Size-matching in lung transplantation by computed tomography for end-stage interstitial disease: a retrospective analysis.

Background: Size matching between donors and recipients is a major issue in lung transplantation (LTx), especially in patients with restrictive lung disease (RLD). This study aims to evaluate computed tomography (CT) as an additional method for defining the total lung capacity (TLC) in patients with end-stage interstitial disease awaiting LTx. Methods: Clinical data and CT scans from patients who underwent a first LTx from January 2014 to July 2018 in Bichat Hospital, Paris, were prospectively included in a database. CT TLC (ctTLC) was retrospectively calculated after semi-automatic contouring of the parenchyma and compared with measured TLC (mTLC) and predicted TLC (pTLC) values. Results: The study group included 89 patients (male:female =68:21; mean age, 59.5±10.0 years). The time between pulmonary function tests (PFTs) and CT scan was 162±270 days [median, 67 days; interquartile range (IQR), 0-233 days]. ctTLC was inferior to mTLC and pTLC (respectively 2,979±1,001 mL, 3,530±1,077 and 6,381±955 mL, P<0.001). The relative difference between CT lung volume (ctLV) and measured lung volume (mLV) was higher on the left than on the right side (25.4% vs. 16.3%, respectively, P=0.11). After exclusion of two outliers, we found a significant correlation between ctTLC and mTLC (r=0.762, P<0.001). Conclusions: CT volume is a feasible method to assess TLC in patients with end-stage interstitial disease awaiting LTx. This study highlights potential size-mismatch for graft selection before LTx and opens the perspective of a prospective trial evaluating impact of size-matching by donor-recipient (D-R) ctTLC ratio on postoperative outcomes.

Is Night Surgery a Nightmare for Lung Transplantation?

Night work is frequently associated with sleep deprivation and is associated with greater surgical and medical complications. Lung transplantation (LT) is carried out both at night and during the day and involves many medical healthcare workers. The goal of the study was to compare morbidity and mortality between LT recipients according to LT operative time. We performed a retrospective, observational, single-center study. When the procedure started between 6 AM and 6 PM, the patient was allocated to the Daytime group. If the procedure started between 6 PM and 6 AM, the patient was allocated to the Nighttime group. Between January 2015 and December 2020, 253 patients were included. A total of 168 (66%) patients were classified into the Day group, and 85 (34%) patients were classified into the Night group. Lung Donors' general characteristics were similar between the groups. The 90-day and one-year mortality rates were similar between the groups (90-days: n = 13 (15%) vs. n = 26 (15%), p = 0.970; 1 year: n = 18 (21%) vs. n = 42 (25%), p = 0.499). Daytime LT was associated with more one-year airway dehiscence (n = 36 (21%) vs. n = 6 (7.1%), p = 0.004). In conclusion, among patients who underwent LT, there was no significant association between operative time and survival.

Survival outcomes following urgent lung transplantation in France and the USA.

INTRODUCTION: Lung graft allocation can be based on a score (Lung Allocation Score) as in the USA or sequential proposals combined with a discrete priority model as in France. We aimed to analyse the impact of allocation policy on the outcome of urgent lung transplantation (LT). METHODS: US United Network for Organ Sharing (UNOS) and French Cristal databases were retrospectively reviewed to analyse LT performed between 2007 and 2017. We analysed the mortality risk of urgent LT by fitting Cox models and adjusted Restricted Mean Survival Time. We then compared the outcome after urgent LT in the UNOS and Cristal groups using a propensity score matching. RESULTS: After exclusion of patients with chronic obstructive pulmonary disease/emphysema and redo LT, 3775 and 12 561 patients underwent urgent LT and non-urgent LT in the USA while 600 and 2071 patients underwent urgent LT and non-urgent LT in France. In univariate analysis, urgent LT was associated with an HR for death of 1.24 (95% CI 1.05 to 1.48) in the Cristal group and 1.12 (95% CI 1.05 to 1.19) in the UNOS group. In multivariate analysis, the effect of urgent LT was attenuated and no longer statistically significant in the Cristal database (HR 1.1 (95% CI 0.91 to 1.33)) while it remained constant and statistically significant in the UNOS database (HR 1.12 (95% CI 1.05 to 1.2)). Survival comparison of urgent LT patients between the two countries was significantly different in favour of the UNOS group (1-year survival rates 84.1% (80.9%-87.3%) vs 75.4% (71.8%-79.1%) and 3-year survival rates 66.3% (61.9%-71.1%) vs 62.7% (58.5%-67.1%), respectively). CONCLUSION: Urgent LT is associated with adverse outcome in the USA and in France with a better prognosis in the US score-based system taking post-transplant survival into account. This difference between two healthcare systems is multifactorial.

Protocol for venoarterial ExtraCorporeal Membrane Oxygenation to reduce morbidity and mortality following bilateral lung TransPlantation: the ECMOToP randomised controlled trial.

INTRODUCTION: Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control 'on-demand' arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental 'systematic' arm, VA-ECMO will be pre-emptively initiated. We hypothesise a 'systematic' strategy will increase the number of ventilatory-free days at day 28. METHODS AND ANALYSIS: We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events. ETHICS AND DISSEMINATION: The sponsor is the Assistance Publique-Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT05664204.

Outcomes and costs with the introduction of robotic-assisted thoracic surgery in public hospitals.

Robotic-assisted thoracic surgery (RATS) is an effective treatment of non-small cell lung cancer (NSCLC) but the effects of its implementation in university hospital networks has not been described. We analyzed the early clinical outcomes, estimated costs, and revenues associated with three robotic systems implemented in the Paris Public Hospital network. A retrospective study included patients who underwent RATS for NSCLC in 2019 and 2020. Ninety-day morbidity, mortality, hospital costs, and hospital revenues were described. Economic analyses were conducted either from the hospital center or from the French health insurance system perspectives. Cost drivers were tested using univariate and multivariable analyses. Sensitivity analyses were performed to assess uncertainty over in-hospital length of stay (LOS), number of robotic surgeries per year, investment cost, operating room occupancy time, maintenance cost, and commercial discount. The study included 188 patients (65.8 ± 9.3 years; Charlson 4.1 ± 1.4; stage I 76.6%). Median in-hospital LOS was 6 days [5-9.5], 90-day mortality was 1.6%. Mean hospital expenses and revenues were €12,732 ± 4914 and €11,983 ± 5708 per patient, respectively. In multivariable analysis, factors associated with hospital costs were body mass index, DLCO, major complications, and transfer to intensive care unit. Sensitivity analyses showed that in-hospital LOS (€11,802-€15,010) and commercial discounts on the list price (€11,458-€12,732) had an important impact on costs. During the first 2 years following the installation of three robotic systems in Paris Public Hospitals, the clinical outcomes of RATS for NSCLC have been satisfactory. Without commercial discount, hospital expenses would have exceeded hospital revenues.Clinical registration number CNIL, N°2221601, CERC-SFCTCV-2021-07-20-Num17_MOPI_robolution.

Acute Pulmonary Edema After Double Mechanical Valve Replacement.

We report a case of a 16-year-old man in cardiogenic shock secondary to On-X mitral prosthesis dysfunction due to leaflet embolization through aortic mechanical prosthesis. He underwent an emergency redo mitral valve replacement and, a few days later, leaflet removal by open aortic surgery with full recovery.

Involvement of an IgE/Mast cell/B cell amplification loop in abdominal aortic aneurysm progression.

AIMS: IgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression. METHODS AND RESULTS: Through histological assays conducted on human surgical samples from AAA patients, we uncovered that activated MCs were enriched at sites of unhealed haematomas, due to subclinical aortic wall fissuring, in close proximity to adventitial IgE+ TLO B cells. Remarkably, in vitro the IgEs deriving from these samples enhanced MC production of IL-4, a cytokine which favors IgE class-switching and production by B cells. Finally, the role of MCs in aneurysmal progression was further analysed in vivo in ApoE-/- mice subjected to angiotensin II infusion aneurysm model, through MC-specific depletion after the establishment of dissecting aneurysms. MC-specific depletion improved intramural haematoma healing and reduced aneurysmal progression. CONCLUSIONS: Our data suggest that MC located close to aortic wall fissures are activated by adventitial TLO B cell-produced IgEs and participate to their own activation by providing support for further IgE synthesis through IL-4 production. By preventing prompt repair of aortic subclinical fissures, such a runaway MC activation loop could precipitate aneurysmal progression, suggesting that MC-targeting treatments may represent an interesting adjunctive therapy for reducing AAA progression.

Ultrasonography in thoracic and abdominal stab wound injury: results from the FETTHA study.

BACKGROUND: While the role of Extended Focused Assessment with Sonography in Trauma (eFAST) is well defined in the management of severe blunt trauma, its performance in injuries caused by stab wounds has been poorly assessed. METHODS: Prospective single centre study which included all patients with stab wounds to the thorax or abdomen between December 2016 and December 2018. All patients underwent initial investigation with both eFAST and CT scan, except in cases of haemodynamic or respiratory instability, and in cases with a positive diagnosis by eFAST in which case surgery without CT scan was performed. RESULTS: Of the 200 consecutive patients included, 14 unstable patients underwent surgery immediately after eFAST. In these 14 patients, 9 had cardiac tamponade identified by eFAST and all were confirmed by surgery. In the remaining 186 patients, the median time between eFAST and CT scan was 30 min (IQR 20-49 min). Test characteristics (including 95% CI) for eFAST compared with reference standard of CT scan for detecting pneumothorax were as follows: sensitivity 77% (54%-92%), specificity 93% (90%-97%), positive predictive value (PPV) 60% (49%-83%), negative predictive value (NPV) 97% (93%-99%). Test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemothorax were as follows: sensitivity 97% (74%-99%), specificity 96% (92%-98%), PPV 83% (63%-93%) and NPV 99% (96%-100%). Finally, test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemoperitoneum were as follows: sensitivity 75% (35%-97%), specificity 97% (93%-99%), PPV 55% (23%-83%) and NPV 99% (96%-99%). CONCLUSIONS: In patients admitted with stab wounds to the torso, eFAST was not sensitive enough to diagnose pneumothorax and haemoperitoneum, but performed better in the detection of cardiac tamponade and haemothorax than the other injuries. More robust multicentre studies are needed to better define the role of eFAST in this specific population.

Single Primary Retrograde Access to Treat Femoro-Popliteal Occlusive Lesions.

INTRODUCTION: The retrograde puncture of a distal artery is considered a bailout procedure in case of anterograde approach failure for peripheral artery disease (PAD) treatment. A single primary retrograde access has been suggested as an efficient and safe option. As scant data are available, we present our results using this approach. MATERIAL AND METHODS: Between August 2019 and October 2022, we performed this technique in selected patients with femoro-popliteal PAD. Chronic total occlusions (CTOs) were selected on the basis of the CTOP classification. An ultrasound-guided retrograde puncture of a tibial artery at the ankle level was performed, followed by the preferential use of 4F materials. Hemostasis of the puncture site was obtained using manual compression. Postoperative duplex scan examination systematically included an evaluation of the punctured artery. Demographics, intraoperative, and follow-up data were collected retrospectively. The results are expressed as means with standard deviations and numbers with percentages when appropriate. RESULTS: In total, 55 procedures were performed in 46 patients (9 bilateral). Of these, 57% (N=26) were considered at risk for femoral puncture (obesity, history of groin surgery, challenging crossover approach) and 54% (N=25) presented with critical limb-threatening ischemia (CLTI). The TASC-II femoro-popliteal classification was generally B (60%) and also C (33%) or D (7%). Mean lesion length was 105.6±49.4 mm and 65% were CTOs. Most patients were operated in an outpatient setting (N=25; 54%) under potentialized local anesthesia (N=41, 89%). The punctured site was the posterior tibial artery in 73% (N=40). The procedure time was 65.1±25.7 minutes, and the fluoroscopy time was 10.7±8.5 minutes. The technical success rate was 100%. There were no intraoperative complications. All patients could walk the same day. One CLTI patient presented an erysipelas related to the puncture in postoperative period. At 30 days, the primary patency of the treated and the punctured arteries were 98% and 100%, respectively. CONCLUSION: A single primary retrograde access can be used safely to treat femoro-popliteal PAD. It represents a valuable alternative to the femoral puncture and allows fast ambulation. Prospective and long-term studies on larger populations are necessary to confirm our results. CLINICAL IMPACT: This study demonstrates that a single primary retrograde access can be used safely without damaging the punctured artery to treat femoro-popliteal lesions, especially in claudicant patients. Chronic total occlusions can be treated successfully using this technique. This approach represents a valuable alternative to the femoral puncture and allows fast ambulation without risk of major bleeding.

Improving clinical suspicion of acute mesenteric ischemia among patients with acute abdomen: a cross-sectional study from an intestinal stroke center.

BACKGROUND: Early diagnosis of acute mesenteric ischemia (AMI) is essential for a favorable outcome. Selection of patients requiring a dedicated multiphasic computed tomography (CT) scan remains a clinical challenge. METHODS: In this cross-sectional diagnostic study conducted from 2016 to 2018, we compared the presentation of AMI patients admitted to an intestinal stroke center to patients with acute abdominal pain of another origin admitted to the emergency room (controls). RESULTS: We included 137 patients-52 with AMI and 85 controls. Patients with AMI [median age: 65 years (interquartile range 55-74)] had arterial and venous AMI in 65% and 35% of cases, respectively. Relative to controls, AMI patients were significantly older, more likely to have risk factors or a history of cardiovascular disease, and more likely to present with sudden-onset and morphine-requiring abdominal pain, hematochezia, guarding, organ dysfunction, higher white blood cell and neutrophil counts, and higher plasma C-reactive protein (CRP) and procalcitonin concentrations. On multivariate analysis, two independent factors were associated with the diagnosis of AMI: the sudden-onset (OR = 20, 95%CI 7-60, p < 0.001) and the morphine-requiring nature of the acute abdominal pain (OR = 6, 95%CI 2-16, p = 0.002). Sudden-onset and/or morphine-requiring abdominal pain was present in 88% of AMI patients versus 28% in controls (p < 0.001). The area under the receiver operating characteristic curve for the diagnosis of AMI was 0.84 (95%CI 0.77-0.91), depending on the number of factors. CONCLUSIONS: Sudden onset and the need for morphine are suggestive of AMI in patients with acute abdominal pain and should prompt multiphasic CT scan including arterial and venous phase images for confirmation.

A 24-Year-Old Woman With Cough, Arthralgia, and Skin Ulcerations.

CASE PRESENTATION: A 24-year-old Senegalese woman without remarkable history except anemia and iron deficiency related to excessive menstrual bleeding and sickle cell trait was admitted to our internal medicine department with 4-month fever, weight loss (-13 kg), dyspnea for limited efforts, intermittent productive cough, and bilateral metacarpophalangeal (MCP) and interphalangeal arthralgia. She was born and lived in France. She traveled previously to Senegal in 2015. She had no history of tobacco, alcohol, or drug use nor proximity with animals. She was taking no medication.

Prolonged mechanical ventilation after lung transplantation: risks factors and consequences on recipient outcome.

Background: Risk factors and the incidence of prolonged mechanical ventilation (PMV) after lung transplantation (LT) have been poorly described. The study assessed predictive factors of PMV after LT. Methods: This observational, retrospective, monocentric study included all patients who received LT in Bichat Claude Bernard Hospital between January 2016 and December 2020. PMV was defined as a duration of MV > 14 days. Independent risk factors for PMV were studied using multivariate analysis. One-year survival depending on PMV was studied using Kaplan Meier and log-rank tests. A p value <0.05 was defined as significant. Results: 224 LT recipients were analysed. 64 (28%) of them received PMV for a median duration of 34 [26-52] days versus 2 [1-3] days without PMV. Independent risk factors for PMV were higher body mass index (BMI) (p = 0.031), diabetes mellitus of the recipient (p = 0.039), ECMO support during surgery (p = 0.029) and intraoperative transfusion >5 red blood cell units (p < 0.001). Increased mortality rates were observed at one-year in recipients who received PMV (44% versus 15%, p < 0.001). Conclusion: PMV was associated with increased morbidity and mortality one-year after LT. Preoperative risk factors (BMI and diabetes mellitus) must be considered when selecting and conditioning the recipients.

AMPK activation by metformin protects against pulmonary hypertension in rats and relaxes isolated human pulmonary artery.

Pulmonary hypertension (PH) is associated with pulmonary vasoconstriction and endothelial dysfunction leading to impaired nitric oxide (NO) and prostacyclin (PGI2) pathways. Metformin, the first line treatment for type 2 diabetes and AMP-activated protein kinase (AMPK) activator, has been recently highlighted as a potential PH treatment. AMPK activation has been reported to improve endothelial function by enhancing endothelial NO synthase (eNOS) activity and to have relaxant effects in blood vessels. In this study, we examined the effect of metformin treatment on PH as well as on NO and PGI2 pathways in monocrotaline (MCT)-injected rats with established PH. Moreover, we investigated the anti-contractile effects of AMPK activators on endothelium-denuded human pulmonary arteries (HPA) from Non-PH and Group 3 PH patients (due to lung diseases and/or hypoxia). Furthermore, we explored the interaction between treprostinil and the AMPK/eNOS pathway. Our results showed that metformin protected against PH progression in MCT rats where it reduced the mean pulmonary artery pressure, pulmonary vascular remodeling and right ventricular hypertrophy and fibrosis compared to vehicle-treated MCT rats. The protective effects on rat lungs were mediated in part by increasing eNOS activity and protein kinase G-1 expression but not through the PGI2 pathway. In addition, incubation with AMPK activators reduced the phenylephrine-induced contraction of endothelium-denuded HPA from Non-PH and PH patients. Finally, treprostinil also augmented eNOS activity in HPA smooth muscle cells. In conclusion, we found that AMPK activation can enhance the NO pathway, attenuate vasoconstriction by direct effects on smooth muscles, and reverse established MCT-induced PH in rats.

Risk of Bronchial Complications After Lung Transplantation With Respiratory Corynebacteria. Results From a Monocenter Retrospective Cohort Study.

Corynebacterium spp. are associated with respiratory infections in immunocompromised hosts. A link with bronchial complications after lung transplantation (LTx) has been suggested. We aimed to assess the link between respiratory sampling of Corynebacterium spp. and significant bronchial complication (SBC) after LTx. We performed a single center retrospective study. Inclusion of LTx recipients with at least one respiratory Corynebacterium spp. sample (July 2014 to December 2018). Subjects were matched to unexposed LTx recipients. Primary outcome was SBC occurrence after Corynebacterium spp. isolation. Secondary outcomes were Corynebacterium spp. persistent sampling, chronic lung allograft dysfunction (CLAD) onset and all-cause mortality. Fifty-nine patients with Corynebacterium spp. sampling with 59 without isolation were included. Corynebacterium spp. identification was not associated with SBC occurrence (32.4% vs. 21.6%, p = 0.342). Previous SBC was associated with further isolation of Corynebacterium spp. (OR 3.94, 95% CI [1.72-9.05]). Previous SBC and corticosteroids pulses in the last 3 months were the only factors associated with increased risk of Corynebacterium spp. isolation in multivariate analysis. Corynebacterium spp. sampling was significantly associated with CLAD onset (27.1% vs. 6.9%, p = 0.021). Corynebacterium spp. isolation was not associated with SBC but with higher risk of CLAD. Whether CLAD evolution is affected by Corynebacterium spp. eradication remains to be investigated.

Low HDL-Cholesterol Concentrations in Lung Transplant Candidates are Strongly Associated With One-Year Mortality After Lung Transplantation.

High-density lipoproteins (HDLs), whose main role is the reverse transport of cholesterol, also have pleiotropic anti-inflammatory, antioxidant, anti-apoptotic and anti-infectious properties. During sepsis, HDL cholesterol (HDL-C) concentration is low, HDL particle functionality is altered, and these modifications are correlated with poor outcomes. Based on the protective effects of HDL, we hypothesized that HDL-C levels could be associated with lung transplantation (LT) outcome. We thus looked for an association between basal HDL-C concentration and one-year mortality after LT. In this single-center prospective study including consecutive LTs from 2015 to 2020, 215 patients were included, essentially pulmonary fibrosis (47%) and chronic obstructive pulmonary disease (COPD) (38%) patients. Mortality rate at one-year was 23%. Basal HDL-C concentration stratified nonsurvivors to survivors at one-year (HDL-C = 1.26 [1.12-1.62] mmol/L vs. HDL-C = 1.55 [1.22-1.97] mmol/L, p = 0.006). Multivariate analysis confirmed that HDL-C concentration during the pretransplant assessment period was the only variable inversely associated with mortality. Moreover, mortality at one-year in patients with HDL-C concentrations ≤1.45 mmol/L was significantly higher (log-rank test, p = 0.00085). In conclusion, low basal HDL-C concentrations in candidates for LT are strongly associated with mortality after LT. To better understand this association, further studies in this field are essential and, in particular, a better characterization of HDL particles seems necessary.

Donors brain-dead after successful resuscitation of cardiac arrest: Early outcome and postoperative complications of lung recipients.

BACKGROUND: The outcomes of lung transplantation (LT) recipients who received a graft from a brain-dead donor after successful resuscitation from cardiac arrest (CA donors) have been poorly described. This study compared the one-year survival of LT recipients depending on the CA status of the donor. METHODS: This prospective observational single-centre study analysed all consecutive patients who underwent LT at Bichat Claude Bernard Hospital, Paris, between January 2016 and December 2020. All donors who experienced CA prior to organ donation, regardless of rhythm or duration, were considered CA donors. The postoperative complications and outcomes of LT recipients were analysed. The one-year survival was compared using Kaplan-Meier curves and log-rank tests. Independent risk factors for one-year mortality were assessed using multivariate analysis (p < 0.05 was considered significant). The Paris North Hospitals Institutional Review Board approved the study. RESULTS: A total of 236 LT recipients were analysed and 66 (28%) received a graft from a CA donor. The median durations of no/low flow were 4 [0-10]/20 [15-30] minutes, respectively. Shockable and non-shockable rhythms were observed in 11 (17%) and 47 (72%) of the CA donors, respectively. The characteristics of the grafts and early postoperative complications were not different in the CA and non-CA groups. Receiving a graft from a CA donor was not an independent risk factor for recipient one-year mortality. CONCLUSION: Receiving a graft from a CA donor did not worsen the outcome of LT recipients. Acceptation of these grafts must be systematically considered to increase the pool of available grafts.