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Background: Up to 10% of epidurals fail due to incorrect catheter placement. We describe a novel optical method to assist epidural catheter insertion in a porcine model. Methods: Optical emissions were tested on ex vivo tissues from porcine paravertebral tissues to identify optical reflective spectra. The wavelengths of 650 and 532 nm differentiated epidural space from the ligamentum flavum. We then used a hollow stylet that contained optical fibers to place epidural needles in anesthetized pigs. Real-time data were displayed on an oscilloscope and stored for analysis. A total of 50 punctures were done in four laboratory pigs. Data were expressed as mean +/- SD. Results: Paired t test shows significant optical differences between the epidural space and the ligamentum flavum at both 650 nm (P < 0.001) and 532 nm (P = 0.014). Mean magnitudes for 650 nm, 532 nm, and their ratio were 3.565 +/- 0.194, 2.542 +/- 0.145, and 0.958 +/- 0.172 at epidural space and 3.842 +/- 0.191, 2.563 +/- 0.131, and 1.228 +/- 0.244 at ligamentum flavum, respectively. There were no differences in the optical characteristics of the ligamentum flavum and epidural space at different levels in the lumbar and thoracic region (two-way ANOVA P > 0.05). Conclusions: This is the first study to introduce a new optical method to localize epidural space in a porcine model. Epidural space could be identified by the changes in the reflective pattern of light emitted at 650 nm, which were specific for the ligamentum flavum and dural tissue. Real-time optical information successfully guided a modified Tuohy needle into the epidural space. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effect of acupoint electrical stimulation with patient-controlled analgesia (PCA) on reducing acute pain, nausea, and vomiting after surgery for nontraumatic spinal cord injury. [ABSTRACT FROM AUTHOR]

Background Context: Postoperative pain control following spine surgery can be difficult. The Enhanced Recovery After Surgery (ERAS) programs use multimodal approaches to manage postoperative pain. While an erector spinae plane block (ESPB) is commonly utilized, the ideal distance for injection from the incision, referred to as the ES (ESPB to mid-surgical level) distance, remains undetermined., Purpose: We evaluated the impact of varying ES distances for ESPB on Numerical Rating Scale (NRS) measures of postoperative pain within the ERAS protocol., Study Design/setting: Retrospective observational study., Patient Sample: Adult patients who underwent elective lumbar spine fusion surgery., Outcome Measures: Primary outcome measures include the comparative postoperative NRS scores across groups at immediate (T1), 24 (T2), 48 (T3), and 72 (T4) hours postsurgery. For secondary outcomes, a propensity matching analysis compared these outcomes between the ERAS and non-ERAS groups, with opioid-related recovery metrics also assessed., Methods: All included patients were assigned to one of three ERAS groups according to the ES distance: Group 1 (G1, ES > 3 segments), Group 2 (G2, ES = 2-3 segments), and Group 3 (G3, ES<2 segments). Each patient underwent a bilateral ultrasound-guided ESPB with 60 mL of diluted ropivacaine or bupivacaine., Results: Patients within the ERAS cohort reported mild pain (NRS < 3), with no significant NRS variation across G1 to G3 at any time. Sixty-five patients were matched across ERAS and non-ERAS groups. The ERAS group exhibited significantly lower NRS scores from T1 to T3 than the non-ERAS group. Total morphine consumption during hospitalization was 26.7 mg for ERAS and 41.5 mg for non-ERAS patients. The ERAS group resumed water and food intake sooner and had less postoperative nausea and vomiting., Conclusions: ESPBs can be effectively administered at or near the mid-surgical level to the low thoracic region for lumbar spine surgeries. Given challenges with sonovisualization, a lumbar ESPB may be preferred to minimize the risk of inadvertent pleural injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Dexmedetomidine is an alpha-2 agonist with anti-anxiety, sedative, and analgesic effects and causes a lesser degree of respiratory depression. We hypothesized that the use of dexmedetomidine in non-intubated video-assisted thoracic surgery (VATS) may reduce opioid-related complications such as postoperative nausea and vomiting (PONV), dyspnea, constipation, dizziness, skin itching, and cause minimal respiratory depression, and stable hemodynamic status., Methods: Patients who underwent non-intubated VATS lung wedge resection with propofol combined with dexmedetomidine (group D) or alfentanil (group O) between December 2016 and May 2022 were enrolled in this retrospective propensity score matching cohort study. Intraoperative vital signs, arterial blood gas data, perioperative results and treatment outcomes were analyzed. Of 100 patients included in the study (group D, 50 and group O, 50 patients), group D had a significantly lower degree of decrement in the heart rate and the blood pressure than group O. Intraoperative one-lung arterial blood gas revealed lower pH and significant ETCO 2 . The common opioid-related side effects, including PONV, dyspnea, constipation, dizziness, and skin itching, all of which occurred more frequently in group O than in group D. Patients in group O had significantly longer postoperative hospital stay and total hospital stay than group D, which might be due to opioid-related side effects postoperatively., Conclusions: The application of dexmedetomidine in non-intubated VATS resulted in a significant reduction in perioperative opioid-related complications and maintenance with acceptable hemodynamic performance. These clinical outcomes found in our retrospective study may enhance patient satisfaction and shorten the hospital stay., (© 2023. The Author(s).)

Purpose: Regulations have broadened to allow moderate sedation administration for gastrointestinal endoscopy by non-anesthesia personnel. The line between moderate and deep sedation is ambiguous. Deep sedation offers patient comfort as well as greater safety concerns. Unintended deep sedation can occur if drug interactions are overlooked. We present a pharmacodynamic model for moderate sedation using midazolam, alfentanil and propofol. The model is suitable for training and devising rationales for appropriate dosing., Methods: The study consists of two parts: modeling and validation. In modeling, patients scheduled for esophagogastroduodenoscopy (EGD) or colonoscopy sedation are enrolled. The modified observer's assessment of alertness/sedation (MOAA/S) score < 4 is defined as loss of response to represent moderate sedation. Two patient groups receiving bronchoscopy or endoscopic retrograde cholangiopancreatography (ERCP) are used for validation. Model performance is assessed by receiver operating characteristic (ROC) curves and area under the curve (AUC). Simulations are performed to demonstrate how the model is used to rationally determine drug regimen for moderate sedation., Results: Interaction between propofol and alfentanil is stronger than the other pairwise combinations. Additional synergy is observed with three drugs. ROC AUC is 0.83 for the modeling group, and 0.96 and 0.93 for ERCP and bronchoscopy groups respectively. Model simulation suggests that 1 mg midazolam, 250 µg alfentanil and propofol maximally benefits from drug interactions and suitable for moderate sedation., Conclusion: We demonstrate the accurate prediction of a three-drug response surface model for moderate sedation and simulation suggests a rational dosing strategy for moderate sedation with midazolam, alfentanil and propofol., (© 2023. The Author(s).)

Background: The association between perioperative blood transfusion and cancer prognosis in patients with head and neck cancer (HNC) receiving surgery remains controversial., Methods: We designed a retrospective observational study of patients with HNC undergoing tumor resection surgery from 2014 to 2017 and followed them up until June 2020. An inverse probability of treatment weighting (IPTW) was applied to balance baseline patient characteristics in the exposed and unexposed groups. COX regression was used for the evaluation of tumor recurrence and overall survival., Results: A total of 683 patients were included; 192 of them (28.1%) received perioperative packed RBC transfusion. Perioperative blood transfusion was significantly associated with HNC recurrence (IPTW adjusted HR: 1.37, 95% CI: 1.1-1.7, p = 0.006) and all-cause mortality (IPTW adjusted HR: 1.37, 95% CI: 1.07-1.74, p = 0.011). Otherwise, there was an increased association with cancer recurrence in a dose-dependent manner., Conclusion: Perioperative transfusion was associated with cancer recurrence and mortality after HNC tumor surgery.

Background: Preclinical studies have shown that local anesthetics may modify the growth and invasion of cancer cells. However, few clinical studies have evaluated their impact on cancer outcomes after tumor resection., Methods: In this single-center cohort study, patients who underwent surgical resection of stage IA through IIIB nonsmall-cell lung cancer and used patient-controlled epidural analgesia from 2005 to 2015 were recruited and followed until May 2017. Data of the epidural bupivacaine dose for each patient were obtained from infusion pump machines. Proportional hazards regression models were used to analyze the associations between bupivacaine dose with postoperative cancer recurrence and all-cause mortality., Results: A total of 464 patients were analyzed. Among these patients, the mean bupivacaine dose was 352 mg (± standard deviation 74 mg). After adjusting for important clinical and pathological covariates, a significant dose-response relationship was observed between epidural bupivacaine dose and all-cause mortality (adjusted hazard ratio: 1.008, 95% confidence interval: 1.001-1.016, p = 0.029). The association between bupivacaine dose and cancer recurrence were not significant (adjusted hazard ratio: 1.000, 95% confidence interval: 0.997-1.002, p = 0.771). Age, sex, body mass index, mean daily maximum pain score, and pathological perineural infiltration were independently associated with bupivacaine dose., Conclusion: A dose-dependent association was found between epidural bupivacaine dose and long-term mortality among patients following surgical resection of nonsmall-cell lung cancer. Our findings do not support the hypothetical anticancer benefits of local anesthetics. More studies are needed to elucidate the role of local anesthetics in cancer treatment., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

High-flow nasal oxygen (HFNO) has been used in "tubeless" shared-airway surgeries but whether HFNO increased the fire hazard is yet to be examined. We used a physical model for simulation to explore fire safety through a series of ignition trials. An HFNO device was attached to a 3D-printed nose with nostrils connected to a degutted raw chicken. The HFNO device was set at twenty combinations of different oxygen concentration and gas flow rate. An electrocautery and diode laser were applied separately to a fat cube in the cavity of the chicken. Ten 30 s trials of continuous energy source application were conducted. An additional trial of continuous energy application was conducted if no ignition was observed for all the ten trials. A total of eight short flashes were observed in one hundred electrocautery tests; however, no continuous fire was observed among them. There were thirty-six events of ignition in one hundred trials with laser, twelve of which turned into violent self-sustained fires. The factors found to be related to a significantly increased chance of ignition included laser application, lower gas flow, and higher FiO 2 . The native tissue and smoke can ignite and turn into violent self-sustained fires under HFNO and continuous laser strikes, even in the absence of combustible materials. The results suggest that airway surgeries must be performed safely with HFNO if only a short intermittent laser is used in low FiO 2 ., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Whether epidural anesthesia and analgesia (EA) improves long-term outcomes after pancreatic cancer surgery remains controversial. We conducted this retrospective cohort study to investigate the influence of EA on cancer recurrence and overall survival after surgery for pancreatic cancer., Methods: We conducted an electronic medical chart review of patients with pancreatic cancer who underwent curative resection at our hospital from 2008 to 2017 and were followed up until December 2019. Patient demographics, anesthetic and surgical characteristics, and pathologic features were also collected. The effects of EA on postoperative cancer recurrence and overall survival were evaluated using proportional hazards regression models with inverse probability of treatment weighting (IPTW) based on propensity scores to balance unequal distributions of observed covariates. For sensitivity analysis, multivariable regression modeling and quintile-stratified propensity adjustments were also used., Results: Among the 252 included patients, the median follow-up period was 15.9 months (interquartile range 6.8-28.2 months), and 88 (35%) received EA after pancreatic cancer surgery. EA was not associated with greater cancer recurrence (IPTW adjusted HR: 0.98; 95% CI, 0.78%-1.24%; p = 0.87) or all-cause mortality (IPTW adjusted HR: 1.02; 95% CI, 0.82%-1.27%; p = 0.85) after pancreatic cancer resection. In sensitivity analysis, both the multivariable and stratified Cox regression analyses failed to demonstrate significant effects of EA on cancer recurrence and survival after surgery., Conclusion: There were no significant associations between EA and cancer recurrence and overall survival after curative surgery for pancreatic cancer. Prospective studies should be considered to elucidate the relationship between EA and cancer outcomes after pancreatic cancer surgery., Competing Interests: Conflicts of interest: Dr. Mei-Yung Tsou, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Objective: Nonintubated anesthesia, electromagnetic navigation (EMN)-guided preoperative localization, and uniportal video-assisted thoracic surgery (VATS) are recent innovations in minimally invasive thoracic surgery. This study aimed to explore the feasibility of applying nonintubated anesthesia in a "one-stage" localization and resection workflow., Methods: Patients who underwent EMN-guided preoperative percutaneous localization with indocyanine green (ICG) and uniportal VATS were included. Perioperative data were compared between patients receiving nonintubated anesthesia and those receiving general anesthesia with endotracheal intubation., Results: Forty-six patients with a total of 50 nodules were included in the study. Overall, finger palpation could be avoided in 94% of the nodules, whereas fluorescent green signals with a clear border on the pleural surface were noted in 91.3% (21 of 23) of nodules in the nonintubated group and 88.9% (24 of 27) of nodules in the intubated group. Intraoperatively, the nonintubated group had a lower median pH (7.33 [interquartile range (IQR), 7.28-7.40] vs 7.41 [IQR, 7.38-7.44]; P  = .003), higher median arterial CO 2 (45.5 [IQR, 41.1-58.7] mm Hg vs 38.4 [IQR, 35.3-40.6] mm Hg; P  < .001), and lower arterial oxygen (322 [IQR, 211-433] mm Hg vs 426 [IQR, 355-471] mm Hg; P  = .005) levels compared with the intubated group. The nonintubated group also had a shorter median registration time (2.0 [IQR, 1.0-3.0] minutes vs 3.0 [IQR, 2.0-8.0] minutes; P  = .008) and total time in the operating room (150 [IQR, 130-175] minutes vs 170 [IQR, 135-203] minutes; P  = .035), whereas no between-group differences were seen in localization and operative time. The duration of chest drainage, postoperative complications, pathologic diagnosis, and margins were similar in the 2 groups., Conclusions: Nonintubated "one-stage" EMN-guided percutaneous ICG localization and uniportal VATS can be an option for selected patients undergoing treatment for small peripheral nodules., (© 2021 The Author(s).)

Intercostal nerve block is a widely used and effective approach to providing regional anesthesia in the thoracic region for pain relief. However, during ultrasound-guided intercostal nerve block, inaccurate identification of the anatomic structures or suboptimal positioning of the needle tip may result in complications and blockade failure. In this study, we designed an intraneedle ultrasound (INUS) system and validated its efficacy in identifying anatomic structures relevant to thoracic region anesthesia. The 20-MHz INUS transducer comprised a single lead magnesium niobate-lead titanate crystal, and gain was set to 20 dB. It fit into a regular 18G needle and emitted radiofrequency-mode ultrasound signals at 1 mm from the needle tip. One hundred intercostal punctures were performed in 10 piglets. Intercostal spaces were identified by surface ultrasound or palpation and located by inserting and advancing the INUS transducer needle until the appropriate anatomy was identified. Blockade success was defined by ideal saline and dye spreading and confirmed by dissection. The pleura had a distinctive ultrasound signal, and successful detection of the intercostal muscles, endothoracic fascia and double-layered parietal and visceral pleura was achieved in all 100 puncture attempts. INUS allows real-time identification of intercostal structures and facilitates successful intercostal nerve blocks., Competing Interests: Conflict of interest disclosure The authors report no competing financial interests nor conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Background: Systemic inflammation correlates closely with tumor invasion and may predict survival in cancer patients. We aimed to compare the prognostic value of various inflammation-based markers in patients with hepatocellular carcinoma., Methods: We consecutively enrolled 1450 patients with primary hepatocellular carcinoma undergoing surgical resection at the medical center between 2005 and 2016 and assessed them through September 2018. Prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio along with their perioperative dynamic changes were analyzed regarding their predictive ability of postoperative disease-free survival and overall survival. We calculated the adjusted hazard ratio (HR) and 95% CI of the association between inflammation-based markers and survival using multiple Cox proportional hazards models. Youden's index of receiver operating characteristics curves was used to determine optimal cut-off points., Results: Prognostic nutritional index was an independent predictor for both disease-free survival (<50.87 vs ≥50.87, HR: 1.274, 95% CI, 1.071-1.517, p = 0.007) and overall survival (<46.65 vs ≥46.65, HR: 1.420, 95% CI, 1.096-1.842, p = 0.008). Besides, the relative change of neutrophil-to-lymphocyte ratio predicted overall survival (<277% vs ≥277%, HR: 1.634, 95% CI, 1.266-2.110, p < 0.001). Combination of both markers offered better prognostic performance for overall survival than either alone. Body mass index, liver cirrhosis, chronic kidney disease, and tumor diameter were significantly associated with both markers., Conclusion: Prognostic nutritional index and perioperative relative change of neutrophil-to-lymphocyte ratio independently predict postoperative survival in patients undergoing surgical resection of hepatocellular carcinoma. These results provided important evidence for risk stratification and individualized anti-cancer therapy., Competing Interests: Conflicts of interest: Dr Ming-Chih Hou and Dr Mei-Yung Tsou, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Objective: The efficacy of parecoxib as pre-emptive analgesia still remains controversial. This study aimed to investigate how pre-emptive analgesia with parecoxib affected postoperative pain trajectories over time in patients undergoing thoracic surgery., Design: Retrospective cohort study., Setting: A single medical centre in Taiwan., Participants: We collected 515 patients undergoing video-assisted thoracoscopic surgery at a tertiary medical centre between September 2016 and August 2017., Interventions: Pre-emptive parecoxib before surgery., Primary and Secondary Outcome Measures: Daily numeric rating pain scores in the first postoperative week., Results: A total of 196 (38.1%) of the recruited patients received parecoxib preoperatively. The latent curve analysis revealed that woman, higher body weight and postoperative use of parecoxib were associated with increased baseline level of pain scores over time (p=0.035, 0.005 and 0.048, respectively) but epidural analgesia and preoperative use of parecoxib were inclined to decrease it (both p<0.001). Regarding the decreasing trends of changes in daily pain scores, older age and epidural analgesia tended to steepen the slope (p=0.014 and <0.001, respectively). Preoperative use of parecoxib were also related to decreased frequency of rescue morphine medication (HR=0.4; 95% CI 0.25 to 0.65)., Conclusions: Pre-emptive analgesia with parecoxib was associated with decreased baseline pain scores but had no connection with pain decreasing trends over time. Latent curve analysis provided insights into the dynamic relationships among the analgesic modalities, patient characteristics and postoperative pain trajectories., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The purpose of this study was to determine the efficacy of a mandibular advancement device (MAD) for increasing patient safety during sedated total knee arthroplasty (TKA) and total hip replacement (THR)., Methods: Forty patients undergoing TKA or THR surgery in the supine or lateral recumbent positions under spinal anesthesia were enrolled. Sedation and oxygenation were administered. The MAD (Sweet Sleep Anti-Snoring Device) was then placed after 15 minutes of observation. SpO2, PetCO2, blood pressure, and respiratory rate were recorded., Results: Sedated patients in the decubitus position had higher saturation nadirs, shorter desaturation durations, shorter airway obstruction durations, and fewer rescue events than those in the supine position. In patients at a high risk of obstructive sleep apnea syndrome (OSAS), desaturation duration, obstruction duration, apnea duration, desaturation duration, and rescue events were significantly lower after MAD placement. However, the saturation nadir did not improve after MAD placement., Conclusion: The MAD may shorten the duration of desaturation events during spontaneous breathing sedative procedures in the lateral recumbent position but not in the supine position. Breathing patterns did not change from nasal breathing to oral breathing or vice versa between pre- and postplacement of the MAD. Sedation score evaluation affects breathing pattern changes from oral breathing to nasal breathing and vice versa., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2020, the Chinese Medical Association.)

Background: The pandemic of SARS-CoV-2 (COVID-19), which began in December 2019, spread mostly from person to person through respiratory droplets. A recommendation was issued to postpone all elective surgical practices. However, some confirmed or suspected COVID-19 patients required life-saving emergent surgeries., Methods: To facilitate emergent surgical interventions for these patients, we have reviewed the current literature and established an algorithm of precautions to be taken by operating room team members during the COVID-19 pandemic., Results: The initial algorithm of preparation for surgical intervention during the COVID-19 pandemic was relatively simple. However, the abrupt increase of confirmed COVID-19 cases due to returned overseas travelers since mid-March 2020 disrupted the routine hospital clinical service. Due to the large number of febrile patients, the algorithm was therefore revised according to travel history, occupation, contact and cluster history (TOCC), unexplained fever/symptoms, and emergent/nonemergent surgery. TOCC (+) patients presenting with otherwise unexplained fever/symptoms would be regarded as belonging to the fifth category of "severe special infectious pneumonia." If the patient requires emergent surgery to relieve the non-life-threatening disorders, two times of negative COVID-19 tests are necessary before the operation is approved. For life-threatening situations without two negative results of COVID-19 tests, the operation schedule should be approved by the Chairman of Surgery Management Committee., Conclusion: The application of a clear and integrated algorithm for operating room team members aids in effective personal protective equipment facilitation to keep both healthcare providers and patients safe as well as to prevent hospital-based transmission of COVID-19., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2020, the Chinese Medical Association.)

The relationship between epidural analgesia and rectal cancer outcome is not fully clarified. We aimed to investigate the putative effect of epidural analgesia on the risks of recurrence and mortality after rectal tumour resection. In this monocentric cohort study, we consecutively enrolled patients with stage I-III rectal cancer who underwent tumour resection from 2005 to 2014. Patients received epidural analgesia or intravenous opioid-based analgesia for postoperative pain control. Primary endpoint was first cancer recurrence. Secondary endpoints were all-cause mortality and cancer-specific mortality. We collected 1282 patients in the inverse probability of treatment weighting analyses, and 237 (18.5%) used epidurals. Follow-up interval was median 46.1 months. Weighted Cox regression analysis showed the association between epidural analgesia and recurrence-free survival was non-significant (adjusted hazard ratio [HR] 0.941, 95% CI 0.791-1.119, p = 0.491). Similarly, the association between epidural analgesia and overall survival (HR 0.997, 95% CI 0.775-1.283, p = 0.984) or cancer-specific survival (HR 1.113, 95% CI 0.826-1.501, p = 0.482) was non-significant either. For sensitivity tests, quintile stratification and stepwise forward model selection analyses showed similar results. We did not find a significant association between epidural analgesia and risk of recurrence, all-cause mortality, or cancer-specific mortality in patients with rectal cancer undergoing tumour resection.

Background: Although previous studies have shown connections between pain and worse cancer outcomes, few clinical studies have evaluated their direct association, and the current study aimed to investigate the potential association between acute pain trajectories and postoperative outcomes after liver cancer surgery., Methods: This retrospective study was conducted in a single medical center and included patients who received liver cancer surgery between January 2010 and December 2016. Maximal pain intensity was recorded daily using a numerical rating scale during the first postoperative week. Group-based trajectory analysis was performed to classify the variations in pain scores over time. Cox and linear regression analyses were used to assess the effect of pain trajectories on recurrence-free survival, overall survival, and length of hospital stay (LOS) after surgery and to explore predictors of these outcomes., Results: A total of 804 patients with 5396 pain score observations were analyzed within the present study. Group-based trajectory analysis categorized the changes in postoperative pain into three groups: group 1 had constantly mild pain (76.6%), group 2 had moderate/severe pain dropping to mild (10.1%), and group 3 had mild pain rebounding to moderate (13.3%). Multivariable analysis demonstrated that on average, group 3 had a 7% increase in LOS compared with the group 1 (p = 0.02) and no significant difference in the LOS was noted between pain trajectory groups 2 and 1 (p = 0.93). Pain trajectories were not associated with recurrence-free survival or overall survival after liver cancer surgery., Conclusion: Acute pain trajectories were associated with LOS but not cancer recurrence and survival after liver cancer surgery. Group-based trajectory analysis provided a promising approach for investigating the complex relationships between variations in postoperative pain over time and clinical outcomes., Competing Interests: Conflicts of Interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2020, the Chinese Medical Association.)

Clinical and pathological predictors have proved to be insufficient in identifying high-risk patients who develop cancer recurrence after tumour resection. We aimed to compare the prognostic ability of various inflammation markers in patients undergoing surgical resection of lung cancer. We consecutively included 2,066 patients with stage I-III non-small-cell lung cancer undergoing surgical resection at the center between 2005 and 2015. We evaluated prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio along with their perioperative changes. We conducted stepwise backward variable elimination and internal validation to compare the selected markers' predictive performance for postoperative recurrence-free survival and overall survival. Preoperative neutrophil-to-lymphocyte ratio independently predicts recurrence-free survival (HR: 1.267, 95% CI 1.064-1.509, p = 0.0079, on base-2 logarithmic scale) and overall survival (HR: 1.357, 95% CI 1.070-1.721, p = 0.0117, on base-2 logarithmic scale). The cut-off value is 2.3 for predicting both recurrence (sensitivity: 46.1% and specificity: 66.7%) and mortality (sensitivity: 84.2% and specificity: 40.4%). Advanced cancer stage, poor tumour differentiation, and presence of perineural infiltration were significantly correlated with higher preoperative neutrophil-to-lymphocyte ratio. We concluded that preoperative neutrophil-to-lymphocyte ratio is superior to prognostic nutritional index and platelet-to-lymphocyte ratio in predicting postoperative recurrence and mortality of patients undergoing surgical resection of non-small-cell lung cancer.

Background: Conflicting evidence underlies the controversial role of allogenic blood transfusion in recurrence of non-small cell lung cancer (NSCLC). Insufficient sample size and failure to measure effects of important confounders in previous studies contribute to the conflicting findings. To overcome these limitations, we applied robust statistics and weighted covariates in a large study cohort., Methods: Cox regression analyses were used to estimate the recurrence and survival in patients with NSCLC disease stages I through III who were transfused for a haemoglobin level less than 8.0 g/dL within seven days after surgical resection. Inverse probability of treatment weighting (IPTW) was used to balance covariates in the sequential cohort of patients receiving an incremental amount of blood. We applied restricted cubic spline functions to characterise dose-response effects of transfusion amount on recurrence and mortality., Results: A total of 209 (11.6%) of 1803 patients received transfusions. Over a median of 42 months after surgery (interquartile range 24.9-71.9), patients who received blood had a greater risk of early recurrence (IPTW-adjusted HR: 1.81, 95% CI: 1.59-2.06, P < 0.001) and all-cause mortality (IPTW-adjusted hazard ratio, HR: 2.38, 95% CI: 1.97-2.87, P < 0.001). A non-linear dose-response occurred between transfusion amount and recurrence or mortality., Conclusions: The greater risk of disease recurrence and early mortality after surgical resection in NSCLC patients who receive blood transfusion supports use of clinical strategies to reduce exposure. Further studies are needed to identify benchmarks to guide evidence-based practices., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Whether epidural analgesia affects cancer outcomes remains controversial. Most previous investigations ignored the confounding potential of important pathological factors on cancer outcomes. This study aimed to assess the association between epidural analgesia and cancer recurrence or death after resections for colon cancer., Design: Retrospective cohort study., Setting: A single-medical centre in Taiwan., Participants: Patients with stage I through III colon cancer undergoing bowel resection and receiving either epidural analgesia or intravenous opioid analgesia from 2005 to 2014., Primary and Secondary Outcome Measures: Primary outcome was postoperative recurrence-free survival and secondary outcome was overall survival., Results: A total of 2748 and 1218 patients were analysed before and after propensity score matching. Cox regression analyses did not demonstrate any association between epidural analgesia and recurrence or death after matching (HR 0.89, 95% CI 0.65 to 1.21 for recurrence; 0.72, 95% CI 0.48 to 1.09 for death). Independent prognostic factors for cancer recurrence and death were higher level of preoperative carcinoembryonic antigen, perioperative blood transfusion, advanced cancer stage and pathological lymphovascular invasion., Conclusions: No definite association was found between epidural analgesia and risk of recurrence or death in patients undergoing colon cancer resection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Nonintubated video-assisted thoracic surgery (VATS) is widely used due to its acceptable postoperative outcomes. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) has been successfully applied in cases of prolonged difficult intubation and intensive respiratory care in patients receiving VATS lobectomy. Thopaz Digital Chest Drainage System (THOPAZ) provides regulated negative pressure close to the patient's chest, optimizing drainage of the pleural and mediastinum. We explored the surgical outcomes of nonintubated VATS lung wedge resection and traditional wedge resection with a double-lumen endotracheal tube., Methods: Patients who received nonintubated VATS lung wedge resection (group A, n = 81) and traditional wedge resection with double-lumen endotracheal tube (group B, n = 79) during the period of November 2015 to April 2018 were enrolled in the study. Demographic data and operation outcomes were obtained and analyzed from review of patient medical charts., Results: Group B had significantly longer mean induction and operative times than group A. Similarly, group B suffered greater intraoperative blood loss, longer postoperative hospital stays, and increased chest tube retention times than group A. Group A had higher partial pressure of carbon dioxide levels in both the pre-one-lung and during one-lung ventilation periods than group B. Furthermore, group A showed lower serum pH levels during one-lung ventilation period. However; group A had significantly higher partial pressure of oxygen levels during one-lung ventilation than group B, although the differences in peripheral oxygen saturation were not statistically significant., Conclusion: Our study demonstrated that nonintubated VATS using THRIVE and THOPAZ in lung wedge resection provides measurable benefits to patients.

Background: Angiopoietin-Tie2 and nitric oxide pathway is crucial in tumor angiogenesis and closely correlates with tumor development, growth, and metastasis. This study aimed to investigate the angiopoietin-Tie2 and nitric oxide signaling of the erythrocyte membrane in response to surgical trauma in head and neck cancer., Methods: We prospectively enrolled the patients with histology-proven head and neck squamous cell carcinoma undergoing surgical resection of primary tumors at the medical center between August and November 2019. We measured the preoperative and postoperative levels of angiopoietin-1, angiopoietin-2 in plasma using enzyme-linked immunosorbent assays, nitric oxide in plasma using nitrate/nitrite colorimetric assays, and Tie2 phosphorylation in erythrocyte membrane using Western blotting., Results: The plasma angiopoietin-1 was downregulated from the median 971.3 pg/mL (interquartile range [IQR] 532.1-1569.3) to 417.9 (IQR 270.5-597.3) after tumor resection (p = 0.0020). Conversely, the plasma angiopoietin-2 was enhanced from 1173.6 pg/mL (IQR 977.7-1450.2) to 2353.7 (IQR 1352.4-2954.3) after surgery (p = 0.0021), with a concomitant increase in plasma nitric oxide level from 7.73 μM (IQR 5.39-10.06) to 10.50 (IQR 7.65-14.18) after surgical resection (p = 0.0093). Subgroup analyses further showed the angiopoietin-Tie2 and nitric oxide signaling was significant only in stage III and IV cancer., Conclusions: The dynamic change of angiopoietin-Tie2 signaling in the erythrocyte membrane along with the enhanced nitric oxide in plasma after tumor resection suggests erythrocytes play a significant role in modulating surgery-induced angiogenesis, which may provide a novel marker for cancer surveillance and control.

Objectives: Tubeless uniportal video-assisted thoracic surgery (VATS), using a uniportal approach and non-intubated anaesthesia while avoiding postoperative chest drain insertion, for patients undergoing thoracoscopic surgery has been demonstrated to be feasible in selected cases. However, to date, the safety of the procedure has not been studied., Methods: We reviewed consecutive patients undergoing non-intubated uniportal VATS for pulmonary wedge resection at 2 medical centres between August 2016 and October 2019. The decision to avoid chest drain insertion was made in selected candidates. For those candidates in whom a tubeless procedure was performed, postoperative chest X-rays (CXRs) were taken on the day of the surgery [operation (OP) day], on postoperative day 1 and 1-2 weeks later. The factors associated with abnormal CXR findings were studied., Results: Among 135 attempts to avoid chest drain insertion, 13 (9.6%) patients ultimately required a postoperative chest drain. Among 122 patients in which a tubeless procedure was performed, 26 (21.3%) and 47 (38.5%) had abnormal CXR findings on OP day and postoperative day 1, respectively. Among them, 3 (2.5%) patients developed clinically significant abnormal CXRs and required intercostal drainage. Primary spontaneous pneumothorax was independently associated with a higher risk of postoperative abnormal CXRs., Conclusions: Tubeless uniportal VATS for pulmonary wedge resection can be safely performed in selected patients. Most patients with postoperative abnormal CXRs presented subclinical symptoms that spontaneously resolved; only 2.5% of patients with postoperative abnormal CXRs required drainage., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: We aimed to determine whether high-dose nitroglycerin, a nitric oxide donor, preserves erythrocyte deformability during cardiopulmonary bypass and examines the signaling pathway of nitric oxide in erythrocytes., Methods: In a randomized and controlled fashion, forty-two patients undergoing cardiac surgery with hypothermic cardiopulmonary bypass were allocated to high-dose (N = 21) and low-dose groups (N = 21). During rewarming period, patients were given intravenous nitroglycerin with an infusion rate 5 and 1 µg·kg -1 ·min -1 in high-dose and low-dose groups, respectively. Tyrosine phosphorylation level of non-muscle myosin IIA in erythrocyte membrane was used as an index of erythrocyte deformability and analyzed using immunoblotting., Results: Tyrosine phosphorylation of non-muscle myosin IIA was significantly enhanced after bypass in high-dose group (3.729 ± 1.700 folds, P = .011) but not low-dose group (1.545 ± 0.595 folds, P = .076). Phosphorylation of aquaporin 1, vasodilator-stimulated phosphoprotein, and focal adhesion kinase in erythrocyte membrane was also upregulated in high-dose group after bypass. Besides, plasma nitric oxide level was highly correlated with fold change of non-muscle myosin IIA phosphorylation (Pearson's correlation coefficient .871)., Conclusions: High-dose nitroglycerin administered during cardiopulmonary bypass improves erythrocyte deformability through activating phosphorylation of aquaporin 1, vasodilator-stimulated phosphoprotein, and focal adhesion kinase in erythrocytes., (© 2020 John Wiley & Sons Ltd.)

Glucose ingestion attenuates the water ingestion-induced increase in the total peripheral vascular resistance and orthostatic tolerance. We investigated the gastrointestinal physiology of glucose by examining the effect of glucose ingestion on the functional expression of focal adhesion kinase (FAK) in red blood cell (RBC) membrane. This study was performed in 24 young, healthy subjects. Blood samples were collected at 5 min before and 25 min and 50 min after an ingestion of 10% glucose water 500 mL, water 500 mL, or normal saline 500 mL. We determined glucose and osmolality in plasma, and phosphorylation of aquaporin 1 (AQP1), glucose transporter 1 (Glut1), and FAK in RBC membrane. Our results showed that glucose ingestion reduced the rise of peripheral vascular resistance after water ingestion and upregulated the serine phosphorylation of Glut1. It also lowered both the serine phosphorylation of FAK and tyrosine phosphorylation of AQP1, compared with the ingestion of either water or saline. In an ex vivo experiment, glucose activated the Glut1 receptor and subsequently reduced the expression of FAK compared with 0.8% saline alone. We concluded that glucose activates Glut1 and subsequently lowers the functional expression of FAK, a cytoskeleton protein of RBCs. The functional change in the RBC membrane proteins in connection with the attenuation of osmopressor response may elucidate the pathophysiology of glucose in postprandial hypotension., Competing Interests: None

There is conflicting evidence whether allogeneic blood transfusion influences survival or cancer recurrence after resection of hepatocellular cancer. We followed up 1469 patients who had undergone hepatocellular resection for a median (IQR [range]) of 45 (21-78 [0-162]) months, of whom 626 (43%) had had blood transfusion within 7 days of surgery. Both disease-free survival and patient survival were measured using a proportional hazards regression model and inverse probability of treatment weighting. We used restricted cubic splines for the association of the number of packed red blood cell units transfused with cancer recurrence and survival. We found that peri-operative blood transfusion was independently associated with survival and cancer recurrence after resection of hepatocellular carcinoma. Adjusted hazard ratios (95%CI) for the association of blood transfusion with cancer recurrence and all-cause mortality were 1.3 (1.1-1.4) and 1.9 (1.6-2.3), p < 0.001 for both. With more units transfused cancer recurrence was more likely and survival was shorter. The association of the number of transfused units was non-linear for cancer recurrence and linear response for all-cause mortality., (© 2019 Association of Anaesthetists.)

Background: Increasing attention has been paid to the predictive power of different prognostic scoring systems for decades. In this study, we compared the abilities of three commonly used scoring systems to predict short-term and long-term mortalities, with the intention of building a better prediction model for critically ill patients. We used the data from the National Health Insurance Research Database (NHIRD) in Taiwan, which included information on patient age, comorbidities, and presence of organ failure to build a new prediction model for short-term and long-term mortalities., Methods: We retrospectively collected the medical records of patients in the intensive care unit of a regional hospital in 2012 and linked them to the claims data from the NHIRD. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Elixhauser Comorbidity Index (ECI), and Charlson Comorbidity Index (CCI) were compared for their predictive abilities. Multiple logistic regression tests were performed, and the results were presented as receiver operating characteristic curves and C-statistic., Results: The APACHE II score has the best predictive power for inhospital mortality (0.79; C - statistic = 0.77 - 0.83) and 1-year mortality (0.77; C - statistic = 0.74 - 0.79). The ECI and CCI alone have poorer predictive power and need to be combined with other variables to be comparable to the APACHE II score, as predictive tools. Using CCI together with age, sex, and whether or not the patient required mechanical ventilation is estimated to have a C-statistic of 0.773 (95% CI 0.744-0.803) for inhospital mortality, 0.782 (95% CI 0.76-0.81) for 30-day mortality, and 0.78 (95% CI 0.75-0.80) for 1-year mortality., Conclusions: We present a new prognostic model that combines CCI with age, sex, and mechanical ventilation status and can predict mortality, comparable to the APACHE II score., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Yu-Ting Hsu et al.)

Background: Microelectrode recording (MER) for target refinement is widely used in deep brain stimulator insertion for Parkinson disease. Signals may be influenced by anesthetics when patients receive general anesthesia (GA). This study determined the inhibitory concentration (IC) of propofol on MER signals when it was coadministered with dexmedetomidine., Methods: Patients were anesthetized with dexmedetomidine (0.5 μg·kg loading, followed by infusion at 0.4 μg·kgh) and propofol through target-controlled infusion for GA with tracheal intubation. The surgeon conducted the online scoring of the background signals, spiking frequency, amplitude, and pattern of single-unit activities by using a 0-10 verbal numerical rating scale (NRS; 0, maximal suppression; 10, minimal suppression), and responses were grouped into suppression (NRS ≤ 6) and nonsuppression (NRS > 6). The median inhibitory concentration (IC50) of propofol (as target effect-site concentrations: Ceprop) was determined using modified Dixon's up-and-down method. Probit regression analysis was further used to obtain the dose-response relationship, and IC05 and IC95 were calculated., Results: Twenty-three adult patients participated in this study. Under the concomitant infusion of dexmedetomidine, the predicted IC50 value (95% CI) of Ceprop for neuronal suppression during MER was 1.29 (1.24-1.34) μg·mL as calculated using modified Dixon's up-and-down method. Using probit analysis, the estimated IC05, IC50, and IC95 values (95% CIs) were 1.17 (0.87-1.23), 1.28 (1.21-1.34), and 1.40 (1.33-1.85) μg·mL, respectively., Conclusion: Our data provided reference values of propofol for dosage adjustment to avoid interference on MER under GA when anesthetics have to be continuously infused during recording.

Background: Chronic pain is a common postoperative complication in patients undergoing major surgery and may significantly affect their quality of life (QOL). Whether patient-controlled analgesia (PCA) can reduce the risk of chronic postsurgical pain and promote long-term QOL is still unclear., Methods: In this prospective cohort study, we followed up patients undergoing major surgery, recorded changes in their postoperative QOL over time using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire and chronic pain events, evaluated the long-term effects of distinct PCA techniques (intravenous, epidural, or none) on their QOL and risk of chronic pain, and explored relevant predictors. The patients' QOL and chronic pain events were collected preoperatively, 3, 6, and 12 months after surgery. Generalized linear mixed models were used to control for individual heterogeneity and adjust for potential confounding factors., Results: We included 328 patients undergoing major surgery from September 22, 2015, to December 31, 2016, in this study. Multivariate regression models showed that patients using intravenous PCA had a better QOL in physical health (adjusted coefficient 3.7, 95% CI, 0.5-8.0) compared with those receiving non-PCA treatments. Distinct PCA techniques did not significantly affect QOL in psychological, social relationship, or environmental domains of the WHOQOL-BREF scale or the risk of chronic postsurgical pain., Conclusion: Patients using intravenous PCA had a better QOL in physical health over time after major surgery, which may have been due to factors other than pain-relieving effects.

Background: Although epidural analgesia (EA) provides reliable pain relief after major operations, few studies have explored how postoperative pain trajectories change over time in patients receiving EA and the associated factors. This study aimed to model the dynamic features of pain trajectories after surgery and investigate factors associated with their variations using latent curve analysis., Methods: This retrospective study was conducted at a single medical center in Taiwan, and data were obtained from patients receiving perioperative EA by electronic chart review. Mean numeric rating pain scores were recorded daily in the first five postoperative days. Patient demographics, surgical sites, and infusion pump settings were also collected. Latent curve models using two latent variables, intercept and slope, were developed to explain the variations in postoperative pain scores over time. The influences of potential predictors of postoperative pain trajectories were further evaluated for the final model determination., Results: Of the 1294 collected patients, the daily pain scores averaged 2.0 to 2.9 for different surgical sites. Among the nine significant factors influencing pain trajectories, chest and lower extremity surgery tended to induce less and more baseline pain, respectively, than those with abdomen surgery (both p < 0.001). In addition, male patients and those with a shorter anesthesia time had less baseline pain (p < 0.001 and p = 0.016, respectively). The older and lighter patients and those with chest surgery or American Society of Anesthesiologists class ≥ 3 tended to have milder decreasing trends in pain trajectories. A higher infusion rate was associated with an elevated baseline level and smoother decreasing trend in pain trajectory. The final model fit our data acceptably (root mean square error of approximation = 0.05, comparative fit index = 0.97)., Conclusion: Latent curve analysis provided insights into the dynamic nature of variations in postoperative pain trajectories. Further studies investigating more factors associated with pain trajectories are warranted to elucidate the mechanisms behind the transitions of pain scores over time after surgery.

The original version of this article unfortunately contained a mistake. The authors observed inadvertent error in Fig. 7d, in which the image of the GFAP/DAPI in the WT saline treated mice was rotated left 90-degree by mistake. The corrected representative image is given below.

Astrocytes play pivotal roles in regulating glutamate homeostasis at tripartite synapses. Inhibition of soluble epoxide hydrolase (sEHi) provides neuroprotection by blocking the degradation of 14,15-epoxyeicosatrienoic acid (14,15-EET), a lipid mediator whose synthesis can be activated downstream from group 1 metabotropic glutamate receptor (mGluR) signaling in astrocytes. However, it is unclear how sEHi regulates glutamate excitotoxicity. Here, we used three primary rat cortical culture systems, neuron-enriched (NE), astrocyte-enriched glia-neuron mix (GN), and purified astrocytes, to delineate the underlying mechanism by which sEHi and 14,15-EET attenuate excitotoxicity. We found that sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) and 14,15-EET both attenuated N-methyl-D-aspartate (NMDA)-induced neurite damage and cell death in GN, not NE, cortical cultures. The anti-excitotoxic effects of 14,15-EET and AUDA were both blocked by the group 1 mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), as were their protective effects against NMDA-disrupted perineuronal astrocyte processes expressing glutamate transporter-1 (GLT-1) and subsequent glutamate uptake. Knockdown of sEH expression also attenuated NMDA neurotoxicity in mGluR5- and GLT-1-dependent manners. The 14,15-EET/AUDA-preserved astroglial integrity was confirmed in glutamate-stimulated primary astrocytes along with the reduction of the c-Jun N-terminal kinase 1 phosphorylation, in which the 14,15-EET effect is mGluR5-dependent. In vivo studies validated that sEHi and genetic deletion of sEH (Ephx2-KO) ameliorated excitotoxic kainic acid-induced seizure, memory impairment, and neuronal loss while preserving GLT-1-expressing perineuronal astrocytes in hippocampal CA3 subregions. These results suggest that 14,15-EET mediates mGluR5-dependent anti-excitotoxicity by protecting astrocytes to maintain glutamate homeostasis, which may account for the beneficial effect of sEH inhibition in excitotoxic brain injury and diseases.

Objectives: We aimed to investigate the factors associated with variations in postoperative pain trajectories over time in patients using intravenous patient-controlled analgesia (IV-PCA) for postoperative pain., Design: Retrospective cohort study., Setting: A single medical centre in Taiwan., Participants: Patients receiving IV-PCA after surgery., Primary and Secondary Outcome Measures: Primary outcome was the postoperative pain scores., Results: A total of 3376 patients and 20 838 pain score observations were analysed using latent curve models. Female and longer anaesthesia time increased the baseline level of pain (p=0.004 and 0.003, respectively), but abdominal surgery and body weight decreased it (both p<0.001). Regarding the trend of pain resolution, lower abdominal surgery steepened the slope (p<0.001); older age, American Society of Anesthesiologists (ASA) class ≥3 and longer anaesthesia time tended to flatten the slope (p<0.001, =0.019 and <0.001, respectively). PCA settings did not affect the variations in postoperative pain trajectories., Conclusions: Patient demographics, ASA class, anaesthesia time and surgical sites worked together to affect postoperative pain trajectories in patients receiving IV-PCA. Latent curve models provided valuable information about the dynamic and complex relationships between the pain trajectories and their influential factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although animal studies have shown that pain can suppress host immunity and promote tumor metastasis, few clinical studies have evaluated the association between acute pain and long-term outcomes after cancer surgery., Methods: Patients undergoing colorectal cancer resection at a medical center between November 2010 and December 2014 were collected. Pain intensity was recorded using a numeric rating scale at 12, 24, 36, 48, 72, 96, and 120 hours postoperatively. Group-based modeling of longitudinal pain scores was used to categorize pain trajectories. Recurrence-free survival and overall survival were analyzed using Cox proportional hazards models., Results: A total of 2401 patients with 13 931 pain score observations were analyzed. The trajectory model identified three groupings of inpatient postsurgical pain, including 70.3% with mild pain dropping to low (group 1), 20.0% with moderate/severe pain dropping to mild (group 2), and 9.7% with moderate pain rebounding to severe (group 3). Univariate models showed that pain trajectories were significantly associated with recurrence-free survival (group 2 vs 1: hazard ratio [HR], 1.23; 95% CI, 1.02-1.47 and group 3 vs 1: HR, 1.63; 95% CI, 1.30-2.04) and overall survival (group 2 vs 1: HR, 1.36; 95% CI, 1.05-1.77 and group 3 vs 1: HR, 1.81; 95% CI, 1.31-2.51). However, the associations disappeared after adjusting for other significant risk factors., Conclusion: Abnormal pain resolution identified by pain trajectory analysis and resulting from complex interactions among disease progression, surgery, and analgesia may be considered as an indicator of an inferior prognosis following colorectal cancer resection.

Background/purpose: Enhanced recovery after surgery (ERAS) is a growing tendency in modern perioperative period management, but no protocol has been established for a strategy that optimally facilitates rapid recovery from anesthesia. We hypothesized that applying a total intravenous anesthesia (TIVA) method to the response surface model (RSM) would allow prediction of the emergence and endotracheal tube extubation in cases undergoing video-assisted thoracotomy surgery (VATS)., Methods: Thirty patients who were scheduled to undergo VATs under TIVA were enrolled. Pharmacokinetic profiles were calculated using a Tivatrainer. Emergence from anesthesia was observed and the exact time point of the regained response (RR) was recorded. The effect of concentration was analyzed and applied to a response surface model., Results: The cumulative prediction curve of the RR was closer to the 50% probability as set by the OAA/S ≥ 4 than by the OAA/S ≥ 2 model. The median, averages, and standard deviations of the time differences were 14.5, 22.05 ± 19.23 min for the OAA/S ≥2 model and 10.4, 14.26 ± 10.40 min for the OAA/S ≥ 4 model., Conclusion: The OAA/S ≥ 4 model could identify the target concentration in propofol-remifentanil pairs that predicted the time of emergence from VATS in 10 min. Our results indicate that RSM can be used to derive an ERAS protocol for VATS under TIVA. Further studies should investigate application of RSM to predict ERAS for various types of procedures., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

During sedated endoscopic examinations, upper airway obstruction occurs. Nasal breathing often shifts to oral breathing during open mouth esophagogastroduodenoscopy (EGD). High-flow nasal cannula (HFNC) which delivers humidified 100% oxygen at 30 L min -1 may prevent hypoxemia. A mandibular advancement (MA) bite block with oxygen inlet directed to both mouth and nose may prevent airway obstruction during sedated EGD. The purpose of this study was to evaluate the efficacy of these airway devices versus standard management. One hundred and eighty-nine patients were assessed for eligibility. One hundred and fifty-three were enrolled. This study randomly assigned eligible patients to three arms: the standard bite block and standard nasal cannula, HFNC, and MA bite block groups. EGD was performed after anaesthetic induction. The primary endpoint was the oxygen desaturation area under curve at 90% (AUC Desat ). The secondary endpoints were percentage of patients with hypoxic, upper airway obstruction, and apnoeic and rescue events. One hundred and fifty-three patients were enrolled. AUCdesat was significantly lower for HFNC and MA bite blocks versus the standard management (p= 0.019). The HFNC reduced hypoxic events by 18% despite similar airway obstruction and apnoeic events as standard group. The MA bite block reduced hypoxic events by 12% and airway obstructions by 32%. The HFNC and MA groups both showed a 16% and 14% reduction in the number of patients who received rescue intervention, respectively, compared to the standard group. The HFNC and MA bite block may both reduce degree and duration of hypoxemia. HFNC may decrease hypoxemic events while maintaining nasal patency is crucial during sedative EGD. The MA bite block may prevent airway obstruction and decrease the need for rescue intervention., Competing Interests: The authors declare no conflicts of interest.

Drug-induced respiratory depression is a major cause of serious adverse events. Adequate oxygenation is very important during sedated esophagogastroduodenoscopy (EGD). Nasal breathing often shifts to oral breathing during open mouth EGD. A mandibular advancement bite block was developed for EGD using computer-assisted design and three-dimensional printing techniques. The mandible is advanced when using this bite block to facilitate airway opening. The device is composed of an oxygen inlet with one opening directed towards the nostril and another opening directed towards the oral cavity. The aim of this bench study was to compare the inspired oxygen concentration (FiO 2 ) provided by the different nasal cannulas, masks, and bite blocks commonly used in sedated EGD. A manikin head was connected to one side of a two-compartment lung model by a 7.0 mm endotracheal tube with its opening in the nasopharyngeal position. The other compartment was driven by a ventilator to mimic "patient" inspiratory effort. Using this spontaneously breathing lung model, we evaluated five nasal cannulas, two face masks, and four new oral bite blocks at different oxygen flow rates and different mouth opening sizes. The respiratory rate was set at 12/min with a tidal volume of 500 mL and 8/min with a tidal volume of 300 mL. Several Pneuflo resistors of different sizes were used in the mouth of the manikin head to generate different degrees of mouth opening. FiO 2 was evaluated continuously via the endotracheal tube. All parameters were evaluated using a Datex anesthesia monitoring system. The mandibular advancement bite block provided the highest FiO 2 under the same supplemental oxygen flow. The FiO 2 was higher for devices with oxygen flow provided via an oral bite block than that provided via the nasal route. Under the same supplemental oxygen flow, the tidal volume and respiratory rate also played an important role in the FiO 2 . A low respiratory rate with a smaller tidal volume has a relative high FiO 2 . The ratio of nasal to oral breathing played an important role in the FiO 2 under hypoventilation but less role under normal ventilation. Bite blocks deliver a higher FiO 2 during EGD. The ratio of nasal to oral breathing, supplemental oxygen flow, tidal volume, and respiratory rate influenced the FiO 2 in most of the supplemental oxygen devices tested, which are often used for conscious sedation in patients undergoing EGD and colonoscopy.

Objectives: Previous studies showed reductions in recurrence and mortality rate of several cancer types in patients receiving perioperative epidural analgesia. This study aimed to investigate the effects of thoracic epidural analgesia on oncological outcomes after resection for lung cancer., Design: Retrospective study using propensity score matching methodology., Setting: Single medical centre in Taiwan., Participants: Patients with stages I-III non-small-cell lung cancer undergoing primary tumour resection between January 2005 and December 2015 and had either epidural analgesia, placed preoperatively and used intra- and postoperatively, or intravenous analgesia were evaluated through May 2017., Primary and Secondary Outcome Measures: Primary endpoint was postoperative recurrence-free survival and secondary endpoint was overall survival., Results: The 3-year recurrence-free and overall survival rates were 69.8% (95% CI 67.4% to 72.2%) and 92.4% (95% CI 91% to 93.8%) in the epidural group and 67.4% (95% CI 62.3% to 72.5%) and 89.6% (95% CI 86.3% to 92.9%) in the non-epidural group, respectively. Multivariable Cox regression analysis before matching demonstrated no significant difference in recurrence or mortality between groups (adjusted HR: 0.93, 95% CI 0.76 to 1.14 for recurrence; 0.81, 95% CI 0.58 to 1.13 for mortality), similar to the results after matching (HR: 0.97, 95% CI 0.71 to 1.31; 0.94, 95% CI 0.57 to 1.54). Independent risk factors for both recurrence and mortality were male, higher pretreatment carcinoembryonic antigen level, advanced cancer stage, poor differentiation, lymphovascular invasion, microscopic necrosis and postoperative radiotherapy., Conclusions: Thoracic epidural analgesia was not associated with better recurrence-free or overall survival in patients receiving surgical resection for stages I-III non-small-cell lung cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Awake craniotomy (AC) is performed to identify cerebral language center. The challenge of anesthesia is to maintain a calm, comfortable, and cooperative patient during the mapping phase. Response surface models (RSMs) are multidrug modeling algorithms. In this pharmacodynamic study, we investigate the first use of RSM with bispectral index (BIS) to predict patient's response to name calling (RNC) and wakefulness (complete neurological tests) during AC., Methods: The study is performed in two phases. We prospectively enrolled 40 patients who received video-assisted thoracoscopic surgery (VATS) using propofol and fentanyl as the modeling group. Effect-site concentrations (Ce) and BIS values were recorded and a RSM is built from the data set. We verified the RSM retrospectively in AC patients, designated as the validation group. Corresponding BIS values were analyzed for RNC and wakefulness., Results: A total of 155 data sets of propofol Ce, fentanyl Ce, and BIS pairs were available for modeling. The range of propofol and fentanyl Ce were 0 to 9.95 μg/mL and 0 to 3.69 ng/mL, respectively. Observed BIS ranged from 21 to 98. The model identified an additive interaction between propofol and an opioid. RNC at BIS 64 is predicted by the model and 70 is required for wakefulness., Conclusion: RSM built from VATS patients is verified with a separate group of AC patient. The BIS target advised for RSM-predicted wakefulness is 70. The model illustrates the timeline to wakefulness during AC under propofol and an opioid. It has implications in guiding, dosing, and estimation of time to wakefulness with propofol and an opioid.

Whether morphine used in human cancer surgery would exert tumor-promoting effects is unclear. This study aimed to investigate the effects of morphine dose on cancer prognosis after colorectal cancer (CRC) resection.In a retrospective study, 1248 patients with stage I through IV CRC undergoing primary tumor resections and using intravenous patient-controlled analgesia for acute surgical pain at a tertiary center between October 2005 and December 2014 were evaluated through August 2016. Progression-free survival (PFS) and overall survival (OS) were analyzed using proportional hazards regression models.Multivariable analysis demonstrated no dose-dependent association between the amount of morphine dose and PFS (adjusted hazard ratio, HR = 1.31, 95% confidence interval, CI = 0.85-2.03) or OS (adjusted HR = 0.86, 95% CI = 0.47-1.55). Patients were further classified into the high-dose and low-dose groups by the median of morphine consumption (49.7 mg), and the morphine doses were mean 75.5 ± standard deviation 28.8 mg and 30.1 ± 12.4 mg in high-dose and low-dose groups, respectively. Multivariable models showed no significant difference in PFS or OS between groups, either (adjusted HR = 1.24, 95% CI = 0.97-1.58 for PFS; adjusted HR = 1.01, 95% CI = 0.71-1.43 for OS).Our results did not support a definite association between postoperative morphine consumption and cancer progression or all-cause mortality in patients following CRC resection.

Background: Few studies have investigated the association between epidural analgesia (EA) and oncologic outcomes in patients following hepatocellular carcinoma (HCC) resection., Methods: This retrospective study was conducted at a single medical center using electronic medical records. Patients with nonmetastatic primary HCC undergoing tumor resection between January 2005 and December 2011 were classified into two groups based on their use of EA or intravenous analgesia. Multivariate Cox regression analyses were used to evaluate the associations between EA and recurrence-free (RFS) and overall (OS) survival. The patients were also propensity score-matched by demographic and important clinicopathologic variables., Results: A total of 744 patients (58.5% receiving EA) with a median follow-up time of 64.5 months and 277 matched pairs were included in the analyses before and after matching. No significant association between EA and cancer recurrence or overall mortality was found before matching (RFS: adjusted hazard ratio [HR] = 0.97, 95% CI: 0.80-1.17; OS: adjusted HR = 0.95, 95% CI: 0.71-1.26). After matching, the association between EA and cancer recurrence or overall mortality remained nonsignificant (RFS: HR = 0.89, 95% CI: 0.68-1.17; OS: HR = 1.20, 95% CI: 0.81-1.78)., Conclusion: This study did not support a definite association between EA and cancer recurrence or OS in patients with primary HCC after surgical resection.

Response surface models (RSMs) were used to predict effects of multiple drugs interactions. Our study was aimed to validate accuracy of the previous published volunteer models during transoesophageal echocardiography (TEE). This is a cross-sectional study with 20 patients scheduled for transesophageal echocardiography in Taipei Veterans General Hospital, Taiwan. Effect-site concentration pairs of alfentanil and propofol were recorded and converted to equivalent remifentanil and propofol effect-site concentrations. Observer's Assessment of Alertness/Sedation (OAA/S) scores were assessed every 2 minutes. Using these data, previous published models of loss of response (LOR), intolerable ventilatory depression (IVD), and loss of response to esophageal instrumentation (LREI) were then estimated. Accuracy of prediction is assessed by calculating the difference between the true response and the model-predicted probability. Clinical events such as interruption of TEE were recorded. The average procedure time was 11 minutes. Accuracy for prediction of LOR and LREI is 63.6% and 38.5%, respectively. There were four patients experienced desaturation for less than 1 minute, which were not predicted by IVD model, and one interruption of TEE due to involuntary movement. The previous published drug-interaction RSMs predict LOR well but not LREI for TEE sedation. Further studies using response surface methodology are needed to improve quality for TEE sedation and clinical implementation.

Several approaches of locating the epidural space have been proposed. However, loss of Resistance method (LOR) remains the most common method for epidural anesthesia. Different optical signals were received from the ligamentum flavum and the epidural space allows operator to pinpoint position of the needle and determine whether the needle tip has entered the epidural space. Optical signals throughout the penetration process was recorded and position of needle tip was confirmed with a C-arm fluoroscopy. 60 lumbar punctures were performed in 20 vivo porcine models, and success rate of locating the epidural space with the optical auxiliary is calculated statistically. The data are expressed in mean ± SD. During all the lumber puncture processes, the strength of optical signals received decreased significantly while the needle tip penetrates the ligamentum flavum and entered the epidural space. The strength of optical signal received when needle tip was in the ligamentum flavum was 1.38 ± 0.57. The signal strength at epidural space was 0.46 ± 0.35. Strength of signal decreased by 67% when entered epidural space, and there is no significant differences in decrease of strength from data obtained from thevertebrae (lumbar segments)L2-L3, L3-L4, and L4-L5. Finally, we calculated with assistance of the proposed optical auxiliary, the success rate for guiding the needle tip to the epidural space using was as high as 87%. It is evidently believed that the optical auxiliary equipped is visualized to assist operators inserting needle accurately and efficiently into epidural space during epidural anesthesia operation.

Background: The aim of the study was to evaluate the effects of high-dose nitroglycerine administered during cardiopulmonary bypass on the intraoperative cerebral saturation and postoperative serum creatinine concentration in cardiac surgery., Methods: In a retrospective cohort study, a total of 239 patients undergoing cardiac surgery with cardiopulmonary bypass at a tertiary medical center were included. General anesthesia consisted of volatile anesthetic and either intravenous loading of high-dose nitroglycerin (infusion rate 10 to 20 mg·h with a total dose of ≥0.5 mg·kg) starting from rewarming of cardiopulmonary bypass throughout the end of the surgery (NTG group; N = 96) or without high-dose nitroglycerin (control group; N = 143). Data for intraoperative cerebral saturation and serum creatinine concentrations before and after cardiac surgery were collected. Propensity score method was used to adjust for potential confounders., Results: Patients receiving high-dose nitroglycerin had significantly lower mean arterial pressure and hematocrit levels during and after cardiopulmonary bypass. The risk of intraoperative cerebral desaturation was left-sided 23.9% versus 38.5% (p = 0.023), right-sided 28.1% versus 35.7% in the NTG and control groups, respectively. The risk of new-onset stroke and postoperative dialysis was 2.1% versus 6.3% and 1.0% versus 3.5% in the NTG and control groups, respectively., Conclusion: An infusion of high-dose nitroglycerin initiating at rewarming of cardiopulmonary bypass and throughout the postbypass interval may induce hypotension and hemodilution in cardiac surgical patients. Cerebral saturation and renal function were well maintained without increasing the risk of stroke and renal replacement therapy after cardiac surgery with cardiopulmonary bypass.