Incidence of sodium-glucose cotransporter-2 inhibitor-associated perioperative ketoacidosis in surgical patients: a prospective cohort study.

PURPOSE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are commonly prescribed anti-diabetic medications with various beneficial effects; however, they have also been associated with ketoacidosis. The aim of this study was to determine the incidence of SGLT2i-associated perioperative ketoacidosis (SAPKA) in surgical patients. METHODS: We conducted a multicenter, prospective cohort study across 16 centers in Japan, enrolling surgical patients with diabetes who were prescribed SGLT2is between January 2021 and August 2022. Patients were monitored until the third postoperative day to screen for SAPKA, defined as urine ketone positivity with a blood pH of < 7.30 and HCO3 level ≤ 18.0 mEq/L, excluding cases of respiratory acidosis. RESULTS: In total, 759 of the 762 evaluated patients were included in the final analysis. Among these, three patients (0.40%) had urine ketones with a blood pH of < 7.30; however, blood gas analysis revealed respiratory acidosis in all three, and none of them was considered to have SAPKA. The estimated incidence of SGLT2i-associated postoperative ketoacidosis was 0% (95% confidence interval, 0%-0.4%). CONCLUSIONS: The observed incidence of SAPKA in our general surgical population was lower than expected. However, given that the study was observational in nature, interpretation of study results warrants careful considerations for biases.

External validation of the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 pneumonia managed on high-flow nasal cannula therapy: a multicenter retrospective observational study in Japan.

BACKGROUND: The HACOR score for predicting treatment failure includes vital signs and acid-base balance factors, whereas the ROX index only considers the respiratory rate, oxygen saturation, and fraction of inspired oxygen (FiO2). We aimed to externally validate the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 (COVID-19) on high-flow nasal cannula (HFNC) therapy in Japan. METHODS: This retrospective, observational, multicenter study included patients, aged ≥ 18 years, diagnosed with COVID-19 and treated with HFNC therapy between January 16, 2020, and March 31, 2022. The HACOR score and ROX index were calculated at 2, 6, 12, 24, and 48 h after stating HFNC therapy. The primary outcome was treatment failure (requirement for intubation or occurrence of death within 7 days). We calculated the area under the receiver operating characteristic curve (AUROC) and assessed the diagnostic performance of these indicators. The 2-h time-point prediction was considered the primary analysis and that of other time-points as the secondary analysis. We also assessed 2-h time-point sensitivity and specificity using previously reported cutoff values (HACOR score > 5, ROX index < 2.85). RESULTS: We analyzed 300 patients from 9 institutions (median age, 60 years; median SpO2/FiO2 ratio at the start of HFNC therapy, 121). Within 7 days of HFNC therapy, treatment failure occurred in 127 (42%) patients. The HACOR score and ROX index at the 2-h time-point exhibited AUROC discrimination values of 0.63 and 0.57 (P = 0.24), respectively. These values varied with temporal changes-0.58 and 0.62 at 6 h, 0.70 and 0.68 at 12 h, 0.68 and 0.69 at 24 h, and 0.75 and 0.75 at 48 h, respectively. The 2-h time-point sensitivity and specificity were 18% and 91% for the HACOR score, respectively, and 3% and 100% for the ROX index, respectively. Visual calibration assessment revealed well calibrated HACOR score, but not ROX index. CONCLUSIONS: In COVID-19 patients receiving HFNC therapy in Japan, the predictive performance of the HACOR score and ROX index at the 2-h time-point may be inadequate. Furthermore, clinicians should be mindful of time-point scores owing to the variation of the models' predictive performance with the time-point. Trial registration UMIN (registration number: UMIN000050024, January 13, 2023).

Concomitant severe traumatic brain injury is not associated with increased red blood cell transfusion volumes in patients with pelvic fractures: A retrospective observational study.

INTRODUCTION: Traumatic brain injury (TBI)-associated coagulopathy significantly influences survival outcomes in patients with multiple injuries. Severe TBI can potentially affect systemic hemostasis due to coagulopathy; however, there is limited evidence regarding whether the risk of hemorrhage increases in patients with pelvic fractures complicated with TBI. Therefore, through multivariable analysis, we aimed to examine the association between severe TBI and increased blood transfusion requirements in patients with pelvic fractures. MATERIALS AND METHODS: This retrospective observational study was conducted at a tertiary care facility in Japan. Patients aged 16 years or older with pelvic fractures who were admitted to our intensive care unit between April 2014 and December 2021 were included in the analysis. The patients were categorized into no to mild and severe TBI groups according to whether the Head Abbreviated Injury Scale (AIS) score was 3 or higher. The primary outcome was the number of red blood cell (RBC) units transfused within 24 h after arrival at the hospital. The primary outcome was analyzed using univariable and multivariable linear regression analyses. The covariates used for the multivariable linear regression analysis were age, sex, antithrombotic therapy, mechanism of injury, Pelvic AIS score, and extravasation on contrast-enhanced computed tomography on admission. RESULTS: We identified 315 eligible patients (221 and 94 in the no to mild and severe TBI groups, respectively). In the univariable analysis, the RBC transfusion volume within 24 h after arrival was significantly higher in the severe TBI group than in the no to mild TBI group (2.53-unit increase; 95 % confidence interval [CI]: 0.46-4.61). However, in the multivariable analysis, no statistically significant association was detected between severe TBI and the RBC transfusion volume within 24 h after arrival at the hospital (0.87-unit increase; 95 % CI: -1.11-2.85). CONCLUSIONS: Concomitant severe TBI was not associated with increased RBC transfusion volumes in patients with pelvic fractures on multivariable analysis.

Intensive care unit mortality and cost-effectiveness associated with intensivist staffing: a Japanese nationwide observational study.

BACKGROUND: Japan has four types of intensive care units (ICUs) that are divided into two categories according to the management fee charged per day: ICU management fees 1 and 2 (ICU1/2) (equivalent to high-intensity staffing) and 3 and 4 (ICU3/4) (equivalent to low-intensity staffing). Although ICU1/2 charges a higher rate than ICU3/4, no cost-effectiveness analysis has been performed for ICU1/2. This study evaluated the clinical outcomes and cost-effectiveness of ICU1/2 compared with those of ICU3/4. METHODS: This retrospective observational study used a nationwide Japanese administrative database to identify patients admitted to ICUs between April 2020 and March 2021 and divided them into the ICU1/2 and ICU3/4 groups. The ICU mortality rates and in-hospital mortality rates were determined, and the incremental cost-effectiveness ratio (ICER) (Japanese Yen (JPY)/QALY), defined as the difference between quality-adjusted life year (QALY) and medical costs, was compared between ICU1/2 and ICU3/4. Data analysis was performed using the Chi-squared test; an ICER of < 5 million JPY/QALY was considered cost-effective. RESULTS: The ICU1/2 group (n = 71,412; 60.7%) had lower ICU mortality rates (ICU 1/2: 2.6% vs. ICU 3/4: 4.3%, p < 0.001) and lower in-hospital mortality rates (ICU 1/2: 6.1% vs. ICU 3/4: 8.9%, p < 0.001) than the ICU3/4 group (n = 46,330; 39.3%). The average cost per patient of ICU1/2 and ICU3/4 was 2,249,270 ± 1,955,953 JPY and 1,682,546 ± 1,588,928 JPY, respectively, with a difference of 566,724. The ICER was 718,659 JPY/QALY, which was below the cost-effectiveness threshold. CONCLUSIONS: ICU1/2 is associated with lower ICU patient mortality than ICU3/4. Treatments under ICU1/2 are more cost-effective than those under ICU3/4, with an ICER of < 5 million JPY/QALY.

Aortic valve replacement in a 41-year-old woman with uncorrected tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries: a case report.

BACKGROUND: Tetralogy of Fallot (TOF) is a complex cyanotic congenital heart disease. As most patients with TOF undergo palliative or radical surgical repair during childhood, cardiac surgery under cardiopulmonary bypass (CPB) for adult survivors with unrepaired TOF is exceedingly rare. CASE PRESENTATION: A 41-year-old woman with unrepaired TOF, pulmonary atresia (PA), and major aortopulmonary collateral arteries (MAPCAs) developed acute infectious endocarditis (IE). As vegetation gradually increased despite intravenous antibiotic administration, she was scheduled for urgent aortic valve replacement under CPB. Pulmonary blood flow was primarily provided by the MAPCAs originating from the descending aorta. Intra-aortic balloon occlusion for MAPCAs was performed to ensure a bloodless surgical field. Aortic valve replacement was successful. CONCLUSION: An adult with uncorrected TOF developed acute IE and subsequently had successful cardiac surgery under CPB. Understanding TOF physiology with PA and MAPCAs, particularly pulmonary blood flow through MAPCAs, is crucial.

Association Between Intraoperative Landiolol Use and In-Hospital Mortality After Coronary Artery Bypass Grafting: A Nationwide Observational Study in Japan.

BACKGROUND: Ischemic heart disease is a leading cause of death worldwide, and coronary artery bypass grafting (CABG) is a major treatment. Landiolol is an ultra-short-acting beta-antagonist known to prevent postoperative atrial fibrillation. However, the effectiveness of intraoperative landiolol on mortality remains unknown. This study aimed to evaluate the association between intraoperative landiolol use and the in-hospital mortality in patients undergoing CABG. METHODS: To conduct this retrospective cohort study, we used data from the Japanese Diagnosis Procedure Combination inpatient database. All patients who underwent CABG during hospitalization between July 1, 2010, and March 31, 2020, were included. Patients who received intraoperative landiolol were defined as the landiolol group, whereas the other patients were defined as the control group. The primary outcome was in-hospital mortality. Propensity score matching was used to compare the landiolol and control groups. RESULTS: In total, 118,506 patients were eligible for this study, including 25,219 (21%) in the landiolol group and 93,287 (79%) in the control group. One-to-one propensity score matching created 24,893 pairs. After propensity score matching, the in-hospital mortality was significantly lower in the landiolol group than that in the control group (3.7% vs 4.3%; odds ratio 0.85; 95% confidence interval 0.78 to 0.94; P = .010). CONCLUSIONS: Intraoperative landiolol use was associated with decreased in-hospital mortality in patients undergoing CABG. Further randomized controlled trials are required to confirm these findings.

Gender Disparities in First Authorship at Three Medical Universities in an Area Affected by the Great East Japan Earthquake.

The Great East Japan Earthquake that occurred on March 11, 2011, was one of the largest natural disasters in modern times. Publication in medical journals is important aspects of the academic promotion process, and is thus important for all scientists. However, little is known about whether and how substantial natural disasters affect gender disparities in academic productivity in disaster-affected areas. We hypothesized that the Great East Japan Earthquake widened the existing disparities in scientific publishing between male and female researchers. To test this hypothesis, this retrospective observational study using existing databases was conducted. We extracted from the MEDLINE database all types of biomedical articles published from March 11, 2007, to March 11, 2015, by three medical universities in a disaster-affected area of Japan. Differences in the proportion of female first authorship during the 4 years before and after the Great East Japan Earthquake were compared. A total of 5,873 papers were analyzed. The proportion of female first authors significantly declined after the Great East Japan Earthquake (20.5% vs. 14.1%; odds ratio 0.64; 95% confidence interval 0.56-0.73). A similar trend was identified across all prespecified subgroups, including clinical department; original article; public medical university; and prestigious journal with impact factor >6. Reference data from two medical universities minimally affected by the Great East Japan Earthquake showed the opposite trend. These results collectively suggest that large natural disasters can reinforce existing gender disparities in first authorship in biomedicine.

Circulating Extracellular Vesicle Levels in Patients with Coronavirus Disease 2019 Coagulopathy: A Prospective Cohort Study.

Coronavirus disease 2019 (COVID-19) is associated with coagulopathy. However, the underlying mechanisms are not completely understood. We evaluated the association between COVID-19 coagulopathy and extracellular vesicle (EV) levels. We hypothesized that several EV levels would be higher in COVID-19 coagulopathy patients than in non-coagulopathy patients. This prospective observational study was conducted in four tertiary care faculties in Japan. We enrolled 99 COVID-19 patients (48 with coagulopathy and 51 without coagulopathy) aged ≥20 years who required hospitalization, and 10 healthy volunteers; we divided the patients into coagulopathy and non-coagulopathy groups according to the D-dimer levels (≥1 µg/mL and <1 µg/mL, respectively). We used flow cytometry to measure the tissue-factor-bearing, endothelium-derived, platelet-derived, monocyte-derived, and neutrophil-derived EV levels in platelet-free plasma. The EV levels were compared between the two COVID-19 groups as well as among the coagulopathy patients, non-coagulopathy patients, and healthy volunteers. No significant difference was found in EV levels between the two groups. Meanwhile, the cluster of differentiation (CD) 41 + EV levels were significantly higher in COVID-19 coagulopathy patients than in healthy volunteers (549.90 [255.05-984.65] vs. 184.3 [150.1-254.1] counts/µL, p = 0.011). Therefore, CD41+ EVs might play an essential role in COVID-19 coagulopathy development.

Long-Term Incidence and Timing of Splenic Pseudoaneurysm Formation after Blunt Splenic Injury: A Descriptive Study.

BACKGROUND: Nonoperative management (NOM) has become a standard strategy for hemodynamically stable patients with blunt splenic injury; however, delayed rupture of splenic pseudoaneurysm (SPA) is a serious complication of NOM. In medical literature, data regarding the long-term incidence of SPA are scarce, and the appropriate timing for performing follow-up contrast-enhanced computed tomography (CT) has not yet been reported. This study aimed to elucidate the long-term incidence and timing of SPA formation after blunt splenic injury in patients treated with NOM. METHODS: This descriptive study was conducted at a tertiary medical center in Japan. Patients with blunt splenic injury who were treated with NOM between April 2014 and August 2020 were included in the analysis. Included patients underwent repeated contrast-enhanced CT to detect SPA formation. The primary outcome was the cumulative incidence of delayed formation of SPA. We also evaluated differences in SPA formation between patients who received transcatheter arterial embolization (TAE; TAE group) and those who did not receive it (non-TAE group) on admission day. RESULTS: Among 49 patients with blunt splenic injury who were treated with NOM, 5 patients (10.2%) had delayed formation of SPA. All cases of SPA formation occurred within 15 days of injury. The incidence of SPA formation was not significantly different between the TAE and non-TAE groups (1/19 vs. 4/30, P = 0.67). CONCLUSIONS: SPA developed in 10% of patients within approximately 2 weeks after blunt splenic injury. Therefore, performing follow-up contrast-enhanced CT in this period after injury may be useful to evaluate delayed formation of SPA. Although our findings are novel, they should be confirmed through future studies with larger sample sizes.

Transcatheter arterial embolization using imipenem/cilastatin sodium and microspheres for traumatic pseudoaneurysm: A case report.

For transcatheter arterial embolization (TAE) of pseudoaneurysms, when the culprit artery is too small or tortuous to be selected with a microcatheter, n-butyl-2-cyanoacrylate (NBCA) may be used as embolic material. Nevertheless, NBCA can cause inadvertent embolization and ischemic complications because liquid adhesives cannot be controlled precisely. In such cases, imipenem/cilastatin sodium (IPM/CS) could be used as an alternative to NBCA for TAE. However, TAE using IPM/CS for traumatic pseudoaneurysms has not been reported previously. Therefore, the possibility of using IPM/CS to embolize refractory traumatic pseudoaneurysms with small culprit arteries remains unknown. A previously healthy 51-year-old man sustained multiple traumatic injuries, including an open pelvic fracture. An emergency TAE for the pelvic fracture, massive blood transfusion, and emergency colostomy and cystostomy were performed on admission day, following which the patient was hemodynamically stable. However, he had repeated episodes of hematochezia due to pelvic pseudoaneurysm on days 18, 53, 60, and 70 after admission despite several TAE attempts using gelatin sponge, coils, and NBCA. During recurrence on day 70, we performed TAE using IPM/CS and microspheres, following which the pseudoaneurysm resolved without rebleeding or obvious ischemic complications. IPM/CS and microspheres could embolize, without rebleeding, the refractory pseudoaneurysm in small and tortuous culprit arteries that could not be embolized with NBCA. For embolization of traumatic pseudoaneurysms with severe tissue damage and small culprit arteries, NBCA might not be able to reach the bleeding point. In such cases, TAE using IPM/CS and microspheres could be a safe and effective procedure.

Corticosteroid use with extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A nationwide observational study.

Aim: Several studies have reported that corticosteroid administration for cardiac arrest patients may improve outcomes. However, these previous studies have not examined the effect of corticosteroid use in out-of-hospital cardiac arrest (OHCA) patients administered extracorporeal cardiopulmonary resuscitation (ECPR). Therefore, we aimed to examine the effectiveness of corticosteroids in OHCA patients administered ECPR. Methods: Using the Japanese Diagnosis Procedure Combination inpatient database, we included OHCA patients who were administered ECPR on the day of admission between July 2010 and March 2019. The patients were categorized into the corticosteroid and control groups according to whether they received corticosteroids on the day of admission or not. The primary outcome was in-hospital mortality and the secondary outcomes included percentages of neurologically favorable survival, major bleeding complications, and infection-related complications. We compared the outcomes using a propensity score matching analysis. Results: We identified 6,142 eligible patients (459 vs 5,683, the corticosteroid and control group, respectively). One-to-four propensity score matching analysis (457 vs 1,827) showed in-hospital mortality was significantly higher in the corticosteroid group compared with the control group (82.1% vs 76.6%; risk difference, 5.5%; 95% CI, 1.5 to 9.5%). Neurologically favorable outcomes did not differ between the two groups (13.6% vs 16.9%; risk difference, -3.3%; 95% CI, -6.9 to 0.3%). The percentage of major bleeding complications and infection-related complications did not significantly differ between the two groups. Conclusions: The results of this study demonstrated that administration of corticosteroids on the day of admission to OHCA patients administered ECPR was associated with increased in-hospital mortality.

The effect of preoperative sodium-glucose cotransporter 2 inhibitors on the incidence of perioperative metabolic acidosis: A retrospective cohort study.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are a novel class of anti-hyperglycemic agents. Although several cases of perioperative euglycemic diabetic ketoacidosis have been linked to these medications, the association remains unclear. This study aimed to examine the association between sodium-glucose cotransporter 2 inhibitor use and the incidence of perioperative metabolic acidosis with euglycemia, the surrogating outcome of perioperative euglycemic diabetic ketoacidosis. METHOD: This was a retrospective, matched cohort study, which was conducted in the intensive care unit of a tertiary care facility in Japan. We identified patients aged 20 years or older with diabetes mellitus who received pharmacologic therapy and were admitted to the intensive care unit after elective surgery between April 2014 and March 2019. We extracted the following data from the electronic medical record for matching: age, sex, surgery year, surgical site, hemoglobin A1c level, and prescription for sodium-glucose cotransporter 2 inhibitors. Eligible patients were divided into two groups, those who were prescribed sodium-glucose cotransporter 2 inhibitors (SGLT2-i group) and those who were not (control group). For each patient in the SGLT2-i group, we randomly selected four patients from the control group matched for the extracted characteristics. The primary outcome was the incidence of metabolic acidosis with an elevated anion gap and euglycemia. The secondary outcome was the lowest pH value of each patient during their ICU stay. RESULTS: A total of 155 patients were included in this study. Patients receiving sodium-glucose cotransporter 2 inhibitors had comparable characteristics to control participants; however, the proportions of patients undergoing dialysis were not similar. Metabolic acidosis with euglycemia was seen in 7/31 (22.6%) patients receiving sodium-glucose cotransporter 2 inhibitors and in 10/124 (8.1%) control patients (p = 0.047). CONCLUSIONS: This study shows that the use of sodium-glucose cotransporter 2 inhibitors is associated with a significantly higher incidence of metabolic acidosis with euglycemia. Patients receiving sodium-glucose cotransporter 2 inhibitors who are scheduled to undergo invasive surgical procedures should be closely monitored for the development of euglycemic diabetic ketoacidosis.

ARDS Clinical Practice Guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

COVID-19 in a Hairy Cell Leukemia Patient: A Rare Case Report.

The detailed clinical course of coronavirus disease 2019 (COVID-19) in patients with hairy cell leukemia (HCL) is rarely reported. We report the first case of HCL diagnosed with prolonged pancytopenia after COVID-19 infection in Japan. We describe the case of a 56-year-old man who was diagnosed with COVID-19. Computed tomography revealed ground-glass opacities in the bilateral lung lobes as well as splenomegaly. Remdesivir and dexamethasone were administered for the treatment of COVID-19. Since the pancytopenia persisted, bone marrow examination was performed, and he was diagnosed with HCL. Although pancytopenia can occur with COVID-19 alone, clinicians should be alerted regarding the presence of hematologic malignancies in patients in whom pancytopenia persists after COVID-19 treatment or in those with splenomegaly. Further, the condition of all previously reported patients with COVID-19 associated with HCL was severe enough to require mechanical ventilation. This is the first case in which the disease was not severe. The interleukin-6 (IL-6) level was lower in this case than in previous cases, suggesting that racial differences in IL-6 production may have contributed to COVID-19 severity.

Sevoflurane administration from extracorporeal membrane oxygenation via the AnaConDa device for a patient with COVID-19: A breakthrough solution for the shortage of intravenous anesthetics.

One of the major issues encountered during the coronavirus disease 2019 (COVID-19) pandemic has been the shortage of intravenous anesthetics. Moreover, patients undergoing extracorporeal membrane oxygenation (ECMO) need large quantities of intravenous anesthetics for sedation. We report the case of a 52-year-old man who was admitted to our hospital due to acute respiratory distress syndrome by COVID-19 and treated with ECMO. As controlling sedation with intravenous anesthetics was challenging, we attempted to administer inhaled anesthetics via the gas flow of ECMO. We decreased the quantity of intravenous anesthetics and opioids. This method might help overcome the shortage of intravenous anesthetics.

ARDS clinical practice guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

Impact of emergency physician-staffed ambulances on preoperative time course and survival among injured patients requiring emergency surgery or transarterial embolization: A retrospective cohort study at a community emergency department in Japan.

Injured patients requiring definitive intervention, such as surgery or transarterial embolization (TAE), are an extremely time-sensitive population. The effect of an emergency physician (EP) patient care delivery system in this important trauma subset remains unclear. We aimed to clarify whether the preoperative time course and mortality among injured patients differ between ambulances staffed by EPs and those staffed by emergency life-saving technicians (ELST). This was a retrospective cohort study at a community emergency department (ED) in Japan. We included all injured patients requiring emergency surgery or TAE who were transported directly from the ED to the operating room from January 2002 to December 2019. The primary exposure was dispatch of an EP-staffed ambulance to the prehospital scene. The primary outcome measures were preoperative time course including prehospital length of stay (LOS), ED LOS, and total time to definitive intervention. The other outcome of interest was in-hospital mortality. One-to-one propensity score matching was performed to compare these outcomes between the groups. Of the 1,020 eligible patients, 353 (34.6%) were transported to the ED by an EP-staffed ambulance. In the propensity score-matched analysis with 295 pairs, the EP group showed a significant increase in median prehospital LOS (71.0 min vs. 41.0 min, P < 0.001) and total time to definitive intervention (189.0 min vs. 177.0 min, P = 0.002) in comparison with the ELST group. Conversely, ED LOS was significantly shorter in the EP group than in the ELST group (120.0 min vs. 131.0 min, P = 0.043). There was no significant difference in mortality between the two groups (8.8% vs.9.8%, P = 0.671). At a community hospital in Japan, EP-staffed ambulances were found to be associated with prolonged prehospital time, delay in definitive treatment, and did not improve survival among injured patients needing definitive hemostatic procedures compared with ELST-staffed ambulances.

Multicentre prospective observational study of sodium-glucose cotransporter-2 inhibitor-associated postoperative ketoacidosis: the SAPKA study protocol.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antihyperglycaemic agents that promote urinary glucose excretion in the renal proximal tubule and have cardio-protective and renal-protective properties. However, there are several safety concerns related to increased risks of hypoglycaemic, urinary tract infections and ketoacidosis. Ketoacidosis is a potentially fatal complication that often presents as euglycaemic ketoacidosis during SGLT2 inhibitor treatment. Furthermore, invasive treatment and related surgical stress may increase the risk of ketogenesis. Therefore, this study aims to clarify the incidence of SGLT2 inhibitor-associated postoperative ketoacidosis (SAPKA) among patients who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia. METHODS AND ANALYSIS: This multicentre, prospective, observational study will recruit 750 adult Japanese patients with diabetes who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia. Urine samples will be collected on postoperative days 0, 1, 2 and 3. Blood gas analysis will be performed when urine ketone positivity is detected. The incidence of postoperative ketoacidosis will be identified based on urine ketone positivity and a blood pH of ≤7.3. The study will also collect data to identify risk factors for SAPKA. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committee of Kyorin University (approval number: 785, 26 October 2020) and local ethical approval will be required at each participating centre. Study findings will be submitted to peer-reviewed journals and abstracts will be submitted to relevant national and international meetings. TRIAL REGISTRATION NUMBER: UMIN000042795.

Case Report: Successful Treatment of Five Critically Ill Coronavirus Disease 2019 Patients Using Combination Therapy With Etoposide and Corticosteroids.

Acute respiratory distress syndrome (ARDS) is the leading cause of mortality in hospitalized patients with coronavirus disease 2019 (COVID-19) because of limited effective therapies. During infection, the accumulation and activation of macrophages and monocytes in the lungs induce inflammatory mediators and contribute to tissue injury, leading to ARDS. However, therapeutic strategies that directly target activated macrophage and monocytes have not been reported. Combination treatment with etoposide (a cytotoxic agent) and a corticosteroid has been widely used for treating hemophagocytic lymphohistiocytosis characterized by the systemic activation of macrophages with overwhelming inflammation. Herein, we present five cases of COVID-19-associated ARDS treated with etoposide and corticosteroids. Three of the five patients were over 65 years of age and had various underlying diseases, including multiple myeloma. Four patients required invasive mechanical ventilation (MV), and one patient refused to be placed on MV due to underlying diseases. All patients were pre-treated with antiviral and/or other anti-inflammatory agents, but their condition deteriorated and hyperinflammation was noted. All five patients responded well to treatment and had an immediate response, as reflected by improvement in their respiratory condition and inflammatory marker levels and rapid resolution of fever after etoposide administration; however, some patients required a second dose of etoposide and longer course of steroids. All patients recovered, and there were no severe adverse events related to the drugs. Following successful treatment in these five patients, we plan to conduct a clinical trial to evaluate the efficacy and safety of combination therapy with etoposide and corticosteroid for treating COVID-19 patients in Japan.