Clinical outcomes of patients with complicated post-operative course after gastrectomy for cancer: a GIRCG study using the GASTRODATA registry.

Gastrectomy for gastric cancer is still performed in Western countries with high morbidity and mortality. Post-operative complications are frequent, and effective diagnosis and treatment of complications is crucial to lower the mortality rates. In 2015, a project was launched by the EGCA with the aim of building an agreement on list and definitions of post-operative complications specific for gastrectomy. In 2018, the platform www.gastrodata.org was launched for collecting cases by utilizing this new complication list. In the present paper, the Italian Research Group for Gastric Cancer endorsed a collection of complicated cases in the period 2015-2019, with the aim of investigating the clinical pictures, diagnostic modalities, and treatment approaches, as well as outcome measures of patients experiencing almost one post-operative complication. Fifteen centers across Italy provided 386 cases with a total of 538 complications (mean 1.4 complication/patient). The most frequent complications were non-surgical infections (gastrointestinal, pulmonary, and urinary) and anastomotic leaks, accounting for 29.2% and 17.3% of complicated patients, with a median Clavien-Dindo score of II and IIIB, respectively. Overall mortality of this series was 12.4%, while mortality of patients with anastomotic leak was 25.4%. The clinical presentation with systemic septic signs, the timing of diagnosis, and the hospital volume were the most relevant factors influencing outcome.

Timing of neonatal mortality and severe morbidity during the postnatal period: a systematic review.

OBJECTIVE: The objective of this review was to determine the timing of overall and cause-specific neonatal mortality and severe morbidity during the postnatal period (1-28 days). INTRODUCTION: Despite significant focus on improving neonatal outcomes, many newborns continue to die or experience adverse health outcomes. While evidence on neonatal mortality and severe morbidity rates and causes are regularly updated, less is known on the specific timing of when they occur in the neonatal period. INCLUSION CRITERIA: This review considered studies that reported on neonatal mortality daily in the first week; weekly in the first month; or day 1, days 2-7, and days 8-28. It also considered studies that reported on timing of severe neonatal morbidity. Studies that reported solely on preterm or high-risk infants were excluded, as these infants require specialized care. Due to the available evidence, mixed samples were included (eg, both preterm and full-term infants), reflecting a neonatal population that may include both low-risk and high-risk infants. METHODS: MEDLINE, Embase, Web of Science, and CINAHL were searched for published studies on December 20, 2019, and updated on May 10, 2021. Critical appraisal was undertaken by 2 independent reviewers using standardized critical appraisal instruments from JBI. Quantitative data were extracted from included studies independently by 2 reviewers using a study-specific data extraction form. All conflicts were resolved through consensus or discussion with a third reviewer. Where possible, quantitative data were pooled in statistical meta-analysis. Where statistical pooling was not possible, findings were reported narratively. RESULTS: A total of 51 studies from 36 articles reported on relevant outcomes. Of the 48 studies that reported on timing of mortality, there were 6,760,731 live births and 47,551 neonatal deaths with timing known. Of the 34 studies that reported daily deaths in the first week, the highest proportion of deaths occurred on the first day (first 24 hours, 38.8%), followed by day 2 (24-48 hours, 12.3%). Considering weekly mortality within the first month (n = 16 studies), the first week had the highest mortality (71.7%). Based on data from 46 studies, the highest proportion of deaths occurred on day 1 (39.5%), followed closely by days 2-7 (36.8%), with the remainder occurring between days 8 and 28 (23.0%). In terms of causes, birth asphyxia accounted for the highest proportion of deaths on day 1 (68.1%), severe infection between days 2 and 7 (48.1%), and diarrhea between days 8 and 28 (62.7%). Due to heterogeneity, neonatal morbidity data were described narratively. The mean critical appraisal score of all studies was 84% (SD = 16%). CONCLUSION: Newborns experience high mortality throughout the entire postnatal period, with the highest mortality rate in the first week, particularly on the first day. Ensuring regular high-quality postnatal visits, particularly within the first week after birth, is paramount to reduce neonatal mortality and severe morbidity.

Effect of procalcitonin on the severity and prognostic value of elderly patients with a severe infection of oral and maxillofacial space.

This study aimed to investigate the effect on the severity and prognostic value of serum procalcitonin for elderly patients with oral and maxillofacial infections. We divided 163 elderly patients with severe oral and maxillofacial infection into survival and death groups according to the prognosis between June 2015 and May 2021, measured serum procalcitonin by enzyme-linked immunosorbent assay on the 1st, 2nd, 3rd, 5th, and 7th day after admission for the dynamic changes of serum procalcitonin level, collected the general physiological and biochemical indexes for the scores of acute physiology and general chronic condition, compared the correlation between serum procalcitonin, mean platelet count and APACHE score, analyzed the prognostic value of serum procalcitonin levels at different time after admission by ROC curve. The serum procalcitonin level increased significantly in both groups after admission, sharply increased at first and then rapidly decreased in the survival group, and continued to rise or declined slowly with fluctuation of high level in the death group. There was a negative correlation between serum procalcitonin level and mean platelet count (r = -0.698, P < .05) and a positive correlation between serum procalcitonin and APACHE II (R = 0.803, P < .05). The ROC curve showed that the serum procalcitonin level had little value on the first day and great value on the third day in predicting the prognosis of elderly patients with severe oral and maxillofacial infection (PCT1d = 0.539, PCT3d = 0.875, P < .05). The serum procalcitonin level is correlated with the severity of the disease in elderly patients with severe oral and maxillofacial space infection. Dynamic observation of it is helpful for the prognosis judgment of patients. After admission, serum procalcitonin level on the third day has a great value for the prognosis judgment of elderly patients with severe oral and maxillofacial space infection.

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.

Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.

OBJECTIVE: To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England. DESIGN: Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England. SETTING: Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data. POPULATION: Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021. MAIN OUTCOME MEASURES: For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020. RESULTS: After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51 655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021. CONCLUSIONS: During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.

Admission Lymphopenia Predicts Infectious Complications and Mortality in Traumatic Brain Injury Victims.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of mortality and disability associated with increased risk of secondary infections. Identifying a readily available biomarker may help direct TBI patient care. Herein, we evaluated whether admission lymphopenia could predict outcomes of TBI patients. METHODS: This is a 10-year retrospective review of TBI patients with a head Abbreviated Injury Score 2 to 6 and absolute lymphocyte counts (ALC) collected within 24 h of admission. Exclusion criteria were death within 24 h of admission and presence of bowel perforation on admission. Demographics, admission data, injury severity score, mechanism of injury, and outcomes were collected. Association between baseline variables and outcomes was analyzed. RESULTS: We included 2,570 patients; 946 (36.8%) presented an ALC ≤1,000 on admission (lymphopenic group). Lymphopenic patients were significantly older, less likely to smoke, and more likely to have heart failure, hypertension, or chronic kidney disease. Lymphopenia was associated with increased risks of mortality (OR = 1.903 [1.389-2.608]; P < 0.001) and pneumonia (OR = 1.510 [1.081-2.111]; P = 0.016), increased LOS (OR = 1.337 [1.217-1.469]; P < 0.001), and likelihood of requiring additional healthcare resources at discharge (OR = 1.669 [1.344-2.073], P < 0.001). Additionally, lymphopenia increased the risk of early in-hospital death (OR = 1.459 [1.097-1.941]; P = 0.009). Subgroup analysis showed that lymphopenia was associated with mortality in polytrauma patients and those who presented with two or more concurrent types of TBI. In all subgroup analyses, lymphopenia was associated with longer length of stay and discharge requiring higher level of care. CONCLUSION: A routine complete blood count with differential for all TBI patients may help predict patient outcomes and direct care accordingly.

Changes in proportionate cardiovascular mortality in patients with chronic infectious and inflammatory conditions in the United States, 1999-2018.

Treatment options for several chronic infectious and inflammatory conditions have expanded in recent years. This may have implications for evolving competing risks for chronic inflammation-associated comorbidities, including cardiovascular diseases (CVDs). Yet sparse data exist on patterns over time in cardiovascular mortality for chronic infectious and inflammatory conditions. We used data from the Centers for Disease Control and Prevention 1999-2018 Multiple Causes of Death database to investigate patterns in CVD mortality from January 1, 1999 to December 31, 2018 in several infectious and inflammatory conditions. Specifically, we determined age-adjusted proportionate CVD mortality separately for patients with the following conditions (as well as the general population): hepatitis C virus (HCV), human immunodeficiency virus (HIV), inflammatory bowel diseases (IBD), psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Proportionate CVD mortality differed significantly in 1999 and 2018 for each condition compared with the general population (p < 0.0001). Proportionate CVD mortality decreased steadily in the general population (40.9 to 30.6%) but increased for patients with HCV (7.0 to 10.2%) and HIV (1.9 to 6.7%). For IBD, PSO, RA, and SLE, proportionate CVD mortality initially decreased followed by plateauing or increasing rates. Underlying disease-specific pathophysiologies, changes in natural history, and competing risks of chronic end-organ diseases contributing to these differences merit further study.

Age-adjusted quick Sequential Organ Failure Assessment score for predicting mortality and disease severity in children with infection: a systematic review and meta-analysis.

We assessed the diagnostic accuracy of the age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) for predicting mortality and disease severity in pediatric patients with suspected or confirmed infection. We conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and Web of Science. Eleven studies with a total of 172,569 patients were included in the meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of the age-adjusted qSOFA for predicting mortality and disease severity were 0.69 (95% confidence interval [CI] 0.53-0.81), 0.71 (95% CI 0.36-0.91), and 6.57 (95% CI 4.46-9.67), respectively. The area under the summary receiver-operating characteristic curve was 0.733. The pooled sensitivity and specificity for predicting mortality were 0.73 (95% CI 0.66-0.79) and 0.63 (95% CI 0.21-0.92), respectively. The pooled sensitivity and specificity for predicting disease severity were 0.73 (95% CI 0.21-0.97) and 0.72 (95% CI 0.11-0.98), respectively. The performance of the age-adjusted qSOFA for predicting mortality and disease severity was better in emergency department patients than in intensive care unit patients. The age-adjusted qSOFA has moderate predictive power and can help in rapidly identifying at-risk children, but its utility may be limited by its insufficient sensitivity.

Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis.

BACKGROUND AND OBJECTIVES: Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation. RESULTS: In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation (P=0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse. CONCLUSIONS: The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3.

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.

Infections and demanding endocrine care contribute to increased mortality in patients with APECED.

OBJECTIVE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) has variable clinical course. Overall mortality is increased but reasons for this remain largely unknown. Our objective was to assess the causes of death and factors contributing to increased mortality. DESIGN: A follow-up study of the Finnish APECED cohort in 1970-2019. METHODS: In 33 deceased patients with APECED, causes of death and clinical course preceding the death were analyzed using national registry data, death certificates, autopsy reports, and patient records. RESULTS: Most common causes leading to death were infections (24%), oral and esophageal malignancies (15%; median age at death 36.7 years; median survival 1.5 years), and diseases of the circulatory system (18%). Adrenal crisis was an independent cause of death in two patients. In addition, in four patients, the adrenal crisis was a complicating factor during a fatal infection. Other APECED manifestations leading to death were hypoparathyroidism, diabetes, and hepatitis. Other causes of death included accidents (12%), alcohol-related causes, and amyotrophic lateral sclerosis. Challenges in overall, and especially in the endocrine, care contributed to deaths related to carcinomas and adrenal crisis. Age at death and year of death correlated (r = 0.345, P = 0.045), suggesting improved longevity. CONCLUSIONS: Infections, malignancies, and diseases of the circulatory system are the most common primary causes of death in patients with APECED. Adrenal crisis is an independent cause of death but more often a contributing factor in fatal infections. Despite the high overall mortality and the demanding care, our results suggest improved patient survival in recent years.

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.

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.

Clinical signs of possible serious infection and associated mortality among young infants presenting at first-level health facilities.

BACKGROUND: The World Health Organization recommends inpatient hospital treatment of young infants up to two months old with any sign of possible serious infection. However, each sign may have a different risk of death. The current study aims to calculate the case fatality ratio for infants with individual or combined signs of possible serious infection, stratified by inpatient or outpatient treatment. METHODS: We analysed data from the African Neonatal Sepsis Trial conducted in five sites in the Democratic Republic of the Congo, Kenya and Nigeria. Trained study nurses classified sick infants as pneumonia (fast breathing in 7-59 days old), severe pneumonia (fast breathing in 0-6 days old), clinical severe infection [severe chest indrawing, high (> = 38°C) or low body temperature (<35.5°C), stopped feeding well, or movement only when stimulated] or critical illness (convulsions, not able to feed at all, or no movement at all), and referred them to a hospital for inpatient treatment. Infants whose caregivers refused referral received outpatient treatment. The case fatality ratio by day 15 was calculated for individual and combined clinical signs and stratified by place of treatment. An infant with signs of clinical severe infection or severe pneumonia was recategorised as having low- (case fatality ratio ≤2%) or moderate- (case fatality ratio >2%) mortality risk. RESULTS: Of 7129 young infants with a possible serious infection, fast breathing (in 7-59 days old) was the most prevalent sign (26%), followed by high body temperature (20%) and severe chest indrawing (19%). Infants with pneumonia had the lowest case fatality ratio (0.2%), followed by severe pneumonia (2.0%), clinical severe infection (2.3%) and critical illness (16.9%). Infants with clinical severe infection had a wide range of case fatality ratios for individual signs (from 0.8% to 11.0%). Infants with pneumonia had similar case fatality ratio for outpatient and inpatient treatment (0.2% vs. 0.3%, p = 0.74). Infants with clinical severe infection or severe pneumonia had a lower case fatality ratio among those who received outpatient treatment compared to inpatient treatment (1.9% vs. 6.5%, p<0.0001). We recategorised infants into low-mortality risk signs (case fatality ratio ≤2%) of clinical severe infection (high body temperature, or severe chest indrawing) or severe pneumonia and moderate-mortality risk signs (case fatality ratio >2%) (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection). We found that both categories had four times lower case fatality ratio when treated as outpatient than inpatient treatment, i.e., 1.0% vs. 4.0% (p<0.0001) and 5.3% vs. 22.4% (p<0.0001), respectively. In contrast, infants with signs of critical illness had nearly two times higher case fatality ratio when treated as outpatient versus inpatient treatment (21.7% vs. 12.1%, p = 0.097). CONCLUSIONS: The mortality risk differs with clinical signs. Young infants with a possible serious infection can be grouped into those with low-mortality risk signs (high body temperature, or severe chest indrawing or severe pneumonia); moderate-mortality risk signs (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection), or high-mortality risk signs (signs of critical illness). New treatment strategies that consider differential mortality risks for the place of treatment and duration of inpatient treatment could be developed and evaluated based on these findings. CLINICAL TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

Long-term mortality due to infection associated with elevated liver enzymes: a population-based cohort study.

We aimed to investigate whether elevated liver enzymes in the adult population were associated with mortality due to infection. As a population-based cohort study, data from the National Health Insurance Service Health Screening Cohort were used. Adult individuals (aged ≥ 40 years) who underwent standardized medical examination between 2002 and 2003 were included, and infectious mortality was defined as mortality due to infection between 2004 and 2015. Aspartate transaminase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), AST/ALT ratio, and dynamic AST/ALT ratio (dAAR) were included in multivariable Cox modeling. A total of 512,746 individuals were included in this study. Infectious mortality occurred in 2444 individuals (0.5%). In the multivariable model, moderate and severe elevation in AST was associated with 1.94-fold [hazard ratio (HR):1.94, 95% confidence interval (CI) 1.71-2.19; P < 0.001] and 3.93-fold (HR: 3.93, 95% CI 3.05-5.07; P < 0.001) higher infectious mortality respectively, compared with the normal AST group. Similar results were observed for moderate and severe elevation in ALT and mild, moderate, and severe elevation in γ-GTP. Additionally, a 1-point increase in the AST/ALT ratio and dAAR was associated with higher infection mortality. Elevated liver enzymes (AST, ALT, AST/ALT ratio, γ-GTP, and dAAR) were associated with increased infectious mortality.

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.

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.

Inhibitor of BRAFV600E Mutation as a Treatment Option for Hairy Cell Leukemia With Deep Neutropenia and Infectious Complications.

Standard therapy in hairy cell leukemia (HCL) is often impossible at the time of deep neutropenia/agranulocytosis with or without infectious complications; it is thus a complex therapeutic problem. Vemurafenib has been used to treat resistant HCL since 2012. Because vemurafenib does not have a myelotoxic effect, we thought that it could be used to treat HCL associated with deep neutropenia/agranulocytosis with or without the development of infectious complications as a preliminary stage before treatment with cladribine. We conducted a retrospective analysis of treatment with vemurafenib followed by a standard course of cladribine provided to 22 patients with deep neutropenia/agranulocytosis with or without infectious complications at diagnosis. Vemurafenib was provided to 22 patients with HCL. The response to therapy was evaluated by complete blood cell count (absolute neutrophil count [ANC], hemoglobin concentration, platelet count, absence of hairy cells), spleen size (assessed by ultrasound), and reduce infectious complications. After that, a standard course of cladribine was provided. Among the 22 patients, the male/female sex ratio was 2:1, and median (range) age was 52 (24-78) years. There were 7 patients with severe infectious manifestations admitted to the intensive care unit, including 1 patient during extracorporeal membrane oxygenation. The median (range) ANC at diagnosis was 0.3 (0.04-0.7) × 109/L. Vemurafenib was provided at a dosage of 240 mg 1 or 2 times a day. In 20 patients, vemurafenib was provided for 3 months or more. In 1 case, the effect was not obtained during 1 month of treatment, and the patient died from severe infectious complications during prolonged agranulocytosis. In 21 patients treated with vemurafenib, an increase of ANC was observed and the infectious complications resolved, thus allowing the application of cladribine therapy. After a standard course (0.1 mg/kg per day for 7 days) of cladribine chemotherapy, 18 patients (90%) experienced complete clinical remission and 2 patients (10%) experienced partial remission with residual splenomegaly. In 1 patient, vemurafenib therapy was still ongoing 2 months after initiating therapy. In cases of proven BRAFV600E mutation, vemurafenib can be successfully used as an effective preliminary therapy in patients with deep neutropenia/agranulocytosis with or without infectious complications before standard therapy with purine analogs.

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.

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.