The effect of anterior quadratus lumborum block on morphine consumption in minimally invasive colorectal surgery: a multicentre, double-blind, prospective randomised placebo-controlled trial.

We investigated the efficacy and safety of a bilateral anterior quadratus lumborum block in patients undergoing minimally invasive colorectal surgery. This was a two-centre, double-blind, prospective, randomised, placebo-controlled trial including 150 patients undergoing laparoscopic colorectal surgery (left- or right hemicolectomy, sigmoidectomy) who were enrolled in the institutional abdominal enhanced recovery programme. Before induction of anaesthesia, patients received a bilateral anterior quadratus lumborum block in the left and right lateral decubitus position under ultrasound guidance and were allocated randomly to receive 30 ml of ropivacaine 0.375% (n = 75) or placebo (saline 0.9%) (n = 75) bilaterally. Postoperatively, all patients received multimodal intravenous analgesia including paracetamol, ketorolac and patient-controlled analgesia with morphine. The primary outcome was morphine consumption during the first 24 h after tracheal extubation. Secondary outcomes included severity of pain; presence and extent of sensory block; incidence of postoperative nausea and vomiting; and hospital duration of stay. We also investigated the need for, and dose of, rescue analgesia. Safety outcomes included the incidence of adverse events. Mean (SD) 24-hour morphine consumption was no different between patients allocated to ropivacaine and placebo (28.6 (22.3) mg vs. 28.4 (22.5) mg, p = 0.966, respectively). While a sensory block could be detected in significantly more patients allocated to the ropivacaine group, no differences were detected in pain scores or other secondary or safety endpoints. Patient satisfaction scores were high in both groups. In laparoscopic colorectal surgery, adding a bilateral anterior quadratus lumborum block to a standard multimodal analgesia regimen did not reduce opioid consumption or improve pain scores.

The effect of the volume of supra-inguinal injected solution on the spread of the injectate under the fascia iliaca: a preliminary study.

The fascia iliaca compartment is the compartment confined by the fascia iliaca (FI) and a muscular layer formed by the iliac- and psoas muscle. This compartment creates a virtual tunnel that contains the femoral nerve (FN), the obturator nerve (ON), and the lateral femoral cutaneous nerve (LFCN) of the lumbar plexus. In this pilot study, we aimed to determine the suggested volume needed to reach the three target nerves of the lumbar plexus (FN, ON, and LFCN) with a single-injection ultrasound-guided supra-inguinal fascia iliaca compartment (S-FICB). A computer tomography (CT scan)-guided step-up/step-down sequence was used to determine the suggested injection volume to target all three nerves. Subsequently, an anatomist blinded for the injected volume and CT findings, dissected the cadavers, and evaluated the spread of dye underneath the fascia iliaca. In total, seven pelvic areas of four cadavers were evaluated on CT scan and dissected. Distribution of dye underneath the FI in relation to the FN, ON, and the LFCN was recorded in all dissected cadavers. Combining CT and dissection findings, the suggested volume to reach the FN, ON, and LFCN with an S-FICB was 40 mL.

Radiological Analysis of Unused Donor Lungs: A Tool to Improve Donor Acceptance for Transplantation?

Despite donor organ shortage, a large proportion of possible donor lungs are declined for transplantation. Criteria for accepting/declining lungs remain controversial because of the lack of adequate tools to aid in decision-making. We collected, air-inflated, and froze a large series of declined/unused donor lungs and subjected these lung specimens to CT examination. Affected target regions were scanned by using micro-CT. Lungs from 28 donors were collected. Two lungs were unused, six were declined for non-allograft-related reasons (collectively denominated nonallograft declines, n = 8), and 20 were declined because of allograft-related reasons. CT scanning demonstrated normal lung parenchyma in only four of eight nonallograft declines, while relatively normal parenchyma was found in 12 of 20 allograft-related declines. CT and micro-CT examinations confirmed the reason for decline in most lungs and revealed unexpected (unknown from clinical files or physical inspection) CT abnormalities in other lungs. CT-based measurements showed a higher mass and density in the lungs with CT alterations compared with lungs without CT abnormalities. CT could aid in the decision-making to accept or decline donor lungs which could lead to an increase in the quantity and quality of lung allografts.

Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial.

Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD-free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx.

Impact of CLAD Phenotype on Survival After Lung Retransplantation: A Multicenter Study.

Chronic lung allograft dysfunction (CLAD) remains a major problem after lung transplantation with no definitive treatment except redo lung transplantation (re-LTx) in selected candidates. However, CLAD is not a homogeneous entity and different phenotypes exist. Therefore, we aimed to evaluate the effect of CLAD phenotypes on survival after re-LTx for CLAD. Patients who underwent re-LTx for respiratory failure secondary to CLAD in four LTx centers between 2003 and 2013 were included in this retrospective analysis. Bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD) were distinguished using pulmonary function, radiology and explant lung histopathology. Patient variables pre- and post-re-LTx were collected and analyzed. A total of 143 patients underwent re-LTx for CLAD resulting in 94 BOS (66%) and 49 rCLAD (34%) patients. Unadjusted and adjusted survival after re-LTx for rCLAD was worse compared to BOS (HR = 2.60, 1.59-4.24; p < 0.0001 and HR = 2.61, 1.51-4.51; p = 0.0006, respectively). Patients waiting at home prior to re-LTx experienced better survival compared to hospitalized patients (HR 0.40; 0.23-0.72; p = 0.0022). Patients with rCLAD redeveloped CLAD earlier and were more likely to redevelop rCLAD. Survival after re-LTx for rCLAD is worse compared to BOS. Consequently, re-LTx for rCLAD should be critically discussed, particularly when additional peri-operative risk factors are present.

Combined or Serial Liver and Lung Transplantation for Epithelioid Hemangioendothelioma: A Case Series.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with variable biological and clinical behavior. There is increasing experience with liver transplantation (LiTx) for hepatic EHE, even in cases of extrahepatic disease localization. Until now, no cases of lung transplantation (LuTx) had been reported for pulmonary EHE. This report describes three cases of EHE with multifocal disease in patients who underwent either serial or combined LiTx and LuTx.

Left mainstem bronchus rupture due to a left-sided double lumen tube.

Double lumen tubes (DLT) are a cornerstone in thoracic anaesthesia to achieve onelung ventilation. Due to the shape and size of these devices, airway injuries might occur. The reported incidence of tracheobronchial ruptures caused by a DLT is very low (0.005% for single-lumen tubes and 0.05% for double-lumen intubations), but the outcome can be life-threatening (1, 2). In the past, treatment of tracheobronchial ruptures was performed surgically, nowadays conservative treatment can be considered (3, 4). Here, we report a case of tracheobronchial rupture during oesophageal surgery.

Combined liver and lung transplantation with extended normothermic lung preservation in a patient with end-stage emphysema complicated by drug-induced acute liver failure.

Isolated lung transplantation (LuTx) and liver transplantation are established treatments for irreversible lung and liver failure. Combined liver and lung transplantation (cLiLuTx) is a less common, but approved therapy of combined organ failure, mostly applied in patients suffering from progressive cystic fibrosis and advanced liver disease. We report a patient who was listed for LuTx due to end-stage chronic obstructive pulmonary disease and who developed drug-induced acute hepatic failure. The only therapeutic option was hyper-urgent cLiLuTx. To correct the poor coagulation in order to reduce the per-operative risk of bleeding, the liver was transplanted first. In anticipation of the longer lung preservation time, cold flushed lungs were preserved on a portable lung perfusion device for ex vivo normothermic perfusion for 11 h 15 min, transplanted sequentially off-pump, and reperfused after a total ex vivo time of 13 h 32 min and 16 h for the first and second lung, respectively. Ten months later, the patient is doing well and no rejection occurred. Normothermic ex vivo lung perfusion may help to prolong preservation time, facilitating long-distance transport and combined organ transplantation.

Azithromycin and the treatment of lymphocytic airway inflammation after lung transplantation.

Lymphocytic airway inflammation is a major risk factor for chronic lung allograft dysfunction, for which there is no established treatment. We investigated whether azithromycin could control lymphocytic airway inflammation and improve allograft function. Fifteen lung transplant recipients demonstrating acute allograft dysfunction due to isolated lymphocytic airway inflammation were prospectively treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC, FEV1 , FEF25-75 , Tiffeneau index) and FeNO were assessed before and up to 12 months after initiation of azithromycin. Radiologic features, local inflammation assessed on airway biopsy (rejection score, IL-17(+) cells/mm(2) lamina propria) and broncho-alveolar lavage fluid (total and differential cell counts, chemokine and cytokine levels); as well as systemic C-reactive protein levels were compared between baseline and after 3 months of treatment. Airflow improved and FeNO decreased to baseline levels after 1 month of azithromycin and were sustained thereafter. After 3 months of treatment, radiologic abnormalities, submucosal cellular inflammation, lavage protein levels of IL-1ß, IL-8/CXCL-8, IP-10/CXCL-10, RANTES/CCL5, MIP1-α/CCL3, MIP-1ß/CCL4, Eotaxin, PDGF-BB, total cell count, neutrophils and eosinophils, as well as plasma C-reactive protein levels all significantly decreased compared to baseline (p < 0.05). Administration of azithromycin was associated with suppression of posttransplant lymphocytic airway inflammation and clinical improvement in lung allograft function.

Approach to one lung ventilation during the surgical resection of an intrathoracic ganglioneuroblastoma in a three-year-old child: a case report and review of the literature.

One lung ventilation (OLV) in children is a challenge and requires creative solutions. A case of OLV with bronchial placement of a fiberscope inspection-guided vascular embolectomy catheter in a three-year-old girl, scheduled for the resection of an intrathoracic tumor through thoracotomy is described. The availability of a broad range of vascular catheters as well as of fiberscope inspection material was decisive in managing the airway intra-operatively. Over the last 20 years, the need for OLV in children has increased, and various methods for performing it have been reported. Knowing all existing strategies in that domain is important to provide optimal perioperative care. In this paper, several methods of OLV in children will be discussed, such as selective endobronchial intubation, types of bronchial blockers, Univent tube, pediatric double lumen tubes, as well as the Marraro double lumen tube.

Gut microbiota-derived propionate reduces cancer cell proliferation in the liver.

BACKGROUND: Metabolites released by the gut microbiota may influence host metabolism and immunity. We have tested the hypothesis that inulin-type fructans (ITF), by promoting microbial production of short-chain fatty acids (SCFA), influence cancer cell proliferation outside the gut. METHODS: Mice transplanted with Bcr-Abl-transfected BaF3 cells, received ITF in their drinking water. Gut microbiota was analysed by 16S rDNA polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) and qPCR. Serum Short-chain fatty acids were quantified by UHPLC-MS. Cell proliferation was evaluated in vivo, by molecular biology and histology, and in vitro. RESULTS: Inulin-type fructans treatment reduces hepatic BaF3 cell infiltration, lessens inflammation and increases portal propionate concentration. In vitro, propionate reduces BaF3 cell growth through a cAMP level-dependent pathway. Furthermore, the activation of free fatty acid receptor 2 (FFA2), a Gi/Gq-protein-coupled receptor also known as GPR43 and that binds propionate, lessens the proliferation of BaF3 and other human cancer cell lines. CONCLUSION: We show for the first time that the fermentation of nutrients such as ITF into propionate can counteract malignant cell proliferation in the liver tissue. Our results support the interest of FFA2 activation as a new strategy for cancer therapeutics. This study highlights the importance of research focusing on gut microbes-host interactions for managing systemic and severe diseases such as leukaemia.

Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability.

BACKGROUND AND AIMS: Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. METHODS: Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. RESULTS: Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. CONCLUSION: We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.

The FiberTAG project: Tagging dietary fibre intake by measuring biomarkers related to the gut microbiota and their interest for health.

The scientific rationale for dietary fibre intake recommendations comes from the recognition of their benefits for health based on studies first published many years ago. It remains unclear which are the key physiological effects generated by dietary fibre in view of the diversity of the food components considered as dietary fibre, of the relevance of their classification (soluble and insoluble) and from the recent discoveries putting forward their interactions with the gut microbiota. The project FiberTAG (Joint Programming Initiative 'A Healthy Diet for a Healthy Life' 2017-2020 https://www.fibertag.eu/) aims to establish a set of biomarkers (markers of gut barrier function and bacterial co-metabolites including volatile compounds and lipid derivatives), measured in different biological compartments (faeces, blood or breath) linking dietary fibre intake and gut microbiota-related health effects. The FiberTAG consortium brings together academic and industrial partners from Belgium, France, Germany and Canada to share data and samples obtained from existing as well as new intervention studies in order to evaluate the relevance of such biomarkers. The FiberTAG consortium is currently working on five existing cohorts (prospective observational or nutritional interventions in healthy or obese patients), and a number of new intervention studies to analyse the effect of insoluble dietary fibre (wheat bran and chitin-glucan, provided by the industrial partners) in healthy individuals or in obese patients at high cardiometabolic risk.

Contribution of the gut microbiota to the regulation of host metabolism and energy balance: a focus on the gut-liver axis.

This review presents mechanistic studies performed in vitro and in animal models, as well as data obtained in patients that contribute to a better understanding of the impact of nutrients interacting with the gut microbiota on metabolic and behavioural alterations linked to obesity. The gut microbiota composition and function are altered in several pathological conditions including obesity and related diseases i.e. non-alcoholic fatty liver diseases (NAFLD). The gut-liver axis is clearly influenced by alterations of the gut barrier that drives inflammation. In addition, recent papers propose that specific metabolites issued from the metabolic cooperation between the gut microbes and host enzymes, modulate inflammation and gene expression in the liver. This review illustrates how dietary intervention with prebiotics or probiotics influences host energy metabolism and inflammation. Indeed, intervention studies are currently underway in obese and NAFLD patients to unravel the relevance of the changes in gut microbiota composition in the management of metabolic and behavioural disorders by nutrients interacting with the gut microbiota. In conclusion, diet is among the main triggers of NAFLD and the gut microbiota is modified accordingly, underlining the importance of the concomitant study of the nutrients and microbial impact on liver health and metabolism, in order to propose innovative, clinically relevant, therapeutic approaches.

Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition.

BACKGROUND: There are only few data relating the metabolic consequences of feeding diets very low in n-3 fatty acids. This experiment carried out in mice aims at studying the impact of dietary n-3 polyunsaturated fatty acids (PUFA) depletion on hepatic metabolism. RESULTS: n-3 PUFA depletion leads to a significant decrease in body weight despite a similar caloric intake or adipose tissue weight. n-3 PUFA depleted mice exhibit hypercholesterolemia (total, HDL, and LDL cholesterol) as well as an increase in hepatic cholesteryl ester and triglycerides content. Fatty acid pattern is profoundly modified in hepatic phospholipids and triglycerides. The decrease in tissue n-3/n-6 PUFA ratio correlates with steatosis. Hepatic mRNA content of key factors involved in lipid metabolism suggest a decreased lipogenesis (SREBP-1c, FAS, PPAR gamma), and an increased beta-oxidation (CPT1, PPAR alpha and PGC1 alpha) without modification of fatty acid esterification (DGAT2, GPAT1), secretion (MTTP) or intracellular transport (L-FABP). Histological analysis reveals alterations of liver morphology, which can not be explained by inflammatory or oxidative stress. However, several proteins involved in the unfolded protein response are decreased in depleted mice. CONCLUSION: n-3 PUFA depletion leads to important metabolic alterations in murine liver. Steatosis occurs through a mechanism independent of the shift between beta-oxidation and lipogenesis. Moreover, long term n-3 PUFA depletion decreases the expression of factors involved in the unfolded protein response, suggesting a lower protection against endoplasmic reticulum stress in hepatocytes upon n-3 PUFA deficiency.

Efficacy of advanced pace-mapping technology for idiopathic premature ventricular complexes ablation.

PURPOSE: Catheter ablation is an effective treatment for premature ventricular complexes (PVCs). Activation mapping is accurate but requires PVCs at the time of the ablation. Pace-mapping correlation (PMC) is a supplemental tool recently developed as an integrated module for an electro-anatomical mapping platform. Our study sought to investigate whether pace-mapping technology provides similar ablation results in patients with low versus high idiopathic PVC burden at the time of ablation and the relationship between sites with the highest PMC and the earliest local activation time (LAT). METHODS: A total of 59 consecutive patients undergoing catheter ablation for idiopathic PVCs were enrolled. Twelve out of 59 patients (20%) were classified in the low PVC burden group (defined as < 2 PVCs/min) and 47/59 (80%) in the high PVC burden group. RESULTS: The most common origin of PVCs was the right ventricular outflow tract (RVOT) followed by aortic cusps, coronary sinus, parahisian region, and aorto-mitral continuity. Procedural and 1-month success rate were 95 and 87% respectively. PVC burden at the time of ablation did not influence the success rate. The median distance between the earliest LAT points and the highest PMC points was 6.4 (4.9-10.6) mm. CONCLUSIONS: Pace-mapping correlation is useful and accurate in localizing the origin of idiopathic PVCs irrespective of the initial PVC burden. It provides optimal ablation results when combined with LAT. Success rate at mid-term follow-up is higher when the origin of PVCs is located in the RVOT as compared to other locations.

The importance of lymphocytes in lung ischemia-reperfusion injury.

In a murine model of lung ischemia-reperfusion injury (IRI), we previously demonstrated that lymphocytes increase in the alveolar space during the ischemic period. We hypothesized that these lymphocytes play an important role during ischemia in the development of lung IRI. In the present study, severe combined immunodeficiency (SCID) mice, lacking T cells, were used to further investigate our hypothesis. SCID and control mice underwent 90 minutes of left lung ischemia followed by 4 hours of reperfusion. A significant decrease in neutrophils, together with lower levels of interleukin-1beta, was found in SCID mice after reperfusion. We concluded that lymphocytes invading the lung during ischemia trigger an inflammatory response upon reperfusion. Antilymphocyte therapies in the donor should be further investigated as treatment strategies against IRI.

Modification of the arterial anastomotic technique improves survival in porcine single lung transplant model.

BACKGROUND: Lung transplantation is a valuable therapeutic option for selected patients with end-stage pulmonary disease. However, this treatment is complicated by ischaemia-reperfusion injury (IRI) of the lung in 10-20% of the recipients. We developed an unilateral porcine lung transplant model to study IRI and describe our experience with two different arterial anastomotic techniques. MATERIAL & METHODS: Twenty four domestic pigs [n = 6 x (donor + recipient)/group] were used in this study. Donor lungs were harvested using an antegrade flush with cold Perfadex and stored in the same solution for +/- 8 hours. Recipient animals underwent a left thoracotomy. After native pneumonectomy, the left donor lung was transplanted in the following order: 1. left atrial cuff; 2. bronchus; 3 pulmonary artery. 2 The outcome in recipients from historical groups differing in anastomotic technique was compared. An end-to-end anastomosis on the left pulmonary artery was performed in group I versus a patch anastomosis on the main pulmonary artery in group II. One hour after reperfusion, the right pulmonary artery and main bronchus were ligated forcing the recipient to survive on the transplanted lung only. The animals were further observed for 6 hours. RESULTS: Survival 6 hours after exclusion of the right lung was 33% (2/6) in group I versus 83% (5/6) in group II. Animals in group I died of right heart failure manifested by acute dilation of the right ventricle following ligation of the hilum of the right lung. CONCLUSION: Single lung transplantation with exclusion of the contralateral native lung is a critical model. Arterial end-to-end anastomosis resulted in an increased right ventricular afterload. The use of a patch technique improved the compliance of the arterial anastomosis and decreased early mortality. This transplant model is currently used in our laboratory to assess new methods for pulmonary preservation.

Are Kupffer cells involved in the metabolic adaptation of the liver to dietary carbohydrates given after fasting?

In rats, a high carbohydrate fat-free (HCFF) diet, given after fasting, induces both hepatic lipogenic and glycogenic enzymes. In the present study, we evaluated the involvement of Kupffer cells in the metabolic events occurring in the liver during the fasting-refeeding transition. Male Wistar rats were fasted for 48 h and received an intravenous injection of either NaCl 0.9% (Gd-) or 10 mg/kg GdCl(3) (Gd+), an inhibitor of Kupffer cells, then fed for 12 h with a HCFF diet. The comparison of colloidal carbon uptake was similar in rats fasted and in rats fasted and then refed a HCFF diet, thus indicating that refeeding does not affect per se Kupffer cell phagocytic activity. The inhibition of Kupffer cells by GdCl(3) did not affect fatty acid synthase (FAS) induction, as shown by the analysis of both FAS mRNA and activity; refeeding a HCFF diet increased the hepatic triglyceride and glycogen content to the same extent in Gd+ and Gd- rats. Our results do not support the involvement of Kupffer cells in the metabolic events occurring in the liver tissue by feeding a HCFF diet after fasting. However, the discussion supports the involvement of Kupffer cells in the modulation of the hepatic lipid metabolism by other nutrients than carbohydrates.