Endothelial biomarkers (Von willebrand factor, BDCA3, urokinase) as predictors of mortality in COVID-19 patients: cohort study.

BACKGROUND: SARS-CoV-2 is a systemic disease that affects endothelial function and leads to coagulation disorders, increasing the risk of mortality. Blood levels of endothelial biomarkers such as Von Willebrand Factor (VWF), Thrombomodulin or Blood Dendritic Cell Antigen-3 (BDCA3), and uUokinase (uPA) increase in patients with severe disease and can be prognostic indicators for mortality. Therefore, the aim of this study was to determine the effect of VWF, BDCA3, and uPA levels on mortality. METHODS: From May 2020 to January 2021, we studied a prospective cohort of hospitalized adult patients with polymerase chain reaction (PCR)-confirmed COVID-19 with a SaO2 ≤ 93% and a PaO2/FiO2 ratio < 300. In-hospital survival was evaluated from admission to death or to a maximum of 60 days of follow-up with Kaplan-Meier survival curves and Cox proportional hazard models as independent predictor measures of endothelial dysfunction. RESULTS: We recruited a total of 165 subjects (73% men) with a median age of 57.3 ± 12.9 years. The most common comorbidities were obesity (39.7%), hypertension (35.4%) and diabetes (30.3%). Endothelial biomarkers were increased in non-survivors compared to survivors. According to the multivariate Cox proportional hazard model, those with an elevated VWF concentration ≥ 4870 pg/ml had a hazard ratio (HR) of 4.06 (95% CI: 1.32-12.5) compared to those with a lower VWF concentration adjusted for age, cerebrovascular events, enoxaparin dose, lactate dehydrogenase (LDH) level, and bilirubin level. uPA and BDCA3 also increased mortality in patients with levels ≥ 460 pg/ml and ≥ 3600 pg/ml, respectively. CONCLUSION: The risk of mortality in those with elevated levels of endothelial biomarkers was observable in this study.

Arsenic may be a carcinogenic determinant of a subset of gallbladder cancer: A pilot study.

Gallbladder cancer (GBC) is one of the deadliest malignancy and treatment options are deplorably limited. Better strategies of prevention are urgently needed but knowledge on risk factors remains scarce. Recent data suggested that arsenic (As) may be involved in GBC carcinogenesis but the question remains debated. To date, there are no data on As measurement in GBC samples. This pilot study aimed to measure As concentrations in tissue samples from patients with GBC compared to non-cancerous gallbladder (NCGB). Included patients underwent cholecystectomy at Hospital Clinico Universidad de Chile, Santiago in Chile, a country with high As exposure, between 2001 and 2020. Tissue samples were preserved in formalin-fixed, paraffin-embedded blocks. Selected samples were retrieved, processed and submitted to inductively coupled plasma mass spectrometry (ICP-MS) to determine As concentrations. A total of 77 patients were included, including 35 GBC and 42 NCGB. The two groups were comparable, except for age (68 vs. 49 years, p < 0.001). Measured in 11 GBC and 38 NCGB, total As was detected in 5 GBC (14%) compared to 0 NCGB samples (p < 0.001). GBC group also showed higher median values of As compared to NCGB (p < 0.001). This pilot study provided a proof-of-concept to measure As concentrations in gallbladder samples and showed higher level of As in GBC samples compared to NCGB, paving the way for future studies aiming to investigate the impact of As on GBC, which may contribute to the prevention of this deadly disease.

Oxidative Stress and Air Pollution: Its Impact on Chronic Respiratory Diseases.

Redox regulation participates in the control of various aspects of metabolism. Reactive oxygen and nitrogen species participate in many reactions under physiological conditions. When these species overcome the antioxidant defense system, a distressed status emerges, increasing biomolecular damage and leading to functional alterations. Air pollution is one of the exogenous sources of reactive oxygen and nitrogen species. Ambient airborne particulate matter (PM) is important because of its complex composition, which includes transition metals and organic compounds. Once in contact with the lungs' epithelium, PM components initiate the synthesis of inflammatory mediators, macrophage activation, modulation of gene expression, and the activation of transcription factors, which are all related to the physiopathology of chronic respiratory diseases, including cancer. Even though the pathophysiological pathways that give rise to the development of distress and biological damage are not fully understood, scientific evidence indicates that redox-dependent signaling pathways are involved. This article presents an overview of the redox interaction of air pollution inside the human body and the courses related to chronic respiratory diseases.

Mitral valve prolapse in patients with atrial septal defect: A quantitative three-dimensional echocardiographic analysis.

INTRODUCTION AND OBJECTIVES: Mitral valve (MV) prolapse is highly prevalent in patients with atrial septal defect (ASD). Abnormal left ventricular geometry has been proposed as the main mechanism of MV prolapse in ASD, however, the changes in the morphology of the MV apparatus remain to be clarified. Our aim was to assess the MV geometry in patients with ASD and MV prolapse. METHODS: We evaluated 99 patients (73% female, median age 40 years) with ASD who underwent a three-dimensional transesophageal echocardiogram. Three-dimensional analysis of the MV was done using dedicated automated software. Transthoracic echocardiographic parameters were assessed post ASD closure in 28 patients. RESULTS: MV prolapse was found in 39% of patients. Although smaller left ventricular dimensions and greater interatrial shunt were found in patients with MV prolapse compared with those without prolapse, there was no difference in the subvalvular parameters. MV prolapse was associated with larger mitral anterior-posterior diameter, anterolateral-posteromedial diameter, anterior perimeter, posterior perimeter, total perimeter, and anterior leaflet area (all p < 0.05). Mitral regurgitation was more frequent in patients with MV prolapse (80 vs. 48%, p = 0.002). CONCLUSIONS: In patients with ASD, the main mechanism of MV prolapse is the presence of an organic primary process of the MV apparatus (excessive anterior mitral leaflet tissue and mitral annular enlargement).

Lung transplantation from uncontrolled and controlled donation after circulatory death: similar outcomes to brain death donors.

Controlled donation after circulatory death donors (cDCD) are becoming a frequent source of lungs grafts worldwide. Conversely, lung transplantations (LTx) from uncontrolled donors (uDCD) are sporadically reported. We aimed to review our institutional experience using both uDCD and cDCD and compare to LTx from brain death donors (DBD). This is a retrospective analysis of all LTx performed between January 2013 and December 2019 in our institution. Donor and recipient characteristics were collected and univariate, multivariate and survival analyses were carried out comparing the three cohorts of donors. A total of 239 (84.7%) LTx were performed from DBD, 29 (10.3%) from cDCD and 14 (5%) from uDCD. There were no statistically significant differences in primary graft dysfunction grade 3 at 72 h, 30- and 90-day mortality, need for extracorporeal membrane oxygenation after procedure, ICU and hospital length of stay, airway complications, CLAD incidence or survival at 1 and 3 years after transplant (DBD: 87.1% and 78.1%; cDCD: 89.7% and 89.7%; uDCD: 85.7% and 85.7% respectively; P = 0.42). Short- and mid-term outcomes are comparable between the three types of donors. These findings may encourage and reinforce all types of donation after circulatory death programmes as a valid and growing source of suitable organs for transplantation.

Wireless Ultrasound-Guided Axillary Vein Cannulation for the Implantation of Cardiovascular Implantable Electric Devices.

INTRODUCTION: Ultrasound guidance for vascular cannulation seems safer and more effective than an anatomical landmark approach, though it has not gained widespread support partly due to workflow interference of wired probes. A wireless ultrasound transducer (WUST) may overcome this issue. We report the effectiveness, time consumption, and safety of the first-in-human experience in axillary vein cannulation guided with a novel WUST for the implantation of cardiovascular implantable electric devices (CIEDs). METHODS AND RESULTS: After a one-month training period, we routinely performed WUST-guided puncture to all first implants, prospectively registering data from the first 50 patients. We analyzed the time needed for preparing the WUST and for achieving each vein cannulation, and the rate of unsuccessful or accidental arterial punctures and complications. WUST-guided axillary vein access was successful in 49 out of 50 patients, totaling 86 cannulated veins. Median WUST preparation time was 55 [44-62] seconds and median time needed for each venous cannulation was 56 [36-71] seconds. A total of 84.9% of the veins were cannulated at the first attempt. There were 7 unsuccessful puncture attempts and 1 accidental arterial puncture. No pneumothorax, hemothorax, or nervous injury occurred in the 49 successfully cannulated patients. The unsuccessful one (distal subclavian occlusion) developed a minor local subcutaneous emphysema with no confirmed radiologic pneumothorax, not requiring intervention. During a follow-up of 2.5 ± 1.1 months, a patient developed a pocket infection, with no other significant complications. CONCLUSION: Ultrasound-guided axillary vein cannulation using a wireless transducer for the implantation of CIEDs is a feasible, fast, and safe method.

Wireless Ultrasound Guidance for Femoral Venous Cannulation in Electrophysiology: Impact on Safety, Efficacy, and Procedural Delay.

BACKGROUND: Ultrasound (US) guidance increases safety and efficacy in vascular cannulation and is considered the standard of care. However, barriers including workflow interference and the need to be assisted by a second operator limit its adoption in clinical routine. The use of wireless US (WUS) may overcome these barriers. The aim of this study was to assess the impact of a novel WUS probe during its initial implantation in an electrophysiology (EP) laboratory. METHODS: Thirty-six patients requiring femoral venous cannulation for EP procedures were included in this single center, prospective, observational study, comparing WUS guidance with the anatomical landmark approach. The primary endpoint was time to successful cannulation. Secondary endpoints included rate of unsuccessful punctures, accidental arterial punctures, and workflow interference. RESULTS: Compared with anatomical landmark approach, WUS guidance significantly reduced mean time to successful cannulation (87.3 ± 94.3 vs 238.1 ± 294.7 seconds, P < 0.01). Workflow interference was predominantly nonexistent or mild and decreased after the first three weeks of use. In addition, WUS guidance improved safety and efficacy, reducing the rate of accidental arterial punctures (0.02 ± 0.1 vs 0.25 ± 0.5 arterial punctures per cannulation, P < 0.05) and unsuccessful attempts (0.26 ± 0.8 vs 1.75 ± 2.1 attempts per cannulation, P < 0.01). CONCLUSIONS: WUS guidance resulted in faster, safer, and more effective femoral venous cannulation than the anatomical landmark approach without adding significant workflow interference. The application of wireless technology in this setting contributed to overcoming some of the barriers preventing a more widespread clinical use of US guidance.

Donor Lung Preservation at 10°C: Clinical and Logistical Impact.

INTRODUCTION: Cold static donor lung preservation at 10°C appears to be a promising method to safely extend the cold ischemic time (CIT) and improve lung transplant (LTx) logistics. METHODS: LTx from November 2021 to February 2023 were included in this single institution, prospective, non-randomized study comparing prolonged preservation at 10°C versus standard preservation on ice. The inclusion criteria for 10°C preservation were suitable grafts for LTx without any donor retrieval concerns. PRIMARY ENDPOINT: primary graft dysfunction (PGD) grade-3 at 72-h. Secondary endpoints: clinical outcomes, cytokine profile and logistical impact. RESULTS: Thirty-three out of fifty-seven cases were preserved at 10°C. Donor and recipient characteristics were similar across the groups. Total preservation times (h:min) were longer (p<0.001) in the 10°C group [1st lung: median 12:09 (IQR 9:23-13:29); 2nd: 14:24 (12:00-16:20)] vs. standard group [1st lung: median 5:47 (IQR 5:18-6:40); 2nd: 7:15 (6:33-7:40)]. PGD grade-3 at 72-h was 9.4% in 10°C group vs. 12.5% in standard group (p=0.440). Length of mechanical ventilation (MV), ICU and hospital stays were similar in both groups. Thirty and ninety-day mortality rates were 0% in 10°C group (vs. 4.2% in standard group). IL-8 concentration was significantly higher 6-h post-LTx in the standard group (p=0.025) and IL-10 concentration was increased 72-h post-LTx in the 10°C group (p=0.045). CONCLUSIONS: Preservation at 10°C may represent a safe and feasible strategy to intentionally prolong the CIT. In our center, extending the CIT at 10°C may allow for semi-elective LTx and improve logistics with similar outcomes compared to the current standard preservation on ice.

Outcomes after lung transplantation from selected donors older than 70 years in a single centre: time to close the debate?

OBJECTIVES: The aim of this study was to compare the outcomes of lung transplantations using grafts from donors aged over 70 years against those performed using younger donors. METHODS: This retrospective single-centre analysis includes lung transplants conducted at our institution from January 2014 to June 2022. Lung recipients were classified into 2 groups based on donor age (group A <70 years; group B ≥70 years). Variables regarding demographics, peri and postoperative outcomes and survival were included. The statistical analysis approach included univariable analysis, propensity score matching to address imbalances in donor variables (smoking status), recipient characteristics (sex, age, diagnosis and lung allocation score) and calendar period and survival analysis. RESULTS: A total of 353 lung transplants were performed in this period, 47 (13.3%) using grafts from donors aged over 70 years. Donors in group B were more frequently women (70.2% vs 51.6%, P = 0.017), with less smoking history (22% vs 43%, P = 0.002) and longer mechanical ventilation time (3 vs 2 days, P = 0.025). Recipients in group B had a higher lung allocation score (37.5 vs 35, P = 0.035). Postoperative variables were comparable between both groups, except for pulmonary function tests. Group B demonstrated lower forced expiratory volume 1 s levels (2070 vs 2580 ml, P = 0.001). The propensity score matching showed a lower chance of chronic lung allograft dysfunction by 12% for group B. One-, three- and five-year survival was equal between the groups. CONCLUSIONS: The use of selected expanded-criteria donors aged over 70 years did not result in increased postoperative morbidity, early mortality or survival in this study.

Outcomes of controlled DCDD lung transplantation after thoraco-abdominal vs abdominal normothermic regional perfusion: The Spanish experience.

BACKGROUND: Thoraco-abdominal normothermic regional perfusion (TA-NRP) has emerged as a strategy for evaluating and recovering the heart in controlled donation after the circulatory determination of death (cDCDD). However, its impact on lung grafts remains largely unknown. We aimed to assess the impact of TA-NRP on the outcomes of recipients of cDCDD lungs. METHODS: This is a retrospective, multicenter, nationwide study describing the outcomes of cDCDD lung transplants (LTs) performed in Spain from January 2021 to November 2023. Patients were divided in 2 groups based on the recovery technique: TA-NRP with the simultaneous recovery of the heart vs abdominal NRP (A-NRP) without simultaneous heart recovery. The primary endpoint was the incidence of Primary Graft Dysfunction (PGD) grade 3 at 72 hours. Secondary endpoints included the overall incidence of PGD, days on mechanical ventilation, intensive care unit (ICU) and hospital length of stay, early survival rates, and mid-term outcomes. RESULTS: Two hundred and eighty three cDCDD LTs were performed during the study period, 28 (10%) using TA-NRP and 255 (90%) using A-NRP. No differences were observed in the incidence of PGD grade 3 at 72 hours between the TA-NRP and the A-NRP group (0% vs 7.6%; p = 0.231), though the overall incidence of PGD was significantly lower with TA-NRP (14.3% vs 41.5%; p = 0.005). We found no significant differences between the groups regarding other post-transplant outcome variables. CONCLUSIONS: TA-NRP allows the simultaneous recovery of both the heart and the lungs in the cDCDD scenario with appropriate LT outcomes comparable to those observed with the A-NRP approach.

Pathological N1/N2 in Clinical Stage I Bronchogenic Carcinoma. Analysis From a Prospective Multicentre Database.

OBJECTIVES: To determine the incidence of occult N1/N2 nodal metastases and associated risk factors in patients with non-small cell lung cancer no larger than 3cm and deemed cN0 by CT and PET-CT in a prospective, multicentre national database. METHODS: Patients with a NSCLC no larger than 3cm, deemed cN0 by PET-CT and CT scan, who had undergone at least a lobectomy, were selected from a national multicentre database of 3533 patients who had undergone anatomic lung resection between 2016 and 2018. Clinical and pathological variables of patients with pN0 and patients with pN1/N2 were compared to identify factors associated with the presence of lymph node metastases. Chi2 and the Mann-Whitney U test were used for categorical and numerical variables, respectively. All variables with p<0.2 in the univariate analysis were included in the multivariate logistic regression analysis. RESULTS: The study included 1205 patients from the cohort. The incidence of occult pN1/N2 disease was 10.70% (95%CI, 9.01-12.58). The multivariable analysis revealed that the degree of differentiation, size, location (central or peripheral) and SUV of the tumour in PET, surgeon experience and number of lymph nodes resected were associated with occult N1/N2 metastases. CONCLUSIONS: The incidence of occult N1/N2 in patients with bronchogenic carcinoma with cN0 tumours no larger than 3cm is no negligible. Data about the degree of differentiation, tumour size in CT scan, maximal uptake of the tumour in PET-CT, location (central or peripheral), number of lymph nodes resected and surgeon seniority is relevant in order to detect patients at risk.

Donor lungs cold preservation at 10 °C offers a potential logistic advantage in lung transplantation.

Donor lung preservation at 10 °C appears to be an innovative and promising method that may improve transplant logistics by extending the cold ischemia time with excellent outcomes. We report the case of two lung transplants from two different donors involving the use of two different preservation methods, highlighting the benefits of using 10 °C lung storage.

Effect of smoking on the redox status of knee osteoarthritis: A preliminary study.

Even though smoking has been scarcely studied in osteoarthritis (OA) etiology, it is considered a controversial risk factor for the disease. Exposure to tobacco smoke has been reported to promote oxidative stress (OS) as part of the damage mechanism. The aim of this study was to assess whether smoking increases cartilage damage through the generation of OS. Peripheral blood (PB) and synovial fluid (SF) samples from patients with OA were analyzed. The samples were stratified according to smoking habit, Kellgren-Lawrence score, pain, and cotinine concentrations in PB. Malondialdehyde (MDA), methylglyoxal (MGO), advanced protein oxidation products (APOPs), and myeloperoxidase (MPO) were assessed; the activity of antioxidant enzymes such as gamma-glutamyl transferase (GGT), glutathione S-transferase (GST) and catalase (CAT), as well as the activity of arginase, which favors the destruction of cartilage, was determined. When stratified by age, for individuals <60 years, the levels of MDA and APOPs and the activity of MPO and GST were higher, as well as antioxidant system activity in the smoking group (OA-S). A greater degree of pain in the OA-S group increased the concentrations of APOPs and arginase activity (P < 0.01 and P < 0.05, respectively). Arginase activity increased significantly with a higher degree of pain (P < 0.01). Active smoking can be an important risk factor for the development of OA by inducing systemic OS in young adults, in addition to reducing antioxidant enzymes in older adults and enhancing the degree of pain and loss of cartilage.

External validation of the European Society of Thoracic Surgeons morbidity and mortality risk models.

OBJECTIVES: There is a wide variety of predictive models of postoperative risk, although some of them are specific to thoracic surgery, none of them is widely used. The European Society for Thoracic Surgery has recently updated its models of cardiopulmonary morbidity (Eurolung 1) and 30-day mortality (Eurolung 2) after anatomic lung resection. The aim of our work is to carry out the external validation of both models in a multicentre national database. METHODS: External validation of Eurolung 1 and Eurolung 2 was evaluated through calibration (calibration plot, Brier score and Hosmer-Lemeshow test) and discrimination [area under receiver operating characteristic curves (AUC ROC)], on a national multicentre database of 2858 patients undergoing anatomic lung resection between 2016 and 2018. RESULTS: For Eurolung 1, calibration plot showed suboptimal overlapping (slope = 0.921) and a Hosmer-Lemeshow test and Brier score of P = 0.353 and 0.104, respectively. In terms of discrimination, AUC ROC for Eurolung 1 was 0.653 (95% confidence interval, 0.623-0.684). In contrast, Eurolung 2 showed a good calibration (slope = 1.038) and a Hosmer-Lemeshow test and Brier score of P = 0.234 and 0.020, respectively. AUC ROC for Eurolung 2 was 0.760 (95% confidence interval, 0.701-0.819). CONCLUSIONS: Thirty-day mortality score (Eurolung 2) seems to be transportable to other anatomic lung-resected patients. On the other hand, postoperative cardiopulmonary morbidity score (Eurolung 1) seems not to have sufficient generalizability for new patients.

Interrupted versus continuous suture for bronchial anastomosis in lung transplantation: does it matter?

OBJECTIVES: Bronchial anastomotic complications remain a major concern in lung transplantation. We aim to compare 2 different techniques, continuous suture (CS) versus interrupted suture (IS) by analysing airway complications requiring intervention. METHODS: Lung transplantations between January 2015 and December 2020 were included. Airway complications requiring intervention were classified following the 2018 International Society for Heart and Lung Transplantation consensus and analysed comparing 3 groups of patients according to surgical technique: group A, both anastomosis performed with CS; group B, both with interrupted; and group C, IS for 1 side and CS for the contralateral side. RESULTS: A total of 461 anastomoses were performed in 245 patients. The incidence of airway complications requiring intervention was 5.7% [95% confidence interval (CI): 2.8-8.6] per patient (14/245) and 3.7% (95% CI: 2.0-5.4) per anastomosis (17/461). Complications that required intervention were present in 5 out of 164 (3.1%) anastomosis with interrupted technique, and in 12/240 (5%) with CS. No significant differences were found between techniques (P = 0.184). No statistical differences were found among group A, B or C in terms of incidence of anastomotic complications, demographics, transplant outcomes or overall survival (log-rank P = 0.513). In a multivariable analysis, right laterality was significantly associated to complications requiring intervention (OR 3.7 [95% CI: 1.1-12.3], P = 0.030). Endoscopic treatment was successful in 12 patients (85.7%). Retransplantation was necessary in 2 patients. CONCLUSIONS: In summary, although it seems that anastomotic complications requiring intervention occur more frequently with CS, there are no statistical differences compared to IS. Endoscopic treatment offers good outcomes in most of the airway complications after lung transplantation.

Surgical Risk Following Anatomic Lung Resection in Thoracic Surgery: A Prediction Model Derived from a Spanish Multicenter Database. / 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.

Post-transplant outcomes of standard and extended criteria donation after circulatory death donor lungs categorized by donation after brain death lung criteria.

OBJECTIVES: Most transplant centres use donation after brain death (DBD) criteria to assess the quality of controlled donation after circulatory death (cDCD) lungs. However, research on the relationship between DBD extended criteria and cDCD lung transplantation outcomes is limited. We investigated the outcomes of using DBD extended criteria donor organs in cDCD lung transplantation, compared to the standard criteria cDCD lung transplantation. METHODS: A retrospective chart review of consecutive cDCD lung referrals to Hospital Universitario Puerta de Hierro-Majadahonda from June 2013 to December 2019 was undertaken. Donors were divided into standard and extended criteria groups. Early outcomes after lung transplant were compared between these groups using the Kaplan-Meier method and log-rank test. RESULTS: Thirty out of 91 cDCD donor lung offers were accepted for transplantation, of which 11 were from standard criteria donors and 19 were extended criteria donors. The baseline characteristics of the 2 recipient groups were similar. There were no differences in the rates of grade 3 primary graft dysfunction at 72 h after lung transplantation (21% vs 18%), duration of mechanical ventilation (48 h vs 36 h), total intensive care unit stay (10 days vs 7 days) and 1-year survival (89% vs 90%). CONCLUSIONS: Carefully selecting cDCD lungs from outside the standard acceptability criteria may expand the existing donor pool with no detrimental effects on lung transplantation outcomes.

Outcomes of surgical resection after neoadjuvant chemoimmunotherapy in locally advanced stage IIIA non-small-cell lung cancer.

OBJECTIVES: This analysis aimed to evaluate perioperative outcomes of surgical resection following neoadjuvant treatment with chemotherapy plus nivolumab in resectable stage IIIA non-small-cell lung cancer. METHODS: Eligible patients received neoadjuvant chemotherapy (paclitaxel + carboplatin) plus nivolumab for 3 cycles. Reassessment of the tumour was carried out after treatment and patients with at least stable disease as best response underwent pulmonary resection. After surgery, patients received adjuvant treatment with nivolumab for 1 year. Surgical data were collected from the NADIM database and patient charts were reviewed for additional surgical details. RESULTS: Among 46 patients who received neoadjuvant treatment, 41 (89.1%) underwent surgery. Two patients rejected surgery and 3 did not fulfil resectability criteria. There were 35 lobectomies (85.3%), 3 of which were sleeve lobectomies (9.4%), 3 bilobectomies (7.3%) and 3 pneumonectomies (7.3%). Video-assisted thoracoscopy was the initial approach in 51.2% of cases, with a conversion rate of 19% (n = 4). There was no operative mortality at either 30 or 90 days. The most common complications were prolonged air leak (n = 8), pneumonia (n = 5) and arrhythmia (n = 4). Complete resection (R0) was achieved in all patients who underwent surgery, downstaging was observed in 37 patients (90.2%) and major pathological response in 34 patients (82.9%). CONCLUSIONS: Surgical resection following induction therapy with chemotherapy plus nivolumab appears to be safe and offers appropriate oncological outcomes. Perioperative morbidity and mortality rates in our study were no higher than previously reported in this setting. A minimally invasive approach is, therefore, feasible.

Effectiveness and Safety of Extracorporeal Shockwave Myocardial Revascularization in Patients With Refractory Angina Pectoris and Heart Failure.

Extracorporeal shockwave myocardial revascularization (ESMR) is a therapy for refractory angina pectoris. Our aim was to assess the efficacy and safety of ESMR in the management of patients with stable coronary artery disease (CAD) and heart failure as well as its effects on inflammation and angiogenesis. In this single-arm prospective trial, we included 48 patients with CAD, myocardial ischemia assessed by radionuclide imaging, echocardiographic evidence of left ventricular systolic dysfunction and without revascularization options. Changes in angina grading score, myocardial perfusion, left ventricular ejection fraction, and six-minute walk test after ESMR therapy were used for efficacy assessment. Changes of inflammation and angiogenesis biomarkers were also evaluated. ESMR therapy was performed using a commercially available cardiac shockwave generator system (Cardiospec; Medispec). After 9 weeks of ESMR therapy, a significant improvement was found regarding the initial angina class, severity of ischemia, left ventricular ejection fraction, and six-minute walk test in most patients. No deleterious side effects after treatment were detected. Regarding biomarkers, endothelial progenitor cells and angiopoietin-3 were significantly increased whereas IL-18 and TGF-ß were significantly decreased after ESMR in the total group. Notably, VEGF, IL-1ß, and lipoxin A4 levels were significantly increased only in patients with myocardial ischemia improvement. In conclusion, ESMR therapy is safe and effective in most but not all patients with CAD and heart failure. ESMR is associated with increased markers of angiogenesis and decreased markers of inflammation. Myocardial ischemia improvement after ESMR is associated with increased markers of angiogenesis and pro-resolving mediators.