Beyond measurement: a deep dive into the commonly used pain scales for postoperative pain assessment.

This review explores the essential methodologies for effective postoperative pain management, focusing on the need for thorough pain assessment tools, as underscored in various existing guidelines. Herein, the strengths and weaknesses of commonly used pain scales for postoperative pain-the Visual Analog Scale, Numeric Rating Scale, Verbal Rating Scale, and Faces Pain Scale-are evaluated, highlighting the importance of selecting appropriate assessment tools based on factors influencing their effectiveness in surgical contexts. By emphasizing the need to comprehend the minimal clinically important difference (MCID) for these scales in evaluating new analgesic interventions and monitoring pain trajectories over time, this review advocates recognizing the limitations of common pain scales to improve pain assessment strategies, ultimately enhancing postoperative pain management. Finally, five recommendations for pain assessment in research on postoperative pain are provided: first, selecting an appropriate pain scale tailored to the patient group, considering the strengths and weaknesses of each scale; second, simultaneously assessing the intensity of postoperative pain at rest and during movement; third, conducting evaluations at specific time points and monitoring trends over time; fourth, extending the focus beyond the intensity of postoperative pain to include its impact on postoperative functional recovery; and lastly, interpreting the findings while considering the MCID, ensuring that it is clinically significant for the chosen pain scale. These recommendations broaden our understanding of postoperative pain and provide insights that contribute to more effective pain management strategies, thereby enhancing patient care outcomes.

Symmetry Engineering of Epitaxial Hf0.5Zr0.5O2 Ultrathin Films.

Robust ferroelectricity in HfO2-based ultrathin films has the potential to revolutionize nonvolatile memory applications in nanoscale electronic devices because of their compatibility with the existing Si technology. However, to fully exploit the potential of ferroelectric HfO2-based thin films, it is crucial to develop strategies for the controlled stabilization of various HfO2-based polymorphs in nanoscale heterostructures. This study demonstrates how substrate-orientation-induced anisotropic strain can engineer the crystal symmetry, structural domain morphology, and growth orientation of ultrathin Hf0.5Zr0.5O2 (HZO) films. Epitaxial ultrathin HZO films were grown on the heterostructures of (001)- and (110)-oriented La2/3Sr1/3MnO3/SrTiO3 (LSMO/STO) substrate. Various structural analyses revealed that the (110)-oriented substrate promotes a higher degree of structural order (crystallinity) with improved stability of the (111)-oriented orthorhombic phase (Pca21) of HZO. Conversely, the (001)-oriented substrate not only induces a distorted orthorhombic structure but also facilitates the partial stabilization of nonpolar phases. Electrical measurements revealed robust ferroelectric properties in epitaxial thin films without any wake-up effect, where the well-ordered crystal symmetry stabilized by STO(110) facilitated better ferroelectric characteristics. This study suggests that tuning the epitaxial growth of ferroelectric HZO through substrate orientation can improve the stability of the metastable ferroelectric orthorhombic phase and thereby offer a better understanding of device applications.

Overview of AlphaFold2 and breakthroughs in overcoming its limitations.

Predicting three-dimensional (3D) protein structures has been challenging for decades. The emergence of AlphaFold2 (AF2), a deep learning-based machine learning method developed by DeepMind, became a game changer in the protein folding community. AF2 can predict a protein's three-dimensional structure with high confidence based on its amino acid sequence. Accurate prediction of protein structures can dramatically accelerate our understanding of biological mechanisms and provide a solid foundation for reliable drug design. Although AF2 breaks through the barriers in predicting protein structures, many rooms remain to be further studied. This review provides a brief historical overview of the development of protein structure prediction, covering template-based, template-free, and machine learning-based methods. In addition to reviewing the potential benefits (Pros) and considerations (Cons) of using AF2, this review summarizes the diverse applications, including protein structure predictions, dynamic changes, point mutation, integration of language model and experimental data, protein complex, and protein-peptide interaction. It underscores recent advancements in efficiency, reliability, and broad application of AF2. This comprehensive review offers valuable insights into the applications of AF2 and AF2-inspired AI methods in structural biology and its potential for clinically significant drug target discovery.

GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain.

The function of peripheral nociceptors, the neurons that relay pain signals to the brain, are frequently tuned by local and systemic modulator substances. In this context, neurohormonal effects are emerging as an important modulatory mechanism, but many aspects remain to be elucidated. Here we report that gonadotropin-releasing hormone (GnRH), a brain-specific neurohormone, can aggravate pain by acting on nociceptors in mice. GnRH and GnRHR, the receptor for GnRH, are expressed in a nociceptor subpopulation. Administration of GnRH and its analogue, localized for selectively affecting the peripheral neurons, deteriorated mechanical pain, which was reproducible in neuropathic conditions. Nociceptor function was promoted by GnRH treatment in vitro, which appears to involve specific sensory transient receptor potential ion channels. These data suggest that peripheral GnRH can positively modulate nociceptor activities in its receptor-specific manner, contributing to pain exacerbation. Our study indicates that GnRH plays an important role in neurohormonal pain modulation via a peripheral mechanism.

Effect of an intravenous acetaminophen/ibuprofen fixed-dose combination on postoperative opioid consumption and pain after video-assisted thoracic surgery: a double-blind randomized controlled trial.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) often induces significant postoperative pain, potentially leading to chronic pain and decreased quality of life. This study aimed to evaluate the acetaminophen/ibuprofen combination effectiveness in reducing analgesic requirements and pain intensity in patients undergoing VATS. STUDY DESIGN: This is a double-blinded randomized controlled trial. METHODS: Adult patients scheduled for elective VATS for lung resection were randomized to receive either intravenous acetaminophen and ibuprofen (intervention group) or 100 mL normal saline (control group). Treatments were administered post-anesthesia induction and every 6 h for three cycles. The primary outcome was total analgesic consumption at 24 h postoperatively. Secondary outcomes were cumulative analgesic consumption at 2 and 48 h; analgesic-related side effects at 2, 24, and 48 h; quality of recovery at 24 h and 48 h postoperatively; pain intensity at rest and during coughing; and rescue analgesics use. Chronic postsurgical pain (CPSP) was assessed through telephone interviews 3 months postoperatively. RESULTS: The study included 96 participants. The intervention group showed significantly lower analgesic consumption at 24 h and 48 h postoperatively (24 h: median difference: - 100 µg equivalent intravenous fentanyl [95% confidence interval (CI) - 200 to - 5 µg], P = 0.037; 48 h: median difference: - 140 µg [95% CI - 320 to - 20 µg], P = 0.035). Compared to the controls, the intervention group exhibited a significantly lower quality of recovery 24 h post-surgery, with no significant difference at 48 h. All pain scores except for coughing at 48 h post-surgery were significantly lower in the intervention group compared to the controls. No significant differences were observed between the groups in postoperative nausea and vomiting occurrence, hospital stay length, and CPSP. CONCLUSION: Perioperative administration of acetaminophen/ibuprofen significantly decreased analgesic needs in patients undergoing VATS, providing an effective postoperative pain management strategy, and potentially minimizing the need for stronger analgesics.

Influence of Aza-Glycine Substitution on the Internalization of Penetratin.

The cell-penetrating peptide (CPP) penetratin has gained much attention over many years due to its potential role as a transporter for a broad range of cargo into cells. The modification of penetratin has been extensively investigated too. Aza-peptides are peptide analogs in which one or more of the amino residues are replaced by a semicarbazide. This substitution results in conformational restrictions and modifications in hydrogen bonding properties, which affect the structure and may lead to enhanced activity and selectivity of the modified peptide. In this work, the Trp residues of penetratin were substituted by aza-glycine or glycine residues to examine the effect of these modifications on the cellular uptake and the internalization mechanism. The substitution of Trp48 or Trp48,56 dramatically reduced the internalization, showing the importance of Trp48 in cellular uptake. Interestingly, while aza-glycine in the position of Trp56 increased the cellular uptake, Gly reduced it. The two Trp-modified derivatives showed altered internalization pathways, too. Based on our knowledge, this is the first study about the effect of aza-amino acid substitution on the cell entry of CPPs. Our results suggest that aza-amino acid insertion is a useful modification to change the internalization of a CPP.

Intraoperative Normal Saline Administration and Acute Kidney Injury in Patients Undergoing Liver Transplantation.

BACKGROUND: Normal saline is still used in patients undergoing living donor liver transplantation (LDLT) with normonatremia. We investigated whether the normal saline administered during LDLT is associated with the increased risk of acute kidney injury (AKI) compared with the balanced crystalloids. METHODS: We reviewed 1011 cases undergoing LDLT. The primary exposure variable was normal saline administered intraoperatively compared with the balanced crystalloid. To compare the risk of AKI after adjusting for potential confounders of baseline characteristics and surgical parameters, a propensity score matching analysis was performed. As a sensitivity analysis, ordinal logistic regression analysis was performed for AKI using inverse probability of treatment weighting (IPTW). RESULTS: The incidence of AKI was significantly higher in the saline group (n = 88/174, 50.6%) than in the balanced group (n = 67/174, 38.5%) after matching (P = .010). The incidence of stage 2 or 3 AKI was also significantly higher in the saline group (n = 26/174, 14.9%) than in the balanced group (n = 43/174, 24.7%) after matching (P = .022). The length of hospital stay was significantly longer in the saline group than in the balanced group after matching. Ordinal logistic regression analysis using IPTW showed that the saline group showed a significant association of saline administration with the risk of AKI (odds ratio 1.23, 95% CI 1.05-1.28, P = .013). CONCLUSION: Our propensity score analysis using propensity score matching and IPTW showed that normal saline administration during LDLT is associated with a high risk of postoperative AKI and longer hospital stays. However, our results should be interpreted carefully due to the relatively long period of data collection.

Challenging issues of implementing enhanced recovery after surgery programs in South Korea.

This review discusses the challenges of implementing enhanced recovery after surgery (ERAS) programs in South Korea. ERAS is a patient-centered perioperative care approach that aims to improve postoperative recovery by minimizing surgical stress and complications. While ERAS has demonstrated significant benefits, its successful implementation faces various barriers such as a lack of manpower and policy support, poor communication and collaboration among perioperative members, resistance to shifting away from outdated practices, and patient-specific risk factors. This review emphasizes the importance of understanding these factors to tailor effective strategies for successful ERAS implementation in South Korea's unique healthcare setting. In this review, we aim to shed light on the current status of ERAS in South Korea and identify key barriers. We hope to encourage Korean anesthesiologists to take a leading role in adopting the ERAS program as the standard for perioperative care. Ultimately, our goal is to improve the surgical outcomes of patients using this proactive approach.

The impact of preoperative coronavirus disease 19 infection on early postoperative mortality during the vaccination era: a nationwide retrospective cohort study.

BACKGROUND: We aimed to investigate the optimal surgical timing in patients with preoperative coronavirus disease 2019 (COVID-19) infection to minimize postoperative morbidity and mortality during the COVID-19 vaccination era. METHODS: The Korean nationwide data on patients who underwent standard surgery under general anesthesia in 2021 were analyzed. Patients were categorized based on the time from COVID-19 diagnosis to surgery: 0-4, 5-8, > 8 weeks, and those without preoperative COVID-19 infection. Multivariable logistic regression analysis, considering preoperative COVID-19 vaccination status (fully vaccinated vs. unvaccinated or partially vaccinated), was performed to associate the preoperative COVID-19 infection timing with 30- and 90-day postoperative mortality and 30-day respiratory complications. RESULTS: Among the 750,175 included patients, 28.2% were preoperatively fully vaccinated. Compared with patients without prior COVID-19 infection, those who had surgery 0-4 weeks (adjusted odds ratio [OR]: 4.28, 95% CI [1.81, 10.13], P = 0.001) and 5-8 weeks (adjusted OR: 3.38, 95% CI [1.54, 7.44], P = 0.002) after COVID-19 infection had a significantly increased risk of 30-day mortality. Preoperative full vaccination was significantly associated with a decrease in 90-day mortality (adjusted OR: 0.93, 95% CI [0.89, 0.98], P = 0.007) and 30-day respiratory complications (adjusted OR: 0.85, 95% CI [0.82, 0.87], P < 0.001), but not with 30-day mortality (P = 0.916). CONCLUSIONS: COVID-19 infection eight weeks preoperatively was associated with an increased 30-day postoperative mortality. Preoperative full vaccination was not associated with 30-day mortality but was related to lower risk of 90-day mortality and 30-day respiratory complications.

Current status of opioid prescription in South Korea using narcotics information management system.

Background: Recognizing the seriousness of the misuse and abuse of medical narcotics, the South Korean government introduced the world's first narcotic management system, the Narcotics Information Management System (NIMS). This study aimed to explore the recent one-year opioid prescribing patterns in South Korea using the NIMS database. Methods: This study analyzed opioid prescription records in South Korea for the year 2022, utilizing the dispensing/administration dataset provided by NIMS. Public data from the Korean Statistical Information Service were also utilized to explore prescription trends over the past four years. The examination covered 16 different opioid analgesics, assessed by the total number of units prescribed based on routes of administration, type of institutions, and patients' sex and age group. Additionally, the disposal rate for each ingredient was computed. Results: In total, 206,941 records of 87,792,968 opioid analgesic units were analyzed. Recently, the overall quantity of prescribed opioid analgesic units has remained relatively stable. The most prescribed ingredient was oral oxycodone, followed by tapentadol and sublingual fentanyl. Tertiary hospitals had the highest number of dispensed units (49.4%), followed by community pharmacies (40.2%). The highest number of prescribed units was attributed to male patients in their 60s. The disposal rates of the oral and transdermal formulations were less than 0.1%. Conclusions: Opioid prescription in South Korea features a high proportion of oral formulations, tertiary hospital administration, pharmacy dispensing, and elderly patients. Sustained education and surveillance of patients and healthcare providers is required.

Randomized controlled trial of the effect of general anesthetics on postoperative recovery after minimally invasive nephrectomy.

BACKGROUND: General anesthetic techniques can affect postoperative recovery. We compared the effect of propofol-based total intravenous anesthesia (TIVA) and desflurane anesthesia on postoperative recovery. METHODS: In this randomized trial, 150 patients undergoing robot-assisted or laparoscopic nephrectomy for renal cancer were randomly allocated to either the TIVA or desflurane anesthesia (DES) group. Postoperative recovery was evaluated using the Korean version of the Quality of Recovery-15 questionnaire (QoR-15K) at 24 h, 48 h, and 72 h postoperatively. A generalized estimating equation (GEE) was performed to analyze longitudinal QoR-15K data. Fentanyl consumption, pain severity, postoperative nausea and vomiting, and quality of life three weeks after discharge were also compared. RESULTS: Data were analyzed for 70 patients in each group. The TIVA group showed significantly higher QoR-15K scores at 24 and 48 h postoperatively (24 h: DES, 96 [77, 109] vs. TIVA, 104 [82, 117], median difference 8 [95% CI: 1, 15], P = 0.029; 48 h: 110 [95, 128] vs. 125 [109, 130], median difference 8 [95% CI: 1, 15], P = 0.022), however not at 72 h (P = 0.400). The GEE revealed significant effects of group (adjusted mean difference 6.2, 95% CI: 0.39, 12.1, P = 0.037) and time (P < 0.001) on postoperative QoR-15K scores without group-time interaction (P = 0.051). However, there were no significant differences in other outcomes, except for fentanyl consumption, within the first 24 h postoperatively. CONCLUSIONS: Propofol-based TIVA showed only a transient improvement in postoperative recovery than desflurane anesthesia, without significant differences in other outcomes.

Dual-channel fluorescent probe for discriminative detection of H2S and N2H4: Exploring sensing mechanism and real-time applications.

A highly efficient system incorporates the real-time visualization of the two toxic molecules (H2S and N2H4) and the recognition of corresponding transforms using a fluorescent sensor. In this paper, a dual-responsive probe (QS-DNP) based on methylquinolinium-salicyaldehyde-2,4-dinitrophenyl was developed that can simultaneously detect H2S and N2H4 at two independent fluorescent channels without signal crosstalk. QS-DNP showed excellent anti-interference, high selectivity, outstanding water solubility, low LOD values (H2S: 51 nM; N2H4: 40 nM), low cytotoxicity, and mitochondrial localization properties. The 2,4-dinitrophenyl site was sensitive to H2S, and the CC bridge was reactive to N2H4, with strong fluorescence at 680 and 488 nm, respectively. The wavelength gap between these two channels is 192 nm; verify that there is no signal crosstalk throughout detection. By this means, the probe was used to simultaneously detect H2S and N2H4 in real soil samples, food samples, and living cells. The endogenous H2S and N2H4 were monitored in HeLa cells and investigated the mitochondria organelle of living cells with a positive charge on QS-DNP. Overall, all results emphasize that the QS-DNP probe is a powerful tool for the simultaneous detection of H2S and N2H4 and presents a potential new sensing approach.

The verification of delta SCF and Slater's transition state theory for the calculation of core ionization energy.

The core ionization energies of second- and third-period elements of the molecules C2 H5 NO2 , SiF4 , Si(CH3 )4 , PF3 , POF3 , PSF3 , CS2 , OCS, SO2 , SO2 F2 , CH3 Cl, CFCl3 , SF5 Cl, and Cl3 PS are calculated by using Hartree-Fock (HF), and Kohn-Sham (KS) with BH&HLYP, B3LYP, and LC-BOP functionals. We used ΔSCF, Slater's transition state (STS), and two previously proposed shifted STS (1) and shifted STS (2) methods, which have been developed. The errors of ΔSCF and STS come mainly from the self-interaction errors (SIE) and can be corrected with a shifting scheme. In this study, we used the shifting parameters determined for each atom. The shifted STS (1) reproduces ΔSCF almost perfectly with mean absolute deviations (MAD) of 0.02 eV. While ΔSCF and STS vary significantly depending on the functional used, the variation of shifted STS (2) is small, and all shifted STS (2) values are close to the observed ones. The deviations of the shifted STS (2) from the experiment are 0.24 eV (BH&HLYP), 0.19 eV (B3LYP), and 0.23 eV (LC-BOP). These results further support the use of shifted STS methods for predicting the core ionization energies.

Comparison of invasive and non-invasive measurements of cardiac index and systemic vascular resistance in living-donor liver transplantation: a prospective, observational study.

BACKGROUND: Based on the controversy surrounding pulmonary artery catheterization (PAC) in surgical patients, we investigated the interchangeability of cardiac index (CI) and systemic vascular resistance (SVR) measurements between ClearSight™ and PAC during living-donor liver transplantation (LDLT). METHODS: This prospective study included consecutively selected LDLT patients. ClearSight™-based CI and SVR measurements were compared with those from PAC at seven LDLT-stage time points. ClearSight™-based systolic (SAP), mean (MAP), and diastolic (DAP) arterial pressures were also compared with those from femoral arterial catheterization (FAC). For the comparison and analysis of ClearSight™ and the reference method, Bland-Altman analysis was used to analyze accuracy while polar and four-quadrant plots were used to analyze the trending ability. RESULTS: From 27 patients, 189 pairs of ClearSight™ and reference values were analyzed. The CI and SVR performance errors (PEs) exhibited poor accuracy between the two methods (51.52 and 51.73%, respectively) in the Bland-Altman analysis. CI and SVR also exhibited unacceptable trending abilities in both the polar and four-quadrant plot analyses. SAP, MAP, and DAP PEs between the two methods displayed favorable accuracy (24.28, 21.18, and 26.26%, respectively). SAP and MAP exhibited acceptable trending ability in the four-quadrant plot between the two methods, but not in the polar plot analyses. CONCLUSIONS: During LDLT, CI and SVR demonstrated poor interchangeability, while SAP and MAP exhibited acceptable interchangeability between ClearSight™ and FAC.

Pulmonary artery catheter monitoring versus arterial waveform-based monitoring during liver transplantation: a retrospective cohort study.

Although pulmonary artery catheter (PAC) has been used during liver transplantation surgery, the usefulness of PAC has rarely been investigated. We evaluated whether the use of PAC is associated with better clinical outcomes compared to arterial waveform-based monitoring after liver transplantation. A total of 1565 cases undergoing liver transplantation were reviewed. We determined whether patients received PAC or not and divided our cohort into the PAC with hemodynamic monitoring using PAC and the non-PAC with arterial waveform-based monitoring using FloTrac-Vigileo. Propensity score matching was performed. Acute kidney injury (AKI), early allograft dysfunction (EAD) and 1-year all-cause mortality or graft failure were compared in the matched cohorts. Logistic regression analysis was performed in the inverse probability of treatment-weighted (IPTW) cohort for postoperative EAD and AKI, respectively. Five-year overall survival was compared between the two groups. In the matched cohort, there was no significant difference in the incidence of AKI, EAD, length of hospital or ICU stay, and 1-year all-cause mortality between the groups. In the IPTW cohort, the use of PAC was not a significant predictor for AKI or EAD (AKI: odds ratio (95% confidence interval) of 1.20 (0.47-1.56), p = 0.229; EAD: 0.99 (0.38-1.14), p = 0.323). There was no significant difference in the survival between groups after propensity score matching (Log-rank test p = 0.578). In conclusion, posttransplant clinical outcomes were not significantly different between the groups with and without PAC. Anesthetic management without the use of PAC may be possible in low-risk patients during liver transplantation. The risk should be carefully assessed by considering MELD scores, ischemic time, surgical history, previous treatment of underlying liver disease, and degree of portal and pulmonary hypertension.Registration: https://clinicaltrials.gov/ct2/show/NCT05457114 (registration date: July 15, 2022).

Ions-Silica Percolated Ionic Dielectric Elastomer Actuator for Soft Robots.

Soft robotics systems are currently under development using ionic electroactive polymers (i-EAP) as soft actuators for the human-machine interface. However, this endeavor has been impeded by the dilemma of reconciling the competing demands of force and strain in i-EAP actuators. Here, the authors present a novel design called "ions-silica percolated ionic dielectric elastomer (i-SPIDER)", which exhibits ionic liquid-confined silica microstructures that effectively resolve the chronic issue of conventional i-EAP actuators. The i-SPIDER actuator demonstrates remarkable electromechanical conversion capacity at low voltage, thanks to improved ion accumulation facilitated by interpreting electrode polarization at the electrolyte-electrode interface. This approach concurrently enhances both strain (by approximately 1.52%) and force (by roughly 1.06 mN) even at low Young's modulus (merely 5.9 MPa). Additionally, by demonstrating arachnid-inspired soft robots endowed with user-desired tasks through control of various form factors, the development of soft robots using the i-SPIDER that can concomitantly enhance strain and force holds promise as a compelling avenue for ushering in the next generation of miniaturized, low-powered soft robotics.

Correlation Between Pain Intensity and Quality of Recovery After Video-Assisted Thoracic Surgery for Lung Cancer Resection.

Purpose: The Quality of Recovery-15 (QoR-15) questionnaire provides a multifaceted assessment of postoperative recovery, and the resulting score is recommended as an endpoint in clinical studies focused on postoperative pain. We aimed to investigate the correlation between the QoR-15 score and postoperative pain intensity in surgical patients. Patients and Methods: Adult patients who underwent video-assisted thoracoscopic surgery (VATS) for lung cancer resection and were enrolled in a prospective registry or in a previous prospective study were included in this study. Baseline and perioperative data, including the results of assessment using the Korean version of the QoR-15 (QoR-15K) questionnaire at 48 hours postoperatively, were collected from the database. Correlations between the QoR-15K total score, questionnaire dimensions, and postoperative pain intensity at 48 hours postoperatively were determined using the Spearman correlation coefficient (ρ). Results: We analyzed a total of 137 eligible patients. Significant negative correlations were noted between the QoR-15K total score and pain intensity at rest (ρ = -0.45, 95% confidence interval [CI]: -0.57 - -0.31, P < 0.001) and during coughing (ρ = -0.55, 95% CI: -0.65 - -0.42, P < 0.001) at 48 hours postoperatively. The pain dimension and pain intensity at 48 hours postoperatively showed significant correlations with physical comfort, emotional state, and physical independence dimensions. Multivariable logistic regression revealed a significant negative association between the pain score at 24 hours postoperatively and good or excellent postoperative recovery. Conclusion: The results support the impact of postoperative pain on the overall postoperative quality of recovery in patients who underwent VATS for lung cancer resection. Moreover, the QoR-15K score may be considered as a primary endpoint in clinical studies on postoperative pain control.

The effect of high perioperative inspiratory oxygen fraction for abdominal surgery on surgical site infection: a systematic review and meta-analysis.

Guidelines from the World Health Organization strongly recommend the use of a high fraction of inspired oxygen (FiO2) in adult patients undergoing general anesthesia to reduce surgical site infection (SSI). However, previous meta-analyses reported inconsistent results. We aimed to address this controversy by focusing specifically on abdominal surgery with relatively high risk of SSI. Medline, EMBASE, and Cochrane CENTRAL databases were searched. Randomized trials of abdominal surgery comparing high to low perioperative FiO2 were included, given that the incidence of SSI was reported as an outcome. Meta-analyses of risk ratios (RR) were performed using a fixed effects model. Subgroup analysis and meta-regression were employed to explore sources of heterogeneity. We included 27 trials involving 15977 patients. The use of high FiO2 significantly reduced the incidence of SSI (n = 27, risk ratio (RR): 0.87; 95% confidence interval (CI): 0.79, 0.95; I2 = 49%, Z = 3.05). Trial sequential analysis (TSA) revealed that z-curve crossed the trial sequential boundary and data are sufficient. This finding held true for the subgroup of emergency operations (n = 2, RR: 0.54; 95% CI: 0.35, 0.84; I2 = 0%, Z = 2.75), procedures using air as carrier gas (n = 9, RR: 0.79; 95% CI: 0.69, 0.91; I2 = 60%, Z = 3.26), and when a high level of FiO2 was maintained for a postoperative 6 h or more (n = 9, RR: 0.68; 95% CI: 0.56, 0.83; I2 = 46%, Z = 3.83). Meta-regression revealed no significant interaction between SSI with any covariates including age, sex, body-mass index, diabetes mellitus, duration of surgery, and smoking. Quality of evidence was assessed to be moderate to very low. Our pooled analysis revealed that the application of high FiO2 reduced the incidence of SSI after abdominal operations. Although TSA demonstrated sufficient data and cumulative analysis crossed the TSA boundary, our results should be interpreted cautiously given the low quality of evidence.Registration: https://www.crd.york.ac.uk/prospero (CRD42022369212) on October 2022.

Computational Investigation of Conformational Properties of Short Azapeptides: Insights from DFT Study and NBO Analysis.

Azapeptides have gained much attention due to their ability to enhance the stability and bioavailability of peptide drugs. Their structural preferences, essential to understanding their function and potential application in the peptide drug design, remain largely unknown. In this work, we systematically investigated the conformational preferences of three azaamino acid residues in tripeptide models, Ac-azaXaa-Pro-NHMe [Xaa = Asn (4), Asp (5), Ala (6)], using the popular DFT functionals, B3LYP and B3LYP-D3. A solvation model density (SMD) was used to mimic the solvation effect on the conformational behaviors of azapeptides in water. During the calculation, we considered the impact of the amide bond in the azapeptide models on the conformational preferences of models 4-6. We analyzed the effect of the HB between the side-chain main chain and main-chain main-chain on the conformational behaviors of azapeptides 4-6. We found that the predicted lowest energy conformation for the three models differs depending on the calculation methods. In the gas phase, B3LYP functional indicates that the conformers tttANP-1 and tttADP-1 of azapeptides 4 and 5 correspond to the type I of ß-turn, the lowest energy conformation with all-trans amide bonds. Considering the dispersion correction, B3LYP-D3 functional predicts the conformers tctANP-2 and tctADP-3 of azapeptide 4 and 5, which contain the cis amide bond preceding the Pro residue, as the lowest energy conformation in the gas phase. The results imply that azaAsx and Pro residues may involve cis-trans isomerization in the gas phase. In water, the predicted lowest energy conformer of azapeptides 4 and 5 differs from the gas phase results and depends on the calculational method. For azapeptide 6, regardless of calculation methods and phases, tttAAP-1 (ß-I turn) is predicted as the lowest energy conformer. The results imply that the effect of the side chain that can form HBs on the conformational preferences of azapeptides 4 and 5 may not be negligible. We compared the theoretical results of azaXaa-Pro models with those of Pro-azaXaa models, showing that incorporating azaamino acid residue in peptides at different positions can significantly impact the folding patterns and stability of azapeptides.