Impact of recipient and donor pretransplantation body mass index on early postosperative complications after lung transplantation.

BACKGROUND: Prior studies have assessed the impact of the pretransplantation recipient body mass index (BMI) on patient outcomes after lung transplantation (LT), but they have not specifically addressed early postoperative complications. Moreover, the impact of donor BMI on these complications has not been evaluated. The first aim of this study was to assess complications during hospitalization in the ICU after LT according to donor and recipient pretransplantation BMI. METHODS: All the recipients who underwent LT at Bichat Claude Bernard Hospital, Paris, between January 2016 and August 2022 were included in this observational retrospective monocentric study. Postoperative complications were analyzed according to recipient and donor BMIs. Univariate and multivariate analyses were also performed. The 90-day and one-year survival rates were studied. P < 0.05 was considered to indicate statistical significance. The Paris-North Hospitals Institutional Review Board approved the study. RESULTS: A total of 304 recipients were analyzed. Being underweight was observed in 41 (13%) recipients, a normal weight in 130 (43%) recipients, and being overweight/obese in 133 (44%) recipients. ECMO support during surgery was significantly more common in the overweight/obese group (p = 0.021), as were respiratory complications (primary graft dysfunction (PGD) (p = 0.006), grade 3 PDG (p = 0.018), neuroblocking agent administration (p = 0.008), prone positioning (p = 0.007)), and KDIGO 3 acute kidney injury (p = 0.036). However, pretransplantation overweight/obese status was not an independent risk factor for 90-day mortality. An overweight or obese donor was associated with a decreased PaO2/FiO2 ratio before organ donation (p < 0.001), without affecting morbidity or mortality after LT. CONCLUSION: Pretransplantation overweight/obesity in recipients is strongly associated with respiratory and renal complications during hospitalization in the ICU after LT.

Liver Involvement in Patients With PiZZ-Emphysema, Candidates for Lung Transplantation.

Information about the prevalence and nature of liver disorders in adults with alpha1-antitrypsin deficiency is scarce. At our center, systematic liver biopsy screening is part of the evaluation before lung transplantation (LT) in the emphysema patients with the PiZZ phenotype. Our aim was to report our experience with this prospective screening. Clinical, liver function, and imaging parameters as well as liver histology data were analyzed for 23 consecutive adult patients with PiZZ severe emphysema referred to our center for consideration of LT from 2006 to 2014. Overall 20 (87%) featured chronic liver disease characterized by a chronic inflammation and/or a significant portal fibrosis on histology. Two of the 23 patients (8.7%) had septal fibrosis according to the Metavir and Ishak scores and met our definition of severe chronic liver disease. They were both clinically asymptomatic with normal liver function tests. On abdominal ultrasonography, the liver appeared normal in one patient and with abnormal contours in the other. Our data indicate that in adults with PiZZ-related emphysema being evaluated for LT, most patients had some histologic involvement. The prevalence of severe liver dysfunction is <10%.

Epidemiology and risk factors of multidrug-resistant bacteria in respiratory samples after lung transplantation.

BACKGROUND: Multidrug-resistant (MDR) bacteria are a growing concern worldwide. The aim of this study was to describe the epidemiology and risk factors of MDR bacteria detected in respiratory invasive samples during hospitalization in the intensive care unit (ICU) after lung transplantation (LT). METHODS: This study was based on a retrospective analysis of 176 patients hospitalized in the ICU after LT in 2006-2012. Respiratory invasive samples were performed according to a routine protocol. MDR pathogens were defined according to in vitro susceptibility tests. RESULTS: A total of 1176 bacteria were cultured. Susceptibility testing was performed on 1046 strains and 404 (39%) MDR were detected in 90 (51%) patients. Pseudomonas aeruginosa, coagulase-negative staphylococci, and Enterobacteriaceae (mainly Enterobacter species) were the most common MDR pathogens. On multivariate analysis, an ICU stay >14 days, presence of a tracheostomy, and previous exposure to broad-spectrum antibiotics were associated with MDR acquisition (odds ratio [OR] 3.7; 95% confidence interval [1.69-8.12]; OR 3.28 [1.05-10.28]; and OR 2.25 [1.17-4.34], respectively). We consistently observed an increasing emergence of resistance to several antibiotics, from week 1 to week 4 of ICU hospitalization: for ticarcillin, piperacillin-tazobactam, ceftazidime, imipenem/cilastatin, amikacin, and ciprofloxacin in P. aeruginosa; and for piperacillin-tazobactam, cefepime, and amikacin in Enterobacteriaceae. CONCLUSION: A large proportion of MDR bacteria are detected on respiratory invasive samples in LT patients, and the risk of their emergence is mainly determined by the previous exposure to broad-spectrum antibiotics and the length of ICU stay. Adequate treatment requires broad-spectrum empiric antibiotic therapy.

Editor's Choice - ECAR (Endovasculaire ou Chirurgie dans les Anévrysmes aorto-iliaques Rompus): A French Randomized Controlled Trial of Endovascular Versus Open Surgical Repair of Ruptured Aorto-iliac Aneurysms.

OBJECTIVES/BACKGROUND: ECAR (Endovasculaire ou Chirurgie dans les Anévrysmes aorto-iliaques Rompus) is a prospective multicentre randomized controlled trial including consecutive patients with ruptured aorto-iliac aneurysms (rAIA) eligible for treatment by either endovascular (EVAR) or open surgical repair (OSR). Inclusion criteria were hemodynamic stability and computed tomography scan demonstrating aorto-iliac rupture. METHODS: Randomization was done by week, synchronously in all centers. The primary end point was 30 day mortality. Secondary end points were post-operative morbidity, length of stay in the intensive care unit (ICU), amount of blood transfused (units) and 6 month mortality. RESULTS: From January 2008 to January 2013, 107 patients (97 men, 10 women; median age 74.4 years) were enrolled in 14 centers: 56 (52.3%) in the EVAR group and 51 (47.7%) in the OSR group. The groups were similar in terms of age, sex, consciousness, systolic blood pressure, Hardman index, IGSII score, type of rupture, use of endoclamping balloon, and levels of troponin, creatinine, and hemoglobin. Delay to treatment was higher in the EVAR group (2.9 vs. 1.3 hours; p < .005). Mortality at 30 days and 1 year were not different between the groups (18% in the EVAR group vs. 24% in the OSR group at 30 days, and 30% vs. 35%, respectively, at 1 year). Total respiratory support time was lower in the EVAR group than in the OSR group (59.3 hours vs. 180.3 hours; p = .007), as were pulmonary complications (15.4% vs. 41.5%, respectively; p = .050), total blood transfusion (6.8 vs. 10.9, respectively; p = .020), and duration of ICU stay (7 days vs. 11.9 days, respectively; p = .010). CONCLUSION: In this study, EVAR was found to be equal to OSR in terms of 30 day and 1 year mortality. However, EVAR was associated with less severe complications and less consumption of hospital resources than OSR.

Controlled donation after circulatory death lung transplantation: Results of the French protocol including in situ abdominal normothermic regional perfusion and ex vivo lung perfusion.

BACKGROUND: The French national protocol for controlled donation after circulatory determination of death (cDCD) includes normothermic regional perfusion (NRP) in case of abdominal organ procurement and additional ex-vivo lung perfusion (EVLP) before considering lung transplantation (LT). METHODS: We made a retrospective study of a prospective registry that included all donors considered for cDCD LT from the beginning of the program in May 2016 to November 2021. RESULTS: One hundred grafts from 14 donor hospitals were accepted by 6 LT centers. The median duration of the agonal phase was 20 minutes [2-166]. The median duration from circulatory arrest to pulmonary flush was 62 minutes [20-90]. Ten lung grafts were not retrieved due to prolonged agonal phases (n = 3), failure of NRP insertion (n = 5), or poor in situ evaluation (n = 2). The remaining 90 lung grafts were all evaluated on EVLP, with a conversion rate of 84% and a cDCD transplantation rate of 76%. The median total preservation time was 707 minutes [543-1038]. Seventy-one bilateral LTs and 5 single LTs were performed for chronic obstructive pulmonary disease (n = 29), pulmonary fibrosis (n = 21), cystic fibrosis (n = 15), pulmonary hypertension (n = 8), graft-versus-host disease (n = 2), and adenosquamous carcinoma (n = 1). The rate of PGD3 was 9% (n = 5). The 1-year survival rate was 93.4%. CONCLUSION: After initial acceptance, cDCD lung grafts led to LT in 76% of cases, with outcomes similar to those already reported in the literature. The relative impacts of NRP and EVLP on the outcome following cDCD LT should be assessed prospectively in the context of comparative studies.

Fungal Isolation in Respiratory Tract After Lung Transplantation: Epidemiology, Clinical Consequences, and Associated Factors.

BACKGROUND: Fungus-positive respiratory samples (FPRS) are common in the intensive Care unit (ICU) and are usually considered to correspond to colonization. The management of FPRS during the early postoperative course after lung transplantation (LT) remains unclear. The epidemiology, clinical consequences, and prognosis of FPRS were assessed in LT recipients. METHODS: Over a 6-year period, we analyzed the postoperative ICU course of 176 LT recipients with a specific focus on microbiological results of routine respiratory samples and clinical course. The outcomes during the ICU stay at day 28 and at 1 year were compared in patients with or without FPRS. Results are expressed as median and interquartile range. RESULTS: In the pretransplantation period, Candida spp were reported in 17% of patients. No routine post-LT antifungal prophylaxis was initiated. In the post-LT period, at least 1 FPRS was observed in 69% of patients (93% Candida spp, 7% Aspergillus spp). Double LT (odds ratio = 4.15, 95% confidence interval [1.67-11.80], P = .0007) was the only risk factor associated with Candida spp in respiratory samples. Antifungal therapy was administered in 58% of patients with post-LT Candida-positive samples. Candida spp in post-LT respiratory samples were not associated with increased ICU, 28-day, or 1-year mortality rates. CONCLUSION: A high prevalence of FPRS is reported after LT, mainly with Candida spp. The lack of association between post-LT FPRS and mortality and morbidity suggests avoiding antifungal therapy in the absence of clinical signs of invasive infection.

[Early outcomes following lung transplantation in patients aged 65 years and older]. / Résultats précoces de la transplantation pulmonaire chez les patients âgés de 65 ans et plus.

INTRODUCTION: The number of lung transplantations performed is increasing worldwide. With an improved experience and outcomes, the age of the recipient on its own has ceased to be an absolute contra-indication. We report our first experience with lung transplantation in patients aged 65 years or older. METHODS: From January 2014 to March 2019, the files of patients aged 65 years or older undergoing lung transplantation were retrospectively reviewed. RESULTS: During the study period, 241 patients underwent lung transplantation in Bichat hospital (Paris, France), including 25 recipients aged 65 years or older. Underlying diagnoses were interstitial (72%) and obstructive (28%) disease. The rate of single lung transplantation was 80%. Sixteen patients required ECMO assistance during the procedure. Early complications were mostly grade III primary graft dysfunction (12%) and cellular rejection (20%). Overall one-year survival rate was 76%. CONCLUSION: After a careful selection of the recipients, the early results of our retrospective single center series are encouraging. We continue to consider lung transplantation in rigorously selected recipients of aged 65 years and more.

Acute Kidney Injury After Lung Transplantation: Perioperative Risk Factors and Outcome.

BACKGROUND: Acute kidney injury (AKI) is associated with increased short-term and long-term mortality and morbidity after lung transplantation (LT). The primary objective of this study was to analyze the perioperative factors associated with AKI according to Kidney Disease: Improving Global Outcome (KDIGO) criteria during hospitalization in an intensive care unit (ICU) after LT. METHODS: This was a single-center, observational, prospective study. AKI was defined according to KDIGO criteria. Results are expressed as median, interquartile range, absolute numbers, and percentages. Statistical analyses were performed using χ2 test, Fisher exact test, and Mann-Whitney U test. P < .05 was considered to be significant. Multivariate analysis was performed to identify independent risk factors. RESULTS: Between January 2016 and April 2018, 94 patients underwent LT (70% bilateral LT). AKI occurred during ICU stay in 46 patients (49%). KDIGO 1 AKI was observed in 16 patients (17%), KDIGO 2 in 14 patients (15%), and KDIGO 3 in 16 patients (17%), including 12 patients (75%) who required renal replacement therapy. AKI occurred before the fifth day after surgery for 38 patients (82% of the AKI patients). On multivariate analysis, independent factors associated with AKI were bilateral LT and mechanical ventilation >3 days (odds ratio [OR] 4.26, 95% confidence interval [CI] [1.49; 13.63] P = .010 and OR 5.56 [1.25; 11.47] P = .018, respectively). AKI and the need for renal replacement therapy were significantly associated with ICU mortality, 28-day mortality, and 1-year mortality. CONCLUSION: AKI is common during ICU stay after LT, especially after bilateral LT, and is associated with prolonged mechanical ventilation and increased short-term and long-term mortality.

[Digestive obstruction: an unusual complication of hereditary multiple exostoses]. / Obstruction digestive : une complication exceptionnelle d'une maladie exostosante.

Hereditary multiple exostoses is an autosomal dominant bone disorder characterized by multiple cartilaginous tumors growing outward from metaphyses of long bones. These tumors are usually located in long bones of the limbs. Exostosis also called osteochondroma can cause many complications, the most serious being malignant transformation as chondrosarcoma. We report a rare phenotype of this disease in a young male patient who presents digestive symptoms caused by a voluminous degenerated lumbar exostosis with anterior abdominal development.

[Acute traumatic rupture of the aortic isthmus]. / Rupture aiguë post-traumatique de l'isthme aortique.

Traumatic rupture of the aortic isthmus is a rare lesion occurring in patients subjected to violent deceleration. Because of the forces involved, it is frequently associated with concomitant life-threatening injuries. Non-invasive examinations such as CT and transesophageal echocardiography aid greatly in making the diagnosis. Urgent conventional repair is still considered the gold standard technique for cases of isolated rupture, or rupture without severe concomitant lesion where aortic clamping and heparinization will not impair post-operative outcomes. Urgent endovascular repair has been shown to be a feasible and efficient technique which may be proposed as a therapeutic option for patients with multiple trauma instead of delayed classical surgical repair after stabilization. Long-term results of endovascular repair need to be assessed before enlarging the indications of this technique in the emergency setting.

[Current knowledge on perioperative treatments of non-small cell lung carcinomas]. / Traitements péri-opératoires des carcinomes bronchiques non à petites cellules.

Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I-III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%. Conversely perioperative treatments were not validated for stage IA and IB patients. In more advanced stage patients, neo-adjuvant radio-chemotherapy has not been validated either. Adjuvant radiotherapy for N2 patients is currently tested in the large international phase 3 trial Lung-ART/IFCT-0503. The development of video-assisted thoracic surgery (VATS) has helped adjuvant chemotherapies for elderly patients. Perioperative targeted treatments in NSCLC with EGFR or ALK molecular alterations is currently assessed in the U.S. ALCHEMIST prospective trial. Finally, the role of immune check-points inhibitors is currently evaluated in a large international phase 3 trial testing adjuvant anti-PD-L1 monoclonal antibody, the BR31/IFCT-1401 trial, while a proof-of principle neo-adjuvant trial IONESCO/IFCT-1601, has just begun by the end of the 2016 year, with survival results of both trials expected in 5 to 7 years.

Severe axonal polyneuropathy after a FK506 overdosage in a lung transplant recipient.

FK506-induced polyneuropathies are rarely encountered. We report a case of axonal sensorimotor polyneuropathy in a lung transplant recipient that occurred during a FK506 overdosage. Onset was acute in the form of severe areflexic tetraparesis and resolution was observed after reduction of dosage. Because of increasing use of FK506 in solid organ transplantation, caution should be paid with FK506 dosage monitoring in cases of peripheral nervous system symptoms.

Early experience with cryopreserved arterial allografts in below-knee revascularization for limb salvage.

BACKGROUND: Below-knee revascularization for limb salvage in the absence of a suitable autogenous saphenous vein is a frequent challenge associated with a high amputation rate. The aim of this prospective study was to evaluate the usefulness of cryopreserved arterial allografts in such cases. METHODS: Arterial allografts were harvested from multiple organ donors and cryopreserved at -80 degrees C. From March 1993 to December 1997, 35 cryopreserved arterial allografts were used as below-knee bypasses for repeated limb salvage in 32 patients. There were 15 men and 17 women with a mean age of 75 years (+/-10.7). Seven patients had rest pain and 25 patients (78%) had gangrene or nonhealing ulceration. Runoff was through a single tibial vessel in 25 cases (71%) and two vessels in 10 cases. Previous ipsilateral bypasses had been done in 26 of 35 limbs (74%). Patients were followed up prospectively for an average period of 18 months (range 2 to 56). RESULTS: Aneurysmal dilatation occurred in two patent grafts, requiring segmental replacement at 13 and 18 months, respectively. The overall primary patency rate was 75% at 6 months, 57% at 12 months, and 39% at 18 months. The overall secondary patency rate was 75% at 6 months, 75% at 12 months, and 59% at 18 months. Overall limb salvage rate was 80% at 12 months, 73% at 18 months. CONCLUSIONS: These early data indicate that below-knee bypass with arterial allografts results in acceptable patency and limb salvage. Arterial allografts may be a useful alternative to other arterial substitutes in a difficult group of patients with critical ischemia and no suitable saphenous vein.

The activity of c-myb antisense oligonucleotide to prevent intimal hyperplasia is nonspecific.

BACKGROUND: We sought to determine the efficacy and specificity of a new c-myb antisense by inhibiting neointimal hyperplasia in a rat abdominal aorta injury model. Using c-myb antisense oligonucleotides, inhibition of vascular smooth muscle cell proliferation has been reported. METHODS: Sixty-six male Wistar rats had a de-endothelialization of the abdominal aorta. Following a double blind randomization protocol, F127 pluronic gel containing one of the five oligonucleotides or plain gel was applied around the aorta: 1) 18-mer c-myb antisense (AS18) with four contiguous guanosines (G-quartet); 2) 15-mer c-myb antisense (AS15) without G-quartet; 3) 1-bp mismatch AS15 without G-quartet (MM1); 4) an oligonucleotide with G-quartet (4G), whereas the other bases were chosen at random; 5) 1-bp mismatch 4G without G-quartet (MM2). After 21 days all rats were sacrificed and aortas harvested for histomorphometric evaluation. Four rats were given fluorescent-labeled oligonucleotides to study in vivo localization after local advential delivery. RESULTS: Morphometric analysis showed significant suppression of neointimal hyperplasia in AS18 and 4G and MM2 groups compared with GEL, AS15 and MM1 groups (p<0.05). The oligonucleotide-labeled aortas showed penetration of the oligonucleotides into the media which increased with time. CONCLUSIONS: Our findings pointed to the potential non specificity of the c-myb antisense oligonucleotide in vivo. Such results will minimize the importance of antisense strategy as a potential therapeutic for preventing neointimal hyperplasia. The two oligonucleotides with a G-quartet inhibited neointimal hyperplasia in our model. Exploring a non-antisense mechanism, G-quartet oligonucleotides as potential drugs to reduce neointimal hyperplasia is attractive.

[Effects of an anti-c-myb antisense oligonucleotide on myo-intimal proliferation. Specificity of action and consequences on vasoreactivity]. / Effets sur la prolifération myo-intimale d'un oligonucléotide antisens dirigé contre le c-myb. Spécificité d' action et conséquences sur la vasoréactivité.

Several reports have shown that an 18-mere antisense oligonucleotide directed against c-myb (AS 18) inhibits the proliferation of smooth muscle. The aims of this study were to confirm the specificity of a new anti-c-myb antisense and to evaluate changes in vasoreactivity following treatment with a c-myb antisense. Five groups of rats. All underwent desendothelialisation of the abdominal aorta. A solution containing pluronic gel, or one of the following oligonucleotides: AS 18, 15 mere antisense directed against c-myb, an aleatory 4G sequence containing 4 consecutive guanosines, a 15 mere antisense mismatch (n = 11), was applied around the aorta. After 21 days, the thickness and mean surface areas of the media and intima were calculated. Four groups of rats were constituted for the vasoreactivity study: control (A), desendothelialisation (B), desendothelialisation + application of AS 18 (C) and application of AS 18 alone (D). One ring per aorta was sampled at the 21st day and analysed in an organ chamber. The following results were obtained: the thickness and average surface areas of the intima were smaller (p < 0.05) in the 4G and AS 18-groups; in group B, none of the 8 segments responded to acetylcholine; in group C, 6 out of 8 segments responded. The contraction study showed no differences between groups A and D or between groups B and C. The authors conclude that the mode of action of AS 18 antisense of c-myb is non-specific but due to the presence of 4 consecutive guanosines in the oligonucleotide. Oligonucleotide with this sequence inhibits myo-intimal hyperplasia and improves endothelium-dependent relaxation in this model without affecting the contraction.

[Severe limb ischemia due to iatrogenic trauma]. / Ischémies sévères des membres dues à des traumatismes iatrogènes.

OBJECTIVES: Assess the frequency, severity and technical problems raised by iatrogenic trauma to the arteries. METHOD: A retrospective study of 45 cases of iatrogenic arterial trauma treated over a 25-year period was studied. RESULTS: The most frequent cause was arterial catheterization (n = 32 including 24 of the lower limbs and 8 for the upper limbs) performed for arteriography (n = 16), coronarography (n = 13) or endovascular therapy (n = 3). Thrombectomy was performed in 24 cases, bypass in 4 and endarterectomy in 4. Post-operative period was uneventful in all except two fatal cases. CONCLUSION: In most cases, iatrogenic arterial trauma can be avoided with proper technique. Prognosis is highly dependent on early care.

[Critical ischemia of the leg. A technique for distal anastomosis in a a small caliber artery]. / Ischémie critique des membres inférieurs. Un artifice pour anastomose distale sur artère de petit calibre.

CRITICAL ISCHEMIA OF THE LOWER LIMBS: This type of lesion, which spontaneously progresses to gangrene and amputation, is encountered more and more frequently. Emergency endoluminal revascularization or bypass surgery is required. When conventional endoluminal techniques cannot be used, a distal graft using the autologous saphenous vein is a promising alternative to achieve patent vascularization and salvage the limb. IF VENOUS MATERIAL IS NOT AVAILABLE: Usable venous material is not always available due to varicosities, thrombus formation, small size or previous surgery (stripping, coronary surgery, prior revascularization procedure); rates reported range from 20 to 40%. For such patients, other veins (external saphenous, arm veins, superficial femoral veins) may be useful but are not always appropriate for distal repair. Different prostheses might also be used but again do not always provide improved permeability. Most teams however use a polytetrafluoroethylene stent for revascularization of the distal leg. Different technical improvements favor success of prosthetic bypasses, but when used below the knee, flow remains less satisfactory than with venous bypasses. VEIN CUFFS: This procedure is a common adjuvant technique positioning a venous cuff between the recipient artery and the prosthesis. The cuff avoids the direct contact between the prosthesis and the fragile artery that is often difficult to suture. RESULTS: Several series have demonstrated that the rate of success of vein cuff procedures remains lower than venous bypass procedures, but also that flow is better than with simple femorotibial prostheses. PATHOGENIC HYPOTHESES: The reduction of the neo-intimal hyperplasia observed in experimental models is insufficient to explain entirely the observed in vivo benefit. The fact that the suture is easier to make is one possible reason. Indeed the rate of failure of simple prosthetic bypass surgery is high in the immediate postoperative period. These cases of thrombosis result from technical insufficiencies and are undoubtedly overcome by the use of the venous cuff.