Derivation and validation of an equation to determine the optimal ventilator setting in children undergoing intracranial revascularization surgery: A single-center retrospective study

Background: It can be difficult to determine the appropriate ventilator settings to maintain normocapnia in children undergoing general anesthesia for surgery for moyamoya disease, especially immediately following anesthesia induction. Aim: We conducted this study to attempt to derive an equation to predict the appropriate ventilator settings and subsequently validated the accuracy of the equation. Methods: A retrospective study of 91 pediatric patients less than 18 years of age who underwent cerebral revascularization for moyamoya disease at our institution. Fifty‐eight patients were used to derive the equation, and the subsequent 33 patients were used to validate the equation. We calculated the required respiratory rate to attain normocapnia based on the median of all values of the minute volume during normocapnia (estimated partial pressure of arterial carbon dioxide of 38‐42 mm Hg) and the assumption that the tidal volume was 8 mL/kg body weight. We derived the regression equation from the derivation data set where the required respiratory rate to attain normocapnia was represented by age. We simplified the equation by rounding coefficients to the nearest integer. The level of agreement between the respiratory rate predicted from the equation and the actual required respiratory rate was assessed in the validation group using Bland‐Altman analysis. Results: The derived equation is tidal volume = 8 mL/kg body weight, respiratory rate = 24‐age/min. Bland‐Altman analysis in the validation group revealed that the mean bias between the predicted and actual respiratory rate was 0.29 (standard deviation, 3.67). The percentage of cases where the predicted rate was within ± 10% and ± 20% of the actual rate was 42.4% and 66.7%, respectively. Conclusions: We derived and validated a simple and easily applicable equation to predict the ventilator settings required to attain normocapnia during general anesthesia in children with moyamoya disease

Validation of the Radford Nomogram to Estimate the Minute Volume Required to Attain Normocapnia in Patients Undergoing General Anesthesia: A Single-Center Retrospective Study

Objective: The Radford nomogram, an old mathematical chart device to estimate the required ventilation for maintaining normocapnia, remains unvalidated in patients undergoing modern, balanced anesthesia. This study aims to investigate the performance of the Radford nomogram in patients undergoing general anesthesia and derive a simple equation to estimate the minute volume required to attain normocapnia (MVnorm). Methods: This single-center retrospective study enrolled 78 patients (age ≥ 18 years) undergoing cerebral revascularization for Moyamoya disease. We defi ned MVnorm as the median of all values of the minute volume during normocapnia (estimated PaCO2: 38–42 mmHg). We examined the agreement level between the estimated minute volume using the Radford nomogram and MVnorm using the Bland–Altman analysis. Furthermore, we developed and validated a simple equation predicting MVnorm based on gender and a multiple of body weight, using a split-sample validation technique. Result: The Radford nomogram tended to overestimate MVnorm with a mean bias of 560 mL/min (95% limits of agreement, -848–1, 968 mL/min). The equation developed using data from the development group (n = 52): required minute volume (mL/min) = 85 × body weight (kg) in male patients and 70 × body weight (kg) in female patients. In the validation group (n = 26), the mean bias of this simple equation was 224 mL/min (95% limits of agreement, -1, 264–1, 712 mL/min). Conclusion: The Radford nomogram overestimates MVnorm in modern, balanced anesthesia. The simple equation using gender and a multiple of body weight yields similar predictive performance to the Radford nomogram

Invasive Respiratory or Vasopressor Support and/or Death as a Proposed Composite Outcome Measure for Perioperative Care Research

BACKGROUND: There is a need for a clinically relevant and feasible outcome measure to facilitate clinical studies in perioperative care medicine. This large-scale retrospective cohort study proposed a novel composite outcome measure comprising invasive respiratory or vasopressor support (IRVS) and death. We described the prevalence of IRVS in patients undergoing major abdominal surgery and assessed the validity of combining IRVS and death to form a composite outcome measure. METHODS: We retrospectively collected perioperative data for 2776 patients undergoing major abdominal surgery (liver, colorectal, gastric, pancreatic, or esophageal resection) at Kyoto University Hospital. We defined IRVS as requirement for mechanical ventilation for ≥24 hours postoperatively, postoperative reintubation, or postoperative vasopressor administration. We evaluated the prevalence of IRVS within 30 postoperative days and examined the association between IRVS and subsequent clinical outcomes. The primary outcome of interest was long-term survival. Multivariable Cox proportional regression analysis was performed to adjust for the baseline patient and operative characteristics. The secondary outcomes were length of hospital stay and hospital mortality. RESULTS: In total, 85 patients (3.1%) received IRVS within 30 postoperative days, 15 of whom died by day 30. Patients with IRVS had a lower long-term survival rate (1- and 3-year survival probabilities, 66.1% and 48.5% vs 95.2% and 84.0%, respectively; P < .001, log-rank test) compared to those without IRVS. IRVS was significantly associated with lower long-term survival after adjustment for the baseline patient and operative characteristics (adjusted hazard ratio, 2.72; 95% confidence interval, 1.97–3.77; P < .001). IRVS was associated with a longer hospital stay (median [interquartile range], 65 [39–326] vs 15 [12–24] days; adjusted P < .001) and a higher hospital mortality (24.7% vs 0.5%; adjusted P < .001). Moreover, IRVS was adversely associated with subsequent clinical outcomes including lower long-term survival (adjusted hazard ratio, 1.78; 95% confidence interval, 1.21–2.63; P = .004) when the analyses were restricted to 30-day survivors. CONCLUSIONS: Patients with IRVS can experience ongoing risk of serious morbidity and less long-term survival even if alive at postoperative day 30. Our findings support the validity of using IRVS and/or death as a composite outcome measure for clinical studies in perioperative care medicine

Identification of 45 New Neutron-Rich Isotopes Produced by In-Flight Fission of a 238U Beam at 345 MeV/nucleon

A search for new isotopes using in-flight fission of a 345 MeV/nucleon 238U beam has been carried out at the RI Beam Factory at the RIKEN Nishina Center. Fission fragments were analyzed and identified by using the superconducting in-flight separator BigRIPS. We observed 45 new neutron-rich isotopes: 71Mn, 73,74Fe, 76Co, 79Ni, 81,82Cu, 84,85Zn, 87Ga, 90Ge, 95Se, 98Br, 101Kr, 103Rb, 106,107Sr, 108,109Y, 111,112Zr, 114,115Nb, 115,116,117Mo, 119,120Tc, 121,122,123,124Ru, 123,124,125,126Rh, 127,128Pd, 133Cd, 138Sn, 140Sb, 143Te, 145I, 148Xe, and 152Ba

Proteomic Identification of Protein Targets for 15-Deoxy-Δ12,14-Prostaglandin J2 in Neuronal Plasma Membrane

15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is one of factors contributed to the neurotoxicity of amyloid β (Aβ), a causative protein of Alzheimer's disease. Type 2 receptor for prostaglandin D2 (DP2) and peroxysome-proliferator activated receptorγ (PPARγ) are identified as the membrane receptor and the nuclear receptor for 15d-PGJ2, respectively. Previously, we reported that the cytotoxicity of 15d-PGJ2 was independent of DP2 and PPARγ, and suggested that 15d-PGJ2 induced apoptosis through the novel specific binding sites of 15d-PGJ2 different from DP2 and PPARγ. To relate the cytotoxicity of 15d-PGJ2 to amyloidoses, we performed binding assay [3H]15d-PGJ2 and specified targets for 15d-PGJ2 associated with cytotoxicity. In the various cell lines, there was a close correlation between the susceptibilities to 15d-PGJ2 and fibrillar Aβ. Specific binding sites of [3H]15d-PGJ2 were detected in rat cortical neurons and human bronchial smooth muscle cells. When the binding assay was performed in subcellular fractions of neurons, the specific binding sites of [3H]15d-PGJ2 were detected in plasma membrane, nuclear and cytosol, but not in microsome. A proteomic approach was used to identify protein targets for 15d-PGJ2 in the plasma membrane. By using biotinylated 15d-PGJ2, eleven proteins were identified as biotin-positive spots and classified into three different functional proteins: glycolytic enzymes (Enolase2, pyruvate kinase M1 (PKM1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH)), molecular chaperones (heat shock protein 8 and T-complex protein 1 subunit α), cytoskeletal proteins (Actin β, F-actin-capping protein, Tubulin β and Internexin α). GAPDH, PKM1 and Tubulin β are Aβ-interacting proteins. Thus, the present study suggested that 15d-PGJ2 plays an important role in amyloidoses not only in the central nervous system but also in the peripheral tissues

Transient acute kidney injury after major abdominal surgery increases chronic kidney disease risk and 1-year mortality

[Purpose] We conducted a retrospective cohort study to determine incidences of transient and persistent acute kidney injury (AKI) after major abdominal surgery and their impacts on long-term outcome. [Materials and methods] We enrolled 3751 patients undergoing major abdominal surgery. Postoperative AKI was classified as transient or persistent based on the return of serum creatinine to the non-AKI range within 7 days post-surgery. Primary outcome was mortality within 1 year. We used multivariable Cox proportional hazard regression analysis to assess independent associations between AKI type and mortality. [Results] Most patients with AKI were classified as transient (84%). Compared to patients without AKI, both patients with transient and persistent AKI demonstrated elevated 1-year mortality rates [adjusted hazard ratio (95% confidence interval): 2.01 (1.34–2.93); P = 0.001, and 6.20 (3.00–11.43); P < 0.001, respectively] and greater risk of chronic kidney disease progression at 1 year [adjusted odds ratio (95% confidence interval): 3.87 (2.12–7.08) and 23.70 (9.64–58.22), respectively; both P < 0.001]. [Conclusions] Although most AKI cases after major abdominal surgery recover completely within 7 days, even these patients with transient AKI are at higher risk for 1-year mortality and chronic kidney disease progression compared to patients without AKI

Eldecalcitol reduces the risk of severe vertebral fractures and improves the health-related quality of life in patients with osteoporosis

Eldecalcitol reduces the risk of vertebral fractures in comparison to alfacalcidol in osteoporotic patients under vitamin D repletion. The aim of this study was to evaluate the effects of eldecalcitol on the spinal location of incident vertebral fractures, the severity of the fractures, and the changes in health-related quality of life (HRQOL) compared with those of alfacalcidol. The post hoc analysis has been performed on the data from the three-year, double-blind, randomized, head-to-head clinical trial of eldecalcitol versus alfacalcidol conducted in Japan. A total of 1054 patients were enrolled and randomized to take 0.75 μg eldecalcitol or 1.0 μg alfacalcidol daily for 3 years. The incidence of vertebral fractures was re-evaluated based on the location on the spine (upper T4–T10; lower T11–L4). The severity of vertebral fractures was determined by the semi-quantitative method, and the change in HRQOL was analyzed by using the Medical Outcomes Study Short Form 36-item questionnaire. The incidence of vertebral fracture at the lower spine was less in the eldecalcitol group than in the alfacalcidol group (p = 0.029). The incidence of severe vertebral fracture (Grade 3) was 3.8 % in the eldecalcitol group and 6.7 % in the alfacalcidol group, demonstrated a significant difference between the 2 groups (p = 0.036). Both eldecalcitol and alfacalcidol improved HRQOL in osteoporotic patients. Although no significant differences in each HRQOL scores were observed between eldecalcitol and alfacalcidol during the observational period, overall improvement from baseline of HRQOL scores were clearly observed in the eldecalcitol group. In conclusion, the incidences of lower spinal vertebral fractures and severe vertebral fractures were reduced further by eldecalcitol compared to alfacalcidol in the 3-year clinical trial. Daily treatment with eldecalcitol is effective in improving HRQOL, possibly owing to the reduced risk of lower spinal vertebral fractures and/or severe vertebral fractures

Factors associated with somnolence during brain function mapping in awake craniotomy

Somnolence during brain function mapping is one of the factors that inhibit the accomplishment of the goals of awake craniotomy. We examined the effect of anesthesia depth measured by bispectral index (BIS) during pre-awake phase on somnolence during brain function mapping and also explored the factors associated with somnolence. We examined the association between BIS values during pre-awake phase and somnolence during the first 30 min of brain function mapping in 55 patients who underwent awake craniotomy at Kyoto University Hospital from 2015 to 2018. The pre-awake BIS value was defined as the mean BIS value for 60 min before the removal of the airway. Somnolence during brain function mapping was the primary outcome, defined as either of the following conditions: inability to follow up, disorientation, or inability to assess speech function. Additionally, we compared patient or perioperative variables between patients with/without somnolence. Somnolence occurred in 14 patients (25.5%), of which 6 patients (10.9%) were unable to complete brain function mapping. There was no significant difference in the pre-awake BIS value between patients with/without somnolence (median: 46 vs. 49, P = 0.192). Somnolence was not significantly associated with age, gender, and the number of preoperative anticonvulsive drugs, but patients with somnolence had a significantly lower preoperative Western Aphasia Battery (WAB) aphasia quotient score (median 93.8 vs. 98.6, P = 0.011). We did not find an association between pre-awake BIS value and somnolence during brain function mapping. Somnolence likely occurs in patients with a low preoperative WAB aphasia quotient score

A Nationwide Questionnaire Survey on Awake Craniotomy in Japan

The number of awake craniotomies is increasing because of its beneficial features. However, not enough information is available regarding the current status of awake craniotomy in Japan. To evaluate the current status of awake craniotomy in institutes, a nationwide questionnaire survey was conducted. From June to August 2019, we conducted a questionnaire survey on awake craniotomy in the neurosurgery department of 45 institutes that perform awake craniotomies in Japan. Responses were obtained from 39 institutes (response rate, 86.7%). The main methods of awake craniotomy were almost the same in all institutes. Twenty-six institutes (66.7%) had fewer than 10 awake craniotomies (low-volume institutes) per year, and 13 high-volume institutes (33.3%) performed more than 10 awake craniotomies annually. Some institutes experienced a relatively high frequency of adverse events. In 11 institutes (28.2%), the frequency of intraoperative seizures was more than 10%. An intraoperative seizure frequency of 1%-9%, 10%-29%, and over 30% was identified in 12 (92%), 0 (0%), and 1 (8%) of the high-volume institutes, which was significantly less than in 16 (62%), 10 (38%), and 0 (0%) of the low-volume institutes (p = 0.0059). The routine usage of preoperative antiepileptic drugs was not different between them, but the old type was used more often in the low-volume institutes (p = 0.0022). Taken together, the annual number of awake craniotomies was less than 10 in over two-thirds of the institutes. Fewer intraoperative seizures were reported in the high-volume institutes, which tend not to preoperatively use the old type of antiepileptic drugs