The association between intraoperative anesthesia methods used during gastric cancer surgery and long-term mortality: A retrospective observational study using a Japanese claims database.

PURPOSE: Various basic and clinical studies have investigated the association between the types of anesthetic agents and prognosis. However, the results have varied among studies and remain controversial. In the present study, we aimed to investigate whether the risk of all-cause mortality differs between inhaled or intravenous anesthetics in patients with gastric cancer undergoing gastrectomy. METHODS: Using a Japanese nationwide insurance claims database, we analyzed patients who underwent gastrectomy under general anesthesia for gastric cancer between January 2005 and September 2019. Postoperative outcomes were compared between two groups: those who received inhaled anesthetics (Sevoflurane, Isoflurane, or Desflurane) and those who received intravenous anesthetics (propofol), using a multivariable Cox proportional hazards model. The primary outcome was overall survival. RESULTS: Among 2671 eligible patients, 2105 were in the inhaled anesthetic group, and 566 were in the intravenous anesthetic group. The median (interquartile range) age was 58 (51-63) years, and 1979 (74.1%) were men. The median follow-up period was 795 days. We identified 56 (2.7%) and 16 (2.8%) deaths during the follow-up period in the inhaled and intravenous anesthetic use groups, respectively. There was no difference in postoperative overall survival between the two groups (hazard ratio, 0.97; 95% confidence interval, 0.56-1.70; P = 0.93). CONCLUSIONS: We found no significant difference in the postoperative risks of overall survival between inhaled and intravenous anesthesia in patients with gastric cancer undergoing gastrectomy.

Safety of sugammadex for myasthaenia gravis patients undergoing general anaesthesia: a retrospective database study.

Background: Using neuromuscular blocking drugs (NMBDs) for patients with myasthaenia gravis remains a challenge in perioperative management. Sugammadex has enabled the safe use of NMBDs. We investigated whether the adverse outcomes, and the treatment used for myasthaenic crises and tracheotomy, are affected by NMBD use in patients with myasthaenia gravis under general anaesthesia. Methods: Patients with myasthaenia gravis who underwent general anaesthesia were retrieved from the Diagnostic Procedure Combination/Per-Diem Payment systems in Japan between 1 January 2010 and 30 November 2020. This database did not contain information on the severity of myasthaenia gravis (Osserman classification). Patients who received rocuronium and sugammadex were compared with those who did not receive NMBDs after propensity-score matching. We excluded patients who underwent emergency or cardiac surgery or tracheal intubation before anaesthesia. The primary outcome was receipt of postoperative treatment used for myasthaenic crises. Results: Among 2304 surgical patients with comorbid myasthaenia gravis, propensity-score matching identified 788 patients administered rocuronium and sugammadex and 449 not administered NMBDs. On comparing the treatment used for myasthaenic crises, we found no significant difference between the two groups (6.2% vs 5.3%; hazard ratio, 1.14; 95% confidence interval, 0.70-1.85). Conclusions: Use of rocuronium and sugammadex in patients with myasthaenia gravis did not significantly affect the receipt of postoperative treatment used for myasthaenic crises compared with no use of NMBDs. As well as the severity of myasthaenia gravis was not fully adjusted, it is unclear whether intraoperative administration of rocuronium with the use of sugammadex postoperatively is acceptable and further investigations are needed.

Hyperchloremia and Postoperative Acute Kidney Injury in Adult Cardiac Patients: A Propensity-Matched Cohort Study.

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 < 0.001). 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.

Hemodynamic Monitoring Using a Pulmonary Artery Catheter Versus the Vigileo/FloTrac System during Elective Cardiac Surgery Based on Real-world Data in Japan.

BACKGROUND: The controversy concerning the benefits of pulmonary artery catheter (PAC)-based hemodynamic monitoring in cardiac surgeries has not been adequately addressed. This study aims to compare the all-cause mortality between the PAC with venous oxygen saturation monitoring and the Vigileo/FloTrac (FloTrac) system with central venous oxygen saturation monitoring in cardiac surgeries. METHODS: This nationwide retrospective study includes adult patients who underwent elective cardiac surgeries between April 2010 and October 2014, based on the Japanese health insurance claims database. The main outcome was 30-day all-cause mortality. Propensity scores (PS) were used to adjust for the confounding factors. Treatment effects were estimated using multivariable logistic regression analysis, including PS. RESULTS: A total of 5,838 patients were included in this study. The crude 30-day mortality rates were 2.4% (8/334) and 1.7% (96/5,504) in the FloTrac and PAC groups, respectively. After PS matching, the ORs for 30-day all-cause mortality, in-hospital mortality after PAC placement (vs. FloTrac) were 0.36 (95% CI: 0.05-2.37; p = 0.28) and 0.59 (95% CI: 0.16-2.20; p = 0.43), respectively. The amount of dobutamine was larger in the PAC group (281 ± 31 mg vs 155 ± 19 mg; p < 0.001). There were no significant differences in the amounts of other inotropes, the volume of fluids, or blood transfusions. CONCLUSIONS: The association between PAC (with venous oxygen saturation monitoring) and mortality in patients who underwent elective cardiac surgeries was unclear compared to FloTrac (with central venous oxygen saturation monitoring). Additional investigation is needed to evaluate the benefits of PAC-specific hemodynamic parameters in this population.

Clinical Significance of Shared T Cell Epitope Analysis in Early De Novo Donor-Specific Anti-HLA Antibody Production After Kidney Transplantation and Comparison With Shared B cell Epitope Analysis.

In pre-sensitizing events, immunological memory is mainly created via indirect allorecognition where CD4+ T cells recognize foreign peptides in the context of self-HLA class II (pHLA) presented on antigen-presenting cells. This recognition makes it possible for naive CD4+ T-helper cells to differentiate into memory cells, resulting in the creation of further antibody memory. These responses contribute to effective secretion of donor-specific anti-HLA antibodies (DSA) after second encounters with the same peptide. Preformed donor-reactive CD4+ memory T cells may induce early immune responses after transplantation; however, the tools to evaluate them are limited. This study evaluated shared T cell epitopes (TEs) between the pre-sensitizing and donor HLA using an in silico assay, an alternative to estimate donor-reactive CD4+ memory T cells before transplantation. In 578 living donor kidney transplants without preformed DSA, 69 patients had anti-HLA antibodies before transplantation. Of them, 40 had shared TEs and were estimated to have donor-reactive CD4+ memory T cells. De novo DSA formation in the early phase was significantly higher in the shared TE-positive group than in the anti-HLA antibody- and shared TE-negative groups (p=0.001 and p=0.02, respectively). In conclusion, evaluation of shared TEs for estimating preformed donor-reactive CD4+ memory T cells may help predict the risk of early de novo DSA formation after kidney transplantation.

Cardiovascular Safety of Celecoxib after Cardiac Surgery with Cardiopulmonary Bypass: A Retrospective Cohort Study.

BACKGROUND: Cardiac surgery is a highly invasive procedure resulting in hypercoagulability due to thoracotomy and cardiopulmonary bypass (CPB). The long-term use of selective cyclooxygenase-2 inhibitors has been shown to increase the risk of adverse cardiovascular (CV) events such as myocardial infarction. This study aimed to determine whether short-term prescription of celecoxib increases CV events in patients who have undergone cardiac surgery with CPB. METHODS: This retrospective observational study included 16,141 patients (≥20 years) who had undergone cardiac surgery with CPB between April 1, 2008 and March 31, 2016. Patients who underwent coronary artery bypass grafting were excluded. Patients who received celecoxib (n = 904) and acetaminophen (n = 5,002) from postoperative day 0 to 30 were extracted and matched by propensity score (PS). The primary outcomes were all-cause death and CV events, defined as coronary artery disease, ischemic stroke, pulmonary embolism, and venous thrombosis, coded using International Classification of Diseases-10 within 30 days after the first postoperative prescription of either medication. Results were assessed using Kaplan-Meier survival analysis and multivariate Cox regression analysis. RESULTS: PS matching created 885 pairs. Multivariate Cox regression analysis showed that prescription of celecoxib after cardiac surgery was not associated with an increase in the primary outcomes when compared with prescription of acetaminophen (hazard ratio, 0.76; 95% confidence interval, 0.35-1.65). CONCLUSIONS: The prescription of celecoxib in patients who had undergone cardiac surgery with cardiopulmonary bypass was not statistically different from the prescription of acetaminophen in the incidence of CV events and death.

Hydrocortisone with fludrocortisone for septic shock: a systematic review and meta-analysis.

AIM: Combined hydrocortisone and fludrocortisone therapy for septic shock has not been evaluated with an independent systematic review. We aimed to elucidate the beneficial effects of a dual corticosteroid treatment regime involving both hydrocortisone and fludrocortisone for adult patients with septic shock on mortality. METHODS: We searched the Medline, Cochrane CENTRAL, and ICHUSHI databases for reports published before April 2019. We included randomized controlled trials that compared the use of both hydrocortisone and fludrocortisone with either corticosteroid-free or hydrocortisone-only treatments on adult patients with septic shock. Three researchers independently reviewed the studies. The meta-analyses were undertaken to assess primary outcome (28-day mortality) and secondary outcomes (in-hospital mortality, long-term mortality, shock reversal, and adverse events). RESULTS: Among the four studies eligible for data synthesis, we included 2,050 patients from three studies for quantitative synthesis. All studies used similar regimens (hydrocortisone and fludrocortisone for 7 days without tapering). The 28-day mortality rate was reduced after dual corticosteroid treatment (risk ratio, 0.88; 95% confidence intervals [CI], 0.78-0.99). The heterogeneity between the studies was low (I 2 = 0%). Patients who underwent dual corticosteroid treatment had lower long-term mortality rates (risk ratio, 0.90; 95% CI, 0.83-0.98) and higher rate of shock reversal after 28 days (odds ratio, 1.06; 95% CI, 1.01-1.12) than control patients. Adverse events (except for hyperglycemia) were similar among the treatment groups. CONCLUSIONS: The available evidence suggests that a combination of fludrocortisone and hydrocortisone is more effective than adjunctive therapy and could be recommended for septic shock.

The association between arterial pulse waveform analysis device and in-hospital mortality in high-risk non-cardiac surgeries.

BACKGROUND: Perioperative goal-directed fluid therapy is used for haemodynamic optimization in high-risk surgeries. Cardiac output monitoring can be performed by a specialized pressure transducer for arterial pulse waveform analysis (S-APWA). No study has assessed whether real-world use of S-APWA is associated with post-operative outcomes; therefore, using a Japanese administrative claims database, we retrospectively investigated whether S-APWA use is associated with in-hospital mortality among patients undergoing high-risk surgery under general anaesthesia. METHODS: Adult patients who underwent high-risk surgery under general anaesthesia and arterial catheterization between 2014 and 2016 were divided into S-APWA and conventional arterial pressure transducer groups, then compared regarding baseline factors and outcomes. Logistic regression analysis was performed to compare in-hospital mortality. Subgroup analyses evaluated S-APWA efficacy and outcomes based on the type of surgery and patients' comorbidity. RESULTS: S-APWA was used in 6859 of 23 655 (29.0%) patients; the crude in-hospital mortality rate was 3.5%. Adjusted analysis showed no significant association between S-APWA use and in-hospital mortality rate (adjusted odds ratio [aOR] = 0.91; 95% confidence interval [CI]: 0.76-1.07; P = .25). S-APWA use was associated with significantly lower in-hospital mortality in patients undergoing vascular surgery (aOR = 0.67; 95% CI: 0.49-0.94), and significantly higher in-hospital mortality in patients undergoing lower limb amputation (aOR = 2.63; 95% CI: 1.32-5.22). S-APWA use and in-hospital mortality were not significantly associated with other subgroups. CONCLUSION: S-APWA use was not associated with in-hospital mortality in the entire study population. However, S-APWA was associated with decreased in-hospital mortality among vascular surgery and increased in-hospital mortality among lower limb amputation.

Correction to: Prophylactic sivelestat for esophagectomy and in-hospital mortality: a propensity score-matched analysis of claims database.

In the original version of the article, the Tables 2 and 3 was published incorrectly. The correct version of Tables 2 and 3 are given below.

Utilization of arterial pulse waveform analysis during non-cardiac surgery in Japan: a retrospective observational study using a nationwide claims database.

Arterial pulse waveform analysis (APWA) is used for cardiac output monitoring. However, data on the frequency of and patient characteristics for specialized pressure transducer for APWA (S-APWA) use are lacking. We retrospectively identified 175,201 patients aged 18 years or older, who underwent non-cardiac surgery under general anesthesia with an arterial catheter from January 1, 2014, to December 31, 2016. We extracted data on patient demographics, comorbidities, surgical and anesthesia characteristics, and hospital characteristics. Among the full study cohort, 24,605 (14.0%) patients were monitored using S-APWA. Further, the use of S-APWA was higher in patients undergoing high-risk surgery than in those undergoing low-risk surgery [high vs low: adjusted odds ratio (aOR) 1.95; 95% confidence interval (CI) 1.76-2.15, moderate vs low: aOR 1.11; 95% CI 1.01-1.22] and those with more comorbidities than in those with less comorbidities (high vs low: aOR 1.49; 95% CI 1.42-1.56, moderate vs low: aOR 1.25; 95% CI 1.20-1.31). S-APWA use was significantly associated with both surgery risk and patients' comorbidities. In conclusion, our study may provide a benchmark for future studies related to the appropriate use of S-APWA.

Prophylactic sivelestat for esophagectomy and in-hospital mortality: a propensity score-matched analysis of claims database.

PURPOSE: Transthoracic esophagectomy is an invasive surgery, and the excessive surgical stress produces inflammatory cytokines, which provoke acute respiratory distress syndrome (ARDS). Sivelestat sodium hydrate-a selective neutrophil elastase inhibitor-is used to treat or prevent ARDS in patients undergoing esophagectomy, although clear evidence is lacking. We investigated the benefits and risk of prophylactic sivelestat. METHODS: This retrospective study used an administrative claims database in Japan. Adult patients who underwent transthoracic esophagectomy from 2010 to 2016 were identified and divided into a prophylactic sivelestat use group and a non-prophylactic use group that included both non-users and therapeutic users. The primary outcome was all-cause in-hospital mortality, and a secondary outcome included the proportion of ARDS. We used 1:1 propensity score matching. For sensitivity analyses, we conducted a 1:2 propensity score matching analysis and several analyses with various patient inclusion criteria. RESULTS: Of the 3391 patients with esophagectomy, 621 received prophylactic sivelestat. On unadjusted analysis, the sivelestat group had a higher proportion of in-hospital mortality (5.3% vs. 2.9%) compared with the control group. We created a matched cohort of 615 pairs, whose baseline characteristics were well balanced. On adjusted analysis using propensity score matching, prophylactic sivelestat administration was not associated with decreased in-hospital mortality [adjusted odds ratio (aOR) 1.65; 95% confidence interval (CI) 0.95-2.88], ARDS rate (aOR 1.25; 95% CI 0.49-3.17). The findings were also consistent with other sensitivity analyses. CONCLUSION: Because mortality and postoperative complications were similar, our findings do not support prophylactic sivelestat administration for patients undergoing esophagectomy.

Preoperative Echocardiography for Patients With Hip Fractures Undergoing Surgery: A Retrospective Cohort Study Using a Nationwide Database.

BACKGROUND: The effect of preoperative transthoracic echocardiography on the clinical outcomes of patients with hip fractures undergoing surgical treatment remains controversial. We hypothesized that preoperative echocardiography is associated with reduced postoperative morbidity and improved patient survival after surgical repair of hip fractures. METHODS: Drawing from a nationwide administrative database, patients undergoing hip fracture surgeries between April 1, 2008 and December 31, 2016 were included. We examined the association of preoperative echocardiography with the incidence of in-hospital mortality using propensity score matching. Secondary outcomes included postoperative complications, the incidence of postoperative intensive care unit admissions, and length of hospital stay. For sensitivity analyses, we restricted the overall cohort to include only hip fracture surgeries performed within 2 days from admission. RESULTS: Overall, 34,679 (52.1%) of 66,620 surgical patients underwent preoperative echocardiography screening. The screened patients (mean [SD] age, 84.3 years [7.7 years]; 79.0% female) were propensity score matched to 31,941 nonscreened patients (mean [SD] age, 82.1 years [8.7 years]; 78.2% female). The overall in-hospital mortality, before propensity matching, was 1.8% (1227 patients). Propensity score matching created a matched cohort of 25,205 pairs of patients. There were no in-hospital mortality differences between the 2 groups (screened versus nonscreened: 417 [1.65%] vs 439 [1.74%]; odds ratio, 0.95; 95% confidence interval, 0.83-1.09; P = .45). Preoperative echocardiography was not associated with reduced postoperative complications and intensive care unit admissions. In sensitivity analysis, we identified 25,637 patients from the overall cohort (38.5%) with hip fracture surgeries performed within 2 days of admission. There were no in-hospital mortality differences between the 2 groups (screened versus nonscreened: 1.67% vs 1.80%; odds ratio, 0.93; 95% confidence interval, 0.72-1.18; P = .53). Findings were also consistent with other sensitivity analyses and subgroup analyses. CONCLUSIONS: This large, retrospective, nationwide cohort study demonstrated that preoperative echocardiography was not associated with reduced in-hospital mortality or postoperative complications.

Preoperative Blood Tests Conducted Before Low-Risk Surgery in Japan: A Retrospective Observational Study Using a Nationwide Insurance Claims Database.

BACKGROUND: Routine preoperative testing is discouraged before low-risk surgery because testing does not provide any beneficial effect in terms of patient outcome. However, few studies have assessed the utilization of hospital health care resources in terms of preoperative tests in a real-world setting. Here, we aimed to assess the prevalence and factors associated with preoperative blood tests before low-risk surgery in Japan. METHODS: In this retrospective observational study, we used the nationwide insurance claims data of Japan. Patients who underwent low-risk surgeries between April 1, 2012 and March 31, 2016, were included. Our primary outcome was the receipt of any preoperative tests within 60 days before an index procedure: complete blood count, basic metabolic panel, coagulation tests, and liver function tests. We performed a descriptive analysis to estimate the proportions of preoperative blood tests, and examined the associations between patient-level and institutional-level factors and preoperative blood tests, using multilevel logistic regression analysis. Interinstitutional variation in the utilization of preoperative tests was summarized using the median odds ratio (OR). RESULTS: The study sample included 59,818 patients (mean [standard deviation] age, 44.0 [11.3] years; 33,574 [56.1%] women) from 9746 institutions. The overall proportion of each test was: complete blood count, 58.7%; metabolic panel, 47.8%; coagulation tests, 36.6%; and liver function tests, 48.5%. The proportion receiving any preoperative tests in the overall sample was 59.5%. Multilevel logistic regression analysis indicated that preoperative blood tests were associated with the Charlson comorbidity index score (score ≥3: adjusted OR, 4.21; 95% confidence interval [CI], 3.69-4.80), anticoagulant use (adjusted OR, 4.12; 95% CI, 2.35-7.22), type of anesthesia (general anesthesia: adjusted OR, 5.69; 95% CI, 4.85-6.68; regional anesthesia: adjusted OR, 3.76; 95% CI, 3.28-4.30), surgical setting (inpatient procedure: adjusted OR, 3.64; 95% CI, 3.30-4.00), and number of beds (≥100 beds: adjusted OR, 3.61; 95% CI, 3.19-4.08). The median institutional-specific proportion of preoperative tests was 40.0% (interquartile range, 0%-100%). The median OR for interinstitutional variation in ordering preoperative tests was 4.34. These findings were consistent across a sensitivity analysis. CONCLUSIONS: Preoperative blood tests were performed before 59.5% of low-risk surgeries. Preoperative tests were associated with the type of anesthesia, patient characteristics, and medical facility status. There was a substantial interinstitutional variation in the utilization of preoperative tests.

Preoperative pulmonary function tests before low-risk surgery in Japan: a retrospective cohort study using a claims database.

PURPOSE: Routine preoperative pulmonary function tests (PFTs) are not recommended prior to low-risk surgery because their prognostic value is limited. However, only a few studies have assessed the utilization of healthcare resources regarding preoperative PFTs in a real-world setting. Here, we aimed to assess the prevalence and determinant factors of preoperative PFTs before low-risk surgery in Japan. METHODS: In this retrospective cohort study, we used the nationwide insurance claims databases. Patients who underwent low-risk surgeries under general anesthesia between April 1, 2012, and March 31, 2016, were included. The primary outcome was the receipt of PFTs within 60 days before an index surgery. We performed descriptive analyses to estimate the rates of preoperative PFTs annually starting in 2012, and examined the associations between patient- and institutional-level factors and preoperative PFTs using multilevel logistic regression analyses. RESULTS: The cohort included 9495 procedures (8866 patients) at 1487 institutions. Preoperative PFTs were conducted before 71.8% of the procedures. The temporal trend of preoperative PFTs remained constant from 72.4% in 2012 to 72.2% in 2015. Multilevel regression analysis revealed that preoperative PFTs were associated with older age, number of beds at a medical facility, and inpatient procedures. The median institutional-specific proportion of PFTs was 75.0% (interquartile range, 14.3-100%) with wide inter-institutional variation. CONCLUSIONS: Our analysis found that preoperative PFTs were performed before 72% of low-risk surgeries under general anesthesia. Apart from age, preoperative PFTs were determined primarily by non-medical factors. Additionally, we observed substantial institutional variation in the use of preoperative PFTs.