascular risk in rheumatoid arthritis (RA). The objective of this study was to determine the association between reducing inflammation with MFR and other measures of cardiovascular risk. METHODS AND RESULTS: Patients with RA with active disease about to initiate a tumor necrosis factor inhibitor were enrolled (NCT02714881). All subjects underwent a cardiac perfusion positron emission tomography scan to quantify MFR at baseline before tumor necrosis factor inhibitor initiation, and after tumor necrosis factor inhibitor initiation at 24 weeks. MFR <2.5 in the absence of obstructive coronary artery disease was defined as coronary microvascular dysfunction. Blood samples at baseline and 24 weeks were measured for inflammatory markers (eg, high-sensitivity C-reactive protein [hsCRP], interleukin-1b, and high-sensitivity cardiac troponin T [hs-cTnT]). The primary outcome was mean MFR before and after tumor necrosis factor inhibitor initiation, with Δhs-cTnT as the secondary outcome. Secondary and exploratory analyses included the correlation between ΔhsCRP and other inflammatory markers with MFR and hs-cTnT. We studied 66 subjects, 82% of which were women, mean RA duration 7.4 years. The median atherosclerotic cardiovascular disease risk was 2.5%; 47% had coronary microvascular dysfunction and 23% had detectable hs-cTnT. We observed no change in mean MFR before (2.65) and after treatment (2.64, P=0.6) or hs-cTnT. A correlation was observed between a reduction in hsCRP and interleukin-1b with a reduction in hs-cTnT. CONCLUSIONS: In this RA cohort with low prevalence of cardiovascular risk factors, nearly 50% of subjects had coronary microvascular dysfunction at baseline. A reduction in inflammation was not associated with improved MFR. However, a modest reduction in interleukin-1b and no other inflammatory pathways was correlated with a reduction in subclinical myocardial injury. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02714881.


Asunto(s)
Artritis Reumatoide , Biomarcadores , Circulación Coronaria , Inflamación , Microcirculación , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Artritis Reumatoide/fisiopatología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/sangre , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Circulación Coronaria/fisiología , Vasos Coronarios/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Reserva del Flujo Fraccional Miocárdico/fisiología , Factores de Riesgo de Enfermedad Cardiaca , Inflamación/sangre , Inflamación/fisiopatología , Mediadores de Inflamación/sangre , Interleucina-1beta/sangre , Imagen de Perfusión Miocárdica/métodos , Tomografía de Emisión de Positrones , Resultado del Tratamiento , Troponina T/sangre , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico
17.
J Clin Rheumatol ; 19(1): 38-42, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23319023

RESUMEN

Oncogenic osteomalacia is a rare paraneoplastic syndrome of systemic bone demineralization secondary to a tumor-induced dysregulation of phosphorus metabolism. The tumor's low prevalence, small size, and variable location often result in years of muscular weakness and bone pain before diagnosis. With complete treatment, patient's symptoms swiftly dissipate. We report the case of a 63-year-old previously healthy man with a 20-month course of musculoskeletal symptoms before diagnosis and resection of a posterior tibial tumor. Postoperatively, the patient had returned to his previous lifestyle when an insufficiency fracture required prophylactic stabilization.


Asunto(s)
Fracturas del Fémur/etiología , Fracturas por Estrés/etiología , Neoplasias de Tejido Conjuntivo/complicaciones , Clavos Ortopédicos , Fracturas del Fémur/diagnóstico , Fracturas del Fémur/cirugía , Fijación Intramedular de Fracturas , Fracturas por Estrés/diagnóstico , Fracturas por Estrés/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteomalacia , Síndromes Paraneoplásicos , Resultado del Tratamiento
18.
J Clin Endocrinol Metab ; 108(11): e1282-e1288, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37227016

RESUMEN

CONTEXT: Zoledronic acid (ZA) administered during the initial hospitalization for a fragility fracture improves the osteoporosis pharmacotherapy rate. Distinguishing the safety profile of inpatient ZA (IP-ZA) in this context is crucial if this approach is to be widely adopted. OBJECTIVE: To study the acute safety profile of IP-ZA. METHODS: An observational study of patients admitted to the Massachusetts General Hospital with fragility fractures who were eligible to receive IP-ZA. Patients were treated with or without IP-ZA. Acetaminophen, either as a single pre-ZA dose or standing multiple-doses-per-day regimen for 48 hours or longer after ZA infusion, was also administered along with protocolized vitamin D and calcium supplementation. Changes in body temperature, serum creatinine, and serum calcium were measured. RESULTS: A total of 285 consecutive patients, meeting inclusion and exclusion criteria, are included in this analysis; 204 patients received IP-ZA. IP-ZA treatment was associated with a transient mean rise of body temperature of 0.31 °C on the day following its administration. Temperatures above 38 °C were seen in 15% of patients in the IP-ZA group and 4% in the nontreated group. Standing multiple-doses-per-day but not a single pre-ZA dose of acetaminophen effectively prevented this temperature increase. IP-ZA did not affect serum creatinine levels. Mean levels of serum total calcium and albumin-corrected calcium decreased by 0.54 mg/dL and 0.40 mg/dL, respectively, at their nadirs (Day 5). No patient experienced symptomatic hypocalcemia. CONCLUSION: IP-ZA along with standing multiple-doses-per-day acetaminophen, administered to patients in the immediate postfracture period, is not associated with significant acute adverse effects.


Asunto(s)
Conservadores de la Densidad Ósea , Fracturas Óseas , Humanos , Acetaminofén , Conservadores de la Densidad Ósea/efectos adversos , Calcio , Creatinina , Difosfonatos/efectos adversos , Fracturas Óseas/prevención & control , Fracturas Óseas/inducido químicamente , Imidazoles/efectos adversos , Pacientes Internos , Ácido Zoledrónico
19.
Arthritis Care Res (Hoboken) ; 75(7): 1563-1570, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-35724301

RESUMEN

OBJECTIVE: To address significant disruptions in didactic education precipitated by the COVID-19 pandemic, a group of rheumatology program directors collaborated with the American College of Rheumatology to create a virtual fellows-in-training (V-FIT) program. METHODS: A working group was composed to develop the virtual didactic program comprising live virtual sessions of core curricular rheumatology topics that were recorded to permit asynchronous learning. Nationally recognized educators were invited to lead sessions to fill the void in didactic education occurring on a broad scale across US rheumatology fellowship training programs. Demographic information, live and asynchronous participation data, and feedback surveys were collected from participants in the program. RESULTS: There were 3 components to V-FIT: the Virtual Rheumatology Learning (ViRL) series, the Virtual Rheumatology Practicum (ViP), and the Virtual Rheumatology Teaching Lessons (ViTLs). The ViRL program had global impact with more than 2,000 learners from more than 55 countries. ViP provided a standardized curriculum of rheumatology topics for incoming first-year fellows. ViTLs addressed advanced and interdisciplinary rheumatic disease topics for learners at all stages. CONCLUSION: With collaboration, adaptation, and innovation, the V-FIT program not only maintained but also enhanced education for rheumatology trainees, was enriched by national and international participation, and provided standardized, broadly accessible content with interdisciplinary learning.


Asunto(s)
COVID-19 , Enfermedades Reumáticas , Reumatología , Humanos , Pandemias , Reumatología/educación , Curriculum , Becas
20.
Arthritis Care Res (Hoboken) ; 75(12): 2435-2441, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37291752

RESUMEN

OBJECTIVE: With the onset of the COVID-19 pandemic, an annual multi-institutional face-to-face rheumatology objective structured clinical examination (ROSCE) was transformed into a virtual format. The educational goals of the virtual ROSCE (vROSCE) were to reproduce the educational value of the previous in-person ROSCE, providing a valuable formative assessment of rheumatology training activities encompassing the 6 Accreditation Council for Graduate Medical Education (ACGME) core competencies for fellows-in-training (FITs). This article describes the novel design, feasibility, and stakeholder value of a vROSCE. METHODS: Through an established collaboration of 5 rheumatology fellowship training programs, in February 2021, a vROSCE was created and conducted using a Zoom platform. Station development included learning objectives, FIT instructions, faculty proctor instructions, and a checklist by which to provide structured formative feedback. An anonymous, optional web-based survey was sent to FIT participants to evaluate the experience. RESULTS: Twenty-three rheumatology FITs from 5 institutions successfully rotated through 6 stations in the vROSCE. Immediate feedback was given to each FIT using standardized rubrics structured around ACGME core competencies. A total of 65% of FITs (15 of 23) responded to the survey, and 93% of survey respondents agreed or strongly agreed that the vROSCE was a helpful educational activity and identified individualized opportunities for improvement. CONCLUSION: A vROSCE is an innovative, feasible, valuable, and well-received educational technology tool. The vROSCE enriched rheumatology FITs' education and offered collaborative learning experiences across institutions.


Asunto(s)
Educación a Distancia , Reumatología , Humanos , Competencia Clínica , Educación de Postgrado en Medicina , Becas , Pandemias
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