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Background The incidence of accidental hypothermia (AH) is low, and the length of hospital stay in patients with AH remains poorly understood. The present study explored which factors were related to prolonged hospitalization among patients with AH using Japan's nationwide registry data. Methods The data from the Hypothermia STUDY 2018, which included patients ≥18 years old with a body temperature ≤ 35 °C, were obtained from a multicenter registry for AH conducted at 89 institutions throughout Japan, collected from December 1, 2018, to February 28, 2019. The patients were divided into a “short-stay patients” group (within 7 days) and “long-stay patients” group (more than 7 days). A logistic regression analysis after multiple imputation was performed to obtain odds ratios (ORs) for prolonged hospitalization with age, frailty, location, causes underlying the hypothermia, temperature, pH, potassium level, and disseminated intravascular coagulation (DIC) score as independent variables. Results In total, 656 patients were included in the study, of which 362 were eligible for the analysis. The median length of hospital stay was 17 days. Of the 362 patients, 265 (73.2%) stayed in the hospital for more than 7 days. The factors associated with prolonged hospitalization were frailty (OR, 2.11; 95% confidence interval [CI], 1.09–4.10; p = 0.027), the occurrence of indoor (OR, 3.20; 95% CI, 1.58–6.46; p = 0.001), alcohol intoxication (OR, 0.17; 95% CI, 0.05–0.56; p = 0.004), pH (OR, 0.07; 95% CI, 0.01–0.76; p = 0.029), potassium level (OR, 1.36; 95% CI, 1.00–1.85; p = 0.048), and DIC score (OR, 1.54; 95% CI, 1.13–2.10; p = 0.006). Conclusions Frailty, indoor situation, alcohol intoxication, pH value, potassium level, and DIC score were factors contributing to prolonged hospitalization in patients with AH. Preventing frailty may help reduce the length of hospital stay in patients with AH. In addition, measuring the pH value and potassium level by an arterial blood gas analysis at the ED is recommended for the early evaluation of AH.

We previously showed that Lactobacillus brevis-derived polyphosphate (poly P) exerts a curative effect on intestinal inflammation. However, whether or not poly P improves the inflammation and injury of distant organs remains unclear. We aimed to investigate the change in the intestinal microbiome and to evaluate the protective effect of poly P on injuries in a cerulein-induced acute pancreatitis (AP) mouse. Poly P was orally administered to BALB/C mice every day for 24 days, and then mice were intraperitoneally injected with cerulein. Before cerulein injection, stool samples were collected and analyzed by 16S rRNA gene sequencing. Mice were sacrificed at 24 h after the last cerulein injection; subsequently, the serum, pancreas, and colon were collected. The microbial profile differed markedly between poly P and control group. Notably, the levels of beneficial bacteria, including Alistipes and Candidatus_Saccharimonas, were significantly increased, while those of the virulent bacteria Desulfovibrio were decreased in the poly P group. The elevations of the serum amylase and lipase levels by cerulein treatment were suppressed by the pre-administration of poly P for 24 days, but not for 7 days. The numbers of cells MPO-positive by immunohistology were decreased and the levels of MCP-1 significantly reduced in the AP + Poly P group. An immunofluorescence analysis showed that the ZO-1 and occludin in the colon was strongly augmented in the epithelial cell membrane layer in the AP + Poly P group. Poly P attenuates AP through both modification of the intestinal microbiome and enhancement of the intestinal barrier integrity.

Background Hypothermia triggers coagulation, which can lead to the development of a life-threatening condition. We previously reported that hypothermia induces platelet activation in the spleen, resulting in microthrombosis after rewarming. However, the changes in whole blood clotting properties that occur remain unclear. Using thromboelastography, we investigated blood clotting activity and the effects of rewarming in a murine model of hypothermia. Methods C57Bl/6 mice were exposed to an ambient temperature of −20 °C under general anesthesia until their rectal temperature decreased to 15 °C. One group of mice was kept at 4 °C for 2 h and then euthanized. Another group was rewarmed, kept in normal conditions for 24 h, and then euthanized. Tissue and citrated whole blood samples were obtained from the mice for histopathological analysis, flow cytometry, and thromboelastography. Results Hypothermia induced the activation of platelets in the spleen; however, rewarming significantly reduced the number of activated platelets in the spleen while their numbers significantly increased in peripheral blood. In hypothermic mice not subjected to rewarming, no increase in activated platelets was observed in peripheral blood. Thromboelastography analysis showed that whole blood samples from the rewarmed mice displayed an enhanced clotting strength. Conclusions Rewarming from hypothermia enhances whole blood coagulation activity accompanied by an increase in the number of active platelets in peripheral blood. This phenomenon may lead to formation of microthrombi and thrombotic disorders.

Pancreatic cancer is associated with a poor prognosis due to challenges in early detection, severe progression of the primary tumor, metastatic lesions, and resistance to antitumor agents. However, previous studies have indicated a relationship between the microbiome and pancreatic cancer outcomes. Our previous study demonstrated that ferrichrome derived from Lactobacillus casei, a probiotic bacteria, exhibited tumor‑suppressive effects in colorectal and gastric cancer, and that the suppressive effects were stronger than conventional antitumor agents, such as 5‑fluorouracil (5‑FU) and cisplatin, suggesting that certain probiotics exert antitumorigenic effects. However, whether or not probiotic‑derived molecules, including ferrichrome, exert a tumor‑suppressive effect in other gastrointestinal tumors, such as pancreatic cancer, remains unclear. In the present study, it was demonstrated that probiotic‑derived ferrichrome inhibited the growth of pancreatic cancer cells, and its tumor‑suppressive effects were further revealed in 5‑FU‑resistant pancreatic cancer cells in vitro and in vivo in a mouse xenograft model. Ferrichrome inhibited the progression of cancer cells via dysregulation of the cell cycle by activating p53. DNA fragmentation and cleavage of poly (ADP‑ribose) polymerase were induced by ferrichrome treatment, suggesting that ferrichrome induced apoptosis in pancreatic cancer cells. A transcriptome analysis revealed that the expression p53‑associated mRNAs was significantly altered by ferrichrome treatment. Thus, the tumor‑suppressive effects of probiotics may mediated by probiotic‑derived molecules, such as ferrichrome, which may have applications as an antitumor drug, even in refractory and 5‑FU‑resistant pancreatic cancer.

To elucidate the effectiveness of extracorporeal membrane oxygenation (ECMO) in accidental hypothermia (AH) patients with and without cardiac arrest (CA), including details of complications.This study was a multicentre, prospective, observational study of AH in Japan. All adult (aged ≥18 years) AH patients with body temperature ≤32 °C who presented to the emergency department between December 2019 and March 2022 were included. Among the patients, those with CA or circulatory instability, defined as severe AH, were selected and divided into the ECMO and non-ECMO groups. We compared 28-day survival and favourable neurological outcomes at discharge between the ECMO and non-ECMO groups by adjusting for the patients' background characteristics using multivariable logistic regression analysis.Among the 499 patients in this study, 242 patients with severe AH were included in the analysis: 41 in the ECMO group and 201 in the non-ECMO group. Multivariable analysis showed that the ECMO group was significantly associated with better 28-day survival and favourable neurological outcomes at discharge in patients with CA compared to the non-ECMO group (odds ratio [OR] 0.17, 95% confidence interval [CI]: 0.05-0.58, and OR 0.22, 95%CI: 0.06-0.81). However, in patients without CA, ECMO not only did not improve 28-day survival and neurological outcomes, but also decreased the number of event-free days (ICU-, ventilator-, and catecholamine administration-free days) and increased the frequency of bleeding complications.ECMO improved survival and neurological outcomes in AH patients with CA, but not in AH patients without CA.

Frostbite occurs when the skin is exposed to localized low temperatures. The main causes of frostbite are thought to be direct cell injury due to freezing of cells and tissue ischemia due to abnormal blood circulation. However, the molecular mechanism of frostbite has not been elucidated. This study aims to explain the molecular dynamics of frostbite using a mouse frostbite model and keratinocyte cell culture. Comprehensive gene expression analysis performed on mouse skin samples revealed that β-catenin signaling is activated by frostbite. Immunohistochemistry showed nuclear translocation of β-catenin in the skin of frostbite model mice that was not observed in mice subjected to a mechanical skin damage model induced by tape stripping. Tissue hypoxia, as detected by pimonidazole staining, coexisted with nuclear expression of β-catenin. In keratinocyte cell cultures, nuclear translocation of β-catenin was induced by hypoxia, but not by low temperature. Hypoxia induced epithelial-mesenchymal transition - an important biological event in the healing process of skin - and in vitro wound-healing activity, both of which were suppressed by β-catenin inhibition. Our results suggest that during frostbite, impaired blood flow causes hypoxia, which in turn activates β-catenin that promotes keratinocyte motility and tissue repair.

To assess heat stroke and heat exhaustion occurrence and response during the coronavirus disease 2019 pandemic in Japan.This retrospective, multicenter, registry-based study describes and compares the characteristics of patients between the months of July and September in 2019 and 2020. Factors affecting heat stroke and heat exhaustion were statistically analyzed. Cramér's V was calculated to determine the effect size for group comparisons. We also investigated the prevalence of mask wearing and details of different cooling methods.No significant differences were observed between 2019 and 2020. In both years, in-hospital mortality rates just exceeded 8%. Individuals65 years old comprised 50% of cases and non-exertional onset (office work and everyday life) comprised 60%-70%, respectively. The recommendations from the Working Group on Heat Stroke Medicine given during the coronavirus disease pandemic in 2019 had a significant impact on the choice of cooling methods. The percentage of cases, for which intravascular temperature management was performed and cooling blankets were used increased, whereas the percentage of cases in which evaporative plus convective cooling was performed decreased. A total of 49 cases of heat stroke in mask wearing were reported.Epidemiological assessments of heat stroke and heat exhaustion did not reveal significant changes between 2019 and 2020. The findings suggest that awareness campaigns regarding heat stroke prevention among the elderly in daily life should be continued in the coronavirus disease 2019 pandemic. In the future, it is also necessary to validate the recommendations of the Working Group on Heatstroke Medicine.

Background Accidental hypothermia (AH) sometimes leads to coagulation disorder, especially in severe AH. We previously demonstrated that intrasplenic platelet activation caused aberrant hemostasis and thrombus formation after rewarming in a murine AH model. However, no study has focused on the appropriate management of platelets causing coagulation activation after rewarming of AH. We investigated whether or not recombinant soluble thrombomodulin (rTM) can suppress thrombosis formation after rewarming using a rat AH model. Methods Wistar rats were exposed to an ambient temperature of −20 °C under general anesthesia until their rectal temperature decreased to 26 °C. The Hypo group rats (n = 5) were immediately euthanized, while the Hypo/Re group (n = 5) and rTM group rats (n = 5), which were administered rTM (1 mg/kg) via the tail vein, were rewarmed until the rectal temperature returned to 34 °C and then euthanized 6 h later. Tissue and blood samples were collected from all rats for histopathological and coagulation analyses at euthanasia. Results There was no significant change in the D-dimer level in the Hypo group rats, while the D-dimer level was significantly elevated at 6 h after rewarming in the Hypo/Re group rats (P = 0.015), and histopathology detected both fibrin and platelets in the renal glomerulus. However, the rTM group rats did not show any elevation of the D-dimer levels at 6 h after rewarming, and no fibrin was noted on histopathology. Conclusions rTM may be useful as an appropriate anticoagulant in cases of aberrant hemostasis after rewarming of AH.

Background Frailty has been associated with a risk of adverse outcomes, and mortality in patients with various conditions. However, there have been few studies on whether or not frailty is associated with mortality in patients with accidental hypothermia (AH). In this study, we aim to determine this association in patients with AH using Japan’s nationwide registry data. Methods The data from the Hypothermia STUDY 2018&19, which included patients of ≥18 years of age with a body temperature of ≤35 °C, were obtained from a multicenter registry for AH conducted at 120 institutions throughout Japan, collected from December 2018 to February 2019 and December 2019 to February 2020. The clinical frailty scale (CFS) score was used to determine the presence and degree of frailty. The primary outcome was the comparison of mortality between the frail and non-frail patient groups. Results In total, 1363 patients were included in the study, of which 920 were eligible for the analysis. The 920 patients were divided into the frail patient group (N = 221) and non-frail patient group (N = 699). After 30-days of hospitalization, 32.6% of frail patients and 20.6% of non-frail patients had died (p p p Conclusions This study showed that frailty was associated with mortality in patients with AH. Preventive interventions for frailty may help to avoid death caused by AH.

Highlights • There has been no consensus on the optimal therapy for isolated superior mesenteric arterial dissection (ISMAD). • ISMAD patients can be treated conservatively if there are no signs of an aneurysm, ulcer-like projection (ULP), and mesenteric ischemia. • When an aneurysm or ULP sign exists, endovascular stenting was able to preserve superior mesenteric artery blood flow with improvement of the dissection., Objectives Isolated superior mesenteric arterial dissection (ISMAD) is an uncommon type of arterial dissection and treated with surgery, stenting, or conservative management. This study aimed to evaluate the criteria for conservative therapy for ISMAD patients based on imaging findings. Methods Eighteen consecutive ISMAD patients without peritoneal irritation at onset were retrospectively studied. The decision to perform stenting was based on the emergence of peritoneal irritation, aneurysm, or mesenteric ischemia. Clinical manifestations, follow-up contrast-enhanced computed tomography (CECT) findings, and patient outcome were evaluated. Results Most patients (16, 89%) were successfully treated conservatively; two patients (11%) required endovascular stenting because of an aneurysm or ulcer-like projection (ULP) sign. The median duration of fasting and hospital stays was 3 (range, 1–8) and 9 (range, 4–34) days, respectively. On CECT, the median distance from the superior mesenteric artery (SMA) origin to the entry site was 12 mm (range, 5–35 mm), and the median length of dissection was 87.5 mm (range, 20–150 mm). Among 16 patients treated conservatively, serial imaging was obtained in 11 patients (69%), and disappearance of the dissection within 4 months occurred in five patients. Two patients treated with endovascular stent underwent follow-up CECT 1 year after onset, and there were no complications. Conclusions ISMAD patients without peritoneal irritation can be treated conservatively if there are no signs of an aneurysm, ULP, or mesenteric ischemia. When an aneurysm or ULP sign exists, endovascular stenting was able to preserve SMA blood flow with the improvement of the dissection.

In this study, we aimed to develop and validate a machine learning-based mortality prediction model for hospitalized heat-related illness patients. After 2393 hospitalized patients were extracted from a multicentered heat-related illness registry in Japan, subjects were divided into the training set for development (n = 1516, data from 2014, 2017–2019) and the test set (n = 877, data from 2020) for validation. Twenty-four variables including characteristics of patients, vital signs, and laboratory test data at hospital arrival were trained as predictor features for machine learning. The outcome was death during hospital stay. In validation, the developed machine learning models (logistic regression, support vector machine, random forest, XGBoost) demonstrated favorable performance for outcome prediction with significantly increased values of the area under the precision-recall curve (AUPR) of 0.415 [95% confidence interval (CI) 0.336–0.494], 0.395 [CI 0.318–0.472], 0.426 [CI 0.346–0.506], and 0.528 [CI 0.442–0.614], respectively, compared to that of the conventional acute physiology and chronic health evaluation (APACHE)-II score of 0.287 [CI 0.222–0.351] as a reference standard. The area under the receiver operating characteristic curve (AUROC) values were also high over 0.92 in all models, although there were no statistical differences compared to APACHE-II. This is the first demonstration of the potential of machine learning-based mortality prediction models for heat-related illnesses.

Aim This study describes the clinical characteristics and outcomes as well as the prognostic factors of patients with accidental hypothermia (AH) using Japan's nationwide registry data. Methods The Hypothermia study 2018 and 2019, which included patients aged 18 years or older with a body temperature of 35°C or less, was a multicenter registry conducted at 87 and 89 institutions throughout Japan, with data collected from December 2018 to February 2019 and December 2019 to February 2020, respectively. Results In total, 1363 patients were enrolled in the registry, of which 1194 were analyzed in this study. The median (interquartile range) age was 79 (68-87) years, and the median (interquartile range) body temperature at the emergency department was 30.8°C (28.4-33.6°C). Forty-three percent of patients with AH had a mild condition, 35.2% moderate, and 21.9% severe. AH occurred in an indoor setting in 73.4% and was caused by acute medical illness in 49.3% of patients. A total of 101 (8.5%) patients suffered from cardiopulmonary arrest on arrival at the hospital. The overall 30-day mortality rate was 24.5%, the median (interquartile range) intensive care unit stay was 4 (2-7) days, and the median (interquartile range) hospital stay was 13 (4-27) days. In the multivariable logistic analysis, the prognostic factors were age (≥75 years old), male, activities of daily living (needing total assistance), cause of AH (trauma, alcohol), Glasgow Coma Scale score, and potassium level (>5.5 mEq/L). Conclusion The mortality rate of AH was 24.5% in Japan. The prognostic factors developed in this study may be useful for the early prediction, prevention, and awareness of severe AH.

Background: Accidental hypothermia (AH) has a low frequency, and the length of hospital stay in patients with AH remains poorly understood. The present study explored which factors were related to long-term hospitalization among patients with AH using Japan’s nationwide registry data.Methods: The data from the Hypothermia STUDY 2018, which included patients ≥ 18 years old with a body temperature ≤ 35°C, were obtained from a multicenter registry for AH conducted at 89 institutions throughout Japan, collected from December 1, 2018, to February 28, 2019. The patients were divided into a “short-stay patients” group (within 7 days) and “long-stay patients” group (more than 7 days). A logistic regression analysis after multiple imputation was performed to obtain odds ratios (ORs) for prolonged hospitalization with age, frailty, cause of hypothermia, mechanism underlying hypothermia, temperature, pH, potassium level, and disseminated intravascular coagulation (DIC) score as independent variables.Results: In total, 656 patients were included in the study, of which 362 were eligible for the analysis. The median length of hospital stay was 17 days. Of the 362 patients, 265 (73.2%) stayed in the hospital for more than 7 days. The factors associated with prolonged hospitalization were frailty (OR, 2.11; 95% confidence interval [CI], 1.09-4.10; p = 0.027), the occurrence of indoor (OR, 3.20; 95% CI, 1.58-6.46; p = 0.001), alcohol intoxication (OR, 0.17; 95% CI, 0.05-0.56; p = 0.004), pH (OR, 0.07; 95% CI, 0.01-0.76; p = 0.029), potassium level (OR, 1.36; 95% CI, 1.00-1.85; p = 0.048), and DIC score (OR, 1.54; 95% CI, 1.13-2.10; p = 0.006). Conclusions: Frailty, indoor situation, alcohol intoxication, pH, potassium level, and DIC score were factors contributing to prolonged hospitalization in patients with AH. These factors can be valuable for the early detection of AH requiring a prolonged hospital stay.

Aim Heat‐related illness is common, but its epidemiology and pathological mechanism remain unclear. The aim of this study was to report current clinical characteristics, prognostic factors, and outcomes of heat‐related illness in Japan. Methods We undertook a prospective multicenter observational study in Japan. Only hospitalized patients with heat‐related illness were enrolled from 1 July to 30 September 2017 and 1 July to 30 September 2018. Results A total of 763 patients were enrolled in the study. Median age was 68 years (interquartile range, 49–82 years) and median body temperature on admission was 38.2°C (interquartile range, 36.8–39.8°C). Non‐exertional cause was 56.9% and exertional cause was 40.0%. The hospital mortality was 4.6%. The median Japanese Association for Acute Medicine disseminated intravascular coagulation (JAAM DIC), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on admission were 1 (0–2), 4 (2–6), and 13 (8–22), respectively. To predict hospital mortality, areas under the receiver operating characteristic curves were 0.776 (JAAM DIC score), 0.825 (SOFA), and 0.878 (APACHE II). There were 632 cases defined as heatstroke by JAAM heat‐related illness criteria, 73 cases diagnosed as having DIC. A total of 16.6% patients had poor neurological outcome (modified Rankin Scale ≥ 4) at hospital discharge. In the multivariate analysis, Glasgow Coma Scale and platelets were independent predictors of mortality. Type of heatstroke, Glasgow Coma Scale, and platelets were independent predictors of poor neurological outcome. Body temperature was not associated with mortality or poor neurological outcome. Conclusions In this study, hospital mortality of heat‐related illness was, Receiver operating characteristic curves of the Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and Japanese Association for Acute Medicine disseminated intravascular coagulation scores for predicting hospital mortality in cases of heat‐related illness in Japan.

Background Despite advances in the diagnosis of pancreatic ductal adenocarcinoma (PDA), histological evaluation of small and poorly defined masses in the pancreas is uncomfortable and unsafe. Methods We herein report a case of early stage PDA, in which multiple KRAS mutations were detected in the pancreatic juice preoperatively. A small hypoechoic area adjacent to the portal vein was detected through endoscopic ultrasound in the pancreatic body. KRAS mutations were evaluated using plasma, and the pancreatic juice by digital PCR. Results Pancreatic duct biopsy and pancreatic juice cytology were performed with no evidence of malignancy; however, KRAS mutations, KRAS G12V and G12D, were detected in the pancreatic juice. Histological assessment of the resected specimen demonstrated a solid tumor with desmoplastic reaction accompanied by carcinoma in situ in the main pancreatic duct where KRAS G12V mutation was identified. More detailed analysis demonstrated KRAS G12D mutation in the cluster of low grade pancreatic intraepithelial neoplasia, implying that the lesion developed independently. Conclusions Our study indicates the potential of “endoscopic liquid biopsy” to capture the driver gene for PDA diagnosis.

Aim This multicenter retrospective observational study aimed to evaluate the efficacy of extracorporeal membrane oxygenation (ECMO) support for septic patients with severe respiratory failure using propensity score analyses. Methods The data of severe sepsis patients from 42 intensive care units between January 2011 and December 2013 were retrospectively collected. Propensity score matching analyses were undertaken for severe respiratory failure patients with/without veno-venous ECMO support. The main outcome was in-hospital all-cause mortality. Results Of 3195 patients with severe sepsis, 570 had severe respiratory failure. Forty patients in the ECMO group were matched with 150 patients in the control group. A survival time analysis revealed no difference in the in-hospital survival (hazard ratio, 0.854; 95% confidence interval, 0.531–1.373; P = 0.515). Two-hundred and eighty-five patients had severe respiratory failure induced by lung infection. Twenty-five ECMO group patients were matched with 89 patients in the control group. In the ECMO group, the survival time was longer than in the control group (hazard ratio, 0.498; 95% confidence interval, 0.279–0.889; P = 0.018). The number of renal replacement therapy- and vasopressor-free days improved. The ECMO group received more red blood cells transfused than the control group, but there was no significant difference in the rate of severe bleeding complications between the groups. Conclusions There was no difference in the in-hospital survival between the ECMO group and control group among overall septic patients with severe respiratory failure. However, in sepsis patients with severe respiratory failure induced by lung infection, ECMO support may improve their survival time.

Background: Currently, it remains controversial whether the Sepsis-3 definition provides the most appropriate criteria for clinical use. The purpose of this study was to compare between the Sepsis-2 and Sepsis-3 definitions using Japan’s nationwide registry. Methods: Data were obtained from a multicenter registry conducted at 42 intensive care units (ICUs) throughout Japan, in which patients received treatment for severe sepsis or septic shock between January 2011 and December 2013. Results: A total of 2797 patients diagnosed using the Sepsis-2 criteria were included in the present study. These patients were categorized into “Severe sepsis” (n = 1154) and “Sepsis-2 shock” (n = 1643) groups. Among the “Sepsis-2 shock” group, patients who did not meet the Sepsis-3 criteria for septic shock were categorized into the “Sepsis-2 shock-only” (n = 448, 27.3%) group, while patients who met the Sepsis-3 criteria for septic shock were categorized into “Sepsis-3 shock (n = 1195, 72.7%)” group. The ICU mortality in the “Sepsis-3 shock” group, “Sepsis-2 shock-only” group, and “Severe sepsis” group was 28.5%, 10.9%, and 14.1%, respectively. We observed no significant difference between the “Severe sepsis” and “Sepsis-2 shock-only” groups in terms of in-hospital survival ( P = .098), while the “Sepsis-3 shock” group had the highest in-hospital mortality rate ( P < .001). In a multivariate logistic regression analysis, liver insufficiency and immunocompromised status were independent prognostic factors in the “Sepsis-2 shock-only” group. In contrast, chronic heart disease and chronic hemodialysis were independent prognostic factors in the “Sepsis-3 shock” group. Conclusions: The ICU mortality of the “Sepsis-2 shock-only” group was significantly low. Besides septic shock diagnosed by the Sepsis-3 definition selects patients with more severe cases of sepsis among the “Sepsis-2 shock” group.

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., other authors: Satoru Hashimoto,Daisuke Hasegawa,Junji Hatakeyama,Naoki Hara,Naoki Higashibeppu,Nana Furushima,Hirotaka Furusono,Yujiro Matsuishi,Tasuku Matsuyama,Yusuke Minematsu,Ryoichi Miyashita,Yuji Miyatake,Megumi Moriyasu,Toru Yamada,Hiroyuki Yamada,Ryo Yamamoto,Takeshi Yoshida,Yuhei Yoshida,Jumpei Yoshimura,Ryuichi Yotsumoto,Hiroshi Yonekura,Takeshi Wada,Eizo Watanabe,Makoto Aoki,Hideki Asai,Takakuni Abe,Yutaka Igarashi,Naoya Iguchi,Masami Ishikawa,Go Ishimaru,Shutaro Isokawa,Ryuta Itakura,Hisashi Imahase,Haruki Imura,Takashi Irinoda,Kenji Uehara,Noritaka Ushio,Takeshi Umegaki,Yuko Egawa,Yuki Enomoto,Kohei Ota,Yoshifumi Ohchi,Takanori Ohno,Hiroyuki Ohbe,Kazuyuki Oka,Nobunaga Okada,Yohei Okada,Hiromu Okano,Jun Okamoto,Hiroshi Okuda,Takayuki Ogura,Yu Onodera,Yuhta Oyama,Motoshi Kainuma,Eisuke Kako,Masahiro Kashiura,Hiromi Kato,Akihiro Kanaya,Tadashi Kaneko,Keita Kanehata,Ken-ichi Kano,Hiroyuki Kawano,Kazuya Kikutani,Hitoshi Kikuchi,Takahiro Kido,Sho Kimura,Hiroyuki Koami,Daisuke Kobashi,Iwao Saiki,Masahito Sakai,Ayaka Sakamoto,Tetsuya Sato,Yasuhiro Shiga,Manabu Shimoto,Shinya Shimoyama,Tomohisa Shoko,Yoh Sugawara,Atsunori Sugita,Satoshi Suzuki,Yuji Suzuki,Tomohiro Suhara,Kenji Sonota,Shuhei Takauji,Kohei Takashima,Sho Takahashi,Yoko Takahashi,Jun Takeshita,Yuuki Tanaka,Akihito Tampo,Taichiro Tsunoyama,Kenichi Tetsuhara,Kentaro Tokunaga,Yoshihiro Tomioka,Kentaro Tomita,Naoki Tominaga,Mitsunobu Toyosaki,Yukitoshi Toyoda,Hiromichi Naito,Isao Nagata,Tadashi Nagato,Yoshimi Nakamura,Yuki Nakamori,Isao Nahara,Hiromu Naraba,Chihiro Narita,Norihiro Nishioka,Tomoya Nishimura,Kei Nishiyama,Tomohisa Nomura,Taiki Haga,Yoshihiro Hagiwara,Katsuhiko Hashimoto,Takeshi Hatachi,Toshiaki Hamasaki,Takuya Hayashi,Minoru Hayashi,Atsuki Hayamizu,Go Haraguchi,Yohei Hirano,Ryo Fujii,Motoki Fujita,Naoyuki Fujimura,Hiraku Funakoshi,Masahito Horiguchi,Jun Maki,Naohisa Masunaga,Yosuke Matsumura,Takuya Mayumi,Keisuke Minami,Yuya Miyazaki,Kazuyuki Miyamoto,Teppei Murata,Machi Yanai,Takao Yano,Kohei Yamada,Naoki Yamada,Tomonori Yamamoto,Shodai Yoshihiro,Hiroshi Tanaka,Osamu Nishida, Guidelines

Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of AT supplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n = 715, AT group; n = 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n = 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P = 0.034). However, quintile-stratified propensity score analysis (n = 1,784, odds ratio: 0.823 [0.646-1.050], P = 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P = 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P = 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between June 1 and September 30, 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as stage III were significantly higher than those of patients classified as stage I or II. There were no deaths among the patients classified as stage I. This novel classification may avoid underestimating the severity of heat-related illness.

The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between 1 June and 30 September 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as Stage III were significantly higher than those of patients classified as Stage I or II. There were no deaths among the patients classified as Stage I. This novel classification may avoid underestimating the severity of heat-related illness.

Background The administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality. Methods This is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used. Results IVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p

Severe sepsis is a major concern in the intensive care unit (ICU), although there is very little epidemiological information regarding severe sepsis in Japan. This study evaluated 3195 patients with severe sepsis in 42 ICUs throughout Japan. The patients with severe sepsis had a mean age of 70 ± 15 years and a mean Acute Physiology and Chronic Health Evaluation II score of 23 ± 9. The estimated survival rates at 28 and 90 days after ICU admission were 73.6 and 56.3 %, respectively. Electronic supplementary material The online version of this article (doi:10.1186/s40560-016-0169-9) contains supplementary material, which is available to authorized users.

A 56-year-old man, who had epigastralgia and abnormal liver function test, was admitted to our hospital. ERCP showed common bile duct dilation and stones. We therefore performed endoscopic lithotripsy after endoscopic sphincterotomy. Ten months later, MRCP showed recurrent CBD stones. After rehospitalization, resection of the dilated bile duct was carried out. This case was diagnosed Todani's type Ib congenital cystic dilatation of common bile duct. Todani's type Ib is rare type of congenital dilatation of bile duct, and is interesting embryologically.