Short- and Long-Term Mortality of Hospitalized Patients With Autoimmune Rheumatic Diseases and Serious Infections: A National Cohort Study.

OBJECTIVE: Infectious conditions are a significant cause of mortality in autoimmune rheumatic diseases (ARD). Among patients hospitalized with an infection, we compared in-hospital and long-term (3-year) mortality between those with and without ARD. METHODS: This retrospective analysis included members of the largest health maintenance organization in Israel, aged > 18 years at the first episode of infection, who required hospitalization during 2003-2019. We compared in-hospital mortality and the results of a 3-year landmark analysis of those who survived the index hospitalization between patients with ARD, according to disease subgroups, and patients without ARD. Additionally, we compared mortality outcomes among patients with ARD, according to subgroup diagnosis, matched in a 1:3 ratio by age, sex, and ethnicity to patients without ARD. RESULTS: Included were 365,247 patients who were admitted for the first time with the diagnosis of a serious infection. Of these, we identified 9755 with rheumatoid arthritis (RA), 1351 with systemic lupus erythematosus, 2120 with spondyloarthritis (SpA), 584 with systemic sclerosis, and 3214 with vasculitis. In a matched multivariate analysis, the risk for in-hospital mortality was lower among patients with RA (odds ratio [OR] 0.89, 95% CI 0.81-0.97) and SpA (OR 0.77, 95% CI 0.63-0.94). In a similar analysis, the risk of 3-year mortality was lower among patients with RA (hazard ratio [HR] 0.82, 95% CI 0.78-0.86) and vasculitis (HR 0.86, 95% CI 0.80-0.93). CONCLUSION: Among patients hospitalized for an infection, the risk of in-hospital and 3-year mortality was not increased among those with ARD compared to those without ARD.

Correlation of clinical sepsis definitions with microbiological characteristics in patients admitted through a sepsis alert system; a prospective cohort study.

BACKGROUND: Sepsis was recently redefined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. With this redefinition (Sepsis-3), clinical and microbiological characteristics of patients with sepsis may differ from the patients fulfilling the previous definition (Sepsis-2). PURPOSE: To describe differences in clinical and microbiological characteristics of sepsis episodes between Sepsis-3 and Sepsis-2. The secondary aim was to compare blood culture outcomes between episodes fulfilling Sepsis-3 and Sepsis-2 criteria, respectively. METHODS: A prospective study design was used to include patients presenting with clinically suspected sepsis in the emergency department. Six blood culture bottles were collected from each patient. Blood cultures were described as having clinically relevant growth, contaminant growth, or no growth. Clinical and laboratory data were collected from medical records and the laboratory information system. RESULTS: The analysis included 514 episodes. There were 357/514 (79.5%) Sepsis-3 and 411/514 (80.0%) Sepsis-2 episodes. In total, 341/514 (66.3%) episodes fulfilled both Sepsis-3 and Sepsis-2 criteria. Blood cultures were positive for clinically relevant growth in 130/357 (36.1%) and 145/411 (35.3%) episodes in Sepsis-3 and Sepsis-2, respectively. Other clinical and microbiological characteristics did not differ between Sepsis-3 and Sepsis-2. CONCLUSIONS: A high proportion of patients included through a sepsis alert system fulfilled both Sepsis-3 and Sepsis-2 criteria. The performance of blood cultures in detection of microorganisms was poor and were similar in Sepsis-3 and Sepsis-2 patients.

Diabetes and the risk of hospitalisation for infection: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: The aim of this work was to assess the association between diabetes and risk for infection-related hospitalisation and mortality. METHODS: We conducted a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study. Diabetes was defined as a fasting glucose ≥7 mmol/l or non-fasting glucose ≥11.1 mmol/l, self-report of a diagnosis of diabetes by a physician, or current diabetes medication use. Hospitalisation for infection was ascertained from hospital discharge records. Participants were followed from 1987-1989 to 2019. RESULTS: We included 12,379 participants (mean age 54.5 years; 24.7% Black race; 54.3% female sex). During a median follow-up of 23.8 years, there were 4229 new hospitalisations for infection. After adjusting for potential confounders, people with (vs without) diabetes at baseline had a higher risk for hospitalisation for infection (HR 1.67 [95% CI 1.52, 1.83]). Results were generally consistent across infection type but the association was especially pronounced for foot infection (HR 5.99 [95% CI 4.38, 8.19]). Diabetes was more strongly associated with hospitalisation for infection in younger participants and Black people. Overall infection mortality was low (362 deaths due to infection) but the adjusted risk was increased for people with diabetes (HR 1.72 [95% CI 1.28, 2.31]). CONCLUSIONS/INTERPRETATION: Diabetes confers significant risk for infection-related hospitalisation. Enhancing prevention and early treatment of infection in those with diabetes is needed to reduce infection-related morbidity and mortality.

Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma.

BACKGROUND: The combination of bortezomib, melphalan, and prednisone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. Daratumumab has shown efficacy in combination with standard-of-care regimens in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 706 patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation to receive nine cycles of bortezomib, melphalan, and prednisone either alone (control group) or with daratumumab (daratumumab group) until disease progression. The primary end point was progression-free survival. RESULTS: At a median follow-up of 16.5 months in a prespecified interim analysis, the 18-month progression-free survival rate was 71.6% (95% confidence interval [CI], 65.5 to 76.8) in the daratumumab group and 50.2% (95% CI, 43.2 to 56.7) in the control group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The overall response rate was 90.9% in the daratumumab group, as compared with 73.9% in the control group (P<0.001), and the rate of complete response or better (including stringent complete response) was 42.6%, versus 24.4% (P<0.001). In the daratumumab group, 22.3% of the patients were negative for minimal residual disease (at a threshold of 1 tumor cell per 105 white cells), as compared with 6.2% of those in the control group (P<0.001). The most common adverse events of grade 3 or 4 were hematologic: neutropenia (in 39.9% of the patients in the daratumumab group and in 38.7% of those in the control group), thrombocytopenia (in 34.4% and 37.6%, respectively), and anemia (in 15.9% and 19.8%, respectively). The rate of grade 3 or 4 infections was 23.1% in the daratumumab group and 14.7% in the control group; the rate of treatment discontinuation due to infections was 0.9% and 1.4%, respectively. Daratumumab-associated infusion-related reactions occurred in 27.7% of the patients. CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, daratumumab combined with bortezomib, melphalan, and prednisone resulted in a lower risk of disease progression or death than the same regimen without daratumumab. The daratumumab-containing regimen was associated with more grade 3 or 4 infections. (Funded by Janssen Research and Development; ALCYONE ClinicalTrials.gov number, NCT02195479 .).

Increased risk of severe infections and mortality in patients with newly diagnosed systemic lupus erythematosus: a population-based study.

OBJECTIVE: To evaluate the risk of severe infection and infection-related mortality among patients with newly diagnosed SLE. METHODS: We conducted an age- and gender-matched cohort study of all patients with incident SLE between 1 January 1997 and 31 March 2015 using administrative health data from British Columbia, Canada. Primary outcome was the first severe infection after SLE onset necessitating hospitalization or occurring during hospitalization. Secondary outcomes were total number of severe infections and infection-related mortality. RESULTS: We identified 5169 SLE patients and matched them with 25 845 non-SLE individuals from the general population, yielding 955 and 1986 first severe infections during 48 367 and 260 712 person-years follow-up, respectively. The crude incidence rate ratios for first severe infection and infection-related mortality were 2.59 (95% CI: 2.39, 2.80) and 2.20 (95% CI: 1.76, 2.73), respectively. The corresponding adjusted hazard ratios were 1.82 (95% CI: 1.66, 1.99) and 1.61 (95% CI: 1.24, 2.08). SLE patients had an increased risk of a greater total number of severe infections with crude rate ratio of 3.24 (95% CI: 3.06, 3.43) and adjusted rate ratio of 2.07 (95% CI: 1.82, 2.36). CONCLUSION: SLE is associated with increased risks of first severe infection (1.8-fold), a greater total number of severe infections (2.1-fold) and infection-related mortality (1.6-fold).

Encapsulating Peritoneal Sclerosis and Mortality Related to Infection in Patients on Combination Once-Weekly Hemodialysis with Peritoneal Dialysis.

INTRODUCTION: Previous studies showed that the combination of peritoneal dialysis (PD) and once-weekly hemodialysis is associated with lower all-cause and cardiovascular mortality. This study aimed to compare the incidence of encapsulating peritoneal sclerosis (EPS) and infection-related mortality among those on combination therapy and those on PD alone. METHODS: This prospective study on the Japanese Renal Data Registry included patients on PD from 2010 to 2014. Subjects were followed up until the end of 2015. Exposure of interest was combination therapy compared with PD alone. Patients who transitioned to combination therapy were matched with those on PD alone by propensity scores. Outcomes were EPS and infection-related mortality. Data were analyzed using Cox regression models. RESULTS: Among the matched cohort, 608 and 869 patients were on combination therapy and on PD alone, respectively. Dialysate-to-plasma creatinine (D/P Cr) ratio decreased over time among those on combination therapy, while the ratio increased among those on PD alone (p = 0.01 by the mixed-effects model). During a median follow-up of 2.5 years, 33 experienced EPS and 55 died of infection. Combination therapy was associated with lower infection-related mortality (HR [95% CI]: 0.52 [0.28-0.95]) but not with EPS (HR: 1.21 [0.61-2.40]). Lower mortality was not limited to intra-abdominal infection but also observed for pulmonary infection. Sensitivity analyses considering the effects of dialysis facilities yielded similar results. CONCLUSIONS: Combination therapy was associated with lower infection-related mortality. It was also associated with a decline in the D/P Cr ratio over time but not with lower incidence of EPS during the short observation period.

Predictors of Survival in Chronic Hemodialysis Patients: A 10-Year Longitudinal Follow-Up Analysis.

BACKGROUND: Risk factors of mortality in chronic hemodialysis patients have not yet been sufficiently evaluated. In particular, chronological transits and interactions of the impact of risk factors have rarely been described. METHODS: This study is a post hoc analysis of the participants in the Olme-sartan Clinical Trial in Okinawan Patients under OKIDS (OCTOPUS) study conducted between June 2006 and June 2011. We additionally followed up on the prognosis of the participants until July 31, 2018. Standardized univariable and multivariable Cox regression analyses were used to evaluate the influences of the participants' baseline characteristics on all-cause mortality. We also evaluated chronological changes in the impacts of risk factors, interactions among predictors, and the influence of missing values using sensitivity analyses. RESULTS: Of the 469 original trial participants, 461 participants were evaluated. The median time of follow-up was 10.2 years. A total of 211 (45.8%) participants were deceased. The leading causes of death were infection (n = 72, 34.1%) and cardiovascular disease (n = 66, 31.3%). Univariate and multivariate Cox regression analyses revealed that the impact of diabetes mellitus, history of coronary intervention, and hypoalbuminemia were significant risk factors for mortality during the whole follow-up period. During the early follow-up period (≤3 years), standardized univariate Cox regression analyses revealed that history of amputation (hazard ratio [HR] = 4.61, p < 0.001), lower dry weight, higher cardiothoracic ratio, and lower potassium levels were statistically significant risks. In those who survived for longer than 3 years, a history of stroke (HR = 1.73, p = 0.006), higher systolic blood pressure, lower serum sodium levels, and higher levels of hemoglobin, and serum phosphate were significant risks. We also observed a stable interaction between the impacts of serum phosphate and albumin on all-cause mortality. CONCLUSION: In chronic hemodialysis patients, targets to improve the short-term prognosis and long-term prognosis are not equivalent. Hyperphosphatemia was a significant risk factor for the all-cause mortality among patients with normal serum albumin levels but not among patients with compromised albumin levels.

Impact of anti-thymocyte globulin dose for graft-versus-host disease prophylaxis in allogeneic hematopoietic cell transplantation from matched unrelated donors: a multicenter experience.

Despite the widespread use of rabbit anti-thymocyte globulin (ATG) to prevent acute and chronic graft-versus-host disease (aGVHD, cGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), convincing evidence about an optimal dose is lacking. We retrospectively evaluated the clinical impact of two different ATG doses (5 vs 6-7.5 mg/kg) in 395 adult patients undergoing HSCT from matched unrelated donors (MUD) at 3 Italian centers. Cumulative incidence of aGVHD and moderate-severe cGVHD did not differ in the 2 groups. We observed a trend toward prolonged overall survival (OS) and disease-free survival (DFS) with lower ATG dose (5-year OS and DFS 56.6% vs. 46.3%, p=0.052, and 46.8% vs. 38.6%, p=0.051, respectively) and no differences in relapse incidence and non-relapse mortality. However, a significantly increased infection-related mortality (IRM) was observed in patients who received a higher ATG dose (16.7% vs. 8.8% in the lower ATG group, p=0.019). Besides, graft and relapse-free survival (GRFS) was superior in the lower ATG group (5-year GRFS 43.1% vs. 32.4%, p=0.014). The negative impact of higher ATG dose on IRM and GRFS was confirmed by multivariate analysis. Our results suggest that ATG doses higher than 5 mg/kg are not required for MUD allo-HCT and seem associated with worse outcomes.

Association of lactate dehydrogenase with mortality in incident hemodialysis patients.

BACKGROUND: Lactate dehydrogenase (LDH) plays a role in the glucose metabolism of the human body. Higher LDH levels have been linked to mortality in various cancer types; however, the relationship between LDH and survival in incident hemodialysis (HD) patients has not yet been examined. We hypothesized that higher LDH level is associated with higher death risk in these patients. METHODS: We examined the association of baseline and time-varying serum LDH with all-cause, cardiovascular and infection-related mortality among 109 632 adult incident HD patients receiving care from a large dialysis organization in the USA during January 2007 to December 2011. Baseline and time-varying survival models were adjusted for demographic variables and available clinical and laboratory surrogates of malnutrition-inflammation complex syndrome. RESULTS: There was a linear association between baseline serum LDH levels and all-cause, cardiovascular and infection-related mortality in both baseline and time-varying models, except for time-varying infection-related mortality. Adjustment for markers of inflammation and malnutrition attenuated the association in all models. In fully adjusted models, baseline LDH levels ≥360 U/L were associated with the highest risk of all-cause mortality (hazard ratios = 1.19, 95% confidence interval 1.14-1.25). In time-varying models, LDH >280 U/L was associated with higher death risk in all three hierarchical models for all-cause and cardiovascular mortality. CONCLUSIONS: Higher LDH level >280 U/L was incrementally associated with higher all-cause and cardiovascular mortality in incident dialysis patients, whereas LDH <240 U/L was associated with better survival. These findings suggest that the assessment of metabolic functions and monitoring for comorbidities may confer survival benefit to dialysis patients.

Analysis of trends and causes of death in SLE patients over a 40-years period in a cohort of patients in the United Kingdom.

BACKGROUND: Systemic Lupus Erythematosus (SLE) an autoimmune rheumatic disease with a complex pathogenesis, remains potentially life-threatening. SLE patients have increased morbidity and premature mortality compared to non-SLE patients. The five-year survival rate has improved from <50% in the 1950s to >90% in the 1980s. Lupus patients still have a mortality risk three times that of the general population. OBJECTIVES: To provide a detailed analysis of the causes of death, main characteristics and trends in the management of the deceased SLE patients from the lupus clinic at the University College London Hospital (UCLH); during the past four decades. METHODS: This was a non-interventional, retrospective study based on historical real-world data from paper and electronic records of patients followed up at UCLH. The analysis focused on data collected between 1st January 1978 and 31th December 2018. We collected the: causes of death, duration of disease, key laboratory and clinical parameters and the treatment received. We compared the results from the four decades to ascertain trends in the causes of mortality. All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS), version 22.0. The 95% confidence intervals for the means of data were calculated. RESULTS: 111 SLE patients (15%), died during follow-up. Their median age was 51 years (interquartile range (IQR) = 38-63 years) and the median duration of disease, 15 years (IQR = 8.5-24 years). The main causes of death in the past 40 years were infection (31.7%), cancer (26.7%) and cardiovascular disease (CVD) (21.8%). 93.6% of these patients were immunosupressed. During the 40-year period, there were several therapeutic developments notably the introduction of mycophenolate mofetil (MMF) and rituximab; the latter initially only given to patients when more conventional inmunosupressants had failed, but more recently offered to patients at diagnosis. There was a statistically significant increase in the use of hydroxycloroquine (HCQ), MMF and rituximab. In contrast, the use of Azathioprine (AZA) and steroids, hardly changed over time. CONCLUSIONS: This retrospective review shows how epidemiological factors, causes of death and treatment of SLE patients have changed during the last 40 years in the UCLH cohort.

History of anemia and long-term mortality due to infection: a cohort study with 12 years follow-up in South Korea.

BACKGROUND: Anemia, which is a condition with reduced healthy red blood cells, is reported to be closely related to the development of infectious diseases. We aimed to investigate the association between history of anemia and 12-year mortality rate due to infections, and compare it with that among non-anemic individuals. METHODS: Data from the National Health Insurance Service Health Screening Cohort were used in this population-based cohort study. Adults who underwent standardized medical examination between and 2002-2003 were included, and the mortality rate due to infection between 2004 and 2015 was analyzed. Individuals were considered to have a history of anemia if the serum hemoglobin level in 2002-2003 was < 12 g/dL for women and < 13 g/dL for men. The severity of anemia at that time was categorized as mild (12 g/dL > hemoglobin ≥11 g/dL in women and 13 g/dL > hemoglobin ≥11 g/dL in men), moderate (hemoglobin 8-10.9 g/dL), or severe (hemoglobin < 8 g/dL). Propensity score (PS) matching and Cox regression analysis were used as statistical methods. RESULTS: Overall, 512,905 individuals were included in this study. The mean age of the participants was 54.5 years old (range: 40-98), and 49,042 (9.6%) individuals were classified in the anemic group, which comprised of 36,383 (7.1%), 11,787 (2.3%), and 872 (0.2%) participants in the mild, moderate, and severe sub-groups, respectively. After PS matching, 49,039 individuals in each group were included in the analysis. The risk of mortality due to infection in the anemic group was 1.77-fold higher (hazard ratio [HR]: 1.77, 95% confidence interval [CI]: 1.52-2.60; P < 0.001) than that in the non-anemic group. In the subgroup analysis, the mild and moderate anemia groups had 1.38-fold (HR: 1.38, 95% CI: 1.23 to 1.55; P < 0.001) and 2.02-fold (HR: 2.02, 95% CI: 1.62 to 2.50; P < 0.001) risk of mortality due to infection compared to that of the non-anemic group, respectively. The severe anemia group did not have a significantly different risk of mortality due to infection (P = 0.448). CONCLUSIONS: History of anemia was associated with increased mortality rate due to infection at 12-year follow-up.

Mortality among pediatric hematopoietic stem cell transplantation patients: Report from a single center in southern Brazil.

INTRODUCTION: HSCT has grown in number in recent years. This treatment in children has its particularities and has been characterized in previous studies only on a limited basis. There are important causes of morbidity and mortality in this group of patients, including evolution of primary disease, graft failure, infectious diseases, and GVHD. The aim of this study was to report case series of TRM within 100 days after transplantation and associated factors. METHODS: Retrospective cohort. All children transplanted between January 1, 2010 and December 31, 2017 were included and those who underwent the first HSCT in another center were excluded. RESULTS: Data from 292 children were analyzed. TRM in 100 days was 5.8%, being significantly higher in patients with umbilical cord blood as the cell source. Infectious complications were frequent in this sample (bacterial infections in 27%, viral infections in 75.3%, and fungal infections in 12%) and both the presence of fungal disease and more than one infection during the follow-up (viral and bacterial, viral and fungal or bacterial and fungal) had statistically significant association with the outcome. CONCLUSIONS: The prognosis in allogeneic HSCT is influenced by the origin of the stem cells, the presence of acute GVHD and the occurrence of infectious diseases. Studies that evaluate pediatric individuals undergoing HSCT and analyze their mortality profile, can improve the management of these patients, possibly leading to a reduction in TRM.

Declining mortality rates in children admitted to ICU following HCT.

We aimed to assess short- and long-term mortality, including factors associated with mortality, for children referred to a pediatric intensive care unit (ICU) at Rigshospitalet, Denmark, following haematopoietic cell transplantation (HCT). Data regarding admission to ICU and mortality following HCT for children below 16 years of age between 2000 and 2017 were retrospectively analyzed. We identified 55 ICU admissions in 39 patients following 46 HCTs. The overall in-ICU, in-hospital, 3-month, and 1-year mortality rates were 33.3%, 43.6%, 46.2%, and 51.3%, respectively. Patients admitted from 2000 to 2010 had a 3-month mortality of 63.2% and 1-year mortality of 68.4%, compared to 30% and 35% (P = .040 and P = .039) for patients admitted from 2011 to 2017. The main reason for ICU admission was respiratory failure (78.2%). Mechanical ventilation (MV) was associated with a higher long-term mortality (P = .044), and use of inotropes or vasopressors was associated with increased mortality at all times (all P > .006). Extracorporeal life support, renal replacement therapy, longer ICU stay, and longer time with MV were not associated with increased mortality. Over the past two decades, mortality was significantly reduced in pediatric HCT patients admitted to the ICU. The cause is probably multifactorial and warrants further studies. Our findings support admissions of critically ill pediatric HCT patients to intensive care with encouraging outcomes of even long-term admissions.

Causes of death in patients undergoing maintenance hemodialysis in Japan: 10-year outcomes of the Q-Cohort Study.

BACKGROUND: Although the mortality rate in patients on hemodialysis remains extremely high, detailed information on causes of death over long-term periods is limited. The aim of this study was to clarify the underlying causes of death in patients undergoing maintenance hemodialysis in Japan. METHODS: This was a 10-year, multicenter, observational study of 3528 outpatients undergoing maintenance hemodialysis in Japan. Clinical outcomes were analyzed and causes of death were classified into six broad categories including cardiovascular diseases, infectious diseases, malignant neoplasms, cachexia, trauma/accidents, and other diseases, and more detailed subcategories. RESULTS: During the 10-year follow-up period, 1748 (49.5%) patients died. The most frequent causes of death were cardiovascular diseases (36.1%), followed by infectious diseases (25.8%) and malignant neoplasms (13.5%). In a detailed classification, sudden death, pulmonary infection, and lung cancer were the most common causes of death in cardiovascular diseases, infectious diseases, and malignant neoplasms, respectively. CONCLUSION: Our study determined details on causes of death in Japanese hemodialysis patients during the 10-year follow-up period. Cardiovascular disease, especially sudden death is noticeable cause of death among patients on hemodialysis.

Prognostic accuracy of qSOFA at triage in patients with suspected infection in a Brazilian emergency department.

OBJECTIVE: To evaluate the prognostic accuracy of qSOFA for predicting in-hospital mortality among patients with suspected infection presenting to the ED of a public tertiary hospital in Brazil. METHODS: We performed a retrospective cohort study of consecutive adult patients (age ≥ 18 years) with suspected infection who presented to an academic tertiary ED in Porto Alegre (Southern Brazil) during an 18-month period. The qSOFA was calculated by using information collected at triage and patients were followed throughout hospitalization for the primary outcome of in-hospital mortality. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratios with corresponding 95% CIs were calculated for the qSOFA and qSOFA65. RESULTS: A total of 7523 ED visits of patients with suspected infection in which an intravenous antibiotic was administered within 24 h were included, which resulted in 908 in-hospital deaths (12.1%). There were 690 (9.2%) patients whose triage qSOFA was ≥2 points. When such cutoff was used, the sensitivity for in-hospital death was 24.6% (95% CI 21.8 to 27.4%) and the specificity was 92.9% (95% CI 92.3% to 93.5%). The sensitivity increased to 67.4% (95% CI 64.2% to 70.3%) when a cutoff of ≥1 was tested, but the specificity decreased to 55.3% (95% CI 54.1% to 56.5%). Using a cutoff of ≥2, the qSOFA65 had a sensitivity of 51.0% (95% CI 47.7% to 54.3%) and a specificity of 75.7% (95% CI 74.6% to 76.7%). CONCLUSIONS: The qSOFA score yielded very low sensitivity in predicting in-hospital mortality. Emergency physicians or ED triage nurses in low-to-middle income countries should not be using qSOFA or qSOFA65 as "rule-out" screening tools in the initial evaluation of patients with suspected infection.

Chronic and End-Stage Kidney Disease in the Neurological Intensive Care Unit.

Patients with renal disease have increased rates of admission to the neurological intensive care unit related to overlapping risk factors for renal and cerebrovascular disease as well as unique risks associated with renal dysfunction alone. Management of acute neurological injury in these patients requires individualized attention to diagnostic and management factors as they relate to coagulopathy, disorders of immune function, encephalopathy and renal replacement modalities. Careful consideration of these brain-kidney interactions is necessary to optimize care for this special patient population and improve neurological and renal outcomes.

Predictive factors of severe infections in patients with systemic necrotizing vasculitides: data from 733 patients enrolled in five randomized controlled trials of the French Vasculitis Study Group.

OBJECTIVES: Infections remain a major cause of morbidity and mortality in systemic necrotizing vasculitides (SNV). We aimed to identify factors predicting severe infections (SI) in SNV. METHODS: Data from five randomized controlled trials (RCTs) enrolling 733 patients were pooled. The primary end point was the occurrence of SI, defined by the need of a hospitalization and/or intravenous anti-infectious treatment and/or leading to death. RESULTS: After a median follow-up of 5.2 (interquartile range 3-9.7) years, 148 (20.2%) patients experienced 189 SI, and 98 (66.2%) presented their first SI within the first 2 years. Median interval from inclusion to SI was 14.9 (4.3-51.7) months. Age ≥65 years (hazard ratio (HR) 1.49 [1.07-2.07]; P=0.019), pulmonary involvement (HR 1.82 [1.26-2.62]; P=0.001) and Five Factor Score ≥1 (HR 1.21 [1.03-1.43]; P=0.019) were independent predictive factors of SI. Regarding induction therapy, the occurrence of SI was associated with the combination of GCs and CYC (HR 1.51 [1.03-2.22]; P = 0.036), while patients receiving only GCs were less likely to present SI (HR 0.69 [0.44-1.07]; P = 0.096). Finally, occurrence of SI had a significant negative impact on survival (P<0.001). CONCLUSION: SI in SNV are frequent and impact mortality. Age, pulmonary involvement and Five Factor Score are baseline independent predictors of SI. No therapeutic regimen was significantly associated with SI but patients receiving glucocorticoids and CYC as induction tended to have more SI.

Large-scale mortality gap between SLE and control population is associated with increased infection-related mortality in lupus.

OBJECTIVE: The aim of the present study was to analyse the incidence, prevalence, mortality and cause of death data of adult SLE patients and matched controls in a full-populational, nationwide, retrospective study. METHODS: This non-interventional study was based on database research of the National Health Insurance Fund of Hungary. A total of 7888 patients were included in the analyses, within which two subgroups of incident patients were created: the 'All incident SLE patients' group consisted of all incident SLE patients (4503 patients), while the 'Treated SLE patients' group contained those who received relevant therapy in the first 6 months after diagnosis (2582 patients). RESULTS: The median age of the SLE population was found to be 46.5 years (women 85%). The incidence rate was 4.86 and 2.78 per 100 000 inhabitants in the 'All incident SLE patients' and 'Treated SLE patients' groups, respectively. The standardized mortality ratio was 1.63 and 2.09 in the 'All incident SLE patients' and 'Treated SLE patients' groups, respectively. Overall survival was significantly lower (P < 0.001) in both groups than in the general population, with hazard ratio = 2.17 in the 'All incident SLE patients' group and hazard ratio = 2.75 in the 'Treated SLE patients' group. There was no significant difference between SLE and control deaths regarding cerebrovascular conditions as the cause of death. Generally, cancer-related deaths were less common, while haematological cancer and infection-related deaths were more common in SLE patients. CONCLUSION: Infections, especially sepsis, had the largest positive effect on top of the extra mortality of SLE. This highlights that SLE patients are at increased risk of infection-related death.

α1-Antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease.

Corticosteroid resistance after acute graft-versus-host disease (SR-aGVHD) results in high morbidity and mortality after allogeneic hematopoietic cell transplantation. Current immunosuppressive therapies for SR-aGVHD provide marginal effectiveness because of poor response or excessive toxicity, primarily from infection. α1-Antitrypsin (AAT), a naturally abundant serine protease inhibitor, is capable of suppressing experimental GVHD by downmodulating inflammation and increasing ratios of regulatory (Treg) to effector T cells (Teffs). In this prospective multicenter clinical study, we sought to determine the safety and response rate of AAT administration in SR-aGVHD. Forty patients with a median age of 59 years received intravenous AAT twice weekly for 4 weeks as first-line treatment of SR-aGVHD. The primary end point was overall response rate (ORR), the proportion of patients with SR-aGVHD in complete (CR) or partial response by day 28 without addition of further immunosuppression. Treatment was well tolerated without drug-related adverse events. A significant increase in serum levels of AAT was observed after treatment. The ORR and CR rates by day 28 were 65% and 35%, respectively, and included responses in all aGVHD target organs. At day 60, responses were sustained in 73% of patients without intervening immunosuppression. Infectious mortality was 10% at 6 months and 2.5% within 30 days of last AAT infusion. Consistent with preclinical data, correlative samples showed an increase in ratio of activated Tregs to Teffs after AAT treatment. These data suggest that AAT is safe and may be potentially efficacious in treating SR-aGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01700036.

A simple score to predict early death after kidney transplantation.

BACKGROUND: Few studies have focused on risk stratification for premature death after transplantation. However, stratification of individual risk is an essential step in personalized care. MATERIAL AND METHODS: We have developed a risk score of early post-transplant death (ORLY score) in a prospective multicentre cohort including 942 patients and validated our model in a retrospective independent replication cohort including 874 patients. RESULTS: 60 patients (6.4%) from the prospective cohort died during the first three-year post-transplant. Age, male gender, diabetes, dialysis duration and chronic respiratory failure were associated with early post-transplant death. The multivariable model exhibited good discrimination ability (C-index = 0.78, 95%CI [0.75-0.81]). ORLY score highly predicted early death after transplantation (1.34; 95%CI, 1.22 to 1.48 for each increase of 1 point in score; P < .001). The predictive value of the score in the validation cohort was close to that observed in the experimental cohort (1.41; 95%CI, 1.27 to 1.56 for each increase of 1 point in score; P < .001). Merging the two cohorts, four categories of risk could be individualized: low, 0-5 (n = 522, mean risk, 1%); intermediate, 6-7 (n = 739, mean risk 4.7%); moderate, 8-10 (n = 429, mean risk 10%); and high risk 11-15 (n = 132, mean risk 19%). CONCLUSIONS: The ORLY score discriminates patients with high risk of early death.