Photoaffinity labeling coupled with proteomics identify PDI-ADAM17 module is targeted by (-)-vinigrol to induce TNFR1 shedding and ameliorate rheumatoid arthritis in mice.

Various biological agents have been developed to target tumor necrosis factor alpha (TNF-α) and its receptor TNFR1 for the rheumatoid arthritis (RA) treatment, whereas small molecules modulating such cytokine receptors are rarely reported in comparison to the biologicals. Here, by revealing the mechanism of action of vinigrol, a diterpenoid natural product, we show that inhibition of the protein disulfide isomerase (PDI, PDIA1) by small molecules activates A disintegrin and metalloprotease 17 (ADAM17) and then leads to the TNFR1 shedding on mouse and human cell membranes. This small-molecule-induced receptor shedding not only effectively blocks the inflammatory response caused by TNF-α in cells, but also reduces the arthritic score and joint damage in the collagen-induced arthritis mouse model. Our study indicates that targeting the PDI-ADAM17 signaling module to regulate the shedding of cytokine receptors by the chemical approach constitutes a promising strategy for alleviating RA.

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.

Tumor aerobic glycolysis confers immune evasion through modulating sensitivity to T cell-mediated bystander killing via TNF-α.

Metabolic reprogramming toward glycolysis is a hallmark of cancer malignancy. The molecular mechanisms by which the tumor glycolysis pathway promotes immune evasion remain to be elucidated. Here, by performing genome-wide CRISPR screens in murine tumor cells co-cultured with cytotoxic T cells (CTLs), we identified that deficiency of two important glycolysis enzymes, Glut1 (glucose transporter 1) and Gpi1 (glucose-6-phosphate isomerase 1), resulted in enhanced killing of tumor cells by CTLs. Mechanistically, Glut1 inactivation causes metabolic rewiring toward oxidative phosphorylation, which generates an excessive amount of reactive oxygen species (ROS). Accumulated ROS potentiate tumor cell death mediated by tumor necrosis factor alpha (TNF-α) in a caspase-8- and Fadd-dependent manner. Genetic and pharmacological inactivation of Glut1 sensitizes tumors to anti-tumor immunity and synergizes with anti-PD-1 therapy through the TNF-α pathway. The mechanistic interplay between tumor-intrinsic glycolysis and TNF-α-induced killing provides new therapeutic strategies to enhance anti-tumor immunity.

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.

Association of intraoperative hypotension and postoperative acute kidney injury after adrenalectomy for pheochromocytoma: a retrospective cohort analysis.

BACKGROUND: Perioperative acute kidney injury (AKI) has been one of the leading causes of morbidity and mortality for surgical patients. Pheochromocytoma is a rare, catecholamine-secreting neuroendocrine neoplasm characterized by typical long-term hypertension that needs surgical resection. Our objective was to determine whether intraoperative mean arterial pressures (MAPs) less than 65 mmHg are associated with postoperative AKI after elective adrenalectomy in patients with pheochromocytoma. METHODS: We performed a retrospective review of patients undergoing adrenalectomy for pheochromocytoma between 1991 and 2019 at Peking Union Medical College Hospital, Beijing, China. Two intraoperative phases, before and after tumor resection, were recognized based on distinctly different hemodynamic characteristics. The authors evaluated the association between AKI and each blood pressure exposure in these two phases. The association between the time spent under different absolute and relative MAP thresholds and AKI was then evaluated adjusting for potential confounding variables. RESULTS: We enrolled 560 cases with 48 patients who developed AKI postoperatively. The baseline and intraoperative characteristics were similar in both groups. Though time-weighted average MAP was not associated with postoperative AKI during the whole operation (OR 1.38; 95% CI, 0.95-2.00; P = 0.087) and before tumor resection phase (OR 0.83; 95% CI, 0.65-1.05; P = 0.12), both time-weighted MAP and time-weighted percentage changes from baseline were strongly associated with postoperative AKI after tumor resection, with OR 3.50, 95% CI (2.25, 5.46) and 2.03, 95% CI (1.56, 2.66) in the univariable logistic analysis respectively, and with OR 2.36, 95% CI (1.46, 3.80) and 1.63, 95% CI (1.23, 2.17) after adjusting sex, surgical type (open vs. laparoscopic) and estimated blood loss in the multiple logistic analysis. At any thresholds of MAP less than 85, 80, 75, 70, and 65 mmHg, prolonged exposure was associated with increased odds of AKI. CONCLUSIONS: We found a significant association between hypotension and postoperative AKI in patients with pheochromocytoma undergoing adrenalectomy in the period after tumor resection. Optimizing hemodynamics, especially blood pressure after the adrenal vessel ligation and tumor is resected, is crucial for the prevention of postoperative AKI in patient with pheochromocytoma, which could be different from general populations.

Risk factors for postoperative complications after pheochromocytoma and/or paraganglioma: a single-center retrospective study.

Background: Perioperative complications are higher in patients with pheochromocytoma and/or paraganglioma. The aim of this study was to identify the risk factors of postoperative complications after pheochromocytoma and/or paraganglioma resection surgery. Method: We retrospectively reviewed 438 patients who underwent laparoscopic or open surgery for pheochromocytoma and/or paraganglioma at our center between January 2014 and December 2019. Demographic characteristics and intraoperative and postoperative data were recorded. Complications were defined as deviations from the normal postoperative course and Clavien-Dindo classification was used to grade the severity of postoperative complication. Patients with complications of grade II or above were included for analysis. Binary logistic regression was used to determine the risk factors for postoperative complications. Results: The median age of the patients was 47 years old. There were 295 cases (67.4%) of phepchromocytoma and 143 cases (32.6%) of paraganglioma. Three hundred sixty-seven (87.8%) patients had laparoscopic approach, and 55 (12.6%) patients had laparotomy; the conversion rate from laparoscopy to laparotomy was 3.7%. Eighty-seven complications occurred in 65 patients (14.8%). No death occurred in our study and transfusion (36, 8.2%) was the most common complication. The mean follow-up length was 14 months. Independent risk factors for postoperative complications included a tumor size larger than 5.6 cm (OR = 2.427, 95% CI 1.284-4.587, P = 0.006), laparotomy (OR 2.590, 95% CI 1.230-5.453, P = 0.012), conversion to laparotomy (OR = 8.384, 95% CI 2.247-31.285, P = 0.002), and the operation time longer than 188 min (OR = 3.709, 95% CI 1.847-7.450, P < 0.001). Conclusion: Complications were not uncommon after pheochromocytoma and/or paraganglioma surgery. Tumor size, surgical type, and operation time were determined as the risk factors for postoperative complications. These factors should be considered to improve perioperative management.

Association between perioperative plasma transfusion and in-hospital mortality in patients undergoing surgeries without massive transfusion: A nationwide retrospective cohort study.

Background: An aggressive plasma transfusion is associated with a decreased mortality in traumatic patients requiring massive transfusion (MT). However, it is controversial whether non-traumatic or non-massively transfused patients can benefit from high doses of plasma. Methods: We performed a nationwide retrospective cohort study using data from Hospital Quality Monitoring System, which collected anonymized inpatient medical records from 31 provinces in mainland China. We included the patients who had at least one record of surgical procedure and received red blood cell transfusion on the day of surgery from 2016 to 2018. We excluded those receiving MT or diagnosed with coagulopathy at admission. The exposure variable was the total volume of fresh frozen plasma (FFP) transfused, and the primary outcome was in-hospital mortality. The relationship between them was assessed using multivariable logistic regression model adjusting 15 potential confounders. Results: A total of 69319 patients were included, and 808 died among them. A 100-ml increase in FFP transfusion volume was associated with a higher in-hospital mortality (odds ratio 1.05, 95% confidence interval 1.04-1.06, p < 0.001) after controlling for the confounders. FFP transfusion volume was also associated with superficial surgical site infection, nosocomial infection, prolonged length of hospital stay, ventilation time, and acute respiratory distress syndrome. The significant association between FFP transfusion volume and in-hospital mortality was extended to the subgroups of cardiac surgery, vascular surgery, and thoracic or abdominal surgery. Conclusions: A higher volume of perioperative FFP transfusion was associated with an increased in-hospital mortality and inferior postoperative outcomes in surgical patients without MT.

High throughput screening for drugs that inhibit 3C-like protease in SARS-CoV-2.

The SARS coronavirus 2 (SARS-CoV-2) pandemic remains a major problem in many parts of the world and infection rates remain at extremely high levels. This high prevalence drives the continued emergence of new variants, and possibly ones that are more vaccine-resistant and that can drive infections even in highly vaccinated populations. The high rate of variant evolution makes clear the need for new therapeutics that can be clinically applied to minimize or eliminate the effects of COVID-19. With a hurdle of 10 years, on average, for first in class small molecule therapeutics to achieve FDA approval, the fastest way to identify therapeutics is by drug repurposing. To this end, we developed a high throughput cell-based screen that incorporates the essential viral 3C-like protease and its peptide cleavage site into a luciferase complementation assay to evaluate the efficacy of known drugs encompassing approximately 15,000 clinical-stage or FDA-approved small molecules. Confirmed inhibitors were also tested to determine their cytotoxic properties. Medicinal chemistry efforts to optimize the hits identified Tranilast as a potential lead. Here, we report the rapid screening and identification of potentially relevant drugs that exhibit selective inhibition of the SARS-CoV-2 viral 3C-like protease.

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.

Obesity paradox among patients undergoing total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Obesity has been recognized as the risk factor for postoperative complication for surgical patients. However, recent studies have showed protective effect of obesity in surgical and non-surgical patients. Our study is to examine the association of body mass index(BMI) with early postoperative complications in patients undergoing total knee arthroplasty. MATERIALS AND METHODS: All patients who had primary total knee arthroplasty between January 2014 and December 2019 were included. Medical records were retrospectively reviewed and BMI was categorized as underweight(BMI < 18.5), normal weight(18.5 < BMI < 24.9), overweight I(25 < BMI < 27.4), overweight II(27.5 < BMI < 29.9), obese I(30 < BMI < 34.9) and obese II(BMI ≥ 35). The association between BMI and occurrence of early postoperative complications was examined and logistic regression was used to calculate relationship between BMI and early postoperative complications. RESULTS: A total of 2969 patients were included in our analysis. The overall complication rate in patients undergoing total knee arthroplasty was 14.8%, with the highest complication being 22.2% in the underweight group, the second highest in the normal weight group(17.5%), the lowest in the overweight I(13.8%) and obese I(12.0%) group and then higher again in obese II group(16.7%). In multivariable analyses, overweight I (OR 0.737, 95% CI 0.559-0.972, P = 0.031) and obese I (OR 0.631, 95% CI 0.449-0.885, P = 0.008) were associated with lower risk of early postoperative complications after total knee arthroplasty. CONCLUSION: In this retrospective study, overweight and obese patients had a lower risk of early postoperative complications after total knee arthroplasty. Further studies are necessary to confirm and investigate the mechanism of obesity paradox in this surgical population. TRIAL REGISTRATION: This study had been registrated in www.chictr.org.cn on 25/10/2021 and the registration ID was ChiCTR2100052408.

[Association of Perioperative Allogeneic Red Blood Cell Transfusion with Postoperative Infections].

Allogeneic red blood cell transfusion can induce transfusion-related immunomodulation while correcting anemia and improving oxygenation,and thus may be associated with the increased risk of postoperative infections.However,the available studies have conflicting conclusions.Preclinical studies demonstrate transfusion-related immunomodulation is associated with transfusion amounts.Stored red blood cells can cause more significant immunosuppression than fresh blood products,while leukoreduction alleviates the negative effect on immune system.However,clinical studies do not reach agreements on these issues.Recently,accumulating multi-center,large-sample-size,real-world studies have reported significant associations of all ogeneic red blood cell transfusion in cardiac,orthopedic,hepatic,pancreatic,gastrointestinal,and vesical surgeries with postoperative infections.Considering the limitations of previous studies,future research should focus on multiple operations,prolong the time interval between transfusion and surgery,include different infections into outcomes,and define the postoperative infections accurately in the premise of adequate samples.High-quality clinical evidence could help to optimize the utilization of blood products and improve the postoperative outcomes.

Predictive Factors for Catecholamine-Induced Cardiomyopathy in Patients with Pheochromocytoma and Paraganglioma.

Objective: To investigate possible predictive factors of catecholamine-induced cardiomyopathy in pheochromocytoma and paraganglioma (CICMPP) patients. Methods: In all, 50 CICMPP patients and 152 pheochromocytoma and paraganglioma (PPGL) patients without CICMPP who were treated in our institution between August 2012 and April 2018 were included in this retrospective study to assess predictors of CICMPP. Results: Patients with CICMPP reported younger onset age, more clinical symptoms and signs, more family history of hypertension, and higher maximum systolic, diastolic, and mean BP and maximum HR. Medical evaluation also showed higher level of blood hematocrit, blood glucose, 24-h urine catecholamines, larger diameter of the tumor and more comorbidities, von Hippel-Lindau syndromes, and metastatic tumors in these patients. Multivariable analysis identified maximum resting HR over 115 beats/min (OR 10.05, 95% CI 3.71-27.20), maximum resting systolic BP over 180 mmHg (OR 7.17, 95% CI 2.22-23.23), blood glucose over 8.0 mmol/L (OR 6.52, 95% CI 2.25-18.86), more than 3 symptoms and signs (OR 6.05, 95% CI 1.86-19.64), and onset age under 40 years (OR 3.74, 95% CI 1.37-10.20) as independent predictors of CICMPP. Female sex (OR 5.06, 95% CI 1.19-21.54), complaint of chest pain (OR 5.84, 95% CI 1.27-26.90), and extra-adrenal tumor (OR 8.64, 95% CI 1.82-40.94) were independent predictors of Takotsubo cardiomyopathy in CICMPP. Conclusion: Maximum resting HR ≥115 beats/min, maximum resting systolic BP ≥180 mmHg, blood glucose ≥8.0 mmol/L, number of symptoms and signs ≥3, and onset age ≤40 years were found to be predictive factors for CICMPP.

Intraoperative thromboelastography-guided transfusion in a patient with factor XI deficiency: A case report.

BACKGROUND: Factor XI (FXI) deficiency, also known as hemophilia C, is a rare bleeding disorder of unpredictable severity that correlates poorly with FXI coagulation activity. This often poses great challenges in perioperative hemostatic management. Thromboelastography (TEG) is a method for testing blood coagulation using a viscoelastic hemostatic assay of whole blood to assess the overall coagulation status. Here, we present the successful application of intraoperative TEG monitoring in an FXI-deficient patient as an individualized blood transfusion strategy. CASE SUMMARY: A 21-year-old male patient with FXI deficiency was scheduled to undergo reconstructive surgery for macrodactyly of the left foot under general anesthesia. To minimize his bleeding risk, he was scheduled to receive fresh frozen plasma (FFP) as an empirical prophylactic FXI replacement at a dose of 15-20 mL/kg body weight (900-1200 mL) before surgery. Subsequent FFP transfusion was to be adjusted according to surgical need. Instead, TEG assessment was used at the beginning and toward the end of his surgery. According to intraoperative TEG results, the normalization of coagulation function was achieved with an infusion of only 800 mL FFP, and blood loss was minimal. The patient showed an uneventful postoperative course and was discharged on postoperative day 8. CONCLUSION: TEG can be readily applied in the intraoperative period to individualize transfusion needs in patients with rare inherited coagulopathy.

Identification of potent small molecule inhibitors of SARS-CoV-2 entry.

The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants.

Expanding restrictive transfusion evidence in surgical practice: a multicentre, prospective cohort study.

BACKGROUND: Findings of observational studies investigating the impact of transfusions are at odds with those of randomised controlled trials, raising concern that observational studies may be inappropriate to inform transfusion decisions. We examined whether observational data could replicate evidence from randomised controlled trials on restrictive transfusion in cardiac and orthopaedic surgery, and be generalised to broader specialties as well as to a lower haemoglobin transfusion threshold (7 g/dL). MATERIAL AND METHODS: A multicentre, prospective cohort study was performed at three representative regional hospitals in China between 2015 and 2016. Participants were surgical inpatients (≥18 years; hospital stay ≥24 h) in six specialties: cardiac, cerebral, vascular (CCV), and orthopaedic, general, thoracic (non-CCV). Patients with a stable haemoglobin (7-10 g/dL) constituted the primary analytic sample, while patients with ≥500 mL intra-operative bleeding were analysed separately to avoid haemoglobin instability. The association of transfusion with surgical outcomes (death, in-hospital complications) was evaluated. RESULTS: The transfusion rate was 10.7% in 36,607 patients (mean age, 52.5±14.3 years; 52.3% female). After restriction, stratification, and propensity score matching to reduce patients' heterogeneity, transfusion was unrelated to death (CCV: odds ratio [OR]=0.74, 95% confidence interval [CI]: 0.16-3.39; non-CCV: OR 0.83, 95% CI: 0.36-1.94) and the composite complication (CCV: OR 1.31, 95% CI: 0.63-2.72; non-CCV: OR=1.24, 95% CI: 0.81-1.90). The results were consistent in subgroups (elderly, coronary heart disease, malignant tumour, severe illness) and applicable to patients with significant bleeding after restoration of a stable haemoglobin. DISCUSSION: Transfusion at a stable haemoglobin concentration of 7-10 g/dL did not alter surgical outcomes. Our results show the feasibility of observational data to expand restrictive transfusion to broader specialties and a lower transfusion threshold in surgical practice.

Association between perioperative allogeneic red blood cell transfusion and infection after clean-contaminated surgery: a retrospective cohort study.

BACKGROUND: Allogeneic red blood cell (RBC) transfusion can induce immunosuppression, which can then increase the susceptibility to postoperative infection. However, studies in different types of surgery show conflicting results regarding this effect. METHODS: In this retrospective cohort study conducted in a tertiary referral centre, we included adult patients undergoing clean-contaminated surgery from 2014 to 2018. Patients who received allogeneic RBC transfusion from preoperative Day 30 to postoperative Day 30 were included into the transfusion group. The control group was matched for the type of surgery in a 1:1 ratio. The primary outcome was infection within 30 days after surgery, which was defined by healthcare-associated infection, and identified mainly based on antibiotic regimens, microbiology tests, and medical notes. RESULTS: Among the 8098 included patients, 1525 (18.8%) developed 1904 episodes of postoperative infection. Perioperative RBC transfusion was associated with an increased risk of postoperative infection after controlling for 27 confounders by multivariable regression analysis (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.39-1.84; P<0.001) and propensity score weighing (OR: 1.64; 95% CI: 1.45-1.85; P<0.001) and matching (OR: 1.70; 95% CI: 1.43-2.01; P<0.001), and a dose-response relationship was observed. The transfusion group also showed higher risks of surgical site infection, pneumonia, bloodstream infection, multiple infections, intensive care admission, unplanned reoperation, prolonged postoperative length of hospital stay, and all-cause death. CONCLUSIONS: Perioperative allogeneic RBC transfusion is associated with an increased risk of infection after clean-contaminated surgery in a dose-response manner. Close monitoring of infections and enhanced prophylactic strategies should be considered after transfusion.

Supraglottic foreign body in a woman with Down's syndrome and congenital heart disease: A case report.

RATIONALE: An impacted foreign body (FB) in the larynx of an adult is a rare but potentially life-threatening occurrence. Patients with Down's syndrome (DS) are vulnerable to airway FB. However, the anesthesia for FB removal can be challenging. This report describes a case in which a FB was impacted between the vestibular folds in an adult with DS, congenital heart disease, and a difficult airway. PATIENT CONCERNS: A 41-year-old woman swallowed a piece of sharp-tipped wooden skewer presented with a sudden onset of aphonia, dysphagia, and an acute sore throat without respiratory difficulty. The patient had DS, congenital heart disease, pulmonary arterial hypertension, and severe obstructive sleep apnea-hypopnea syndrome. The airway evaluation indicated that ventilation and intubation would be difficult due to retrognathia, macroglossia, adenotonsillar hypertrophy, and Mallampati's classification III. DIAGNOSIS: The clinical symptoms and laboratory examination confirmed FB penetrated between the vestibular folds. INTERVENTIONS: After careful multidisciplinary preoperative assessment and preparation, the FB was removed successfully by direct laryngoscopy under moderate sedation and spontaneous ventilation, with the application of 1% lidocaine as topical anesthesia. OUTCOMES: The laryngeal FB was removed successfully without any complications. And the patient was discharged home the next day. LESSONS: This case report shows the importance of anesthetic depth for laryngeal FB removal. The use of moderate sedation (allowing spontaneous ventilation) and adequate analgesia combined with local anesthesia enabled the patient to withstand the stress of direct laryngoscopy. Appropriate assessment, careful preparation, and multidisciplinary collaboration yielded the smooth removal of a laryngeal FB in an adult with DS.

A comparative study of fibrinogen measurement using TEG® functional fibrinogen and Clauss in adolescents undergoing scoliosis surgery.

INTRODUCTION: Thromboelastography (TEG®) functional fibrinogen (FF) test is a point-of-care test for fibrinogen measurement and is preferred for its rapid turnaround time. This study was designed to compare TEG® functional fibrinogen level (FLEV) with classic Clauss fibrinogen in patients undergoing scoliosis surgery and to evaluate the concordance between the two methods. METHODS: Patients in this study were part of a larger study evaluating the effect of fibrinogen concentrate (FC) supplementation on perioperative blood loss in scoliosis surgery. Paired samples for TEG® FF and Clauss fibrinogen assays were taken from 40 patients at three different timepoints perioperatively. The agreement between FLEV and Clauss was assessed, and the possibility of using FLEV measurements to predict Clauss fibrinogen was explored. RESULTS: One hundred and seventeen paired samples from 39 patients were finally analyzed. Pearson correlation test confirmed positive linear correlations between FLEV and Clauss at all three timepoints (r = .70, .67, and .66 at baseline, before FC administration, and after FC administration, respectively; P < .001 for all) and together for all measures (r = .76, P < .001), while Bland-Altman plots showed FLEV significantly overestimated Clauss constantly. Optimum diagnostic values of FLEV at 4.27 and 3.77 g/L were generated to predict normal fibrinogen as Clauss ≥ 3.0 g/L (AUROC 0.941, 95% CI: 0.891-0.991) and critical intraoperative hypofibrinogenemia as Clauss ≤ 2.0g/L (AUROC 0.894, 95% CI: 0.838-0.950), respectively. CONCLUSIONS: In adolescents undergoing scoliosis surgery, FLEV correlated linearly with Clauss fibrinogen. Though FLEV overestimates Clauss constantly, FLEV values are able to predict hypofibrinogenemia and normal fibrinogen with both AUROC > 0.85.

An animal model of transfusion-related acute lung injury and the role of soluble CD40 ligand.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is a life-threatening complication of transfusion and is one of leading causes of transfusion-associated fatalities. However, the pathogenesis of TRALI is still unclear. Soluble CD40 ligand (sCD40L) is a proinflammatory cytokine that accumulates during blood component storage and is involved in transfusion reactions. The objective of this study was to establish a clinically relevant TRALI animal model and to evaluate the role of sCD40L in TRALI. MATERIALS AND METHODS: Rats' red-blood-cell (RBC) suspensions were prepared, and the quality of RBC was evaluated. A trauma-haemorrhage-transfusion strategy was applied to build the animal model. Lung oedema was evaluated by histopathology examination, total bronchoalveolar lavage fluid (BALF) protein concentration, Evans blue dye (EBD) leakage and inflammatory cytokines. The sCD40L concentrations were measured. RESULTS: Storage lesions of RBCs gradually increased over time. Obvious histological evidence of lung injury of rats transfused with a 35-day RBC was observed. The total BALF protein concentration, EBD leakage, inflammatory cytokines concentration were increased significantly in the Day 35 group. The sCD40L concentration increased significantly in the storage RBC suspension over time but was slightly elevated in rat plasma. CONCLUSIONS: These findings indicated successful establishment of a TRALI animal model with trauma-haemorrhage-transfusion, in which sCD40L may play a minor role in the development of TRALI.

A Survey of Surgical Patient's Perception about Anesthesiologist in a Large Scale Comprehensive Hospital in China.

Objectives This study aim to evaluate patient's perception about anesthesiologists' job roles and investigate their expectations for anesthesia care.Methods We designed a self-administered questionnaire for this cross-sectional survey study and delivered questionnaire forms to adult in-patients who were scheduled for elective surgery before pre-operative anesthetic visit the day before surgery. We collected information of respondents' demographic data, education background, health literacy and previous experience of anesthesia, perception of anesthesiologist's job, the expectation on anesthesia care. Descriptive analyses, χ [2] test and multiple linear regression analysis were used for data analysis. Results Of 550 participants, 521（94.7%）completed the questionnaire. In these respondents, 335 (64.3%) considered anesthesiology as an independent medical discipline, 225 (43.2%) believed that anesthesiology department was an independent clinical department, and 243 (46.6%) recognized anesthesiologists as qualified doctors. Only 21.5% of them knew that anesthesiologists also work in the intensive care unit and 26.9% of them knew that anesthesiologists also work in pain clinic as well. Younger patients (ß=-0.044, P<0.001), those with higher education (ß=1.200, P<0.001), or with better health literacy (ß=0.781, P=0.005) had significant more knowledge about the job roles of anesthesiologists. Most patients demanded pre-anesthetic visit (80.5%), expected availability of preoperative anesthetic clinic (74.1%), wished to receive more information about anesthesia (91.3%) and anesthesiologist (77.4%).Conclusions Patients' perception about anesthesiologists might be limited. Efforts should be made on education about anesthesia, especially for elderly patients and those under-educated patients. Preoperative anesthetic clinic is expected by most in-patients.