Synthesis and evaluation of antibody-drug conjugates with high drug-to-antibody ratio using dimaleimide-DM1 as a linker- payload.

The notable characteristics of recently emerged Antibody-Drug Conjugates (ADCs) encompass the targeting of Human Epidermal growth factor Receptor 2 (HER2) through monoclonal antibodies (mAbs) and a high ratio of drug to antibody (DAR). The achievements of Kadcyla® (T-DM1) and Enhertu® (T-Dxd) have demonstrated that HER2-targeting antibodies, such as trastuzumab, have shown to be competitive in terms of efficacy and price for development. Furthermore, with the arrival of T-Dxd and Trodelvy®, high-DAR (7-8) ADCs, which differ from the moderate DAR (3-4) ADCs that were formerly regarded as conventional, are being acknowledged for their worth. Following this trend of drug development, we endeavored to develop a high-DAR ADC using a straightforward approach involving the utilization of DM1, a highly potent substance, in combination with the widely recognized trastuzumab. To achieve a high DAR, DM1 was conjugated to reduced cysteine through the simple design and synthesis of various dimaleimide linkers with differing lengths. Using LC and MS analysis, we have demonstrated that our synthesis methodology is uncomplicated and efficacious, yielding trastuzumab-based ADCs that exhibit a remarkable degree of uniformity. These ADCs have been experimentally substantiated to exert an inhibitory effect on cancer cells in vitro, thus affirming their value as noteworthy additions to the realm of ADCs.

Channelled versus nonchannelled Macintosh videolaryngoscope blades in patients with a cervical collar: a randomized controlled noninferiority trial.

PURPOSE: Channelled blades have the advantage of avoiding stylet use and potential airway injury during videolaryngoscopic intubation. Nevertheless, the effectiveness of channelled Macintosh-type blades has not yet been fully established. We sought to assess the utility of channelled Macintosh-type blades for videolaryngoscopic intubation under cervical spine immobilization. METHODS: We conducted a randomized controlled noninferiority trial in neurosurgical patients with a difficult airway simulated by a cervical collar. Videolaryngoscopic intubation with a reinforced tracheal tube was performed using a channelled Macintosh-type blade without a stylet (channelled group, n = 130) or a nonchannelled Macintosh-type blade with a stylet (nonchannelled group, n = 131). The primary outcome was intubation success rate. Secondary outcomes included time to intubation and incidence or severity of intubation-related complications (subglottic, lingual, and dental injuries; bleeding; sore throat; and hoarseness). RESULTS: The initial intubation success rate was 98% and 99% in the channelled and nonchannelled groups, respectively, showing the noninferiority of the channelled group (difference in proportions -0.8%; 95% confidence interval [CI], -4.8% to 2.9%; predefined noninferiority margin, -5%; P = 0.62). Fewer participants in the channelled group had subglottic injuries than in the nonchannelled group (32% [32/100] vs 57% [54/95]; difference in proportions, -25%; 95% CI, -39% to -11%; P < 0.001). There were no significant differences between the two groups in the overall intubation success rate, time to intubation, and incidence or severity of other intubation-related complications. CONCLUSIONS: For videolaryngoscopic intubation in patients with a cervical collar, channelled Macintosh-type blades are an alternative to nonchannelled Macintosh-type blades, with a noninferior initial intubation success rate and a lower incidence of subglottic injury. STUDY REGISTRATION: CRIS.nih.go.kr ( KCT0005186 ); first submitted 29 June 2020.

RéSUMé: OBJECTIF: Les lames avec canal ont l'avantage de ne pas nécessiter l'utilisation d'un stylet et d'ainsi éviter les lésions potentielles des voies aériennes lors de l'intubation vidéolaryngoscopique. Néanmoins, l'efficacité des lames avec canal de type Macintosh n'a pas encore été pleinement établie. Nous avons cherché à évaluer l'utilité des lames avec canal de type Macintosh pour l'intubation vidéolaryngoscopique lorsque le rachis cervical était immobilisé. MéTHODE: Nous avons mené une étude randomisée contrôlée de non-infériorité chez des patient·es de neurochirurgie présentant des voies aériennes difficiles simulées par le port d'un collier cervical. L'intubation vidéolaryngoscopique avec une sonde trachéale renforcée a été réalisée à l'aide d'une lame Macintosh avec canal sans stylet (groupe avec canal, n = 130) ou d'une lame Macintosh sans canal avec stylet (groupe sans canal, n = 131). Le critère d'évaluation principal était le taux de réussite de l'intubation. Les critères d'évaluation secondaires comprenaient le temps d'intubation et l'incidence ou la gravité des complications liées à l'intubation (lésions sous-glottiques, linguales et dentaires, saignements, maux de gorge et enrouement). RéSULTATS: Le taux de réussite initial de l'intubation était de 98 % et 99 % dans les groupes avec et sans canal, respectivement, montrant la non-infériorité du groupe lame avec canal (différence de proportions −0,8 %; intervalle de confiance [IC] à 95 %, −4,8 % à 2,9 %; marge de non-infériorité prédéfinie, −5 %; P = 0,62). Les lésions sous-glottiques ont été moins nombreuses dans le groupe avec canal que dans le groupe sans canal (32 % [32/100] vs 57 % [54/95]; différence de proportions, −25 %; IC 95 %, −39 % à −11 %; P < 0,001). Il n'y avait pas de différences significatives entre les deux groupes en matière de taux global de réussite de l'intubation, de temps d'intubation et d'incidence ou de gravité des autres complications liées à l'intubation. CONCLUSION: Pour l'intubation vidéolaryngoscopique des patient·es portant un collier cervical, les lames avec canal de type Macintosh constituent une alternative aux lames sans canal de type Macintosh, avec un taux de réussite d'intubation initial non inférieur et une incidence plus faible de lésions sous-glottiques. ENREGISTREMENT DE L'éTUDE: CRIS.nih.go.kr ( KCT0005186 ); première soumission le 29 juin 2020.

SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity.

ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer.

Acquired Cross-Resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC Paralogs.

Small cell lung cancer (SCLC) presents as a highly chemosensitive malignancy but acquires cross-resistance after relapse. This transformation is nearly inevitable in patients but has been difficult to capture in laboratory models. Here, we present a preclinical system that recapitulates acquired cross-resistance, developed from 51 patient-derived xenograft (PDX) models. Each model was tested in vivo against three clinical regimens: cisplatin plus etoposide, olaparib plus temozolomide, and topotecan. These drug-response profiles captured hallmark clinical features of SCLC, such as the emergence of treatment-refractory disease after early relapse. For one patient, serial PDX models revealed that cross-resistance was acquired through MYC amplification on extrachromosomal DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC, and this was corroborated in tumor biopsies from relapsed patients. We conclude that ecDNAs with MYC paralogs are recurrent drivers of cross-resistance in SCLC. SIGNIFICANCE: SCLC is initially chemosensitive, but acquired cross-resistance renders this disease refractory to further treatment and ultimately fatal. The genomic drivers of this transformation are unknown. We use a population of PDX models to discover that amplifications of MYC paralogs on ecDNA are recurrent drivers of acquired cross-resistance in SCLC. This article is featured in Selected Articles from This Issue, p. 695.

High Intraoperative Serum Lactate Level is Associated with Acute Kidney Injury after Brain Tumor Resection.

BACKGROUND: Postoperative acute kidney injury (AKI) is associated with poor clinical outcomes. Identification of risk factors for postoperative AKI is clinically important. Serum lactate can increase in situations of inadequate oxygen delivery and is widely used to assess a patient's clinical course. We investigated the association between intraoperative serum lactate levels and AKI after brain tumor resection. METHODS: Demographics, medical and surgical history, tumor characteristics, surgery, anesthesia, preoperative and intraoperative blood test results, and postoperative clinical outcomes were retrospectively collected from 4131 patients who had undergone brain tumor resection. Patients were divided into high (n=1078) and low (n=3053) lactate groups based on an intraoperative maximum serum lactate level of 3.35 mmol/L. After propensity score matching, 1005 patients were included per group. AKI was diagnosed using the Kidney Disease Improving Global Outcomes criteria, based on serum creatinine levels within 7 days after surgery. RESULTS: Postoperative AKI was observed in 53 (1.3%) patients and was more frequent in those with high lactate both before (3.2% [n=35] vs. 0.6% [n=18]; P < 0.001) and after (3.3% [n=33] vs. 0.6% [n=6]; P < 0.001) propensity score matching. Intraoperative predictors of postoperative AKI were maximum serum lactate levels > 3.35 mmol/L (odds ratio [95% confidence interval], 3.57 [1.45-8.74], P = 0.005), minimum blood pH (odds ratio per 1 unit, 0.01 [0.00-0.24], P = 0.004), minimum hematocrit (odds ratio per 1%, 0.91 [0.84-1.00], P = 0.037), and mean serum glucose levels > 200 mg/dL (odds ratio, 6.22 [1.75-22.16], P = 0.005). CONCLUSION: High intraoperative serum lactate levels were associated with AKI after brain tumor resection.

Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis.

BACKGRUOUND: Many studies have shown that Hashimoto's thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC. METHODS: This study included two types of research. RESULTS: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies. RESULTS: Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT. CONCLUSION: This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

Association between body composition and the risk of mortality in the obese population in the United States.

Background: Recent studies have presented the concept of the obesity paradox, suggesting that individuals with obesity have a lower risk of death than those without obesity. This paradox may arise because body mass index (BMI) alone is insufficient to understand body composition accurately. This study investigated the relationship between fat and muscle mass and the risk of mortality in individuals with overweight/obesity. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006 and 2011 to 2018, which were linked to mortality information obtained from the National Death Index. Multiple Cox regression analyses were performed to estimate mortality risk. Subgroup analysis was conducted using propensity score-matched (PSM) data for age, sex, and race/ethnicity. Results: This study included 16,555 participants who were overweight/obese (BMI≥25 kg/m2). An increase in appendicular skeletal muscle mass index was associated with a lower mortality risk (hazard ratio [HR]: 0.856; 95% confidence interval [CI]: 0.802-0.915). This finding was consistent with the subgroup analysis of the PSM data. Contrastingly, a high fat mass index was associated with an increased risk of mortality. Sarcopenic overweight/obesity was significantly associated with high mortality compared to obesity without sarcopenia (HR: 1.612, 95%CI: 1.328-1.957). This elevated risk was significant in both age- and sex-based subgroups. This finding was consistent with the subgroup analysis using PSM data. Conclusion: In contrast to the obesity paradox, a simple increase in BMI does not protect against mortality. Instead, low body fat and high muscle mass reduce mortality risk.

Machine learning model for predicting immediate postoperative desaturation using spirometry signal data.

Postoperative desaturation is a common post-surgery pulmonary complication. The real-time prediction of postoperative desaturation can become a preventive measure, and real-time changes in spirometry data can provide valuable information on respiratory mechanics. However, there is a lack of related research, specifically on using spirometry signals as inputs to machine learning (ML) models. We developed an ML model and postoperative desaturation prediction index (DPI) by analyzing intraoperative spirometry signals in patients undergoing laparoscopic surgery. We analyzed spirometry data from patients who underwent laparoscopic, robot-assisted gynecologic, or urologic surgery, identifying postoperative desaturation as a peripheral arterial oxygen saturation level below 95%, despite facial oxygen mask usage. We fitted the ML model on two separate datasets collected during different periods. (Datasets A and B). Dataset A (Normal 133, Desaturation 74) was used for the entire experimental process, including ML model fitting, statistical analysis, and DPI determination. Dataset B (Normal 20, Desaturation 4) was only used for verify the ML model and DPI. Four feature categories-signal property, inter-/intra-position correlation, peak value/interval variability, and demographics-were incorporated into the ML models via filter and wrapper feature selection methods. In experiments, the ML model achieved an adequate predictive capacity for postoperative desaturation, and the performance of the DPI was unbiased.

Erratum: Correction of Affiliations in the Article "Preoperative Prognostic Nutritional Index Is a Prognostic Indicator of Cancer-Specific Survival in Patients Undergoing Endometrial Cancer Surgery".

This corrects the article on p. e163 in vol. 38, PMID: 37270918.

Effect of driving pressure-guided positive end-expiratory pressure on postoperative pulmonary complications in patients undergoing laparoscopic or robotic surgery: a randomised controlled trial.

BACKGROUND: Individualised positive end-expiratory pressure (PEEP) improves respiratory mechanics. However, whether PEEP reduces postoperative pulmonary complications (PPCs) remains unclear. We investigated whether driving pressure-guided PEEP reduces PPCs after laparoscopic/robotic abdominal surgery. METHODS: This single-centre, randomised controlled trial enrolled patients at risk for PPCs undergoing laparoscopic or robotic lower abdominal surgery. The individualised group received driving pressure-guided PEEP, whereas the comparator group received 5 cm H2O fixed PEEP during surgery. Both groups received a tidal volume of 8 ml kg-1 ideal body weight. The primary outcome analysed per protocol was a composite of pulmonary complications (defined by pre-specified clinical and radiological criteria) within 7 postoperative days after surgery. RESULTS: Some 384 patients (median age: 67 yr [inter-quartile range: 61-73]; 66 [18%] female) were randomised. Mean (standard deviation) PEEP in patients randomised to individualised PEEP (n=178) was 13.6 cm H2O (2.1). Individualised PEEP resulted in lower mean driving pressures (14.7 cm H2O [2.6]), compared with 185 patients randomised to standard PEEP (18.4 cm H2O [3.2]; mean difference: -3.7 cm H2O [95% confidence interval (CI): -4.3 to -3.1 cm H2O]; P<0.001). There was no difference in the incidence of pulmonary complications between individualised (25/178 [14.0%]) vs standard PEEP (36/185 [19.5%]; risk ratio [95% CI], 0.72 [0.45-1.15]; P=0.215). Pulmonary complications as a result of desaturation were less frequent in patients randomised to individualised PEEP (8/178 [4.5%], compared with standard PEEP (30/185 [16.2%], risk ratio [95% CI], 0.28 [0.13-0.59]; P=0.001). CONCLUSIONS: Driving pressure-guided PEEP did not decrease the incidence of pulmonary complications within 7 days of laparoscopic or robotic lower abdominal surgery, although uncertainty remains given the lower than anticipated event rate for the primary outcome. CLINICAL TRIAL REGISTRATION: KCT0004888 (http://cris.nih.go.kr, registration date: April 6, 2020).

Direct versus indirect epiglottis elevation in cervical spine movement during videolaryngoscopic intubation under manual in-line stabilization: a randomized controlled trial.

BACKGROUND: During videolaryngoscopic intubation, direct epiglottis elevation provides a higher percentage of glottic opening score than indirect epiglottis elevation. In this randomized controlled trial, we compared cervical spine movement during videolaryngoscopic intubation under manual in-line stabilization between the two glottis exposure methods. METHODS: Videolaryngoscopic intubation under manual in-line stabilization was performed using C-MAC® D-blade: direct (n = 51) and indirect (n = 51) epiglottis elevation groups. The percentage of glottic opening score was set equally at 50% during videolaryngoscopic intubation in both groups. The primary outcome measure was cervical spine movement during videolaryngoscopic intubation at the occiput-C1, C1-C2, and C2-C5. The secondary outcome measures included intubation performance (intubation success rate and intubation time). RESULTS: Cervical spine movement during videolaryngoscopic intubation was significantly smaller at the occiput-C1 in the direct epiglottis elevation group than in the indirect epiglottis elevation group (mean [standard deviation] 3.9 [4.0] vs. 5.8 [3.4] °, P = 0.011), whereas it was not significantly different at the C1-C2 and C2-C5 between the two groups. All intubations were successful on the first attempt, achieving a percentage of glottic opening score of 50% in both groups. Intubation time was longer in the direct epiglottis elevation group (median [interquartile range] 29.0 [24.0-35.0] vs. 22.0 [18.0-27.0] s, P < 0.001). CONCLUSIONS: When performing videolaryngoscopic intubation under manual in-line stabilization, direct epiglottis elevation can be more beneficial than indirect epiglottis elevation in reducing cervical spine movement during videolaryngoscopic intubation at the occiput-C1. TRIAL REGISTRATION: Clinical Research Information Service (number: KCT0006239, date: 10/06/2021).

Pleth variability index during preoxygenation could predict anesthesia-induced hypotension: A prospective, observational study.

STUDY OBJECTIVE: To determine whether changes in the pleth variability index (PVi) during preoxygenation with forced ventilation for 1 min could predict anesthesia-induced hypotension. DESIGN: Prospective, observational study. SETTING: A tertiary teaching hospital. PATIENTS: Ninety-six patients who underwent general anesthesia using total intravenous anesthesia were enrolled. INTERVENTIONS: Upon the patient's arrival at the preoperative waiting area, a PVi sensor was affixed to their fourth fingertip. For preoxygenation, forced ventilation of 8 breaths/min in a 1:2 inspiratory-expiratory ratio was conducted using the guidance of an audio file. One minute after preoxygenation, anesthetic administration was initiated. Blood pressure was measured for the next 15 min. MEASUREMENTS: We calculated the difference (dPVi) and percentage of change (%PVi) between the PVi values immediately before and after forced ventilation. Anesthesia-induced hypotension was defined as a mean arterial pressure of <60 mmHg within 15 min after the infusion of anesthetics. MAIN RESULTS: Overall, 87 patients were included in the final analysis. Anesthesia-induced hypotension occurred in 31 (35.6%) of the 87 patients. Receiver operating characteristic curve analyses identified a cut-off value of -2 for dPVi, with an area under the curve of 0.691 (95% confidence interval [CI], 0.564-0.818; P < 0.001) and a cut-off value of -7.6% for %PVi, with an area under the curve of 0.711 (95% CI, 0.589-0.832; P < 0.001). Further, multivariate logistic regression analysis showed that a low %PVi with an odds ratio of 9.856 (95% CI, 3.131-31.032; P < 0.001) was a significant determinant of anesthesia-induced hypotension. CONCLUSIONS: Hypotension frequently occurs during general anesthesia induction and can impact outcomes. Additionally, the percentage change in the PVi before and after preoxygenation using deep breathing can be used to predict anesthesia-induced hypotension.

Cholecystectomy increases the risk of metabolic syndrome in the Korean population: a longitudinal cohort study.

Background: Cholecystectomy is a common surgical procedure to treat symptomatic gallstones; however, the long-term outcomes after cholecystectomy are unknown. Therefore, we aimed to investigate whether incident metabolic syndrome (MetS) is associated with cholecystectomy through a large, population-based, longitudinal study. Methods: Subjects aged ≥20 years who underwent cholecystectomy from 2010 to 2014 (n=76,485) and controls (n=76,485), matched for age and sex, were identified from the Korean National Health Insurance Corporation. Cox proportional hazards analyses were performed to evaluate the association between cases and incident MetS, and hazard ratios and 95% confidence intervals (CIs) were calculated. Results: A total of 152,970 patients were included. Mean age was 52.47±12.76 years, and 50.65% of participants were male. During the follow-up period, there were 38,979 (25.48%) newly diagnosed MetS cases in the study participants. The risk of MetS in the cholecystectomy group was approximately 20% higher than that in the control group [adjusted odds ratio (OR), 1.20; 95% CI: 1.17-1.23]. In the fully adjusted models, the corresponding ORs for new-onset high waist circumference (WC), low high-density lipoprotein cholesterol (HDL-C) levels, high triglycerides (TG) levels, high blood pressure (BP), and high blood glucose levels were 1.16 (1.13-1.19), 1.19 (1.16-1.22), 1.25 (1.22-1.28), 1.27 (1.23-1.31), and 1.21 (1.18-1.24), respectively. Cholecystectomy was an independent risk factor of incident MetS, after adjusting for potential confounding factors. In the subgroup analyses, the cholecystectomy group had a higher risk of MetS than the control group in subjects without hypertension or dyslipidemia, respectively. Conclusions: In this large, population-based study, cholecystectomy was associated with an increased risk of developing MetS, independent of other confounding factors. Therefore, careful monitoring of metabolic variables and long-term follow-up are required to evaluate MetS risk after cholecystectomy.

Laser guidance for ultrasound-guided radial artery catheterization using smart glasses: a randomized trial.

PURPOSE: The use of smart glasses during ultrasound-guided needle procedures may reduce operators' head movements but has not been shown to improve procedural performance. Laser guidance has been shown to decrease the time required for ultrasound-guided procedures in phantom models but has not been tested clinically. We hypothesized that adding laser guidance to the use of smart glasses for ultrasound-guided radial artery catheterization using the long axis approach would improve performance by relatively inexperienced users unfamilar with these techniques. METHODS: In an unblinded controlled trial, we enrolled 52 patients requiring radial artery catheterization under anesthesia, randomized into two groups: smart glasses only (SO) (control; N = 26) or smart glasses with laser guidance group (SL) (N = 26). We assessed catheterization time (primary outcome), the number of needle redirections, first-pass success rate, and operator satisfaction (100 = most satisfactory; 0 = unsatisfactory). RESULTS: Comparing the SL with the SO group, catheterization time was shorter (median [interquartile range], 13 [9-20] sec vs 24 [18-46] sec, P < 0.001) and the number of needle redirections was lower (0 [0-1] vs 3 [1-3], P < 0.001) while the first-pass success rate (50% vs 12%, P = 0.007) and operator satisfaction score (85 [76-95] vs 52 [44-74], P < 0.001) were higher. CONCLUSION: Laser guidance improved the performance of ultrasound-guided radial artery catheterization using smart glasses in users inexperienced in the long axis in-plane approach. Nevertheless, it is unclear whether these findings are clinically significant. STUDY REGISTRATION DATE: CRIS.nih.go.kr (KCT0007168); registered 8 April 2022.

RéSUMé: OBJECTIF: L'utilisation de lunettes intelligentes pendant les procédures de ponctions échoguidées peut réduire les mouvements de la tête des opérateurs et opératrices, mais il n'a pas été démontré qu'elle améliorait les performances procédurales. Il a été démontré que le guidage laser réduisait le temps requis pour les interventions échoguidées sur des modèles fantômes, mais cette modalité n'a pas été testée cliniquement. Nous avons émis l'hypothèse que l'ajout d'un guidage laser à l'utilisation de lunettes intelligentes pour le cathétérisme échoguidé de l'artère radiale en utilisant une approche longitudinale (long axe) améliorerait les performances d'utilisateurs et utilisatrices relativement inexpérimenté·es et peu familier·ères avec ces techniques. MéTHODE: Dans une étude contrôlée sans insu, nous avons recruté et randomisé en deux groupes 52 patient·es nécessitant un cathétérisme de l'artère radiale sous anesthésie : lunettes intelligentes uniquement (LIU) (témoin N = 26) ou lunettes intelligentes avec guidage laser (LIL) (N = 26). Nous avons évalué le temps de cathétérisme (critère d'évaluation principal), le nombre de réorientation d'aiguilles, le taux de réussite au premier passage et la satisfaction de l'opérateur·trice (100 = le plus satisfaisant; 0 = insatisfaisant). RéSULTATS: En comparant le groupe LIL au groupe LIU, le temps de cathétérisme était plus court (médiane [écart interquartile], 13 [9-20] sec vs 24 [18­46] sec, P < 0,001) et le nombre de réorientations d'aiguilles était plus faible (0 [0­1] vs 3 [1­3], P < 0,001), tandis que le taux de réussite au premier passage (50 % vs 12 %, P = 0,007) et le score de satisfaction des opératrices et opérateurs (85 [76­95] vs 52 [44­74], P < 0,001) étaient plus élevés. CONCLUSION: Le guidage laser à l'aide de lunettes intelligentes a amélioré les performances du cathétérisme échoguidé de l'artère radiale chez des utilisateurs et utilisatrices inexpérimenté·es en approche longitudinale. Nous ne pouvons toutefois pas déterminer si ces résultats sont cliniquement significatifs. DATE D'ENREGISTREMENT DE L'éTUDE: CRIS.nih.go.kr (KCT0007168); enregistré le 8 avril 2022.

Autonomic responses during bladder hydrodistention under general versus spinal anaesthesia in patients with interstitial cystitis/bladder pain syndrome: a randomized clinical trial.

Blocking the abrupt increase in systolic blood pressure associated with autonomic response during bladder hydrodistention in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) is essential for patient safety. We conducted this study to compare autonomic responses during bladder hydrodistention in patients with IC/BPS under general and spinal anaesthesia. Thirty-six patients were randomly allocated to a general anaesthesia (GA, n = 18) or a spinal anaesthesia (SA, n = 18) group. Blood pressure and heart rate were measured continuously and ΔSBP, defined as maximum increases in SBP during bladder hydrodistention from baseline, was compared between groups. Heart rate variability was analysed using electrocardiograms. The post-anaesthesia care unit assessed postoperative pain using a numeric (0-10) rating scale. Our analyses yield a significantly greater ΔSBP (73.0 [26.0-86.1] vs. 2.0 [- 4.0 to 6.0] mmHg), a significantly lower root-mean-square of successive differences in heart rate variability after bladder hydrodistention (10.8 [7.7-19.8] vs. 20.6 [15.1-44.7] ms), and significantly higher postoperative pain scores (3.5 [0.0-5.5] vs. 0.0 [0.0-0.0]) in the GA compared to the SA group. These findings suggest that SA has advantages over GA for bladder hydrodistention in preventing an abrupt increase in SBP and postoperative pain in IC/BPS patients.

Preoperative Prognostic Nutritional Index Is a Prognostic Indicator of Cancer-Specific Survival in Patients Undergoing Endometrial Cancer Surgery.

BACKGROUND: The prognostic nutritional index (PNI) reflects systemic inflammation and nutritional status. This study aimed to evaluate the effect of preoperative PNI on postoperative cancer-specific survival in patients with endometrial cancer (EC). METHODS: Demographic, laboratory, and clinical data were retrospectively collected from 894 patients who underwent surgical resection of EC. Preoperative PNIs were determined from the serum albumin concentration and total lymphocyte count, which were measured within 1 month before surgery. Patients were classified into high PNI (n = 619) and low PNI (n = 275) groups according to the preoperative PNI cut-off value of 50.6. The stabilized inverse probability of treatment weighting (IPTW) method was used to reduce bias: a weighting cohort divided into high PNI (n = 615.4) and low PNI (n = 272.3) groups. The primary outcome measure was postoperative cancer-specific survival. RESULTS: The postoperative cancer-specific survival rate was higher in the high PNI group than the low PNI group in the unadjusted cohort (93.1% vs. 81.5%; proportion difference [95% confidence interval; 95% CI], 11.6% [6.6-16.6%]; P < 0.001) and in the IPTW-adjusted cohort (91.4% vs. 86.0%; 5.4% [0.8-10.2%]; P = 0.021). In the multivariate Cox proportional hazard regression model in the IPTW-adjusted cohort, high preoperative PNI (hazard ratio [95% CI], 0.60 [0.38-0.96]; P = 0.032) was an independent determinant of postoperative cancer-specific mortality. The multivariate-adjusted restricted cubic spline curve for the Cox regression model showed a significant negative association between preoperative PNI and postoperative cancer-specific mortality (P < 0.001). CONCLUSION: High preoperative PNI was associated with improved postoperative cancer-specific survival in patients undergoing surgery for EC.

Effect of abdominal binder on shoulder pain after laparoscopic gynecologic surgery: A randomized, controlled trial.

BACKGROUND: To evaluate the impact of abdominal binder (AB) use on postoperative shoulder pain in patients recovering from laparoscopic gynecologic surgery. METHODS: This was a prospective randomized study conducted in a tertiary teaching hospital. Overall, 144 patients underwent laparoscopic gynecologic surgery. The postoperative use of an AB for 24 hours was added to the pulmonary recruitment maneuver. RESULTS: Of 144 consenting patients, 72 patients each were allocated to the AB and control groups, respectively, and 14 patients were excluded. Finally, 130 patients were analyzed, with 68 in the AB group and 62 in the control group. There was no difference in the incidence of postoperative shoulder pain between the 2 groups (55.9% vs 56.5%, P = 1.000). The severity of the worst shoulder pain, measured using a numerical rating scale, did not differ between the 2 groups (Median [interquartile range] 2 [0-5] vs 2 [0-5]; P = .865). The severity of surgical site pain, pain and nausea medications, and the ambulation time were not different in the 2 groups. CONCLUSION: The use of an AB was not beneficial for postoperative shoulder pain following laparoscopic gynecologic surgery. Surgical site pain, ambulation time, and postoperative nausea and vomiting were not improved with the use of an AB.

Comparison of the recovery profile of remimazolam with flumazenil and propofol anesthesia for open thyroidectomy.

BACKGROUND: Previous studies have consistently reported a slower recovery of consciousness following remimazolam-based total intravenous anesthesia without flumazenil than with propofol. This study aimed to compare the reversal effect of flumazenil on the recovery of consciousness after remimazolam-based total intravenous anesthesia with the propofol recovery profile. METHODS: This prospective, single-blinded, randomized trial included 57 patients undergoing elective open thyroidectomy at a tertiary university hospital. Patients were randomly allocated to receive either remimazolam- or propofol-based total intravenous anesthesia (remimazolam group: 28 patients, propofol group: 29 patients). The primary outcome was the time from the end of general anesthesia to first eye opening (min). The secondary outcomes were the time from the end of the general anesthesia to extubation (min), initial modified Aldrete score measured at the post-anesthesia care unit, length of stay at the post-anesthesia care unit (min), occurrence of postoperative nausea and vomiting during the first 24 h postoperatively, and Korean version of Quality of Recovery-15 score at 24 h postoperatively. RESULTS: The remimazolam group showed significantly faster first eye opening time (2.3 [interquartile range, IQR: 1.8-3.3] min vs. 5.0 [IQR: 3.5-7.8] min, median difference:-2.7 [95% confidence interval, CI: -3.7 to -1.5] min, P < 0.001) and extubation time (3.2 [IQR: 2.4-4.2] min vs. 5.7 [IQR: 4.7-8.3] min, median difference: -2.7 [97.5% CI: -5.0 to -1.6] min, P < 0.001). There were no significant differences in other postoperative outcomes. CONCLUSIONS: The planned incorporation of flumazenil with remimazolam-based total intravenous anesthesia provided rapid and reliable recovery of consciousness.

Effects of Scalp Nerve Block on the Quality of Recovery after Minicraniotomy for Clipping of Unruptured Intracranial Aneurysms : A Randomized Controlled Trial.

OBJECTIVE: This study compared the quality of recovery (QoR) after minicraniotomy for clipping of unruptured intracranial aneurysms (UIAs) between patients with and without scalp nerve block (SNB). METHODS: Patients were randomly assigned to the SNB (SNB using ropivacaine with epinephrine, n=27) and control (SNB using normal saline, n=25) groups. SNB was performed at the end of surgery. To assess postoperative QoR, the QoR-40, a patient-reported questionnaire, was used. The QoR-40 scores were measured preoperatively, 1-3 days postoperatively, at hospital discharge, and 1 month postoperatively. Pain and intravenous patient-controlled analgesia (IV-PCA) consumption were evaluated 3, 6, 9, and 12 hours and 1-3 days postoperatively. RESULTS: All QoR-40 scores, including those measured 1 day postoperatively (primary outcome measure; 155.0 [141.0-176.0] vs. 161.0 [140.5-179.5], p=0.464), did not significantly differ between the SNB and control groups. The SNB group had significantly less severe pain 3 (numeric rating scale [NRS]; 3.0 [2.0-4.0] vs. 5.0 [3.5-5.5], p=0.029), 9 (NRS; 3.0 [2.0-4.0] vs. 4.0 [3.0-5.0], p=0.048), and 12 (NRS; 3.0 [2.0-4.0] vs. 4.0 [3.0-5.0], p=0.035) hours postoperatively. The total amount of IV-PCA consumed was significantly less 3 hours postoperatively in the SNB group (2.0 [1.0-4.0] vs. 4.0 [2.0-5.0] mL, p=0.044). CONCLUSION: After minicraniotomy for clipping of UIAs, SNB reduced pain and IV-PCA consumption in the early postoperative period but did not improve the QoR-40 scores.