Objective. To assess the mortality profile of systemic lupus erythematosus (SLE) patients in France using multiple-cause-of-death analysis.Methods. Data were collected between 2000 and 2009 in the French Epidemiological Center for the Medical Causes of Death database, and death certificates issued upon the death of an adult for whom SLE was an underlying cause of death (UCD) or a nonunderlying cause of death (NUCD) were evaluated using multiple-cause-of-death analysis. Sex, age, sex ratio, standardized mortality rates, as well as frequency of the various causes of death were assessed, at both a national and a regional level. For the main causes of death, the observed number of deaths in relation to the expected number of deaths (O:E ratio) (standardized for age and sex) was calculated.Results. During the study period, 1,593 deaths related to SLE were identified. The mean ؎ SD age at death was 63.5 ؎ 18.4 years and the sex ratio (female: male) was 3.5. The mean standardized mortality rate was 3.2 per 1 million people (range 2.7-4.1). When SLE was the UCD (n ‫؍‬ 637), the main NUCDs were cardiovascular diseases (49.5%), infectious diseases (24.5%), and renal failure (23.2%). When SLE was an NUCD (n ‫؍‬ 956), the most common UCDs were cardiovascular diseases (35.7%), neoplasms (13.9%), and infectious diseases (10.3%). The overall O:E ratio was >1 for infectious and cardiovascular diseases and renal failure (especially among people <40 years of age for the latter 2 causes), but was <1 for neoplasms.Conclusion. Cardiovascular disease is the leading cause of death associated with SLE in France.Systemic lupus erythematosus (SLE) is a rare systemic autoimmune disease (1). The overall mortality rate among patients with SLE has improved dramatically over the past 50 years: the 5-year survival rate was ϳ50% in the 1950s, and it has increased worldwide to Ͼ90% since the 1990s. Nevertheless, the mortality rate is still higher among SLE patients than among the general population, with standardized mortality ratios of 2-5 in epidemiologic studies (2-13).Causes of death among SLE patients include active SLE, infections, cancer, renal failure, cardiovascular events, and non-SLE-related conditions. A bimodal distribution of mortality in SLE has been reported, with a first peak within the first year after diagnosis, mostly attributable to active disease and infections, and a second peak occurring later and mainly due to cardiovascular events (14). Yet, this distribution is not universally observed (15), and the exact burden of each cause of mortality varies across studies (available online at http://fr.ap-hm.fr/sites/default/files/ mortalup_supplements.pdf).Although recent studies have shown that infections are the main cause of death in SLE, others have demonstrated that cardiovascular diseases are a new leading cause (2-16). These discrepancies may be due to methodologic limitations. Indeed, available published data are mostly from single-center cohorts of limited size and/or with short followup duration, with only a few events ...

Severe acute respiratory syndrome coronavirus 2 is the cause of the ongoing coronavirus disease-19 (COVID-19) pandemic. Mortality is mainly due to acute respiratory distress syndrome (ARDS) [1]. High blood pressure appeared to be an independent factor for severity in patients with COVID-19 [2, 3]. The renin-angiotensin system (RAS) is a hemodynamic and biological system that regulates blood pressure, plasma potassium, and the stability of pulmonary epithelial membranes (Fig. 1) [4]. In this system, two antagonistic pathways are balanced. The first is the angiotensinogen pathway that transforms angiotensinogen into angiotensin I (by renin), and then converts it into angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II attaches to angiotensin II type 1 receptor (AT1R) and activates the system to induce vasoconstriction, aldosterone secretion stimulation, hypokalemia, and pulmonary epithelium degradation [5]. The second way in which the angiotensin system is balanced involves a second angiotensin converting enzyme (ACE2) [6, 7]. This pathway transforms a part of angiotensin I [1-10] and angiotensin II [1-8] before it attaches to its AT1R receptor. The angiotensin I and II phosphorylation products are angiotensin 1-9 and angiotensin 1-7. They attach to the angiotensin II type 2 receptor receiver, inducing antagonist effects compared with AT1R [8]. In the infection phase (Fig. 2), COVID-19 virus uses the enzymatic receptor of ACE2 to penetrate the host cell [9, 10]. Coronavirus binding with ACE2 has been shown to lead to a downregulation of ACE2 [11], contributing to an increase in

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Background: Cell therapy is a therapeutic option for patients presenting with nonrevascularizable critical limb ischemia (CLI). However there is a lack of firm evidence on its efficacy because of the paucity of randomized controlled trials. Methods and Results:The BALI trial was a multicenter, randomized, controlled, double-blind clinical trial that included 38 patients. For all of them, 500 mL of bone marrow were collected for preparation of a BM-MNC product that was implanted in patients assigned to active treatment. For the placebo group, a placebo cell-free product was implanted. Within 6 months after inclusion, major amputations had to be performed in 5 of the 19 placebo-treated patients and in 3 of the 17 BM-MNC-treated patients. According to a classical logistic regression analysis there was no significant difference. However, when using the jackknife analysis, 6 months after inclusion BM-MNC implantation was associated with a lower risk of major amputation (odds ratio (OR): 0.55; 95% confidence interval (CI): 0.52-0.58; P<0.0001) and of occurrence of any event (major or minor amputation, or revascularization) (OR: 0.30; 95% CI: 0.29-0.31; P<0.0001). The secondary endpoints (i.e., pain, ulcers, TcPO2, and ankle-brachial index value) were not statistically different between groups. Conclusions:Our results suggested that cell therapy reduced the risk of major amputation in patients presenting with nonrevascularizable CLI.