Tunable biomimetic materials elaborated by ice templating and self-assembly of collagen for tubular tissue engineering.

Synthetic tubular grafts currently used in clinical context fail frequently, and the expectations that biomimetic materials could tackle these limitations are high. However, developing tubular materials presenting structural, compositional and functional properties close to those of native tissues remains an unmet challenge. Here we describe a combination of ice templating and topotactic fibrillogenesis of type I collagen, the main component of tissues' extracellular matrix, yielding highly concentrated yet porous tubular collagen materials with controlled hierarchical architecture at multiple length scales, the hallmark of native tissues' organization. By modulating the thermal conductivity of the cylindrical molds, we tune the macroscopic porosity defined by ice. Coupling the aforementioned porosity patterns with two different fibrillogenesis routes results in a new family of tubular materials whose textural features and the supramolecular arrangement of type I collagen are achieved. The resulting materials present hierarchical elastic properties and are successfully colonized by human endothelial cells and alveolar epithelial cells on the luminal side, and by human mesenchymal stem cells on the external side. The proposed straightforward protocol is likely to be adapted for larger graft sizes that address ever-growing clinical needs, such as peripheral arterial disease or tracheal and bronchial reconstructions.

What's new in minimally invasive thoracic surgery? Clinical application of augmented reality and learning opportunities in surgical simulation.

Lung cancer represents the most lethal cancer worldwide. Surgery is the treatment of choice for early-stage non-small cell lung cancer, with an overall survival that can reach 90% at 5 years, but its detection is difficult to achieve due to the lack of symptoms. Screening programs are crucial to identify small cancer. Minimally invasive surgery has modified the therapeutical approach of these tumors, becoming the standard of care, with an important clinical yield in terms of reduction of postoperative pain and length of hospital stay. The aim of this mini-review is to explore and describe two important and innovative aspects in the context of "growing opportunities in minimally invasive thoracic surgery": the clinical application of augmented reality and its advantages for patient and surgeon, and the pedagogical issue through simulation-based training.

Preliminary results in tracheal replacement using stented aortic matrices for primary extensive tracheal cancer.

Objective: Recent studies have demonstrated the feasibility and favorable long-term results of tracheobronchial replacement using stented cryopreserved aortic allografts. We propose to investigate the outcomes of this emerging technique in the subgroup of patients with extensive tracheal cancer. Methods: This study was based on 13 patients with primary extensive tracheal cancer extracted from the prospective registry TRITON-01 (ClinicalTrials.gov Identifier: NCT04263129), which included 40 patients in total. We analyzed early and late outcomes in this subset of patients. Results: From March 2019 to September 2022, 13 patients were included in the study. There were 9 female and 4 male patients, with a mean age of 53.9 years [36-71 years]. They had tracheal replacement for extended adenoid cystic carcinoma (n = 11), squamous cell carcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). A venovenous extracorporeal membrane oxygenation was used in the 6 last cases. The mean length of resection was 81 mm [50-120 mm]. There was no 30-day postoperative mortality. A complete resection (R0) was achieved in 11 patients. The main late complications consisted of tracheal granulomas related to the stent and requiring repeated bronchoscopies (n = 9), pneumonia (n = 3), airway infection (n = 1), bronchoesophageal fistula (n = 1), mechanical stent obstruction requiring change (n = 2), and mediastinitis treated by antibiotics, drainage, and omentoplasty (n = 1). With a maximal follow-up of 3 years and 7 months, cancer recurrence was observed in 2 patients. All patients were alive at last follow-up except 2 (84.6%). Conclusions: Airway replacement using stented CAA represents a feasible and promising solution for extensive tracheal cancer.

Analysis of Risk Factors for Tracheal Stenosis Managed during COVID-19 Pandemic: A Retrospective, Case-Control Study from Two European Referral Centre.

INTRODUCTION: Benign subglottic/tracheal stenosis (SG/TS) is a life-threatening condition commonly caused by prolonged endotracheal intubation or tracheostomy. Invasive mechanical ventilation was frequently used to manage severe COVID-19, resulting in an increased number of patients with various degrees of residual stenosis following respiratory weaning. The aim of this study was to compare demographics, radiological characteristics, and surgical outcomes between COVID-19 and non-COVID patients treated for tracheal stenosis and investigate the potential differences between the groups. MATERIALS AND METHODS: We retrospectively retrieved electronical medical records of patients managed at two referral centers for airways diseases (IRCCS Humanitas Research Hospital and Avicenne Hospital) with tracheal stenosis between March 2020 and May 2022 and grouped according to SAR-CoV-2 infection status. All patients underwent a radiological and endoscopic evaluation followed by multidisciplinary team consultation. Follow-up was performed through quarterly outpatient consultation. Clinical findings and outcomes were analyzed by using SPPS software. A significance level of 5% (p < 0.05) was adopted for comparisons. RESULTS: A total of 59 patients with a mean age of 56.4 (±13.4) years were surgically managed. Tracheal stenosis was COVID related in 36 (61%) patients. Obesity was frequent in the COVID-19 group (29.7 ± 5.4 vs. 26.9 ± 3, p = 0.043) while no difference was found regarding age, sex, number, and types of comorbidities between the two groups. In the COVID-19 group, orotracheal intubation lasted longer (17.7 ± 14.5 vs. 9.7 ± 5.8 days, p = 0.001), tracheotomy (80%, p = 0.003) as well as re-tracheotomy (6% of cases, p = 0.025) were more frequent and tracheotomy maintenance was longer (21.5 ± 11.9 days, p = 0.006) when compared to the non-COVID group. COVID-19 stenosis was located more distal from vocal folds (3.0 ± 1.86 vs. 1.8 ± 2.03 cm) yet without evidence of a difference (p = 0.07). The number of tracheal rings involved was lower in the non-COVID group (1.7 ± 1 vs. 2.6 ± 0.8 p = 0.001) and stenosis were more frequently managed by rigid bronchoscopy (74% vs. 47%, p = 0.04) when compared to the COVID-19 group. Finally, no difference in recurrence rate was detected between the groups (35% vs. 15%, p = 0.18). CONCLUSIONS: Obesity, a longer time of intubation, tracheostomy, re-tracheostomy, and longer decannulation time occurred more frequently in COVID-related tracheal stenosis. These events may explain the higher number of tracheal rings involved, although we cannot exclude the direct role of SARS-CoV-2 infection in the genesis of tracheal stenosis. Further studies with in vitro/in vivo models will be helpful to better understand the role of inflammatory status caused by SARS-CoV-2 in upper airways.

Thrombosis of Medium-Sized and Large Arteries During Covid-19 Infection: Results of the COVIVASC Study.

BACKGROUND: COVID-19 infection is associated not only with venous thromboses but also with arterial thromboses (COV-ATs) in relation with an endothelial dysfunction, a coagulopathy and rhythm disorders. The incidence, the topography, and the prognosis of COV-ATs remain poorly known. The objective of this study was to report the overall experience of the Greater Paris University Hospitals (Assistance Publique - Hopitaux de Paris, AP-HP) during the first pandemic wave of COVID-19 infection. METHODS: After approval by the ethics committee, a study using the AP-HP clinical data warehouse was carried out between March and May 2020. Overall, 124,609 patients had a polymerase chain reaction for COVID-19 in our hospitals, of which 25,345 were positive. From 20,710 exploitable stays, patients tested positive for COVID who presented an episode of acute COV-AT (except coronary and intracranial arteries) were selected on the basis of the French medical classification for clinical procedures codes. The data are presented as absolute values with percentages and/or means with standard deviation. RESULTS: Over the studied period, 60 patients (aged 71±14 years, 42 men) presented a COV-AT at the time of their hospitalization, an incidence of 0.2%. The arterial complication occurred 3±7 days after the COVID infection and was inaugural in 30% of the cases (n = 18). The sites of COV-AT were the lower extremities (n = 35%, 58%), the abdominal aorta (n = 10%, 17%), the thoracic aorta (n = 7%, 12%), the upper limbs (n = 7%, 12%), the cerebral arteries (n = 7%, 12%), the digestive arteries (n = 6%, 10%), the renal arteries (n = 2%, 3%), and the ophthalmic artery (n = 1%, 2%). Multiple COV-ATs were observed in 13 patients (22%). At the time of diagnosis, 20 (33%) patients were in intensive care, including six (10%) patients who were intubated. On computed tomography angiography, COVID lesions were classified as moderate and severe in 25 (42%) and 21 (35%) cases, respectively. Revascularization was attempted in 27 patients (45%), by open surgery in 16 cases, using endovascular techniques in 8 cases and with a hybrid approach in three cases. Six patients (22%) required reinterventions. The duration of hospitalization was 12±9 days. Early mortality (in-hospital or at 30 days) was 30% (n = 18). Nine (15%) patients presented severe nonlethal ischemic complications. CONCLUSIONS: Arterial involvement is rare during COVID-19 infection. The aorta and the arteries of the limbs are the privileged sites. The morbi-mortality of these patients is high. Future studies will have to determine if the systematization of anticoagulation therapy decreases the incidence and the severity of the condition.

Airway replacement using stented aortic matrices: Long-term follow-up and results of the TRITON-01 study in 35 adult patients.

Over the past 25 years, we have demonstrated the feasibility of airway bioengineering using stented aortic matrices experimentally then in a first-in-human trial (n = 13). The present TRITON-01 study analyzed all the patients who had airway replacement at our center to confirm that this innovative approach can be now used as usual care. For each patient, the following data were prospectively collected: postoperative mortality and morbidity, late airway complications, stent removal and status at last follow-up on November 2, 2021. From October 2009 to October 2021, 35 patients had airway replacement for malignant (n = 29) or benign (n = 6) lesions. The 30-day postoperative mortality and morbidity rates were 2.9% (n = 1/35) and 22.9% (n = 8/35) respectively. At a median follow-up of 29.5 months (range 1-133 months), 27 patients were alive. There have been no deaths directly related to the implanted bioprosthesis. Eighteen patients (52.9%) had stent-related granulomas requiring a bronchoscopic treatment. Ten among 35 patients (28.6%) achieved a stent free survival. The actuarial 2- and 5-year survival rates (Kaplan-Meier estimates) were respectively 88% and 75%. The TRITON-01 study confirmed that airway replacement using stented aortic matrices can be proposed as usual care at our center. Clinicaltrials.gov Identifier: NCT04263129.

Case Report: Laryngotracheal Post-Intubation/Tracheostomy Stenosis in COVID-19 Patients.

Introduction: The novel Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), has spread rapidly to become a major global public health emergency since March 2020. Laryngotracheal stenosis (LTS) has been observed more frequently since the onset of the COVID-19 pandemic. Methods: All patients referred to our 24/7 Airway Diseases Center for laryngotracheal post-intubation/tracheostomy stenosis from May 2020 to May 2021were evaluated retrospectively. Patient data on comorbidities, diagnosis, type of procedures, lengths of ICU stay and invasive mechanical ventilation, medical treatment, and the severity of illness were recorded. Results: This case series included nine patients (five women and four men), with a mean age of 52.9 years, most with a BMI >30, all with a severe illness revealed by the Simplified Acute Physiology Score (SAPS) II >31. From May 2020 to May 2021, 21 procedures were performed on seven patients, consisting of bronchoscopic rigid interventions, T-tube Montgomery tracheostomy, and one cricotracheal resection with end-to-end anastomosis. Histologic examination of tracheal biopsies showed an inflammatory state of the airway mucosa. Two patients only had medical therapy. Discussion and Conclusions: Pneumonia caused by SARSCoV-2 can lead to severe acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. The time of intubation, the drugs used, the prone position, comorbidities (diabetes, obesity), and the inflammatory state of the upper airways linked to the viral infection, predispose to an increased tendency to stenosis and its recurrence. A conservative approach with medical and endoscopic treatment should be preferred in case of persistence of local airways inflammation. Further studies with a larger sample of patients will help to a better understanding of the disease, reduce the prevalence, and improve its treatment.

Maintaining Surgical Treatment of Non-Small Cell Lung Cancer During the COVID-19 Pandemic in Paris.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak was officially declared in France on March 14, 2020. The objective of this study is to report the incidence and outcome of COVID-19 after surgical resection of non-small cell lung cancer in Paris Public Hospitals during the pandemic. METHODS: We retrospective analyzed a prospective database including all patients who underwent non-small cell lung cancer resection between March 14, 2020, and May 11, 2020, in the 5 thoracic surgery units of Paris Public Hospitals. The primary endpoint was the occurrence of SARS-CoV-2 infection during the first 30 days after surgery. RESULTS: Study group included 115 patients (male 57%, age 64.6 ± 10.7 years, adenocarcinoma 66%, cT1 62%, cN0 82%). During the first month after surgery, 6 patients (5%) were diagnosed with COVID-19. As compared with COVID-negative patients, COVID-positive patients were more likely to be operated on during the first month of the pandemic (100% vs 54%, P = .03) and to be on corticosteroids preoperatively (33% vs 4%, P = .03). Postoperative COVID-19 was associated with an increased rate of readmission (50% vs 5%, P = .004), but no difference in 30-day morbidity (for the study group: grade 2, 24%; grade 3, 7%; grade 4, 1%) or mortality (n = 1 COVID-negative patient, 0.9%). Immediate oncologic outcomes did not differ significantly between groups (R0 resection 99%, nodal upstaging 14%, adjuvant chemotherapy 29%). CONCLUSIONS: During the COVID-19 pandemic, surgical treatment of non-small cell lung cancer was associated with a rate of postoperative COVID-19 of 5% with a significant impact on readmissions but not on other outcomes studied.

A recurrent lung abscess caused by delayed diagnosis of unique co-infection with Abiotrophia defectiva.

We report the case of a lung abscess due to Prevotella baroniae with a co-infection by Abiotrophia defective, which is a 'nutritionally variant streptococci' (NVS), in a 48-year-old patient. The delayed diagnosis of this co-infection led to multiple failures of medical treatment and need for surgery. Pathogenicity of these bacteria is well known, particularly in endocarditis, but not in lung infection. In pulmonary abscesses, co-infection with NVS is difficult to detect. It may explain some medical treatment failures. This case highlights the importance to systematically search for and consider NVS in such clinical contexts.

Chest Tubes: Generalities.

Insertion, management, and withdrawal of chest tubes is part of the routine activity of thoracic surgeons. The selection of the chest tube and the strategy for each of these steps is usually built on knowledge, practice, experience, and judgment. The indication to insert a chest tube into the pleural cavity is the presence of air or fluid within it. Various types and sizes of chest tubes are now commercially available.

Lung cancer in elderly patients.

There is a worldwide-accepted evidence of a population shift toward older ages. This shift favors an increased risk of developing lung cancer that is primarily a disease of older populations. Decision making is extremely difficult in elderly patients, since this group is under-represented in clinical trials with only 25% of them historically opening to patients older than 65 years. For all these reasons, a "customized" preoperative assessment to identify physiological or pathological frailty should be encouraged since standard tools may be less reliable. The work already done to improve patient selection for lung surgery in the elderly population clearly shows that surgical resection seems the treatment of choice for early stage lung cancer. Further studies are required to improve outcome by reducing postoperative morbidity and mortality.

Role of cytokine profile in the differential diagnosis between acute lung rejection and pulmonary infections after lung transplantation†.

OBJECTIVES: Acute lung rejection (ALR) is a relatively frequent complication during the first year after lung transplantation (LT). It is characterized by perivascular/bronchial mononuclear inflammation mediated by several cytokines. The aim of our study was to monitor a panel of cytokines extracted from the bronchoalveolar lavage (BAL) during the first year after LT and correlate them with clinical ALR. METHODS: Twenty double lung transplant recipients were prospectively assessed. Fifteen (75%) were affected by cystic fibrosis (CF). BAL was collected at seven different steps (pretransplant, immediately post-transplant, after 1 week, 1, 3, 6 months and 1 year). A panel of six cytokines was analysed: tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α and IL-10. We correlated the cytokine levels with clinical ALR episodes, bacterial and cytomegalovirus (CMV) infections. RESULTS: One hundred and thirty-eight BAL samples were collected and analysed. In CF patients, the levels of proinflammatory cytokines significantly dropped immediately after the transplant while they increased in all the other patients. Four patients (20%) died between 6 months and 1 year. Nine patients (45%) showed one clinical ALR episode within 6 months; in 6 (30%) patients, a bacterial pneumonia was diagnosed and 5 (25%) developed CMV infection. No differences with the complication rate between CF and non-CF patients were observed. During the infection episodes, all proinflammatory cytokines increased with low levels of IL-10; in case of ALR, levels of IL-1ß and MIP-1α increased significantly (P = 0.01 and P < 0.0001), IL-10 levels were higher compared with the infection episodes (P = 0.03). No significant changes were observed for TNF-α, IL-6 and IL-8. CONCLUSIONS: The BAL cytokine profile (IL-1ß, MIP-1α and IL-10) seems useful to differentiate ALR and infections.

Uniportal video assisted thoracoscopic lobectomy: going directly from open surgery to a single port approach.

Uniportal video-assisted thoracoscopy (VATS) has gaining a special place in the thoracic surgery scenario; nowadays even major pulmonary resections can be performed through this approach. We hereby review our initial experience with uniportal VAT lobectomy, performed passing directly from the open approach to a single port approach. We attempted 26 lobectomies through VATS with a single incision of about 5 cm and 22 of them were completed: eight left lower lobectomies, six right upper lobectomies, five left upper lobectomies and three right lower lobectomies. At pathological staging all but four patients were stage I; three patients were T2N1M0 and one had a micrometastasis in a lymph node of station 7 (T1N2M0-Stage IIIA) and they all underwent adjuvant chemotherapy. No perioperative mortality was observed. One patient had a myocardial infarction in the first postoperative day requiring placement of four stents and another one required thoracentesis after drainage removal. The mean time for drainage removal was 3 days and the length of hospitalization was 4.2±1.1. Pain as measured by the visual analogical scale (VAS) scale was graded as 4.9, 2.6 and 0.5 during the first postoperative day, at discharge and after 1 month respectively.

New predictors of response to neoadjuvant chemotherapy and survival for invasive thymoma: a retrospective analysis.

BACKGROUND: Cell-cycle protein (p27, p21, and p53) expression can predict response to neoadjuvant chemotherapy and prognosis in some neoplasms. This study evaluated whether these markers could also be effective in invasive thymoma during a multimodality treatment. METHODS: Between 1989 and 2008, 33 patients with invasive thymoma underwent surgical resection after neoadjuvant chemotherapy. Expression of p27, p21, and p53 was assessed using immunohistochemistry in specimens retrieved pre and post chemotherapy. Factors influencing response to neoadjuvant chemotherapy and survival were investigated by univariate and multivariate analysis. Good response was defined as complete disappearance of tumor at imaging or necrosis >90% at pathologic studies. RESULTS: Twelve patients disclosed an imaging good response. Complete resection was possible in 17 patients, 9 of whom had presented imaging good response and 11 of whom had revealed pathologic good response. On univariate analysis both imaging and pathologic poor responses were significantly associated with incomplete resection (P = 0.04 and P = 0.03, respectively) and preneoadjuvant triple combination of p27 low, p21 low, and p53 high expressions (P = 0.001 and P < 0.0001, respectively), the last factor being the only one selected on logistic regression (P = 0.01 and P = 0.005, respectively). Long-term survival analysis was negatively influenced by triple combination of p27, p21, and p53 (P < 0.0001) and incomplete resection (P < 0.0001), which were also selected on Cox's regression (P = 0.004 and P = 0.02, respectively). CONCLUSIONS: The triple combination of p27 low, p21 low, and p53 high expressions was the most significant predictor of imaging and pathologic poor responses to neoadjuvant chemotherapy in invasive thymoma. This combination together with incomplete resection was also the most significant negative predictor of long-term survival.