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Biomedical subjects

Philip Seo

Publications and source records attributed to Philip Seo.

8 recordsLinked to original sources

Development of comprehensive disease assessment in systemic vasculitis.

The systemic vasculitides are multisystem disorders with considerable mortality and morbidity and frequent relapses. In the absence of reliable serological markers, accurate clinical tools are required to assess disease activity and damage for treatment decisions, and for the performance of clinical trials. This article reviews and summarises the development and use of disease assessment tools for determining activity and damage in systemic vasculitis and reports ongoing initiatives for further development of disease assessment tools. A literature search was conducted using PubMed and reference lists for vasculitis, assessment, clinical trials, outcome and prognosis. The findings indicate that comprehensive disease assessment in vasculitis requires documentation of disease activity, chronic irreversible damage and impairment of function.

Humans↗

Damage caused by Wegener's granulomatosis and its treatment: prospective data from the Wegener's Granulomatosis Etanercept Trial (WGET).

OBJECTIVE: To analyze damage occurring in patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET) and to correlate that damage with disease activity, adverse events, and quality of life. METHODS: The Vasculitis Damage Index (VDI) was applied to all 180 patients at trial entry and every 6 months throughout the trial. Items of damage were analyzed by presumed etiology (i.e., secondary to WG, to therapy, or both) and time of occurrence. Spearman's rank correlation coefficients were calculated between VDI scores and the Birmingham Vasculitis Activity Score for WG (BVAS/WG), frequency of flares, number of adverse events, and the patients' quality-of-life assessments. RESULTS: The mean VDI score was 1.3 at the study enrollment and 1.8 at the end of the trial. This increase was due to damage that occurred despite (or because of) therapy, including visual impairment, hearing loss, nasal blockade, pulmonary fibrosis, hypertension, renal insufficiency, peripheral neuropathy, gonadal failure, and diabetes mellitus. Only 11% of the enrolled patients had not sustained a single VDI item after 1 year of enrollment. When adjusted for baseline VDI, the baseline BVAS/WG correlated moderately well with the VDI score at 1 year (r = 0.20, P = 0.015). Increases in adjusted VDI scores also correlated with the number of adverse events, particularly among patients with limited WG (P = 0.06). CONCLUSION: Damage from both active disease and its treatment remain important problems for patients with WG. Despite the dramatic improvements in patient survival achieved over the last several decades, only a few patients with WG emerge from a period of active disease without sustaining some damage from the disease itself, its treatment, or both. An important measure of future therapeutic approaches will be their ability to reduce the damage accrued over time.

Double-Blind Method↗

Current status of outcome measures in vasculitis: focus on Wegener's granulomatosis and microscopic polyangiitis. Report from OMERACT 7.

The complexity of assessing disease activity, disease status, and damage in the vasculitides reflects the multisystemic pathologic manifestations of these often chronic illnesses. Major progress has been made in the past decade in the development of validated and widely accepted outcome measures for use in clinical trials. Over time, these tools have been regularly revised, expanded, and supplemented with new measures of disease prognosis and damage. As a result clinical research in this area has become increasingly complex. This article critically reviews the current status of tools for assessing disease activity and damage in "ANCA-associated" vasculitides (Wegener's granulomatosis and microscopic polyangiitis), summarizes the current level of validation of each measure, addresses central problems and controversies to be considered during development of new vasculitis assessment tools, and proposes a series of research agendas for consideration by the vasculitis research community.

Clinical Trials as Topic↗

The antineutrophil cytoplasmic antibody-associated vasculitides.

Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome are small- to medium-vessel vasculitides linked by overlapping pathology and the presence of antineutrophil cytoplasmic antibodies (ANCA). Commonly referred to as the ANCA-associated vasculitides, these diseases are challenging to diagnose and to treat. Distinguishing the ANCA-associated vasculitides from other forms of vasculitis or nonvasculitic processes (such as infection) can be particularly difficult. This review describes the clinical and pathologic hallmarks of the ANCA-associated vasculitides, discusses the role of ANCA assays in diagnosis and treatment, and outlines an approach to the evaluation and management of these diseases.

Antibodies, Antineutrophil Cytoplasmic↗

Cases from the medical grand rounds of the Osler Medical Service at Johns Hopkins University.

A 77-year-old man was in good health until he complained of fatigue 3 weeks before presentation. Two weeks before admission, he developed gradually worsening shortness of breath. One week before admission, he developed a cough that initially was nonproductive but later was associated with hemoptysis.His past medical history was remarkable for a history of colon cancer (Dukes' stage III), for which he underwent a hemicolectomy and treatment with adjuvant chemotherapy in 1993. He had a myocardial infarction in 1986 and underwent coronary artery bypass surgery in 1999. He also had a history of hypertension, type 2 diabetes, and gout. He smoked in the past but had stopped more than 30 years ago.He was initially evaluated by his primary care physician, who noted that he complained of diaphoresis but denied fevers, chills, or contact with others who were ill. His physical examination was remarkable for bilateral crackles that were more pronounced on the right. A chest radiograph demonstrated bilateral pulmonary infiltrates (Figure 1). He was treated with amoxicillin. The next day, however, his physician noted that his dyspnea had worsened and that his oxygen saturation on room air was poor. He was therefore admitted for further evaluation. The amoxicillin was discontinued, and he was treated with levofloxacin, followed by ceftriaxone and azithromycin as his pulmonary status continued to deteriorate. He received intravenous diuretic agents, which failed to improve his respiratory status. During the initial phase of hospitalization, he was anemic, with a hematocrit of 21.3%. His serum creatinine level, which had been 1.0 mg/dL in 1999, was now 2.5 mg/dL. Urinalysis was remarkable for the presence of numerous red blood cells. His oxygen requirement increased, and he eventually required a 100% nonrebreather mask. A computed tomographic scan of the chest demonstrated prominent alveolar opacities throughout the right upper, middle, and lower lobes, with similar opacities in the left upper and left lower lobes (Figure 2). An echocardiogram showed an ejection fraction of 50%, as well as mild mitral regurgitation. Serologies were remarkable for an antinuclear antibody titer of 1:320 and a P-antineutrophil cytoplasmic antibody (P-ANCA) titer of greater than 1:320. C-ANCA was negative. Anti-glomerular basement membrane and anti-human immunodeficiency virus antibodies were undetectable.

Aged↗