Background: Hyperglycemia has shown a negative association with cognitive dysfunction. We analyzed patients with high preoperative blood glucose level and hemoglobin A1c (HbA1c) level to determine the prevalence of postoperative delirium. Methods: We reviewed a database of 23,532 patients with diabetes who underwent non-cardiac surgery. Acute hyperglycemia was defined as fasting blood glucose > 140 mg/dl or random glucose > 180 mg/dl within 24 h before surgery. Chronic hyperglycemia was defined as HbA1c level above 6.5% within three months before surgery. The incidence of delirium was compared according to the presence of acute and chronic hyperglycemia. Results: Of the 23,532 diabetic patients, 21,585 had available preoperative blood glucose level within 24 h before surgery, and 18,452 patients reported levels indicating acute hyperglycemia. Of the 8,927 patients with available HbA1c level within three months before surgery, 5,522 had levels indicating chronic hyperglycemia. After adjustment with inverse probability weighting, acute hyperglycemia was related to higher incidence of delirium (hazard ratio: 1.33, 95% CI [1.10,1.62], P = 0.004 for delirium) compared with controls without acute hyperglycemia. On the other hand, chronic hyperglycemia did not correlate with postoperative delirium. Conclusions Preoperative acute hyperglycemia was associated with postoperative delirium, whereas chronic hyperglycemia was not significantly associated with postoperative delirium. Irrespective of chronic hyperglycemia, acute glycemic control in surgical patients could be crucial for preventing postoperative delirium.

Background: Perioperative adverse cardiac events (PACE), a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, and stroke during 30-day postoperative period, is associated with long-term mortality, but with limited clinical evidence. We compared long-term mortality with PACE using data from nationwide multicenter electronic health records. Methods: Data from 7 hospitals, converted to Observational Medical Outcomes Partnership Common Data Model, were used. We extracted records of 277,787 adult patients over 18 years old undergoing non-cardiac surgery for the first time at the hospital and had medical records for more than 180 days before surgery. We performed propensity score matching and then an aggregated meta‑analysis. Results: After 1:4 propensity score matching, 7,970 patients with PACE and 28,807 patients without PACE were matched. The meta‑analysis showed that PACE was associated with higher one-year mortality risk (hazard ratio [HR]: 1.33, 95% CI [1.10, 1.60], P = 0.005) and higher three-year mortality (HR: 1.18, 95% CI [1.01, 1.38], P = 0.038). In subgroup analysis, the risk of one-year mortality by PACE became greater with higher-risk surgical procedures (HR: 1.20, 95% CI [1.04, 1.39], P = 0.020 for low-risk surgery; HR: 1.69, 95% CI [1.45, 1.96], P < 0.001 for intermediate-risk; and HR: 2.38, 95% CI [1.47, 3.86], P = 0.034 for high-risk). Conclusions A nationwide multicenter study showed that PACE was significantly associated with increased one-year mortality. This association was stronger in high-risk surgery, older, male, and chronic kidney disease subgroups. Further studies to improve mortality associated with PACE are needed.

Purpose: Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer. Materials and Methods: We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment. Results: Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors. Conclusion Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

Prediction of fluid responsiveness has been considered an essential tool for modern fluid management. However, most studies in this field have focused on patients in intensive care unit despite numerous research throughout several decades. Therefore, the present narrative review aims to show the representative method’s feasibility, advantages, and limitations in predicting fluid responsiveness, focusing on the operating room environments. Firstly, we described the predictors of fluid responsiveness based on heart-lung interaction, including pulse pressure and stroke volume variations, the measurement of respiratory variations of inferior vena cava diameter, and the end-expiratory occlusion test and addressed their limitations. Subsequently, the passive leg raising test and mini-fluid challenge tests were also mentioned, which assess fluid responsiveness by mimicking a classic fluid challenge. In the last part of this review, we pointed out the pitfalls of fluid management based on fluid responsiveness prediction, which emphasized the importance of individualized decision-making. Understanding the available representative methods to predict fluid responsiveness and their associated benefits and drawbacks through this review will aid anesthesiologists in choosing the most reliable methods for optimal fluid administration in each patient during anesthesia in the operating room.

Background: To evaluate the association between inflammation and nutrition-based biomarkers and postoperative outcomes after non-cardiac surgery. Methods: Between January 2011 and June 2019, a total of 102,052 patients undergoing non-cardiac surgery were evaluated, with C-reactive protein (CRP), albumin, and complete blood count (CBC) measured within six months before surgery. We assessed their CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow Prognostic Score (mGPS). We determined the best cut-off values by using the receiver operating characteristic (ROC) curves. Patients were divided into high and low groups according to the estimated threshold, and we compared the one-year mortality. Results: The one-year mortality of the entire sample was 4.2%. ROC analysis revealed areas under the curve of 0.796, 0.743, 0.670, and 0.708 for CAR, NLR, PLR, and mGPS, respectively. According to the estimated threshold, high CAR, NLR, PLR, and mGPS were associated with increased one-year mortality (1.7% vs. 11.7%, hazard ratio [HR]: 2.38, 95% CI [2.05, 2.76], P < 0.001 for CAR; 2.2% vs. 10.3%, HR: 1.81, 95% CI [1.62, 2.03], P < 0.001 for NLR; 2.6% vs. 10.5%, HR: 1.86, 95% CI [1.73, 2.01], P < 0.001 for PLR; and 2.3% vs. 16.3%, HR: 2.37, 95% CI [2.07, 2.72], P < 0.001 for mGPS). Conclusions Preoperative CAR, NRL, PLR, and mGPS were associated with postoperative mortality. Our findings may be helpful in predicting mortality after non-cardiac surgery.

Objective: To investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN). Methods: We reviewed the records of patients with genetically confirmed PKAN who received bilateral GPi-DBS for refractory dystonia and were clinically followed up for at least 2 years postoperatively at two centers in Korea. Pre- and postoperative Burke– Fahn–Marsden Dystonia Rating Scale motor subscale (BFMDRS-M) scores, disability subscale (BFMDRS-D) scores, and qualitative clinical information were prospectively collected. Descriptive analysis was performed for BFMDRS-M scores, BFMDRSD scores, and the orofacial, axial, and limb subscores of the BFMDRS-M at 6–12, 24–36, and 60–72 months postoperatively. Results: Five classic-type, four atypical-type, and one unknown-type PKAN cases were identified. The mean preoperative BFMDRS-M score was 92.1 for the classic type and 38.5 for the atypical or unknown type, with a mean BFMDRS follow-up of 50.7 months and a clinical follow-up of 69.0 months. The mean improvements in BFMDRS-M score were 11.3%, 41.3%, and 30.5% at 6–12, 24–36, and 60–72 months, respectively. In four patients with full regular evaluations until 60–72 months, improvements in the orofacial, axial, and limb subscores persisted, but the disability scores worsened from 24–36 months post-operation compared to the baseline, mainly owing to the aggravation of eating and feeding disabilities. Conclusion The benefits of GPi-DBS on dystonia may persist for more than 5 years in PKAN. The effects on patients’ subjective disability may have a shorter duration despite improvements in dystonia owing to the complex manifestations of PKAN.

Background: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. Methods: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. Results: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P= 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). Conclusion Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

Background: An epidural blood patch (EBP) is a procedure to treat intracranial hypotension that does not respond to conservative treatment. EBPs are commonly repeated when the symptoms persist. In this study, we used a large single-center retrospective cohort and evaluated the factors associated with repeated EBPs. Methods: From January 2010 to December 2020, a total of 596 patients were treated with EBPs for intracranial hypotension. We evaluated the factors associated with repeated EBPs in the entire population, in patients with spontaneous intracranial hypotension (SIH), and in those with available myelographies. Results: In a total of 596 patients, 125 (21.1%) patients required repeated EBPs, and 96/278 (34.5%) in SIH and 29/314 (9.2%) in iatrogenic population. In patients with SIH, international normalized ratio (INR) and cerebrospinal fluid (CSF) leakage on myelographies consistently exhibited significant associations (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.02–1.87; P = 0.043 and OR, 2.18; 95% CI, 1.28–3.69; P = 0.004). In patients with iatrogenic injury, INR and CSF leakage on myelogram did not show difference in repeated EBPs. Conclusions Repeated EBPs may be more frequently required in patients with SIH.Prolonged INR and CSF leakage were associated with repeated EBPs in patient with SIH. Further studies are needed to determine factors associated with repeated EBP requirements.

Background: The clinical efficacy of preoperative 2D-echocardiographic assessment of pulmonary arterial pressure (PAP) has not been evaluated fully in liver transplantation (LT) recipients. Methods: From October 2010 to February 2017, a total of 344 LT recipients who underwent preoperative 2D-echocardiography and intraoperative right heart catheterization (RHC) was enrolled and stratified according to etiology, disease progression, and clinical setting. The correlation of right ventricular systolic pressure (RVSP) on preoperative 2D-echocardiography with mean and systolic PAP on intraoperative RHC was evaluated, and the predictive value of RVSP > 50 mmHg to identify mean PAP > 35 mmHg was estimated. Results: In the overall population, significant but weak correlations were observed (R = 0.27; P < 0.001 for systolic PAP, R = 0.24; P < 0.001 for mean PAP). The positive and negative predictive values of RVSP > 50 mmHg identifying mean PAP > 35 mmHg were 37.5% and 49.9%, respectively. In the subgroup analyses, correlations were not significant in recipients of deceased donor type LT (R = 0.129; P = 0.224 for systolic PAP, R = 0.163; P = 0.126 for mean PAP) or in recipients with poorly controlled ascites (R = 0.215; P = 0.072 for systolic PAP, R = 0.21; P = 0.079 for mean PAP). Conclusion In LT recipients, the correlation between RVSP on preoperative 2D-echocardiography and PAP on intraoperative RHC was weak; thus, preoperative 2D-echocardiography might not be the optimal tool for predicting intraoperative PAP. In LT candidates at risk of pulmonary hypertension, RHC should be considered.

Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.