Spatial mode cleaning and efficient nonlinear pulse compression to sub-50†fs in a gas-filled multipass cell.

We demonstrate a gas-filled multipass cell (MPC) that cleaned the spatial mode of a spatial-filter-free 250 W, 100 kHz, 445 fs driven source based on an Innoslab amplifier and compressed the pulse duration to 41 fs simultaneously. The multipass cell acted as a spatial filter and benefited from its discrete waveguide nature, in which the input beam quality factor M2 was improved from 1.53 to a near-diffraction-limited value of 1.21 at 96% transmission.

Transverse interlaminar ultrasound-guided C1-C2 puncture for the intrathecal administration of nusinersen in patients with spinal muscular atrophy.

INTRODUCTION/AIMS: Severe spinal deformities and previous spinal orthopedic instrumentation may result in substantial technical challenges for nusinersen delivery through lumbar puncture in patients with spinal muscular atrophy (SMA). The aim of this paper was to review our experience with ultrasound-guided cervical puncture as an alternative approach for the intrathecal administration of nusinersen. METHODS: This was a retrospective medical record review of transverse interlaminar ultrasound-guided C1-C2 puncture for nusinersen delivery in SMA patients. The details of puncture, complications, and success rate of the procedure were summarized. RESULTS: There were four patients who received a total of 13 cervical punctures for nusinersen delivery. All procedures were technically successful with no major complications. Full doses of nusinersen were delivered intrathecally. DISCUSSION: Transverse interlaminar ultrasound-guided C1-C2 puncture is an alternative approach for administering nusinersen if lumbar puncture fails. The success of the technique requires a thorough preprocedural evaluation of cervical spine imaging, sound knowledge of the cervical sonoanatomy and careful manipulation of the needle.

An ambulatory dental treatment of a child with Rett syndrome and limited mouth opening under muscle relaxant-free general anesthesia: a case report.

BACKGROUND: Rett Syndrome (RTT) is a rare, severe, and progressive developmental disorder with intellectual disability. Anesthesia in RTT patients presents a range of challenges. We report a child with RTT who received dental treatment under muscle relaxant-free general anesthesia in our ambulatory center. CASE PRESENTATION: A 15-year-old girl with RTT was admitted to our dental clinic with multiple dental caries and residual roots. Dental treatment was scheduled under ambulatory general anesthesia. After anesthesia induction, a nasal tube was initiated under the guidance of a fiberoptic bronchoscope. Multimodal analgesia, body temperature monitoring, and postoperative nausea and vomiting prevention were applied. No muscle relaxants were used throughout the process. The endotracheal tube was successfully removed after the operation and the patient was discharged home the same day. CONCLUSION: An individualized anesthesia strategy enabled a quick and safe recovery for this RTT patient after dental treatment under muscle relaxant-free general anesthesia.

Machine learning approach for predicting post-intubation hemodynamic instability (PIHI) index values: towards enhanced perioperative anesthesia quality and safety.

BACKGROUND: Adequate preoperative evaluation of the post-intubation hemodynamic instability (PIHI) is crucial for accurate risk assessment and efficient anesthesia management. However, the incorporation of this evaluation within a predictive framework have been insufficiently addressed and executed. This study aims to developed a machine learning approach for preoperatively and precisely predicting the PIHI index values. METHODS: In this retrospective study, the valid features were collected from 23,305 adult surgical patients at Peking Union Medical College Hospital between 2012 and 2020. Three hemodynamic response sequences including systolic pressure, diastolic pressure and heart rate, were utilized to design the post-intubation hemodynamic instability (PIHI) index by computing the integrated coefficient of variation (ICV) values. Different types of machine learning models were constructed to predict the ICV values, leveraging preoperative patient information and initiatory drug infusion. The models were trained and cross-validated based on balanced data using the SMOTETomek technique, and their performance was evaluated according to the mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE) and R-squared index (R2). RESULTS: The ICV values were proved to be consistent with the anesthetists' ratings with Spearman correlation coefficient of 0.877 (P < 0.001), affirming its capability to effectively capture the PIHI variations. The extra tree regression model outperformed the other models in predicting the ICV values with the smallest MAE (0.0512, 95% CI: 0.0511-0.0513), RMSE (0.0792, 95% CI: 0.0790-0.0794), and MAPE (0.2086, 95% CI: 0.2077-0.2095) and the largest R2 (0.9047, 95% CI: 0.9043-0.9052). It was found that the features of age and preoperative hemodynamic status were the most important features for accurately predicting the ICV values. CONCLUSIONS: Our results demonstrate the potential of the machine learning approach in predicting PIHI index values, thereby preoperatively informing anesthetists the possible anesthetic risk and enabling the implementation of individualized and precise anesthesia interventions.

[Clinicians' Practice and Opinions on Sedation Therapy in End-Stage Patients].

Objective To investigate clinicians' practice and opinions on sedation therapy in end-stage patients at Peking Union Medical College Hospital. Methods From August,2022 to April,2023,an online questionnaire survey was conducted among clinicians involved in end-stage patient management. Results A total of 205 questionnaires were distributed,with an effective response rate of 56.1%.Among the clinicians,55.7% of them had experience of applying sedation therapy in end-stage patients;85.2% of clinicians believed that sedation could relieve the suffering of terminal patients from physical refractory symptoms;75.7% of clinicians considered that sedation therapy could be used to relieve agony from psycho-existential distress.Most clinicians had concerns about sedation therapy due to the lack of legal support(86.1%)and the lack of understanding of patients or families(59.1%).The majority (90.4%) of clinicians were willing to receive training on palliative sedation. Conclusions A majority of clinicians agree that sedation therapy could relieve the physical distress and psycho-existential distress in end-stage patients.However,most clinicians have concerns about the application of sedation therapy due to the lack of legal support.It is necessary to enhance the training on palliative sedation.

Association between Storage Time of Transfused Red Blood Cells and Infection after Clean-contaminated Surgery: A Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to investigate the association between storage time of transfused red blood cells and risks of infections after clean-contaminated surgery. SUMMARY BACKGROUND DATA: Storage lesions of red blood cells can aggravate transfusion-related immunomodulation. Very few randomized controlled trials have investigated the impacts of storage time on postoperative outcomes in non-cardiac patients. METHODS: We included adult patients who had undergone clean-contaminated surgery from 2014 to 2018 and received allogeneic red blood cell transfusion. In transfusion episode-level analysis, the exposure was the storage time of each transfusion episode. In patient-level analysis, the exposures were the mean, weighted mean, maximum storage time, and Scalar Age of Blood Index of red blood cells transfused into each patient. The primary outcome was infections that developed after transfusions within postoperative Day 30. RESULTS: The 4046 included patients received 11604 transfusion episodes. Of these, 1025 (25.3%) patients developed postoperative infections. An increased storage time of transfused red blood cells was not associated with increased odds of postoperative infections in either transfusion episode-level analysis [odds ratio (OR) 1.03 per five days, 95% confidence interval (CI) 0.95 to 1.11] or patient-level analysis (mean: OR 1.02, 95% CI 0.95 to 1.10; weighted mean: OR 1.02, 95% CI 0.95 to 1.10; maximum: OR 1.06, 95% CI 0.98 to 1.14; Scalar Age of Blood Index: OR 0.99, 95% CI 0.96 to 1.03), after adjusting 17 confounders. CONCLUSIONS: Prolonged storage time of transfused red blood cells was not associated with increased risks of infections after clean-contaminated surgery.

Aggressive intraoperative warming versus routine thermal management during non-cardiac surgery (PROTECT): a multicentre, parallel group, superiority trial.

BACKGROUND: Moderate intraoperative hypothermia promotes myocardial injury, surgical site infections, and blood loss. Whether aggressive warming to a truly normothermic temperature near 37°C improves outcomes remains unknown. We aimed to test the hypothesis that aggressive intraoperative warming reduces major perioperative complications. METHODS: In this multicentre, parallel group, superiority trial, patients at 12 sites in China and at the Cleveland Clinic in the USA were randomly assigned (1:1) to receive either aggressive warming to a target core temperature of 37°C (aggressively warmed group) or routine thermal management to a target of 35·5°C (routine thermal management group) during non-cardiac surgery. Randomisation was stratified by site, with computer-generated, randomly sized blocks. Eligible patients (aged ≥45 years) had at least one cardiovascular risk factor, were scheduled for inpatient non-cardiac surgery expected to last 2-6 h with general anaesthesia, and were expected to have at least half of the anterior skin surface available for warming. Patients requiring dialysis and those with a body-mass index exceeding 30 kg/m2 were excluded. The primary outcome was a composite of myocardial injury (troponin elevation, apparently of ischaemic origin), non-fatal cardiac arrest, and all-cause mortality within 30 days of surgery, as assessed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03111875. FINDINGS: Between March 27, 2017, and March 16, 2021, 5056 participants were enrolled, of whom 5013 were included in the intention-to-treat population (2507 in the aggressively warmed group and 2506 in the routine thermal management group). Patients assigned to aggressive warming had a mean final intraoperative core temperature of 37·1°C (SD 0·3) whereas the routine thermal management group averaged 35·6°C (SD 0·3). At least one of the primary outcome components (myocardial injury after non-cardiac surgery, cardiac arrest, or mortality) occurred in 246 (9·9%) of 2497 patients in the aggressively warmed group and in 239 (9·6%) of 2490 patients in the routine thermal management group. The common effect relative risk of aggressive versus routine thermal management was an estimated 1·04 (95% CI 0·87-1·24, p=0·69). There were 39 adverse events in patients assigned to aggressive warming (17 of which were serious) and 54 in those assigned to routine thermal management (30 of which were serious). One serious adverse event, in an aggressively warmed patient, was deemed to be possibly related to thermal management. INTERPRETATION: The incidence of a 30-day composite of major cardiovascular outcomes did not differ significantly in patients randomised to 35·5°C and to 37°C. At least over a 1·5°C range from very mild hypothermia to full normothermia, there was no evidence that any substantive outcome varied. Keeping core temperature at least 35·5°C in surgical patients appears sufficient. FUNDING: 3M and the Health and Medical Research Fund, Food and Health Bureau, Hong Kong. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

417†W, 2.38†mJ Innoslab amplifier compressible to a high pulse quality of 406†fs.

We demonstrate a 417 W, 175 kHz Innoslab chirped pulse amplification laser compressible to short and clean 406 fs pulse duration. A spectral bandwidth (full width at half maximum, FWHM) of ∼3 nm was maintained at full pump power, and the pulses exhibited good pulse quality in a wide tunable pulse energy range from 1.7 mJ to a maximum of 2.38 mJ. At the maximum output power, the compressed pulses were nearly pedestal free. The comprehensive effects of residual high-order dispersion from the front end, the gain shaping effects of the amplifier, and the slight mismatch of third-order dispersion (TOD) between the stretcher (CFBG) and the gating compressor, along with the small nonlinear phase shift accumulated in the amplifier, could have facilitated the high pulse quality. To the best of our knowledge, this is the shortest pulse duration from the Innoslab amplifiers at hundreds of watts average power in the millijoule energy regime.

Dual-slab Yb:KGd(WO4)2 regenerative amplifier for spectral shaping and high-power output.

A high-power regenerative amplifier (RA) based on dual-slab Yb:KGd(WO4)2 (Yb:KGW) was demonstrated, which provided a maximum average power of 33.7 W at a repetition rate of 75-200 kHz before compression with a central wavelength of 1039 nm, corresponding to an optical-to-optical conversion efficiency of 51.4%. To the best of our knowledge, this is the highest average power from the Yb:KGW solid-state RA. The compressed pulse duration of 205 fs was realized under the maximum output power. By adjusting the gain of the crystals, respectively, the spectral shaping can be achieved. A combination spectrum with root-mean-square (RMS) bandwidth of 4.5 nm was generated with a central wavelength of 1035 nm at an output power of 20 W, the compressed pulse duration was 159 fs. Meanwhile, effective mitigation of thermal effects by dual-slab configuration guaranteed the nearly diffraction-limited beam quality: M x2 = 1.17 and M y2 = 1.20.

Temporal trends and geographic variations in perioperative red blood cell transfusion in major surgical procedures from 2013 to 2018 in China.

BACKGROUND AND OBJECTIVES: Transfusion-related guidelines promote restrictive blood transfusion. However, whether these guidelines have been successfully translated into clinical practice in China is unknown. This study aimed to provide updated information about the temporal trends in the prevalence of perioperative red blood cell (RBC) transfusion in China. MATERIALS AND METHODS: We analysed data from the Hospital Quality Monitoring System database (2013-2018) to investigate the prevalence of perioperative RBC transfusion in patients undergoing craniotomy for cerebral aneurysms or arteriovenous malformations, sternotomy for mitral valve replacement, open thoracotomy lobectomy, open gastrectomy and hip arthroplasty. Mixed-effects logistic regression models quantified the likelihood of RBC transfusions. RESULTS: The study included 438,183 patients, with 44,697 (10.20%) receiving perioperative RBC transfusions. Introducing transfusion-related guidelines in China markedly decreased the prevalence of RBC transfusion among patients who underwent major surgical procedures in the following years. The prevalence of RBC transfusion for hip arthroplasty was 17.34% in 2013 and 7.03% in 2018. After adjusting for patient risk factors, the odds ratio of RBC transfusion for hip arthroplasty was significantly lower in 2018 (0.74, 95% confidence intervals [CI] 0.53-1.02) than in 2013 (1.84, 95% CI 1.37-2.48). CONCLUSION: The prevalence of perioperative RBC transfusion decreased from 2013 to 2018 in China, supporting the potential beneficial effects of transfusion-related guidelines. Considering the geographic variations in RBC transfusion, reducing heterogeneity may impact public health by improving surgical outcomes.

Burnout Among Chinese Anesthesiologists After the COVID-19 Pandemic Peak: A National Survey.

BACKGROUND: Evidence has shown that large-scale pandemics can have prolonged psychological impacts on health care professionals. The current study aimed to evaluate the prevalence of burnout after the coronavirus disease 2019 (COVID-19) epidemic peak and to explore the prolonged impact of COVID-19 on burnout among Chinese anesthesiologists. METHODS: From August 2021 to October 2021, a nationwide cross-sectional survey was conducted. Burnout was measured using the Maslach Burnout Inventory-Human Service Survey. Basic demographic information, exposure to COVID-19, and perceived institutional support were documented. Validated tools measuring mental health status, including anxiety, depression, post-traumatic stress disorder (PTSD) and resilience, were also used to provide additional information on psychological distress. RESULTS: Of the 8850 anesthesiologists from the 218 institutions who were invited to participate, 6331 (74.93%) completed the surveys and were included in the analysis. A total of 52.7% (95% confidence interval [CI], 51.5-53.9) met the criteria for burnout. Depression, anxiety, and PTSD were positively associated with burnout. After pooled multivariate analysis adjusting for potential confounding factors, among the COVID-19 exposure parameters, redeployment outside normal professional boundaries remained associated with an increased risk of burnout (odds ratio, 0.84; 95% CI, 0.72-0.92; P = .039). Higher perceived institutional support and resilience could act as protective factors against burnout. CONCLUSIONS: The impact of the COVID-19 epidemic on the psychological well-being of anesthesiologists still exists more than 1 year after the outbreak. Building better institutional support and cultivating stronger resilience may be helpful future intervention measures.

Occupational Factors Associated With Time to Breastfeeding Discontinuation After Return to Work Among Female Anesthesiologists in China: A Nationwide Survey.

BACKGROUND: Breast milk is of great benefit to both infants and mothers. Due to occupational barriers, female physicians are at high risk of unintentionally discontinuing breastfeeding. However, evidence among anesthesiologists was limited. The purpose of this study was to investigate occupational factors associated with time to breastfeeding discontinuation among female anesthesiologists following maternity leave in China. METHODS: We conducted a nationwide survey of female anesthesiologists who had given birth since January 1, 2015. A 60-item anonymous questionnaire was developed to collect information regarding breastfeeding practices and related factors. The questionnaire was revised based on the recommendations of 15 experts and feedback from the pilot survey. The survey was distributed by the Chinese Society of Anesthesiology. RESULTS: The completion rate was 57.9%. In total, 1364 responders were analyzed from all 31 provinces of Mainland China. In total, 1311 (96.1%) responders reported a reduction in breast milk supply on returning to work. Among the 1161 responders who discontinued breastfeeding, 836 (72.0%) did not achieve desired goals due to occupational factors. The median [interquartile range] of maternity leave length and breastfeeding duration were 5 [4-6] months and 10 [7-12] months, respectively. The following occupational factors were associated with longer time to breastfeeding discontinuation after adjusting for confounding effects of personal factors: length of maternity leave (hazard ratio [HR] per month 0.44; 95% confidence interval [CI], 0.36-0.54; P < .001), pumping breast milk during work time (HR, 0.04; 95% CI, 0.02-0.08; P < .001), support from colleagues (HR, 0.92; 95% CI, 0.86-0.99; P = .032), and additional nonclinical activities (HR, 0.87; 95% CI, 0.77-0.98; P = .022). Trainees under supervision (HR, 1.20; 95% CI, 1.06-1.43; P = .005) and the need to remain in the operating room during cases (HR, 2.59; 95% CI, 1.09-6.12; P = .031) were associated with shorter time to breastfeeding discontinuation. Approximately 899 (65.9%) responders pumped breast milk during work time. Among them, reduction in pumping frequency (HR, 1.17; 95% CI, 1.00-1.36; P = .049) and difficulty in finding opportunities for pumping (HR, 2.34; 95% CI, 1.36-4.03; P = .002) were associated with shorter time to breastfeeding discontinuation. CONCLUSIONS: We identified modifiable occupational factors associated with time to breastfeeding discontinuation. These findings underscored the necessity of facilitating breastfeeding in the workplace, including encouraging longer maternity leave and breastfeeding breaks, considering the feasibility of pumping in daily case assignments, establishing supportive culture, providing lactation rooms, and offering nonclinical activities.

Intraoperative Blood Pressure Lability Acts as a Key Mediator in the Impacts of Goal-Directed Fluid Therapy on Postoperative Complications in Patients Undergoing Major Spine Surgery.

Objective Although goal-directed fluid therapy (GDFT) has been proven to be effective in reducing the incidence of postoperative complications, the underlying mechanisms remain unknown. The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications. We further tested the role of this mediation effect using mean arterial pressure, a hemodynamic indicator. Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis. We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications. We conducted mediation analysis using the mediation package in R (version 3.1.2), based on 5,000 bootstrapped samples, adjusting for covariates. Results Among the 300 patients in the study, 40% (120/300) developed postoperative complications within 30 days. GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders (odds ratio: 0.460, 95% CI: 0.278, 0.761; P = 0.003). The total effect of GDFT on postoperative complications was -0.18 (95% CI: -0.28, -0.07; P < 0.01). The average causal mediation effect was -0.08 (95% CI: -0.15, -0.04; P < 0.01). The average direct effect was -0.09 (95% CI: -0.20, 0.03; P = 0.17). The proportion mediated was 49.9% (95% CI: 18.3%, 140.0%). Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications. Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.

Effect of active warming on perioperative cardiovascular outcomes: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The objective of this study was to provide an updated review on the active warming effects on major adverse cardiac events, 30-day all-cause mortality, and myocardial injury after noncardiac surgery. METHOD: We systematically searched MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, Web of Science, and Chinese BioMedical Literature Database. We included randomized controlled trials of adult population undergoing noncardiac surgeries that concentrate on the comparison of active warming methods and passive thermal management. Cochrane Collaboration's tool was applied for risk-of-bias assessment. We used trial sequential analysis to evaluate the possibility of false positive or negative results. RESULTS: A total of 13,316 unique records were identified, of which only 19 with reported perioperative cardiovascular outcomes were included in the systematic review and nine of them were included in final meta-analysis. No statistically significant difference between active warming methods and routine care was found in major adverse cardiac events (RR 0.56, 95% confidence interval (CI) 0.14-2.21, I2 = 71%, number of events 59 vs. 70), 30-day all-cause mortality (RR 0.81, 95% CI 0.43-1.54, I2 = 0%, number of events 17 vs. 21), and myocardial injury after noncardiac surgery (RR 0.61, 95% CI 0.17-2.22, I2 = 79%, number of events 236 vs. 234). Trial sequential analysis suggests that current trials did not reach the minimum information size regarding the major cardiovascular events. CONCLUSIONS: Compared to routine perioperative care, we found that active warming methods are not necessary for cardiovascular prevention in patients undergoing noncardiac surgery.

Lipids, lipid-modifying drug target genes and migraine: a Mendelian randomization study.

INTRODUCTION: Migraine, a prevalent headache disorder with unclear mechanisms and limited treatments, may be influenced by dyslipidemia and genetic factors. Statins and emerging lipid-modifying agents show potential but lack evidence for migraine management. Mendelian Randomization analysis offers insights into causal relationships and therapeutic targets. This study aims to explore genetically predicted lipid traits, drug targets, and their association with migraine risk. METHOD: We conducted Mendelian randomization (MR) analyses utilizing genetic variants associated with lipid traits and variants in genes encoding the protein targets of various classes of lipid-lowering drugs. The specific drug classes investigated included HMGCR, PCSK9, NPC1L1, ABCG5/ABCG8, LDLR, LPL, ANGPTL3, APOB, CETP, and APOC3. To determine the effects on migraine risk, we meta-analyzed MR estimates for regional variants using data from two large sample sets. The genetic variants were weighted based on their associations with specific lipid traits, such as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Apolipoprotein A1, and Apolipoprotein B. To obtain association weights, we utilized data from lipid genetics consortia. For lipid-modifying drug targets that exhibited suggestive significance, we further employed expression quantitative trait locus (eQTL) data. Additionally, we performed colocalization analysis to assess genetic confounding. RESULT: The use of genetic proxies for HMGCR inhibition demonstrated a significant association with a decreased risk of migraine in the FinnGen dataset (OR = 0.64, 95% CI: 0.46-0.88, p = 0.0006) and a nearly significant association in the Choquet dataset (OR = 0.78, 95% CI: 0.60-1.01, p = 0.06). When pooling the estimates, the overall effect size showed a reduced risk of migraine (OR = 0.73, 95% CI: 0.60-0.89, p = 0.0016). Similarly, genetic mimicry of LPL enhancement was associated with a lower risk of migraine in the FinnGen dataset (OR = 0.82, 95% CI: 0.69-0.96, p = 0.01) and the Choquet dataset (OR = 0.91, 95% CI: 0.83-0.99, p = 0.03). Pooling the estimates showed a consistent effect size (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002). Sensitivity analyses yielded no statistically significant evidence of bias arising from pleiotropy or genetic confounding. CONCLUSION: In the study, it was observed that among the 10 lipid-lowering drug targets investigated, LPL and HMGCR showed significant associations with migraine risk. These findings indicate that LPL and HMGCR have the potential to serve as candidate drug targets for the treatment or prevention of migraines.

[Standard Process for Palliative Sedation in Peking Union Medical College Hospital].

End-stage patients experience unbearable pain because of refractory symptoms.Palliative sedation is a form of palliative care which relieves patients' agony by lowering their consciousness.Standard palliative sedation can help patients die with dignity.It is distinct from euthanasia and does not alter the survival of patients.Sufficient palliative care is the premise of palliative sedation.Repeated and detailed clinical evaluation,as well as multidisciplinary involvement,is necessary for the standardized implementation of palliative sedation.Here,we proposed the standard process and specifications of palliative sedation in Peking Union Medical College Hospital.Furthermore,we reported a case of palliative sedation for an advanced cancer patient with refractory delirium and living pain to demonstrate its application in clinical practice.

Astrocyte-microglia interaction through C3/C3aR pathway modulates neuropathic pain in rats model of chronic constriction injury.

Neuropathic pain (NP) is the cardinal symptom of neural injury, and its underlying molecular mechanism needs further investigation. Complements, especially complement 3 (C3), are involved in the pathophysiology of many neurological disorders, while the specific role of C3 in NP is still obscure. In this study, we found that both C3 and its receptor C3aR were upregulated in the spinal dorsal horn in a rat chronic constriction injury (CCI) model. In addition, C3 was mainly detected in astrocytes, while C3aR was expressed in microglia and neuron. Intrathecal injection of C3 antibody and C3aR antagonist alleviated NP in CCI model together with reduced M1 polarization of microglia. Our finding suggested that blockade of the C3/C3aR pathway might be a novel strategy for NP.

Generating real-world evidence compatible with evidence from randomized controlled trials: a novel observational study design applicable to surgical transfusion research.

BACKGROUND: Numerous observational studies have revealed an increased risk of death and complications with transfusion, but this observation has not been confirmed in randomized controlled trials (RCTs). The "transfusion kills patients" paradox persists in real-world observational studies despite application of analytic methods such as propensity-score matching. We propose a new design to address this long-term existing issue, which if left unresolved, will be deleterious to the healthy generation of evidence that supports optimized transfusion practice. METHODS: In the new design, we stress three aspects for reconciling observational studies and RCTs on transfusion safety: (1) re-definition of the study population according to a stable hemoglobin range (gray zone of transfusion decision; 7.5-9.5 g/dL in this study); (2) selection of comparison groups according to a trigger value (last hemoglobin measurement before transfusion; nadir during hospital stay for control); (3) dealing with patient heterogeneity according to standardized mean difference (SMD) values. We applied the new design to hospitalized older patients (aged ≥60 years) undergoing general surgery at four academic/teaching hospitals. Four datasets were analyzed: a base population before (Base Match-) and after (Base Match+) propensity-score matching to simulate previous observational studies; a study population before (Study Match-) and after (Study Match+) propensity-score matching to demonstrate effects of our design. RESULTS: Of 6141 older patients, 662 (10.78%) were transfused and showed high heterogeneity compared with those not receiving transfusion, particularly regarding preoperative hemoglobin (mean: 11.0 vs. 13.5 g/dL) and intraoperative bleeding (≥500 mL: 37.9% vs. 2.1%). Patient heterogeneity was reduced with the new design; SMD of the two variables was reduced from approximately 100% (Base Match-) to 0% (Study Match+). Transfusion was related to a higher risk of death and complications in Base Match- (odds ratio [OR], 95% confidence interval [CI]: 2.68, 1.86-3.86) and Base Match+ (2.24, 1.43-3.49), but not in Study Match- (0.77, 0.32-1.86) or Study Match+ (0.66, 0.23-1.89). CONCLUSIONS: We show how choice of study population and analysis could affect real-world study findings. Our results following the new design are in accordance with relevant RCTs, highlighting its value in accelerating the pace of transfusion evidence generation and generalization.

Preoperative Anxiety in Chinese Adult Patients Undergoing Elective Surgeries: A Multicenter Cross-Sectional Study.

BACKGROUND: Preoperative anxiety is associated with increased use of anesthetics and poorer postoperative outcomes. However, the prevalence of preoperative anxiety has not been characterized in Chinese patients. In this study, we aimed to estimate the overall prevalence of preoperative anxiety in Chinese adult patients and to explore the sociodemographic and clinical factors associated with preoperative anxiety in China. METHODS: This study was a multicenter cross-sectional study conducted at 32 tertiary referral centers in China from September 1 to October 31, 2020. Adult patients scheduled for elective surgery were evaluated by the 7-item Perioperative Anxiety Scale (PAS-7) for preoperative anxiety after entrance to the operating zone. RESULTS: A total of 5191 patients were recruited, and 5018 of them were analyzed. The prevalence of preoperative anxiety measured by PAS-7 was 15.8% (95% CI 14.8 to 16.9%). Multivariable analyses showed female sex, younger age, non-retired, first in a lifetime surgery, surgery of higher risk, and poorer preoperative sleep were associated with higher prevalence of preoperative anxiety. CONCLUSIONS: Preoperative anxiety was relatively common (prevalence of 15.8%) among adult Chinese patients undergoing elective surgeries. Further studies are needed using suitable assessment tools to better characterize preoperative anxiety, and additional focus should be placed on perioperative education and intervention, especially in primary hospitals. TRIAL REGISTRATION: This study was registered prospectively at www.chictr.org.cn (ChiCTR1900027639) on November 22, 2019.

Validation of a Prediction Model for Intraoperative Hypothermia in Patients Receiving General Anesthesia.

Objectives: There have been no fully validated tools for the rapid identification of surgical patients at risk of intraoperative hypothermia. The objective of this study was to validate the performance of a previously established prediction model in estimating the risk of intraoperative hypothermia in a prospective cohort. Methods: In this observational study, consecutive adults scheduled for elective surgery under general anesthesia were enrolled prospectively at a tertiary hospital between September 4, 2020, and December 28, 2020. An intraoperative hypothermia risk score was calculated by a mobile application of the prediction model. A wireless axillary thermometer was used to continuously measure perioperative core temperature as the reference standard. The discrimination and calibration of the model were assessed, using the area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow goodness-of-fit test, and Brier score. Results: Among 227 participants, 99 (43.6%) developed intraoperative hypothermia, and 10 (4.6%) received intraoperative active warming with forced-air warming. The model had an AUC of 0.700 (95% confidence interval [CI], 0.632-0.768) in the overall cohort with adequate calibration (Hosmer-Lemeshow χ 2 = 13.8, P=0.087; Brier score = 0.33 [95% CI, 0.29-0.37]). We categorized the risk scores into low-risk, moderate-risk, and high-risk groups, in which the incidence of intraoperative hypothermia was 23.0% (95% CI, 12.4-33.5), 43.4% (95% CI, 33.7-53.2), and 62.7% (95% CI, 51.5-74.3), respectively (P for trend <0.001). Conclusions: The intraoperative hypothermia prediction model demonstrated possibly helpful discrimination and adequate calibration in our prospective validation. These findings suggest that the risk screening model could facilitate future perioperative temperature management.