Highlights • Results of a 6-year multicenter surveillance on the application of “JACE” for treatment of burns over 30% total body surface area were analyzed. • The surveillance included 118 Japanese ...hospitals, with 216 patients and 718 graft sites. • The mean cultural epidermal autograft (CEA) take rates at week 4 were 66% (sites) and 68% (patients). • Artificial dermis provided an adequate wound bed. • Application of CEA in combination with wide split-thickness auto or patch autograft increased the CEA take rate.
Abstract
Background
Trends in the incidence and outcomes of sepsis using a Japanese nationwide database were investigated.
Methods
This was a retrospective cohort study. Adult patients, who had both ...presumed serious infections and acute organ dysfunction, between 2010 and 2017 were extracted using a combined method of administrative and electronic health record data from the Japanese nationwide medical claim database, which covered 71.5% of all acute care hospitals in 2017. Presumed serious infection was defined using blood culture test records and antibiotic administration. Acute organ dysfunction was defined using records of diagnosis according to the international statistical classification of diseases and related health problems, 10th revision, and records of organ support. The primary outcomes were the annual incidence of sepsis and death in sepsis per 1000 inpatients. The secondary outcomes were in-hospital mortality rate and length of hospital stay in patients with sepsis.
Results
The analyzed dataset included 50,490,128 adult inpatients admitted between 2010 and 2017. Of these, 2,043,073 (4.0%) patients had sepsis. During the 8-year period, the annual proportion of patients with sepsis across inpatients significantly increased (slope = + 0.30%/year,
P
< 0.0001), accounting for 4.9% of the total inpatients in 2017. The annual death rate of sepsis per 1000 inpatients significantly increased (slope = + 1.8/1000 inpatients year,
P
= 0.0001), accounting for 7.8 deaths per 1000 inpatients in 2017. The in-hospital mortality rate and median (interquartile range) length of hospital stay significantly decreased (
P
< 0.001) over the study period and were 18.3% and 27 (15–50) days in 2017, respectively.
Conclusions
The Japanese nationwide data indicate that the annual incidence of sepsis and death in inpatients with sepsis significantly increased; however, the annual mortality rates and length of hospital stay in patients with sepsis significantly decreased. The increasing incidence of sepsis and death in sepsis appear to be a significant and ongoing issue.
Induced pluripotent stem cells (iPSCs) can now be produced from various somatic cell (SC) lines by ectopic expression of the four transcription factors. Although the procedure has been demonstrated ...to induce global change in gene and microRNA expressions and even epigenetic modification, it remains largely unknown how this transcription factor-induced reprogramming affects the total glycan repertoire expressed on the cells. Here we performed a comprehensive glycan analysis using 114 types of human iPSCs generated from five different SCs and compared their glycomes with those of human embryonic stem cells (ESCs; nine cell types) using a high density lectin microarray. In unsupervised cluster analysis of the results obtained by lectin microarray, both undifferentiated iPSCs and ESCs were clustered as one large group. However, they were clearly separated from the group of differentiated SCs, whereas all of the four SCs had apparently distinct glycome profiles from one another, demonstrating that SCs with originally distinct glycan profiles have acquired those similar to ESCs upon induction of pluripotency. Thirty-eight lectins discriminating between SCs and iPSCs/ESCs were statistically selected, and characteristic features of the pluripotent state were then obtained at the level of the cellular glycome. The expression profiles of relevant glycosyltransferase genes agreed well with the results obtained by lectin microarray. Among the 38 lectins, rBC2LCN was found to detect only undifferentiated iPSCs/ESCs and not differentiated SCs. Hence, the high density lectin microarray has proved to be valid for not only comprehensive analysis of glycans but also diagnosis of stem cells under the concept of the cellular glycome.
Ventilator-associated pneumonia (VAP) is a common and serious problem in intensive care units (ICUs). Several studies have suggested that the Gram stain of endotracheal aspirates is a useful method ...for accurately diagnosing VAP. However, the usefulness of the Gram stain in predicting which microorganisms cause VAP has not been established. The purpose of this study was to evaluate whether a Gram stain of endotracheal aspirates could be used to determine appropriate initial antimicrobial therapy for VAP.
Data on consecutive episodes of microbiologically confirmed VAP were collected from February 2013 to February 2016 in the ICU of a tertiary care hospital in Japan. We constructed two hypothetical empirical antimicrobial treatment algorithms for VAP: a guidelines-based algorithm (GLBA) based on the recommendations of the American Thoracic Society-Infectious Diseases Society of America (ATS-IDSA) guidelines and a Gram stain-based algorithm (GSBA) which limited the choice of initial antimicrobials according to the results of bedside Gram stains. The GLBA and the GSBA were retrospectively reviewed for each VAP episode. The initial coverage rates and the selection of broad-spectrum antimicrobial agents were compared between the two algorithms.
During the study period, 219 suspected VAP episodes were observed and 131 episodes were assessed for analysis. Appropriate antimicrobial coverage rates were not significantly different between the two algorithms (GLBA 95.4% versus GSBA 92.4%; p = 0.134). The number of episodes for which antimethicillin-resistant Staphylococcus aureus agents were selected as an initial treatment was larger in the GLBA than in the GSBA (71.0% versus 31.3%; p < 0.001), as were the number of episodes for which antipseudomonal agents were recommended as an initial treatment (70.2% versus 51.9%; p < 0.001).
Antimicrobial treatment based on Gram stain results may restrict the administration of broad-spectrum antimicrobial agents without increasing the risk of treatment failure.
UMIN-CTR, UMIN000026457 . Registered 8 March 2017 (retrospectively registered).
The gut is an important target organ for stress caused by severe insults such as sepsis, trauma, burn, shock, bleeding and infection. Severe insult to the gut is considered to have an important role ...in promoting infectious complications and multiple organ dysfunction syndrome. These are sequelae of interactions between deteriorated intestinal epithelium, the immune system and commensal bacteria. The gut is the “motor” of multiple organ failure, and now it is recognized that gut dysfunction is a causative factor in disease progression. The gut flora and environment are significantly altered in critically ill patients, and the number of obligate anaerobes is associated with prognosis. Synbiotic therapy is a combination of probiotics and prebiotics. Probiotic, prebiotic and synbiotic treatment has been shown to be a promising therapy to maintain and repair the gut microbiota and gut environment. In the critically ill, such as major abdominal surgery, trauma and ICU patients, synbiotic therapy has been shown to significantly reduce septic complications. Further basic and clinical research would clarify the underlying mechanisms of the therapeutic effect of probiotic/synbiotic treatment and define the appropriate conditions for use.
Background The appropriate duration of antibiotic treatment in patients with bacterial sepsis remains unclear. The purpose of this study was to evaluate the association of a shorter course of ...antibiotics on 28-day mortality in comparison with a longer course using a national database in Japan. Methods We conducted a post hoc analysis from the retrospective observational study of patients with sepsis using a Japanese claims database from 2010 to 2017. The patient dataset was divided into short-course (less than or equai to 7 days) and long-course (greater than or equal to 8 days) groups according to the duration of initial antibiotic administration. Subsequently, propensity score matching was performed to adjust the baseline imbalance between the two groups. The primary outcome was 28-day mortality. The secondary outcomes were re-initiated antibiotics at 3 and 7 days, during hospitalization, administration period, antibiotic-free days, and medical cost. Results After propensity score matching, 448,146 pairs were analyzed. The 28-day mortality was significantly lower in the short-course group (hazard ratio, 0.94; 95% CI, 0.92-0.95; P < 0.001), while the occurrence of re-initiated antibiotics at 3 and 7 days and during hospitalization were significantly higher in the short-course group (P < 0.001). Antibiotic-free days (median IQR) were significantly shorter in the long-course group (21 days 17 days, 23 days vs. 17 days 14 days, 19 days, P < 0.001), and short-course administration contributed to a decrease in medical costs (coefficient $-212, 95% CI; - 223 to - 201, P < 0.001). Subgroup analyses showed a significant decrease in the 28-day mortality of the patients in the short-course group in patients of male sex (hazard ratio: 0.91, 95% CI; 0.89-0.93), community-onset sepsis (hazard ratio; 0.95, 95% CI; 0.93-0.98), abdominal infection (hazard ratio; 0.92, 95% CI; 0.88-0.97) and heart infection (hazard ratio; 0.74, 95% CI; 0.61-0.90), while a significant increase was observed in patients with non-community-onset sepsis (hazard ratio; 1.09, 95% CI; 1.06-1.12). Conclusions The 28-day mortality was significantly lower in the short-course group, even though there was a higher rate of re-initiated antibiotics in the short course. Keywords: Sepsis, Antibiotics, Duration of treatment, Short-course
A substantial number of sepsis patients require specialized care, including multidisciplinary care, close monitoring, and artificial organ support in the intensive care unit (ICU). However, the ...efficacy of ICU management on clinical outcomes remains insufficiently researched. Therefore, we tested the hypothesis that ICU admission would increase the survival rate among sepsis patients.
We conducted a retrospective study using the nationwide medical claims database of sepsis patients in Japan from 2010 to 2017 with propensity score matching to adjust for baseline imbalances. Patients aged over 20 years, with a combined diagnosis of presumed serious infection and organ failure, were included in this study. The primary outcome studied was the in-hospital mortality among non-ICU and ICU patients. In addition to propensity score matching, we performed a multivariable logistic regression analysis for the primary outcome. As the treatment policy was not extracted from the database, we performed sensitivity analyses to determine mortality differences in adults (20 ≤ age ≤ 64), independent patients, patients without malignant tumors, based on the assumption that treatment intensity is likely to increase in those population.
Among 1,167,901 sepsis patients (974,289 in non-ICU and 193,612 in ICU settings), the unadjusted in-hospital mortality was 22.5% among non-ICU patients and 26.2% among ICU patients (3.7% 95% CI 3.5-3.9). After propensity score matching, the in-hospital mortality was 29.2% among non-ICU patients and 25.8% among ICU patients (Formula: see text 3.4% 95% CI Formula: see text 3.7 to Formula: see text 3.1). In-hospital mortality with a multivariable regression analysis (Formula: see text 5.0% 95% CI Formula: see text 5.2 to Formula: see text 4.8) was comparable with the results of the propensity score matching analysis. In the sensitivity analyses, the mortality differences between non-ICU and ICU in adults, independent patients, and patients without malignant tumors were Formula: see text 2.7% 95% CI Formula: see text 3.3 to Formula: see text 2.2, Formula: see text 5.8% 95% CI Formula: see text 6.4 to Formula: see text 5.2, and Formula: see text 1.3% 95% CI Formula: see text 1.7 to Formula: see text 1.0, respectively.
Herein, using the nationwide medical claims database, we demonstrated that ICU admission was potentially associated with decreasing in-hospital mortality among sepsis patients. Further investigations are warranted to validate these results and elucidate the mechanisms favoring ICU management on clinical outcomes.
Background Sepsis is the leading cause of death worldwide. Although the mortality of sepsis patients has been decreasing over the past decade, the trend of medical costs and cost-effectiveness for ...sepsis treatment remains insufficiently determined. Methods We conducted a retrospective study using the nationwide medical claims database of sepsis patients in Japan between 2010 and 2017. After selecting sepsis patients with a combined diagnosis of presumed serious infection and organ failure, patients over the age of 20 were included in this study. We investigated the annual trend of medical costs during the study period. The primary outcome was the annual trend of the effective cost per survivor, calculated from the gross medical cost and number of survivors per year. Subsequently, we performed subgroup and multiple regression analyses to evaluate the association between the annual trend and medical costs. Results Among 50,490,128 adult patients with claims, a total of 1,276,678 patients with sepsis were selected from the database. Yearly gross medical costs to treat sepsis gradually increased over the decade from $3.04 billion in 2010 to $4.38 billion in 2017, whereas the total medical cost per hospitalization declined (rate = - $1075/year, p < 0.0001). While the survival rate of sepsis patients improved during the study period, the effective cost per survivor significantly decreased (rate = - $1806/year 95% CI - $2432 to - $1179, p = 0.001). In the subgroup analysis, the trend of decreasing medical cost per hospitalization remained consistent among the subpopulation of age, sex, and site of infection. After adjusting for age, sex (male), number of chronic diseases, site of infection, intensive care unit (ICU) admission, surgery, and length of hospital stay, the admission year was significantly associated with reduced medical costs. Conclusions We demonstrated an improvement in annual cost-effectiveness in patients with sepsis between 2010 and 2017. The annual trend of reduced costs was consistent after adjustment with the confounders altering hospital expenses. Keywords: Medical cost, Cost-effectiveness, Sepsis, Diagnosis procedure combination, Critical care
The benefits and harm caused by anticoagulant treatments for sepsis induced disseminated intravascular coagulation (DIC) remain unclear. Therefore, we performed a network meta-analysis to assess the ...effect of available anticoagulant treatments on patient mortality, DIC resolution and the incidence of bleeding complication in patients with septic DIC.
We considered all studies from four recent systematic reviews and searched the PubMed, MEDLINE, and Cochrane databases for other studies that investigated anticoagulant treatment for septic DIC using antithrombin, thrombomodulin, heparin, or protease inhibitors in adult critically ill patients. These four anticoagulants and placebo were compared. The primary outcome in this study was patient mortality, and the secondary outcomes were the DIC resolution rate and incidence of bleeding complications.
The network meta-analysis included 1340 patients from nine studies. There were no significant differences in the risks of mortality and bleeding complications among all direct comparisons and the network meta-analysis. Using a placebo was associated with a significantly lower rate of DIC resolution, compared to antithrombin in the direct comparison (odds ratio OR: 0.20, 95% credible interval 95% CrI: 0.046–0.81) and in the network meta-analysis (OR: 0.20, 95% CrI: 0.043–0.84).
Our study revealed no significant differences in the risks for mortality and bleeding complications when a placebo and all four anticoagulants were compared in septic DIC patients. The results also indicated that antithrombin was associated with a five-fold higher likelihood of DIC resolution, compared to placebo.
•We performed a network meta-analysis to assess effect of anticoagulants in septic DIC.•Risks of mortality and complications were similar among 4 anticoagulants and placebo.•There is insufficient evidence regarding the effects of anticoagulants for septic DIC.
This study demonstrates that podocalyxin, a heavily glycosylated type 1 transmembrane protein, is a glycoprotein ligand of rBC2LCN on human induced pluripotent stem (iPS) cells and embryonic stem ...(ES) cells. When analyzed by DNA microarray, podocalyxin was found to be highly expressed in both iPS cells and ES cells. The carbohydrate antigens of rBC2LCN are expressed on O‐glycans of podocalyxin, since alkaline hydrolysis greatly reduced the binding of rBC2LCN to human iPS cells and ES cells. rBC2LCN bound to an O‐glycan carrying H type 3 epitope structure isolated from iPS cells, suggesting that H type 3 is a novel pluripotency glycan marker.
In comprehensive glycome analysis with a high‐density lectin microarray, we have previously shown that the recombinant N‐terminal domain of the lectin BC2L‐C from Burkholderia cenocepacia (rBC2LCN) binds exclusively to undifferentiated human induced pluripotent stem (iPS) cells and embryonic stem (ES) cells but not to differentiated somatic cells. Here we demonstrate that podocalyxin, a heavily glycosylated type 1 transmembrane protein, is a glycoprotein ligand of rBC2LCN on human iPS cells and ES cells. When analyzed by DNA microarray, podocalyxin was found to be highly expressed in both iPS cells and ES cells. Western and lectin blotting revealed that rBC2LCN binds to podocalyxin with a high molecular weight of more than 240 kDa in undifferentiated iPS cells of six different origins and four ES cell lines, but no binding was observed in either differentiated mouse feeder cells or somatic cells. The specific binding of rBC2LCN to podocalyxin prepared from a large set of iPS cells (138 types) and ES cells (15 types) was also confirmed using a high‐throughput antibody‐overlay lectin microarray. Alkaline digestion greatly reduced the binding of rBC2LCN to podocalyxin, indicating that the major glycan ligands of rBC2LCN are presented on O‐glycans. Furthermore, rBC2LCN was found to exhibit significant affinity to a branched O‐glycan comprising an H type 3 structure (Ka, 2.5 × 104 M−1) prepared from human 201B7 iPS cells, indicating that H type 3 is a most probable potential pluripotency marker. We conclude that podocalyxin is a glycoprotein ligand of rBC2LCN on human iPS cells and ES cells.
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