Influence of psychological factors and pain sensitivity on the efficacy of opioid-free anesthesia: A randomized clinical trial.

OBJECTIVE: This study aimed to investigate the effects of opioid-free anesthesia (OFA) in laparoscopic gastrectomy and identify the psychological factors that could influence the efficacy of OFA. METHOD: 120 patients undergoing laparoscopic gastrectomy were allocated to either the opioid-based anesthesia group (OA) (n = 60) or the OFA (n = 60) group. Remifentanil was administered to the OA group intraoperatively, whereas dexmedetomidine and lidocaine were administered to the OFA group. The interaction effect of the psychological factors on OFA was analyzed using the aligned rank transform for nonparametric factorial analyses. RESULTS: The opioid requirement for 24 h after surgery was lower in the OFA group than in the OA group (fentanyl equivalent dose 727 vs. 650 µg, p = 0.036). The effect of OFA was influenced by the pain catastrophizing scale (p = 0.041), temporal pain summation (p = 0.046), and pressure pain tolerance (p = 0.034). This indicates that patients with pain catastrophizing or high pain sensitivity significantly benefited from OFA, whereas patients without these characteristics did not. CONCLUSIONS: This study demonstrated that OFA with dexmedetomidine and lidocaine effectively reduced the postoperative 24-h opioid requirements following laparoscopic gastrectomy, which was modified by baseline pain catastrophizing and pain sensitivity. CLINICAL TRIAL REGISTRY: The study protocol was approved by the Institutional Review Board of Yonsei University Health System Gangnam Severance Hospital (#3-2021-0295) and registered at ClinicalTrials.gov (NCT05076903).

The impact of circulatory arrest with selective antegrade cerebral perfusion on brain functional connectivity and postoperative cognitive function.

Aortic surgery is one of the most challenging types of surgeries, which is possibly related to cognitive sequelae. We aimed to investigate the changes in resting-state functional connectivity (rsFC) associated with intraoperative circulatory arrest (CA) in aortic surgery, exploring the relationship between the altered connectivity and postoperative cognitive functions. Thirty-eight patients participated in this study (14 with CA, 24 without). Functional magnetic resonance imaging was scanned on the fifth day after surgery or after the resolution of delirium if it was developed. We assessed the differences in the development of postoperative cognitive changes and rsFC between patients with and without CA. The occurrence of postoperative delirium and postoperative cognitive dysfunction was not significantly different between the patients with and without the application of CA. However, patients with CA showed increased in posterior cingulate cortex-based connectivity with the right superior temporal gyrus, right precuneus, and right hippocampus, and medial prefrontal cortex-based connectivity with the dorsolateral prefrontal cortex. The application of moderate hypothermic CA with unilateral antegrade cerebral perfusion is unlikely to affect aspects of postoperative cognitive changes, whereas it may lead to increased rsFC of the default mode network at a subclinical level following acute brain insults.

Risk of Secondary Cancer after Adjuvant Tamoxifen Treatment for Ductal Carcinoma In Situ: A Nationwide Cohort Study in South Korea.

Endocrine therapy is the mainstay treatment for hormone receptor-positive ductal carcinoma in situ. The aim of this study was to examine the long-term secondary malignancy risk of tamoxifen therapy. The data of patients diagnosed with breast cancer between January 2007 and December 2015 were retrieved from the database of the Health Insurance Review and Assessment Service of South Korea. The International Classification of Diseases, 10th revision, was used to track all-site cancers. Age at the time of surgery, chronic disease status, and type of surgery were considered covariates in the propensity score matching analysis. The median follow-up duration was 89 months. Forty-one patients in the tamoxifen group and nine in the control group developed endometrial cancer. The Cox regression hazard ratio model showed that tamoxifen therapy was the only significant predictor of the development of endometrial cancer (hazard ratio, 2.791; 95% confidence interval, 1.355-5.747; p = 0.0054). No other type of cancer was associated with long-term tamoxifen use. In consonance with the established knowledge, the real-world data in this study demonstrated that tamoxifen therapy is related to an increased incidence of endometrial cancer.

Relationship between body mass index and risk of delirium in an intensive care unit.

OBJECTIVE: Delirium in the intensive care unit (ICU) is a common and critical condition that leads to poor prognosis in older patients, but the association between body mass index (BMI) and the incidence of delirium remains unclear. METHODS: We retrospectively analyzed 5,622 patients admitted to the ICU of a tertiary referral hospital between 2013 and 2022. We collected sociodemographic data, vital signs, laboratory results, and delirium scale scores. We subdivided the patients into four categories: underweight (<18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (>25 kg/m2). The primary outcome was the incidence of delirium according to the BMI categories. We performed multivariable logistic regression analysis, adjusted for sex, age, past smoking and alcohol history, benzodiazepine use, and laboratory abnormalities. RESULTS: Among the 5,622 patients in the ICU (mean age, 72.9 years; male, 60.1%; mean BMI, 24.2 kg/m2), the incidence of delirium was 19.0% (1,069 patients). The mean modified incidence of delirium was higher among underweight patients (odds ratio [OR]=1.51, confidence interval [CI]=1.07-2.12, p = 0.02) than among normal-weight patients. Overweight and obese status were not independently associated with delirium (OR=0.90, CI=0.70-1.17, p = 0.43; OR= 0.97; CI=0.77-1.21, p = 0.78, respectively). The area under the receiver-operating characteristic curve of the multivariable logistic regression model was 0.71 (95% CI=0.69-0.73). CONCLUSIONS: Underweight status is an independent risk factor for delirium in the ICU. Additional caution is required when evaluating underweight patients for delirium. Obese or overweight status are not associated with delirium, providing evidence for the obesity paradox.

Association between preoperative frontal electroencephalogram alpha asymmetry and postoperative quality of recovery: an observational study.

BACKGROUND: Left-sided frontal alpha asymmetry on electroencephalograms, which indicates decreased relative left-hemispheric activity, has been associated with depression, anxiety, and stress responsivity. We aimed to evaluate the association between perioperative measures of frontal alpha asymmetry and quality of recovery (QoR) after surgery. METHODS: We enrolled 110 female patients undergoing thyroidectomy and recorded perioperative electroencephalograms. The power of the prefrontal alpha band (8-13 Hz) was measured in the Fp1 and Fp2 leads. Left-sided frontal alpha asymmetry was defined as a higher alpha band power in Fp1 than in Fp2 and vice versa. QoR was assessed using the QoR-15 score on the day before surgery and postoperative days 1 and 2. The primary study endpoint was a difference in postoperative global QoR-15 score between preoperative left-sided and right-sided alpha asymmetry groups. The predictability of frontal alpha asymmetry for poor QoR-15 score was also evaluated. RESULTS: The global QoR-15 score showed a significant group-by-time interaction, and post-hoc analysis revealed significantly lower scores on postoperative days 1 (P=0.006) and 2 (P<0.001) in the left-sided frontal alpha asymmetry group. In the multivariate logistic regression analysis, preoperative left-sided frontal alpha asymmetry was associated with a 3.3-fold increased risk of the lowest tertile for the postoperative day 1 QoR-15 score (95% CI: 1.31-8.24; P=0.011). CONCLUSIONS: Preoperative left-sided frontal alpha asymmetry was independently associated with a lower postoperative QoR-15 score in female patients undergoing thyroidectomy, highlighting the potential role of preoperative frontal electroencephalography in predicting patient-centred outcomes after surgery. CLINICAL TRIAL REGISTRATION: KCT0006586 (http://cris.nih.go.kr/).

Marked Reduction in the Risk of Dementia in Patients with Breast Cancer: A Nationwide Population-Based Cohort Study.

PURPOSE: An inverse relationship between cancer and neurodegenerative disease, which presents the possibility of a reduced risk of dementia in cancer patients, has been suggested previously. However, a nationwide longitudinal population-based study of specific types of cancer with due consideration of treatment effects has not been conducted. Materials and Methods: This nationwide population-based cohort study used data obtained in a 12-year period (January 2007- December 2018) in the Korean National Health Insurance claims database. All female breast cancer patients (age ≥ 50 years) diagnosed between 2009 and 2010 were included after excluding those with physician visits for any cancer during a 2-year period (2007-2008). Patients with senile cataract constituted the control group. The main study outcome was the risk of developing dementia. RESULTS: From a total of 90,396 and 85,906 patients with breast cancer and cataract, respectively, patients without behavior codes were excluded. Data for 15,407 breast cancer patients and 7,020 controls were analyzed before matching. After matching for comorbidities and age, either group comprised 2,252 patients. The median follow-up time was 104.1±24.0 months after matching. After matching, breast cancer was a predictor of a lower risk of for dementia (hazard ratio, 0.091; 95% confidence interval, 0.075 to 0.111; p < 0.001). In breast cancer patients, receiving chemotherapy and endocrine therapy did not significantly affect the incidence of dementia. CONCLUSION: Breast cancer was associated with a remarkably decreased risk of dementia. The findings strongly suggest an inverse relationship between cancer and neurodegeneration, regardless of the adverse effects of cancer treatment on cognitive function.

Association between tamoxifen and incidence of osteoporosis in Korean patients with ductal carcinoma in situ.

Introduction: The partial estrogen-agonist action of tamoxifen on bone receptors has beneficial effects on bone mineral density. However, in premenopausal women, the use of tamoxifen causes systemic estrogen depletion, which has detrimental effects on bone health. We aim to investigate the association between tamoxifen and osteoporosis in the real world using data from a longitudinal nationwide cohort of Korean patients. Methods: Data were collected from the National Health Insurance claims database in South Korea. Osteoporosis was defined by diagnostic codes accompanying prescription data for osteoporosis. The cumulative incidence was analyzed by Kaplan-Meier survival curves and the risk factors were analyzed using a multivariable Cox proportional hazard regression model. Results: Between 2009 and 2015, of the 4,654 women with ductal carcinoma in situ (DCIS) without prior osteoporosis, 2,970 were prescribed tamoxifen and 1,684 were not. A total of 356 DCIS survivors were later diagnosed with osteoporosis during a median follow-up period of 84 months. In the overall population, tamoxifen was associated with a low risk of osteoporosis, before and after propensity matching adjusted for age, operation type, and comorbidities (before matching, hazard ratio [HR]=0.69, 95% confidence interval [CI]=0.559-0.851, p<0.001; after matching, HR=0.664, 95% CI=0.513-0.858, p=0.002). In the subgroup analysis, findings were consistent in postmenopausal women but were not evident in the younger age group. Conclusion: In a nationwide cohort study, a low risk of osteoporosis was associated with the use of tamoxifen. The protective effect of tamoxifen was more profound in older women and was not related to the incidence of osteoporosis in younger women.

Risk of developing depression from endocrine treatment: A nationwide cohort study of women administered treatment for breast cancer in South Korea.

Background: Although previous studies demonstrated no association between depression and tamoxifen in patients with breast cancer, there is still a limited amount of long-term follow-up data. This study aimed to evaluate the relationship between endocrine treatment and the risk of depression. Methods: This nationwide population-based cohort study used data obtained over a 14-year period (January 2007 to December 2021) from the Korean National Health Insurance claims database. All female patients with breast cancer were included. We examined the incidence of depression in patients who underwent endocrine treatment, and those who did not undergo endocrine treatment constituted the control group. Results: The data from 11,109 patients who underwent endocrine treatment and 6,615 control patients between 2009 and 2010 were analyzed. After performing matching for comorbidities and age, both groups comprised 6,532 patients. The median follow-up were 119.71 months. Before and after matching was performed, the endocrine treatment was not a significant risk factor for developing depression (p=0.7295 and p=0.2668, respectively), nor was it a significant factor for an increased risk for suicide attempt (p=0.6381 and p=0.8366, respectively). Conclusions: Using a real-world population-based cohort, this study demonstrated that there is no evidence that the endocrine treatment increases the risk of depression.

Delirium-related factors and their prognostic value in patients undergoing craniotomy for brain metastasis.

Background: Delirium is characterized by acute brain dysfunction. Although delirium significantly affects the quality of life of patients with brain metastases, little is known about delirium in patients who undergo craniotomy for brain metastases. This study aimed to identify the factors influencing the occurrence of delirium following craniotomy for brain metastases and determine its impact on patient prognosis. Method: A total of 153 patients who underwent craniotomy for brain metastases between March 2013 and December 2020 were evaluated for clinical and radiological factors related to the occurrence of delirium. Statistical analysis was conducted by dividing the patients into two groups based on the presence of delirium, and statistical significance was confirmed by adjusting the clinical characteristics of the patients with brain metastases using propensity score matching (PSM). The effect of delirium on patient survival was subsequently evaluated using Kaplan-Meier analysis. Results: Of 153 patients, 14 (9.2%) had delirium. Age (P = 0.002), sex (P = 0.007), and presence of postoperative hematoma (P = 0.001) were significantly different between the delirium and non-delirium groups. When the matched patients (14 patients in each group) were compared using PSM, postoperative hematoma showed a statistically significant difference (P = 0.036) between the delirium and non-delirium groups. Kaplan-Meier survival analysis revealed that the delirium group had poorer prognosis (log-rank score of 0.0032) than the non-delirium group. Conclusion: In addition to the previously identified factors, postoperative hematoma was identified as a strong predictor of postoperative delirium. Also, the negative impact of delirium on patient prognosis including low survival rate was confirmed.

The Effects of Transcranial Direct Current Stimulation on the Cognitive and Behavioral Changes After Electrode Implantation Surgery in Rats.

Postoperative delirium can lead to increased morbidity and mortality, and may even be a potentially life-threatening clinical syndrome. However, the neural mechanism underlying this condition has not been fully understood and there is little knowledge regarding potential preventive strategies. To date, investigation of transcranial direct current stimulation (tDCS) for the relief of symptoms caused by neuropsychiatric disorders and the enhancement of cognitive performance has led to promising results. In this study, we demonstrated that tDCS has a possible effect on the fast recovery from delirium in rats after microelectrode implant surgery, as demonstrated by postoperative behavior and neurophysiology compared with sham stimulation. This is the first study to describe the possible effects of tDCS for the fast recovery from delirium based on the study of both electroencephalography and behavioral changes. Postoperative rats showed decreased attention, which is the core symptom of delirium. However, anodal tDCS over the right frontal area immediately after surgery exhibited positive effects on acute attentional deficit. It was found that relative power of theta was lower in the tDCS group than in the sham group after surgery, suggesting that the decrease might be the underlying reason for the positive effects of tDCS. Connectivity analysis revealed that tDCS could modulate effective connectivity and synchronization of brain activity among different brain areas, including the frontal cortex, parietal cortex, and thalamus. It was concluded that anodal tDCS on the right frontal regions may have the potential to help patients recover quickly from delirium.

Cortical and subcortical changes in resting-state functional connectivity before and during an episode of postoperative delirium.

OBJECTIVE: Delirium is an acute brain failure related to uncertain problems in neural connectivity, including aberrant functional interactions between remote cortical regions. This study aimed to elucidate the underlying neural mechanisms of delirium by clarifying the changes in resting-state functional connectivity induced by postoperative delirium using imaging data scanned before and after surgery. METHOD: Fifty-eight patients with a femoral neck fracture were preoperatively scanned using resting-state functional magnetic resonance imaging. Twenty-five patients developed postoperative delirium, and 14 of those had follow-up scans during delirium. Eighteen patients without delirium completed follow-up scans 5 or 6 days after surgery. We assessed group differences in voxel-based connectivity, in which the seeds were the posterior cingulate cortex, medial prefrontal cortex and 11 subcortical regions. Connections between the subcortical regions were also examined. RESULTS: The results showed four major findings during delirium. Both the posterior cingulate cortex and medial prefrontal cortex were strongly connected to the dorsolateral prefrontal cortex. The posterior cingulate cortex had hyperconnectivity with the inferior parietal lobule, whereas the medial prefrontal cortex had hyperconnectivity with the frontopolar cortex and hypoconnectivity with the superior frontal gyrus. Connectivity of the striatum with the anterior cingulate cortex and insula was increased. Disconnections were found between the lower subcortical regions including the neurotransmitter origins and the striatum/thalamus in the upper level. CONCLUSIONS: Our findings suggest that cortical dysfunction during delirium is characterized by a diminution of the anticorrelation between the default mode network and task-positive regions, excessive internal connections in the posterior default mode network and a complex imbalance of internal connectivity in the anterior default mode network. These dysfunctions can be attributed to the loss of reciprocity between the default mode network and central executive network associated with defective function in the salience network, which might be closely linked to aberrant subcortical neurotransmission-related connectivity and striato-cortical connectivity.

Amide proton transfer imaging seems to provide higher diagnostic performance in post-treatment high-grade gliomas than methionine positron emission tomography.

OBJECTIVES: To compare the diagnostic performance of amide proton transfer (APT) imaging and 11-C methionine positron emission tomography (MET-PET) for in vivo molecular imaging of protein metabolism in post-treatment gliomas. MATERIALS AND METHODS: This study included 43 patients (12 low and 31 high grade) with post-treatment gliomas who underwent both APT and MET-PET imaging within 3 weeks. APT-weighted voxel values and semi-quantitative tumour-to-normal ratios (TNR) were obtained from tumour portions. The voxel-wise relationships between TNR and APT were assessed. The diagnostic performance for recurrence of high-grade gliomas was calculated, using the area under the receiver operating characteristic curve (AUC) with maximum (TNRmax and APTmax) and 90% histogram values (TNR90 and APT90). RESULTS: A moderate positive correlation between TNR and APT was found in low-grade recurrences (r = 0.47, p < 0.001), but not in high-grade ones (r = -0.24, p < 0.001). For distinguishing recurrence in post-treatment high-grade gliomas, APTmax (AUC, 0.88) and APT90 (AUC, 0.78-0.83) had a similar to better diagnostic performance than TNRmax (AUC, 0.71, p = 0.08) or TNR90 (AUC, 0.53-0.59, p = 0.01-0.05). CONCLUSIONS: In post-treatment high-grade gliomas, APT provides different regional information to MET-PET and provides higher diagnostic performance. This difference needs to be considered when using APT or MET-PET as a surrogate marker for tumour protein metabolism. KEY POINTS: • APT and TNR values in low-grade recurrence showed a moderate voxel-wise correlation. • APT and TNR demonstrated regional differences in post-treatment high-grade gliomas. • APT90 showed better diagnostic performance than TNR90 in high-grade recurrence.

Delirium characteristics and outcomes in medical and surgical lnpatients: A subgroup analysis.

PURPOSE: Persistent delirium can negatively affect patients, increase healthcare costs, and extend the length of hospital stays. This investigation was undertaken to explore associations between patient characteristics and delirium outcomes. MATERIALS AND METHODS: Intensive care unit (ICU) and medical and surgical ward inpatients for whom psychiatric consultation was requested for delirium were included in this study. Delirium screening and ongoing assessments were conducted using the Confusion Assessment Method for ICU patients. RESULTS: Postoperative delirium developing as a secondary complication following surgery was found to be of significantly longer duration and associated with greater length of hospitalization compared with postoperative delirium attributable to surgery and delirium in medical patients. Medical patients with delirium had lower delirium recovery rates at discharge compared with surgical patients. CONCLUSIONS: The findings that patient type and timing of postoperative delirium are associated with differential delirium outcomes suggest that targeted screening and intervention approaches may be needed. Medical patients were more likely to be discharged before recovery from delirium compared with surgical patients. Differences in underlying chronic medical conditions may account for the observed differences in discharge condition between medical and surgical patients with delirium.

Effects of a combination treatment of KD5040 and L-dopa in a mouse model of Parkinson's disease.

BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well. METHODS: The effects of KD5040 and l -dopa on motor function, expression levels of substance P (SP) and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor cortex were assessed using behavioral assays, immunohistochemistry, Western blot analyses, and liquid chromatography tandem mass spectrometry in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition, the antidyskinetic effects of KD5040 on pathological movements triggered by l -dopa were investigated by testing abnormal involuntary movements (AIMs) and measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa (DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response element-binding (CREB) protein in the striatum. RESULTS: KD5040 synergistically improved the motor function when low-dose l -dopa (LL) was co-administered. In addition, it significantly reversed MPTP-induced lowering of SP, improved ENK levels in the basal ganglia, and ameliorated abnormal reduction in glutamate content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced by high-dose l -dopa. CONCLUSIONS: KD5040 lowered the effective dose of l -dopa and alleviated LID. These findings suggest that KD5040 may be used as an adjunct therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in patients with PD.

Non-invasive detection of intracranial hypertension using a simplified intracranial hemo- and hydro-dynamics model.

BACKGROUND: Monitoring of intracranial pressure (ICP) is highly important for detecting abnormal brain conditions such as intracranial hemorrhage, cerebral edema, or brain tumor. Until now, the monitoring of ICP requires an invasive method which has many disadvantages including the risk of infections, hemorrhage, or brain herniation. Therefore, many non-invasive methods have been proposed for estimating ICP. However, these methods are still insufficient to estimate sudden increases in ICP. METHODS: We proposed a simplified intracranial hemo- and hydro-dynamics model that consisted of two simple resistance circuits. From this proposed model, we designed an ICP estimation algorithm to trace ICP changes. First, we performed a simulation based on the original Ursino model with the real arterial blood pressure to investigate our proposed approach. We subsequently applied it to experimental data that were measured during the Valsalva maneuver (VM) and resting state, respectively. RESULTS: Simulation result revealed a small root mean square error (RMSE) between the estimated ICP by our approach and the reference ICP derived from the original Ursino model. Compared to the pulsatility index (PI) based approach and Kashif's model, our proposed method showed more statistically significant difference between VM and resting state. CONCLUSION: Our proposed method successfully tracked sudden ICP increases. Therefore, our method may serve as a suitable tool for non-invasive ICP monitoring.