Potential causal associations between leisure sedentary behaviors, physical activity, sleep traits, and myopia: a Mendelian randomization study.

BACKGROUND: Myopia is the most prevalent refractive error and a growing global health concern that significantly affects visual function. Researchers have recently emphasized considerably on the influence of lifestyle on myopia incidence and development. This study investigates the relationship between leisure sedentary behaviors (LSB)/physical activity (PA)/sleep traits and myopia. METHODS: LSB, PA, and sleep trait-associated genetic variants were used as instrument variables in a Mendelian randomization (MR) study to examine their causal effects on myopia. Summary genome-wide association studies (GWASs) statistical data for LSB and PA were obtained from UK Biobank, and the data of sleep traits was obtained from UK Biobank, UK Biobank and 23andMe, and FinnGen. We used summary statistics data for myopia from MRC IEU. The MR analyses was performed using the inverse variance-weighted (IVW), MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier methods. RESULTS: Computer use was genetically predicted to increase the myopia risk [IVW odds ratio (OR) = 1.057; 95% confidence interval (CI), 1.038-1.078; P = 7.04 × 10- 9]. The self-reported moderate-to-vigorous physical activity (MVPA) (IVW OR = 0.962; 95% CI, 0.932-0.993; P = 1.57 × 10- 2) and television watching (IVW OR = 0.973; 95% CI, 0.961-0.985, P = 1.93 × 10- 5) were significantly associated with a lower myopia risk. However, genetically predicted sleep traits or accelerometer-measured physical activity had no significant associations with myopia. CONCLUSION: Our results indicated that computer use is a risk factor for myopia, whereas television watching and MVPA may protect against myopia. These findings shed new light on possible strategies for reducing the prevalence of myopia.

Effect of acute pain on the association between preoperative cognitive impairment and postoperative delirium: a secondary analysis of three trials.

BACKGROUND: The association between preoperative cognitive impairment, postoperative pain, and postoperative delirium in older patients after noncardiac surgery is not known. METHODS: This was a secondary analysis of datasets from three previous studies. Patients aged ≥55 yr who underwent elective noncardiac surgery were enrolled. Preoperative cognitive impairment was defined as Mini-Mental State Examination <27. Pain intensity with movement was assessed using an 11-point numeric rating scale at 12-h intervals during the first 72 h after surgery; time-weighted average (TWA) pain score was calculated. Primary outcome was the occurrence of delirium within the first 5 postoperative days. Mediation analysis was used to investigate the relationships between cognitive impairment, pain score, and delirium. RESULTS: A total of 1497 patients were included. Prevalence of preoperative cognitive impairment was 40.3% (603/1497). Patients with cognitive impairment suffered higher TWA pain score within 72 h (4 [3-5] vs 3 [2-5], P=0.004) and more delirium within 5 days (12.9% [78/603] vs 4.9% [44/894], P<0.001) when compared with those without. Total and direct associations between cognitive impairment and delirium were (adjusted ß) 8.3% (95% confidence interval [CI], 4.8-12.0%; P<0.001) and 7.8% (95% CI, 4.4-12.0%; P<0.001), respectively. A significant indirect association with acute pain was observed between cognitive impairment and delirium (adjusted ß=0.4%; 95% CI, 0.1-1.0%; P=0.006), accounting for 4.9% of the total effect. CONCLUSIONS: The association between preoperative cognitive impairment and delirium is significantly mediated by acute pain in patients after noncardiac surgery. Considering the small effect size, clinical significance of this mediation effect requires further investigation.

The effect of dexmedetomidine on intraoperative blood glucose homeostasis: secondary analysis of a randomized controlled trial.

PURPOSE: To investigate the effect of dexmedetomidine on intraoperative blood glucose hemostasis in elderly patients undergoing non-cardiac major surgery. METHODS: This was secondary analysis of a randomized controlled trial. Patients in dexmedetomidine group received a loading dose dexmedetomidine (0.6 µg/kg in 10 min before anaesthesia induction) followed by a continuous infusion (0.5 µg/kg/hr) till 1 h before the end of surgery. Patients in control group received volume-matched normal saline at the same time interval. Primary outcome was the incidence of intraoperative hyperglycemia (blood glucose higher than 10 mmol/L). RESULTS: 303 patients in dexmedetomidine group and 306 patients in control group were analysed. The incidence of intraoperative hyperglycemia showed no statistical significance between dexmedetomidine group and control group (27.4% vs. 22.5%, RR = 1.22, 95%CI 0.92-1.60, P = 0.167). Median value of glycemic variation in dexmedetomidine group (2.5, IQR 1.4-3.7, mmol) was slightly lower than that in control group (2.6, IQR 1.5-4.0, mmol), P = 0.034. In multivariable logistic analysis, history of diabetes (OR 3.007, 95%CI 1.826-4.950, P < 0.001), higher baseline blood glucose (OR 1.353, 95%CI 1.174-1.560, P < 0.001) and prolonged surgery time (OR 1.197, 95%CI 1.083-1.324, P < 0.001) were independent risk factors of hyperglycaemia. CONCLUSIONS: Dexmedetomidine presented no effect on intraoperative hyperglycemia in elderly patients undergoing major non-cardiac surgery. TRIAL REGISTRATION: Present study was registered at Chinese Clinical Trial Registry on December 1, 2015 ( www.chictr.org.cn , registration number ChiCTR-IPR-15007654).

Parecoxib Supplementation to Morphine Analgesia Decreases Incidence of Delirium in Elderly Patients After Hip or Knee Replacement Surgery: A Randomized Controlled Trial.

BACKGROUND: Severe pain and high-dose opioids are both associated with increased risk of postoperative delirium. The authors investigated whether parecoxib-supplemented IV morphine analgesia could decrease the incidence of delirium in elderly patients after total hip or knee replacement surgery. METHODS: In a randomized, double-blind, 2-center trial, patients of 60 years or older who underwent elective total hip or knee replacement surgery were assigned in a 1:1 ratio to receive either parecoxib (40 mg at the end of surgery and then every 12 hours for 3 days) or placebo (normal saline). All patients received combined spinal-epidural anesthesia during surgery and IV morphine for postoperative analgesia. The primary outcome was the incidence of delirium within 5 days after surgery. RESULTS: Between January 2011 and May 2013, 620 patients were enrolled and were included in the intention-to-treat and safety analyses. The incidence of delirium was significantly reduced from 11.0% (34/310) with placebo to 6.2% (19/310) with parecoxib (relative risk 0.56, 95% confidence interval 0.33-0.96, P = .031). The severity of pain and the cumulative consumptions of morphine at 24, 48, and 72 hours after surgery were significantly lower with parecoxib than with placebo (all P < .001), although the differences were small. There was no difference in the incidence of postoperative complications between the 2 groups (12.3% [38/310] with placebo versus 11.6% [36/310] with parecoxib; P = .80). CONCLUSIONS: For low-risk elderly patients undergoing elective total hip or knee replacement surgery, multidose parecoxib supplemented to IV morphine decreased the incidence of postoperative delirium without increasing adverse events.

Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials.

STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.

TRIANGLE operation, combined with adequate adjuvant chemotherapy, can improve the prognosis of pancreatic head cancer: A retrospective study.

BACKGROUND: The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein, celiac axis-common hepatic artery, and superior mesenteric artery to improve patient prognosis. Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy (PD). AIM: To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC. METHODS: This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023, with or without the TRIANGLE operation. Patients were divided into the PDTRIANGLE and PDnon-TRIANGLE groups. Surgical and survival outcomes were compared between the two groups. Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy ≥ 6 months. RESULTS: The PDTRIANGLE and PDnon-TRIANGLE groups included 52 and 55 patients, respectively. There were no significant differences in the baseline characteristics or perioperative indexes between the two groups. Furthermore, the recurrence rate was lower in the PDTRIANGLE group than in the PDnon-TRIANGLE group (48.1% vs 81.8%, P < 0.001), and the local recurrence rate of PDAC decreased from 37.8% to 16.0%. Multivariate Cox regression analysis revealed that PDTRIANGLE (HR = 0.424; 95%CI: 0.256-0.702; P = 0.001), adequate adjuvant chemotherapy ≥ 6 months (HR = 0.370; 95%CI: 0.222-0.618; P < 0.001) and margin status (HR = 2.255; 95%CI: 1.252-4.064; P = 0.007) were found to be independent factors for the recurrence rate. CONCLUSION: The TRIANGLE operation is safe for PDAC patients undergoing PD. Moreover, it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

Effect of intraoperative dexmedetomidine on long-term survival in older patients after major noncardiac surgery: 3-year follow-up of a randomized trial.

STUDY OBJECTIVE: To assess the impact of intraoperative dexmedetomidine on long-term outcomes of older patients following major noncardiac surgery mainly for cancer. DESIGN: A long-term follow-up of patients enrolled in a randomized trial. SETTING: The initial trial was performed in a tertiary care hospital in Beijing, China. PARTICIPANTS: Patients aged 60 years or older who were scheduled for major noncardiac surgery. INTERVENTION: Participants were randomized to receive either dexmedetomidine (a loading dose of 0.6 µg/kg over 10 min, followed by a continuous infusion of 0.5 µg/kg/h until 1 h before end of surgery) or placebo during anesthesia. MEASUREMENTS: The primary endpoint was overall survival. Secondary endpoints included recurrence-free survival and event-free survival. Cox proportional hazard models were used to adjust for predefined confounding factors. Propensity score matching was employed for sensitive analysis. RESULTS: Among 620 patients who were randomized in the initial trial, 619 were included in the long-term analysis (mean age 69 years, 40% female, 77% oncological surgery). The median follow-up duration was 42 months (interquartile range 41 to 45). Overall survival did not differ between the two groups: there were 49/309 (15.9%) deaths with dexmedetomidine versus 63/310 (20.3%) with placebo (adjusted hazard ratio [HR] 0.78, 95% CI 0.53-1.13, P = 0.187). Recurrence-free survival was improved with dexmedetomidine (68/309 [22.0%] events with dexmedetomidine versus 98/310 [31.6%] with placebo; adjusted HR 0.67, 95% CI 0.49-0.92, P = 0.012). Event-free survival was also improved with dexmedetomidine (120/309 [38.8%] events with dexmedetomidine versus 145/310 [46.8%] with placebo; adjusted HR 0.78, 95% CI 0.61-1.00, P = 0.047). Results were similar after propensity-score matching and in the subgroup of cancer patients. CONCLUSIONS: In older patients having major noncardiac surgery mainly for cancer, intraoperative dexmedetomidine did not improve overall survival but was associated with improved recurrence-free and event-free survivals.

The sensitivity and specificity of statistical rules for diagnosing delayed neurocognitive recovery with Montreal cognitive assessment in elderly surgical patients: A cohort study.

Delayed neurocognitive recovery (DNR) is common in elderly patients after major noncardiac surgery. This study was designed to investigate the best statistical rule in diagnosing DNR with the Montreal cognitive assessment (MoCA) in elderly surgical patients.This was a cohort study. One hundred seventy-five elderly (60 years or over) patients who were scheduled to undergo major noncardiac surgery were enrolled. A battery of neuropsychological tests and the MoCA were employed to test cognitive function at the day before and on fifth day after surgery. Fifty-three age- and education-matched nonsurgical control subjects completed cognitive assessment with the same instruments at the same time interval. The definition of the international study of postoperative cognitive dysfunction (ISPOCD 1) was adopted as the standard reference for diagnosing DNR. With the MoCA, the following rules were used to diagnose DNR: the cut-off point of ≤26; the 1 standard deviation decline from baseline; the 2 scores decline from baseline; and the Z score of ≥1.96. The sensitivity and specificity as well as the area under receiver operating characteristic curve for the above rules in diagnosis of DNR were calculated.The incidence of DNR was 13.1% (23/175) according to the ISPOCD1 definition. When compared with the standard reference, the 2 scores rule showed the best combination of sensitivity (82.6%, 95% confidence interval [CI] 67.1%-98.1%) and specificity (82.2%, 95% CI 76.2%-88.3%); it also had the largest area under receiver operating characteristic curve (0.824, 95% CI 0.728-0.921, P < .001). The cut-off point rule showed high sensitivity (95.7%) and low specificity (37.5%), whereas the 1 standard deviation and the Z score rules showed low sensitivity (47.8% and 21.7%, respectively) and high specificity (93.4% and 97.3%, respectively).Compared with the ISPOCD1 definition, the 2 scores rule with MoCA had the best combination of sensitivity and specificity to diagnose DNR.

Dexmedetomidine in combination with morphine improves postoperative analgesia and sleep quality in elderly patients after open abdominal surgery: A pilot randomized control trial.

BACKGROUND: Dexmedetomidine in combination with opioids has been used for postoperative analgesia. The purpose of this study was to investigate the impacts of dexmedetomidine supplemented intravenous analgesia on morphine consumption and subjective sleep quality in elderly patients after open abdominal surgery. METHODS: This was a pilot randomized controlled trial. 58 elderly patients (age ≥ 60 years) who underwent open abdominal surgery were randomized to receive either dexmedetomidine supplemented morphine analgesia (0.5 mg/ml morphine plus 2 µg/ml dexmedetomidine in 100 ml normal saline, DEX group) or morphine analgesia (0.5 mg/ml morphine in 100 ml normal saline, CTRL group) for 72 hours after surgery. Patient-controlled analgesia pump was programmed to deliver a 2ml bolus with a lockout interval of 8 minutes and a background infusion at a rate of 1 ml/h. The primary endpoint was 72-hour morphine consumption. Secondary endpoints included pain intensity, subjective sleep quality, and 30-day complications and mortality after surgery. RESULTS: The 72-hour morphine consumption was lower in the DEX group than in the CTRL group (median 39.0 mg [interquartile range 37.3, 41.0] in the DEX group vs. 49.0 mg [45.5, 50.0] in the CTRL group; median difference -9.0 mg [95% CI -10.0, -6.0], P < 0.001). The intensity of pain within 48 hours was lower (P<0.001 at 4, 12 and 48 hours, P = 0.007 at 24 hours) whereas the subjective quality of sleep was higher (P = 0.031 during the night of surgery and P<0.001 during the 1st night after surgery, respectively) in the DEX group than in the CTRL group. The incidence of 30-day complications did not differ significantly between groups, but it was slightly lower in the DEX group (P = 0.060). There were no significant differences between groups regarding 30-day mortality and the incidences of adverse events. CONCLUSIONS: For elderly patients after open abdominal surgery, dexmedetomidine supplemented analgesia decreases morphine consumption, improves analgesic effects and subjective sleep quality without increasing adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-14005620.

Impact of dexmedetomidine infusion during general anaesthesia on incidence of postoperative delirium in elderly patients after major non-cardiac surgery: study protocol of a randomised, double-blinded and placebo-controlled trial.

INTRODUCTION: Delirium is a common complication in the elderly after surgery and is associated with worse outcomes. Multiple risk factors are related with postoperative delirium, such as exposure to general anaesthetics, pain and postoperative inflammatory response. Preclinical and clinical studies have shown that dexmedetomidine attenuated neurotoxicity induced by general anaesthetics, improved postoperative analgesia and inhibited inflammatory response after surgery. Several studies found that intraoperative use of dexmedetomidine can prevent postoperative delirium, but data were inconsistent. This study was designed to investigate the impact of dexmedetomidine administered during general anaesthesia in preventing delirium in the elderly after major non-cardiac surgery. METHODS AND ANALYSIS: This is a randomised, double-blinded and placebo-controlled trial. 620 elderly patients (age ≥60 years) who are scheduled to undertake elective major non-cardiac surgery (with an expected duration ≥2 hours) are randomly divided into two groups. For patients in the dexmedetomidine group, a loading dose dexmedetomidine (0.6 µg/kg) will be administered 10 min before anaesthesia induction, followed by a continuous infusion at a rate of 0.5 µg/kg/hour until 1 hour before the end of surgery. For patients in the control group, normal saline will be administered with an identical rate as in the dexmedetomidine group. The primary endpoint is the incidence of delirium during the first five postoperative days. The secondary endpoints include pain intensity, cumulative opioid consumption and subjective sleep quality during the first three postoperative days, as well as the incidence of non-delirium complications and all-cause mortality within 30 days after surgery. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Ethics Committee of Peking University First Hospital (2015-987) and registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn) with identifier ChiCTR-IPR-15007654. The results of the study will be presented at academic conferences and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCRR-IPR-15007654; Pre-results.

Noninvasive Tumor Grading of Glioblastomas Before Surgery Using Arterial Spin Labeling. A Cohort Study.

OBJECTIVE: To assess the clinical value of using arterial spin labeling (ASL) technique preoperatively for non-invasive tumor grading in glioblastoma (GBM) patients. STUDY DESIGN: Forty-nine patients with GBMs were selected, including 21 patients with high-grade gliomas and 28 patients with low-grade gliomas. ASL perfusion imaging was performed with GE Signa Excite HD 3.0 T MR scanning system (GE Healthcare). Relative cerebral blood flow (rCBF) and relative tumor blood flow (rTBF) were quantified in all patients. Statistical analysis was performed with STATA version 12.0 software. Further, relevant human cohort studies published in Chinese and English languages were identified by database searches and screened. Data was extracted and meta-analysis was performed using Comprehensive Meta-analysis version 2.0 software. RESULTS: The ratios of rTBF to rCBF in the contralateral white matter, contralateral gray matter, and contralateral hemisphere of high-grade gliomas were higher than low-grade gliomas (all p < 0.05). ASL results in the solid tumors revealed that rCBF was greater in high-grade gliomas. Such differences in rCBF were not significant (p > 0.05) when 2 and 5 cm distances from tumor margin were compared. Importantly, rCBF values showed statistical differences when the 2 cm distance was compared with the 5 cm distance from tumor margin (all p < 0.05). Finally, meta-analysis results supported the conclusion that rCBF and rTBF values were significantly higher in high-grade GBM as compared to low-grade GBM. CONCLUSION: We present convincing data that ASL is highly effective in differentiating between high-grade and low-grade gliomas, and thus is a useful tool for preoperative evaluation of GBM.