Double negative (DN) T cells are expanded in patients with systemic lupus erythematosus (SLE) and stimulate autoantibody production as efficiently as CD4+ T cells. In this study, we demonstrate that DN T cells from patients with SLE produce significant amounts of IL-17 and IFN-γ, and expand when stimulated in vitro with an anti-CD3 Ab in the presence of accessory cells. Furthermore, IL-17+ and DN T cells are found in kidney biopsies of patients with lupus nephritis. Our findings establish that DN T cells produce the inflammatory cytokines IL-17 and IFN-γ, and suggest that they contribute to the pathogenesis of kidney damage in patients with SLE.

IMPORTANCE Patients undergoing hemodialysis have an annual mortality rate exceeding 20%, comparable to many types of cancer. Past research has shown that patients with cancer overestimate their likelihood of survival relative to their physicians, but this relationship has not been examined in patients with noncancer diagnoses. Perceptions of prognosis and transplant candidacy may influence goals of care.OBJECTIVES To compare the perceptions of hemodialysis patients and their nephrologists concerning prognosis and the likelihood of transplant; to follow actual survival; and to explore the relationship between patients' expectations and their goals of care.DESIGN We completed a medical record abstraction to estimate 1-year mortality risk among patients who underwent dialysis at any time from November 1, 2010, through September 1, 2011. We then conducted in-person interviews with eligible patients whose predicted 1-year mortality, based on validated prognostic tools, was at least 20%. We also interviewed their nephrologists. We compared patients' and physicians' expectations about 1-and 5-year survival and transplant candidacy and measured the association between patients' expectations and goals of care. We then followed actual survival using Kaplan-Meier methods.SETTING AND PARTICIPANTS Two dialysis units in Boston. Two hundred seven patients undergoing hemodialysis included in the medical record review, with 62 eligible patients interviewed.MAIN OUTCOMES AND MEASURES Predicted 1-year mortality risk using validated prognostic tools; actual survival; patients' and physicians' expectations about 1-year survival and likelihood of transplant; and patients' goals of care. RESULTSOf the 207 hemodialysis patients, 72.5% had a predicted 1-year mortality of at least 20%. Of the 80 patients eligible for interview, 62 participated (response rate, 78%). Patients were significantly more optimistic than their nephrologists about 1-and 5-year survival (P < .001 for both) and were more likely to think they were transplant candidates (37 [66%] vs 22 [39%] [P = .008]). Of the 81% of patients reporting a 90% chance or greater of being alive at 1 year, 18 (44%) preferred care focused on extending life, even if it meant more discomfort, compared with 1 (9%) among patients reporting a lower chance of survival (P = .045). Actual survival was 93% at 1 year but decreased to 79% by 17 months and 56% by 23 months. CONCLUSIONS AND RELEVANCEHemodialysis patients are more optimistic about prognosis and transplant candidacy than their nephrologists. In our sample, patients' expectations about 1-year survival were more accurate than those of their nephrologists, but their longer-term survival expectations dramatically overestimated even their 2-year survival rates. Patients' prognostic expectations are associated with their treatment preferences. Our findings suggest the need for interventions to help providers communicate effectively with patients about prognosis.

Coal mining remains a sizable industry, with millions of working and retired coal miners worldwide. This article provides an update on recent advances in the understanding of respiratory health issues in coal miners and focuses on the spectrum of disease caused by inhalation of coal mine dust, termed coal mine dust lung disease. In addition to the historical interstitial lung diseases (coal worker's pneumoconiosis, silicosis, and mixed dust pneumoconiosis), coal miners are at risk for dust-related diffuse fibrosis and chronic airway diseases, including emphysema and chronic bronchitis. Recent recognition of rapidly progressive pneumoconiosis in younger miners, mainly in the eastern United States, has increased the sense of urgency and the need for vigilance in medical research, clinical diagnosis, and exposure prevention. Given the risk for disease progression even after exposure removal, along with few medical treatment options, there is an important role for chest physicians in the recognition and management of lung disease associated with work in coal mining.

Despite the lack of development of detectable resistance, MRSA exposed to vancomycin for prolonged periods may begin to develop vancomycin tolerance and decreased autolysis. In addition, suppression of agr function appears to end after vancomycin is stopped. Whether these changes are prerequisites for attenuated vancomycin efficacy and the development of glycopeptide resistance warrants further study. The development of vancomycin resistance may be more difficult under conditions where vancomycin serum concentrations are maintained >10 mg/L.

Rationale: Recent reports of progressive massive fibrosis and rapidly progressive pneumoconiosis in U.S. coal miners have raised concerns about excessive exposures to coal mine dust, despite reports of declining dust levels.Objectives: To evaluate the histologic abnormalities and retained dust particles in available coal miner lung pathology specimens, and to compare these findings with those derived from corresponding chest radiographs.Methods: Miners with severe disease and available lung tissue were identified through investigator outreach. Demographic as well as smoking and work history information was obtained. Chest radiographs were interpreted according to the International Labor Organization classification scheme to determine if criteria for rapidly progressive pneumoconiosis were confirmed. Pathology slides were scored by three expert pulmonary pathologists using a standardized nomenclature and scoring system. Measurements and Main Results:Thirteen cases were reviewed, many of which had features of accelerated silicosis and mixed dust lesions. Twelve had progressive massive fibrosis, and 11 had silicosis. Only four had classic lesions of simple coal workers' pneumoconiosis. Four had diffuse interstitial fibrosis with chronic inflammation, and two had focal alveolar proteinosis. Polarized light microscopy revealed large amounts of birefringent mineral dust particles consistent with silica and silicates; carbonaceous coal dust was less prominent. On the basis of chest imaging studies, specimens with features of silicosis were significantly associated (P = 0.047) with rounded (type p, q, or r) opacities, whereas grade 3 interstitial fibrosis was associated (P = 0.02) with the presence of irregular (type s, t, or u) opacities.Conclusions: Our findings suggest that rapidly progressive pneumoconiosis in these miners was associated with exposure to coal mine dust containing high concentrations of respirable silica and silicates.

The new england journal of medicine n engl j med 348;23 www.nejm.org june 5, 2003 2330This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.

Objectives To evaluate respiratory related mortality among underground coal miners after 37 years of follow-up. Methods Underlying cause of death for 9033 underground coal miners from 31 US mines enrolled between 1969 and 1971 was evaluated with life table analysis. Cox proportional hazards models were fitted to evaluate the exposure-response relationships between cumulative exposure to coal mine dust and respirable silica and mortality from pneumoconiosis, chronic obstructive pulmonary disease (COPD) and lung cancer. Results Excess mortality was observed for pneumoconiosis (SMR=79.70, 95% CI 72.1 to 87.67), COPD (SMR=1.11, 95% CI 0.99 to 1.24) and lung cancer (SMR=1.08; 95% CI 1.00 to 1.18). Coal mine dust exposure increased risk for mortality from pneumoconiosis and COPD. Mortality from COPD was significantly elevated among ever smokers and former smokers (HR=1.84, 95% CI 1.05 to 3.22; HRK=1.52, 95% CI 0.98 to 2.34, respectively) but not current smokers (HR=0.99, 95% CI 0.76 to 1.28). Respirable silica was positively associated with mortality from pneumoconiosis (HR=1.33, 95% CI 0.94 to 1.33) and COPD (HR=1.04, 95% CI 0.96 to 1.52) in models controlling for coal mine dust. We saw a significant relationship between coal mine dust exposure and lung cancer mortality (HR=1.70; 95% CI 1.02 to 2.83) but not with respirable silica (HR=1.05; 95% CI 0.90 to 1.23). In the most recent follow-up period (2000–2007) both exposures were positively associated with lung cancer mortality, coal mine dust significantly so. Conclusions Our findings support previous studies showing that exposure to coal mine dust and respirable silica leads to increased mortality from malignant and non-malignant respiratory diseases even in the absence of smoking.

Susceptible workers exposed to coal mine and silica dust may develop a variety of pulmonary diseases. The prime example is classical pneumoconiosis, a nodular interstitial lung disease that, in severe cases, may lead to progressive massive fibrosis (PMF) . Exposure to silica and coal mine dusts may also result in pulmonary scarring in a pattern that mimics idiopathic pulmonary fibrosis, and in chronic obstructive pulmonary disease (COPD), including emphysema and chronic bronchitis, that appears indistinguishable from obstructive lung disease caused by exposure to tobacco smoke. Coal mine and silica dust may therefore result in restrictive, obstructive, or mixed patterns of impairment on pulmonary function testing. Most physicians are aware of the nodular fibrosing pulmonary tissue reactions in response to retained dust, but they may not realize that these other reactions of the pulmonary parenchyma and airways to dust exist and can result in significant respiratory dysfunction in sensitive individuals. This article discusses current data on exposure to coal mine and silica dust in the United States, the epidemiology of the diseases caused by these exposures, and new concepts of causation and pathogenesis. We also review the patterns of pulmonary disease and impairment that may result.