Short-range interactions between fibrocytes and CD8+ T cells in COPD bronchial inflammatory response.

Bronchi of chronic obstructive pulmonary disease (COPD) are the site of extensive cell infiltration, allowing persistent contact between resident cells and immune cells. Tissue fibrocytes interaction with CD8+ T cells and its consequences were investigated using a combination of in situ, in vitro experiments and mathematical modeling. We show that fibrocytes and CD8+ T cells are found in the vicinity of distal airways and that potential interactions are more frequent in tissues from COPD patients compared to those of control subjects. Increased proximity and clusterization between CD8+ T cells and fibrocytes are associated with altered lung function. Tissular CD8+ T cells from COPD patients promote fibrocyte chemotaxis via the CXCL8-CXCR1/2 axis. Live imaging shows that CD8+ T cells establish short-term interactions with fibrocytes, that trigger CD8+ T cell proliferation in a CD54- and CD86-dependent manner, pro-inflammatory cytokines production, CD8+ T cell cytotoxic activity against bronchial epithelial cells and fibrocyte immunomodulatory properties. We defined a computational model describing these intercellular interactions and calibrated the parameters based on our experimental measurements. We show the model's ability to reproduce histological ex vivo characteristics, and observe an important contribution of fibrocyte-mediated CD8+ T cell proliferation in COPD development. Using the model to test therapeutic scenarios, we predict a recovery time of several years, and the failure of targeting chemotaxis or interacting processes. Altogether, our study reveals that local interactions between fibrocytes and CD8+ T cells could jeopardize the balance between protective immunity and chronic inflammation in the bronchi of COPD patients.

Prediction of survival after a lung transplant at 1 year (SALTO cohort) using information available at different key time points.

OBJECTIVES: A lung transplant is the final treatment option for end-stage lung disease. We evaluated the individual risk of 1-year mortality at each stage of the lung transplant process. METHODS: This study was a retrospective analysis of patients undergoing bilateral lung transplants between January 2014 and December 2019 in 3 French academic centres. Patients were randomly divided into development and validation cohorts. Three multivariable logistic regression models of 1-year mortality were applied (i) at recipient registration, (ii) the graft allocation and (iii) after the operation. The 1-year mortality was predicted for individual patients assigned to 3 risk groups at time points A to C. RESULTS: The study population consisted of 478 patients with a mean (standard deviation) age of 49.0 (14.3) years. The 1-year mortality rate was 23.0%. There were no significant differences in patient characteristics between the development (n = 319) and validation (n = 159) cohorts. The models analysed recipient, donor and intraoperative variables. The discriminatory power (area under the receiver operating characteristic curve) was 0.67 (0.62-0.73), 0.70 (0.63-0.77) and 0.82 (0.77-0.88), respectively, in the development cohort and 0.74 (0.64-0.85), 0.76 (0.66-0.86) and 0.87 (0.79 - 0.95), respectively, in the validation cohort. Survival rates were significantly different among the low- (< 15%), intermediate- (15%-45%) and high-risk (> 45%) groups in both cohorts. CONCLUSIONS: Risk prediction models allow estimation of the 1-year mortality risk of individual patients during the lung transplant process. These models may help caregivers identify high-risk patients at times A to C and reduce the risk at subsequent time points.

Immersive Three-dimensional Computed Tomography to Plan Chest Wall Resection for Lung Cancer.

PURPOSE: Chest wall resections for lung cancer treatment remain difficult to plan using standard 2-dimensional computed tomography. Although virtual reality headsets have been used in many medical contexts, they have not been used in chest wall resection planning. DESCRIPTION: We compared preoperative planning of a chest wall surgical resection for lung cancer treatment between senior and resident surgeons who used an immersive virtual reality device and a 2-dimensional computed tomography. EVALUATION: Chest wall resection planning was more accurate when surgeons used virtual reality vs computed tomography analysis (28.6% vs 18.3%, P = .018), and this was particularly true in the resident surgeon group (27.4% vs 8.3%, P = .0025). Predictions regarding the need for chest wall substitutes were also more accurate when they were made using virtual reality vs computed tomography analysis in all groups (96% vs 68.5%, P < .0001). Other studied parameters were not affected by the use of the virtual reality tool. CONCLUSIONS: Virtual reality may offer enhanced accuracy for chest wall resection and reconstruction planning for lung cancer treatment.

Cervicotomy using a hemi-clamshell approach for a rare enlarged substernal goitre.

The substernal goitre is defined as a goitre for which >50% of the mass is located below the superior orifice of the thorax, surgical resection remains the reference treatment, the approach used is the cervicotomy, which often allows to extract the mediastinal portion of the plunging goitre, and we report a rare case of a huge cancerous plunging goitre whose complete resection required the enlargement of the cervicotomy in right hemi-clamshell, for the carcinological, vascular and recurrent control.

Chest wall resection and reconstruction for primary and metastatic sarcomas: an 11-year retrospective cohort study.

OBJECTIVES: Chest wall sarcomas are rare, aggressive malignancies, the management of which mainly revolves around surgery. Radical tumour excision with free margins represents the optimal treatment for loco-regional clinically resectable disease. The objective of this study was to review our 11-year experience with chest wall resection for primary and metastatic sarcomas, focusing on surgical techniques and strategies for reconstruction. METHODS: Retrospective analysis of a comprehensive database of patients who underwent chest wall resection for primary or secondary sarcoma at our Institute from January 2009 to December 2019. RESULTS: Out of 26 patients, 21 (81%) suffered from primary chest wall sarcoma, while 5 (19%) had recurring disease. The median number of resected ribs was 3. Sternal resection was performed in 6 cases (23%). Prosthetic thoracic reconstruction was deemed necessary in 24 cases (92%). Tumour recurrence was observed in 15 patients (58%). The median overall survival was 73.6 months. Primary and secondary tumours showed comparable survival (P = 0.49). At univariate analysis, disease recurrence and infiltrated margins on pathological specimens were associated with poorer survival (P = 0.014 and 0.022, respectively). In patients with primary sarcoma, the median progression-free survival was 13.3 months. Associated visceral resections were significantly associated to postoperative complications (P = 0.02). CONCLUSIONS: Chest wall resection followed by prosthetic reconstruction is feasible in carefully selected patients and should be performed by experienced surgeons with the aim of achieving free resection margins, resulting in improved long-term outcomes.