Search

Background: Ketamine administration during stable propofol anesthesia is known to be associated with an increase in bispectral index (BIS) but a "deepening" in the level of hypnosis. This study aimed to evaluate the association between the effect-site concentration of ketamine (CeK) and 2 electroencephalogram (EEG)-derived parameters, the BIS and spectral edge frequency (SEF95), after the administration of a ketamine bolus. Secondary aims included investigating the BIS and SEF95 variations with time and changes in the surgical pleth index (SPI)., Methods: We conducted an observational, prospective, single-center study analyzing intraoperative data from 14 adult female patients undergoing breast oncologic surgery. During stable propofol-remifentanil target-controlled infusion (TCI) anesthesia, a ketamine analgesic bolus was delivered with the target CeK set to 1 μg.mL-1 (Domino model) corresponding to a dose of 0.57 mg.kg-1 (interquartile range [IQR] 0.56-0.57 mg.kg-1). Once the CeK reached a value of 1 μg.mL-1, the target CeK was set to 0 μg.mL-1. We determined the median BIS, SEF95, and SPI trends with time and as a function of the modeled CeK., Results: BIS and SEF95 showed no significant change from when ketamine was administered to when CeK=1 μg.mL-1, but a significant increase was observed at lower CeKs. The maximum BIS was reached at 16.0 minutes [10.2-22.7 minutes] after CeK=1 μg.mL-1, at CeK=0.22 μg.mL-1 [0.12-0.41 μg.mL-1]. The peak SEF95 value was observed at 10.0 minutes [8.62-14.1 minutes] after CeK=1 μg.mL-1, at CeK=0.43 μg.mL-1 [0.25-0.50 μg.mL-1]. No significant association was found between CeK and the registered SPI values., Conclusions: Our results show that BIS and SEF95, but not SPI, follow a CeK-dependent trend after administering a ketamine bolus. Interestingly, their peak values were not reached at CeK=1 μg.mL-1, but after several minutes after the drug infusion at CeKs in the 0.2 to 0.5 μg.mL-1 range. This may be explained by the specific pharmacodynamics of ketamine and its varying effects at different concentrations, as well as by the time delay associated with the calculation of the BIS., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Background/Objectives: Managing postoperative pain in patients with obesity is challenging. Although using a combination of pain relief methods is recommended for these patients, the true effectiveness of various intravenous non-opioid analgesics and adjuvants in multimodal anesthesia needs to be better defined. Methods: A systematic review and network meta-analysis was performed to evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, ketamine, α-2 agonists, lidocaine, magnesium, and oral gabapentinoids in adult surgical patients with obesity. The analysis aimed to compare these treatments to a placebo/no treatment or alternative analgesics, with a primary focus on postoperative pain and secondary endpoints including rescue analgesia, postoperative nausea and vomiting (PONV), and recovery quality. English-language randomized controlled trials across PubMed, Scopus, Web of Science, CINAHL, and EMBASE were considered. Quality and evidence certainty were assessed with the RoB 2 tool and GRADE, and data was analyzed with R software. Results: NSAIDs, along with acetaminophen, lidocaine, α-2 agonists, ketamine, and oral gabapentinoids, effectively reduce early postoperative pain. NSAIDs, particularly ibuprofen, as well as acetaminophen, ketamine, and lidocaine, also show benefits in later postoperative stages. Intravenous non-opioid analgesics and adjuvants show some degree of benefit in reducing PONV and the need for rescue analgesic therapy when using α-2 agonists alone or combined with oral gabapentinoids, notably decreasing the likelihood of PONV. Ketamine, lidocaine, and α-2 agonists are shown to enhance postoperative recovery and care quality. Conclusions: Intravenous non-opioid analgesics and adjuvants are valuable in multimodal anesthesia for pain management in adult surgical patients suffering from obesity.

Cornified skin appendages, such as hair and nails, are major evolutionary innovations of terrestrial vertebrates. Human hair and nails consist largely of special intermediate filament proteins, known as hair keratins, which are expressed under the control of the transcription factor Hoxc13. Here, we show that the cornified claws of Xenopus frogs contain homologs of hair keratins and the genes encoding these keratins are flanked by promoters in which binding sites of Hoxc13 are conserved. Furthermore, these keratins and Hoxc13 are co-expressed in the claw-forming epithelium of frog toe tips. Upon deletion of hoxc13, the expression of hair keratin homologs is abolished and the development of cornified claws is abrogated in X. tropicalis. These results indicate that Hoxc13-dependent expression of hair keratin homologs evolved already in stem tetrapods, presumably as a mechanism for protecting toe tips, and that this ancestral genetic program was coopted to the growth of hair in mammals., (© 2024. The Author(s).)

CRISPR-mediated simultaneous targeting of candidate tumor suppressor genes in Xenopus tropicalis allows fast functional assessment of co-driver genes for various solid tumors. Genotyping of tumors that emerge in the mosaic mutant animals rapidly exposes the gene mutations under positive selection for tumor establishment. However, applying this simple approach to the blood lineage has not been attempted. Multiple hematologic malignancies have mutations in EZH2, encoding the catalytic subunit of the Polycomb Repressive Complex 2. Interestingly, EZH2 can act as an oncogene or a tumor suppressor, depending on cellular context and disease stage. We show here that mosaic CRISPR/Cas9 mediated ezh2 disruption in the blood lineage resulted in early and penetrant acute myeloid leukemia (AML) induction. While animals were co-targeted with an sgRNA that induces notch1 gain-of-function mutations, sequencing of leukemias revealed positive selection towards biallelic ezh2 mutations regardless of notch1 mutational status. Co-targeting dnm2, recurrently mutated in T/ETP-ALL, induced a switch from myeloid towards acute T-cell leukemia. Both myeloid and T-cell leukemias engrafted in immunocompromised hosts. These data underline the potential of Xenopus tropicalis for modeling human leukemia, where mosaic gene disruption, combined with deep amplicon sequencing of the targeted genomic regions, can rapidly and efficiently expose co-operating driver gene mutations., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Various pharmacokinetic/pharmacodynamic (PK/PD) models have been developed to accurately dose propofol administration during total intravenous anesthesia with target-controlled infusion (TIVA-TCI). We aim to clinically compare the performance of the Schnider model and the new and general-purpose Eleveld PK/PD model during TIVA-TCI., Methods: We conducted a prospective observational study at a single center, enrolling 78 female patients, including 37 adults (aged < 65 years) and 41 elderly patients (aged ≥ 65 years). These patients underwent breast surgery with propofol-remifentanil TIVA-TCI guided by the bispectral index (BIS) for depth of anesthesia monitoring (target value 40-60) and the surgical plethysmographic index (SPI) for antinociception monitoring (target value 20-50) without neuromuscular blockade. The concentration at the effect site of propofol (CeP) at loss of responsiveness (LoR) during anesthesia maintenance (MA) and at return of responsiveness (RoR), the duration of surgery and anesthesia (min), the time to RoR (min), the propofol total dose (mg), the deepening of anesthesia events (DAEs), burst suppression events (BSEs), light anesthesia events (LAEs) and unwanted spontaneous responsiveness events (USREs) were considered to compare the two PK/PD models., Results: Patients undergoing BIS-SPI-guided TIVA-TCI with the Eleveld PK/PD model showed a lower CeP at LoR (1.7 (1.36-2.25) vs. 3.60 (3.00-4.18) μg/mL, p < 0.001), higher CePMA (2.80 (2.55-3.40) vs. 2.30 (1.80-2.50) μg/mL, p < 0.001) and at RoR (1.48 (1.08-1.80) vs. 0.64 (0.55-0.81) μg/mL, p < 0.001) than with the Schnider PK/PD model. Anesthetic hysteresis was observed only in the Schnider PK/PD model group ( p < 0.001). DAEs (69.2% vs. 30.8%, p = 0.001) and BSEs (28.2% vs. 5.1%, p = 0.013) were more frequent with the Eleveld PK/PD model than with the Schnider PK/PD model in the general patient population. DAEs (63.2% vs. 27.3%, p = 0.030) and BSEs (31.6% vs. 4.5%, p = 0.036) were more frequent with the Eleveld PK/PD model than with the Schnider PK/PD model in the elderly., Conclusions: The Schnider and Eleveld PK/PD models impact CePs differently. A greater incidence of DAEs and BSEs in the elderly suggests more attention is necessary in this group of patients undergoing BIS-SPI-guided TIVA-TCI with the Eleveld PK/PD than with the Schnider model.

Purpose: Laparoscopic bariatric surgeries can cause intense postoperative pain. Opioid medication can alleviate the pain but can have harmful side effects especially in patients with obstructive sleep apnea. To promote early recovery, enhanced recovery after surgery guideline advises minimizing opioid use and opting for alternative analgesics. This paper aims to investigate the effect of regional anesthesia techniques through a systematic review and network meta-analysis. Primary outcome is postoperative morphine equivalent consumption at 24 h., Methods: Search was conducted in the following databases: PubMed, CENTRAL, Scopus, and EMBASE, from the inception until 10 January 2023. The eligibility criteria were determined by PICOS, including postoperative opioid consumption, pain scores, time to ambulate, use of additional analgesics, and adverse events. The quality assessment was performed using the Risk of Bias 2 Tool, and the certainty of evidence was assessed using the GRADE approach. Funnel plots were used to evaluate publication bias., Results: We included 22 studies in quantitative synthesis. A review of 12 studies found that all techniques had a lower mean consumption of opioids compared to placebo or no intervention, with TAP block having the greatest reduction. The quality of evidence for postoperative pain, PONV, time to deambulate, and use of rescue analgesics, was rated as moderate, with TAP block being the most effective intervention. There was no publication bias in any outcome., Conclusions: TAP block is superior to other regional anesthesia techniques in reducing opioid consumption, pain, PONV, and use of rescue analgesics in bariatric surgery. However, further research is needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Study Objective: To estimate the incidence of unwanted spontaneous responsiveness and burst suppression (BSupp) in patients undergoing state entropy (SE) and surgical pleth index (SPI)-guided total intravenous anesthesia (TIVA) with target-controlled infusion (TCI)., Design: Observational, prospective, single-center study., Settings: Operating room., Patients: 107 adult (<65 years) and elderly (≥65 years) women undergoing breast surgery., Interventions: Propofol-remifentanil TIVA-TCI-guided by SE for depth of anesthesia monitoring (target value 40-60) and SPI for antinociception monitoring (target value 20-50) without neuromuscular blockade., Measurements: Age; body mass index; American Society of Anesthesiologists physical status classification; concentration at the effect site of propofol (CeP) and remifentanil (CeR) at loss of responsiveness (LoR), median during anesthesia maintenance (MdM), and at return of responsiveness (RoR); propofol infusion duration; incidence of postoperative delirium (POD) with Confusing Assessment Method for the Intensive Care Unit., Main Results: During SE-SPI-guided TIVA-TCI, 13.1% of patients showed unwanted spontaneous responsiveness, whereas 45.8% showed BSupp. Unwanted spontaneous responsiveness was observed mainly in adults (p < 0.05), and higher CeP RoR (p < 0.05) was registered. BSupp was observed mainly in patients showing a lower CeP MdM (p < 0.01) and CeP RoR (p < 0.05). Unwanted spontaneous responsiveness and BSupp were not associated with significant differences in CeRs. An age-related hysteresis effect was observed, resulting in higher CeP LoR than CeP RoR (p < 0.001). 12.2% of patients showed POD. Only preoperative serum albumin was associated with increased likelihood of POD (p = 0.046)., Conclusions: The SE-SPI-guided TIVA-TCI did not prevent unwanted spontaneous responsiveness and BSupp. CeP RoR may be used as a proxy for anesthetic sensitivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Unexpected pathogen transmission between animals, humans and their shared environments can impact all aspects of society. The Tripartite organisations-the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the World Organisation for Animal Health (WOAH)-have been collaborating for over two decades. The inclusion of the United Nations Environment Program (UNEP) with the Tripartite, forming the 'Quadripartite' in 2021, creates a new and important avenue to engage environment sectors in the development of additional tools and resources for One Health coordination and improved health security globally. Beginning formally in 2010, the Tripartite set out strategic directions for the coordination of global activities to address health risks at the human-animal-environment interface. This paper highlights the historical background of this collaboration in the specific area of health security, using country examples to demonstrate lessons learnt and the evolution and pairing of Tripartite programmes and processes to jointly develop and deliver capacity strengthening tools to countries and strengthen performance for iterative evaluations. Evaluation frameworks, such as the International Health Regulations (IHR) Monitoring and Evaluation Framework, the WOAH Performance of Veterinary Services (PVS) Pathway and the FAO multisectoral evaluation tools for epidemiology and surveillance, support a shared global vision for health security, ultimately serving to inform decision making and provide a systematic approach for improved One Health capacity strengthening in countries. Supported by the IHR-PVS National Bridging Workshops and the development of the Tripartite Zoonoses Guide and related operational tools, the Tripartite and now Quadripartite, are working alongside countries to address critical gaps at the human-animal-environment interface., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: T-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm closely related to T-cell acute lymphoblastic leukaemia (T-ALL). Despite their similarities, and contrary to T-ALL, studies on paediatric T-LBL are scarce and, therefore, its molecular landscape has not yet been fully elucidated. Thus, the aims of this study were to characterize the genetic and molecular heterogeneity of paediatric T-LBL and to evaluate novel molecular markers differentiating this entity from T-ALL., Procedure: Thirty-three paediatric T-LBL patients were analyzed using an integrated approach, including targeted next-generation sequencing, RNA-sequencing transcriptome analysis and copy-number arrays., Results: Copy number and mutational analyses allowed the detection of recurrent homozygous deletions of 9p/CDKN2A (78%), trisomy 20 (19%) and gains of 17q24-q25 (16%), as well as frequent mutations of NOTCH1 (62%), followed by the BCL11B (23%), WT1 (19%) and FBXW7, PHF6 and RPL10 genes (15%, respectively). This genetic profile did not differ from that described in T-ALL in terms of mutation incidence and global genomic complexity level, but unveiled virtually exclusive 17q25 gains and trisomy 20 in T-LBL. Additionally, we identified novel gene fusions in paediatric T-LBL, including NOTCH1-IKZF2, RNGTT-SNAP91 and DDX3X-MLLT10, the last being the only one previously described in T-ALL. Moreover, clinical correlations highlighted the presence of Notch pathway alterations as a factor related to favourable outcome., Conclusions: In summary, the genomic landscape of paediatric T-LBL is similar to that observed in T-ALL, and Notch signaling pathway deregulation remains the cornerstone in its pathogenesis, including not only mutations but fusion genes targeting NOTCH1., (© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: The use of high-flow nasal oxygen (HFNO) has the potential to improve patient safety by limiting hypoxaemia during gastrointestinal endoscopy. The degree of benefit is not adequately established., Methods: English language literature searches of PubMed, Scopus, Web of Science, and Cochrane Library electronic databases were performed to identify randomised controlled trials comparing HFNO and conventional oxygen therapy (COT) for patients undergoing gastrointestinal endoscopy under deep sedation. The primary endpoint was the incidence of hypoxic events observed during endoscopic procedures. The secondary endpoints were the incidence of recourse to rescue manoeuvres, procedure interruption, and adverse events. A meta-analysis and a post hoc trial sequence analysis were performed., Results: A total of 2867 patients from six randomised controlled trials were considered. Desaturation was observed in 5.2% and 27.2% of patients receiving HFNO and COT, respectively. Desaturation <90% was observed in 1.8% and 12.6% of the patients receiving HFNO and COT, respectively. In the subgroup analysis, desaturation occurrence was lower during HFNO than during COT in non-obese patients (2.2% vs 25.2%) and obese patients (22.9% vs 43.3%). Desaturation occurrence was lower during maximum (3.6% vs 26.9%) and minimum (15.9% vs 29.8%) HFNO therapy than during COT. HFNO showed a lower recurrence to rescue manoeuvres rate (4.7% vs 34.3%), a lower procedure interruption rate (0.4% vs 6.7%), and a lower adverse events rate (18.7% vs 21%) than COT. A high level of heterogeneity between the studies precluded confidence in drawing inference from the meta-analysis., Conclusions: The evidence reviewed suggests that compared with COT, HFNO has fewer hypoxaemic events during gastrointestinal endoscopy, but this may not apply to all patients and clinical scenarios., (© 2022 The Author(s).)

Background: Enhanced recovery after bariatric surgery (ERABS) is an approach developed to improve outcomes in obese surgical patients. Unfortunately, it is not evenly implemented in Italy. The Italian Society for the Surgery of Obesity and Metabolic Diseases and the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care joined in drafting an official statement on ERABS., Methods: To assess the effectiveness and safety of ERABS and to develop evidence-based recommendations with regard to pre-, intra-, and post-operative care for obese patients undergoing ERABS, a 13-member expert task force of surgeons and anesthesiologists from Italian certified IFSO center of excellence in bariatric surgery was established and a review of English-language papers conducted. Oxford 2011 Levels of Evidence and U.S. Preventive Services Task Force Grade Definitions were used to grade the level of evidence and the strength of recommendations, respectively. The supporting evidence and recommendations were reviewed and discussed by the entire group at meetings to achieve a final consensus., Results: Compared to the conventional approach, ERABS reduces the length of hospital stay and does not heighten the risk of major post-operative complications, re-operations, and hospital re-admissions, nor does it increase the overall surgical costs. A total of 25 recommendations were proposed, covering pre-operative evaluation and care (7 items), intra-operative management (1 item, 11 sub-items), and post-operative care and discharge (6 items)., Conclusions: ERABS is an effective and safe approach. The recommendations allow the proper management of obese patients undergoing ERABS for a better outcome., (© 2022. The Author(s).)

Introduction: Preoperative neurocognitive disorder (preO-NCD) is a common condition affecting 14-51. 7% of the elderly population. General anesthesia has already been associated with the one-year post-operative neurocognitive disorder (PostO-NCD), specifically, a deficit in executive function, measured by the Trail Making Test B (TMT-B), but its long-term effects on cognitive function have not been investigated. We aimed to detect preO-NCD prevalence in patients scheduled for cardiac surgery and further investigate the possible role of previous general anesthesia (pGA) in general preoperative cognitive status [measured via the Montreal Cognitive Assessment (MoCA)] and/or in executive functioning (measured via TMT-B)., Methods: In this observational, prospective study, 151 adult patients scheduled for elective cardiac surgery underwent MoCA and TMT-B. Data on age, education, pGA, comorbidities, and laboratory results were collected., Results: We discovered a general cognitive function impairment of 79.5% and an executive function impairment of 22%. Aging is associated with an increased likelihood (OR 2.99, p = 0.047) and education with a decreased likelihood (OR 0.35, p = 0.0045) of general cognitive impairment, but only education was significantly associated with a decreased likelihood (OR 0.22, p = 0.021) of executive function impairment. While pGA did not significantly affect preO-NCD, a noteworthy interaction between aging and pGA was found, resulting in a synergistic effect, increasing the likelihood of executive function impairment (OR 9.740, p = 0.0174)., Conclusion: We found a high prevalence of preO-NCD in patients scheduled for cardiac surgery. General cognitive function impairment is highly associated with advancing age (not pGA). However, older patients with at least one pGA appeared to be at an increased risk of preO-NCD, especially executive function impairment, suggesting that TMT-B should be associated with MoCA in the preoperative cognitive evaluation in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Linassi, De Laurenzis, Maran, Gadaldi, Spano', Gerosa, Pittarello, Zanatta and Carron.)

There has been an increase in surgical interventions in frailer elderly with concomitant chronic diseases. The purpose of this paper was to evaluate the impact of aging and comorbidities on outcomes in patients who underwent surgery for the treatment of colorectal cancer (CRC) in Veneto Region (Northeastern Italy). This is a retrospective cohort study in patients ≥ 40 years who underwent elective or urgent CRC surgical resection between January 2013 and December 2015. Independent variables included: age, sex, and comorbidities. We analyzed variables associated with the surgical procedure, such as stoma creation, hospitalization during the year before the index surgery, the surgical approach used, the American Society of Anesthesiologists (ASA) score, and the Charlson Comorbidity Index score. Eight thousand four hundred and forty-seven patients with CRC underwent surgical resection. Patient age affected both pre- and post-resection LOS as well as the overall survival (OS); however, it did not affect the 30-day readmission and reoperation rates. Multivariate analysis showed that age represented a risk factor for longer preoperative and postoperative LOS as well as for 30-day and 365-day mortality, but it was not associated with an increased risk of 30-day reoperation and 30-day readmission. Chronic Heart Failure increased the 30-day mortality risk by four times, the preoperative LOS by 51%, and the postoperative LOS by 33%. Chronic renal failure was associated with a 74% higher 30-day readmission rate. Advanced age and comorbidities require a careful preoperative evaluation and appropriate perioperative management to improve surgical outcomes in older patients undergoing elective or urgent CRC resection., (© 2021. The Author(s).)

Background: Postoperative cognitive decline occurs commonly after cardiac surgery. The available literature is inconclusive on the role of intraoperative causal or protective factors., Methods: We systematically reviewed studies evaluating delayed neurocognitive recovery (DNR), postoperative neurocognitive disorder (NCD), stroke, and the mortality rates among patients undergoing hypothermic or normothermic cardiopulmonary bypass (CPB). We further performed a subgroup analysis for age, surgery type (coronary artery bypass grafting [CABG], valve surgery, or combined), and the mean arterial blood pressure (MAP) during CPB, and conducted a proportion meta-analysis after calculation of single proportions and confidence intervals (CIs)., Results: We included a total of 58 studies with 9609 patients in our analysis. Among these, 1906 of 4010 patients (47.5%) had DNR, and 2071 of 7160 (28.9%) had postoperative NCD. Ninety of 4625 patients (2.0%) had a stroke, and 174 of 7589 (2.3%) died. There was no statistically significant relationship between the considered variables and DNR, NCD, stroke, and mortality. In the subgroup analysis comparing hypothermic with normothermic CPB, we found higher NCD rates after combined surgery; for normothermic CPB cases only, the rates of DNR and NCD were lower after combined surgery compared with CABG surgery. A MAP >70 mm Hg compared with MAP=50-70 mm Hg during CPB was associated with a lower rate of DNR., Conclusions: Temperature, MAP during cardiopulmonary bypass age, and surgery type were not associated with neurocognitive disorders, stroke, and mortality in cardiac surgery. Normothermic cardiopulmonary bypass, particularly when performed with MAP >70 mm Hg, may reduce the risk of postoperative neurocognitive decline after cardiac surgery., Prospero Registration Number: CRD42019140844., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)