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The majority of patients (8/11) had kidney involvement, with 6 patients undergoing kidney biopsy to confirm this (Figure 1A). Two patients underwent an interval kidney biopsy to confirm histologic disease remission (Figure 1B). Eleven patients with active, organ-threatening AAV were treated without any oral or intravenous glucocorticoids (Table 1); six patients presented with de novo disease and five with relapse. Six patients had granulomatosis with polyangiitis (GPA) and five patients had microscopic polyangiitis. [Extracted from the article]

The majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells. CD8+ T cells from these patients have enlarged mitochondria and lower spare respiratory capacity associated with increased cell death upon rechallenge with TCR stimulation. These mitochondrial abnormalities can be phenocopied by exposing CD8+ T cells from healthy volunteers to type I IFN and TCR stimulation. Mechanistically these 'SLE-like' conditions increase CD8+ T cell NAD+ consumption resulting in impaired mitochondrial respiration and reduced cell viability, both of which can be rectified by NAD+ supplementation. Our data suggest that type I IFN exposure contributes to SLE pathogenesis by promoting CD8+ T cell death via metabolic rewiring. Lupus pathogenesis is associated with high type 1 interferon stimulated gene (ISG) expression. Here, the authors correlate ISG expression in CD8+ T cells from lupus nephritis patients with abnormal mitochondrial function, implicating increased NAD consumption and reduced cell viability in the pathogenesis. [ABSTRACT FROM AUTHOR]

Background Current guidelines advise that rituximab or cyclophosphamide should be used for the treatment of organ-threatening disease in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), although few studies have examined the efficacy and safety of these agents in combination. Methods We conducted a single-centre cohort study of 66 patients treated with a combination of oral corticosteroids, rituximab and low-dose pulsed intravenous cyclophosphamide followed by a maintenance regimen of azathioprine and tapered steroid for the treatment of biopsy-proven renal involvement in AAV. Patients were followed for a median of 56 months. Case–control analysis with 198 propensity-matched cases from European Vasculitis Study Group (EUVAS) trials compared long-term differences in relapse-free, renal and patient survival. Results At entry, the median Birmingham Vasculitis Activity Score (BVAS) was 19 and estimated glomerular filtration rate was 25 mL/min. Cumulative doses of rituximab, cyclophosphamide and corticosteroids were 2, 3 and 4.2 g, respectively, at 6 months. A total of 94% of patients achieved disease remission by 6 months (BVAS < 0) and patient and renal survival were 84 and 95%, respectively, at 5 years. A total of 84% achieved ANCA-negative status and 57% remained B cell deplete at 2 years, which was associated with low rates of major relapse (15% at 5 years). The serious infection rate during long-term follow-up was 1.24 per 10 patient-years. Treatment with this regimen was associated with a reduced risk of death {hazard ratio [HR] 0.29 [95% confidence interval (CI) 0.125–0.675], P = 0.004}, progression to end-stage renal disease (ESRD) [HR 0.20 (95% CI 0.06–0.65), P = 0.007] and relapse [HR 0.49 (95% CI 0.25–0.97), P = 0.04] compared with propensity-matched patients enrolled in EUVAS trials. Conclusions This regimen is potentially superior to current standards of care, and controlled studies are warranted to establish the utility of combination drug approaches in the treatment of AAV. [ABSTRACT FROM AUTHOR]

Objective. B cell depletion, most commonly with rituximab, is an evolving therapeutic approach in SLE. Infusion reactions after rituximab are common, and may prevent re-treatment in patients who previously demonstrated beneficial response. We have used ofatumumab, a fully humanized anti-CD20 mAb, as an alternative B cell-depleting agent in patients with SLE who are rituximab-intolerant due to severe infusion reactions. Methods. A single-centre retrospective case series of 16 patients were treated with ofatumumab for SLE between 2012 and 2015. Results. Ofatumumab infusion was well tolerated in 14/16 patients, in whom the median age was 34 (range 19-55) and the median duration of SLE 9.2 years (0.6-28.5). The cohort was heavily pre-treated, with 50% having prior CYC exposure, and a median cumulative dose of prior rituximab 4 g (1-6). Twelve patients were treated for LN, one for extra-renal flare and one for remission maintenance. B cell-depletion was achieved in 12/14 patients, with comparable reconstitution kinetics to a previous cohort treated with rituximab at our centre, and was associated with improvements in serological markers of disease activity, including ANA, anti-dsDNA antibody and complement levels. Half of the patients with LN achieved renal remission by 6 months. Progressive disease that was unresponsive to augmented immunosuppression with CYC was seen in five patients. During long-term follow-up (median 28 months), five grade III infections were reported, and there were no malignancies or deaths. Conclusion. In this pre-treated cohort with long-standing SLE, ofatumumab was a well-tolerated, safe and effective alternative to rituximab for B cell-depletion therapy. [ABSTRACT FROM AUTHOR]

Objectives. The aim was to investigate whether the signalling lymphocyte activation molecule (SLAM) signalling pathways contribute to LN and whether SLAM receptors could be valuable biomarkers of dis- ease activity. Methods. Peripheral blood mononuclear cells from 30National Research Ethics Service SLE patients with biopsy-proven LN were analysed by flow cytometry. Clinical measures of disease activity were assessed. The expression of the SLAM family receptors on T-cell subpopulations [CD4, CD8 and double negative (DN) T cells] was measured and compared between lupus patients with active renal disease and those in remission. Results. The frequency of CD8 T cells expressing SLAMF3, SLAMF5 and SLAMF7 was significantly lower in LN patients who were in remission. In contrast, these subsets were similar in patients with active renal disease and in healthy individuals. Patients with active nephritis had an increased percentage of circulating monocytes, consistent with a potential role played by these cells in glomerular inflammation. Changes in the frequency of DN T cells positive for SLAMF2, SLAMF4 and SLAMF7 were observed in lupus patients irrespective of the disease activity. We detected alterations in the cellular expression of the SLAM family receptors, but these changes were less obvious and did not reveal any specific pattern. The percentage of DN T cells expressing SLAMF6 could predict the clinical response to B-cell depletion in patients with LN. Conclusion. Our study demonstrates altered expression of the SLAM family receptors in SLE T lymphocytes. This is consistent with the importance of the SLAM-associated pathways in lupus pathogenesis. [ABSTRACT FROM AUTHOR]

The article discusses how leadership and strategies for business continuity add value to an organization's performance. Risk-management planning helps reduce the potential cost of loss. A crisis requires an organization's people to get out of their comfort zone. The financial concerns could be calculated and accounted for to some degree with risk-management planning.

The article focuses on the role of power, politics and leadership in the workplace. Topics discussed include the views of psychologist David McClelland on embracing power for achievement motivation, the views of the American scholar Warren Bennis on the standard criteria for managers such as technical competence and skills and the association between power and achievement and affiliation.

Objectives. B cell depletion is an effective treatment strategy in ANCA-associated vasculitis (AAV). Ofatumumab is a fully humanized anti-CD20 mAb that has shown efficacy in the treatment of haematological malignancy and RA. The use of ofatumumab in the treatment of AAV has not previously been reported. Methods. This study was based on a case series of eight patients who received ofatumumab, in conjunction with low-dose CYC and oral steroids, in the treatment of AAV. Results. Eight patients received ofatumumab: seven for remission induction in active disease (three relapsing; four with new disease) and one for remission maintenance. B cell depletion was achieved in all patients by 1 month, and was sustained for at least 6 months. All patients with active disease achieved clinical remission (BVAS of zero, or BVAS ≤5 if all scores due to persistent urinary abnormalities in the presence of stable or improving renal function) by 3 months. This was associated with a rapid fall in ANCA titres, reduced inflammatory responses and improvements in renal function. At 12 months, three patients had repopulated B cells associated with the recurrence of circulating ANCAs, although no patients experienced major clinical relapse in the first 24 months. No unexpected side effects were observed. Conclusion. Treatment with ofatumumab resulted in similar serological and clinical responses to those seen in previous cohorts treated at our centre with a comparable CS, CYC and rituximab-based regimen. Ofatumumab should be considered an alternative B cell depleting agent in patients who are intolerant of, or unresponsive to, rituximab. [ABSTRACT FROM AUTHOR]

The article discusses the need to encourage diversity of thought among employees and reasons for diversity of thought. The role of human resources leader in framing and implementing talent management strategies which include attracting, selecting, engaging, developing, and retaining employees in an organization, is discussed. The article also suggests tips for promoting work satisfaction and engagement.

The article focuses on the decision of Marissa Mayer, chief executive officer of Yahoo, on the elimination of flexible work arrangements (FWAs) in the company. It states that Mayer wants to improve employee performance by changing the work environment and increasing the job opportunities for collaboration. It mentions the factors to improve employee performance, such as motivation, ability, and work environment.

The article offers information on the development of return on investment (ROI) in business. It mentions the use of a business model developed by Don Kirkpatrick to evaluate the outcome of employees' training and job performance. It notes the utilization of organization's learning-management system (LMS) software application in evaluating the cost of training. Moreover, it mentions the necessity of human resources (HR) management systems' unification to enable talent management strategy.

The article examines the strategy used by different types of companies to fill leadership roles and evaluate their efficiency in meeting future leadership transitions in the U.S. It notes that most organizations do not have preferred strategy for selecting their successors. It finds out that more than half of the total number of chief executive officers (CEOs ) have less than five years in their positions. It is expected that organizations will be pressured to plan for succession.

The article focuses on the need for the human resources (HR) department to prepare for possible changes in the supply and demand for labor in the U.S. The author suggests on the need for the HR department to assess the workforce to identify gaps between current skills and the skills needed in the future. He also points out that forecasting of labor supply and demand needs an understanding of both the internal and external environments.

The article reviews the significant elements of an effective talent-management process of General Electric Co. (GE) in the U.S. It cites the company's performance-management discussion, which is accordingly designed to engage in a stringent evaluation against leadership development needs and competencies. It also states that GE has been known for its strong financial performance, which is achieved through people.

A letter to the editor is presented in response to the article "Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria," in issue number 2004;350 of "New England Journal of Medicine"

The article discusses on how Internet change the way human resources do business through an Employee Self-Service program. The programs concept first emerged as a great opportunity for human resources departments to transfer transactions or activities to an employee through an Intranet, a by product of the Internet and would allow its personnel to focus more on strategic and value added processes. Employee self service offers a consumer a certain control and speed.

The article examines the impact of unions on leadership and the corporate three Rs--right people, right structure, and right time. Human resource professionals are focusing their efforts on assuring their leaders hire, promote, and retain the right people. HR has helped leaders determine the right organization structure in order to gain operational efficiencies. These three Rs are considered as the formula for success. However, an aspect that HR does not always consider a part of the formula is interference. In this article, "interference" specifically refers to unions. The article also presents some of the points to understand employee behavior.

Focuses on a study which tested the Hersey and Blanchard situational leadership theory (SLT) among 151 senior executives within service and manufacturing businesses of a large Fortune 100 company. What SLT focused on; Techniques used to test the central hypotheses of SLT; Results of the study.

Background: Tacrolimus (TAC) is effective in treating membranous nephropathy (MN); however relapses are frequent after treatment cessation. We conducted a randomised controlled trial to examine whether the addition of mycophenolate mofetil (MMF) to TAC would reduce relapse rate.Methods: Forty patients with biopsy proven idiopathic MN and nephrotic syndrome were randomly assigned to receive either TAC monotherapy (n = 20) or TAC combined with MMF (n = 20) for 12 months. When patients had been in remission for 1 year on treatment the MMF was stopped and the TAC gradually withdrawn in both groups over 6 months. Patients also received supportive treatment with angiotensin blockade, statins, diuretics and anticoagulation as needed. Primary endpoint was relapse rate following treatment withdrawal. Secondary outcomes were remission rate, time to remission and change in renal function.Results: 16/20 (80%) of patients in the TAC group achieved remission compared to 19/20 (95%) in the TAC/MMF group (p = 0.34). The median time to remission in the TAC group was 54 weeks compared to 40 weeks in the TAC/MMF group (p = 0.46). There was no difference in the relapse rate between the groups: 8/16 (50%) patients in the TAC group relapsed compared to 8/19 (42%) in the TAC/MMF group (p = 0.7). The addition of MMF to TAC did not adversely affect the safety of the treatment.Conclusions: Addition of MMF to TAC does not alter the relapse rate of nephrotic syndrome in patients with MN.Trial Registration: This trial is registered with EudraCTN2008-001009-41 . Trial registration date 2008-10-08. [ABSTRACT FROM AUTHOR]

A correction to the article "A novel glucocorticoid-free maintenance regimen for anti-neutrophil cytoplasm antibody-associated vasculitis" is presented.

The article focuses on the strategies for improvement of talent acquisition. Topics discussed include impact of social media on the traditional recruiting sources, several reasons for difficulty filling jobs, which include lack of technical competencies, lack of workplace competence, and poor image of the business sector, and impact of developing early relationship during the recruitment process.