The impact of perioperative ketamine or esketamine on the subjective quality of recovery after surgery: a meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to evaluate the impact of ketamine/esketamine on postoperative subjective quality of recovery (QoR). METHODS: MEDLINE, Embase, Cochrane library, and Google Scholar were searched for randomised controlled trials (RCTs) that examined the impacts of perioperative ketamine/esketamine use and postoperative QoR. The primary outcome was subjective QoR (QoR-9, QoR-15, QoR-40) on postoperative day (POD) 1-3, whereas the secondary outcomes included pain severity, anxiety scores, depression scores, risk of adverse events (i.e. nausea, vomiting, dizziness, drowsiness), and length of stay. RESULTS: The analysis included 18 RCTs (1554 participants; ketamine: seven trials, esketamine: 11 trials), of which 15 were conducted in China. Ketamine/esketamine improved the QoR scores on PODs 1 and 2 compared with the control (standardised mean difference [SMD]: 0.63, P<0.0001 for POD 1; SMD: 0.56, P=0.04 for POD 2), without beneficial effect on POD 3. Subgroup analyses revealed significant differences in QoR scores on POD 1 by regimen (SMD: esketamine 1.14, ketamine 0.01) and country (SMD: China 0.82, other countries -0.21). The emotional domain of QoR was improved from PODs 1 to 3, whereas the other domains were only improved on POD 1. Lower postoperative anxiety (SMD: -0.48, P=0.003) and depression (SMD: -0.72, P=0.001) scores were also observed with ketamine/esketamine use. Furthermore, pain severity was reduced on PODs 1 and 2, with no difference in the risk of adverse events or length of stay. CONCLUSIONS: This meta-analysis demonstrated that ketamine/esketamine use in the perioperative period is associated with improved early subjective QoR, pain severity, and psychological symptoms without an increase in the likelihood of adverse events. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023477580).

Are current wound classifications valid for predicting prognosis in people treated for limb-threatening diabetic foot ulcers?

This study aims to investigate whether the current wound classifications were valid for the treatment prognosis of subjects treated for limb-threatening diabetic foot ulcers (LTDFU). A total of 1548 patients with LTDFU and infection were studied, with wounds recorded using the Wagner, Texas, PEDIS and WIfI classifications while major lower extremity amputations (LEAs) or in-hospital mortality incidences were defined as poor outcomes. Among them, 153 (9.9%) patients received major LEAs and 38 (2.5%) patients died. After adjustments, the Wagner classification and Texas stage as well as clinical factors such as comorbidity with major adverse cardiac events (MACE), being under dialysis and having serum levels of C-reactive protein (CRP) and albumin were independent factors for prognosis. For patients without dialysis, Wagner and Texas stage stood out independently for prognosis. For patients on dialysis, only levels of CRP (odds ratio [OR] = 2.2 in Wagner, OR = 2.0 in WIfI, OR = 2.2 in Texas, OR = 2.3 in PEDIS) and albumin (OR = 0.4 in four classifications) were valid predictors. The Wagner system and Texas stage were valid for predicting prognosis in treatment for LTDFUs, suggesting a role of vascular perfusion. MACE history, levels of CRP and albumin level should assist in prediction; more significantly, only levels of CRP and albumin appeared valid for those subjects undergoing dialysis.

A combined bioinformatics and experimental approach identifies RMI2 as a Wnt/ß-catenin signaling target gene related to hepatocellular carcinoma.

BACKGROUND: The Wnt/ß-catenin signaling pathway plays an important role in embryogenesis and tumorigenesis. In human cancer, abnormal activity of Wnt/ß-catenin signaling pathway induces overexpressed of downstream genes, and initiate oncogene. There are several target genes known to be key players in tumorigenesis, such as c-myc, cyclin D1, MMPs or survivin. Therefore, identifying the target genes of Wnt/ß-catenin signaling pathway is important to understanding Wnt/ß-catenin-mediated carcinogenesis. In this study, we developed a combined bioinformatics and experimental approach to find potential target genes. METHODS: Luciferase reporter assay was used to analyze the promoter activity of RMI2. WST1 cell proliferation assays and transwell assays were performed to determine the proliferation and migration capacities of RMI2 overexpressing or knockdown stable hepatic cells. Finally, xenograft experiments were performed to measure the tumor formation capacity in vivo. RESULTS: The results showed that RMI2 mRNA was upregulated after LiCl treatment and Wnt3a-conditioned medium in a culture of SK-hep-1 cell lines. A chromatin immunoprecipitation (ChIP) assay showed that the ß-catenin/T cell-specific factor (TCF) complex binds to the putative TCF binding site of the RMI2 promoter. We then found a TCF binding site at - 333/- 326 of the RMI2 promoter, which is crucial for ß-catenin responsiveness in liver cell lines. RMI2 was overexpressed in hepatoma tissue and cell lines, and it promoted the migration and invasion of HCC cells. Moreover, RMI2 upregulated the expression of epithelial-mesenchymal transition (EMT) markers and the Wnt3a/ß-catenin-related genes, but silencing RMI2 had the opposite effects. Notably, the expression of RMI2 was positively correlated with the clinical data of HCC patients who had significantly shorter overall survival (OS) and disease-free survival (DFS) (Both: P < 0.05). In addition, a total of 373 HCC patients' data from the Caner Genome Atlas project (TCGA) were used to validate our findings. CONCLUSIONS: Taking all these findings together, we determined that RMI2 was a new target gene of the Wnt/ß-catenin signaling pathway. We also found that RMI2 promotes EMT markers, HCC cell invasion, and metastasis, which indicated that RMI2 is a potential target for preventing or at least mitigating the progression of HCC.

Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: 2022 update.

Osteoporosis greatly increases the risk of fractures. Osteoporotic fractures negatively impact quality of life, increase the burden of care, and increase mortality. Taiwan is an area with a high prevalence of osteoporosis. This updated summary of guidelines has been developed by experts of the Taiwan Osteoporosis Association with the intention of reducing the risks of osteoporotic fractures and improving the quality of care for patients with osteoporosis. The updated guidelines compile the latest evidence to provide clinicians and other healthcare professionals with practical recommendations for the prevention, diagnosis, and management of osteoporosis under clinical settings in Taiwan.

Association of scalp block with intraoperative hemodynamic profiles and postoperative pain outcomes at 24-48 hours following craniotomy: An updated systematic review and meta-analysis of randomized controlled studies.

BACKGROUND: Despite the demonstrated analgesic efficacy of scalp block (SB) during the immediate postoperative period, the impact of SB on pain outcomes at postoperative 24 and 48 h in adults receiving craniotomy remains unclear. METHODS: The databases of Medline, Embase, and Cochrane Central Register were searched from inception to January 2022 for available randomized controlled trials (RCTs). The primary outcome was the severity of pain at postoperative 24 and 48 h, while the secondary outcomes included morphine consumption, hemodynamic profiles after surgical incision and in the postanesthesia care unit (PACU), and risk of postoperative nausea/vomiting (PONV). RESULTS: Meta-analysis of 12 studies revealed a lower pain score [MD = -0.83, p = 0.03, 375 patients, certainty of evidence (COE): low] and morphine consumption (MD = -9.21 mg, p = 0.03, 246 patients, COE: low) at postoperative 24 h, while there were no differences in these pain outcomes at postoperative 48 h (COE: low). The use of SB significantly decreased intraoperative heart rate (MD = -10.9 beats/min, p < 0.0001, 189 patients, COE: moderate) and mean blood pressure (MD = -13.02 mmHg, p < 0.00001, 189 patients, COE: moderate) after surgical incision, but these hemodynamic profiles were comparable in both groups in the PACU setting. There was also no difference in the risk of PONV between the two groups (RR = 0.78, p = 0.2, 299 patients, COE: high). CONCLUSION: This meta-analysis demonstrated that scalp block not only provided hemodynamic stability immediately after surgical incision but was also associated with a lower pain score and morphine consumption at postoperative 24 h. Further studies are needed for elucidation of its findings.

Tuning surface d bands with bimetallic electrodes to facilitate electron transport across molecular junctions.

Understanding chemical bonding and conductivity at the electrode-molecule interface is key for the operation of single-molecule junctions. Here we apply the d-band theory that describes interfacial interactions between adsorbates and transition metal surfaces to study electron transport across these devices. We realized bimetallic Au electrodes modified with a monoatomic Ag adlayer to connect α,ω-alkanoic acids (HO2C(CH2)nCO2H). The force required to break the molecule-electrode binding and the contact conductance Gn=0 are 1.1 nN and 0.29 G0 (the conductance quantum, 1 G0 = 2e2/h ≈ 77.5 µS), which makes these junctions, respectively, 1.3-1.8 times stronger and 40-60-fold more conductive than junctions with bare Au or Ag electrodes. A similar performance was found for Au electrodes modified by Cu monolayers. By integrating the Newns-Anderson model with the Hammer-Nørskov d-band model, we explain how the surface d bands strengthen the adsorption and promote interfacial electron transport, which provides an alternative avenue for the optimization of molecular electronic devices.

The effect of cricoid pressure on tracheal intubation in adult patients: a systematic review and meta-analysis.

PURPOSE: This meta-analysis aimed to assess the impact of cricoid pressure (CP) application on intubation outcomes. SOURCE: Electronic databases (i.e., MEDLINE, PubMed, Embase, and Cochrane review) were searched from inception to 2 June 2020 for randomized-controlled trials that assessed the intubation outcomes in adult patients using laryngoscopic approaches with and without the application of CP (i.e., CP vs non-CP group). The primary outcome was the successful first-attempt intubation rate (SFAIR), and the secondary outcomes were intubation time, incidences of poor laryngoscopic views (i.e., Cormack and Lehane grade 3-4), airway complications, and pulmonary aspiration. PRINCIPAL FINDINGS: A total of five trials (published from 2005 to 2018) were included, and all tracheal intubations were performed by anesthesiologists or nurse anesthetists with a video (n = 3) or Macintosh laryngoscope (n = 2) in the operating room. We found no significant difference in SFAIR (risk ratio [RR], 0.98; P = 0.37), incidence of poor laryngoscopic views (RR, 1.49; P = 0.21), and risk of sore throat (RR, 1.17; P = 0.73) between the two groups. Nevertheless, the intubation time on the first successful attempt was slightly longer (weighted mean difference = 4.40 sec, P = 0.002) and risk of hoarseness was higher (RR, 1.70; P = 0.03) in the CP group compared with in the non-CP group. The secondary outcome "pulmonary aspiration" was not analyzed because only one trial was available. CONCLUSION: The application of CP did not have a negative impact on the SFAIR or laryngoscopic view. Nevertheless, this maneuver may slightly prolong intubation time and increase the risk of postoperative hoarseness.

RéSUMé: OBJECTIF : Cette méta-analyse a pour but d'évaluer l'impact de l'application d'une pression cricoïdienne (PC) sur les résultats de l'intubation. SOURCE : Les bases de données électroniques (c.-à-d., MEDLINE, PubMed, Embase, et Cochrane review) ont été examinées de leur création jusqu'au 2 juin 2020 pour en tirer les études randomisées contrôlées évaluant les résultats d'intubation chez les patients adultes utilisant des approches laryngoscopiques avec ou sans application de PC (soit groupe PC et non-PC). Le critère d'évaluation principal était le taux d'intubations réussies à la première tentative, et les critères secondaires incluaient le temps d'intubation, l'incidence de mauvaises vues laryngoscopies (grades 3-4 de Cormack et Lehane), les complications au niveau des voies aériennes et l'aspiration pulmonaire. CONSTATATIONS PRINCIPALES : Cinq études au total (publiées entre 2005 et 2018) ont été incluses, et toutes les intubations trachéales ont été réalisées par des anesthésiologistes ou infirmiers anesthésistes à l'aide d'un vidéolaryngoscope (n = 3) ou d'une lame de Macintosh (n = 2) en salle d'opération. Nous n'avons trouvé aucune différence significative dans le taux d'intubations réussies à la première tentative (risque relatif [RR], 0,98; P = 0,37), dans l'incidence de mauvaises vues laryngoscopiques (RR, 1,49; P = 0,21) ou dans le risque de maux de gorge (RR, 1,17; P = 0,73) entre les deux groupes. En revanche, le temps d'intubation lors de la première tentative réussie était légèrement plus long (différence moyenne pondérée = 4,40 sec, P = 0,002) et le risque d'enrouement était plus élevé (RR, 1,70; P = 0,03) dans le groupe PC que dans le groupe non-PC. Le critère d'évaluation secondaire « aspiration pulmonaire ¼ n'a pas été analysé parce qu'une seule étude le mesurait. CONCLUSION : L'application de PC n'a pas eu d'impact négatif sur le taux d'intubations réussies à la première tentative ou la vue laryngoscopique. Par contre, cette manœuvre pourrait légèrement prolonger le temps d'intubation et augmenter le risque d'enrouement postopératoire.

The analysis for time of referral to a medical center among patients with diabetic foot infection.

BACKGROUND: Diabetic foot infection (DFI) is a limb- and life-threatening complication for diabetic patients needing immediate and comprehensive treatment. Early referral of DFI patients to a diabetic foot center is recommended but there appears limited validated evidence, with the association between referral time and clinical outcomes of limb- preservation or in-hospital mortality still lacking. METHODS: This retrospective research studied consecutive type 2 diabetic patients with DFI treated at the major diabetic foot center in Taiwan from 2014 to 2017. Six hundred and sixty-eight patients presented with limb-threatening DFI. After stratifying their referral days into quartiles, the demographic information and clinical outcomes were analyzed. RESULTS: One hundred and seventy-two patients were placed in the first quartile (Q1) with less than 9 days of referral time; 164 in the second quartile (Q2) with 9-21 days; 167 in the third quartile (Q3) with 21-59 days; and 165 in the fourth quartile (Q4) with >59 days. End-stage renal disease (ESRD), major adverse cardiac events (MACE) and peripheral arterial disease (PAD) were noted as being higher in the Q4 group compared with the Q1 group (25.45% vs 20.35% in ESRD, 47.27% vs 26.16% in MACE and 78.79% vs 52.33% in PAD respectively). The Q1 group had more patients presenting with systemic inflammatory responsive syndrome (SIRS) (29.07% in Q1 vs 25.45% in Q4 respectively, P=0.019). Regarding poor outcome (major lower-extremity amputation (LEA) or in-hospital mortality), the Q4 group had 21.21% of patients in this category and the Q1 group had 10.47%. The odds ratio of each increased referral day on poor prognosis was 1.006 with 95% confidence interval 1.003-1.010 (P=<0.001). In subgroups, the impact on poor prognosis by day was most obvious in patients with SIRS (OR 1.011, 95% CI 1.004-1.018, P=0.003) and those with PAD (OR 1.004, 95% CI 1.001-1.008, P=0.028). CONCLUSIONS: The deferred referral of DFI patients to the diabetic foot center might be associated with poor treatment outcome either in major LEA or mortality, particularly in patients with SIRS or PAD. Both physician and patient awareness of disease severity and overcoming the referral barrier is suggested. TRIAL REGISTRATION: Not applicable.

Efficacy and airway complications of Parker Flex-Tip tubes and standard endotracheal tubes during airway manipulation: A meta-analysis and trial sequential analysis.

BACKGROUND: Despite reported superior intubation outcomes associated with Parker Flex-Tip (PFT) tubes compared with those associated with standard polyvinylchloride tubes, the efficacy and safety of PFT tubes remain uncertain. OBJECTIVES: To compare the intubation outcomes between PFT and conventional standard polyvinylchloride tubes. DESIGN: Meta-analysis of randomised controlled trials. DATA SOURCES: Embase, Medline, Google Scholar, PubMed and the Cochrane controlled trials register from inception until 3 January 2021. ELIGIBILITY CRITERIA: All randomised trials comparing intubation outcomes between PFT (PFT group) and standard polyvinylchloride (standard polyvinylchloride group) tubes. RESULTS: Analysis of the 13 eligible trials showed no significant difference in successful first-attempt intubation rate [risk ratio (RR) 1.20, 95% confidence interval (CI) 0.99 to 1.44] (6 trials, 568 participants), trauma risk (RR 0.83, 95% CI 0.67 to 1.03) (5 trials, 501 participants) as well as the overall risks of epistaxis (RR 0.58, 95% CI 0.26 to 1.31) (3 trials, 262 participants), sore throat (RR 0.90, 95% CI 0.70 to 1.17) (4 trials, 451 participants) and hoarseness (RR 0.71, 95% CI 0.44 to 1.14) (4 trials, 451 participants) between the two groups. However, the intubation time was slightly shorter (weighted mean difference -4.2 s, 95% CI -7.4 to -1.0 s) (8 trials, 759 participants) and the risks of severe epistaxis (RR 0.15, 95% CI 0.03 to 0.84) (3 trials, 262 participants) and overall difficulty in airway manipulation (RR 0.48, 95% CI 0.29 to 0.80) (8 trials, 647 participants) were lower in the PFT group than those in the standard polyvinylchloride group. Trial sequential analysis conclusively confirmed a shorter intubation time with PFT tubes than with standard polyvinylchloride tubes, whereas other intubation outcomes were inconclusive. CONCLUSION: The use of PFT tubes for airway manipulation was associated with a shorter intubation time compared with the standard polyvinylchloride tubes. The results of trial sequential analysis suggest the need for further trials and meta-analysis to compare other intubation outcomes associated with the two devices. TRIAL REGISTRATION: PROSPERO CRD42020197670.

In Vivo Submillisecond Two-Photon Optogenetics with Temporally Focused Patterned Light.

To better examine circuit mechanisms underlying perception and behavior, researchers need tools to enable temporally precise control of action-potential generation of individual cells from neuronal ensembles. Here we demonstrate that such precision can be achieved with two-photon (2P) temporally focused computer-generated holography to control neuronal excitability at the supragranular layers of anesthetized and awake visual cortex in both male and female mice. Using 2P-guided whole-cell or cell-attached recordings in positive neurons expressing any of the three opsins ReaChR, CoChR, or ChrimsonR, we investigated the dependence of spiking activity on the opsin's channel kinetics. We found that in all cases the use of brief illumination (≤10 ms) induces spikes of millisecond temporal resolution and submillisecond precision, which were preserved upon repetitive illuminations up to tens of hertz. To reach high temporal precision, we used a large illumination spot covering the entire cell body and an amplified laser at high peak power and low excitation intensity (on average ≤0.2 mW/µm2), thus minimizing the risk for nonlinear photodamage effects. Finally, by combining 2P holographic excitation with electrophysiological recordings and calcium imaging using GCaMP6s, we investigated the factors, including illumination shape and intensity, opsin distribution in the target cell, and cell morphology, which affect the spatial selectivity of single-cell and multicell holographic activation. Parallel optical control of neuronal activity with cellular resolution and millisecond temporal precision should make it easier to investigate neuronal connections and find further links between connectivity, microcircuit dynamics, and brain functions.SIGNIFICANCE STATEMENT Recent developments in the field of optogenetics has enabled researchers to probe the neuronal microcircuit with light by optically actuating genetically encoded light-sensitive opsins expressed in the target cells. Here, we applied holographic light shaping and temporal focusing to simultaneously deliver axially confined holographic patterns to opsin-positive cells in the living mouse cortex. Parallel illumination efficiently induced action potentials with high temporal resolution and precision for three opsins of different kinetics. We extended the parallel optogenetic activation at low intensity to multiple neurons and concurrently monitored their calcium dynamics. These results demonstrate fast and temporally precise in vivo control of a neuronal subpopulation, opening new opportunities for revealing circuit mechanisms underlying brain functions.

The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies.

BACKGROUND: The association between immune-related adverse events (irAEs) and survival outcomes in patients with advanced melanoma receiving therapy with immune checkpoint inhibitors (ICIs) has not been well established, particularly in Asian melanoma. METHODS: We retrospectively reviewed 49 melanoma patients undergoing therapy with ICIs (anti-PD-1 monotherapy), and analyzed the correlation between irAEs and clinical outcomes including progression-free survival (PFS) and overall survival (OS). RESULTS: Overall, the patients who experienced grade 1-2 irAEs had longer PFS (median PFS, 4.6 vs. 2.5 months; HR, 0.52; 95% CI: 0.27-0.98; p = 0.042) and OS (median OS, 15.2 vs. 5.7 months; HR, 0.50; 95% CI: 0.24-1.02; p = 0.058) than the patients who did not experience irAEs. Regarding the type of irAE, the patients with either skin/vitiligo or endocrine irAEs showed better PFS (median PFS, 6.1 vs. 2.7 months; HR, 0.40, 95% CI: 0.21-0.74; p = 0.003) and OS (median OS, 18.7 vs. 4.5 months; HR, 0.34, 95% CI: 0.17-0.69, p = 0.003) than patients without any of these irAEs. CONCLUSIONS: Melanoma patients undergoing anti-PD-1 monotherapy and experiencing mild-to-moderate irAEs (grade 1-2), particularly skin (vitiligo)/endocrine irAEs had favorable survival outcomes. Therefore, the association between irAEs and the clinical outcomes in melanoma patients undergoing anti-PD-1 ICIs may be severity and type dependent.