Advancements in genetically modified insect pest-resistant crops in India.

MAIN CONCLUSION: The review offers insights into the current state of research on insect pest-resistant GM crops and the regulations governing the cultivation of GM crops in India. India has a rich crop diversity of more than 160 major and minor crops through its diverse agroclimatic conditions. Insect pests alone cause around USD 36 billion in crop loss annually in India. The last two decades witnessed considerable progress in managing insect pests by adopting innovative techniques including transgenics. In research, significant advancement has been brought in insect pest-resistant transgenics in India since its inception in 2002. However, any events have not been endorsed owing to biosafety impediments, except Bt cotton reaching the commercial release stage. A landmark decision to exempt certain types of gene-edited plants from genetically modified organism (GMO) regulations offers great promise for developing novel insect-resistant crops in India. The article reviews the current research on insect pest-resistant transgenics and its regulations in India.

Prophylactic dexamethasone for rebound pain after peripheral nerve block in adult surgical patients: systematic review, meta-analysis, and trial sequential analysis of randomised controlled trials.

BACKGROUND: Rebound pain occurs after the resolution of peripheral nerve block and hampers patient recovery in the postoperative period. We sought to synthesise available data from randomised controlled trials (RCTs) evaluating the efficacy of prophylactic dexamethasone for rebound pain in adult patients undergoing surgery with a peripheral nerve block. METHODS: In this systematic review and meta-analysis, RCTs reporting rebound pain and use of dexamethasone in the context of a peripheral nerve block were searched in various databases and updated in May 2023. The primary outcome was the incidence of rebound pain; secondary outcomes included the severity and time to onset of rebound pain, patient satisfaction with pain control, sleep disturbance because of pain, and adverse effects of dexamethasone. Subgroup analysis was conducted based on the effect of route of administration (intravenous or perineural) on the incidence of rebound pain. Trial sequential analysis was performed to rule out the possibility of a false positive result. RESULTS: Seven RCTs comprising 574 patients were included in this review. The dexamethasone group was associated with a reduction in the incidence of rebound pain with an odds ratio of 0.16 (95% confidence interval 0.10-0.27, P=0.00, I2=0%) compared with the control group. Trial sequential analysis confirmed the adequate information size for the beneficial effect of dexamethasone. Subgroup analysis showed that both intravenous and perineural administration were associated with a significant reduction in the incidence of rebound pain. CONCLUSIONS: Current evidence suggests that both intravenous and perineural dexamethasone reduce the incidence of rebound pain after a peripheral nerve block provided for postoperative analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023424031.

Loss-of-Resistance Versus Dynamic Pressure-Sensing Technology for Successful Placement of Thoracic Epidural Catheters: A Randomized Clinical Trial.

BACKGROUND: The traditional loss-of-resistance (LOR) technique for thoracic epidural catheter placement can be associated with a high primary failure rate. In this study, we compared the traditional LOR technique and dynamic pressure-sensing (DPS) technology for primary success rate and secondary outcomes pertinent to identifying the thoracic epidural space. METHODS: This pragmatic, randomized, patient- and assessor-blinded superiority trial enrolled patients ages 18 to 75 years, scheduled for major thoracic or abdominal surgeries at a tertiary care teaching hospital. Anesthesiology trainees (residents and fellows) placed thoracic epidural catheters under faculty supervision and rescue. The primary outcome was the success rate of thoracic epidural catheter placement, evaluated by the loss of cold sensation in the thoracic dermatomes 20 minutes after injecting the epidural test dose. Secondary outcomes included procedural time, ease of catheter placement, the presence of a positive falling meniscus sign, early hemodynamic changes, and unintended dural punctures. Additionally, we explored outcomes that included number of attempts, needle depth to epidural space, need for faculty to rescue the procedure from the trainee, patient-rated procedural discomfort, pain at the epidural insertion site, postoperative pain scores, and opioid consumption over 48 hours. RESULTS: Between March 2019 and June 2020, 133 patients were enrolled; 117 were included in the final analysis (n = 57 for the LOR group; n = 60 for the DPS group). The primary success rate of epidural catheter placement was 91.2% (52 of 57) in the LOR group and 96.7% (58 of 60) in the DPS group (95% confidence interval [CI] of difference in proportions: -0.054 [-0.14 to 0.03]; P = .264). No difference was observed in procedural time between the 2 groups (median interquartile range [IQR] in minutes: LOR 5.0 [7.0], DPS 5.5 [7.0]; P = .982). The number of patients with epidural analgesia onset at 10 minutes was 49.1% (28 of 57) in the LOR group compared to 31.7% (19 of 60) in the DPS group ( P = .062). There were 2 cases of unintended dural punctures in each group. Other secondary or exploratory outcomes were not significantly different between the groups. CONCLUSIONS: Our trial did not establish the superiority of the DPS technique over the traditional LOR method for identifying the thoracic epidural space ( Clinicaltrials.gov identifier: NCT03826186).

The impact of spinal versus general anesthesia on the variability of surgical times: a systematic review and meta-analysis.

BACKGROUND: With spinal anesthesia, when cases are taking longer than usual, there may be behavioural tendencies for surgical teams to work more quickly. We conducted a systematic review with meta-analysis to examine standard deviations of surgical times for single-dose spinal anesthetics versus general anesthesia. We compared ratios of mean surgical times as a secondary endpoint. METHODS: We included randomized trials of humans where general or spinal anesthesia was used for one category of surgical procedure (e.g., hip arthroplasty) and the article reported the means and standard deviations of operative durations. We used statistical methods suitable for surgical times following log-normal distributions. We used generalized confidence intervals to calculate point estimates of ratios and standard errors for each study, followed by pooling among studies using DerSimonian and Laird random-effects meta-analysis with Knapp-Hartung adjustment. RESULTS: Among the 77 included studies, 96% were of high quality for our endpoint (i.e., had a low risk of bias), as no (0%) study focused on comparing variability of surgical times and none had surgical time as the primary endpoint. Spinal anesthesia was associated with 6.6% smaller standard deviations than general anesthesia (95% confidence interval, 15.8% smaller to 1.9% larger, P = 0.13). By meta-regression, there was no significant association of the ratios of standard deviations with study quality (P = 0.39), year of publication (P = 0.76), or categories of procedures (all five P ≥ 0.28). Spinal anesthesia was associated with 1.1% smaller means than general anesthesia (95% confidence interval, 3.7% smaller to 1.5% larger, P = 0.42). There were no significant associations between the ratios of means and study quality (P = 0.47), year of publication (P = 0.95), or categories of procedures (all five, P ≥ 0.63). CONCLUSIONS: The results of this systematic review and meta-analysis show with high confidence that the effect of choosing spinal anesthesia on variability in surgical time, if present, is sufficiently small to have no substantive direct economic effect. The same conclusion applies to mean surgical time. Therefore, although anesthetic choice has a clinical (biological) impact and affects anesthesia times, the direct effects on surgical times and workflow are minimal at most. Anesthetic choice does not influence operating theatre productivity via changes to surgical times. The impact of spinal anesthetic effects is limited to nonoperative times (e.g., reducing anesthesia-controlled times by using a block room before the patient enters the operating room). STUDY REGISTRATION: PROSPERO ( CRD42023461952 ); first submitted 8 September 2023.

RéSUMé: CONTEXTE: Lors de l'utilisation de rachianesthésie, si les cas prennent plus de temps que d'habitude, les équipes chirurgicales pourraient avoir tendance à travailler plus rapidement. Nous avons réalisé une revue systématique avec méta-analyse pour examiner les écarts types des temps chirurgicaux pour les rachianesthésies en dose unique par rapport à l'anesthésie générale. Nous avons comparé les rapports des durées chirurgicales moyennes comme critère d'évaluation secondaire. MéTHODE: Nous avons inclus des études randomisées chez l'humain dans lesquelles l'anesthésie générale ou rachidienne avait été utilisée pour une catégorie d'intervention chirurgicale (par exemple, l'arthroplastie de la hanche) et pour lesquelles les moyennes et les écarts types des durées opératoires étaient rapportés. Nous avons utilisé des méthodes statistiques adaptées aux temps chirurgicaux suivant des distributions log-normales. Nous avons utilisé des intervalles de confiance généralisés pour calculer des estimations ponctuelles des ratios et des erreurs-types pour chaque étude, suivis d'un regroupement entre les études à l'aide d'une méta-analyse à effets aléatoires de DerSimonian et Laird avec ajustement de Knapp-Hartung. RéSULTATS: Parmi les 77 études incluses, 96 % étaient de haute qualité pour notre critère d'évaluation (c'est-à-dire qu'elles présentaient un faible risque de biais), car aucune étude (0 %) ne s'est concentrée sur la comparaison de la variabilité des temps chirurgicaux et aucune n'avait le temps chirurgical comme critère d'évaluation principal. La rachianesthésie était associée à des écarts types inférieurs de 6,6 % à ceux de l'anesthésie générale (intervalle de confiance à 95 %, 15,8 % plus petit à 1,9 % plus grand, P = 0,13). Par métarégression, il n'y avait pas d'association significative entre les ratios des écarts types et la qualité de l'étude (P = 0,39), l'année de publication (P = 0,76), ou des catégories de procédures (les cinq P ≥ 0,28). La rachianesthésie était associée à des moyennes inférieures de 1,1 % à celles de l'anesthésie générale (intervalle de confiance à 95 %, 3,7 % plus petit à 1,5 % plus grand, P = 0,42). Il n'y a pas eu d'association significative entre les ratios des moyennes et la qualité des études (P = 0,47), l'année de publication (P = 0,95), ou les catégories de procédures (toutes les cinq, P ≥ 0,63). CONCLUSION: Les résultats de cette revue systématique et de cette méta-analyse montrent avec un degré de confiance élevé que l'effet du choix de la rachianesthésie sur la variabilité du temps chirurgical, le cas échéant, est suffisamment faible pour n'avoir aucun effet économique direct substantiel. La même conclusion s'applique au temps chirurgical moyen. Par conséquent, bien que le choix de l'anesthésie ait un impact clinique (biologique) et affecte les temps d'anesthésie, les effets directs sur les temps chirurgicaux et le flux de travail sont tout au plus minimes. Le choix du type d'anesthésie n'influence pas la productivité de la salle d'opération en modifiant les temps chirurgicaux. L'impact des effets de la rachianesthésie est limité aux périodes non opératoires (p. ex., réduire les temps de contrôle de l'anesthésie en utilisant une salle de bloc avant que le patient ou la patiente n'entre en salle d'opération). ENREGISTREMENT DE L'éTUDE: PROSPERO ( CRD42023461952 ); première soumission le 8 septembre 2023.

Current concepts and targets for preventing the transition of acute to chronic postsurgical pain.

PURPOSE OF REVIEW: It is estimated that approximately a third of patients undergoing certain surgeries may report some degree of persistent pain postoperatively. Chronic postsurgical pain (CPSP) reduces quality of life, is challenging to treat, and has significant socio-economic impact. RECENT FINDINGS: From an epidemiological perspective, factors that predispose patients to the development of CPSP may be considered in relation to the patient, the procedure or, the care environment. Prevention or management of transition from acute to chronic pain often need a multidisciplinary approach beginning early in the preoperative period and continuing beyond surgical admission. The current concepts regarding the role of central and peripheral nervous systems in chronification of pain may provide targets for future therapies but, the current evidence seems to suggest that a multimodal analgesic approach of preventive analgesia along with a continued follow-up and treatment after hospital discharge may hold the key to identify and manage the transitioning of acute to chronic pain. SUMMARY: A comprehensive multidisciplinary approach with prior identification of risk factors, minimizing the surgical insult and a culture of utilizing multimodal analgesia and continued surveillance beyond the period of hospitalization is an important step towards reducing the development of chronic pain. A transitional pain service model may accomplish many of these goals.

Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-Analysis.

PURPOSE: Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients. METHODS: We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology. RESULTS: We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared to fixed LMWH dosing, anti-Xa-guided dosing may reduce deep vein thrombosis [adjusted odds ratio (aOR); 0.52, 95% CI: 0.40-0.69], pulmonary embolism (aOR: 0.48, 95% CI: 0.30-0.78) or any VTE (aOR: 0.54, 95% CI: 0.42-0.69), though all estimates are based on low certainty evidence. There was an uncertain effect on mortality (aOR: 1.06, 95% CI: 0.85-1.32) and bleeding events (aOR: 0.84, 95% CI: 0.50-1.39), limited by serious imprecision. We used several sensitivity and subgroup analyses to confirm the validity of our assumptions. CONCLUSION: Anti-Xa-guided dosing may be more effective than fixed dosing for prevention of deep vein thrombosis, pulmonary embolism, and VTE for adult trauma patients. These promising findings justify the need for a high-quality randomized study with the potential to deliver practice changing results.

Diversity of transgenes in sustainable management of insect pests.

Insecticidal transgenes, when incorporated and expressed in plants, confer resistance against insects by producing several products having insecticidal properties. Protease inhibitors, lectins, amylase inhibitors, and chitinase genes are associated with the natural defenses developed by plants to counter insect attacks. Several toxin genes are also derived from spiders and scorpions for protection against insects. Bacillus thuringiensis Berliner is a microbial source of insecticidal toxins. Several methods have facilitated the large-scale production of transgenic plants. Bt-derived cry, cyt, vip, and sip genes, plant-derived genes such as lectins, protease inhibitors, and alpha-amylase inhibitors, insect cell wall-degrading enzymes like chitinase and some proteins like arcelins, plant defensins, and ribosome-inactivating proteins have been successfully utilized to impart resistance to insects. Besides, transgenic plants expressing double-stranded RNA have been developed with enhanced resistance. However, the long-term effects of transgenes on insect resistance, the environment, and human health must be thoroughly investigated before they are made available for commercial planting. In this chapter, the present status, prospects, and future scope of transgenes for insect pest management have been summarized and discussed.

Neuromodulation using a hybrid technique of combined perineural local anesthetic and nerve stimulation in six challenging clinical scenarios.

PURPOSE: Postamputation pain is challenging because of complex mechanisms involving a multitude of pain pathways and psychological factors. This patient population also tends to have extensive comorbidities with or without a background of chronic pain. Electrical neuromodulation such as peripheral nerve stimulation has gained traction in the realm of chronic pain. Recently, the off-label use of hybrid perineural nerve stimulation in combination with locoregional block via the stimulating nerve block catheter has been described in single-center case reports. CLINICAL FEATURES: Herein, we present a case series of six patients from two different Canadian hospitals using such a hybrid technique in three different clinical scenarios. These scenarios were (1) local anesthetic dose minimization in the presence of multiple nerve block catheters, (2) analgesia augmentation when local anesthetic alone is insufficient, and (3) provision of an analgesic adjunct as part of a multimodal regimen. A stimulating sciatic nerve block catheter was inserted under ultrasound and nerve stimulation guidance for these cases. Patients tended to experience pain on the subsequent postoperative days whereby the off-label use of nerve stimulation successfully reduced their pain score and stabilized or decreased their opioid consumption or minimized the need to increase the local anesthetic dose when doing so could have precipitated local anesthetic toxicity. CONCLUSION: Our case series supports the feasibility of using a combination of low-frequency perineural stimulation and local anesthetic infusion via a single perineural nerve block catheter to manage challenging postamputation pain.

RéSUMé: OBJECTIF: La douleur post-amputation est difficile à soulager en raison de mécanismes complexes impliquant une multitude de voies de la douleur et de facteurs psychologiques. Cette population de patients a également tendance à présenter de nombreuses comorbidités, avec ou sans antécédents de douleur chronique. Les techniques de neuromodulation électrique, telle que la stimulation nerveuse périphérique, sont de plus en plus populaires dans le domaine de la douleur chronique. Récemment, des présentations de cas monocentriques ont décrit l'utilisation hors indication d'une modalité hybride de stimulation nerveuse périneurale en combinaison avec un bloc locorégional via un cathéter de bloc nerveux stimulant. CARACTéRISTIQUES CLINIQUES: Nous présentons ici une série de cas de six patients de deux hôpitaux canadiens différents utilisant une telle technique hybride dans trois cas cliniques différents. Ces cas étaient (1) la minimisation de la dose d'anesthésique local en présence de plusieurs cathéters de blocs nerveux, (2) l'augmentation de l'analgésie lorsque l'anesthésique local seul était insuffisant, et (3) la fourniture d'un adjuvant analgésique dans le cadre d'un régime multimodal. Un cathéter stimulant pour l'administration d'un bloc du nerf sciatique a été inséré sous échoguidage et guide de stimulation nerveuse pour ces cas. Les patients ont eu tendance à ressentir de la douleur les jours postopératoires suivants, et l'utilisation hors indication de la stimulation nerveuse a alors réussi à réduire leur score de douleur, à stabiliser ou diminuer leur consommation d'opioïdes, ou à réduire la nécessité d'augmenter la dose d'anesthésique local alors que cela aurait pu précipiter une toxicité anesthésique locale. CONCLUSION: Notre série de cas soutient la faisabilité de l'utilisation d'une technique combinée de stimulation périnerveuse à basse fréquence et de perfusion d'anesthésique local via un seul cathéter de bloc nerveux périneural pour prendre en charge la douleur post-amputation.

Comparison of the Quality of Recovery-15 score in patients undergoing oncoplastic breast-conserving surgery under monitored anesthesia care versus general anesthesia: a prospective quality improvement study.

PURPOSE: Whether changing the institutional practice from general anesthesia (GA) to monitored anesthesia care (MAC) affects postoperative quality of recovery for oncoplastic breast-conserving surgery (BCS) is currently unknown. We designed this quasi-experimental study to evaluate a quality improvement (QI) initiative instituted in Edmonton, AB, Canada. METHODS: We chose a prospective controlled cohort study design for this QI study, where patients underwent oncoplastic BCS under MAC in one hospital and BCS under GA at another hospital (control). A total of 125 patients undergoing surgery between May 2021 and February 2022 were enrolled. Exclusion criteria were male sex, total mastectomy, or age under 18. All other patients were included. The primary outcome was the change in Quality of Recovery-15 score at 24 hr compared with a preoperative baseline. Secondary outcomes included intra- and postoperative time profiles, perioperative analgesic and antiemetic use and length of hospital stay. Statistical analysis included a propensity score analysis to account for confounding variables. RESULTS: Sixty-four patients received GA and 61 MAC. No enrolled patients were lost to follow up but two were excluded secondarily. No patients receiving MAC needed conversion to GA or unplanned airway management. Monitored anesthesia care was associated with superior outcomes for the primary outcome (ß/SE[ß], 3.31; 99.5% confidence interval, 0.45 to 6.17; P = 0.001) and most secondary outcomes, when accounting for confounding factors. CONCLUSIONS: A care transformation initiative for patients undergoing oncoplastic BCS under MAC was associated with a higher quality recovery profile and shorter length of stay without any increase in perioperative or postoperative adverse events.

RéSUMé: OBJECTIF: On ignore actuellement si le fait de modifier la pratique institutionnelle de l'anesthésie générale (AG) à la sédation procédurale (monitored anesthesia care) affecte la qualité de la récupération postopératoire en cas de chirurgie mammaire conservatrice oncoplastique. Nous avons conçu cette étude quasi expérimentale pour évaluer une initiative d'amélioration de la qualité mise en place à Edmonton, Alberta, Canada. MéTHODE: Nous avons choisi une méthodologie d'étude de cohorte prospective contrôlée pour cette étude d'amélioration de la qualité, dans laquelle des patientes ont bénéficié d'une chirurgie mammaire conservatrice oncoplastique sous sédation procédurale dans un hôpital et de la même chirurgie sous anesthésie générale dans un autre hôpital (groupe témoin). Au total, 125 patientes bénéficiant d'une intervention chirurgicale entre mai 2021 et février 2022 ont été recrutées. Les critères d'exclusion étaient le sexe masculin, la mastectomie totale ou un âge de moins de 18 ans. Toutes les autres personnes ont été incluses. Le critère d'évaluation principal était la variation du score de Qualité de la récupération 15 à 24 heures par rapport aux valeurs initiales préopératoires. Les critères d'évaluation secondaires comprenaient les profils temporels per- et postopératoires, l'utilisation périopératoire d'analgésiques et d'antiémétiques et la durée du séjour à l'hôpital. L'analyse statistique comprenait une analyse par score de propension pour tenir compte des variables de confusion. RéSULTATS: Soixante-quatre patientes ont reçu une anesthésie générale et 61 une sédation procédurale. Aucune patiente recrutée n'a été perdue au suivi, mais deux ont été exclues secondairement. Aucune patiente recevant une sédation procédurale n'a eu besoin d'une conversion en anesthésie générale ou d'une prise en charge non planifiée des voies aériennes. La sédation procédurale était associée à des issues supérieures pour le critère d'évaluation principal (ß/ET[ß], 3,31; intervalle de confiance à 99,5 %, 0,45 à 6,17; P = 0,001) et la plupart des critères d'évaluation secondaires, en tenant compte des facteurs de confusion. CONCLUSION: Une initiative de transformation des soins pour les patientes bénéficiant d'une chirurgie mammaire conservatrice oncoplastique sous sédation procédurale a été associée à un profil de récupération de meilleure qualité et à une durée de séjour plus courte sans augmentation des événements indésirables périopératoires ou postopératoires.

Diagnostic Performance of Airway Ultrasound for the Assessment of Difficult Laryngoscopy: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to review and appraise the evidence regarding airway ultrasound assessment in predicting difficult laryngoscopy in adult patients. DESIGN: A systematic review of the literature was conducted according to the Cochrane collaboration guidelines and the recommendations for the systematic review and meta-analysis of diagnostic studies. Observational studies that evaluated the diagnostic performance of airway ultrasound for the prediction of difficult laryngoscopy were included for consideration. SETTING: Literature searches were performed in 4 databases (PubMed [Medline], Embase, Clinical Trials, and Google Scholar) to identify all observational studies using any ultrasound technique to assess difficult laryngoscopy. The search terms included "sonography," "ultrasound," "airway," "difficult airway," "difficult laryngoscopy," "Cormack," "risk factors," "ultrasound at the point of care," "difficult ventilation," "difficult intubation" and others, combined with sensitive filters. The search was done for studies performed in the last 20 years in English or Spanish. PARTICIPANTS: Adult patients older than 18 years old under general anesthesia for an elective procedure. Evident anatomic airway abnormalities, obstetric populations, those using an alternative imaging method besides ultrasound, and animal studies were excluded. INTERVENTIONS: Preoperative bedside ultrasound measuring distances and ratios from the skin to different reference points, such as the ratio of the hyomental distance in a neutral position (HMDN) and hyomental distance in extension (HMDR), HMDN, and the skin-to-epiglottis distance (SED), the preepiglottic area, and tongue thickness, among others. MEASUREMENTS AND MAIN RESULTS: A total of 24 studies evaluated the prediction of a difficult laryngoscopy using airway ultrasound. The diagnostic performance and the number of ultrasound parameters reported in the studies were variable. Meta-analysis was performed for 3 measurements consistently included in most studies. The SED and the HMDR ratio presented a sensitivity of 75% and 61%, respectively, and a specificity of 86% and 88%, respectively. The ratio of the preepiglottic distance to the epiglottic distance at the midpoint of the vocal cords (pre-E/E-VC) presented the best performance for predicting a difficult laryngoscopy (sensitivity: 82%, specificity: 83%, diagnostic odds ratio: 22.2). CONCLUSION: With the currently available evidence, the 3 commonly used point-of-care ultrasound measures used to identify difficult laryngoscopy, (SED, HMDR, and pre-E/E-VC), showed better sensitivity and similar specificity to clinical measures. Future studies and more data may change the authors' confidence in these conclusions, given the wide variability of measurements noted in studies.

Feasibility and Utility of Routine Point-of-Care Gastric Ultrasonography in Patients Undergoing Upper Gastrointestinal Endoscopy Procedures: A Prospective Cohort Study.

OBJECTIVES: Previous studies have indicated that point-of-care ultrasonography (POCUS) of the gastric antrum can predict the adequacy of fasting before surgery and anesthesia. The aim of this study was to evaluate the utility of gastric POCUS in patients undergoing upper gastrointestinal (GI) endoscopy procedures. METHODS: We performed a single-center cohort study in patients undergoing upper GI endoscopy. Consenting patient's gastric antrum was scanned before anesthetic care for endoscopy to determine the cross-sectional area (CSA) and qualitatively determine safe and unsafe contents. Further, an estimate of residual gastric volume was determined using the formula and the nomogram methods. Subsequently, gastric secretions aspirated during endoscopy were quantified and further correlated with nomogram and formula-based assessments. No patient required a change in the primary anesthetic plan except for using rapid sequence induction in those with unsafe contents on POCUS scans. RESULTS: Qualitative ultrasound measurements consistently determined safe and unsafe gastric residual contents in 83 patients enrolled in the study. Unsafe contents were determined by qualitative scans in 4 out of 83 cases (5%) despite adequate fasting status. Quantitatively, only a moderate correlation was demonstrated between measured gastric volumes and nomogram (r = .40, 95% CI: 0.20, 0.57; P = .0002) or formula-based (r = .38, 95% CI: 0.17, 0.55; P = .0004) determinations of residual gastric volumes. CONCLUSION: In daily clinical practice, qualitative POCUS determination of residual gastric content is a feasible and useful technique to identify patients at risk of aspiration before upper GI endoscopy procedures.

The practice of regional anesthesia during the COVID-19 pandemic: an international survey of members of three regional anesthesia societies.

PURPOSE: To determine the preferences and attitudes of members of regional anesthesia societies during the COVID-19 pandemic. METHODS: We distributed an electronic survey to members of the American Society of Regional Anesthesia and Pain Medicine, Regional Anaesthesia-UK, and the European Society of Regional Anaesthesia & Pain Therapy. A questionnaire consisting of 19 questions was developed by a panel of experienced regional anesthesiologists and distributed by email to the participants. The survey covered the following domains: participant information, practice settings, preference for the type of anesthetic technique, the use of personal protective equipment, and oxygen therapy. RESULTS: The survey was completed by 729 participants from 73 different countries, with a response rate of 20.1% (729/3,630) for the number of emails opened and 8.5% (729/8,572) for the number of emails sent. Most respondents (87.7%) identified as anesthesia staff (faculty or consultant) and practiced obstetric and non-obstetric anesthesia (55.3%). The practice of regional anesthesia either expanded or remained the same, with only 2% of respondents decreasing their use compared with the pre-pandemic period. The top reasons for an increase in the use of regional anesthesia was to reduce the need for an aerosol-generating medical procedure and to reduce the risk of possible complications to patients. The most common reason for decreased use of regional anesthesia was the risk of urgent conversion to general anesthesia. Approximately 70% of the responders used airborne precautions when providing care to a patient under regional anesthesia. The most common oxygen delivery method was nasal prongs (cannula) with a surgical mask layered over it (61%). CONCLUSIONS: Given the perceived benefits of regional over general anesthesia, approximately half of the members of three regional anesthesia societies seem to have expanded their use of regional anesthesia techniques during the initial surge of the COVID-19 pandemic.

RéSUMé: OBJECTIF: Déterminer les préférences et les attitudes des membres des sociétés d'anesthésie régionale pendant la pandémie de COVID-19. MéTHODE: Nous avons distribué un sondage électronique aux membres de l'American Society of Regional Anesthesia and Pain Medicine, de Regional Anesthesia-UK et de l'European Society of Regional Anaesthesia & Pain Therapy. Un questionnaire composé de 19 questions a été élaboré par un panel d'anesthésiologistes régionaux d'expérience et distribué par courriel aux participants. Le sondage couvrait les domaines suivants : les renseignements sur les participants, les contextes de pratique, leur préférence quant au type de technique d'anesthésie, l'utilisation d'équipement de protection individuelle et l'oxygénothérapie RéSULTATS: Le sondage a été complété par 729 participants provenant de 73 pays différents, avec un taux de réponse de 20,1 % (729/3630) pour le nombre de courriels ouverts et de 8,5 % (729/8572) pour le nombre de courriels envoyés. La plupart des répondants (87,7 %) se sont identifiés comme anesthésiologistes (académique ou consultant) et pratiquaient l'anesthésie obstétricale et non obstétricale (55,3 %). Leur pratique de l'anesthésie régionale s'est étendue ou est demeurée inchangée, et seulement 2 % des répondants ont indiqué avoir diminué leur utilisation de cette pratique par rapport à la période pré-pandémique. Les principales raisons d'une augmentation de l'utilisation de l'anesthésie régionale étaient de réduire la nécessité d'une intervention médicale générant des aérosols et de réduire le risque de complications potentielles pour les patients. La raison la plus courante de diminution du recours à l'anesthésie régionale était le risque de conversion urgente à une anesthésie générale. Environ 70 % des intervenants ont utilisé des précautions en matière de propagation des aérosols lorsqu'ils procuraient des soins à un patient sous anesthésie régionale. La méthode d'administration d'oxygène la plus fréquemment utilisée était les canules nasales avec un masque chirurgical superposé (61 %). CONCLUSION: Compte tenu des avantages perçus de l'anesthésie régionale par rapport à l'anesthésie générale, environ la moitié des membres de trois sociétés d'anesthésie régionale semblent avoir élargi leur utilisation des techniques d'anesthésie régionale pendant la vague initiale de la pandémie de COVID-19.

Discovery of new anticancer thiourea-azetidine hybrids: design, synthesis, in vitro antiproliferative, SAR, in silico molecular docking against VEGFR-2, ADMET, toxicity, and DFT studies.

With the aim to discover potent and novel antitumor agents, a series of thiourea compounds bearing 3-(4-methoxyphenyl)azetidine moiety were designed according to the essential pharmacophoric features of the reported VEGFR-2 inhibitors and synthesized. All the synthesized compounds were evaluated for their in vitro anticancer activity against various human cancer cell lines (lung (A549), prostate (PC3), breast (MCF-7), liver (HepG2), colon (HCT-116), ovarian (SKOV-3), skin (A431), brain (U251) and kidney (786-O)). 3-(4-Methoxy-3-(2-methoxypyridin-4-yl)phenyl)-N-(4-methoxyphenyl)azetidine-1-carbothioamide (3B) was found to be most potent member against PC3, U251, A431, and 786-O cancer cell lines with EC50 values 0.25, 0.6, 0.03, and 0.03 µM, respectively and showed more potency than Doxorubicin in PC3, A431, and 786-O cell lines. Compounds 1B to 7B showed EC50 values ranging from 0.03 to 12.55 µM in A431 cell line. Compound 3-(4-methoxy-3-(pyridin-4-yl)phenyl)-N-(4-methoxyphenyl)azetidine-1-carbothioamide (1B) was found to be highly efficient in A431 and 786-O cell line with EC50 values of 0.77 and 0.73 µM respectively. All the compounds exhibited good to moderate cytotoxic activity. The pharmacophoric features and molecular docking studies confirmed the potentialities of compounds 1B, 2B, 3B and 5B to be VEGFR-2 inhibitors. Moreover, in silico ADMET prediction indicated that most of the synthesized compounds have drug-like properties, possess low adverse effects and toxicity. In addition, the DFT studies for the most active compounds (1B and 3B) were carried out. In the end, our studies revealed that the compounds 1B and 3B represent promising anticancer potentialities through their VEGFR-2 inhibition.

How I Do It: Technical report on surgically-initiated rectus sheath catheter using catheter-over-needle assembly.

Development of chronic postsurgical pain following major abdominal or pelvic surgeries is increasingly recognized. Multimodal analgesia including regional anesthesia such as rectus sheath block is growing in popularity. While the literature mainly describes ultrasound-guided rectus sheath blocks, there are many advantages to surgically-initiated rectus sheath catheter performed at the end of surgery. In this technical description, we describe the rationale and technique of surgical insertion of rectus sheath catheters following major urologic surgery with midline incision which is routinely performed by urologists at our institution. Furthermore, we would like to highlight the type of catheter used during rectus sheath catheter insertion, namely the catheter-over-needle assembly. It is simple to insert while minimizes complications such as local anesthetic leakage at the insertion site causing dressing disruption and premature catheter dislodgement, as the catheter-over-needle assembly fits snugly with the skin after insertion.

Azetidines of pharmacological interest.

Azetidines are almost unexplored among nitrogen-containing saturated heterocycles due to difficulties associated with their synthesis. However, over the past few years, attempts have been made by scientists to advance their synthetic feasibility. Compounds with the azetidine moiety display an important and diverse range of pharmacological activities, such as anticancer, antibacterial, antimicrobial, antischizophrenic, antimalarial, antiobesity, anti-inflammatory, antidiabetic, antiviral, antioxidant, analgesic, and dopamine antagonist activities, and are also useful for the treatment of central nervous system disorders and so forth. Owing to its satisfactory stability, molecular rigidity, and chemical and biological properties, azetidine has emerged as a valuable scaffold and it has drawn the attention of medicinal researchers. The present review sheds light on the traditional method of synthesis of azetidine and advancements in synthetic methodology over the past few years, along with its application with various examples, and its biological significance.

Effect of combining peri-hamstring injection or anterior obturator nerve block on the analgesic efficacy of adductor canal block for anterior cruciate ligament reconstruction: a randomised controlled trial.

BACKGROUND: Pain after anterior cruciate ligament reconstruction (ACLR) with autologous hamstring graft can be attributed to both arthroscopic surgery and the graft donor site. This study investigated whether donor site pain control was superior with the addition of either peri-hamstring injection or anterior division obturator nerve block in comparison with adductor canal block (ACB) alone. METHODS: Patients scheduled to undergo knee arthroscopy with ACLR using a graft from the ipsilateral hamstring were randomised to one of three groups. All patients received ACB and multimodal analgesia. Subjects in Group H received peri-hamstring local anaesthetic injection while subjects in Group O received an anterior division of the obturator nerve block, and subjects in Group C served as a control group (ACB alone). RESULTS: In 105 subjects undergoing ACLR, there was no significant difference between groups H, O, and C for the primary outcome of pain on movement as assessed by numerical rating scale (NRS) on knee flexion at 2 h after operation (P=0.11). There was no difference in NRS at any time point in the first 48 h after operation, nor was there a difference in oxycodone consumption between the three groups at 24 h (P=0.2). Worst knee pain was initially at the graft donor site in all three groups, which transitioned to anterior knee pain after 12 h. CONCLUSIONS: The addition of ultrasound-guided peri-hamstring injection or anterior division of obturator nerve block to ACB did not result in a significant reduction in pain or opioid consumption after ACLR with ipsilateral hamstring graft. CLINICAL TRIAL REGISTRATION: NCT01868282.

The impact of sevoflurane anesthesia on postoperative renal function: a systematic review and meta-analysis of randomized-controlled trials.

PURPOSE: Renal damage secondary to fluoride ions and compound A (CpdA) after sevoflurane anesthesia remains unclear. For safety reasons, some countries still recommend minimum fresh-gas flows (FGFs) with sevoflurane. We review the evidence regarding the intraoperative use of sevoflurane for anesthesia maintenance and postoperative renal function compared with other anesthetic agents used for anesthetic maintenance. Secondarily, we examine the effects of peak plasma fluoride and CpdA levels and the effect of FGF and duration of anesthesia on these parameters. SOURCE: The databases of MEDLINE (OVID and Pubmed), EMBASE, the Cochrane Library, Health Technology Assessment Database, CINAHL, and Web of Science were searched from inception until 23 April 2020 to identify randomized-controlled trials (RCTs) in humans utilizing sevoflurane or an alternative anesthetic for anesthesia maintenance with subsequent measurements of renal function. Two different paired reviewers independently selected the studies and extracted data. The quality of the evidence was appraised using GRADE recommendations. PRINCIPAL FINDINGS: Of 3,766 publications screened, 41 RCTs in human patients were identified. There was no difference between creatinine at 24 hr (21 studies; n = 1,529), or creatinine clearance (CCR) at 24 hr (12 studies; n = 728) in the sevoflurane vs alternative anesthetic groups. Peak fluoride and fluoride measured at 24 hr were higher with sevoflurane compared with other inhaled anesthetics. Subgroup analyses for sevoflurane usage in various contexts showed no significant difference between sevoflurane and alternative anesthetics for creatinine or CCR at 24 hr at varying FGF, duration of exposure, baseline renal function, or absorbent use. CONCLUSIONS: We did not find any association between the use of sevoflurane and postoperative renal impairment compared with other agents used for anesthesia maintenance. The scientific basis for recommending higher FGF with the use of sevoflurane needs to be revisited.

RéSUMé: OBJECTIF: Les lésions rénales secondaires aux ions fluorure et au composé A (CpdA) après une anesthésie au sévoflurane demeurent incertaines. Pour des raisons de sécurité, certains pays recommandent encore des débits de gaz frais (DGF) minimaux lors de l'utilisation du sévoflurane. Nous avons passé en revue les données probantes concernant l'utilisation peropératoire de sévoflurane pour le maintien de l'anesthésie sur la fonction rénale postopératoire comparativement à d'autres agents anesthésiques utilisés pour le maintien de l'anesthésie. En analyse secondaire, nous avons examiné les effets des taux plasmatiques maximaux de fluorure et de CpdA et l'effet du DGF et de la durée de l'anesthésie sur ces paramètres. SOURCE: Des recherches ont été menées dans les bases de données de MEDLINE (OVID et Pubmed), EMBASE, the Cochrane Library, Health Technology Assessment Database, CINAHL et Web of Science, de leur création jusqu'au 23 avril 2020. Nous y avons identifié les études randomisées contrôlées (ERC) réalisées sur des sujets humains utilisant du sévoflurane ou un agent anesthésique alternatif pour le maintien de l'anesthésie et présentant des mesures subséquentes de la fonction rénale. Deux différents réviseurs appariés ont sélectionné de manière indépendante les études et extrait les données. La qualité des données probantes a été évaluée à l'aide des recommandations GRADE. CONSTATATIONS PRINCIPALES: Parmi les 3766 publications passées en revue, 41 ERC réalisées chez des patients humains ont été identifiées. Aucune différence n'a été observée en ce qui touchait à la valeur de créatinine à 24 h (21 études; n = 1529) ou de la clairance de la créatinine (CCR) à 24 h (12 études; n = 728) dans les groupes sévoflurane vs autres anesthésiques. Les taux maximaux de fluorure et le fluorure mesuré à 24 h étaient plus élevés lors de l'utilisation de sévoflurane que d'autres agents anesthésiques halogénés. Les analyses de sous-groupe portant sur l'utilisation du sévoflurane dans divers contextes n'ont démontré aucune différence significative entre le sévoflurane et les autres anesthésiques en matière de valeur de créatinine ou de CCR à 24 h selon différents DGF, durées d'exposition, fonctions rénales de base ou absorbants. CONCLUSION: Nous n'avons pas trouvé d'association entre l'utilisation du sévoflurane et des détériorations de la fonction rénale postopératoires par rapport aux autres agents utilisés pour le maintien de l'anesthésie. Les raisons scientifiques sur lesquelles repose la recommandation d'un DGF plus élevé lors de l'utilisation de sévoflurane doivent être réexaminées.

Evaluation of online clinical pharmacology curriculum resources for medical students.

AIMS: To identify and evaluate clinical pharmacology (CP) online curricular (e-Learning) resources that are internationally available for medical students. METHODS: Literature searches of Medline, EMBASE and ERIC databases and an online survey of faculty members of international English language medical schools, were used to identify CP e-Learning resources. Resources that were accessible online in English and aimed to improve the quality of prescribing specific medications were then evaluated using a summary percentage score for comprehensiveness, usability and quality, and for content suitability. RESULTS: Our literature searches and survey of 252 faculty (40.7% response rate) in 219 medical schools identified 22 and 59 resources respectively. After screening and removing duplicates, 8 eligible resources remained for evaluation. Mean total score was 53% (standard deviation = 13). The Australian National Prescribing Curriculum, ranked highest with a score of 77%, based primarily on very good ratings for usability, quality and suitable content. CONCLUSION: Using a novel method and evaluation metric to identify, classify, and rate English language CP e-Learning resources, the National Prescribing Curriculum was the highest ranked open access resource. Future work is required to implement and evaluate its effectiveness on prescribing competence.

Bilateral Thoracic Paravertebral Blocks Compared to Thoracic Epidural Analgesia After Midline Laparotomy: A Pragmatic Noninferiority Clinical Trial.

BACKGROUND: Bilateral paravertebral block (PVB) is a suitable alternative to thoracic epidural analgesia (TEA) for abdominal surgeries. This randomized clinical trial aims to determine if PVB is noninferior to TEA in terms of analgesia after midline laparotomy. METHODS: Seventy American Society of Anesthesiologists (ASA) class I-III patients undergoing a laparotomy through a midline incision were randomized to receive either TEA (TEA group) or continuous bilateral PVB (PVB group) as a part of a multimodal analgesia regimen in an open-label design. Noninferiority was to be concluded if the mean between-group difference in pain on movement at the 24 postoperative hours was within a margin of 2 points on a 0-10 numerical rating scale (NRS). Pain score at rest and on movement, analgesic consumption, hemodynamics, and adverse events during the first 72 postoperative hours were the secondary outcome measures assessed for superiority. Postblock and steady-state plasma concentrations of ropivacaine and pattern of dye spread were also recorded in the PVB group. RESULTS: The primary outcome of pain scores on movement at 24 postoperative hours was noninferior in PVB group in comparison to TEA group (mean difference [95% confidence interval {CI}], 0.43 [-0.72-1.58]). The pain scores at rest and on movement at other time points of assessment were within clinically acceptable limits in both groups with no significant differences between the groups over time. Arterial plasma ropivacaine levels were within safe limits, while steady-state venous level was higher than an acceptable threshold in 9 of 34 cases. CONCLUSIONS: As a component of multimodal analgesia, bilateral PVB provides noninferior analgesia compared to TEA for midline laparotomy.