Transesophageal Echocardiography-Guided Extracorporeal Membrane Oxygenation Cannulation in COVID-19 Patients.

OBJECTIVES: A paucity of data supports the use of transesophageal echocardiography (TEE) for bedside extracorporeal membrane oxygenation (ECMO) cannulation. Concerns have been raised about performing TEEs in patients with COVID-19. The authors describe the use and safety of TEE guidance for ECMO cannulation for COVID-19. DESIGN: Single-center retrospective cohort study. SETTING: The study took place in the intensive care unit of an academic tertiary center. PARTICIPANTS: The authors included 107 patients with confirmed SARS-CoV-2 infection who underwent bedside venovenous ECMO (VV ECMO) cannulation under TEE guidance between May 2020 and June 2021. INTERVENTIONS: TEE-guided bedside VV ECMO cannulation. MEASUREMENTS: Patient characteristics, physiologic and ventilatory parameters, and echocardiographic findings were analyzed. The primary outcome was the number of successful TEE-guided bedside cannulations without complications. The secondary outcomes were cannulation complications, frequency of cannula repositioning, and TEE-related complications. MAIN RESULTS: TEE-guided cannulation was successful in 99% of the patients. Initial cannula position was adequate in all but 1 patient. Fourteen patients (13%) required cannula repositioning during ECMO support. Forty-five patients (42%) had right ventricular systolic dysfunction, and 9 (8%) had left ventricular systolic dysfunction. Twelve patients (11%) had intracardiac thrombi. One superficial arterial injury and 1 pneumothorax occurred. No pericardial tamponade, hemothorax or intraabdominal bleeding occurred in the authors' cohort. No TEE-related complications or COVID-19 infection of healthcare providers were reported during this study. CONCLUSIONS: Bedside TEE guidance for VV ECMO cannulation is safe in patients with severe respiratory failure due to COVID-19. No tamponade or hemothorax, nor TEE-related complications were observed in the authors' cohort.

Pushing the Envelope for Donor Lungs.

The shortage of organ donors remains the major limiting factor in lung transplant, with the number of patients on the waiting list largely exceeding the number of available organ donors. Another issue is the low utilization rate seen in some types of donors. Therefore, novel strategies are continuously being explored to increase the donor pool. Advanced age, smoking history, positive serologies, and size mismatch are common criteria that decrease the rate of use when it comes to organ utilization. Questioning these limitations is one of the purposes of this review. Challenging these limitations by adapting novel donor management strategies could help to increase the rate of suitable lungs for transplantation while still maintaining good outcomes. A second goal is to present the latest advances in organ donation after controlled and uncontrolled cardiac death, and also on how to improve these lungs on ex vivo platforms for assessment and future specific therapies. Finally, pushing the limit of the donor envelope also means reviewing some of the recent improvements made in lung preservation itself, as well as upcoming experimental research fields. In summary, donor lung optimization refers to a global care strategy to increase the total numbers of available allografts, and preserve or improve organ quality without paying the price of early-, mid-, or long-term negative outcomes after transplantation.

Treatment with 3-aminobenzamide during ex vivo lung perfusion of damaged rat lungs reduces graft injury and dysfunction after transplantation.

Ex vivo lung perfusion (EVLP) with pharmacological reconditioning may increase donor lung utilization for transplantation (LTx). 3-Aminobenzamide (3-AB), an inhibitor of poly(ADP-ribose) polymerase (PARP), reduces ex vivo lung injury in rat lungs damaged by warm ischemia (WI). Here we determined the effects of 3-AB reconditioning on graft outcome after LTx. Three groups of donor lungs were studied: Control (Ctrl): 1 hour WI + 3 hours cold ischemia (CI) + LTx; EVLP: 1 hour WI + 3 hours EVLP + LTx; EVLP + 3-AB: 1 hour WI + 3 hours EVLP + 3-AB (1 mg. mL-1 ) + LTx. Two hours after LTx, we determined lung graft compliance, edema, histology, neutrophil counts in bronchoalveolar lavage (BAL), mRNA levels of adhesion molecules within the graft, as well as concentrations of interleukin-6 and 10 (IL-6, IL-10) in BAL and plasma. 3-AB reconditioning during EVLP improved compliance and reduced lung edema, neutrophil infiltration, and the expression of adhesion molecules within the transplanted lungs. 3-AB also attenuated the IL-6/IL-10 ratio in BAL and plasma, supporting an improved balance between pro- and anti-inflammatory mediators. Thus, 3-AB reconditioning during EVLP of rat lung grafts damaged by WI markedly reduces inflammation, edema, and physiological deterioration after LTx, supporting the use of PARP inhibitors for the rehabilitation of damaged lungs during EVLP.

Impact of Compliance With Components of an ERAS Pathway on the Outcomes of Anatomic VATS Pulmonary Resections.

OBJECTIVES: Implementation of an Enhanced Recovery After Surgery (ERAS) program is associated with better postoperative outcomes. The aim of this study was to evaluate the impact of ERAS compliance (overall and to specific elements of the program) on them. DESIGN: Retrospective analysis of prospectively collected data. SETTING: University hospital, monocentric. PARTICIPANTS: All adult (≥18 years old) patients undergoing video-assisted thoracic surgery (VATS) anatomic pulmonary resection. INTERVENTIONS: ERAS-governed VATS anatomic pulmonary resection. MEASUREMENTS AND MAIN RESULTS: Demographics, surgical characteristics and pre-, peri-, and postoperative compliance with 16 elements of the ERAS program were assessed. Postoperative outcomes and length of stay were compared between low- (<75% of adherence) and high-compliance (≥75%) groups. From April 2017 to November 2018, 192 ERAS patients (female/male: 98/94) of median age of 66 years (interquartile range 58-71) underwent VATS resection (109 lobectomies, 83 segmentectomies). There was no 30-day mortality and resurgery rate was 5.7%. Overall ERAS compliance was 76%. High compliance was associated with fewer complications (18% v 48%, p < 0.0001) and lower rate of delayed discharge (37% v 60%, p = 0.0013). Early removal of chest tubes (odds ratio [OR]: 0.26, p < 0.002), use of electronic drainage (OR: 0.39, p = 0.036), opioid cessation on day 3 (OR: 0.28, p = 0.016), and early feeding (OR: 0.12, p = 0.014) were associated with reduced rates of postoperative complications. Shorter hospital stay was correlated with early removal of chest tubes (OR: 0.12, p < 0.0001) and opioid cessation on day 3 (OR: 0.23, p = 0.001). CONCLUSIONS: High ERAS compliance is associated with better postoperative outcomes in patients undergoing anatomic pulmonary VATS resections.

[Pulmonary metastasectomy]. / Métastases pulmonaires†: une maladie chirurgicale†?

The lung is the second site of metastasis after the liver, affecting 30 to 40 % of all patients with a malignant tumor. Chemotherapy seems to be ineffective for some types of tumor. Although there are no prospective randomized studies that confirm the benefit of surgical pulmonary metastasectomy, many studies have shown the existence of a group of patients with pulmonary metastases who benefit from a complete resection for curative purposes in case of complete resection of lung metastases. Different approaches are known to achieve a complete resection with maximum lung parenchyma sparing. Minimal invasive approaches appear to offer a better quality of life and have equivalent oncologic outcomes compared to the open approach.

Au cours d'un cancer, 40 % des patients vont développer des métastases pulmonaires et dans cette situation un traitement seul de chimiothérapie est généralement peu efficace. Même s'il n'existe pas d'études randomisées prospectives qui confirment le bénéfice de la métastasectomie pulmonaire chirurgicale, diverses études ont montré l'existence d'un groupe de patients atteints de métastases pulmonaires qui bénéficient d'une résection à visée curative en cas de résection complète des métastases pulmonaires. Différentes approches chirurgicales peuvent être utilisées ayant pour but principal une résection complète et une épargne maximale du parenchyme pulmonaire. Les approches minimales invasives semblent offrir une meilleure qualité de vie et un résultat oncologique équivalent à l'approche par voie ouverte.

A plea for thoracoscopic resection of solitary pulmonary nodule in cancer patients.

BACKGROUND: Solitary pulmonary nodules (SPN) are frequently detected in cancer patients. These lesions are often considered as pulmonary metastases and increasingly treated by non-surgical techniques without histological confirmation. The aim of this study is to determine the histological nature of SPN resected by thoracoscopy and to identify risk factors of malignancy. METHODS: Single-institution retrospective analysis of all consecutive patients with previously known malignancies who underwent thoracoscopic resection of SPN with unknown diagnosis between 2001 and 2014. RESULTS: One hundred and forty cancer patients underwent thoracoscopic resection of a SPN. The resected SPN was benign in 34 patients (24.3%) and malignant in 106 patients. The latter were metastasis in 70 patients (50%) and a primary lung cancer in 36 patients (25.7%). Upon univariate analysis, malignancy was significantly associated with age >60 years, disease-free interval ≥24 months, SPN size >8 mm, upper lobe localization and SUVmax > 2.5 on PET-CT. Upon multivariate analysis, upper lobe localization and SUVmax > 2.5 were associated with malignancy. Smoking was significantly associated with SPN containing primary lung cancer. CONCLUSION: In this series, only 50% of SPN in patients with known malignant disease were pulmonary metastases and 25% had a newly diagnosed NSCLC. Smoking was associated with primary lung cancer but no other predictor was found to allow the distinction between pulmonary metastasis and lung cancer. These results endorse the need of histological confirmation of SPN in patients with previous malignancies to avoid diagnostic uncertainty and suboptimal treatments.

Survival and Local Recurrence After Video-Assisted Thoracoscopic Lung Metastasectomy.

BACKGROUND: Pulmonary metastasectomy is increasingly performed in selected patients by video-assisted thoracic surgery (VATS) on the base of thin-slice high-resolution CT-Scan (HRCT). This study determines the overall survival and ipsilateral recurrence rate and of patients undergoing after VATS lung metastasectomy. PATIENTS AND METHOD: Retrospective single institution study of all patients who underwent VATS pulmonary metastasectomy on the base of HRCT with curative intent between 2005 and 2014. RESULTS: Seventy-seven patients (41 males, 36 females) underwent VATS pulmonary metastasectomy for solitary (n = 63) or multiple (n = 14) lung metastases in the context of colorectal carcinoma (n = 26), sarcoma (n = 17), melanoma (n = 16), or other primaries (n = 18). Nine patients had bilateral lung metastases and underwent synchronous (n = 4) or sequential (n = 5) VATS resections. Preoperative CT-guided hook wire localization of the lesions was performed in 65 patients (84 %). The postoperative mortality and morbidity rates were 0 and 5.2 %, respectively. During a mean follow-up time of 24 months (range 1­120 months), tumor progression occurred in 46 patients. Twenty-three patients (30 %) had pulmonary recurrence only, of them, eight patients (10 %) in the operated lungs. Seven of eight patients with recurrence in the operated lungs underwent a second metastasectomy by VATS (n = 5) or thoracotomy (n = 2). The overall 5-year survival rate was 54 % and without difference between patients without tumor recurrence and those with pulmonary recurrence treated by re-metastasectomy. CONCLUSION: Ipsilateral recurrence remains low after VATS pulmonary metastasectomy guided by preoperative HRCT and can be efficiently treated by re-metastasectomy.

Enhanced recovery after chest wall resection and reconstruction: a clinical practice review.

Since the late 1990s, and Henrik Kehlet's hypothesis that a reduction of the body's stress response to major surgeries could decrease postoperative morbidity, "Enhanced Recovery After Surgery" (ERAS) care pathways have been streamlined. They are now well accepted and considered standard in many surgical disciplines. Yet, to this day, there is no specific ERAS protocol for chest wall resections (CWRs), the removal of a full-thickness portion of the chest wall, including muscle, bone and possibly skin. This is most unfortunate because these are high-risk surgeries, which carry high morbidity rates. In this review, we propose an overview of the current key elements of the ERAS guidelines for thoracic surgery that might apply to CWRs. A successful ERAS pathway for CWR patients would entail, as is the standard approach, three parts: pre-, peri- and postoperative elements. Preoperative items would include specific information, targeted patient education, involvement of all members of the team, including the plastic surgeons, smoking cessation, dedicated nutrition and carbohydrate loading. Perioperative items would likely be standard for thoracotomy patients, namely carefully selective pre-anesthesia sedative medication only in some rare instances, low-molecular-weight heparin throughout, antibiotic prophylaxis, minimization of postoperative nausea and vomiting, avoidance of fluid overload and of urinary drainage. Postoperative elements would include early mobilization and feeding, swift discontinuation of intravenous fluid supply and chest tube removal as soon as safe. Optimal pain management throughout also appears to be critical to minimize the risk of respiratory complications. Together, all these items are achievable and may hold the key to successful introduction of ERAS pathways to the benefit of CWR patients.

CT-Derived Sarcopenia and Outcomes after Thoracoscopic Pulmonary Resection for Non-Small Cell Lung Cancer.

We aimed to evaluate whether computed tomography (CT)-derived preoperative sarcopenia measures were associated with postoperative outcomes and survival after video-assisted thoracoscopic (VATS) anatomical pulmonary resection in patients with early-stage non-small cell lung cancer (NSCLC). We retrospectively reviewed all consecutive patients that underwent VATS anatomical pulmonary resection for NSCLC between 2012 and 2019. Skeletal muscle mass was measured at L3 vertebral level on preoperative CT or PET/CT scans to identify sarcopenic patients according to established threshold values. We compared postoperative outcomes and survival of sarcopenic vs. non-sarcopenic patients. A total of 401 patients underwent VATS anatomical pulmonary resection for NSCLC. Sarcopenia was identified in 92 patients (23%). Sarcopenic patients were predominantly males (75% vs. 25%; p < 0.001) and had a lower BMI (21.4 vs. 26.5 kg/m2; p < 0.001). The overall postoperative complication rate was significantly higher (53.2% vs. 39.2%; p = 0.017) in sarcopenic patients and the length of hospital stay was prolonged (8 vs. 6 days; p = 0.032). Two factors were associated with postoperative morbidity in multivariate analysis: BMI and American Society of Anesthesiologists score >2. Median overall survival was comparable between groups (41 vs. 46 months; p = 0.240). CT-derived sarcopenia appeared to have a small impact on early postoperative clinical outcomes, but no effect on overall survival after VATS anatomical lung resection for NSCLC.

Local control and short-term outcomes after video-assisted thoracoscopic surgery segmentectomy versus lobectomy for pT1c pN0 non-small-cell lung cancer.

OBJECTIVES: The aim of this study was to compare short-term outcomes and local control in pT1c pN0 non-small-cell lung cancer that were intentionally treated by video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy. METHODS: Multicentre retrospective study of consecutive patients undergoing VATS lobectomy (VL) or VATS segmentectomy (VS) for pT1c pN0 non-small-cell lung cancer from January 2014 to October 2021. Patients' characteristics, postoperative outcomes and survival were compared. RESULTS: In total, 162 patients underwent VL (n = 81) or VS (n = 81). Except for age [median (interquartile range) 68 (60-73) vs 71 (65-76) years; P = 0.034] and past medical history of cancer (32% vs 48%; P = 0.038), there was no difference between VL and VS in terms of demographics and comorbidities. Overall 30-day postoperative morbidity was similar in both groups (34% vs 30%; P = 0.5). The median time for chest tube removal [3 (1-5) vs 2 (1-3) days; P = 0.002] and median postoperative length of stay [6 (4-9) vs 5 (3-7) days; P = 0.039] were in favour of the VS group. Significantly larger tumour size (mean ± standard deviation 25.1 ± 3.1 vs 23.6 ± 3.1 mm; P = 0.001) and an increased number of lymph nodes removal [median (interquartile range) 14 (9-23) vs 10 (6-15); P < 0.001] were found in the VL group. During the follow-up [median (interquartile range) 31 (14-48) months], no statistical difference was found for local and distant recurrence in VL groups (12.3%) and VS group (6.1%) (P = 0.183). Overall survival (80% vs 80%) was comparable between both groups (P = 0.166). CONCLUSIONS: Despite a short follow-up, our preliminary data shows that local control is comparable for VL and VS.

Pulmonary endarterectomy in severe chronic thromboembolic pulmonary hypertension: the Toronto experience.

Background: Pulmonary endarterectomy (PEA) in severe chronic thromboembolic pulmonary hypertension (CTEPH) is associated with higher risks. However, recent evidence suggests that these risks may be mitigated with the use of extracorporeal membrane oxygenation (ECMO). Methods: We performed a retrospective analysis of 401 consecutive patients undergoing PEA at the Toronto General Hospital between August 2005 and March 2020. Patients with severe CTEPH defined by pulmonary vascular resistance (PVR) >1,000 dynes.s.cm-5 at the time of diagnosis were compared to those with PVR <1,000 dynes.s.cm-5. Results: The New York Heart Association (NYHA) functional class, brain natriuretic peptide (BNP) and 6-minute walk distance were worse in patients with PVR >1,000 dynes.s.cm-5. A greater proportion of patients with PVR >1,000 dynes.s.cm-5 was treated with targeted pulmonary hypertension (PH) medical therapy (38% vs. 18%, P<0.001) and initiated on inotropic support (7% vs. 0.3%, P<0.001) before PEA. Since 2014, the ECMO utilization rate increased in patients with PVR >1,000 dynes.s.cm-5 compared to those with PVR <1,000 dynes.s.cm-5 (18% vs. 3.1%, P<0.001). The hospital mortality in patients with PVR >1,000 dynes.s.cm-5 decreased from 10.3% in 2005-2013 to 1.6% in 2014-2020 (P=0.05), while the hospital mortality in patients with PVR <1,000 dynes.s.cm-5 remained stable (1.2% in 2005-2013 vs. 2.7% in 2014-2020, P=0.4). The overall survival reached 84% at 10 years in patients with PVR >1,000 dynes.s.cm-5 compared to 78% in patients with PVR <1,000 dynes.s.cm-5 (P=0.7). Conclusions: The early and long-term results of PEA in patients with severe CTEPH are excellent despite greater postoperative risks. ECMO as a bridge to recovery after PEA can be useful in patients with severe CTEPH.

Is faster better? Impact of operative time on postoperative outcomes after VATS anatomical pulmonary resection.

Background: Video-assisted thoracic surgery (VATS) is now the preferred approach for standard anatomical pulmonary resections. This study evaluates the impact of operative time (OT) on post-operative outcomes after VATS anatomical pulmonary resection for non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed all consecutive patients undergoing VATS lobectomy or segmentectomy for NSCLC between November 2010 and December 2019. Postoperative outcomes were compared between short (<150 minutes) and long (≥150 minutes) OT groups. A multivariable analysis was performed to identify predictors of long OT and overall post-operative complications. Results: A total of 670 patients underwent lobectomy (n=496, 74%) or segmentectomy (n=174, 26%) for NSCLC. Mediastinal lymph node dissection was performed in 621 patients (92.7%). The median OT was 141 minutes (SD: 47 minutes) and 387 patients (57.8%) were operated within 150 minutes. Neoadjuvant chemotherapy was given in 25 patients (3.7%). Conversion thoracotomy was realized in 40 patients (6%). Shorter OT was significantly associated with decreased post-operative overall complication rate (30% vs. 41%; P=0.003), shorter median length of drainage (3 vs. 4 days; P<0.001) and shorter median length of hospital stay (6 vs. 7 days; P<0.001). On multivariable analysis, long OT (≥150 minutes) (OR 1.64, P=0.006), ASA score >2 (OR 1.87, P=0.001), FEV1 <80% (OR 1.47, P=0.046) and DLCO <80% (OR 1.5, P=0.045) were significantly associated with postoperative complications. Two predictors of long OT were identified: neoadjuvant chemotherapy (OR 3.11, P=0.01) and lobectomy (OR 1.5, P=0.032). Conclusions: A prolonged OT is significantly associated with postoperative complications in our collective of patients undergoing VATS anatomical pulmonary resection.

The size and sternal involvement of chest wall resections for malignant disease predict postoperative morbidity.

Background: Chest wall resections/reconstructions are a validated approach to manage tumors invading the thorax. However, how resection characteristics affect postoperative morbidity and mortality is unknown. We determined the impact of chest wall resection size and location on patient short and long-term postoperative outcomes. Methods: We reviewed all consecutive patients who underwent resections/reconstructions for chest wall tumors between 2003 and 2018. The impact of chest wall resection size and location and reconstruction on perioperative morbidity/mortality and oncological outcome were evaluated for each patient. Results: Ninety-three chest wall resections were performed in 88 patients for primary (sarcoma, breast cancer, n=66, 71%) and metastatic (n=27, 29%) chest wall tumors. The mean chest bony resection size was 107 (range, 15-375) cm2 and involved ribs only in 57% (n=53) or ribs combined to sternal/clavicular resections in 43% of patients (n=40). Chest defect reconstruction methods included muscle flaps alone (14%) prosthetic material alone (25%) or a combination of both (61%). Early systemic postoperative complications included pneumonia (n=15, 16%), atelectasis (n=6, 6%), pleural effusion (n=15, 16%) and arrhythmia (n=6, 6%). The most frequent long-term reconstructive complications included wound dehiscence (n=4), mesh infection (n=5) and seroma (n=4). Uni- and multivariable analyses indicated that chest wall resection size (>114 cm2) and location (sternum) were significantly associated with the occurrence of pneumonia and atelectasis [odds ratio (OR) =3.67, P=0.05; OR =78.92, P=0.02, respectively]. Disease-free and overall survival were 37±43 and 48±42 months for primary malignancy and of 24±33 and 48±53 months for metastatic chest wall tumors respectively with a mean follow-up of 46±44 months. Conclusions: Chest wall resections present good long-term oncological outcomes. A resection size above 114 cm2 and the involvement of the sternum are significantly associated with higher rates of postoperative pneumonia/atelectasis. This subgroup of patients should have reinforced perioperative physical therapy protocols.

Central venoarterial extracorporeal membrane oxygenation as a bridge to recovery after pulmonary endarterectomy in patients with decompensated right heart failure.

INTRODUCTION: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) and decompensated right heart failure (DRHF) have worse outcomes after pulmonary endarterectomy (PEA). We reviewed the role of central veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as a bridge to recovery after PEA in these patients. METHODS: Of 388 consecutive patients undergoing PEA, 40 (10.3%) were admitted with DRHF before PEA. This group was compared to the remaining 348 patients undergoing PEA (elective group). We also compared 2 periods: 2005-2013 (n = 120) and 2014-2019 (n = 268) after which early central VA-ECMO was introduced as a strategy to manage difficulty weaning from cardiopulmonary bypass (CPB). RESULTS: The proportion of patients with DRHF remained similar between the first and second period (13% vs 9%, p = .2). The number of VA-ECMO bridge to recovery increased from 0.8% in 2005-2013 to 6.3% in 2014-2019 (p = .02). In the second period, 29% of DRHF patients were transitioned intraoperatively from CPB to central VA-ECMO for a median duration of 3 (2-7) days. After the introduction of central VA-ECMO as a bridge to recovery, the hospital mortality in patients with DRHF dropped from 31% in 2005-2013 to 4% in 2014-2019 (p = .03). In the long-term, the functional recovery and survival after discharged from hospital was similar between the DRHF group and the elective group. However, at 5 years, DRHF patients more frequently required PH targeted medical therapy (45% vs 20% in the elective group, p = .002). CONCLUSIONS: Central VA-ECMO as a bridge to recovery is an important treatment strategy that can decrease hospital mortality in patients with DRHF and lead to excellent long-term outcome.

Effectiveness of rib fixation compared to pain medication alone on pain control in patients with uncomplicated rib fractures: study protocol of a pragmatic multicenter randomized controlled trial-the PAROS study (Pain After Rib OSteosynthesis).

BACKGROUND: Persistent pain and disability following rib fractures result in a large psycho-socio-economic impact for health-care system. Benefits of rib osteosynthesis are well documented in patients with flail chest that necessitates invasive ventilation. In patients with uncomplicated and simple rib fractures, indication for rib osteosynthesis is not clear. The aim of this trial is to compare pain at 2 months after rib osteosynthesis versus medical therapy. METHODS: This trial is a pragmatic multicenter, randomized, superiority, controlled, two-arm, not-blinded, trial that compares pain evolution between rib fixation and standard pain medication versus standard pain medication alone in patients with uncomplicated rib fractures. The study takes place in three hospitals of Thoracic Surgery of Western Switzerland. Primary outcome is pain measured by the brief pain inventory (BPI) questionnaire at 2 months post-surgery. The study includes follow-up assessments at 1, 2, 3, 6, and 12 months after discharge. To be able to detect at least 2 point-difference on the BPI between both groups (standard deviation 2) with 90% power and two-sided 5% type I error, 46 patients per group are required. Adjusting for 10% drop-outs leads to 51 patients per group. DISCUSSION: Uncomplicated rib fractures have a significant medico-economic impact. Surgical treatment with rib fixation could result in better clinical recovery of patients with uncomplicated rib fractures. These improved outcomes could include less acute and chronic pain, improved pulmonary function and quality of life, and shorter return to work. Finally, surgical treatment could then result in less financial costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04745520 . Registered on 8 February 2021.

Evaluation of 10°C as the optimal storage temperature for aspiration-injured donor lungs in a large animal transplant model.

BACKGROUND: Our recent work has challenged 4°C as an optimal lung preservation temperature by showing storage at 10°C to allow for the extension of preservation periods. Despite these findings, the impact of 10°C storage has not been evaluated in the setting of injured donor lungs. METHODS: Aspiration injury was created through bronchoscopic delivery of gastric juice (pH: 1.8). Injured donor lungs (n = 5/group) were then procured and blindly randomized to storage at 4°C (on ice) or at 10°C (in a thermoelectric cooler) for 12 hours. A third group included immediate transplantation. A left lung transplant was performed thereafter followed by 4 hours of graft evaluation. RESULTS: After transplantation, lungs stored at 10°C showed significantly better oxygenation when compared to 4°C group (343 ± 43 mm Hg vs 128 ± 76 mm Hg, p = 0.03). Active metabolism occurred during the 12 hours storage period at 10°C, producing cytoprotective metabolites within the graft. When compared to lungs undergoing immediate transplant, lungs preserved at 10°C tended to have lower peak airway pressures (p = 0.15) and higher dynamic lung compliances (p = 0.09). Circulating cell-free mitochondrial DNA within the recipient plasma was significantly lower for lungs stored at 10°C in comparison to those underwent immediate transplant (p = 0.048), alongside a tendency of lower levels of tissue apoptotic cell death (p = 0.075). CONCLUSIONS: We demonstrate 10°C as a potentially superior storage temperature for injured donor lungs in a pig model when compared to the current clinical standard (4°C) and immediate transplantation. Continuing protective metabolism at 10°C for donor lungs may result in better transplant outcomes.

Ex vivo enzymatic treatment converts blood type A donor lungs into universal blood type lungs.

Donor organ allocation is dependent on ABO matching, restricting the opportunity for some patients to receive a life-saving transplant. The enzymes FpGalNAc deacetylase and FpGalactosaminidase, used in combination, have been described to effectively convert group A (ABO-A) red blood cells (RBCs) to group O (ABO-O). Here, we study the safety and preclinical efficacy of using these enzymes to remove A antigen (A-Ag) from human donor lungs using ex vivo lung perfusion (EVLP). First, the ability of these enzymes to remove A-Ag in organ perfusate solutions was examined on five human ABO-A1 RBC samples and three human aortae after static incubation. The enzymes removed greater than 99 and 90% A-Ag from RBCs and aortae, respectively, at concentrations as low as 1 µg/ml. Eight ABO-A1 human lungs were then treated by EVLP. Baseline analyses of A-Ag in lungs revealed expression predominantly in the endothelial and epithelial cells. EVLP of lungs with enzyme-containing perfusate removed over 97% of endothelial A-Ag within 4 hours. No treatment-related acute lung toxicity was observed. An ABO-incompatible transplant was then simulated with an ex vivo model of antibody-mediated rejection using ABO-O plasma as the surrogate for the recipient circulation using three donor lungs. The treatment of donor lungs minimized antibody binding, complement deposition, and antibody-mediated injury as compared with control lungs. These results show that depletion of donor lung A-Ag can be achieved with EVLP treatment. This strategy has the potential to expand ABO-incompatible lung transplantation and lead to improvements in fairness of organ allocation.

Early discharge after thoracoscopic anatomical pulmonary resection for non-small-cell lung cancer.

OBJECTIVES: Although video-assisted thoracic surgery (VATS) has shortened hospitalization duration for non-small-cell lung cancer (NSCLC) patients, the factors associated with early discharge remain unclear. This study aimed to identify patients eligible for a 72-h stay after VATS anatomical resection. METHODS: Monocentric retrospective study including all consecutive patients undergoing VATS anatomical resection for NSCLC between February 2010 and December 2019. Two groups were defined according to the discharge: 'early discharge' (within 72 postoperative hours) and 'routine discharge' (at >72 postoperative hours). RESULTS: A total of 660 patients with a median age of 66.5 years (interquartile range 60-73 years) (female/male: 321/339) underwent VATS anatomical pulmonary resection for NSCLC [segmentectomy in 169 (25.6%), lobectomy in 481 (72.9%), bilobectomy in 8 (1.2%) and pneumonectomy in 2 (0.3%) patients]. The cardiopulmonary and Clavien-Dindo III-IV postoperative complication rates were 32.6% and 7.7%, respectively. The median postoperative length of stay was 6 days (interquartile range 4-10 days). In total, 119 patients (18%) could be discharged within 72 h of surgery. On multivariable analysis, the factors significantly associated with an increased likelihood of early discharge were: body mass index >20 kg/m2 [odds ratio (OR) 2.37], absence of prior cardiopathy (OR 2), diffusing capacity of the lung for carbon monoxide >60% (OR 1.82), inclusion in an enhanced recovery after surgery protocol (OR 2.23), use of a single chest tube (OR 5.73) and postoperative transfer to the ward (OR 4.84). Factors significantly associated with a decreased likelihood of early discharge were: age >60 years (OR 0.53), American Society of Anaesthesiologists score >2 (OR 0.46) and use of an epidural catheter (OR 0.41). Readmission rates were not statistically different between both groups (5.9% vs 3.1%; P = 0.17). CONCLUSIONS: Age, pulmonary functions and comorbidities may influence discharge after VATS anatomical resection. The early discharge does not increase readmission rates.

Survival prognostic and recurrence risk factors after single pulmonary metastasectomy.

BACKGROUND: Identification of the prognostic factors of recurrence and survival after single pulmonary metastasectomy (PM). METHODS: Retrospective analysis of all consecutive patients who underwent PM for a single lung metastasis between 2003 and 2018. RESULTS: A total of 162 patients with a median age of 64 years underwent single PM. Video-Assisted Thoracic Surgery (VATS) was performed in 83.9% of cases. Surgical resection was achieved by wedge in 73.5%, segmentectomy in 7.4%, lobectomy in 17.9% and pneumonectomy in 1.2% of cases. The median durations of hospital stay and of drainage were 4 days (IQR 3-7) and 1 day (IQR 1-2), respectively. During the follow-up (median 31 months; IQR 15-58), 93 patients (57.4%) presented recurrences and repeated PM could be realized in 35 patients (21.6%) achieved by VATS in 77.1%. Non-colorectal tumour (HR 1.84), age < 70 years (HR 1.77) and previous extra-thoracic metastases (HR 1.61) were identified as prognostic factors of recurrence. Overall survival at 5-year was estimated at 67%. Non-colorectal tumour (HR 2.40) and mediastinal lymph nodes involvement (HR 3.42) were significantly associated with an increased risk of death. CONCLUSIONS: Despite high recurrence rates after PM, surgical resection shows low morbidity rate and acceptable long-term survival, thus should remain the standard treatment for single pulmonary metastases. TRIAL REGISTRATION: The Local Ethics Committee approved the study (No. 2019-02,474) and individual consent was waived.

Effects of cold or warm ischemia and ex-vivo lung perfusion on the release of damage associated molecular patterns and inflammatory cytokines in experimental lung transplantation.

BACKGROUND: Lung transplantation (LTx) is associated with sterile inflammation, possibly related to the release of damage associated molecular patterns (DAMPs) by injured allograft cells. We have measured cellular damage and the release of DAMPs and cytokines in an experimental model of LTx after cold or warm ischemia and examined the effect of pretreatment with ex-vivo lung perfusion (EVLP). METHODS: Rat lungs were exposed to cold ischemia alone (CI group) or with 3h EVLP (CI-E group), warm ischemia alone (WI group) or with 3 hour EVLP (WI-E group), followed by LTx (2 hour). Bronchoalveolar lavage (BAL) was performed before (right lung) or after (left lung) LTx to measure LDH (marker of cellular injury), the DAMPs HMGB1, IL-33, HSP-70 and S100A8, and the cytokines IL-1ß, IL-6, TNFα, and CXCL-1. Graft oxygenation capacity and static compliance after LTx were also determined. RESULTS: Compared to CI, WI displayed cellular damage and inflammation without any increase of DAMPs after ischemia alone, but with a significant increase of HMGB1 and functional impairment after LTx. EVLP promoted significant inflammation in both cold (CI-E) and warm (WI-E) groups, which was not associated with cell death or DAMP release at the end of EVLP, but with the release of S100A8 after LTx. EVLP reduced graft damage and dysfunction in warm ischemic, but not cold ischemic, lungs. CONCLUSIONS: The pathomechanisms of sterile lung inflammation during LTx are significantly dependent on the conditions. The release of HMGB1 (in the absence of EVLP) and S100A8 (following EVLP) may be important factors in the pathogenesis of LTx.