Knockout of myoc Provides Evidence for the Role of Myocilin in Zebrafish Sex Determination Associated with Wnt Signalling Downregulation

Myocilin is a secreted glycoprotein with a poorly understood biological function and it is mainly known as the first glaucoma gene. To explore the normal role of this protein in vivo we developed a myoc knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. This line carries a homozygous variant (c.236_239delinsAAAGGGGAAGGGGA) that is predicted to result in a loss-of-function of the protein because of a premature termination codon p.(V75EfsX60) that resulted in a significant reduction of myoc mRNA levels. Immunohistochemistry showed the presence of myocilin in wild-type embryonic (96 h post-fertilization) anterior segment eye structures and caudal muscles. The protein was also detected in different adult ocular and non-ocular tissues. No gross macroscopic or microscopic alterations were identified in the KO zebrafish, but, remarkably, we observed absence of females among the adult KO animals and apoptosis in the immature juvenile gonad (28 dpf) of these animals, which is characteristic of male development. Transcriptomic analysis showed that adult KO males overexpressed key genes involved in male sex determination and presented differentially expressed Wnt signalling genes. These results show that myocilin is required for ovary differentiation in zebrafish and provides in vivo support for the role of myocilin as a Wnt signalling pathway modulator. In summary, this myoc KO zebrafish line can be useful to investigate the elusive function of this protein, and it provides evidence for the unexpected function of myocilin as a key factor in zebrafish sex determination

Riesgo quirúrgico tras resección pulmonar anatómica en cirugía torácica. Modelo predictivo a partir de una base de datos nacional multicéntrica

Introduction: the aim of this study was to develop a surgical risk prediction model in patients undergoing anatomic lung resections from the registry of the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). Methods: data were collected from 3,533 patients undergoing anatomic lung resection for any diagnosis between December 20, 2016 and March 20, 2018. We defined a combined outcome variable: death or Clavien Dindo grade IV complication at 90 days after surgery. Univariate and multivariate analyses were performed by logistic regression. Internal validation of the model was performed using resampling techniques. Results: the incidence of the outcome variable was 4.29% (95% CI 3.6-4.9). The variables remaining in the final logistic model were: age, sex, previous lung cancer resection, dyspnea (mMRC), right pneumonectomy, and ppo DLCO. The performance parameters of the model adjusted by resampling were: C-statistic 0.712 (95% CI 0.648-0.750), Brier score 0.042 and bootstrap shrinkage 0.854. Conclusions: the risk prediction model obtained from the GEVATS database is a simple, valid, and reliable model that is a useful tool for establishing the risk of a patient undergoing anatomic lung resection

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Resultados de la estadificación clínica ganglionar mediastínica del cáncer pulmonar quirúrgico: datos de la cohorte prospectiva nacional del Grupo Español de Cirugía Torácica Videoasistida

Introducción: El objetivo del estudio es valorar el rendimiento diagnóstico de la tomografía computarizada (TC) y la tomografía por emisión de positrones (PET) en la estadificación clínica mediastínica del cáncer pulmonar quirúrgico según los datos de la cohorte prospectiva del Grupo Español de Cirugía Torácica Videoasistida (GEVATS). Métodos: Se han analizado 2.782 pacientes intervenidos por carcinoma pulmonar primario. Se ha estudiado el acierto diagnóstico en la estadificación mediastínica (cN2). Se ha realizado un análisis bivariante y multivariante de los factores que influyen en el acierto. Se ha estudiado el riesgo de pN2 inesperado en los factores con los que se recomienda una prueba invasiva de estadificación: cN1, tumor central o tamaño mayor de 3cm. Resultados: El acierto global de la TC y PET en conjunto es del 82,9% con VPP y VPN de 0,21 y 0,93. En tumores mayores de 3cm y a mayor SUVmax del mediastino, el acierto es menor, OR de 0,59 (0,44 - 0,79) y 0,71 (0,66 - 0,75), respectivamente. En el abordaje VATS el acierto es mayor, OR de 2,04 (1,52 - 2,73). El riesgo de pN2 inesperado aumenta con el número de los factores cN1, tumor central o tamaño mayor de 3cm: entre el 4,5% (0 factores) y 18,8% (3 factores), pero no hay diferencias significativas con la realización de prueba invasiva. Conclusiones: La TC y PET en conjunto tienen un elevado valor predictivo negativo. Su acierto global es menor en tumores mayores de 3cm y SUVmax del mediastino elevado, y mayor en el abordaje VATS. El riesgo de pN2 inesperado es mayor si cN1, tumor central o mayor de 3cm y no varía significativamente con prueba invasiva

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care