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1.
EClinicalMedicine ; 75: 102772, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39170939

ABSTRACT

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition with a high incidence and mortality rate in intensive care unit (ICU) admissions. Early identification of patients at high risk for developing ARDS is crucial for timely intervention and improved clinical outcomes. However, the complex pathophysiology of ARDS makes early prediction challenging. This study aimed to develop an artificial intelligence (AI) model for automated lung lesion segmentation and early prediction of ARDS to facilitate timely intervention in the intensive care unit. Methods: A total of 928 ICU patients with chest computed tomography (CT) scans were included from November 2018 to November 2021 at three centers in China. Patients were divided into a retrospective cohort for model development and internal validation, and three independent cohorts for external validation. A deep learning-based framework using the UNet Transformer (UNETR) model was developed to perform the segmentation of lung lesions and early prediction of ARDS. We employed various data augmentation techniques using the Medical Open Network for AI (MONAI) framework, enhancing the training sample diversity and improving the model's generalization capabilities. The performance of the deep learning-based framework was compared with a Densenet-based image classification network and evaluated in external and prospective validation cohorts. The segmentation performance was assessed using the Dice coefficient (DC), and the prediction performance was assessed using area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The contributions of different features to ARDS prediction were visualized using Shapley Explanation Plots. This study was registered with the China Clinical Trial Registration Centre (ChiCTR2200058700). Findings: The segmentation task using the deep learning framework achieved a DC of 0.734 ± 0.137 in the validation set. For the prediction task, the deep learning-based framework achieved AUCs of 0.916 [0.858-0.961], 0.865 [0.774-0.945], 0.901 [0.835-0.955], and 0.876 [0.804-0.936] in the internal validation cohort, external validation cohort I, external validation cohort II, and prospective validation cohort, respectively. It outperformed the Densenet-based image classification network in terms of prediction accuracy. Moreover, the ARDS prediction model identified lung lesion features and clinical parameters such as C-reactive protein, albumin, bilirubin, platelet count, and age as significant contributors to ARDS prediction. Interpretation: The deep learning-based framework using the UNETR model demonstrated high accuracy and robustness in lung lesion segmentation and early ARDS prediction, and had good generalization ability and clinical applicability. Funding: This study was supported by grants from the Shanghai Renji Hospital Clinical Research Innovation and Cultivation Fund (RJPY-DZX-008) and Shanghai Science and Technology Development Funds (22YF1423300).

2.
Heliyon ; 10(12): e32311, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39183849

ABSTRACT

Background: Traumatic injuries, surgery, and chronic diseases lead to soft tissue wounds. Stimulating normal wound healing (WH) is important for tissue repair and restoration of homeostasis. Lack of angiogenesis impedes wound healing and is noted in chronic wounds. The goal of this investigation was to thoroughly assess the present state and patterns of investigations on angiogenesis in WH by the use of bibliometric analysis. Methods: Studies examining angiogenesis and WH were sourced from the database of the Web of Science Core Collection. Only studies that fulfilled the inclusion criteria were chosen for the purpose of investigation. To analyze the publications included in this research, bibliometric and visual analysis techniques were applied utilizing tools like VOSviewer and CiteSpace. Results: For the analysis, 11,558 papers were considered. The number of publications increased annually from 2013 to 2023. China, the USA, and South Korea were the top nations in this subject, accounting for 41.1 %, 19.4 %, and 5.8 % of published articles, respectively. The author and institution with the greatest number of publications were found to be Chang J and Shanghai Jiao Tong University. PLOS One had the greatest publication count among journals, whereas Biomaterials had the greatest number of citations and was often mentioned in co-citations. Angiogenesis-related biomedical engineering and tissue engineering were the topics that received the most research attention. Recent studies have focused on vascular endothelial growth factor and carboxymethyl chitosan as emerging areas of interest. Conclusion: In this investigation, we compiled the features of publications and determined the most impactful nations, organizations, writers, periodicals, popular subjects, and patterns concerning the process of angiogenesis in the context of WH.

3.
iScience ; 27(2): 109019, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38352222

ABSTRACT

Dexamethasone is commonly used as an adjuvant to prolong peripheral nerve block analgesia, but the optimal timing is unclear. This randomized equivalence trial tested whether preoperative versus postoperative intravenous dexamethasone have equivalent analgesic effects when combined with interscalene brachial plexus block for shoulder surgery. 168 patients were randomized to receive 5 mg dexamethasone either preoperatively or postoperatively. The primary outcome was duration of analgesia, analyzed for equivalence with a 2-h margin. The mean durations were equivalent between groups (11.5 h preoperative versus 10.7 h postoperative). The confidence intervals fell within the equivalence margin. There were no other clinically significant differences in secondary outcomes like time to first analgesia, motor recovery, opioid consumption, blood glucose, or complications. In conclusion, as an adjuvant for nerve block, preoperative and postoperative intravenous dexamethasone provide equivalent analgesic duration, allowing for flexibility in clinical use. This addresses previous uncertainty about timing while demonstrating equivalent efficacy.

4.
J Integr Neurosci ; 22(5): 110, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37735113

ABSTRACT

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. The purpose of this study was to investigate the mechanism through which metformin improves postoperative cognitive function. METHODS: In the in vivo experiment, 18-month-old Sprague-Dawley (SD) rats were randomly divided into four groups (n = 12 in each group): the control, metformin, operation, and operation plus metformin groups. The animals were pretreated with metformin by gavage once daily for two weeks. The Morris water maze (MWM) was used to measure cognitive ability. In the in vitro experiment, BV2 cells were divided into five groups: the control, metformin, lipopolysaccharide (LPS), LPS plus metformin, and LPS plus metformin plus compound C groups. We stimulated microglia with LPS (500 ng/mL). Immunofluorescence and Western blotting were used to assess ROS (reactive oxygen species) levels, autophagy-associated protein levels and adenosine monophosphate-activated protein kinase (AMPK)/regulator factor 2-related enzyme 1 (SIRT1) signaling pathway activity in the rat cortex and microglial cells. RESULTS: In the MWM test, the metformin-pretreated rats spent a higher proportion of time in the target quadrant. Immunofluorescence showed that the fluorescence intensity of LC3 in the cortex was increased in rats pretreated with metformin. Western blotting indicated that metformin upregulated the expression of autophagy-related and AMPK/SIRT1 signaling pathway-related proteins in the cortex after surgery. By activating the AMPK/SIRT1 signaling pathway in vitro, metformin reduced microglial activation and oxidative stress and promoted autophagy. CONCLUSIONS: Through the AMPK/SIRT1 pathway, metformin can boost autophagy and reduce oxidative stress in cortical microglia in older rats, in turn improving postoperative cognitive function.


Subject(s)
Postoperative Cognitive Complications , Humans , Aged , Animals , Rats , Infant , Rats, Sprague-Dawley , Postoperative Cognitive Complications/prevention & control , AMP-Activated Protein Kinases , Sirtuin 1 , Lipopolysaccharides
5.
Quant Imaging Med Surg ; 13(7): 4641-4647, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37456323

ABSTRACT

Background: The transversus abdominis plane (TAP) block is a widely used, safe and effective technique for abdominal surgery analgesia, but its range of blocking is not sufficient for some surgeries requiring a large incision. Here we present the novel concept of an ultrasound-guided linea semilunaris block, a modified approach to TAP block, which can potentially offer a wider blocking range. Methods: Patients undergoing open colorectal surgery at the Shanghai Jiaotong University Affiliated Sixth People's Hospital between May and July 2021 were enrolled to receive ultrasound-guided linea semilunaris block. All blocks were performed in the holding area of the operating theater under routine hemodynamic monitoring while patients were conscious with low-dose opioids. All patients were supine, and a linear probe identified the semilunar line as the connection between the transverse and rectus muscles. Next, 20 mL of 0.25% ropivacaine was injected in the semilunar line using the in-plane technique bilaterally. The main indicator of the blocking range was measured. Postoperatively, the visual analog score (VAS) from 4 to 24 h (every 2 h), the time of the first remedial analgesia, the bowel movement starting time and complications were also recorded. Results: A total of 31 potentially eligible studies were identified for inclusion. The extent of the cutaneous sensory block was: 3.46±0.59 cm below the xiphoid, 1.74±0.37 cm above the symphysis pubis, 2.02±1.24 cm outside the left midclavicular line, and 2.19±1.25 cm outside the right midclavicular line. The highest and lowest median [interquartile range (IQR)] VAS pain scores were 4 [4-5] of 10 h and 2 [1-2] of 4 h postoperatively. The bowel movement starting time was 3.7±1.1 days after gastrointestinal surgery. There were four patients with nausea and vomiting but none had adverse reactions attributable to local anesthetic (LA) poisoning. Conclusions: The ultrasound-guided umbilical paramedian semilunaris approach to TAP block is a safe and effective technique in clinical practice, which may provide more effective analgesia than traditional TAP block for open colorectal surgery with a median abdominal incision. Further randomized controlled trials are needed to confirm our results.

6.
Front Surg ; 10: 927168, 2023.
Article in English | MEDLINE | ID: mdl-37114154

ABSTRACT

Introduction: Sepsis delays wound healing owing to uncontrolled inflammation. A single perioperative dose of dexamethasone is widely used because of its anti-inflammatory effects. However, the effects of dexamethasone on wound healing in sepsis remain unclear. Methods: We discuss the methods to obtain dose curves and explore the safe dosage range for wound healing in mice with or without sepsis. A saline or LPS intraperitoneal injection was applied to C57BL/6 mice. After 24 hours, the mice received a saline or DEX intraperitoneal injection and full-thickness, dorsal wounding operation. Wound healing was observed by image record, immunofluorescence and histological staining. Inflammatory cytokines and M1/M2 macrophages in wounds were determined by ELISA and immunofluorescence, respectively. Results: Dose-response curves reflected the safe dosage range of DEX in mice with or without sepsis, from 0.121 to 2.03 mg/kg and from 0 to 0.633 mg/kg, respectively. we found that a single dose of dexamethasone (1 mg/kg, i.p.) promoted wound healing in septic mice, but delayed wound healing in normal mice. In normal mice, dexamethasone delays inflammation, resulting in an insufficient number of macrophages during the healing process. In septic mice, dexamethasone alleviated excessive inflammation and maintained the balance of M1/M2 macrophages in the early and late healing process. Discussion: In summary, the safe dosage range of dexamethasone in septic mice is wider than that in normal mice. A single dose of dexamethasone (1 mg/kg) increased wound healing in septic mice, but delayed it in normal mice. Our findings provide helpful suggestions for the rational use of dexamethasone.

7.
Int Wound J ; 20(6): 2141-2150, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36856736

ABSTRACT

This study explored the effect of perioperative use of low-dose dexamethasone on inflammatory factors in drainage fluid and wound healing after thyroid surgery. In the prospective, double-blinded, randomised controlled study, adults who underwent elective thyroidectomy received 0.1 mg/kg of intravenous dexamethasone or a matching volume of placebo (saline) after induction of general anaesthesia. The primary outcome was IL6 and IL10 concentration in drainage at 24 hours postoperative. The secondary endpoint was the SBSES (modified Stony Brook Scar Evaluation Scale) total score at 1 week postoperative. From 8 July to 17 December 2020, 64 patients (mean [SD] age, 40.42 [9.52]; 13 males [20.31%]) were recruited, received operation, and completed the 1-month follow-up. Inflammatory factors in drainage did not differ between the two groups but only had significant differences at different timepoint. The dexamethasone group patients had a higher SBSES total score at 1 week after the treatment but, without statistical significance (dexamethasone vs placebo: 3.13 ± 1.24 vs 2.97 ± 0.93, P = .571). The dexamethasone group patients had a higher SBSES total score (dexamethasone vs placebo: 3.103 ± 1.148 vs 2.868 ± 0.827, P = .011) and colour score (dexamethasone vs placebo: 0.603 ± 0.493 vs 0.412 ± 0.496, P = .026) at 1-week follow-up than the placebo group patients. Preoperative single small-dose intravenous dexamethasone did not show to improve wound healing quality nor reduce incision inflammation but may release pain, and reduce tissue angiogenesis, and thus the scar redness.


Subject(s)
Dexamethasone , Thyroid Gland , Adult , Male , Humans , Dexamethasone/therapeutic use , Thyroid Gland/surgery , Cicatrix/drug therapy , Prospective Studies , Drainage , Perioperative Period , Wound Healing , Pain, Postoperative/drug therapy , Double-Blind Method , Treatment Outcome
8.
Lancet Reg Health West Pac ; 33: 100694, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36777445

ABSTRACT

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

9.
Front Med (Lausanne) ; 9: 830689, 2022.
Article in English | MEDLINE | ID: mdl-35602505

ABSTRACT

Background: The median effective analgesic concentration (MEAC; EC50 = effective concentration in 50% patients) of ropivacaine in sciatic nerve block guided by ultrasound (US) required for effective postoperative analgesia following arthroscopic anterior cruciate ligament (ACL) reconstruction has not yet been found. This study aimed to determine the effectiveness of MEAC of 20 ml ropivacaine of postoperative anesthesia for patients after ACL reconstruction. Methods: In total, 29 patients who underwent elective arthroscopic ACL reconstruction were enrolled in this study. All the subjects were given 20 ml of 0.2% ropivacaine for femoral nerve block. A concentration of 20 ml ropivacaine administered to the sciatic nerve was measured by applying the up-and-down sequential method (UDM). The starting concentration was 0.2% in the first patient, and the next patient received decremented 0.025% ropivacaine if the prior patient's postoperative visual analog pain score was <4 in the initial 8 h. Otherwise, the participant was given an incremental dose of 0.025% ropivacaine. The EC50 of ropivacaine was determined by using centered isotonic, linear-logarithmic, exponential regressions, and linear regression. The "goodness of fit" was compared among various models by calculating the residual standard errors. Results: The concentration of ropivacaine administered ranged from 0.1 to 0.2%. The EC50 [95% confidence interval (CI)] determined by four statistical methods (centered isotonic, exponential regressions, linear-logarithmic, and linear regression) was 0.115, 0.113% (0.108, 0.343%), 0.142% (0.112, 0.347%), and 0.129% (0.103, 0.359%), respectively. Among all models, the residual standard error was the smallest for the exponential regression (0.2243). Conclusion: The EC50 of ropivacaine in US-guided sciatic nerve block was 0.113-0.142%, and exponential regression model best matched the data.

12.
Br J Anaesth ; 126(3): 684-691, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33495020

ABSTRACT

BACKGROUND: With the increasing prevalence of children who are overweight and with obesity, anaesthesiologists must determine the optimal dosing of medications given the altered pharmacokinetics and pharmacodynamics in this population. We therefore determined the single dose of dexmedetomidine that provided sufficient sedation in 95% (ED95) of children with and without obesity as measured by a minimum Ramsay sedation score (RSS) of 4. METHODS: Forty children with obesity (BMI >95th percentile for age and gender) and 40 children with normal weight (BMI 25th-84th percentile), aged 3-17 yr, ASA physical status 1-2, undergoing elective surgery, were recruited. The biased coin design was used to determine the target dose. Positive responses were defined as achievement of adequate sedation (RSS ≥4). The initial dose for both groups was dexmedetomidine 0.3 µg kg-1 i.v. infusion for 10 min. An increment or decrement of 0.1 µg kg-1 was used depending on the responses. Isotonic regression and bootstrapping methods were used to determine the ED95 and 95% confidence intervals (CIs), respectively. RESULTS: The ED95 of dexmedetomidine for adequate sedation in children with obesity was 0.75 µg kg-1 with 95% CI of 0.638-0.780 µg kg-1, overlapping the CI of the ED95 estimate of 0.74 µg kg-1 (95% CI: 0.598-0.779 µg kg-1) for their normal-weight peers. CONCLUSIONS: The ED95 values of dexmedetomidine administered over 10 min were 0.75 and 0.74 µg kg-1 in paediatric subjects with and without obesity, respectively, based on total body weight. CLINICAL TRIAL REGISTRATION: ChiCTR1800014266.


Subject(s)
Conscious Sedation/methods , Dexmedetomidine/administration & dosage , Drug Dosage Calculations , Hypnotics and Sedatives/administration & dosage , Obesity/metabolism , Adolescent , Body Mass Index , Child , Child, Preschool , Conscious Sedation/statistics & numerical data , Dexmedetomidine/pharmacokinetics , Dose-Response Relationship, Drug , Elective Surgical Procedures , Humans , Hypnotics and Sedatives/pharmacokinetics , Infusions, Intravenous
13.
Am J Emerg Med ; 38(6): 1137-1140, 2020 06.
Article in English | MEDLINE | ID: mdl-31685304

ABSTRACT

BACKGROUND: To determine the level of inspiratory pressure minimizing the risk of gastric insufflation while providing adequate pulmonary ventilation. METHODS: In this prospective, randomized, double-blind study, patients were allocated to one of the two groups (P10, P15) defined by the inspiratory pressure applied during controlled-pressure ventilation: 10 and 15 cm H2O. Anesthesia was induced using propofol and sufentanil; no neuromuscular-blocking agent was administered. Once loss of eyelash reflex occurred, facemask ventilation was started for a 2-min period. The cross-sectional antral area was measured using ultrasonography before and after facemask ventilation. Respiratory parameters were recorded. RESULTS: Forty patients were analyzed. Mean tidal volume was about 7 ml/kg in group P10, and was >11 ml/kg in group P15 in the same period. As indicated by ultrasonography test, the antral area in P15 group was markedly incresed compared with P10 group. CONCLUSION: Inspiratory pressure of 10 cm H2O allowed for reduced occurrence of gastric insufflation with proper lung ventilation during induction of anesthesia with sufentanil and propofol in nonparalyzed and nonobese patients.


Subject(s)
Anesthesia, General/methods , Insufflation/adverse effects , Intraoperative Complications/prevention & control , Laryngeal Masks/standards , Respiration, Artificial/instrumentation , Stomach/injuries , Air Pressure , Cross-Sectional Studies , Double-Blind Method , Female , Humans , Intraoperative Complications/diagnosis , Male , Middle Aged , Prospective Studies , Stomach/diagnostic imaging , Tidal Volume , Ultrasonography
14.
World J Surg ; 43(7): 1721-1727, 2019 07.
Article in English | MEDLINE | ID: mdl-30963205

ABSTRACT

BACKGROUND: The aims of this study were to assess the effect of perioperative dexamethasone on postoperative thyroid surgery recovery using measures of wound drainage volume and C-reactive protein (CRP) levels and leukocyte counts. MATERIALS AND METHODS: From January to September 2014, healthy patients, aged between 18 and 65 years, had elective thyroid surgery in the tertiary hospital. Eligible patients were randomized into either group D (dexamethasone 0.1 mg/kg IV) or group S (saline IV) after anesthesia induction. At the end of surgery, a drainage tube was placed at the thyroid bed with a negative pressure ball connected outside the wound. Drainage fluids were collected after thyroid surgery. The fluid volume and the levels of C-reactive protein and leukocyte counts inside were analyzed. All patients were followed up for 1 month. RESULTS: The median total drainage in group D (n = 103) was 43 ml (IQR: 21-83 ml), and 68 ml (IQR: 35-104 ml) in group S (n = 111), P = 0.002. More patients in group D were discharged on postoperative day 2 (74.8% vs. 54.1%, P = 0.002). The CRP levels and leukocyte counts were much less in group D than in group S (P = 0.002 and P < 0.001, respectively). Two patients (one in each group) had wound infections 1 week after surgery that healed one additional week later. CONCLUSIONS: One perioperative small dose of dexamethasone reduced wound drainage volume and inflammatory content after thyroid surgery, thereby possibly contributing to early recovery. The effects of dexamethasone have never been evaluated before under these conditions. REGISTRATION NUMBER: NCT02304250 ( http://www.clinicaltrials.gov ).


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Dexamethasone/administration & dosage , Elective Surgical Procedures , Perioperative Care/methods , Surgical Wound Infection/prevention & control , Thyroidectomy , Adolescent , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Biomarkers/metabolism , C-Reactive Protein/metabolism , Dexamethasone/therapeutic use , Double-Blind Method , Drainage , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Injections, Intravenous , Leukocyte Count , Male , Middle Aged , Prospective Studies , Surgical Wound Infection/diagnosis , Surgical Wound Infection/metabolism , Treatment Outcome , Young Adult
16.
Br J Pharmacol ; 174(13): 1984-2000, 2017 07.
Article in English | MEDLINE | ID: mdl-28369981

ABSTRACT

BACKGROUND AND PURPOSE: Exaggerated hypotension following administration of propofol is strongly predicted in patients with hypertension. Increased PKCs play a crucial role in regulating vascular tone. We studied whether propofol induces vasodilation by inhibiting increased PKC activity in spontaneously hypertensive rats (SHRs) and, if so, whether contractile Ca2+ sensitization pathways and filamentous-globular (F/G) actin dynamics were involved. EXPERIMENTAL APPROACH: Rings of thoracic aorta, denuded of endothelium, from normotensive Wistar-Kyoto (WKY) rats and SHR were prepared for functional studies. Expression and activity of PKCs in vascular smooth muscle (VSM) cells were determined by Western blot analysis and elisa respectively. Phosphorylation of the key proteins in PKC Ca2+ sensitization pathways was also examined. Actin polymerization was evaluated by differential centrifugation to probe G- and F-actin content. KEY RESULTS: Basal expression and activity of PKCß2 and PKCθ were increased in aortic VSMs of SHR, compared with those from WKY rats. Vasorelaxation of SHR aortas by propofol was markedly attenuated by LY333531 (a specific PKCß inhibitor) or the PKCθ pseudo-substrate inhibitor. Furthermore, noradrenaline-enhanced phosphorylation, and the translocation of PKCß2 and PKCθ, was inhibited by propofol, with decreased actin polymerization and PKCß2-mediated Ca2+ sensitization pathway in SHR aortas. CONCLUSION AND IMPLICATIONS: Propofol suppressed increased PKCß2 and PKCθ activity, which was partly responsible for exaggerated vasodilation in SHR. This suppression results in inhibition of actin polymerization, as well as that of the PKCß2- but not PKCθ-mediated, Ca2+ sensitization pathway. These data provide a novel explanation for the unwanted side effects of propofol.


Subject(s)
Aorta, Thoracic/drug effects , Propofol/pharmacology , Protein Kinase C beta/antagonists & inhibitors , Protein Kinase C/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Vasodilation/drug effects , Actins/antagonists & inhibitors , Actins/metabolism , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Male , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Polymerization/drug effects , Protein Kinase C/metabolism , Protein Kinase C beta/metabolism , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Structure-Activity Relationship
17.
J Gerontol A Biol Sci Med Sci ; 72(12): 1689-1696, 2017 Nov 09.
Article in English | MEDLINE | ID: mdl-28180239

ABSTRACT

BACKGROUND: Hypotheses on the development of postoperative delirium (PD) include "neuroinflammatory," "neuronal aging," "oxidative stress," "neurotransmitter deficiency," and "neuroendocrine." Here, we employed metabolomics to determine the serum metabolites in the baseline associated with an increased risk of PD. METHODS: Two hundred and nine elderly hip-fracture patients who had undergone hemiarthroplasty and had completed our assessments were selected. Fasting venous blood was collected at 7:00 on the morning of surgery and a serum sample bank was created for analysis. On the first 3 postoperative days, the patients were assessed twice daily using the Confusion Assessment Method - Chinese Revision. Ultimately, 43 patients were diagnosed with PD, who comprised the PD group. Meanwhile, 43 matched non-PD patients were selected based on age, sex, and body mass index. Serum samples from the two groups were analyzed by gas chromatography-time-of-flight mass spectrometry and Acquity ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. RESULTS: The demographic characteristics of the groups were matched. Four metabolites associated with an increased risk of PD were identified, including S-methylcysteine, linolenic acid, eicosapentaenoic acid, and linoleic acid. CONCLUSIONS: Multiple metabolic pathways in the PD group altered before surgery, including deficiency of ω3 and ω6 fatty acids, energy metabolism and oxidative stress with interactions between hypoxia and mitochondrial dysfunction, in addition to glutamate-glutamine cycle dysfunction. These metabolic abnormalities could possibly increase the fragility of the brain and then contribute to PD.


Subject(s)
Delirium/epidemiology , Hip Fractures/blood , Hip Fractures/surgery , Metabolomics , Postoperative Complications/epidemiology , Aged , Female , Humans , Male , Preoperative Period
18.
JAMA Surg ; 152(4): 369-376, 2017 04 01.
Article in English | MEDLINE | ID: mdl-28052158

ABSTRACT

Importance: Secondary triage from nontertiary centers is vital to trauma system success. It remains unclear what factors are associated with nontransfer among patients who should be considered for transfer to facilities providing higher-level care. Objective: To identify factors associated with nontransfer among patients meeting American College of Surgeons (ACS) guideline criteria for transfer from nontertiary centers. Design, Setting, and Participants: A retrospective cohort study was performed using multilevel logistic regression to ascertain factors associated with nontransfer from nontertiary centers, including demographics, injury characteristics, and center resources. With information obtained from the National Trauma Data Bank (January 1, 2007, to December 31, 2012), relative proportion of variance in outcome across centers was determined for patient-level and center-level attributes. In all, 96 528 patients taken to nontertiary centers (levels III, IV, V, and nontrauma centers) that met ACS guideline transfer criteria were eligible for inclusion. Data analysis was performed from March 17, 2016, to May 20, 2016. Main Outcomes and Measures: The primary outcome was nontransfer from a nontertiary center. Results: Among 96 528 patients meeting ACS guideline criteria for transfer taken initially to nontertiary centers, 55 611 (57.6%) were male and the median age was 52 years (interquartile range, 28-77 years). Only 19 396 patients (20.1%) underwent transfer. Patient-level factors associated with nontransfer included age older than 65 years (adjusted odds ratio [AOR], 1.70; 95% CI, 1.46-1.98; P < .001), severe chest injury (AOR, 1.63; 95% CI, 1.42-1.89; P < .001), and commercial insurance (vs self-pay: AOR, 1.39; 95% CI, 1.15-1.67; P < .001). Center-level factors associated with nontransfer included larger bed size (>600 vs <200 beds: AOR, 9.22; 95% CI, 7.70-11.05; P < .001), nontrauma center (vs level III centers: AOR, 2.71; 95% CI, 2.44-3.01; P < .001), university affiliation (vs community: AOR, 9.68; 95% CI, 8.03-11.66; P < .001), more trauma surgeons (per surgeon: AOR, 1.08; 95% CI, 1.06-1.09; P < .001), and more neurosurgeons (per surgeon: AOR, 1.25; 95% CI, 1.23-1.28; P < .001). For-profit status was associated with nontransfer at nontrauma centers (AOR, 1.55; 95% CI, 1.39-1.74; P < .001), but not at level III, IV, and V trauma centers. Overall, patient-level factors accounted for 36% and center-level factors accounted for 58% of the variation in transfer practices. Patient-level factors accounted for more variation at level III, IV, and V trauma centers (44%), but less variation at nontrauma centers (13%). Conclusions and Relevance: Only 1 in 5 patients meeting ACS transfer criteria underwent transfer. Factors associated with nontransfer may be useful for trauma system stakeholders to target education and outreach to guide development of more inclusive trauma systems. Further study is necessary to critically evaluate whether these ACS criteria identify patients who require transfer.


Subject(s)
Guideline Adherence , Patient Selection , Patient Transfer , Trauma Centers , Wounds and Injuries/therapy , Adolescent , Adult , Aged , Female , Humans , Logistic Models , Male , Middle Aged , Practice Guidelines as Topic , Retrospective Studies , Triage , United States/epidemiology , Wounds and Injuries/mortality , Young Adult
19.
J Clin Anesth ; 35: 85-89, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27871600

ABSTRACT

STUDY OBJECTIVE: To compare the ease of laryngeal mask airway (LMA) insertion and fiberoptic view of LMA after placement using the Discopo visual stylet-guided insertion and conventional blind technique. DESIGN: Prospective, randomized controlled study. SETTING: Operating room in a university hospital. PATIENTS: One hundred adult patients scheduled for elective surgery under LMA general anesthesia were enrolled. INTERVENTIONS: Patients were randomly allocated to 2 groups: GLMA group using a visual stylet-guided technique (n=50) and BLMA group using standard blind technique (n=50). Correct placement of the LMA was confirmed using clinical test along with fiberoptic assessment. MEASUREMENTS: Unblinded data were collected about the insertion time, the first attempt success rate, the LMA position adjustment rate, fiberoptic view of LMA anatomical position, hemodynamic responses, and the adverse insertion responses (bucking, breathholding, and laryngospasm). Blinded data were recorded about postoperative airway morbidity (visible blood staining on LMA at removal, sore throat, and hoarseness). MAIN RESULTS: Insertion was more frequently successful at the first attempt in GLMA than that in BLMA group (100% vs 92%; P=.041). The time taken for establishing effective airway was shorter in GLMA than that in BLMA (54.8 vs 62.9 seconds; P=.001). The patients in BLMA group required more readjustment and reinsertion than those in GLMA group (38% vs 0%; P=.000). The fiberoptic view was significantly better in GLMA group (P<.001). No difference between the 2 groups existed regarding hemodynamic stress responses, incidences of adverse insertion responses, and postoperative airway morbidity. CONCLUSIONS: By direct visualizing the whole process of LMA insertion, the Discopo visual stylet increases the success rate and accuracy rate of LMA placement without increasing hemodynamic stress response or incidences of adverse events.


Subject(s)
Anesthesia, General/methods , Intubation, Intratracheal/instrumentation , Intubation, Intratracheal/methods , Adult , Elective Surgical Procedures , Female , Fiber Optic Technology , Hemodynamics , Humans , Intubation, Intratracheal/adverse effects , Laryngeal Masks/adverse effects , Male , Middle Aged , Pharynx/injuries , Prospective Studies , Random Allocation , Time Factors
20.
Cell Physiol Biochem ; 40(1-2): 379-390, 2016.
Article in English | MEDLINE | ID: mdl-27866196

ABSTRACT

BACKGROUND/AIMS: Phorbol myristate acetate (PMA) exerts a pleiotropic effect on the growth and differentiation of various cells. Protein kinase Cs (PKCs) plays a central role in mediating the effects of PMA on cells. The present study investigated whether the down-regulation of protein kinase C-ε (PKC-ε) is involved in the inhibition of vascular smooth muscle cell (VSMC) proliferation caused by prolonged PMA incubation. METHODS: Using cell counting, Cell Counting Kit-8 (CCK-8) and EdU incorporation assay on VSMCs, we evaluated the inhibitory effects of prolonged incubation of PMA, of lentiviruses carrying the short-hairpin RNAs (shRNA) of PKC-ε and of the PKC-ε inhibitor peptide on the proliferation and viability of cells. The effect of PKC-ε down-regulation on growth of rat breast cancer SHZ-88 cells was also measured. RESULTS: The prolonged incubation of VSMCs with PMA for up to 72 hours resulted in attenuated cell growth rates in a time-dependent manner. The expression of PKC-ε, as assessed by Western blotting, was also decreased accordingly. Notably, the number of EdU-positive cells and the cell viability of VSMCs were decreased by shRNA of PKC-ε and the PKC-ε inhibitor peptide, respectively. The proliferation of rat breast cancer SHZ-88 cells was also attenuated by lentivirus-induced shRNA silencing of PKC-ε. CONCLUSIONS: Prolonged incubation of PMA can inhibit the expression of PKC-ε. The effect results in the inhibition of VSMC proliferation. PKC-ε silencing can also attenuate breast cancer cell growth, suggesting that PKC-ε may be a potential target for anti-cancer drugs.


Subject(s)
Down-Regulation/drug effects , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/enzymology , Protein Kinase C-epsilon/metabolism , Tetradecanoylphorbol Acetate/pharmacology , Animals , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Cell Survival/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Gene Silencing/drug effects , MAP Kinase Signaling System/drug effects , Mice, Nude , Myocytes, Smooth Muscle/drug effects , RNA, Small Interfering/metabolism
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