Published papers

BACKGROUND: The utility of using indirect calorimetry (IC) to estimate energy needs and methods for its application to this purpose remain unclear. This systematic review investigated whether using IC to estimate energy expenditure in critically ill patients is more meaningful for improving survival than other estimation methods. METHODS: Comprehensive searches were conducted in MEDLINE using PubMed, Cochrane Central Register of Controlled Trials, and Igaku-Chuo-Zasshi up to March 2023. RESULTS: Nine RCTs involving 1178 patients were included in the meta-analysis. The evidence obtained suggested that energy delivery by IC improved short-term mortality (risk ratio, 0.86; 95% confidence interval [CI], 0.70 to 1.06). However, the use of IC did not appear to affect the length of ICU stay (mean difference [MD], 0.86; 95% CI, -0.98 to 2.70) or the duration of mechanical ventilation (MD, 0.66; 95% CI, -0.39 to 1.72). Post hoc analyses using short-term mortality as the outcome found no significant difference by target calories in resting energy expenditure, whereas more frequent IC estimates were associated with lower short-term mortality and were more effective in mechanically ventilated patients. CONCLUSIONS: This updated meta-analysis revealed that the use of IC may improve short-term mortality in patients with critical illness and did not increase adverse events.

Background & aims: High-fat, low-carbohydrate enteral nutrition has gained attention, with expectations of an improved respiratory condition, fewer complications, and lower mortality. The present study performed a systematic review and meta-analysis of randomized controlled trials to examine the effects of high-fat, low-carbohydrate enteral nutrition in critically ill adult patients. Methods: We searched MEDLINE via Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), and ICHUSHI for randomized controlled trials comparing high-fat, low-carbohydrate enteral nutrition to standard enteral nutrition in critically ill adult patients who received enteral nutrition. The primary outcome was mortality. Secondary outcomes included intensive care unit (ICU) mortality, length of ICU stay, length of mechanical ventilation, and adverse events of diarrhea and gastric residual volume. We examined the risk of bias using the Cochrane risk-of-bias tool for randomized trials version 2. We assessed the overall certainty of evidence based on the Grading of Recommendations Assessment, Development, and Evaluation methodology. Synthesis results were calculated with risk ratios and 95% confidence intervals using a Mantel-Haenszel random-effects model. Results: Eight trials with 607 patients were included. The effects of high-fat, low-carbohydrate enteral nutrition on mortality did not significantly differ from those of standard enteral nutrition (62/280 [22.1%] vs. 39/207 [18.8%], risk ratios = 1.14, 95% confidence intervals 0.80 to 1.62, P = 0.47). No significant differences were observed in ICU mortality, ICU length of stay, diarrhea, or gastric residual volume between the two groups. However, high-fat, low-carbohydrate enteral nutrition was associated with a significantly shorter duration of mechanical ventilation (mean difference −1.72 days, 95% confidence intervals −2.93 to −0.50, P = 0.005). Conclusion: High-fat, low-carbohydrate enteral nutrition may not affect mortality, but may decrease the duration of mechanical ventilation in critically ill adult patients. Limitations include the small number of studies and potential for bias. Further research is needed to confirm these results and investigate effects on other outcomes and in a subgroup of patients requiring mechanical ventilation.

Purpose: While follow-up CT and prophylactic embolization with angiography are often conducted during non-operative management (NOM) for BLSI, particularly in a high-grade injury, the utility of early repeated CT for preventing unexpected hemorrhage remains unclear. This study aimed to elucidate whether early follow-up computerized tomography (CT) within 7 days after admission would decrease unexpected hemostatic procedures on pediatric blunt liver and spleen injury (BLSI). Methods: A post-hoc analysis of a multicenter observational cohort study on pediatric patients with BLSI (2008–2019) was conducted on those who underwent NOM, in whom the timing of follow-up CT were decided by treating physicians. The incidence of unexpected hemostatic procedure (laparotomy and/or emergency angiography for ruptured pseudoaneurysm) and complications related to BLSI were compared between patients with and without early follow-up CT within 7 days. Inverse probability weighting with propensity scores adjusted patient demographics, comorbidities, mechanism and severity of injury, initial resuscitation, and institutional characteristics. Results: Among 1320 included patients, 552 underwent early follow-up CT. Approximately 25% of patients underwent angiography on the day of admission. The incidence of unexpected hemostasis was similar between patients with and without early repeat CT (8 [1.4%] vs. 6 [0.8%]; adjusted OR, 1.44 [0.62–3.34]; p = 0.40). Patients with repeat CT scans more frequently underwent multiple angiographies (OR, 2.79 [1.32–5.88]) and had more complications related to BLSI, particularly bile leak (OR, 1.73 [1.04–2.87]). Conclusion: Follow-up CT scans within 7 days was not associated with reduced unexpected hemostasis in NOM for pediatric BLSI.

Background: Remdesivir, an antiviral nucleotide analog prodrug, is approved for clinical use against COVID-19 worldwide. However, its effectiveness varies depending on the respiratory failure status of patients. This study aimed to evaluate the effectiveness of remdesivir treatment based on the severity of respiratory failure, as indicated by the oxygen demand upon hospital admission. Subgroups analyses were conducted to identify patient groups that might benefit from remdesivir treatment. Methods: This retrospective observational study (the J-RECOVER) enrolled patients with COVID-19 from 64 institutions in Japan between January 1 and September 30, 2020. Patients aged ≥ 18 years who were administered remdesivir within 3 days of hospital admission were included. A total of 3,591 patients were included, and propensity score overlap weighting analysis was used to compare in-hospital mortality based on respiratory failure status at admission between remdesivir and control groups. Subgroup analyses identified specific patient populations that may benefit most from remdesivir treatment, considering factors such as respiratory status and renal function. Results: The overlap weighting (OW)-adjusted odds ratio (OR) for mortality in overall cohort, mild cases without supplemental oxygen, moderate cases requiring supplemental oxygen, and severe cases requiring ventilation was (OR, 0.65 (95% confidence interval (CI), 0.36–1.19; P = 0.16), 0.11 (95% CI, 0.01–1.03; P = 0.05). 0.82 (95% CI, 0.31–2.16; P = 0.69), and 0.78 (95% CI, 0.28–2.17; P = 0.63), respectively. A trend toward improvement in mortality was observed in respiratory indicators, such as SpO2 ≥ 94% (OR, 0.43; 95% CI, 0.19–0.99; P = 0.04), oxygen support with FiO2 < 0.5 (OR, 0.40; 95% CI, 0.16–0.97; P = 0.04), and PFR ≥ 300 (OR, 0.17; 95% CI, 0.03–0.94; P = 0.04). Subgroup analyses indicated improved mortality in patients with an estimated glomerular filtration rate (eGFR) of > 60 mL/min per 1.73 m2 (OR, 0.29; 95% CI, 0.09–0.94; P = 0.03), with a p-value for interaction of P = 0.18. Conclusion: Remdesivir treatment may reduce the risk of in-hospital mortality in patients with mild respiratory distress. Subgroup analysis suggested that remdesivir treatment may improve mortality in patients with eGFR ≥ 60 mL/min per 1.73 m2.

Background: Advances in healthcare and the development of various technologies have improved disease-free longevity. Although the number of healthy centenarians is gradually increasing, studies on postinjury functions among centenarians are lacking. Therefore, we aimed to determine the clinical predictors of mortality and unfavorable functions after injury among centenarians. Method: A retrospective study was conducted using a nationwide trauma database, and data from patients aged ≥ 100 years across ≥ 250 institutions during 2019–2022 were analyzed. Patient demographics, comorbidities, mechanism of injury, injury severity, vital signs on arrival, and pre- and in-hospital treatments were compared between survivors and non-survivors as well as between survivors who had and did not have the ability to live independently at discharge, which was defined as Glasgow Outcome Scale (GCS) score of ≤ 3. Independent predictors of in-hospital mortality and unfavorable functions after injury were examined using a generalized estimating equation model to account for institutional and regional differences in the management and characteristics of centenarians. Results: Of the 409 centenarians, 384 (93.9%) survived to discharge. Although 208 (50.9%) patients had lived independently before the injury, only 91 (22.2%) could live independently at discharge. All patients had blunt injury, and fall from standing was the most frequent (86.6%) mechanism. The injury severity score was 10 ± 5, and surgery/angiography was performed in < 2% of the centenarians, except for fracture fixation in the extremity/pelvis, which was conducted in 225 (55.0%) patients. The adjusted model revealed three independent predictors of in-hospital mortality: male gender, mechanism of injury other than fall from standing, and GCS score on arrival. In contrast, only injury severity in the extremity/pelvis was an independent predictor of unfavorable functions after injury. Conclusion: Male gender, mechanisms of injury other than fall from standing, and GCS on arrival were associated with higher in-hospital mortality. Injury severity in the extremity/pelvis was related to dependent living after injury among centenarians.

Background: Pediatric trauma patients often have disability after successful resuscitation for hemorrhage. Clinical characteristics related to dependency on living following injury were elucidated among pediatric patients without traumatic brain injury. Methods: This retrospective cohort study used the 2019–2021 Japan Trauma Data Bank and included pediatric patients aged ≤16 years without head injury (Abbreviated Injury Scale [AIS] ≥ 2). The unfavorable function was defined as dependency in daily life at discharge (Glasgow Outcome Scale ≤ 3), and predictors for unfavorable functional outcomes were examined using a generalized estimating equations (GEE) model, including age, sex, physical disability before injury, injury mechanism, transportation time, prehospital procedures, vital signs on arrival, surgery in each body region, transfusion, AIS in each region, and institutions. Furthermore, these factors were analyzed separately in toddler/preschool (≤5 years), school age (6–11 years), and adolescence (12–16 years). Results: Among 1,412 patients eligible for the study, 137 had an unfavorable physical function at discharge. The GEE model revealed that female sex, physical disability before injury, prehospital transfusion, lower Glasgow Coma Score (GCS) score on arrival, neck surgery, and higher AIS in the neck and extremity/pelvis were independently associated with unfavorable function at discharge. In age-specific analyses, physical disability before injury strongly predicted worse functional outcomes in toddlers/preschoolers, whereas higher AIS in the chest and lower systolic blood pressure on arrival were additional predictors of dependent living among adolescents. Conclusions: Severe neck/extremity/pelvis injury and lower GCS on arrival are associated with unfavorable functional outcomes in patients with pediatric trauma.

BACKGROUND: Fungal infections are significant complications of severe coronavirus disease 2019 (COVID-19). Although various risk factors for poor outcomes in patients with COVID-19 have been identified, clinical and treatment factors associated with fungal infections in patients with severe COVID-19 remain unclear. This study aimed to elucidate clinical factors associated with fungal infections during severe COVID-19 treatment. METHODS: This was a post hoc analysis of the J-RECOVER study, a multicenter retrospective observational study involving patients with COVID-19 who required admission at 66 hospitals between January and September 2020. Inclusion criteria were ages ≥ 18 years, COVID-19 diagnosis with reverse-transcription polymerase chain reaction, and treatment with mechanical ventilation (MV). Patients who received antifungal drugs before MV were excluded. Potential predictors were identified through univariate analysis of patient and treatment characteristics between patients with- and those without fungal infection, which was defined as antifungal agent use for ≥ 5 days. To account for facility-specific data clustering, generalized estimating equations (GEE) were employed as adjusted analyses to calculate the relative risks of potentially associated factors. Two sensitivity analyses were performed with modified definitions for the two groups: patients who received antifungal drugs for ≤ 4 days were excluded, and fungal infection was re-defined as antifungal drug use for ≥ 14 days. RESULTS: Among 4,915 patients in the J-RECOVER study, 559 adults with COVID-19 who required MV were included. Fungal infections occurred in 57 (10.2%) patients. Univariate analyses identified age, age ≥ 65 years, D-dimer level, remdesivir use, steroid use, and duration of steroid therapy as potential predictors of fungal infections. Multivariate analysis using GEE on these six factors revealed that only the duration of steroid use was significantly associated with an increased risk of fungal infection (odds ratio [OR] for a day increase: 1.01; 95% confidence interval [CI]: 1.00-1.01; p < 0.001). The two sensitivity analyses similarly showed that the duration of steroid use was associated with fungal infection (odds ratio for a day increase: 1.01; 95% CI: 1.00-1.01; p < 0.001 for both). CONCLUSIONS: In patients with severe COVID-19 requiring MV, each additional day of steroid use was associated with prolonged use of antifungal medications for ≥ 5 days.

Background and aims: Critically ill pediatric patients, particularly infants, require sufficient nutrition even in the acute phase because they are at a high risk of malnutrition. Water restrictions are frequently required to avoid the adverse effects of fluid overload. Administration of energy or protein-dense enteral formulas is considered a potential therapeutic strategy to achieve these requirements simultaneously. This study aimed to assess efficacy and safety of energy or protein-dense enteral formula through a systematic review and meta-analysis. Methods: We searched MEDLINE via PubMed, Cochrane Central Register of Controlled Trials, and Igaku-Chuo-Zasshi in April 2023 for randomized controlled trials comparing high-density formulas (more than 0.9 kcal/mL) to standard-density formulas (0.67 to less than 0.9 kcal/mL) in critically ill pediatric patients undergoing enteral nutrition by artificial formula. The primary outcome was mortality, and secondary outcomes included length of stay in the intensive care unit (ICU), duration of mechanical ventilation, adverse events (emesis, diarrhea, and gastrointestinal bleeding), and weight-for-age Z score (WAZ). Data extraction and risk of bias assessment were performed by two independent reviewers using the Cochrane risk-of-bias tool. A meta-analysis was conducted using a random-effects model, and the certainty of the findings was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Results: Seven studies involving 542 patients were included in the meta-analysis. Six of these seven studies included patients with congenital heart disease, and the remaining study included infants with acute respiratory failure due to viral infection. The effects on mortality were not significant (risk ratio: 2.05, 95 % confidence interval: [CI] 0.76–5.50, P = 0.16, low certainty). No significant effects were observed on length of ICU stay, length of hospital stay, duration of mechanical ventilation, or adverse events. High-density formulas had a significant effect on increasing WAZ (mean difference: 0.61, 95 % CI: 0.28–0.94, P < 0.001, low certainty). Conclusion: Our results showed that the administration of high-density formulas was effective in increasing WAZ. Further investigation will contribute to improving the certainty of this evidence.

Background: The discussion is ongoing about appropriate indications for laparoscopic surgery in trauma patients. As timing and risks of conversion to laparotomy remain unclear, we aimed to elucidate characteristics of and risks for conversion following laparoscopic surgery, using a nationwide database. Methods: A retrospective observational study was conducted, using Japanese Trauma Data Bank (2004–2018). We included adult trauma patients who underwent laparoscopic surgery as an initial surgical intervention. Conversion to laparotomy was defined as laparotomy at the initial surgery. Patient demographics, mechanism and severity of injury, injured organs, timing of surgery, and clinical outcomes were compared between patients with and without conversion. Risks for conversion were analyzed focusing on indications for laparoscopic surgery, after adjusting patient and institution characteristics. Results: Among 444 patients eligible for the study, 31 required conversions to laparotomy. The number of laparoscopic surgeries gradually increased over the study period (0.5–4.5% of trauma laparotomy), without changes in conversion rates (5–10%). Patients who underwent conversion had more severe abdominal injuries compared with those who did not (AIS 3 vs 2). While length of hospital stay and in-hospital mortality were comparable, abdominal complications were higher among patients with conversion (12.9 vs. 2.9%), particularly when laparoscopy was performed for peritonitis (OR, 22.08 [5.11–95.39]). A generalized estimating equation model adjusted patient background and identified hemoperitoneum and peritoneal penetration as risks for conversion (OR, 24.07 [7.35–78.75] and 8.26 [1.20– 56.75], respectively). Conclusions: Trauma laparoscopy for hemoperitoneum and peritoneal penetration were associated with higher incidence of conversion to open laparotomy.

Background: The role of lactate level in selecting the timing of definitive surgery for isolated extremity fracture remains unclear. Therefore, we aimed to elucidate the use of preoperative lactate level for predicting early postoperative complications. Methods: This was a single-center retrospective observational study of patients with isolated extremity fracture who underwent orthopedic surgery. Patients who underwent lactate level assessment within 24 h prior to surgery were included. The incidence of early postoperative complications was compared between patients with a preoperative lactate level of ≥ 2 and < 2 mmol/L. Moreover, subgroup analyses were performed based on the time from hospital arrival to surgery and fracture type. Results: In total, 187 patients were included in the study. The incidence of postoperative complications was significantly higher in patients with a preoperative lactate level of ≥ 2 mmol/L than those with a preoperative lactate level of < 2 mmol/L. This result did not change after adjusting for age and severity. Further, a high preoperative lactate level was associated with a greater incidence of postoperative complications in patients who underwent definitive surgery within 6 h after arrival. Conclusion: A preoperative lactate level of ≥ 2 mmol/L was associated with a greater incidence of early postoperative complications in isolated extremity fractures. Nevertheless, this correlation was only observed among patients who underwent definitive fixation within 6 h after hospital arrival.

Background: Ultrasound is frequently used in emergency departments (EDs) for patient evaluation and diagnosis. Despite the risk of probe contamination from body fluids and blood, the rate of such contamination remains unclear. Aim: This study aimed to evaluate bacterial contamination of ultrasound probes in EDs, focusing on hospital types and reprocessing methods. Methods: A multi-centre prospective observational study was conducted at a university hospital, a non-academic tertiary hospital, and a regional hospital in 2023. Samples were collected from probes used on ED patients. Reprocessing methods included water-moistened wipes alone, water-moistened wipes with ethanol wipes, quaternary ammonium wipes alone, and quaternary ammonium wipes with ethanol or hypochlorite wipes. Outcomes included the level of bacterial contamination, measured by colony-forming units (cfu) per total surface area of each probe, and resistant bacterial strains. Findings: The median cfu was 10 (IQR: 0–50) at the university hospital, 40 (10–135) at the non-academic tertiary hospital, and 30 (1–95) at the regional hospital. By reprocessing method, the median cfu was 20 (1–90) for water-moistened wipes alone, 10 (0–20) for water-moistened wipes and additional ethanol wipe, 90 (40–180) for quaternary ammonium wipes alone, and 20 (1–50) for quaternary ammonium wipe and additional ethanol or hypochlorite wipe. Resistant bacterial strains were found on 18.2% of probes. Conclusion: High levels of bacterial contamination, including resistant strains, were observed on ultrasound probes in EDs, regardless of facility type and reprocessing method.

BACKGROUND: To elucidate the association between blood glucose levels at the return of spontaneous circulation (ROSC) and neurological outcomes following out-of-hospital cardiac arrest (OHCA), a post hoc analysis was conducted using data from a prospective observational study involving 41 hospitals in Tokyo and its suburbs from 2019 to 2021. Adults with nontraumatic OHCA who achieved ROSC were included. METHODS: A total of 1533 patients were analyzed. A spline curve for estimating neurological outcomes (Cerebral Performance Category score ≤2 at 30 days) by blood glucose level at ROSC was generated. Patients were classified into low, moderate, and high blood glucose groups, defined as <100, 100-300, and ≥300 mg/dL, respectively. Neurological outcomes were compared using generalized estimating equations adjusted for patient and institutional characteristics. RESULTS: Favorable neurologic outcomes were fewer in the low and high blood glucose groups than in the moderate group (8/132 [6.1 %] and 62/485 [12.8 %] vs. 181/807 [22.4 %]). The adjusted model revealed that low and high glucose levels at ROSC were associated with fewer favorable outcomes (odds ratios, 0.43 [0.18-0.96] and 0.59 [0.42-0.84]). High blood glucose levels showed unfavorable effects in subgroups with cardiogenic or noncardiogenic etiology, age <65 years, and low-flow time ≤30 min, whereas low blood glucose levels showed unfavorable effects only in cardiogenic cases. CONCLUSIONS: Blood glucose levels <100 and ≥300 mg/dL were associated with unfavorable neurological outcomes, with a nonlinear inverted U-shaped relationship.