Circulating Vesicular-bound HLA-G as Noninvasive Predictive Biomarker of CLAD After Lung Transplantation.

BACKGROUND: Circulating extracellular vesicles (EVs) have shown promising results as noninvasive biomarkers for predicting disease outcomes in solid organ transplantation. Because in situ graft cell expression of the tolerogenic molecule HLA-G is associated with acceptance after lung transplantation (LTx), we hypothesized that plasma EV-bound HLA-G (HLA-GEV) levels could predict chronic lung allograft dysfunction (CLAD) development. METHODS: We analyzed 78 LTx recipients from the Cohort-for-Lung-Transplantation cohort, all in a stable (STA) state within the first year post-LTx. At 3 y, 41 patients remained STA, and 37 had CLAD (bronchiolitis obliterans syndrome, BOS, [n = 32] or restrictive allograft syndrome [n = 5]). HLA-GEV plasma levels were measured at month 6 (M6) and M12 in 78 patients. CLAD occurrence and graft failure at 3 y post-LTx were assessed according to early HLA-GEV plasma levels. RESULTS: In patients with subsequent BOS, (1) HLA-GEV levels at M12 were significantly lower than those in STA patients (P = 0.013) and (2) also significantly lower than their previous levels at M6 (P = 0.04).A lower incidence of CLAD and BOS and higher graft survival at 3 y were observed in patients with high HLA-GEV plasma levels at M12 (high versus low HLA-GEVs patients [cutoff 21.3 ng/mL]: freedom from CLAD, P = 0.002; freedom from BOS, P < 0.001; and graft survival, P = 0.04, [log-rank]). Furthermore, in multivariate analyses, low HLA-GEV levels at M12 were independently associated with a subsequent risk of CLAD, BOS, and graft failure at 3 y (P = 0.015, P = 0.036, and P = 0.026, respectively [Cox models]). CONCLUSIONS: This exploratory study suggests the potential of EV-bound HLA-G plasma levels as a liquid biopsy in predicting CLAD/BOS onset and subsequent graft failure.

Kidney After Lung Transplants or Combined Kidney-Lung Transplantation: A Single-Center Retrospective Cohort Study.

BACKGROUND End-stage renal disease is a major issue in the management of patients undergoing lung transplantation. Combined kidney-lung transplantation (CKLT) and kidney after lung transplantation (KALT) are the 2 preferred solutions to manage this situation. To evaluate these strategies, we describe kidney and lung graft outcomes and patient survival in patients managed with CKLT and KALT. MATERIAL AND METHODS We conducted a retrospective single-center cohort study. Patients who underwent a CKLT or a KALT were included in this study. Retrospective extraction of data from medical records was performed. RESULTS Seventeen patients underwent CKLT and 9 underwent KALT. Most of the patients had cystic fibrosis and presented renal failure related to anti-calcineurin toxicity. The 30-day and 1-year survival of CKLT recipients were both 75.6%. No patients with KALT died during the follow-up. Kidney graft prognosis was almost exclusively influenced by patient survival in relation to postoperative lung transplant complications. The rate of severe surgical complications was close to 60% for CKLT compared with 30% for KALT. The kidney graft function (estimated kidney graft function) did not differ according to the transplantation strategy. CONCLUSIONS KALT is a safe option, with postoperative morbidity and renal graft function identical to those of kidney transplantation in non-lung-transplanted patients. The results of CKLT depend mainly on the morbidity associated with lung transplantation but remain an attractive option for patients with respiratory failure associated with end-stage renal disease. The choice of transplant strategy must also take into account the most ethical and efficient allocation of kidney grafts.

SARS-CoV2 infection in whole lung primarily targets macrophages that display subset-specific responses.

Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems do not recapitulate the histoarchitecture and cellular composition of respiratory tissues. To address this, we developed an innovative ex vivo model of whole human lung infection with SARS-CoV-2, leveraging a lung transplantation technique. Through single-cell RNA-seq, we identified that alveolar and monocyte-derived macrophages (AMs and MoMacs) were initial targets of the virus. Exposure of isolated lung AMs, MoMacs, classical monocytes and non-classical monocytes (ncMos) to SARS-CoV-2 variants revealed that while all subsets responded, MoMacs produced higher levels of inflammatory cytokines than AMs, and ncMos contributed the least. A Wuhan lineage appeared to be more potent than a D614G virus, in a dose-dependent manner. Amidst the ambiguity in the literature regarding the initial SARS-CoV-2 cell target, our study reveals that AMs and MoMacs are dominant primary entry points for the virus, and suggests that their responses may conduct subsequent injury, depending on their abundance, the viral strain and dose. Interfering on virus interaction with lung macrophages should be considered in prophylactic strategies.

Real-world outcomes of lobectomy, segmentectomy and wedge resection for the treatment of stage c-IA lung carcinoma.

OBJECTIVES: To determine safety and survival outcomes associated with lobectomy, segmentectomy and wedge resection for early-stage lung cancer by quiring the French population-based registry EPIdemiology in THORacic surgery (EPITHOR). METHODS: Retrospective analysis of 19 452 patients with stage c IA lung carcinoma who underwent lobectomy, segmentectomy or wedge resection between 2016 and 2022 with curative-intent. Main outcome measures were 90-day mortality and 5-year overall survival estimates. Proportional hazards regression and propensity score matching were used to adjust outcomes for key patient, tumour and practice environment factors. RESULTS: The treatment distribution was 72.2% for lobectomy, 21.5% for segmentectomy and 6.3% for wedge. Unadjusted 90-day mortality rates were 1.6%, 1.2% and 1.1%, respectively (P = 0.10). Unadjusted 5-year overall survival estimates were 80%, 78% and 70%, with significant inter-group survival curves differences (P < 0.0001). Multivariable proportional hazards regression showed that wedge was associated with worse overall survival [adjusted hazard ratio (AHR), 1.23 (95% confidence interval 1.03-1.47); P = 0.021] compared with lobectomy, while no significant difference was disclosed when comparing segmentectomy to lobectomy (1.08 [0.97-1.20]; P = 0.162). The three-way propensity score analyses confirmed similar 90-day mortality rate for wedge resection and segmentectomy compared with lobectomy (hazard ratio: 0.43; 95% confidence interval 0.16-1.11; P = 0.081 and 0.99; 0.48-2.10; P = 0.998, respectively), but poorer overall survival (1.45; 1.13-1.86; P = 0.003 and 1.31; 1-1.71; P = 0.048, respectively). CONCLUSIONS: Wedge resection was associated with comparable 90-day mortality but lower overall survival when compared to lobectomy. Overall, all types of sublobar resections may not offer equivalent oncologic effectiveness in real-world settings.

Successful lung transplantation in genetic methionyl-tRNA synthetase-related alveolar proteinosis/lung fibrosis without recurrence under methionine supplementation: Medium-term outcome in 4 cases.

Pulmonary alveolar proteinosis (PAP) results from the accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages, and can be associated with pulmonary fibrosis, with a need for lung transplantation (LTx). Causes of PAP are autoimmune (90%-95%), secondary (5%), or hereditary (<1%). Patients with hereditary PAP are generally not considered for isolated LTx, due to the high probability of recurrence after LTx, and only a challenging scenario with sequential LTx followed by hematopoietic stem cell transplantation (HSCT) was reported as successful. Recently, a new genetic cause of PAP linked to mutations in the methionyl-tRNA synthetase (MARS) gene has been reported, with a highly variable clinical presentation. Because clinical correction of the defective MARS activity with methionine supplementation has been reported in nontransplanted children, we reassessed the feasibility of LTx for candidates with MARS-related PAP/fibrosis. We report 3 cases of LTx performed for MARS-related pulmonary alveolar proteinosis-pulmonary fibrosis without recurrence under methionine supplementation, whereas another fourth case transplanted without supplementation had fatal PAP recurrence. These results suggest the effectiveness of methionine in correcting defective MARS activity and also looking for this very rare diagnosis in case of unclassified PAP/fibrosis. It argues for not excluding the feasibility of isolated LTx in patients with MARS mutation.

Lobar or sublobar resection of peripheral stage I non-small cell lung cancer.

PURPOSE OF REVIEW: We aim to highlight two recent clinical trials that have altered the approach of the management of stage I nonsmall cell lung cancer. RECENT FINDINGS: The JCOG 0802 and CALGB 140503 trials demonstrated that sublobar resection is noninferior to lobectomy for overall and disease-free survival in patients with stage I nonsmall cell lung cancer. SUMMARY: Since 1962, lobectomy has been deemed the gold standard treatment for operable lung cancer. However, two recent clinical trials have demonstrated that, for select patients, sublobar resection is oncologically noninferior; results, which are leading us into a new era for the surgical management of lung cancer. Notwithstanding the progress made by these studies and the opportunities that have been put forth, questions remain. This review aims at reviewing the results of both trials and to discuss future perspectives for the surgical treatment of lung cancer.

Optimizing lung cancer radiation therapy: A systematic review of multifactorial risk assessment for radiation-induced lung toxicity.

BACKGROUND: Radiation therapy (RT) is essential in treating advanced lung cancer, but may lead to radiation pneumonitis (RP). This systematic review investigates the use of pulmonary function tests (PFT) and other parameters to predict and mitigate RP, thereby improving RT planning. METHODS: A systematic review sifted through PubMed and on BioMed Central, targeting articles from September 2005 to December 2022 containing the keywords: Lung Cancer, Radiotherapy, and pulmonary function test. RESULTS: From 1153 articles, 80 were included. RP was assessed using CTCAEv.4 in 30 % of these. Six studies evaluated post-RT quality of life in lung cancer patients, reporting no decline. Patients with RP and chronic obstructive pulmonary disease (COPD) generally exhibited poorer overall survival. Notably, forced expiratory volume in one second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) declined 24 months post-RT, while forced vital capacity (FVC) stayed stable. In the majority of studies, age over 60, tumors located in the lower part of the lung, and low FEV1 before RT were associated with a higher risk of RP. Dosimetric factors (V5, V20, MLD) and metabolic imaging emerged as significant predictors of RP risk. A clinical checklist blending patient and tumor characteristics, PFT results, and dosimetric criteria was proposed for assessing RP risk before RT. CONCLUSION: The review reveals the multifactorial nature of RP development following RT in lung cancer. This approach should guide individualized management and calls for a prospective study to validate these findings and enhance RP prevention strategies.

Differential early response of monocyte/macrophage subsets to intra-operative corticosteroid administration in lung transplantation.

Introduction: Lung transplantation often results in primary and/or chronic dysfunctions that are related to early perioperative innate allo-responses where myeloid subsets play a major role. Corticosteroids are administered upon surgery as a standard-of-care but their action on the different myeloid cell subsets in that context is not known. Methods: To address this issue, we used a cross-circulatory platform perfusing an extracorporeal lung coupled to cell mapping in the pig model, that enabled us to study the recruited cells in the allogeneic lung over 10 hours. Results: Myeloid cells, i.e. granulocytes and monocytic cells including classical CD14pos and non-classical/intermediate CD16pos cells, were the dominantly recruited subsets, with the latter upregulating the membrane expression of MHC class II and CD80/86 molecules. Whereas corticosteroids did not reduce the different cell subset recruitment, they potently dampened the MHC class II and CD80/86 expression on monocytic cells and not on alveolar macrophages. Besides, corticosteroids induced a temporary and partial anti-inflammatory gene profile depending on cytokines and monocyte/macrophage subsets. Discussion: This work documents the baseline effects of the standard-of-care corticosteroid treatment for early innate allo-responses. These insights will enable further optimization and improvement of lung transplantation outcomes.

Donor/recipient origin of lung cancer after lung transplantation by DNA short tandem repeat analysis.

Background: Lung cancer is more common in posttransplant recipients than in the general population. The objective of this study was to examine the chimerism donor/recipient cell origin of graft cancer in recipients of lung transplant. Methods: A retrospective chart review was conducted at Foch Hospital for all lung transplantations from 1989 to 2020. Short tandem repeat PCR (STR-PCR) analysis, the gold standard technique for chimerism quantification, was used to determine the donor/recipient cell origin of lung cancers in transplant patients. Results: Fourteen (1.4%) of the 1,026 patients were found to have graft lung cancer after lung transplantation, and one developed two different lung tumors in the same lobe. Among the 15 lung tumors, 10 (67%) presented with adenocarcinoma, four (27%) with squamous cell carcinoma and one with small cell lung cancer. STR analysis showed that the origin of the cancer was the donor in 10 patients (71%), the recipient in three patients (21%), and was undetermined in one patient. Median time to diagnosis was 62 months. Conclusion: The prevalence of lung cancer in lung transplant recipients is very low. However, the results of our study showed heterogeneity of genetic alterations, with 21% being of recipient origin. Our results highlight the importance of donor selection and medical supervision after lung transplantation.

Chronic pain after posterolateral and axillary approaches to lung surgery: a monocentric observational study.

PURPOSE: Post-thoracotomy pain syndrome (PTPS) and chronic postsurgical neuropathic pain (CPNP) were evaluated 4 months after thoracic surgery whether the approach was a posterolateral (PL) incision or the less invasive axillary (AX) one. METHODS: Patients, 79 in each group, undergoing a thoracotomy between July 2014 and November 2015 were analyzed 4 months after surgery in this prospective monocentric cohort study. RESULTS: More PL patients suffered PTPS (60.8% vs. 40.5%; p = 0.017) but CPNP was equally present (45.8% and 46.9% in the PL and AX groups). Patients with PTPS have more limited daily activities (p < 0.001) but a similar psychological disability (i.e., catastrophism). Patients with CPNP have an even greater limitation of daily activities (p = 0.007) and more catastrophism (p = 0.0002). Intensity of pain during mobilization of the homolateral shoulder at postoperative day 6 (OR = 1.40, CI 95% [1.13-1.75], p = 0.002); age (OR = 0.97 [0.94-1.00], p = 0.022), and presence of pain before surgery (OR = 2.22 [1.00-4.92], p = 0.049) are related to the occurrence of PTPS; while, height of hypoesthesia area on the breast line measured 6 days after surgery is the only factor related to that of CPNP (OR = 1.14 [1.01-1.30], p = 0.036). CONCLUSION: Minimally invasive surgery was associated with less frequent PTPS, but with equal risk of CPNP. Pain before surgery and its postoperative intensity are associated with PTPS. This must lead to a more aggressive care of pain patients before surgery and of a better management of postoperative pain. CPNP can be forecasted according to the early postoperative height of hypoesthesia area on the breast line.

Results of Lung Transplantation for Cystic Fibrosis With Selected Donors Over 65 Years Old.

Lung transplantation is limited by the shortage of suitable donors. Many programs have begun to use extended criteria donors. Donors over 65 years old are rarely reported, especially for young cystic fibrosis recipients. This monocentric study was conducted for cystic fibrosis recipients from January 2005 to December 2019, comparing two cohorts according to lung donor age (<65 years or ≥65 years). The primary objective was to assess the survival rate at 3 years using a Cox multivariable model. Of the 356 lung recipients, 326 had donors under 65 years, and 30 had donors over 65 years. Donors' characteristics did not differ significantly in terms of sex, time on mechanical ventilation before retrieval, and partial pressure of arterial oxygen/fraction of inspired oxygen ratio. There were no significant differences in post-operative mechanical ventilation duration and incidence of grade 3 primary graft dysfunction between the two groups. At 1, 3, and 5 years, the percentage of predicted forced expiratory volume in 1 s (p = 0.767) and survival rate did not differ between groups (p = 0.924). The use of lungs from donors over 65 years for cystic fibrosis recipients allows extension of the donor pool without compromising results. Longer follow-up is needed to assess the long-term effects of this practice.

Complementary Therapy Learning in the Setting of Lung Transplantation: A Single-Center Observational Study of Appropriation and Efficacy.

Transplanted patients could benefit from complementary techniques. This prospective single-center, open study, performed in a tertiary university hospital, evaluates the appropriation and efficacy of a toolbox-kit of complementary techniques. Self-hypnosis, sophrology, relaxation, holistic gymnastics, and transcutaneous electric nerve stimulation (TENS) were taught to adult patients scheduled for double-lung transplantation. Patients were asked to use them before and after transplantation, as needed. The primary outcome was appropriation of each technique within the first three postoperative months. Secondary outcomes included efficacy on pain, anxiety, stress, sleep, and quality-of-life. Among the 80 patients included from May 2017 to September 2020, 59 were evaluated at the 4th postoperative month. Over the 4359 sessions performed, the most frequent technique used before surgery was relaxation. After transplantation, the techniques most frequently used were relaxation and TENS. TENS was the best technique in terms of autonomy, usability, adaptation, and compliance. Self-appropriation of relaxation was the easiest, while self-appropriation of holistic gymnastics was difficult but appreciated by patients. In conclusion: the appropriation by patients of complementary therapies such as mind-body therapies, TENS and holistic gymnastics is feasible in lung transplantation. Even after a short training session, patients regularly practiced these therapies, mainly TENS and relaxation.

Perioperative Outcomes During Double-Lung Transplantation and Retransplantation in Cystic Fibrosis Patients: A Monocentric Cohort Study.

OBJECTIVE: Life expectancy for lung-transplant patients, especially those with cystic fibrosis (CF), is leading increasingly to more retransplantations. DESIGN: Retrospective monocentric cohort study. SETTING: Foch University Hospital, Suresnes, France. PARTICIPANTS: CF patients having had a primary double-lung transplantation (pLgTx) or a retransplantation (reLgTx) from 2012 to 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors compared the main intraoperative and early postoperative features between pLgTx (n = 258) and reLgTx (n = 24). Demographic characteristics were similar. No patients with retransplantations had a preoperative bridge with extracorporeal membrane oxygenation (ECMO); however, 23 patients had it in the pLgTx group (p = 0.24). Patients with retransplants had longer second graft ischemic time (p = 0.02), larger intraoperative bleeding volume (p = 0.001) and blood transfusion (p = 0.009 for packed red blood cells), increased blood lactate concentrations (p = 0.002), and higher norepinephrine dose at end-surgery (p = 0.001). Extracorporeal membrane oxygenation was used during surgery in 94 patients in the pLgTx group and 12 patients in the reLgTx group (p = 0.39). Extracorporeal membrane oxygenation could not be weaned after surgery in 55 patients in the pLgTx group and 4 in the reLgTx group (p = 0.54). Despite worse preoperative renal function in the reLgTx group (p < 0.001), there was no difference concerning renal replacement therapy in the intensive care unit between groups (p = 0.08). There were no differences between groups concerning the main complications, including primary graft dysfunction. Although the difference was not statistically different (p = 0.17), mortality was 3 times higher in the reLgTx group. CONCLUSIONS: Intraoperative period of retransplantation was more convoluted but had a similar ECMO profile to primary transplantation. In addition, the early postoperative period was similar.

Contemporary Outcomes for the Curative Treatment of Colorectal Cancer Pulmonary Metastases.

PURPOSE: Treatment of pulmonary metastases (PM) from colorectal cancer (CRC) is the standard of care by several guidelines from Europe and the USA, but the validity of this strategy has been recently questioned, and the available evidence supporting this strategy is weak. We report the outcomes of a curative intent strategy in a very recent and homogenous series of patients. METHODS: We did a retrospective review of all curative intent surgical or ablative treatment of PM from CRC performed consecutively in 3 French institutions from January 2015 to December 2019. Demographics, clinicopathological, and molecular characteristics were evaluated. Cox regression models were used to identify prognostic factors related to local recurrence and disease-free survival. RESULTS: Records from 152 patients were reviewed. One-hundred thirty-five patients (88%) had surgical metastasectomy. Median age was 67 years. Most of the patients had a single lesion (66%), and 16% had synchronous PM. Eighty-one patients (53%) experienced recurrence, and the thorax was the most common site of recurrence. Median disease-free survival and overall survival were 35 months and 78 months after PM treatment. At the end of the study, only 17% of the patients died. Pulmonary tumor burden was correlated with disease-free survival in univariate analysis, but multivariate analysis did not find any prognostic factor independently associated with local recurrence or survival. CONCLUSION: Our finds corroborate existing recommendation for the invasive treatment of PM from CRC in selected patients.

Comprehensive assessment of postoperative mobility during the first days after mini-invasive lung surgery: A prospective observational study.

STUDY OBJECTIVE: Postoperative physical therapy and early mobilization are major elements for enhanced recovery after surgery. In contrast with supervised physical therapy sessions that can be monitored, self-mobilization is not easily quantifiable and has so far been estimated mainly through patient auto-reports. This study aimed to perform a comprehensive and objective evaluation of postoperative mobility. DESIGN: Prospective observational study. SETTING: Postoperative setting. PATIENTS: Patients undergoing mini-invasive lung surgery. INTERVENTIONS: Measurement of postoperative mobility during the first five postoperative days using an accelerometer (ActiGraph GT3X). MEASUREMENTS: The primary outcome was the number of daily steps. Secondary outcomes included physical activity duration and intensity, sedentary time, number of breaks in sedentary time, sedentary patterns, daily evaluation by physiotherapists, postoperative complications, and acceptability of wearing the accelerometer. MAIN RESULTS: Sixty patients were included in the study, of whom 56 provided at least one day of valid accelerometry data. There was no significant change during the first four PODs concerning the number of daily steps nor the mean cadence. One-minute cadence peak, total activity counts, and duration of light-intensity physical activity increased over time (p = 0.032, p = 0.001 and p = 0.001, respectively). Sedentary patterns changed favorably over time, with a decrease in prolonged sedentary bouts (≥ 60 consecutive min) (p < 0.001), and an increase in shorter bouts (< 10 min) (p = 0.001). Similar results were observed when analysis was adjusted for the day of the week when the surgery took place. The median acceptability of wearing the accelerometer was excellent (median 10 [9-10] on a 10-point Likert scale). Three patients had major complications. CONCLUSIONS: Our findings suggest that daily steps may not be the only relevant indicator of early mobility following thoracic surgery and that accelerometry is suitable to follow patients' early postoperative activity.

Prospective Radiologic-Pathologic Correlation of Macroscopic Volume and Microscopic Extension of Nonsolid Lung Nodules on Thin-section CT Images for Sublobar Resection and Stereotactic Radiotherapy Planning.

INTRODUCTION: The objective of this study was to determine whether computed tomography (CT) could be a useful tool for nonsolid lung nodule (NSN) treatment planning, surgery or stereotactic body radiation therapy (SBRT), by assessing the macroscopic and microscopic extension of these nodules. METHODS: The study prospectively included 23 patients undergoing anatomic resection at the Foch Hospital in 2020/2021 for NSN with a ground-glass component of more than 50%. Firstly, for each patient, both the macroscopic dimensions of the NSN were assessed on CT and during pathologic analysis. Secondly, the microscopic extension was assessed during pathologic examination. Wilcoxon sign rank tests were used to compare these dimensions. Spearman correlation test and Bland-Altman analysis were used to evaluate the agreement between radiological and pathologic measurements. RESULTS: On CT, the median largest diameter and volume of NSN were 21 mm and 3780 cc, while on pathologic analysis, they were 15 mm and 1800 cc, respectively. Therefore, the largest diameter and volume of the NSN were significantly higher on CT than on pathological analysis. For microscopic extension, the median largest diameter and volume of NSN were 17 mm and 2040 cc, respectively. No significant difference was observed between the macroscopic size and the microscopic extension assessed during pathologic analysis. Moreover, correlation analysis and Bland-Altman plots showed that radiological and pathologic measurements could provide equivalent precision. CONCLUSION: Our study showed that CT did not underestimate the macroscopic size and microscopic extension of NSN and confirmed that CT can be used for NSN treatment planning.

Ruxolitinib inhibits cytokine production by human lung macrophages without impairing phagocytic ability.

Background: The Janus kinase (JAK) 1/2 inhibitor ruxolitinib has been approved in an indication of myelofibrosis and is a candidate for the treatment of a number of inflammatory or autoimmune diseases. We assessed the effects of ruxolitinib on lipopolysaccharide (LPS)- and poly (I:C)-induced cytokine production by human lung macrophages (LMs) and on the LMs' phagocytic activity. Methods: Human LMs were isolated from patients operated on for lung carcinoma. The LMs were cultured with ruxolitinib (0.5 × 10-7 M to 10-5 M) or budesonide (10-11 to 10-8 M) and then stimulated with LPS (10 ng·ml-1) or poly (I:C) (10 µg·ml-1) for 24 h. Cytokines released by the LMs into the supernatants were measured using ELISAs. The phagocytosis of labelled bioparticles was assessed using flow cytometry. Results: Ruxolitinib inhibited both the LPS- and poly (I:C)-stimulated production of tumor necrosis factor alpha, interleukin (IL)-6, IL-10, chemokines CCL2, and CXCL10 in a concentration-dependent manner. Ruxolitinib also inhibited the poly (I:C)- induced (but not the LPS-induced) production of IL-1ß. Budesonide inhibited cytokine production more strongly than ruxolitinib but failed to mitigate the production of CXCL10. The LMs' phagocytic activity was not impaired by the highest tested concentration (10-5 M) of ruxolitinib. Conclusion: Clinically relevant concentrations of ruxolitinib inhibited the LPS- and poly (I:C)-stimulated production of cytokines by human LMs but did not impair their phagocytic activity. Overall, ruxolitinib's anti-inflammatory activities are less intense than (but somewhat different from) those of budesonide-particularly with regard to the production of the corticosteroid-resistant chemokine CXCL-10. Our results indicate that treatment with a JAK inhibitor might be a valuable anti-inflammatory strategy in chronic obstructive pulmonary disease, Th1-high asthma, and both viral and non-viral acute respiratory distress syndromes (including coronavirus disease 2019).

Early Postoperative Pain Trajectories after Posterolateral and Axillary Approaches to Thoracic Surgery: A Prospective Monocentric Observational Study.

Less-invasive thoracotomies may reduce early postoperative pain. The aims of this study were to identify pain trajectories from postoperative days 0-5 after posterolateral and axillary thoracotomies and to identify potential factors related to the worst trajectory. Patients undergoing a posterolateral (92 patients) or axillary (89 patients) thoracotomy between July 2014 and November 2015 were analyzed in this prospective monocentric cohort study. The best-fitting model resulted in four pain trajectory groups: trajectory 1, the "worst", with 29.8% of the patients with permanent significant pain; trajectory 2 with patients with low pain (32.6%); trajectory 3 with patients with a steep decrease in pain (22.7%); and trajectory 4 with patients with a steep increase (14.9%). According to a multinomial logistic model multivariable analysis, some predictive factors allow for differentiation between trajectory groups 1 and 2. Risk factors for permanent pain are the existence of preoperative pain (OR = 6.94, CI 95% (1.54-31.27)) and scar length (OR = 1.20 (1.05-1.38)). In contrast, ASA class III is a protective factor in group 1 (OR = 0.02 (0.001-0.52)). In conclusion, early postoperative pain can be characterized by four trajectories and preoperative pain is a major factor for the worst trajectory of early postoperative pain.

A Horseshoe Intralobar Lung Sequestration Resection by Bilateral Robot-Assisted Surgery.

We present the case of a 20-year-old male patient presenting a right lower intralobar pulmonary "horseshoe" sequestration extending into the left cavity supplied by 4 aberrant arteries from the thoracic descending aorta. The surgical approach for this exceptional and challenging presentation was based on thorough analysis of the chest computed tomography scan aided by 3-dimensional reconstructions. The latter helped us better understand this complex malformation. Surgery was done by robot-assisted bilateral approach with en bloc extraction through the left side.

Blood Lactate During Double-Lung Transplantation: A Predictor of Grade-3 Primary Graft Dysfunction.

OBJECTIVE: Many prognostic factors of grade-3 primary graft dysfunction at postoperative day 3 (PGD3-T72) have been reported, but intraoperative blood lactate level has not been studied. The present retrospective study was done to test the hypothesis that intraoperative blood lactate level (BLL) could be a predictor of PGD3-T72 after double-lung transplantation. DESIGN: Retrospective monocentric cohort study. SETTING: Foch University Hospital, Suresnes, France. PARTICIPANTS: Patients having received a double-lung transplantation between 2012 and 2019. Patients transplanted twice during the study period, having undergone a multiorgan transplantation, or cardiopulmonary bypass, and those under preoperative extracorporeal membrane oxygenation, were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis was performed on a cohort of 449 patients. Seventy-two (16%) patients had a PGD3-T72. Blood lactate level increased throughout surgery to reach a median value of 2.2 (1.6-3.2) mmol/L in the No-PGD3-T72 group and 3.4 (2.3-5.0) mmol/L in the PGD3-T72 group after second lung implantation. The best predictive model for PGD3-T72 was obtained adding a lactate threshold of 2.6 mmol/L at the end of surgery to the clinical model, and the area under the curve was 0.867, with a sensitivity = 76.9% and specificity = 85.4%. Repeated-measures mixed model of BLL during surgery remained significant after adjustment for covariates (F ratio= 4.22, p < 0.001 for interaction). CONCLUSIONS: Blood lactate level increases during surgery and reaches a maximum after the second lung implantation. A value below the threshold of 2.6 mmol/L at the end of surgery has a high negative predictive value for the occurrence of a grade-3 primary graft dysfunction at postoperative day 3.