RESUMEN

OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are commonly present in rheumatoid arthritis (RA) without a clear rationale for their coexistence. Moreover, autoantibodies develop against proteins with different posttranslational modifications and native proteins without obvious unifying characteristics of the antigens. We undertook this study to broadly evaluate autoantibody binding in seronegative and seropositive RA to identify novel features of reactivity. METHODS: An array was created using a total of 172,828 native peptides, citrulline-containing peptides, and homocitrulline-containing peptides derived primarily from proteins citrullinated in the rheumatoid joint. IgG and IgM binding to peptides were compared between cyclic citrullinated peptide (CCP)-positive RF+, CCP+RF-, CCP-RF+, and CCP-RF- serum from RA patients (n = 48) and controls (n = 12). IgG-bound and endogenously citrullinated peptides were analyzed for amino acid patterns and predictors of intrinsic disorder, i.e., unstable 3-dimensional structure. Binding to IgG-derived peptides was specifically evaluated. Enzyme-linked immunosorbent assay confirmed key results. RESULTS: Broadly, CCP+RF+ patients had high citrulline-specific IgG binding to array peptides and CCP+RF- and CCP-RF+ patients had modest citrulline-specific IgG binding (median Z scores 3.02, 1.42, and 0.75, respectively; P < 0.0001). All RA groups had low homocitrulline-specific binding. CCP+RF+ patients had moderate IgG binding to native peptides (median Z score 2.38; P < 0.0001). The highest IgG binding was to citrulline-containing peptides, irrespective of protein identity, especially if citrulline was adjacent to glycine or serine, motifs also seen in endogenous citrullination in the rheumatoid joint. Highly bound peptides had multiple features predictive of disorder. IgG from CCP+RF+ patients targeted citrulline-containing IgG-derived peptides. CONCLUSION: Disordered antigens, which are frequently citrullinated, and common epitopes for ACPAs and RF are potentially unifying features for RA autoantibodies.

Asunto(s)

RESUMEN

A chronic obstructive pulmonary disease care service improves timely access to follow-up care and patient education at the time of transition from hospital to home.

RESUMEN

Effective uptake of tumor cell-derived antigens by antigen-presenting cells is achieved pre-clinically by in situ labeling of tumor with α-gal glycolipids that bind the naturally occurring anti-Gal antibody. We evaluated toxicity and feasibility of intratumoral injections of α-gal glycolipids as an autologous tumor antigen-targeted immunotherapy in melanoma patients (pts). Pts with unresectable metastatic melanoma, at least one cutaneous, subcutaneous, or palpable lymph node metastasis, and serum anti-Gal titer ≥1:50 were eligible for two intratumoral α-gal glycolipid injections given 4 weeks apart (cohort I: 0.1 mg/injection; cohort II: 1.0 mg/injection; cohort III: 10 mg/injection). Monitoring included blood for clinical, autoimmune, and immunological analyses and core tumor biopsies. Treatment outcome was determined 8 weeks after the first α-gal glycolipid injection. Nine pts received two intratumoral injections of α-gal glycolipids (3 pts/cohort). Injection-site toxicity was mild, and no systemic toxicity or autoimmunity could be attributed to the therapy. Two pts had stable disease by RECIST lasting 8 and 7 months. Tumor nodule biopsies revealed minimal to no change in inflammatory infiltrate between pre- and post-treatment biopsies except for 1 pt (cohort III) with a post-treatment inflammatory infiltrate. Two and four weeks post-injection, treated nodules in 5 of 9 pts exhibited tumor cell necrosis without neutrophilic or lymphocytic inflammatory response. Non-treated tumor nodules in 2 of 4 evaluable pts also showed necrosis. Repeated intratumoral injections of α-gal glycolipids are well tolerated, and tumor necrosis was seen in some tumor nodule biopsies after tumor injection with α-gal glycolipids.

Asunto(s)

RESUMEN

The Coordinated-Transitional Care (C-TraC) Program was designed to improve care coordination and outcomes among veterans with high-risk conditions discharged to community settings from the William S. Middleton Memorial Veterans Hospital, in Madison, Wisconsin. Under the program, patients work with nurse case managers on care and health issues, including medication reconciliation, before and after hospital discharge, with all contacts made by phone once the patient is at home. Patients who received the C-TraC protocol experienced one-third fewer rehospitalizations than those in a baseline comparison group, producing an estimated savings of $1,225 per patient net of programmatic costs. This model requires a relatively small amount of resources to operate and may represent a viable alternative for hospitals seeking to offer improved transitional care as encouraged by the Affordable Care Act. In particular, the model may be attractive for providers in rural areas or other care settings challenged by wide geographic dispersion of patients or by constrained resources.

Asunto(s)

RESUMEN

BACKGROUND: Third-year internal medicine residents participating in a quality improvement rotation identified gaps between the Joint Commission's ORYX quality guidelines and clinical practices for the inpatient management of heart failure (HF) at the William S. Middleton Memorial Veterans Hospital. Residents focused on the performance metrics associated with tobacco-cessation counselling documentation, ejection fraction assessment and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescriptions. METHODS: After analysing data collected by the External Peer Review Program, residents reviewed the institution's admissions and discharge processes with the aim of improving quality and compliance. In redesigning these processes, residents created an admissions template and a discharge face sheet, and compared specific ORYX measure compliance rates before and after institution-wide implementation. RESULTS: Following implementation of the tobacco-cessation admissions template, 100% of HF patients who used tobacco received documented cessation counselling, compared with 59% prior to intervention (p<0.01, n=32). Following implementation of the mandatory discharge face sheet, 97% of HF patients (compared with 92% preintervention, p>0.05) received comprehensive discharge instruction; LV function assessment went from 98% to 100% (p>0.05); and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription for left ventricular systolic dysfunction at discharge (or documentation of a contra-indication) went from 82% to 100% (p<0.01, n=48). DISCUSSION: By implementing a standardised admissions template and a mandatory discharge face sheet, the hospital improved its processes of documentation and increased adherence to quality-performance measures. By strengthening residents' learning and commitment to quality improvement, the hospital created a foundation for future changes in the systems that affect patient care.

RESUMEN

BACKGROUND: Third-year internal medicine residents participating in a quality improvement rotation identified gaps between the Joint Commission's ORYX quality guidelines and clinical practices for the inpatient management of heart failure (HF) at the William S. Middleton Memorial Veterans Hospital. Residents focused on the performance metrics associated with tobacco-cessation counselling documentation, ejection fraction assessment and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescriptions. METHODS: After analysing data collected by the External Peer Review Program, residents reviewed the institution's admissions and discharge processes with the aim of improving quality and compliance. In redesigning these processes, residents created an admissions template and a discharge face sheet, and compared specific ORYX measure compliance rates before and after institution-wide implementation. RESULTS: Following implementation of the tobacco-cessation admissions template, 100% of HF patients who used tobacco received documented cessation counselling, compared with 59% prior to intervention (p<0.01, n=32). Following implementation of the mandatory discharge face sheet, 97% of HF patients (compared with 92% preintervention, p>0.05) received comprehensive discharge instruction; LV function assessment went from 98% to 100% (p>0.05); and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription for left ventricular systolic dysfunction at discharge (or documentation of a contra-indication) went from 82% to 100% (p<0.01, n=48). DISCUSSION: By implementing a standardised admissions template and a mandatory discharge face sheet, the hospital improved its processes of documentation and increased adherence to quality-performance measures. By strengthening residents' learning and commitment to quality improvement, the hospital created a foundation for future changes in the systems that affect patient care.

Asunto(s)

RESUMEN

Rheumatoid vasculitis is a rare but serious complication of rheumatoid arthritis. Herein we examine the pathophysiology, epidemiology, clinical diagnosis, and treatment of rheumatoid vasculitis. Seropositivity, specific HLA variations, and tobacco use are among the genetic and environmental predictors of rheumatoid vasculitis. Fortunately, recent reports have noted declines in the prevalence of rheumatoid vasculitis. Nevertheless, proper recognition of systemic manifestations may assist in pathologically confirming the diagnosis, determining the extent of disease, and guiding treatment. Contemporary treatment reports are discussed in the context of the ongoing debate regarding whether new agents may trigger, treat, or even prevent rheumatoid vasculitis. Evolving genetic, histopathologic, and immunologic studies partnered with ongoing clinical experience with biologics offer promise to inform future prevention and treatment of rheumatoid vasculitis.

Asunto(s)

RESUMEN

OBJECTIVES: The purpose of this study was to examine prevalence trends of serious extra-articular manifestations (EAMs) in a data set representing both hospitalized and ambulatory patients with RA. METHODS: This retrospective cohort study used serial cross-sectional data to examine the prevalence of serious EAMs in patients with RA from 1985 to 2006 across the United States (US) Veteran's Health Administration system. Serious EAMs included rheumatoid carditis, RA lung disease, FS and pooled EAM rates included previously reported vasculitis prevalence as queried by ICD-9 searches. Statistical analysis employed auto-regression and time series analysis using the Chow and Durbin-Watson tests to detect breakpoints and linear time-trends. RESULTS: Among 3 million veterans, including >35,000 RA patients annually, we noted declining RA hospitalizations emphasizing the importance of examining both the inpatient and outpatient settings to assess EAM prevalence. Individual EAM trends varied, demonstrating linear declines in FS, increases in RA lung disease and significant breakpoint declines in carditis and pooled serious EAMs. Pooled EAM prevalence dropped around 2000, from an early linear trend peak of 10% among inpatients, to <7% among both inpatients and outpatients by 2006. CONCLUSIONS: Overall, serious EAMs of RA have declined among US veterans in both the inpatient and outpatient settings, with the exception of RA lung disease likely reflecting improved detection. Breakpoints in pooled EAM prevalence appear to demonstrate consistent, true declines in severe RA extra-articular disease around 2000. Future work should explore the relationship between temporal EAM trends and specific RA therapies including adoption of biological agents.

Asunto(s)

RESUMEN

Patient safety and quality of care are public concerns that demand personal responsibility at all levels of the health care organization. Senior residents in our graduate medical education program took responsibility for a capstone quality improvement project designed to transform them into champions for health care quality. Residents (n = 26) participated alone or in pairs in a 1-month faculty-mentored rotation at the Veterans Administration Hospital during the 2007-2008 academic year. They completed a Web-based curriculum, identified a quality-of-care issue, applied Plan-Do-Study-Act cycles, authored a report, and engaged colleagues in their innovations during a department-wide presentation. Results indicated that residents demonstrated significantly enhanced knowledge and attitudes about patient safety and quality improvement and provided consistently positive faculty and rotation evaluations. In addition, residents generated 20 quality improvement project proposals with a 50% rate of hospital-wide implementation, leading to meaningful changes in the systems that affect patient care.

Asunto(s)

RESUMEN

We describe a case of bacterial meningitis in a 37 year old man resulting from the direct extension of an spontaneously occurring ischiorectal abscess into the intradural space. The patient presented with back pain and urinary retention and this was followed by the development of headache, photophobia and a left VIth nerve palsy. The patient was not diabetic or immunocompromised. He was treated with broad spectrum antibiotics and with drainage of the ischiorectal abscess; no organism was grown from blood, abscess contents or cerebrospinal fluid. He went on to make a full recovery.

Asunto(s)

RESUMEN

OBJECTIVE: To examine trends in the prevalence of rheumatoid vasculitis in a national US population comprising both hospitalized and ambulatory patients with rheumatoid arthritis (RA). METHODS: In this serial cross-sectional study, we analyzed data on hospitalized and ambulatory patients spanning 22 years (1985-2006) and 10 years (1997-2006), respectively, to determine the prevalence of rheumatoid vasculitis, as defined by the International Classification of Diseases, Ninth Revision. Our search encompassed data collected on a predominantly male study population during 10 million hospitalizations and outpatient visits, and included annual data on >37,000 RA patients. To test for a decrease in rheumatoid vasculitis prevalence, breakpoint analysis was performed using stepwise Chow and Durbin-Watson tests. RESULTS: There was a clear decline in the prevalence of rheumatoid vasculitis, and this decline remained evident even after accounting for a decreased number of hospitalizations among RA patients. Peak prevalence occurred among hospitalized patients in the 1980s, and prevalence gradually declined throughout the 1990s. Furthermore, simultaneous breakpoints representing a significant drop in rheumatoid vasculitis prevalence between the years 2000 and 2001 were demonstrated for both inpatients (P < 0.000) and outpatients (P < 0.003). The prevalence of vasculitis dropped 53% among inpatients and 31% among outpatients between 2000 and 2001. CONCLUSION: Our results demonstrate a significant decline in rheumatoid vasculitis prevalence after 2000 in this nationwide sample of hospitalized and ambulatory patients. The clear, consistent drop in prevalence provides an opportunity for the formulation of causal hypotheses, including consideration of the impact of biologic agents used to treat RA, on rheumatoid vasculitis.

Asunto(s)

RESUMEN

PURPOSE: We examined in vivo particle-mediated epidermal delivery (PMED) of cDNAs for gp100 and granulocyte macrophage colony-stimulating factor (GM-CSF) into uninvolved skin of melanoma patients. The aims of this phase I study were to assess the safety and immunologic effects of PMED of these genes in melanoma patients. EXPERIMENTAL DESIGN: Two treatment groups of six patients each were evaluated. Group I received PMED with cDNA for gp100, and group II received PMED with cDNA for GM-CSF followed by PMED for gp100 at the same site. One vaccine site per treatment cycle was biopsied and divided for protein extraction and sectioning to assess transgene expression, gold-bead penetration, and dendritic cell infiltration. Exploratory immunologic monitoring of HLA-A2(+) patients included flow cytometric analyses of peripheral blood lymphocytes and evaluation of delayed-type hypersensitivity to gp100 peptide. RESULTS: Local toxicity in both groups was mild and resolved within 2 weeks. No systemic toxicity could be attributed to the vaccines. Monitoring for autoimmunity showed no induction of pathologic autoantibodies. GM-CSF transgene expression in vaccinated skin sites was detected. GM-CSF and gp100 PMED yielded a greater infiltration of dendritic cells into vaccine sites than did gp100 PMED only. Exploratory immunologic monitoring suggested modest activation of an antimelanoma response. CONCLUSIONS: PMED with cDNAs for gp100 alone or in combination with GM-CSF is well tolerated by patients with melanoma. Moreover, pathologic autoimmunity was not shown. This technique yields biologically active transgene expression in normal human skin. Although modest immune responses were observed, additional investigation is needed to determine how to best utilize PMED to induce antimelanoma immune responses.

Asunto(s)

RESUMEN

It is widely held that determination of increased levels of serum autoantibodies can play an important role in the diagnosis and, in some cases, management of many autoimmune diseases. It is also widely held that such testing is fraught with problems relating to accuracy and detection of clinically relevant autoantibodies. Attempts to standardize autoantibody testing by making available standard reference sera, have helped to some degree to improve the testing. Nevertheless, problems still exist and may be causing the delayed diagnosis of severely debilitating and sometimes fatal autoimmune diseases. This paper discusses current practice, as well as, possible new approaches intended to make more robust, autoantibody determinations in all fields of medicine.

Asunto(s)

RESUMEN

Rheumatoid arthritis (RA) is often considered a T cell-mediated disease, yet recent studies describe benefit with rituximab, a monoclonal antibody directed against the B cell antigen CD20. We report our experience using rituximab for 5 patients with severe, disease-modifying antirheumatic drug (DMARD)-refractory RA. Five patients with seropositive, erosive RA received rituximab as 4 weekly doses of 375 mg/m. Four subjects experienced remission lasting 5 to 12 months after noting lack of efficacy with antitumor necrosis factor (TNF) therapy. All patients have relapsed, with signs and symptoms of RA returning a mean of 8 months after therapy. Rituximab appears to be a safe and potentially helpful treatment of refractory RA and, until U.S. Food and Drug Administration approval, could be considered for compassionate use in people who have failed multiple DMARDs. Individuals who do not respond to anti-TNF therapy could experience arthritis that is perpetuated by B cell more than T cell function; these patients could be most likely to respond to rituximab. Further studies are needed to clarify the optimal dose and frequency of rituximab therapy, and its role in combination therapy for individuals with RA.