The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J‐SSCG 2020), a Japanese‐specific set of clinical practice guidelines for sepsis and septic shock created as revised from J‐SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English‐language version of these guidelines was created based on the contents of the original Japanese‐language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high‐quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J‐SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU‐acquired weakness [ICU‐AW], post‐intensive care syndrome [PICS], and body temperature management). The J‐SSCG 2020 covered a total of 22 areas with four additional new areas (patient‐ and family‐centered care, sepsis treatment system, neuro‐intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large‐scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE‐based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J‐SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

Age is an independent risk factor of multiple organ failure in patients with sepsis. However, the age-related mechanisms of injury are not known. AMPK is a crucial regulator of energy homeostasis, which controls mitochondrial biogenesis by activation of peroxisome proliferator-activated receptor-γ coactivator-α (PGC-1α) and disposal of defective organelles by autophagy. We investigated whether AMPK dysregulation might contribute to age-dependent liver injury in young (2-3 mo) and mature male mice (11-13 mo) subjected to sepsis. Liver damage was higher in mature mice than in young mice and was associated with impairment of hepatocyte mitochondrial function, structure, and biogenesis and reduced autophagy. At molecular analysis, there was a time-dependent nuclear translocation of the active phosphorylated catalytic subunits AMPKα1/α2 and PGC-1α in young, but not in mature, mice after sepsis. Treatment with the AMPK activator 5-amino-4-imidazolecarboxamide riboside-1-β-d-ribofuranoside (AICAR) improved liver mitochondrial structure in both age groups compared with vehicle. In loss-of-function studies, young knockout mice with systemic deficiency of AMPKα1 exhibited greater liver injury than did wild-type mice after sepsis. Our study suggests that AMPK is important for liver metabolic recovery during sepsis. Although its function may diminish with age, pharmacological activation of AMPK may be of therapeutic benefit.-Inata, Y., Kikuchi, S., Samraj, R. S., Hake, P. W., O'Connor, M., Ledford, J. R., O'Connor, J., Lahni, P., Wolfe, V., Piraino, G., Zingarelli, B. Autophagy and mitochondrial biogenesis impairment contribute to age-dependent liver injury in experimental sepsis: dysregulation of AMP-activated protein kinase pathway.

Age represents a major risk factor for multiple organ failure, including cardiac dysfunction, in patients with sepsis. AMP-activated protein kinase (AMPK) is a crucial regulator of energy homeostasis that controls mitochondrial biogenesis by activation of peroxisome proliferator-activated receptor-γ coactivator-1α and disposal of defective organelles by autophagy. We investigated whether AMPK dysregulation contributes to age-dependent cardiac injury in young (2-3 mo) and mature adult (11-13 mo) male mice subjected to sepsis by cecal ligation and puncture and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside affords cardioprotective effects. Plasma proinflammatory cytokines and myokine follistatin were similarly elevated in vehicle-treated young and mature adult mice at 18 h after sepsis. However, despite equivalent troponin I and T levels compared with similarly treated young mice, vehicle-treated mature adult mice exhibited more severe cardiac damage by light and electron microscopy analyses with more marked intercellular edema, inflammatory cell infiltration, and mitochondrial derangement. Echocardiography revealed that vehicle-treated young mice exhibited left ventricular dysfunction after sepsis, whereas mature adult mice exhibited a reduction in stroke volume without apparent changes in load-dependent indexes of cardiac function. At molecular analysis, phosphorylation of the catalytic subunits AMPK-α/α was associated with nuclear translocation of peroxisome proliferator-activated receptor-γ coactivator-1α in vehicle-treated young but not mature adult mice. Treatment with 5-amino-4-imidazole carboxamide riboside ameliorated cardiac architecture derangement in mice of both ages. These cardioprotective effects were associated with attenuation of the systemic inflammatory response and amelioration of cardiac dysfunction in young mice only, not in mature adult animals. NEW & NOTEWORTHY Our data suggest that sepsis-induced cardiac dysfunction manifests with age-dependent characteristics, which are associated with a distinct regulation of AMP-activated protein kinase-dependent metabolic pathways. Consistent with this age-related deterioration, pharmacological activation of AMP-activated protein kinase may afford cardioprotective effects allowing a partial recovery of cardiac function in young but not mature age.

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We performed a retrospective, observational study of patients who had spent > 14 days in the paediatric intensive care unit (PICU) of our hospital from 2011 to 2013. Specifically, long-term mortality, functional outcome, and PICU resource occupancy were examined. All prolonged-stay patients in our study were < 15 years of age. Favourable outcomes were defined as a Pediatric Overall Performance Category (POPC) score of 1-2, and unfavourable outcomes as a POPC score of 3-6 or death. During the study period, there were 1082 PICU admissions involving 805 patients, 111 (13.8%) of whom had one or more prolonged PICU stays. Among these patients, 100 (90%) survived to PICU discharge and 92 (83%) survived to hospital discharge. At the 3-year follow-up, the survival rate was 75% (77/102; nine patients were lost to follow-up) and the favourable outcome rate was 43% (44/ 102) (57% among survivors). Prolonged PICU-stay patients accounted for 50.5% of the PICU patient-days. Extremely prolonged stays (≥ 28 days) correlate with low favourable outcome rates (P = 0.03), but did not correlate with mortality rates (P = 0.16).Conclusion: Although prolonged PICU-stay patients utilized many PICU resources, most survived at least 3 years, and > 50% of the survivors had a favourable functional outcome (POPC score). What is Known:• The number of patients with prolonged paediatric intensive care unit (PICU) stays is increasing.• These patients utilize many resources and are at high risk for mortality and disabilities. What is New:• Although prolonged-stay patients accounted for 50% of PICU patient-days, their 3-year survival rate and favourable functional outcome rate (based on Pediatric Overall Performance Category scores) were relatively high. • Extremely prolonged stays (≥ 28 days) correlate with low favourable functional outcomes but not with mortality.

Objectives:Healthcare-associated infections after pediatric cardiac surgery are significant causes of morbidity and mortality. We aimed to identify the risk factors for the occurrence of healthcare-associated infections after pediatric cardiac surgery.Design:Retrospective, single-center observational study.Setting:PICU at a tertiary children’s hospital.Patients:Consecutive pediatric patients less than or equal to 18 years old admitted to the PICU after cardiac surgery, between January 2013 and December 2015.Interventions:None.Measurements and Main Results:All the data were retrospectively collected from the medical records of patients. We assessed the first surgery during a single PICU stay and identified four common healthcare-associated infections, including bloodstream infection, surgical site infection, pneumonia, and urinary tract infection, according to the definitions of the Centers for Disease Control and Prevention and National Healthcare Safety Network. We assessed the pre-, intra-, and early postoperative potential risk factors for these healthcare-associated infections via multivariable analysis. In total, 526 cardiac surgeries (394 patients) were included. We identified 81 cases of healthcare-associated infections, including, bloodstream infections (n = 30), surgical site infections (n = 30), urinary tract infections (n = 13), and pneumonia (n = 8). In the case of 71 of the surgeries (13.5%), at least one healthcare-associated infection was reported. Multivariable analysis indicated the following risk factors for postoperative healthcare-associated infections: mechanical ventilation greater than or equal to 3 days (odds ratio, 4.81; 95% CI, 1.89–12.8), dopamine use (odds ratio, 3.87; 95% CI, 1.53–10.3), genetic abnormality (odds ratio, 2.53; 95% CI, 1.17–5.45), and delayed sternal closure (odds ratio, 3.78; 95% CI, 1.16–12.8).Conclusions:Mechanical ventilation greater than or equal to 3 days, dopamine use, genetic abnormality, and delayed sternal closure were associated with healthcare-associated infections after pediatric cardiac surgery. Since the use of dopamine is an easily modifiable risk factor, and may serve as a potential target to reduce healthcare-associated infections, further studies are needed to establish whether dopamine negatively impacts the development of healthcare-associated infections.

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