Grupo español de cirugía torácica asistida por videoimagen: método, auditoría y resultados iniciales de una cohorte nacional prospectiva de pacientes tratados con resecciones anatómicas del pulmón

Introduction: our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). Methods: we conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for '90-day mortality' and 'Grade IIIb-V complications'. Results: the series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). Conclusions: more than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort

Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria

Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions

Comparison of two concentrations of bupivacaine by continuous paravertebral infusion after thoracotomy with pulmonary resection: a double-blind, randomized clinical trial

Background and objectives: Post-thoracotomy pain management should be based on a multimodal approach that includes continuous regional analgesia. The objective of this study was to compare the analgesic efficacy of two concentrations of bupivacaine (0.2 % and 0.3 %) through a paravertebral catheter, both group plus fentanyl 2 mcg/ml. Methods: We conducted a randomized double-blind clinical trial to compare these two concentrations in patients undergoing pulmonary resection by thoracotomy in Donostia University Hospital between November 2010 and May 2011 (n = 59). The paravertebral catheter was placed prior to the surgical intervention, with the patient awake and sitting upright. Data were analyzed on an intention-to-treat basis. The Chi-squared test was used for qualitative variables and Student's t-tests or Mann-Whitney-Wilcoxon tests for quantitative variables, depending on the distribution of the variables. Statistical analysis was performed using IBM SPSS software (Version 17). Results: We did not find statistically significant differences in postoperative pulmonary function (p = 0.49), self-perceived pain (VAS; p = 0.28) or cumulative morphine consumption (p = 0.101) in the two groups. We observed adverse effects in 8 patients in group 1 (29.6 %) and in 12 patients (37.5 %) in group 2, the difference not being statistically significant (p = 0.52). Conclusions: Continuous thoracic paravertebral block for 48 hours is a good technique for the management of postoperative pain after pulmonary resection by thoracotomy. With moderate doses of local anesthetics (bupivacaine 0.20 %) we achieved good pain control and observed few systemic complications than major doses (bupivacaine 0.30 %).Antecedentes y objetivos: El manejo del dolor post-toracotomía debe basarse en un enfoque multimodal que incluye la analgesia regional continua. El objetivo de este estudio fue comparar la eficacia analgésica de dos concentraciones de bupivacaína (0,2 y 0,3 %) a través de un catéter paravertebral, ambos grupos más fentanilo 2 mcg/ml. Material y métodos: Se realizó un ensayo clínico aleatorizado, doble ciego, para comparar estas dos concentraciones en pacientes sometidos a resección pulmonar por toracotomía en el Hospital Universitario Donostia entre noviembre de 2010 y mayo de 2011 (n = 59). El catéter paravertebral se colocó antes de la intervención quirúrgica, con el paciente despierto en posición sentada. Los datos se analizaron sobre la base de intención de tratar. Se utilizó la prueba de Chi cuadrado para variables cualitativas y la t de Student o pruebas de Mann-Whitney-Wilcoxon para las variables cuantitativas, en función de la distribución de las variables. El análisis estadístico se realizó utilizando el software de IBM SPSS (versión 17). Resultados: No se encontraron diferencias estadísticamente significativas en la función pulmonar postoperatoria (p = 0,49), la percepción subjetiva de dolor (VAS; p = 0,28) o el consumo de morfina acumulada (p = 0,101) en los dos grupos. Hemos observado efectos adversos en 8 pacientes del grupo 1 (29,6 %) y en 12 pacientes (37,5 %) del grupo 2; la diferencia no fue estadísticamente significativa (p = 0,52). Conclusiones: El bloqueo paravertebral torácico continuo durante 48 horas es una buena técnica para el manejo del dolor postoperatorio después de la resección pulmonar por toracotomía. Con dosis moderadas de anestésicos locales (bupivacaína 0,20 %) se logró un buen control del dolor y observamos un número menor de complicaciones sistémicas que el grupo de dosis mayores (bupivacaína 0,30 %)

Creation of a multidisciplinary and multicenter study group for the use of 3D printing in general thoracic surgery: lessons learned in our first year experience

Introduction: In recent years, the use of 3D printing in medicine has grown exponentially, but the use of 3D technology has not been equally adopted by the different medical specialties. Published 3D printing activity in general thoracic surgery is scarce and has been mostly limited to case reports. The aim of this report was to reflect on the results and lessons learned from a newly created multidisciplinary and multicenter 3D unit of the Spanish Society of Thoracic Surgery (SECT). Methods: This is a pilot study to determine the feasibility and usefulness of printing 3D models for patients with thoracic malignancy or airway complications, based on real data. We designed a point-of-care 3D printing workflow involving thoracic surgeons, radiologists with experience in intrathoracic pathology, and engineers with experience in additive manufacturing. Results: In the first year of operation we generated 26 three-dimensional models out of 27 cases received (96.3%). In 9 cases a virtual model was sufficient for optimal patient handling, while in 17 cases a 3D model was printed. Per pathology, cases were classified as airway stenosis after lung transplantation (7 cases, 25.9%), tracheal pathology (7 cases, 25.9%), chest tumors (6 cases, 22.2%) carcinoid tumors (4 cases, 14.8%), mediastinal tumors (2 cases, 7.4%) and Pancoast tumors (one case, 3.7%). Conclusion: A multidisciplinary 3D laboratory is feasible in a hospital setting, and working as a multicenter group increases the number of cases and diversity of pathologies thus providing further opportunity to study the benefits of the 3D printing technology in general thoracic surgery

Phage lysins against pneumococcal colonization

35 p.-7 fig.-1 tab.Bacteriophage-encoded lytic enzymes, also named lysins, or enzybiotics, are efficient agents to kill bacterial pathogens. Colonization of the respiratory tract by Streptococcus pneumoniae is a prerequisite for the establishment of the infection process. Hence, we have evaluated the antibacterial activity of three different lysins against pneumococcal colonization using human nasopharyngeal and lung epithelial cells as well as a mouse model of nasopharyngeal colonization. The lysins tested were the wild type Cpl-1, the engineered Cpl-7S, and the chimera Cpl-711. Moreover, we have included amoxicillin as a comparator antibiotic. Human epithelial cells were infected with three different multidrug-resistant clinical isolates of S. pneumoniae followed by a single dose of the corresponding lysin. The antimicrobial activity of these lysins was also evaluated using a mouse nasopharyngeal carriage model. Exposure of infected epithelial cells to Cpl-7S did not result in the killing of any of the pneumococcal strains investigated. However, treatment with Cpl-1 or Cpl-711 increased the killing of S. pneumoniae adhered to both types of human epithelial cells with Cpl-711 being more effective than Cpl-1, at sub-inhibitory concentrations. In addition, treatment with amoxicillin had no effect reducing the carrier state whereas mice treated by the intranasal route with Cpl-711 showed significantly reduced nasopharyngeal colonization with no detection of bacterial load in 20-40% of the mice. This study indicates that Cpl-1 and Cpl-711 lysins might be promising antimicrobial candidates for therapy against pneumococcal colonization.This work was supported by grants SAF2017-83388 and SAF2017-88664 from Ministerio de Economía y Competitividad (MINECO)Peer reviewe

Creation of a multidisciplinary and multicenter study group for the use of 3D printing in general thoracic surgery: lessons learned in our first year experience

Jon Zabaleta,1 Borja Aguinagalde,1 Iker López,1 Stephany M Laguna,1 Mikel Mendoza,2 Ainhoa Galardi,2 Luis Matey,3,4 Andrea Larrañaga,4 Gorka Baqueriza,5 Ander Izeta61Thoracic surgery service, Donostia University Hospital, IIS Biodonostia, San Sebastian, Spain; 2Radiology service, Donostia Universitary Hospital, San Sebastian, Spain; 3Additive Manufacturing, Ceit-IK4, San Sebastian, Spain; 4School of Engineering, Tecnun-University of Navarra, Pamplona, Spain; 5Additive Manufacturing, Tknika-Basque Centre of Research and Applied Innovation in Vocational Education and Training; 6Tissue Engineering Group, IIS Biodonostia, San Sebastian, SpainIntroduction: In recent years, the use of 3D printing in medicine has grown exponentially, but the use of 3D technology has not been equally adopted by the different medical specialties. Published 3D printing activity in general thoracic surgery is scarce and has been mostly limited to case reports. The aim of this report was to reflect on the results and lessons learned from a newly created multidisciplinary and multicenter 3D unit of the Spanish Society of Thoracic Surgery (SECT).Methods: This is a pilot study to determine the feasibility and usefulness of printing 3D models for patients with thoracic malignancy or airway complications, based on real data. We designed a point-of-care 3D printing workflow involving thoracic surgeons, radiologists with experience in intrathoracic pathology, and engineers with experience in additive manufacturing.Results: In the first year of operation we generated 26 three-dimensional models out of 27 cases received (96.3%). In 9 cases a virtual model was sufficient for optimal patient handling, while in 17 cases a 3D model was printed. Per pathology, cases were classified as airway stenosis after lung transplantation (7 cases, 25.9%), tracheal pathology (7 cases, 25.9%), chest tumors (6 cases, 22.2%) carcinoid tumors (4 cases, 14.8%), mediastinal tumors (2 cases, 7.4%) and Pancoast tumors (one case, 3.7%).Conclusion: A multidisciplinary 3D laboratory is feasible in a hospital setting, and working as a multicenter group increases the number of cases and diversity of pathologies thus providing further opportunity to study the benefits of the 3D printing technology in general thoracic surgery.Keywords: 3d printing, thoracic surgery, multidisciplinary group, preoperative stud

Emergence of amoxicillin-resistant variants of Spain9V-ST156 pneumococci expressing serotype 11A correlates with their ability to evade the host immune response

12 p.-5 fig.-1 tab.Capsular switching allows pre-existing clones of Streptococcus pneumoniae expressing vaccine serotypes to escape the vaccine-induced immunity by acquisition of capsular genes from pneumococci of a non-vaccine serotype. Here, we have analysed the clonal composition of 492 clinical isolates of serotype 11A causing invasive disease in Spain (2000–2012), and their ability to evade the host immune response. Antibiograms, serotyping and molecular typing were performed. The restriction profiles of pbp2x, pbp1a and pbp2b genes were also analysed. Interaction with the complement components C1q, C3b, C4BP, and factor H was explored whereas opsonophagocytosis assays were performed using a human cell line differentiated to neutrophils. Biofilm formation and the polymorphisms of the major autolysin LytA were evaluated. The main genotypes of the 11A pneumococci were: ST62 (447 isolates, 90.6%), followed by ST6521 (35 isolates, 7.3%) and ST838 (10 isolates, 2.1%). Beta lactam resistant serotype 11A variants of genotypes ST838 and ST6521 closely related to the Spain9V-ST156 clone were first detected in 2005. A different pattern of evasion of complement immunity and phagocytosis was observed between genotypes. The emergence of one vaccine escape variant of Spain9V-ST156 (ST652111A), showing a high potential to avoid the host immune response, was observed.In addition, isolates of ST652111A showed higher ability to produce biofilms than ST83811A or ST6211A, which may have contributed to the emergence of this PEN-resistant ST652111A genotype in the last few years. The emergence of penicillin-resistant 11A invasive variants of the highly successful ST156 clonal complex merits close monitoring.Peer reviewe

Creation of a multidisciplinary and multicenter study group for the use of 3D printing in general thoracic surgery: lessons learned in our first year experience

Introduction: In recent years, the use of 3D printing in medicine has grown exponentially, but the use of 3D technology has not been equally adopted by the different medical specialties. Published 3D printing activity in general thoracic surgery is scarce and has been mostly limited to case reports. The aim of this report was to reflect on the results and lessons learned from a newly created multidisciplinary and multicenter 3D unit of the Spanish Society of Thoracic Surgery (SECT). Methods: This is a pilot study to determine the feasibility and usefulness of printing 3D models for patients with thoracic malignancy or airway complications, based on real data. We designed a point-of-care 3D printing workflow involving thoracic surgeons, radiologists with experience in intrathoracic pathology, and engineers with experience in additive manufacturing. Results: In the first year of operation we generated 26 three-dimensional models out of 27 cases received (96.3%). In 9 cases a virtual model was sufficient for optimal patient handling, while in 17 cases a 3D model was printed. Per pathology, cases were classified as airway stenosis after lung transplantation (7 cases, 25.9%), tracheal pathology (7 cases, 25.9%), chest tumors (6 cases, 22.2%) carcinoid tumors (4 cases, 14.8%), mediastinal tumors (2 cases, 7.4%) and Pancoast tumors (one case, 3.7%). Conclusion: A multidisciplinary 3D laboratory is feasible in a hospital setting, and working as a multicenter group increases the number of cases and diversity of pathologies thus providing further opportunity to study the benefits of the 3D printing technology in general thoracic surgery