Effects of goal-directed analgesia using the analgesia nociception index in children undergoing surgery for moyamoya disease: A randomised controlled trial.

BACKGROUND: The potential benefits of Analgesia Nociception Index guided intra-operative analgesia on intra-operative opioid consumption remains to be demonstrated in paediatric anaesthesia. OBJECTIVES: This study aimed to explore the effects of Analgesia Nociception Index guided analgesia on sufentanil consumption during anaesthesia and postoperative pain scores in paediatric patients with moyamoya disease. DESIGN: A prospective randomised controlled study. SETTING: Seoul National University Children's Hospital, Seoul, Republic of Korea. PATIENTS: A total of 40 children scheduled for encephaloduroarteriosynangiosis. MAIN OUTCOME MEASURES: The primary outcome was total intra-operative sufentanil consumption, and the secondary outcomes included postoperative pain scores and incidence of opioid-related adverse events. RESULTS: The Analgesia Nociception Index group showed lower intra-operative sufentanil consumption (in µg kg-1 h-1) compared with the Standard group (0.30 ±â€Š0.12 and 0.39 ±â€Š0.17, respectively; mean difference, -0.09; 95% confidence interval, -0.19 to 0.00; P = 0.049). Postoperatively, compared with the Standard group, the Analgesia Nociception Index group reported lower median pain scores at 18 and 24 h and maximum pain within 24 h (1 [0 to 2] vs. 3 [2 to 5]; P = 0.004, 1 [0 to 2] vs. 3 [1 to 4]; P = 0.041, and 4 [3 to 5] vs. 5 [4 to 7]; P = 0.045, respectively), with fewer patients experiencing nausea (3 [15%] vs. 10 [50%], P = 0.043). CONCLUSION: The Analgesia Nociception Index guided analgesic protocol can reduce intra-operative sufentanil consumption and postoperative pain within 24 h with fewer nausea symptoms in paediatric patients with moyamoya disease who undergo encephaloduroarteriosynangiosis. TRIAL REGISTRATION NUMBER: NCT05672212 (registered at clinicaltrials, principal investigator: K.E.H., registration date: 2 January 2023).

Atmospheric particulate matter and hypoxaemia in Korean children receiving general anaesthesia: A retrospective analysis.

BACKGROUND: The association between the concentration of atmospheric particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia in children receiving general anaesthesia is unclear. OBJECTIVE: To investigate the association between the exposure to of particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% for more than 1 min, in children. DESIGN: Retrospective study. SETTING: Single-centre. PARTICIPANTS: Children aged 18 years or younger who received general anaesthesia between January 2019 and October 2020. INTERVENTION: Information on daily levels of particulate matter with a diameter 10 µm or less and 2.5 µm or less measured within a neighbourhood corresponding to the area defined by the hospital's zip code was obtained from publicly available air-quality data. MAIN OUTCOME MEASURES: The primary outcome was intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% lasting for more than 1 min, manually verified by anaesthesiologists using vital sign registry data extracted at 2 s intervals. RESULTS: Of the patients finally analysed, 3.85% (489/13 175) experienced intra-operative hypoxaemia. Higher levels of particulate matter 10 µm or less in diameter (≥81 µg m-3, 472/12 900, 3.7%) were associated with an increased occurrence of intra-operative hypoxaemia compared with lower particulate matter concentrations [<81 µg m-3, 17/275, 6.2%; adjusted odds ratio, 1.71; 95% confidence interval (CI), 1.04 to 2.83; P = 0.035]. CONCLUSION: The level of particulate matter on the day of surgery pose a risk of intra-operative hypoxaemia in children receiving general anaesthesia. If the concentrations of particulate matter 10 µm or less in diameter on the day of surgery are high, children receiving general anaesthesia should be managed with increased caution.

Targeting cyclooxygenase-2 for chemoprevention of inflammation-associated intestinal carcinogenesis: An update.

Mounting evidence from preclinical and clinical studies suggests that persistent inflammation functions as a driving force in the journey to cancer. Cyclooxygenase-2 (COX-2) is a key enzyme involved in inflammatory signaling. While being transiently upregulated upon inflammatory stimuli, COX-2 has been found to be consistently overexpressed in human colorectal cancer and several other malignancies. The association between chronic inflammation and cancer has been revisited: cancer can arise when inflammation fails to resolve. Besides its proinflammatory functions, COX-2 also catalyzes the production of pro-resolving as well as anti-inflammatory metabolites from polyunsaturated fatty acids. This may account for the side effects caused by long term use of some COX-2 inhibitory drugs during the cancer chemopreventive trials. This review summarizes the latest findings highlighting the dual functions of COX-2 in the context of its implications in the development, maintenance, and progression of cancer.

Determination of optimal positive end-expiratory pressure using electrical impedance tomography in infants under general anesthesia: Comparison between supine and prone positions.

AIMS: This study determined the optimal positive end-expiratory pressure levels in infants in supine and prone positions under general anesthesia using electrical impedance tomography (EIT). METHODS: This prospective observational single-centre study included infants scheduled for surgery in the prone position. An electrical impedance tomography sensor was applied after inducing general anesthesia. The optimal positive end-expiratory pressure in the supine position was determined in a decremental trial based on EIT and compliance. Subsequently, the patient's position was changed to prone. Electrical impedance tomography parameters, including global inhomogeneity index, regional ventilation delay, opening pressure, the centre of ventilation, and pendelluft volume, were continuously obtained up to 1 h after prone positioning. The optimal positive end-expiratory pressure in the prone position was similarly determined. RESULTS: Data from 30 infants were analyzed. The mean value of electrical impedance tomography-based optimal positive end-expiratory pressure in the prone position was significantly higher than that in the supine position [10.9 (1.6) cmH2O and 6.1 (0.9) cmH2O, respectively (p < .001)]. Significant differences were observed between electrical impedance tomography- and compliance-based optimal positive end-expiratory pressure. Peak and mean airway, plateau, and driving pressures increased 1 h after prone positioning compared with those in the supine position. In addition, the centre of ventilation for balance in ventilation between the ventral and dorsal regions improved. CONCLUSION: The prone position required higher positive end-expiratory pressure than the supine position in mechanically ventilated infants under general anesthesia. EIT is a promising tool to find the optimal positive end-expiratory pressure, which needs to be individualized.

Talaromides A-C, Bioactive Cyclic Heptapeptides from Talaromyces siglerae Isolated from a Marine Sponge.

Three new cyclic heptapeptides, talaromides A-C (1-3), were isolated from cultures produced by the fungus Talaromyces siglerae (Ascomycota), isolated from an unidentified sponge. The structures, featuring an unusual proline-anthranilic moiety, were elucidated by analysis of spectroscopic data and chemical transformations, including the advanced Marfey's method and GITC derivatization. Talaromides A and B inhibited migration activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.

Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis.

Valosin-containing protein (VCP)/p97, an AAA+ ATPase critical for maintaining proteostasis, emerges as a promising target for cancer therapy. This study reveals that targeting VCP selectively eliminates breast cancer cells while sparing non-transformed cells by inducing paraptosis, a non-apoptotic cell death mechanism characterized by endoplasmic reticulum and mitochondria dilation. Intriguingly, oncogenic HRas sensitizes non-transformed cells to VCP inhibition-mediated paraptosis. The susceptibility of cancer cells to VCP inhibition is attributed to the non-attenuation and recovery of protein synthesis under proteotoxic stress. Mechanistically, mTORC2/Akt activation and eIF3d-dependent translation contribute to translational rebound and amplification of proteotoxic stress. Furthermore, the ATF4/DDIT4 axis augments VCP inhibition-mediated paraptosis by activating Akt. Given that hyperactive Akt counteracts chemotherapeutic-induced apoptosis, VCP inhibition presents a promising therapeutic avenue to exploit Akt-associated vulnerabilities in cancer cells by triggering paraptosis while safeguarding normal cells.

Ultrasound-guided selective supraclavicular nerve block for postoperative pain control in children receiving Hickman catheter or chemoport insertion: A randomized controlled trial.

BACKGROUND: Optimal pain management after insertion of a central venous catheter in children remains unclear. AIM: This study aimed to evaluate the effects of a selective supraclavicular nerve block on postoperative analgesia in pediatric patients undergoing hickman catheter or chemoport insertion. METHODS: Fifty patients aged 3-18 years scheduled for elective Hickman or chemoport insertion were randomized into two groups of 25 each: one group received an ultrasound-guided selective supraclavicular nerve block with 0.1 mL/kg of 0.5% ropivacaine (SSCNB group), and the other group did not receive a nerve block (control group). The primary outcome was the postoperative Wong-Baker Faces Pain Rating Scale score measured between 10 and 30 min after surgery. Secondary outcomes included pain scores at 1, 3, and 24 h after the surgery, block-related complications, length of stay in the postanesthesia care unit, postoperative analgesic consumption, and time to first analgesic use 24 h after surgery. RESULTS: The worst pain score within 30 min in the recovery room was significantly lower in the SSCNB group compared to the control group (6 [5-7] vs. 3 [2-4]; median difference, -3; 95% CI, -4 to -1; p < .001). Pain scores at 1, 3, and 24 h after surgery were also significantly lower in the SSCNB group. The need for both opioid and non-opioid analgesics in the postoperative period was significantly lower in the SSCNB group (36.0% vs. 0%; p = .002 and 44.0% vs. 16.0%; mean difference, -28%; 95% CI, -56 to 0.19; p = .033, respectively), while other secondary outcomes were not significantly different between the two groups. CONCLUSIONS: Ultrasound-guided SSCNB is an effective method for managing postoperative pain in children undergoing Hickman catheter or chemoport insertion, reducing the need for analgesics within 24 h after surgery.

Necrotizing Primary Angiitis of the Central Nervous System Mimicking Brain Abscess: A Case Report and Literature Review.

Primary angiitis of the central nervous system (PACNS) is a rare vasculitis in the central nervous system. Herein, we report a case of diagnosis and treatment of necrotic pattern PACNS, which was difficult to differentiate from a brain abscess. A 19-year-old male presented with blurred vision and a headache. Brain MRI revealed irregular rim-enhancing necrotic masses with central diffusion-high signal intensity in the corpus callosum and peripheral diffusion-high signal intensity in the left parietotemporal periventricular area. Susceptibility-weighted imaging revealed multiple punctate hemorrhages in the lesions. The patient was diagnosed with unusual abscess or tumefactive PACNS. Therefore, we initially treated the patient with antibiotics to rule out brain abscess. However, the brain lesions did not improve on follow-up MRI after the antibiotic treatment. Surgical biopsy was performed, and the histopathological diagnosis was PACNS with a necrotic pattern. The necrotic lesions became smaller on follow-up MRI after high-dose corticosteroid treatment.

Higher portal venous pulsatility is associated with worse clinical outcomes following congenital heart surgery: a single-centre prospective cohort study.

PURPOSE: Increased portal venous flow pulsatility is associated with major complications after adult cardiac surgery. Nevertheless, no data are available for pediatric patients with congenital heart disease. We hypothesized that Doppler parameters including portal flow pulsatility could be associated with postoperative outcomes in children undergoing various cardiac surgeries. METHODS: We conducted a prospective observational cohort study in children undergoing congenital cardiac surgery. We obtained postoperative portal, splenic, and hepatic venous Doppler data and perioperative clinical data including major postoperative complications. Portal and splenic venous flow pulsatility were calculated. We evaluated the association between venous Doppler parameters and adverse outcomes. The primary objective was to determine whether postoperative portal flow pulsatility could indicate major complications following congenital heart surgery. RESULTS: In this study, we enrolled 389 children, 74 of whom experienced major postoperative complications. The mean (standard deviation) portal pulsatility (44 [30]% vs 25 [14]%; 95% confidence interval [CI] for mean difference, 12 to 26; P < 0.001] and splenic pulsatility indices (41 [30]% vs 26 [16]%; 95% CI, 7 to 23; P < 0.001) were significantly higher in children with postoperative complications than in those without complications. The portal pulsatility index was able to help identify postoperative complications in biventricular patients and univentricular patients receiving bidirectional cavopulmonary shunt whereas it did not in other univentricular patients. An increased postoperative portal pulsatility index was significantly associated with major complications after pediatric cardiac surgery (odds ratio, 1.40; 95% CI, 1.29 to 1.91; P < 0.001). CONCLUSIONS: Higher portal venous pulsatility is associated with major postoperative complications in children undergoing cardiac surgery. Nevertheless, more data are needed to conclude the efficacy of portal venous pulsatility in patients with univentricular physiology. STUDY REGISTRATION: ClinicalTrials.gov (NCT03990779); registered 19 June 2019.

RéSUMé: OBJECTIF: L'augmentation de la pulsatilité du flux de la veine porte est associée à des complications majeures après une chirurgie cardiaque chez l'adulte. Néanmoins, aucune donnée n'est disponible pour la patientèle pédiatrique atteinte de cardiopathie congénitale. Nous avons émis l'hypothèse que les paramètres Doppler, y compris la pulsatilité du flux de la veine porte, pourraient être associés aux devenirs postopératoires des enfants bénéficiant de diverses chirurgies cardiaques. MéTHODE: Nous avons réalisé une étude de cohorte observationnelle prospective portant sur des enfants bénéficiant d'une chirurgie cardiaque congénitale. Nous avons obtenu des données Doppler des veines porte, spléniques et hépatiques postopératoires ainsi que des données cliniques périopératoires, y compris les complications postopératoires majeures. La pulsatilité du flux des veines porte et spléniques a été calculée. Nous avons évalué l'association entre les paramètres Doppler veineux et les issues indésirables. L'objectif principal était de déterminer si la pulsatilité du flux postopératoire de la veine porte pouvait constituer un indicateur des complications majeures après une chirurgie cardiaque congénitale. RéSULTATS: Dans cette étude, nous avons recruté 389 enfants, dont 74 ont présenté des complications postopératoires majeures. La pulsatilité moyenne de la veine porte (écart type) (44 [30] % vs 25 [14] %; intervalle de confiance [IC] à 95 % pour la différence moyenne, 12 à 26; P < 0,001] et les indices de pulsatilité splénique (41 [30] % vs 26 [16] %; IC 95 %, 7 à 23; P < 0,001) étaient significativement plus élevés chez les enfants présentant des complications postopératoires que chez les enfants sans complications. L'indice de pulsatilité de la veine porte a permis d'identifier les complications postopératoires chez les patient·es biventriculaires et les patient·es univentriculaires recevant une anastomose cavo-pulmonaire bidirectionnelle (procédure de Glenn), alors que ce n'était pas le cas chez les autres patient·es univentriculaires. Une augmentation postopératoire de l'indice de pulsatilité de la veine porte était significativement associée à des complications majeures après une chirurgie cardiaque pédiatrique (rapport de cotes, 1,40; IC 95 %, 1,29 à 1,91; P < 0,001). CONCLUSION: Une pulsatilité plus élevée de la veine porte est associée à des complications postopératoires majeures chez les enfants bénéficiant d'une chirurgie cardiaque. Néanmoins, davantage de données sont nécessaires pour conclure à l'efficacité de la pulsatilité de la veine porte chez les patient·es présentant une physiologie univentriculaire. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT03990779); enregistrée le 19 juin 2019.

Irisin reduces amyloid-ß by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling.

A pathological hallmark of Alzheimer's disease (AD) is the deposition of amyloid-ß (Aß) protein in the brain. Physical exercise has been shown to reduce Aß burden in various AD mouse models, but the underlying mechanisms have not been elucidated. Irisin, an exercise-induced hormone, is the secreted form of fibronectin type-III-domain-containing 5 (FNDC5). Here, using a three-dimensional (3D) cell culture model of AD, we show that irisin significantly reduces Aß pathology by increasing astrocytic release of the Aß-degrading enzyme neprilysin (NEP). This is mediated by downregulation of ERK-STAT3 signaling. Finally, we show that integrin αV/ß5 acts as the irisin receptor on astrocytes required for irisin-induced release of astrocytic NEP, leading to clearance of Aß. Our findings reveal for the first time a cellular and molecular mechanism by which exercise-induced irisin attenuates Aß pathology, suggesting a new target pathway for therapies aimed at the prevention and treatment of AD.

Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis.

Oncogenic cell-surface membrane proteins contribute to the phenotypic and functional characteristics of cancer stem cells (CSCs). We employed a proximity-labeling proteomic approach to quantitatively analyze the cell-surface membrane proteins in close proximity to CD147 in CSCs. Furthermore, we compared CSCs to non-CSCs to identify CSC-specific cell-surface membrane proteins that are closely interact with CD147 and revealed that lateral interaction between CD147 and CD276 concealed within the lipid raft microdomain in CSCs, confers resistance to docetaxel, a commonly used chemotherapy agent for various cancer types, including metastatic breast cancer. Moreover, we investigated the clinical relevance of CD147 and CD276 co-expression in HER2+ breast cancer (BC) and triple-negative breast cancer patients who underwent chemotherapy. We observed poor disease-free survival and Overall survival rates in patients of CD147 and CD276 (p = 0.04 and 0.08, respectively). Subsequent immunohistochemical analysis in independent cohorts of HER2+ BC support for the association between co-expression of CD147 and CD276 and a poor response to chemotherapy. Collectively, our study suggests that the lateral interaction between CD147 and its proximal partners, such as CD276, may serve as a poor prognostic factor in BC and a predictive marker for the critical phenotypic determinant of BC stemness.

Effect of tidal volume change on pressure-based prediction of fluid responsiveness in children.

INTRODUCTION: It is known that pulse pressure variation and systolic pressure variation cannot predict fluid responsiveness in children. In adults, the ability of these dynamic parameters to predict fluid responsiveness is improved by increasing tidal volume. We planned to investigate whether pulse pressure variation or systolic pressure variation can predict fluid responsiveness in children when augmented by increasing tidal volume by conducting a prospective study. METHODS: We enrolled children younger than 7 years who underwent cardiac surgery for atrial septal defect or ventricular septal defect. After sternum closure, pulse pressure variation and systolic pressure variation were continuously recorded while changing the tidal volume to 6, 10, and 14 mL/kg. Fluid loading was done with 10 mL/kg of crystalloids for 10 min, and stroke volume index was measured via transesophageal echocardiography. Children whose stroke volume index increased by more than 15% after the fluid loading were defined as responders to fluid therapy. We set primary outcome as the predictability of pulse pressure variation and systolic pressure variation for fluid responsiveness and measured the area under the curve of receiver operating characteristics curve. RESULTS: Twenty-six children were included, of which 15 were responders. At the tidal volume of 14 mL/kg, the area under the curves of receiver operating characteristics curves of pulse pressure variation and systolic pressure variation were 0.576 (p = .517) and 0.548 (p = .678), respectively. The differences in dynamic parameters between responders and nonresponders were not significant. DISCUSSION: Failure of pulse pressure variation or systolic pressure variation at augmented tidal volume in children may be due to difference in their arterial compliance from those of adults. Large compliance of thoracic wall may be another reason. CONCLUSIONS: Augmented pulse pressure variation or systolic pressure variation due to increased tidal volume cannot predict fluid responsiveness in children after simple cardiac surgery.

Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma.

Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received pembrolizumab for ≤2 years. Patients in CR who discontinued treatment and subsequently experienced PD were eligible for second-course pembrolizumab. Primary end points were the objective response rate (ORR) using blinded central review and safety. The median follow-up was 63.7 months. ORR was 71.4% (95% confidence interval [CI], 64.8-77.4; CR, 27.6%; partial response, 43.8%). Median duration of response (DOR) was 16.6 months; median progression-free survival was 13.7 months. A quarter of responders, including half of complete responders, maintained a response for ≥4 years. Median overall survival was not achieved. Among 20 patients receiving second-course pembrolizumab, ORR for 19 evaluable patients was 73.7% (95% CI, 48.8-90.8); median DOR was 15.2 months. Any-grade treatment-related adverse events occurred in 72.9% of patients and grade 3 or 4 adverse events occurred in 12.9% of patients; no treatment-related deaths occurred. Single-agent pembrolizumab can induce durable responses, particularly in patients achieving CR. Second-course pembrolizumab frequently reinduced sustained responses after relapse from initial CR.

Conventional reversal of rocuronium-induced neuromuscular blockade by sugammadex in Korean children: pharmacokinetics, efficacy, and safety analyses.

Background: Sugammadex is known to reverse neuromuscular blockade induced by non-depolarizing agents. In children, the recommended dose for reversal of moderate neuromuscular blockade is 2 mg/kg. We investigated the pharmacokinetics and pharmacodynamics of sugammadex in Korean children. Methods: Children (2-17 years of age) undergoing brain or spine surgery were enrolled and randomly assigned to control (neostigmine) and 2, 4, or 8 mg/kg sugammadex groups. Following induction of anesthesia and monitoring of the response to train-of-four stimulation, 1 mg/kg rocuronium was intravenously administered. Upon reappearance of the second twitch to train-of-four stimulation, the study drug was administered according to group allocation. The plasma concentrations of rocuronium and sugammadex were serially measured at nine predefined time points following study drug administration. To determine efficacy, we measured the time elapsed from drug administration to recovery of T4/T1 ≥ 0.9. For pharmacokinetics, non-compartmental analysis was performed and we monitored adverse event occurrence from the time of study drug administration until 24 h post-surgery. Results: Among the 29 enrolled participants, the sugammadex (2 mg/kg) and control groups showed recovery times [median (interquartile range)] of 1.3 (1.0-1.9) and 7.7 (5.3-21.0) min, respectively (p = 0.002). There were no significant differences in recovery time among the participants in sugammadex groups. The pharmacokinetics of sugammadex were comparable to those of literature findings. Although two hypotensive events related to sugammadex were observed, no intervention was necessary. Conclusion: The findings of this pharmacokinetic analysis and efficacy study of sugammadex in Korean children indicated that sugammadex (2 mg/kg) may be safely administered for reversing moderate neuromuscular blockade. Some differences in pharmacokinetics of sugammadex were observed according to age. Clinical Trial Registration: http://clinicaltrials.gov (NCT04347486).

Evaluation of Portal, Splenic, and Hepatic Vein Flows in Children Undergoing Congenital Heart Surgery.

OBJECTIVE: Little is known about changes in portal, splenic, and hepatic vein flow patterns in children undergoing congenital heart surgery. This study aimed to determine the characteristics of portal, splenic, and hepatic vein flow patterns using ultrasonography in children undergoing cardiac surgery. DESIGN: Single-center, prospective observational study. SETTING: Tertiary children's hospital, operating room. PARTICIPANTS: Children undergoing cardiac surgery. MEASUREMENT AND MAIN RESULTS: The authors obtained ultrasound data from the heart, inferior vena cava, portal, splenic, and hepatic veins before and after surgeries. In the biventricular group, which included children with atrial and ventricular septal defects and pulmonary stenosis (n = 246), the portal pulsatility index decreased from 38.7% to 25.6% (p < 0.001) after surgery. The preoperative portal pulsatility index was significantly higher in patients with pulmonary hypertension (43.3% v 27.4%; p < 0.001). In the single-ventricle group (n = 77), maximum portal vein flow velocities of Fontan patients were significantly lower (13.5 cm/s) compared with that of patients with modified Blalock-Taussig shunt (19.7 cm/s; p = 0.035) or bidirectional cavopulmonary shunt (23.1 cm/s; p < 0.001). The cardiac index was inversely correlated with the portal pulsatility index in the bidirectional cavopulmonary shunt and Fontan circulation. (ß = -5.693, r2 = 0.473; p = 0.001) The portal pulsatility index was correlated with splenic venous pulsatility and hepatic venous atrial reverse flow velocity in biventricular and single-ventricle groups. CONCLUSIONS: The characteristics of venous Doppler patterns in the portal, splenic, and hepatic veins differed according to congenital heart disease. Further studies are required to determine the association between splanchnic venous Doppler findings and clinical outcomes in this population.

Comparison of effects of volatile and intravenous anesthetics on pupillary function during general anesthesia in children: A prospective observational study.

BACKGROUND: The light reflex, which reflects central nervous system dysfunction, can also be affected by anesthetic agents. AIMS: We evaluated whether these effects differed according to the anesthetic agent in pediatric patients. METHODS: Twenty children aged 3-12 years who were scheduled to undergo elective surgery under general anesthesia were randomly allocated to propofol and sevoflurane groups and underwent pupillometric assessments at five points during anesthesia: T1, after confirming loss of consciousness; T2, after endotracheal intubation; T3, at the time of skin incision; T4, 1 h after skin incision; and T5, before endotracheal extubation. The primary outcome was the Neurological Pupil index at T4, and the secondary outcomes were other pupillometric parameters, including pupil diameter, percentage of change in pupil diameter, dilation velocity, and constriction velocity. RESULTS: At T4, the Neurological Pupil index was significantly lower in the sevoflurane group (median difference, 0.30; 95% CI, 0.00 to 0.70; p = .036). Furthermore, the Neurological Pupil index at all time points was lower in the sevoflurane group. The time-and-group interaction effects on constriction velocity and dilation velocity were significantly different [F(1, 4) = 16.68, p = .002; F(1, 4) = 14.78, p = .008, respectively] but were not different on the Neurological Pupil index, pupil diameter, and percentage of change in pupil diameter. No intergroup differences were observed in the baseline characteristics, the flow rate of remifentanil at each time point, and total infused remifentanil. CONCLUSION: The Neurological Pupil index value in pediatric patients under general anesthesia is affected by the anesthetic agent used; this factor requires consideration in evaluations of the Neurological Pupil index during general anesthesia.

Machine learning-based prediction of intraoperative hypoxemia for pediatric patients.

BACKGROUND: Reducing the duration of intraoperative hypoxemia in pediatric patients by means of rapid detection and early intervention is considered crucial by clinicians. We aimed to develop and validate a machine learning model that can predict intraoperative hypoxemia events 1 min ahead in children undergoing general anesthesia. METHODS: This retrospective study used prospectively collected intraoperative vital signs and parameters from the anesthesia ventilator machine extracted every 2 s in pediatric patients undergoing surgery under general anesthesia between January 2019 and October 2020 in a tertiary academic hospital. Intraoperative hypoxemia was defined as oxygen saturation <95% at any point during surgery. Three common machine learning techniques were employed to develop models using the training dataset: gradient-boosting machine (GBM), long short-term memory (LSTM), and transformer. The performances of the models were compared using the area under the receiver operating characteristics curve using randomly assigned internal testing dataset. We also validated the developed models using temporal holdout dataset. Pediatric patient surgery cases between November 2020 and January 2021 were used. The performances of the models were compared using the area under the receiver operating characteristic curve (AUROC). RESULTS: In total, 1,540 (11.73%) patients with intraoperative hypoxemia out of 13,130 patients' records with 2,367 episodes were included for developing the model dataset. After model development, 200 (13.25%) of the 1,510 patients' records with 289 episodes were used for holdout validation. Among the models developed, the GBM had the highest AUROC of 0.904 (95% confidence interval [CI] 0.902 to 0.906), which was significantly higher than that of the LSTM (0.843, 95% CI 0.840 to 0.846 P < .001) and the transformer model (0.885, 95% CI, 0.882-0.887, P < .001). In holdout validation, GBM also demonstrated best performance with an AUROC of 0.939 (95% CI 0.936 to 0.941) which was better than LSTM (0.904, 95% CI 0.900 to 0.907, P < .001) and the transformer model (0.929, 95% CI 0.926 to 0.932, P < .001). CONCLUSIONS: Machine learning models can be used to predict upcoming intraoperative hypoxemia in real-time based on the biosignals acquired by patient monitors, which can be useful for clinicians for prediction and proactive treatment of hypoxemia in an intraoperative setting.

Prevalence of asthma in preterm and associated risk factors based on prescription data from the Korean National Health Insurance database.

We retrospectively analyzed National Health Insurance claims data (January 2002-December 2018) to determine the asthma prevalence and risk factors among preterm infants born in Korea. Patients with asthma were defined as those with a history of asthma medication prescriptions at least twice per year with International Classification of Diseases, Tenth Edition codes J45 and J46. We enrolled 99,139 preterm infants. The prevalence of asthma among preterm and term infants was 32.7% and 26.9%, 21.2% and 19.1%, 6.7% and 5.9%, 2.0%, and 1.6%, and 2.4% and 1.6% at 2, 5, 10, 15, and 16 years of age, respectively. The relative risk (RR) of asthma in preterm infants was 1.1-fold that in female preterm infants. The RR of asthma medication prescriptions for infants with extreme prematurity was 1.92-fold that of infants with moderate/late pre-term status. Among preterm with bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS) without comorbidities, the RRs for the number of asthma medication prescriptions were 1.34 and 1.06, respectively. This study revealed a higher prevalence of asthma among preterm infants than that in term infants. Male sex, extreme prematurity, BPD, and RDS were identified as risk factors for asthma medication prescriptions in preterm infants.

Lactate oxidase/vSIRPα conjugates efficiently consume tumor-produced lactates and locally produce tumor-necrotic H2O2 to suppress tumor growth.

Aggressive tumor formation often leads to excessive anaerobic glycolysis and massive production and accumulation of lactate in the tumor microenvironment (TME). To significantly curb lactate accumulation in TME, in this study, lactate oxidase (LOX) was used as a potential therapeutic enzyme and signal regulatory protein α variant (vSIRPα) as a tumor cell targeting ligand. SpyCatcher protein and SpyTag peptide were genetically fused to LOX and vSIRPα, respectively, to form SC-LOX and ST-vSIRPα and tumor-targeting LOX/vSIRPα conjugates were constructed via a SpyCatcher/SpyTag protein ligation system. LOX/vSIRPα conjugates selectively bound to the CD47-overexpressing mouse melanoma B16-F10 cells and effectively consumed lactate produced by the B16-F10 cells, generating adequate amounts of hydrogen peroxide (H2O2), which induces drastic necrotic tumor cell death. Local treatments of B16-F10 tumor-bearing mice with LOX/vSIRPα conjugates significantly suppressed B16-F10 tumor growth in vivo without any severe side effects. Tumor-targeting vSIRPα may allow longer retention of LOX in tumor sites, effectively consuming surrounding lactate in TME and locally generating adequate amounts of cytotoxic H2O2 to suppress tumor growth. The approach restraining the local lactate concentration and H2O2 in TME using LOX and vSIRPα could offer new opportunities for developing enzyme/targeting ligand conjugate-based therapeutic tools for tumor treatment.

Effect of Tulobuterol Patch Versus Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies: A Randomized Controlled Trial.

BACKGROUND: Perioperative respiratory adverse events are common in children. We aimed to evaluate the effect of the transdermal ß-2 agonist, tulobuterol, compared with that of placebo on the incidence of perioperative respiratory adverse events in pediatric patients undergoing tonsillectomy. METHODS: In this triple-blinded (patient, anesthesia provider, and outcome assessor) randomized controlled trial, 188 patients were randomly allocated to receive tulobuterol or a placebo. The tulobuterol groups received a tulobuterol patch (1 mg) masked with a bandage, whereas the placebo only received the bandage. The assigned bandage was applied to the patients 8 to 10 hours before the surgery. The primary outcome was the occurrence of any perioperative respiratory adverse events: oxygen desaturation <95%, airway obstruction, laryngospasm, bronchospasm, severe coughing, or stridor. The outcomes were evaluated using the average relative effect test, which estimates the effect of individual components of a composite outcome and then averages effects across components. RESULTS: A total of 88 and 94 patients who received tulobuterol and placebo, respectively, were analyzed. The incidence of any perioperative respiratory adverse event was lower with tulobuterol (n = 13/88; 14.7%) than that with the placebo (n = 40/94; 42.5%), with an estimated average relative risk (95% confidence interval) across components of 0.35 (0.20-0.60; P < .001). The symptoms of airway obstruction were lower with tulobuterol (n = 8/88; 9.0%) than that with the placebo (n = 32/94; 34.0%), with relative risk (95% CI) of 0.31 (0.17-0.56; P < .001). The occurrence of severe coughing was lower with tulobuterol (n = 1/88; 1.1%) than that with the placebo (n = 8/94; 8.5%), with relative risk (95% CI) of 0.15 (0.03-0.68; P = .014). CONCLUSIONS: In preschool children undergoing tonsillectomy, the preoperative application of a tulobuterol patch could decrease the occurrence of perioperative respiratory adverse events. Further studies are needed to elucidate the effect of the tulobuterol patch in a broad spectrum of pediatric anesthesia.