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Purpose Although the most recent systematic review and meta-analyses on acute respiratory distress syndrome (ARDS) have shown that the use of steroids decreases mortality in adult patients, its benefits and risks may differ depending on the type and dosage of the steroid. Therefore, we conducted a network meta-analysis (NMA) to compare the differences in the efficacy among different doses and types of steroids. Methods We searched MEDLINE, CENTRAL, ICHUSHI, ClinicalTrials.gov, and WHO ICTRP databases from the earliest records to March 2021 for randomized control trials, which compared steroids with placebo or conventional therapy for ARDS. Using the random-effects model, we compared various categories of steroids (high-dose methylprednisolone, low-dose methylprednisolone, hydrocortisone, dexamethasone, and no steroid) concerning hospital mortality, incidence of infection, and ventilator-free days (VFD). Results We analyzed nine studies involving adult patients (n = 1212). Although there were no significant differences between the groups in terms of the mortality and incidence of infection, the number of VFD were greater when using low-dose methylprednisolone than when not using any steroids (Mean difference: 6.06; 95% confidence intervals: [2.5, 10.5]). Moreover, the rank probability showed that low-dose methylprednisolone might be the optimal treatment, whereas using no steroid or high-dose methylprednisolone may be inferior to other treatments in terms of mortality, infection, and VFD. Conclusion This NMA suggested that the effect of steroids on the outcome in patients with ARDS might depend on the type of the steroid drug administered. Moreover, further studies are needed to identify the optimal type and dosage. Supplementary Information The online version contains supplementary material available at 10.1007/s00540-021-03016-5.

Background Historically, β-blockers have been considered to be relatively contraindicated for septic shock because they may cause cardiac suppression. On the other hand, there is an increasing interest in the use of β-blockers for treating patients with sepsis with persistent tachycardia despite initial resuscitation. Research Question Do ultrashort-acting β-blockers such as esmolol and landiolol improve mortality in patients with sepsis with persistent tachycardia despite initial resuscitation? Study Design and Methods This was a systematic review and meta-analysis. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with esmolol or landiolol. We updated our search on April 20, 2020. Two independent reviewers assessed whether titles and abstracts met the following eligibility criteria: (1) RCT, (2) patients with sepsis and septic shock ≥ 18 years of age, and (3) treatment with either esmolol/landiolol or placebo/no interventions. Two authors independently extracted selected patient and study characteristics and outcomes. The results of all analyses are presented using random effect models. Results Seven RCTs with a pooled sample size of 613 patients were included. Of these, six RCTs with 572 patients reported 28-day mortality. Esmolol or landiolol use in patients with sepsis and septic shock was significantly associated with lower 28-day mortality (risk ratio, 0.68; 95% CI, 0.54-0.85; P Interpretation The use of ultrashort-acting β-blockers such as esmolol and landiolol in patients with sepsis with persistent tachycardia despite initial resuscitation was associated with significantly lower 28-day mortality. Trial Registry UMIN Clinical Trials Registry; No.: UMIN000040174; URL: https://www.umin.ac.jp/ctr/index.htm

Spontaneous abdominal wall hematomas are relatively rare and mainly attributed to anticoagulation and severe cough. Despite the high incidence of anticoagulation-related bleeding complications, there are no reports of spontaneous abdominal wall hematomas during extracorporeal membrane oxygenation (ECMO). We report a case of a spontaneous rectus sheath hematoma caused by alternation of the lateral semi-prone position during ECMO in a 76-year-old female patient with severe acute respiratory distress syndrome. Unfractionated heparin 12,000-14,000 units/day was administered for anticoagulation during ECMO. From Day 6 of ECMO, the patient who was under deep sedation was alternately placed in the left and right lateral semi-prone positions every 4 h, for approximately 20 h per day. On Day 12 of ECMO, the patient developed hypotension with anemia and a palpable mass in the right lower abdomen. Abdominal ultrasonographic imaging revealed a huge echo-free space centered in the right lower abdomen. Emergency contrast-enhanced computed tomography (CT) scanning showed extravasation from the superior and inferior epigastric arteries as well as a rectus sheath hematoma. Despite no apparent contrast leakage, an inferior epigastric artery embolization was undertaken because the patient was on ECMO. On Day 13 after ECMO initiation, ECMO and anticoagulation were discontinued. On CT scanning a week later, the hematoma had reduced. In conclusion, spontaneous abdominal wall hematoma is a rare and important complication that might occur during ECMO. Thus, careful physical examination should be routinely conducted when the patient is semi-prone during ECMO.

Background The exacerbation of intracranial bleeding is critical in traumatic brain injury (TBI) patients. Tranexamic acid (TXA) has been used to improve outcomes in TBI patient. However, the effectiveness of TXA treatment remains unclear. This study aimed to assess the effect of administration of TXA on clinical outcomes in patients with TBI by systematically reviewing the literature and synthesizing evidence of randomized controlled trials (RCTs). Methods MEDLINE, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (ICHUSHI) Web were searched. Selection criteria included randomized controlled trials with clinical outcomes of adult TBI patients administered TXA or placebo within 24 h after admission. Two investigators independently screened citations and conducted data extraction. The primary “critical” outcome was all-cause mortality. The secondary “important” outcomes were good neurological outcome rates, enlargement of bleeding, incidence of ischemia, and hemorrhagic intracranial complications. Random effect estimators with weights calculated by the inverse variance method were used to report risk ratios (RRs). Results A total of 640 records were screened. Seven studies were included for quantitative analysis. Of 10,044 patients from seven of the included studies, 5076 were randomly assigned to the TXA treatment group, and 4968 were assigned to placebo. In the TXA treatment group, 914 patients (18.0%) died, while 961 patients (19.3%) died in the placebo group. There was no significant difference between groups (RR, 0.93; 95% confidence interval, 0.86–1.01). No significant differences between the groups in other important outcomes were also observed. Conclusions TXA treatment demonstrated a tendency to reduce head trauma-related deaths in the TBI population, with no significant incidence of thromboembolic events. TXA treatment may therefore be suggested in the initial TBI care.

The effect of nutrition support therapy on prevention of readmission among patients with acute heart failure (HF) in an intensive care unit (ICU) setting remains unclear. We hypothesized that nutrition support therapy might decrease the readmission rate among these patients. Thus, we conducted a single-center prospective observational study to verify this hypothesis.Patients diagnosed with acute HF admitted to the ICU for more than 14 days between April 2016 and March 2017 were included in the analysis. The primary outcome was the relationship between nutritional intake and HF-related hospital readmission due to HF at 180 days after discharge. We divided the participants into 2 groups: patients who were not readmitted to hospital within 180 days after discharge (non-readmission group) and patients who were readmitted within this timeframe (HF-related readmission group). Data were expressed as median (interquartile range).Sixty patients required readmission due to HF-related events (HF-related readmission group). On the other hand, 127 patients did not require readmission (non-readmission group). The calorie and protein intake on day 3 after ICU admission in the HF-related readmission group was significantly higher than that in the non-readmission group [20.5 (14.2, 27.8) vs. 27.7 (22.5, 31.2) kcal/kg/day, p 0.001; 0.7 (0.5, 0.9) vs. 0.9 (0.7, 1.2) g/kg/day, p 0.001, respectively]. Similarly, the protein intake values on day 7 were also significantly higher in the HF-related readmission group [0.8 (0.6, 1.0) vs. 0.9 (0.7, 1.2) g/kg/day, p = 0.04]. Multivariate analysis indicated that total caloric intake on day 3 was an independent factor affecting readmission (odds ratio = 1.05, 95% confidence interval = 1.01-1.09, p = 0.006). In addition, when the cut off value of calorie intake was set to 18 kcal/kg/day, the group ingesting ≥18 kcal/kg/day on day 3 had a significantly higher readmission rate within 180 days after discharge.Our data showed that total calorie intake ≥18 kcal/kg/day on day 3 might increase the readmission rate among patients with acute HF.

Objective Although several studies have demonstrated that noncardiac surgery in patients with hypertrophic cardiomyopathy (HCM) is safe, the long-term outcomes remain unclear. Therefore, the authors investigated the postoperative long-term outcomes of patients with HCM who underwent noncardiac surgery at their hospital. Design Retrospective review. Setting Single university hospital. Participants Seventy-two consecutive patients with HCM who underwent noncardiac surgery. Intervention No intervention. Measurements and Main Results The incidence of HCM-related events during the patient’s hospital stay were evaluated as the short-term outcomes, and HCM-related events after discharge were evaluated as the long-term outcomes. HCM-related events were defined as sudden death, implantable cardioverter-defibrillator discharge with successful recovery from cardiopulmonary arrest, death due to heart failure, hospitalization for heart failure, myocardial infarction, and thrombosis caused by atrial fibrillation. The median postoperative follow-up was 1,382 days (3.8 years). Short-term mortality and morbidity rates were both 1.3%, whereas long-term mortality and morbidity rates were 4.2% and 15%, respectively. The 5-year event-free rate was 76%, whereas the postoperative HCM-related mortality rate was 4.2%. Conclusions This study suggests that noncardiac surgery in patients with HCM is safe in terms of both short- and long-term outcomes. To confirm the findings, additional studies, such as prospective, multicenter, observational studies, should be conducted.

The usefulness and safety of continuous glucose monitoring (CGM) systems in adult patients with severe coronavirus disease (COVID-19) have been reported. Using CGM might reduce the exposure patients and healthcare workers to COVID-19 and limit the use of personal protective equipment during the pandemic. CGM devices measure glucose in the subcutaneous interstitial fluid, but the accuracy of this technique has not been established in critically ill patients. The artificial pancreas, STG-55 (Nikkiso, Tokyo), is a closed-loop device that conducts continuous blood glucose monitoring using a peripheral vein. We used the STG-55 for glucose control in a 60-year-old woman with severe COVID-19 admitted to the intensive care unit. Due to severe respiratory failure, the patient was intubated, and extracorporeal membrane oxygenation was introduced. Because she had hyperglycemia despite high-dose intravenous insulin therapy, we decided to use STG-55 for glucose control. The STG-55 safely titrated the insulin infusion and monitored glucose levels. Fifty-six hours after adopting the STG-55, it was removed because the blood sampling failed. No episodes of hypoglycemia were observed despite deep sedation during this period. In conclusion, this case demonstrates the potential utility of an artificial pancreas in patients with severe COVID-19.

Objectives Hyperchloremia is a potential risk factor for acute kidney injury (AKI) in critically ill patients. However, the relationship between hyperchloremia and postoperative AKI in adult patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB) remains unclear. The authors aimed to determine whether postoperative hyperchloremia was associated with postoperative AKI in these populations. Objectives Retrospective, single-center study. Setting Tertiary care hospital. Participants Adult patients who underwent cardiovascular surgery with CPB. Interventions None. Measurements and Main Results Patients with and without postoperative hyperchloremia were matched (1:1). The primary outcome was the rate of postoperative AKI diagnosed using the Kidney Disease: Improving Global Outcomes consensus criteria. Postoperative hyperchloremia was defined as postoperative serum chloride levels of >110 mmol/L during the first 48 hours. An increase in serum chloride levels (Δ[Cl–]) was defined as the difference between the preoperative and maximum postoperative serum chloride levels during the first 48 hours ([Cl–]max). Propensity-score matching and univariate and multivariate logistic regression analyses were employed. A total of 323 patients were included. Propensity-score matching selected 55 pairs for the final comparison. The incidence of postoperative AKI did not differ between the two groups (47% v 46%, p = 1.0). In the multivariate logistic regression analysis, Δ[Cl–] was associated independently with the development of postoperative AKI (odds ratio, 1.13; 95% confidence interval, 1.06-1.21; p Conclusions Exposure to postoperative hyperchloremia was not associated with postoperative AKI in adult patients undergoing cardiovascular surgery with CPB. However, an increase in the serum chloride level might be associated with postoperative AKI.

Blood purification has been widely performed for critically ill patients, even in cases without renal failure. Effective anticoagulation of the extracorporeal circuit is necessary to prevent circuit clotting. We hypothesized that administration of recombinant human-soluble thrombomodulin (rhsTM) to septic patients undergoing blood purification may prevent circuit clotting, because this agent regulates coagulation. We performed a retrospective, single-center, propensity-matched cohort study in the intensive care unit of Nishichita General Hospital. We included septic patients admitted to the intensive care unit from May 2015 to August 2020 who underwent blood purification. Patients who received rhsTM during intensive care unit admission to the end of the first blood purification (rhsTM group) were matched 1:1 with other patients (control group). The primary outcome was the occurrence of circuit clotting during the first blood purification. A total of 138 patients were included in the study [43 patients (31%) in the rhsTM group and 95 patients (69%) in the control group]. After propensity score matching, 42 pairs of patients were selected, and patients in the rhsTM group had a lower incidence of circuit clotting (21 vs. 55%, P = 0.003). One case of major bleeding occurred in the rhsTM group, but there was no difference in the incidence of major bleeding between groups (2 vs. 0%, P = 1.0). In conclusion, this propensity-matched cohort study indicated that the administration of rhsTM to septic patients undergoing blood purification may prevent extracorporeal circuit clotting.

The use of standardized internal hospital phone numbers for cardiac arrest is advocated in Europe. We evaluated the current status of variations in medical emergency call numbers for in-hospital patients in Japan and whether anesthesiologists would approve a standardized number. From June 2018 to August 2018, a questionnaire survey was mailed to anesthesiologists in 1373 Japanese Society of Anesthesiologists (JSA)-accredited hospitals. The basis for opinions on using a standardized cardiac arrest call number in all Japanese hospitals was evaluated. Of 1373 facilities (response rate, 58%, n = 800), 741/776 (96%) reported a response system for in-hospital cardiac arrest; 638/710 (90%) responded to cardiac arrest through loudspeaker broadcast, audible to both patients and staff; 346/777 (48%) used a number between one and five digits long, four-digit numbers being the most common. Across Japan, 370 different numbers were reported. Only 385/688 (56%) of respondents had the emergency number memorized. Finally, 423/776 (55%) respondents approved standardizing a hospital telephone number for summoning help. Multivariate analysis showed that facilities where the anesthesiologists already memorized the call number were the only reason identified for opposition to the standardization. Although 96% of JSA-accredited hospitals had a response system for in-hospital cardiac arrests, discussions for standardization of a unified number need to be encouraged for improved emergency response.

Aim Sepsis treatment has been standardized in many countries worldwide. However, treatment of sepsis in Japan has developed independently, and how Japanese physicians actually treat sepsis patients nationwide remains uninvestigated. The aim of this study was to clarify the current practice for septic patients in Japan and how it differs from standard care throughout the world. Methods This study was designed as a prospective, cross‐sectional, self‐reported questionnaire‐ and Web‐based electronic survey in Japan. The survey was undertaken to assess respondents’ clinical practices and preferences regarding treatment strategies, sepsis assessment, and management in the setting of critical illness. An exploratory factor analysis and a hierarchical cluster analysis were carried out to identify the treatments distinctive to Japan, called “Galápagos therapies”. Results The final analysis included 295 respondents. According to the factor analysis, we defined anticoagulant therapy for disseminated intravascular coagulation, antimediator renal replacement therapy, and others as Galápagos therapies. These Galápagos therapies were undertaken by approximately two‐thirds of the Japanese physicians who responded. We classified Japanese physicians according to three patterns of clinical practice carried out for sepsis: (i) those who do not perform Galápagos therapies but do perform worldwide standardized care, (ii) those who perform Galápagos therapies on top of worldwide standardized care, (iii) those who do not perform worldwide standardized care. Conclusion On the basis of a nationwide questionnaire‐based survey in Japan, we clarified distinctive sepsis treatments performed in Japan, such as antimediator renal replacement therapy and treatment for sepsis‐induced disseminated intravascular coagulation., On the basis of a nationwide questionnaire‐based survey in Japan, we clarified distinctive sepsis treatments performed in Japan, such as antimediator renal replacement therapy and sepsis‐induced disseminated intravascular coagulation treatment. In this article, we defined them as Galápagos therapies and advocate their unique clinical concept; however, evaluation of the effectiveness of the Galápagos therapies will require a detailed analysis of the data on a patient level.

Although tight glucose control might reduce inflammation after cardiac surgery, it remains unclear whether inflammation can be controlled by maintaining glucose levels within 110–180 mg/dL. We hypothesized that a glucose target range of 110–180 mg/dL decreases inflammation after cardiovascular surgery. This retrospective study included 72 cardiovascular surgery patients divided into two groups according to the glucose control approach. Patients allocated to the closed-loop group received closed-loop glucose control (target glucose levels at 110–180 mg/dL) from admission to the intensive care unit until 9 a.m. on postoperative day (POD) 1. Patients allocated to the conventional group received conventional glucose control using a sliding scale method to maintain blood glucose levels

This study evaluated the prognostic value of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) together with host-related factors in patients with unresectable advanced gastric cancer. The study enrolled 262 patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2007 to 2015. Clinicopathological information and systemic inflammatory response data were analyzed for associations between baseline cancer-related prognostic variables and survival outcomes. The median survival time was significantly lower for patients with high ALP, high LDH, high total bilirubin, high aspartate aminotransferase, high alanine transaminase, high gamma-glutamyltransferase, high creatinine, a Glasgow prognostic score (GPS) of 1 or 2 score compared to GPS 0, higher compared to lower neutrophil to lymphocyte ratio (NLR) 3.9, lower compared to higher prognostic nutrition index 36.1, T3–4 compared to T1–2 tumor and diffuse-type compared to intestinal-type histology. Multivariate survival analysis identified high ALP 322 (HR 1.808; 95% CI 1.015–3.220; P = 0.044), T2–3 (HR 2.622; 95% CI 1.224–5.618; P = 0.013), and diffuse-type gastric cancer (HR 2.325; 95% CI 1.341–4.032; P = 0.003) as significant independent predictors of worse prognosis in the studied group of cancer patients. High level of ALP is an independent, worse prognosis factor for patients receiving chemotherapy for unresectable and recurrent gastric cancer.

Surgical stress induces hyperglycemia and gives rise to glucose toxicity, which causes infectious diseases, resulting in unfavorable surgical outcomes. Intensive insulin treatment can control short- and long-term complications in patients with not only diabetes mellitus, but also surgical diabetes; however, it is associated with an increased risk of hypoglycemia. The wearable artificial pancreas was originally developed to control glucose levels in patients with type 1 diabetes, progressing to a device with enhanced stability and safety for these patients. Its usability has further progressed to include patients with type 2 diabetes. The bedside artificial pancreas is the only closed-loop-type artificial pancreas which can maintain stable glycemic control in accordance with a target blood glucose range, based on the patient's actual blood glucose levels. Moreover, this stable glycemic control with a low variation in blood glucose concentration within the target range is produced without any hypoglycemia. Significant advances of this device will now occur due to the approval of treatment for perioperative glycemic control by the Japanese Health Care Insurance System in 2016. Along with an increase in the number of mainly elderly patients with low glucose tolerance, it is expected that the role of the artificial pancreas will increase in the future. Considering the current state and expense of regenerative and transplant medicine, along with donor shortages, further development of the artificial pancreas and associated glycemic control can be expected.

The aim of this pilot study was to investigate the effects of a preoperative immune-modulating diet (IMD) before thoracoscopic esophagectomy for patients with esophageal cancer. Thirty patients who were diagnosed with resectable esophageal cancer were assigned to two groups: the IMD (n = 15) and the standard liquid diet (SLD; n = 15) groups. We evaluated postoperative parameters, such as the incidence of complications and the postoperative levels of cytokines as the primary endpoints. The secondary endpoint was the length of hospital stay. The peak levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α appeared on postoperative day (POD) 1 and POD 2 in the IMD and SLD group, respectively. The peak level of C-reactive protein (CRP) appeared on POD 3 in both groups (IMD 9.9 mg/dL, SLD 15.2 mg/dL). Overall, TNF-α levels in the IMD group were lower than those in the SLD group (P = 0.033). Furthermore, IL-6 (P = 0.182) and CRP (P = 0.191) levels, and the incidence of postoperative pneumonia (7.1 vs. 26.7%; P = 0.330) tended to be lower in the IMD group than in the SLD group. Preoperative IMD suppressed the elevation of the TNF-α levels after thoracoscopic esophagectomy in patients with esophageal cancer, although no different tendency was detected in terms of IL-6, CRP or postoperative complications.

SummaryRecombinant human soluble thrombomodulin (ART-123) is a novel anticoagulant for patients with disseminated intravascular coagulation (DIC). It is widely used in clinical settings throughout Japan. Furthermore, a global Phase 3 study is currently being conducted. In healthy subjects, ART-123 is excreted mainly via the kidneys. Therefore, ART-123 dose decrease was recommended in DIC patients with severe renal dysfunction. However, the pharmacokinetics of ART-123 in DIC patients with severe acute renal dysfunction has not been elucidated. In an open-label, multicentre, prospective, clinical pharmacological study, we investigated the pharmacokinetics and safety of ART-123 upon repeated administration to DIC patients. ART-123 was administered to patients at a dose of 130 or 380 U/kg/day for six consecutive days. Plasma concentrations of ART-123 were measured at 21 time points until eight days after the final administration. Urinary excretion rates during the first 24 hours (h) were calculated. Patient renal functions were evaluated by measuring 24-h creatinine clearance (Ccr). Forty-three patients were enrolled in the present study. The urinary excretion rates of ART-123 correlated closely with 24-h Ccr. Total body clearance of ART-123 was also weakly related with 24-h Ccr. However, the plasma concentrations of ART-123 were not considerably different among patients with different renal function. Two patients had subcutaneous haemorrhage as an adverse event related to ART-123. In conclusion, plasma concentrations of ART-123 may not be different among patients with different renal functions. ART-123 was well tolerated in these patients.

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

The optimal target blood glucose concentration for acute glycemic control remains unclear because few studies have directly compared 144–180 with 110–144 or >180 mg/dL. Accordingly, we performed a network meta-analysis to compare four different target blood glucose levels ( 180 mg/dL) in terms of the benefit and risk of insulin therapy. We included all of the studies from three systematic reviews and searched the PubMed and Cochrane databases for other studies investigating glucose targets among critically ill patients. The primary outcome was hospital mortality, and the secondary outcomes were sepsis or bloodstream infection and the risk of hypoglycemia. Network meta-analysis to identify an optimal target glucose concentration. The network meta-analysis included 18,098 patients from 35 studies. There were no significant differences in the risk of mortality and infection among the four blood glucose ranges overall or in subgroup analysis. Conversely, target concentrations of 180 mg/dL. However, there were no significant differences between the target concentrations of 144–180 and >180 mg/dL. This network meta-analysis found no significant difference in the risk of mortality and infection among four target blood glucose ranges in critically ill patients, but indicated that target blood glucose levels of 180 mg/dL. Further studies are required to refute or confirm our findings.

The present study aimed to evaluate the efficacy and safety of trastuzumab plus chemotherapy for patients with unresectable advanced or recurrent gastric cancer. A retrospective analysis of 213 patients with unresectable advanced or recurrent gastric cancer who received systemic chemotherapy, including 15 patients who were also administered trastuzumab, at Kochi Medical School between 2007 and 2013 was performed. The overall survival was compared between patients who received trastuzumab plus chemotherapy and patients who received chemotherapy alone, and the safety and efficacy of the trastuzumab-containing regimen was evaluated. Human epidermal growth factor receptor (HER)2 status was examined in 86 patients, of whom 15 (17.4%) exhibited strong positive HER2 expression. The rate of strong positive HER2 expression was significantly higher for intestinal type tumors compared with diffuse type tumors [23.6 (13/55) vs. 6.5% (2/31); P=0.044]. The median overall survival of the patients treated with trastuzumab was significantly longer compared with that for patients who were not treated with trastuzumab (22.9 vs. 11.6 months; P=0.014). The objective response rate and disease control rate for trastuzumab plus chemotherapy were 46.7 and 86.7%, respectively. Frequently encountered grade 3-4 toxicities included neutropenia (26.7%; 4/15), anemia (13.3%; 2/15) and fatigue (13.3%; 2/15). Trastuzumab plus chemotherapy is effective for patients with HER2-positive advanced or recurrent gastric cancer, and the frequencies of hematological and non-hematological toxicities experienced by patients in the present study indicated that it can be safely administered clinically.

The most common sites of breast cancer metastasis are the bone, liver, lung and brain, while gastrointestinal metastasis from breast cancer is rare. We herein present the case of a 68-year-old woman who was admitted to our department with nausea and appetite loss. The patient's medical history included right mastectomy with sentinel lymph node biopsy 5 years earlier for invasive lobular carcinoma, measuring 6.2 cm in greatest diameter, without lymphovascular invasion. Two years after the surgery, the patient developed brain metastasis and underwent metastasectomy to control the neurological symptoms, including unsteadiness and asthenia. After the second surgery, the patient received systemic chemotherapy using S-1, followed by bevacizumab plus paclitaxel. However, due to bevacizumab-related cardiotoxicity, the treatment was switched to eribulin. On esophagogastroduodenoscopy, an elevated lesion was identified in the antrum, causing severe narrowing of the gastric outlet. Biopsy and histological examination of the tumor revealed infiltration of the gastric wall by undifferentiated neoplastic cells with poor adhesion, morphologically similar to invasive lobular carcinoma, and immunohistochemical staining was positive for estrogen receptor, mammaglobin and GATA3. Finally, 18F-2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography combined with computed tomography imaging revealed FDG uptake across the thickness of the antral wall. The patient was diagnosed with gastric metastasis from the original breast cancer and subsequently underwent endoscopic self-expandable metallic stent (SEMS) placement. There were no procedure-related adverse events, and the patient remained alive under best supportive care 4 months after SEMS placement. To the best of our knowledge, this is the first reported case of gastric outlet obstruction caused by metastatic breast carcinoma managed by SEMS placement. While such a diagnosis is rare, clinicians treating patients with gastric metastases should be aware of possible gastric outlet obstruction and SEMS placement as an effective palliative intervention.

A 57-year-old woman was diagnosed with type I glycogen storage disease in her twenties. She had undergone hepatectomy under general anesthesia with epidural anesthesia. Fifty minutes after the induction of anesthesia, a 20-gauge venous catheter was inserted in the patient's right hand, and an artificial pancreas (STG-55, Nikkiso Co., Tokyo, Japan) was connected for continuous glucose monitoring and automatic glucose control. Insulin was infused when the blood glucose level reached 120 mg/dL or higher, and glucose was infused when the level fell to 100 mg/dL or lower. After the Pringle maneuver, the blood glucose level increased, and insulin was administered automatically via an artificial pancreas. Hypoglycemia did not occur during the operation. After total parenteral nutrition was started in the intensive care unit (ICU), the blood glucose level increased, and the artificial pancreas controlled the blood glucose level through automatic insulin administration. Thirty-four hours after admission to the ICU, the artificial pancreas was removed because the blood sampling failed. After the removal of the artificial pancreas, blood glucose level was measured every 2 h until extubation. During the ICU stay, hypoglycemia never occurred, with the average blood glucose level being 144 mg/dL. In conclusion, the use of an artificial pancreas for perioperative blood glucose management in a patient with glycogen storage disease had the beneficial effect of enabling the management of blood glucose levels without hypoglycemia.

Atrial fibrillation (AF) is associated with mortality after cardiac surgery. Several studies have reported that landiolol might help to prevent postoperative AF. The objective of this study was to investigate whether low-dose landiolol is useful in terms of balance of benefit and risk.We conducted a meta-analysis after systematically searching the PubMed, the Cochrane library and the ICHUSHI to identify randomized, controlled trials investigating the preventive effect of landiolol on incidence of AF after cardiac surgery.Six randomized trial with 571 patients were included.The primary outcome was incidence of AF after surgery, while secondary outcomes were mortality and complications.Incidence of AF within 1week after surgery was significantly lower in the landiolol group than in the control group (odds ratio, 0.27; 95% confidence interval, 0.18-0.42; p0.001). Three of the 6 studies reported data regarding in-hospital mortality and complications, showing no significant differences between groups (0.7 vs 3.0%; OR, 0.45; 95% CI, 0.07-2.74; p=0.39; and 4.5 vs 9.7%; OR, 0.45; 95% CI, 0.16-1.23; p=0.12, respectively).Our systematic review revealed that low-dose landiolol might help to prevent AF after cardiac surgery and further large trials are needed to evaluate safety because mortality and morbidity rate were very low in included studies.

Background We examined whether perioperative intensive insulin therapy (IIT) using an artificial pancreas (AP) with a closed-loop glycemic control system can be used to prevent hypoglycemia in surgical patients. Methods Between 2006 and 2012, perioperative glycemic control using an AP was performed in 427 patients undergoing general surgery. A total of 305 patients undergoing IIT using an AP in the target blood glucose range of 80 to 110 mg/dL were enrolled in the study. Data were collected prospectively and were reviewed or analyzed retrospectively. Results No patients had hypoglycemia. Perioperative mean blood glucose level and achievement rates in target blood glucose range of 80 to 110 mg/dL were 100.5 ± 11.9 mg/dL and 88.1% ± 16.0%, respectively. For the 3 primary operative methods, including hepatic, pancreatic, and esophageal resections, there were no significant differences in glycemic control stability between the types of surgery. Conclusion Perioperative IIT using an AP with a closed-loop glycemic control system can be used to prevent hypoglycemia and maintain stable glycemic control with less variability of blood glucose concentration.

Preoperative carbohydrate loading enhances insulin action by approximately 50 %. In some Japanese hospitals, preoperative oral rehydration therapy is performed for preventing dehydration during surgery. We hypothesized that preoperative oral rehydration therapy with a 2.5 % carbohydrate beverage that is widely used in Japan can enhance insulin action. Therefore, we investigated the effect of this 2.5 % carbohydrate beverage on insulin action in volunteers. Six healthy volunteers participated in this crossover randomized study. The participants were segregated into 2 groups: an oral rehydration therapy with 2.5 % carbohydrate beverage group (group A) and a control group (group B). Subjects in group B were allowed to drink only water from 9 pm the day before the test; conversely, group A fasted from 9 pm onward and drank 500 ml of the beverage containing 2.5 % carbohydrate (OS-1; Otsuka Pharmaceutical Factory, Tokushima, Japan) between 9 and 12 pm and again at 6.30 am. At 8.30 am, a hyperinsulinemic normoglycemic clamp was initiated using an artificial pancreas STG-22 (Nikkiso, Tokyo, Japan). Insulin action was evaluated in both groups using the glucose infusion rate. Blood glucose levels at the initiation of the clamp procedure were similar. However, the glucose infusion rate for group A was significantly higher than that of group B (8.6 ± 1.5 vs. 6.8 ± 2.0 mg/kg/min, p = 0.009). In conclusion, the hyperinsulinemic normoglycemic clamp using an artificial pancreas showed that the administration of a 2.5 % carbohydrate oral rehydration solution for preoperative oral rehydration therapy improves insulin action in volunteers.

A closed-loop glycemic control system using an artificial pancreas has been applied with many clinical benefits in Japan since 1987. To update this system incorporating user-friendly features, we developed a novel artificial pancreas (STG-55). The purpose of this study was to evaluate STG-55 for device usability, performance of blood glucose measurement, glycemic control characteristics in vivo in animal experiments, and evaluate its clinical feasibility. There are several features for usability improvement based on the design concepts, such as compactness, display monitor, batteries, guidance function, and reduction of the preparation time. All animal study data were compared with a clinically available artificial pancreas system in Japan (control device: STG-22). We examined correlations of both blood glucose levels between two groups (STG-55 vs. control) using Clarke's error grid analysis, and also compared mean glucose infusion rate (GIR) during glucose clamp. The results showed strong correlation in blood glucose concentrations (Pearson's product-moment correlation coefficient: 0.97; n = 1636). Clarke's error grid analysis showed that 98.4% of the data fell in Zones A and B, which represent clinically accurate or benign errors, respectively. The difference in mean GIRs was less than 0.2 mg/kg/min, which was considered not significant. Clinical feasibility study demonstrated sufficient glycemic control maintaining target glucose range between 80 and 110 (mg/dL), and between 140 and 160 without any hypoglycemia. In conclusion, STG-55 was a clinically acceptable artificial pancreas with improved interface and usability. A closed-loop glycemic control system with STG-55 would be a useful tool for surgical and critical patients in intensive care units, as well as diabetic patients.

Hydroxyethyl starch (HES) is widely used to prevent and treat spinal anesthesia-induced hypotension during cesarean section. However, the use of saline-based HES may lead to hyperchloremia. This study aimed to clarify the effects of saline-based HES on umbilical cord chloride level at delivery. We retrospectively analyzed 93 consecutive single-pregnancy patients who underwent cesarean section with combined spinal-epidural anesthesia. The patients were divided into two groups, depending on the use of 6% HES 130/0.4: group A (461 ± 167 ml of saline-based HES was administered; 43 patients) and group B (HES not administered; 50 patients). The major outcome was umbilical cord chloride level at delivery. The volume infused from operating room admission until delivery was not significantly different between groups. The umbilical cord chloride level at delivery was statistically significantly higher in group A than in group B, but clinically similar (108 ± 2 vs. 107 ± 2 mmol/l, P = 0.02). No differences were observed in the Apgar score or other umbilical cord laboratory data at delivery (Na+, K+, pH, base excess). In conclusion, we suggest that although the use of up to 500 ml of saline-based HES during cesarean section influences umbilical cord blood electrolytes, the effect is not of a clinically significant magnitude.

The incidence of diabetes is increasing at an unprecedented pace and has become a serious health concern worldwide during the last two decades. Despite this, adequate glycemic control using an artificial pancreas has not been established, although the 21st century has seen rapid developments in this area. Herein, we review current topics in glycemic control for both the wearable artificial pancreas for type 1 and type 2 diabetic patients and the bedside artificial pancreas for surgical diabetic patients. In type 1 diabetic patients, nocturnal hypoglycemia associated with insulin therapy remains a serious problem that could be addressed by the recent development of a wearable artificial pancreas. This smart phone-like device, comprising a real-time, continuous glucose monitoring system and insulin pump system, could potentially significantly reduce nocturnal hypoglycemia compared with conventional glycemic control. Of particular interest in this space are the recent inventions of a low-glucose suspend feature in the portable systems that automatically stops insulin delivery 2 h following a glucose sensor value

A 59-year-old man was referred to the Kochi Medical School Hospital due to left shoulder pain. Physical examination revealed a nodular, painful mass lesion in the subcutaneous tissue of the right chest wall, with a diameter of ~2 cm. Esophagogastroduodenoscopy revealed a large ulcerated tumor in the lower gastric body near the lesser curvature, and biopsy specimens of the gastric and humeral lesions revealed poorly differentiated adenocarcinoma. Abdominal computed tomography revealed multiple low-density lesions in the liver and a well-defined, 2.2-cm mass in the subcutaneous tissue of the right chest wall. The diagnosis was advanced gastric cancer with metastases to the liver, bone and skin, and systemic chemotherapy with radiotherapy for the bone metastasis was recommended. The patient also underwent distal gastrectomy to control bleeding from the primary gastric cancer lesion due to unresolved anemia, not improving by blood transfusion, and a low hemoglobin level. The subcutaneous tumor in the right chest wall was resected at the same time, to alleviate the pain caused by the mass. Macroscopic examination of the resected specimen revealed a well-circumscribed, solid tumor, measuring 2.2×2.1 cm, with a firm consistency. Microscopic examination showed infiltration of poorly differentiated adenocarcinoma cells into the subcutaneous tissue. Subcutaneous metastasis from gastric cancer is a rare manifestation, with a reported incidence of 0.8–1.0%. Cutaneous metastasis of cancer generally appears late in the course of the disease. Surgical resection of metastatic skin tumors is occasionally undertaken as palliative treatment to improve the patient's quality of life by controlling severe symptoms, including pain and hemorrhage.

Background and purpose The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] 10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc. This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. Methods Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. Results A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs. Conclusions Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals. Electronic supplementary material The online version of this article (10.1186/s40560-017-0270-8) contains supplementary material, which is available to authorized users.

Background: The STG-22t is the only continuous blood glucose monitoring system currently available. The aim of this study is to determine the accuracy and reliability of the STG-22t for continuously monitoring blood glucose level in post-surgical patients. Methods: Fifty patients scheduled for routine surgery were studied in surgical intensive care unit (ICU) of a university hospital. After admission to the ICU, the STG22t was connected to the patients. An attending physician obtained blood samples from a radial arterial catheter. Blood glucose level was measured using the ABLt800FLEX immediately after blood collection at 0, 4, 8, and 16 h post-admission to the ICU (total of 200 blood glucose values). Results: The correlation coefficient (R 2 ) was 0.96. In the Clarke error grid, 100% of the paired measurements were in the clinically acceptable zone A and B. The Bland and Altman analysis showed that bias limits of agreement (percent error) were 0.04(0.7) 0.35(6.3)mmol (mg/dl) (7%), 0.11(2) 1.22(22) (15%) and 0.33(6) 1.28(23) (10%) in hypoglycemia (o70(3.89)mmol (mg/dl), normoglycemia (3.89(70)‐10(180) mmol (mg/dl), and hyperglycemia (410(180)mmol (mg/dl), respectively. Conclusions: The STG-22t can be used for measuring blood glucose level continuously and measurement results are consistent with intermittent measurement (percentage error within 15%). Therefore, the STG-22t is a useful device for monitoring in blood glucose level in the ICU for 16 h.

This clinical study aimed to compare a novel and conventional artificial pancreas (AP) used in surgical patients for perioperative glycemic control, with respect to usability, blood glucose measurements, and glycemic control characteristics. From July in 2010 to March in 2015, 177 patients underwent perioperative glycemic control using a novel AP. Among them, 166 patients were eligible for inclusion in this study. Intensive insulin therapy (IIT) targeting a blood glucose range of 80–110 mg/dL was implemented in 82 patients (49 %), and the remaining 84 patients (51 %) received a less-intensive regime of insulin therapy. Data were collected prospectively and were reviewed or analyzed retrospectively. A comparison study of 324 patients undergoing IIT for glycemic control using a novel (n = 82) or conventional AP (n = 242) was conducted retrospectively. All patients had no hypoglycemia. The comparison study revealed no significant differences in perioperative mean blood glucose level, achievement rates for target blood glucose range, and variability in blood glucose level achieved with IIT between the novel AP and conventional AP groups. The usability, performance with respect to blood glucose measurement, and glycemic control characteristics of IIT were comparable between novel and conventional AP systems. However, the novel AP was easier to manipulate than the conventional AP due to its smaller size, lower weight, and shorter time for preparation. In the near future, this novel AP system might be accepted worldwide as a safe and useful device for use in perioperative glycemic control.

Blood glucose management is important in the intensive care unit (ICU). Although we have used an intravenous continuous glucose monitor for blood glucose management to avoid hypoglycemia, there has been a problem with interruption of blood glucose measurement caused by blood removal failure [1]. A previous study reported that a subcutaneous continuous glucose monitor was reliable for use in critically ill patients [2].

Few studies have reported that fever is caused by intravenous sedative drugs even though these agents are widely used. We present a case of propofol-induced drug fever. A 57-year-old woman underwent hepatic segmentectomy. Although she was diagnosed with type I glycogen storage disease when in her twenties, her liver function was normal. As the operative hemorrhage was high, the patient was transferred to the intensive care unit (ICU). Her temperature at ICU admission was 35.8 °C, and sedation with propofol and dexmedetomidine was initiated. Two hours after admission to the ICU, the patient had a fever of 38–39.5 °C. Remittent fever persisted until day 5 after surgery. Because of her persistent fever, pneumonia was suspected and antibiotics were initiated on day 4 after surgery. As the fever persisted after the initiation of antibiotics, drug fever was suspected. On day 5 after surgery, propofol infusion was discontinued and the patient was extubated. Her temperature of 37.7 °C at the discontinuation of propofol infusion, and rapidly decreased to 36.1 °C in the following 3 h. Propofol-induced drug fever must be considered in cases of fever of unknown origin when patients receive propofol and appear inappropriately well for the degree of fever that they have.

A 67-year-old woman underwent right radical neck dissection for cervical lymph node metastasis from maxillary gingival carcinoma. Two months later, metastasis in the left superior internal jugular lymph nodes were discovered, and left radical neck dissection was performed. Postoperatively, airway obstruction occurred despite performing extubation after confirming that the patient had fully recovered from anesthesia. Bilateral hypoglossal nerve palsy was diagnosed and the patient was reintubated. After extubation on the following day, airway obstruction was relieved, but slurred speech and impaired swallowing were persistent. In view of this, hypoglossal nerve function should be examined before the second radical neck dissection on the contralateral side.

Sugammadex, a new reversal agent for rocuronium, encapsulates the rocuronium molecule and results in rapid reversal of rocuronium-induced neuromuscular blockade. A case in which sugammadex was used to treat an anaphylactic reaction that occurred after rocuronium is presented. The binding/encapsulation of rocuronium by sugammadex may selectively eliminate the antigenic quaternary ammonium activity of circulating rocuronium, and prevent the propagation of rocuronium-induced anaphylaxis.

As disseminated intravascular coagulation (DIC) causes multiple organ failure, recombinant thrombomodulin (rTM) is widely used in Japan for treating DIC. However, the optimal timing of rTM administration has not yet been determined. We hypothesized that the administration of rTM before progression of disease causing DIC might be better for the treatment of DIC than that after progression of disease. A total of 101 patients received rTM in the intensive care unit (ICU) between August 2008 and November 2013 were enrolled. Depending on survival at hospital discharge, the patients were divided into survivor (group S) and non-survivor groups (group NS). Patient characteristics before DIC development, acute physiology and chronic health evaluation II (APACHEII) score and sequential organ failure assessment (SOFA) score at the start of rTM administration, rTM administration dose, duration of time between the onset of disease causing DIC and rTM administration, and combination therapy were collected. Group S had 57 patients, and group NS had 44 patients. More than 70% of patients in group S were administrated rTM within 1 day from the onset of disease causing DIC (0 days, 40% vs 20%; 1 day, 33% vs 30%; more than 2 days, 26% vs 50%). At the start of the rTM administration, the APACHEII and SOFA scores were significantly lower in group S (26 ± 6 vs 32 ± 6, p

OBJECTIVE Intensive insulin therapy (IIT) reduces morbidity and mortality in patients in surgical intensive care units. The aim of this study is to assess the effect of IIT using a closed-loop system in hepatectomized patients. RESEARCH DESIGN AND METHODS Patients were randomly assigned to receive IIT using a closed-loop system: an artificial pancreas (AP group) or conventional insulin therapy using the sliding-scale method (SS group). RESULTS The incidence of surgical-site infection in the AP group was significantly lower than that in the SS group. The length of hospitalization required for patients in the AP group was significantly shorter than that in the SS group. CONCLUSIONS Total hospital costs for patients in the AP group were significantly lower than for patients in the SS group. IIT using a closed-loop system maintained near-normoglycemia and contributed to a reduction in the incidence of SSI and total hospital costs due to shortened hospitalization.

I dedicate this paper to the late Prof. Yukihiko Nose with all my heart. In 2001, under the direction of Prof. Nose and Prof. Brunicardi at Baylor College of Medicine, we published a review article entitled "Artificial endocrine pancreas" in JACS. Subsequently, we reported that perioperative tight glycemic control (TGC) using an artificial pancreas (AP) with a closed-loop system could stably maintain near-normoglycemia in total-pancreatectomized dogs. Based on this experimental study in Houston, since 2006, we have introduced perioperative TGC using an AP into clinical use in Kochi. As of 2011, this novel TGC method has provided safe and stable blood glucose levels in more than 400 surgical patients. In this paper, we report new clinical findings regarding perioperative TGC using an AP in total-pancreatectomized patients. TGC using an AP enables us to achieve stable glycemic control not only without hypoglycemia and hyperglycemia but also with less variation in blood glucose concentration from the target blood glucose range, even in patients with the most serious form of diabetes, so-called "brittle diabetes", undergoing total pancreatectomy. To the best of our knowledge, this is the first clinical report of TGC using an AP in patients undergoing total pancreatic resection.

Blood glucose control in ICUs and operation rooms has some issues. First, hypoglycemia worsens the neurological prognosis of ICU patients and should definitely be avoided. To avoid hypoglycemic attacks require extensive attention by hospital staff. The two biggest advantages of continuous monitoring are the avoidance of hypoglycemia and the reduced workload for ICU staff. However, to achievement of automating blood glucose control, closed loop continuous glucose monitoring is essential. In this review, topics of blood glucose management in ICUs and operation rooms are introduced and advantages and limitations of closed loop continuous glucose monitoring are discussed.

Intrathoracic procedures can be performed with thoracoscopy in esophagectomy because the laparoscopic technique has recently been developed. During intrathoracic procedures, prone positioning of the patient allows gravity to facilitate optimal exposure of the esophagus, thereby affording a superb surgical view. In the current study, we compared the influence of prone positioning with lateral decubitus positioning on oxygenation in esophagectomy. We enrolled 18 patients and divided them into two groups: patients who underwent esophagectomy via thoracoscopy in the prone position (group P) and patients who underwent thoracotomy in the lateral decubitus position (control group, group L). Arterial blood gas analyses were performed before the operation was started (T1), 20 min after the initiation of one-lung ventilation (OLV) (T2), and two other points. The P/F ratio at T2 in group P was higher. Further, percent (%) change of the P/F ratios from T1 and thereafter in group P was higher at all points. We thought the reason why the prone position had contributed to maintenance oxygenation was as follows. First, the functional residual capacity and ventilation/perfusion matching in the prone position are satisfactory. Second, a bronchial blocker might contribute to reduction of atelectasis. Third, minimally invasive esophagectomy might reduce respiratory complications and blood loss because this procedure reduces edema and inflammation in the lung. In conclusion, the oxygenation provided by prone positioning is better than that provided by the lateral decubitus position during OLV in esophagectomy.

Perioperative glycemic control is important for reducing postoperative infectious complications. However, clinical trials have shown that efforts to maintain normoglycemia in intensive care unit patients result in deviation of glucose levels from the optimal range, and frequent attacks of hypoglycemia. Tight glycemic control is even more challenging in those undergoing pancreatic resection. Removal of lesions and surrounding normal pancreatic tissue often cause hormone deficiencies that lead to the destruction of glucose homeostasis, which is termed pancreatogenic diabetes. Pancreatogenic diabetes is characterized by the occurrence of hyperglycemia and iatrogenic severe hypoglycemia, which adversely effects patient recovery. Postoperatively, a variety of factors including surgical stress, inflammatory cytokines, sympathomimetic drug therapy, and aggressive nutritional support can also affect glycemic control. This review discusses the endocrine aspects of pancreatic resection and highlights postoperative glycemic control using a closed-loop system or artificial pancreas. In previous experiments, we have demonstrated the reliability of the artificial pancreas in dogs with total pancreatectomy, and its postoperative clinical use has been shown to be effective and safe, without the occurrence of hypoglycemic episodes, even in patients after total pancreatectomy. Considering the increasing requirement for tight perioperative glycemic control and the recognized risk of hypoglycemia, we propose the use of an artificial endocrine pancreas that is able to monitor continuously blood glucose concentrations with proven accuracy, and administer automatically substances to return blood glucose concentration to the optimal narrow range.

Glucose metabolism is adversely affected in patients following major surgery. Patients may develop hyperglycemia due to a combination of surgical stress and postoperative insulin resistance. A randomized trial was conducted to elucidate the effect of preoperative supplementation with carbohydrates and branched-chain amino acids on postoperative insulin resistance in patients undergoing hepatic resection. A total of 26 patients undergoing a hepatectomy for the treatment of a hepatic neoplasm were randomly assigned to receive a preoperative supplement of carbohydrate and branched-chain amino acid-enriched nutrient mixture or not. The postoperative blood glucose level and the total insulin requirement for normoglycemic control during the 16 h following hepatic resection were determined using the artificial pancreas STG-22. Postoperative insulin requirements for normoglycemic control in the group with preoperative nutritional support was significantly lower than that in the control group (P = 0.039). There was no incidence of hypoglycemia (

Background and aims Hyperglycemia induced by surgical stress often causes the dysregulation of liver metabolism and immune function resulting in impaired post-operative recovery. The aim of this study was to evaluate the usefulness of a closed-loop system providing continuous monitoring and strict control of post-operative blood glucose in patients after hepatic resection. Patients and methods A total of 19 patients who underwent hepatic resection for primary liver tumor between August and December 2006 were enrolled in the study. Following surgery, blood glucose was continuously monitored by the STG-22 closed-loop system. Glucose levels were controlled using either a manual injection of insulin according to the commonly used sliding scale (manual insulin group, n = 9) or a programmed infusion of insulin determined by the control algorithm of the STG-22 (programmed insulin group, n = 10). The total amount of insulin used in the first 16 h following hepatic resection in the two groups was measured. Results In the manual insulin group, post-operative blood glucose rose initially and reached a plateau of approximately 250 mg/dl between 4 h and 7 h post-hepatectomy and then returned towards normal levels by 16 h. In the programmed insulin group, blood glucose was steadily lowered, reaching the target zone (90–110 mg/dl) by 12 h post-surgery. The total amount of insulin administered per patient during the first 16 h post-surgery was significantly higher in the programmed insulin group (183 ± 188 IU) than in the manual insulin group (8 ± 7 IU; P < 0.001). No hypoglycemia was observed in either group. Conclusions Post-operative hyperglycemia was observed for up to 16 h in hepatectomized patients. In this post-operative hyperglycemic state, the STG-22 closed-loop system safely and quickly achieved glycemic control, indicating its clinical value in the post-operative management of hepatectomized patients.

5-aminolevulinic acid (ALA) is a naturally occurring amino acid that is a protoporphyrin IX (PpIX) precursor and a next-generation photosensitive substance. After exogenous administration of ALA, PpIX specifically accumulates in cancer cells owing to the impaired metabolism of ALA to PpIX in mitochondria, which results in a red fluorescence following irradiation with blue light and the formation of singlet oxygen. Fluorescence navigation by photodynamic diagnosis (PDD) using ALA provides good visualization and detection of gastric cancer lesions and is a potentially valuable diagnostic tool for gastric cancer for evaluating both the surgical resection margins and extension of the lesion. Furthermore, PDD using ALA might be used to detect peritoneal metastases during preoperative staging laparoscopy, where it could provide useful information for the selection of a therapeutic approach. Another promising application for this modality is in the evaluation of lymph node metastases. Photodynamic therapy (PDT) using ALA to cause selective damage based on the accumulation of a photosensitizer in malignant tissue is expected to be a non-invasive endoscopic treatment for superficial early gastric cancer. ALA has the potential to be used not only as a diagnostic agent but also as a therapeutic drug, resulting in a new strategy for cancer diagnosis and therapy. Here, we review the current use of PDD and PDT in gastric cancer and evaluate its future potential beyond conventional modalities combined with a light energy upconverter, a light-emitting diode and near-infrared rays as light sources.

To evaluate a closed-loop system providing continuous monitoring and strict control of perioperative blood glucose following pancreatic resection.Prospective, randomized clinical trial.Thirty patients who had pancreatic resection for pancreatic neoplasm.Patients were prospectively randomized. Perioperative blood glucose levels were continuously monitored using an artificial endocrine pancreas (STG-22). Glucose levels were controlled using either the sliding scale method (sliding scale group, n = 13) or the artificial pancreas (artificial pancreas group, n = 17).Incidence of severe hypoglycemia (40 mg/dL) during the intensive care period following pancreatic resection in patients monitored with the artificial pancreas. The secondary outcome measure was the total amount of insulin required for glycemic control in the first 18 hours after pancreatic resection in each patient group.In the sliding scale group, postoperative blood glucose levels rose initially before reaching a plateau of approximately 200 mg/dL between 4 and 6 hours after pancreatectomy. The levels remained high for 18 hours postoperatively. In the artificial pancreas group, blood glucose levels reduced steadily, reaching the target zone (80-110 mg/dL) by 6 hours after surgery. The total insulin dose administered per patient during the first postoperative 18 hours was significantly higher in the artificial pancreas group (mean [SD], 107 [109] IU) than the sliding scale group (8 [6] IU; P.01). Neither group showed hypoglycemia.Perioperative use of an artificial endocrine pancreas to control pancreatogenic diabetes after pancreatic resection is an easy and effective way to maintain near-normal blood glucose levels. The artificial pancreas shows promise for use as insulin treatment for patients with pancreatogenic diabetes after pancreatic resection.