Integrating an addiction team into the management of patients transplanted for alcohol-associated liver disease reduces the risk of severe relapse.

Background & Aims: Liver transplantation (LT) is a last resort treatment for patients at high risk of mortality from end-stage liver disease. Over the past years, alcohol-associated liver disease has become the most frequent indication for LT in the world. The outcomes of LT for alcohol-associated liver disease are good, but return to alcohol use is detrimental for medium-term survival because of cancer development, cardiovascular events, and recurrent alcohol-associated cirrhosis. Several strategies have been developed to prevent return to alcohol use during the pre- or post-LT period, but there are no specific recommendations. Therefore, the main objective of this study was to investigate if the integration of an addiction team in a LT unit affected the rate of severe alcohol relapse after LT. The secondary objectives were to assess the effects of addiction follow up on cardiovascular events, cancer, and overall survival. Methods: This study was a retrospective comparison between centres with or without addiction monitoring. Results: The study included 611 patients of which 79.4% were male with a mean age of 55.4 years at the time of LT, 190 were managed by an integrated addiction team. The overall alcohol relapse rate was 28.9% and the rate of severe relapse was 13.0%. Patients with addiction follow-up had significantly less frequent severe alcohol relapse than those in the control group (p = 0.0218). Addiction follow up (odds ratio = 0.19; p = 0.001) and age at LT (odds ratio = 1.23; p = 0.02) remained significantly associated with post-LT cardiovascular events. Conclusions: Our study confirms the benefits of integrating an addiction team to reduce return to alcohol use after LT. Clinical Trials registration: This study is registered at ClinicalTrials.gov (NCT04964687). Impact and implications: The main indication for liver transplantation is alcohol-associated cirrhosis. There are currently no specific recommendations on the addiction monitoring of transplant candidates, although severe return to alcohol use after liver transplantation has a negative impact on long-term survival of patients. In this study, we explored the impact of a systematic addiction intervention on the return to alcohol use rates. In our transplantation centre, we demonstrated the interest of an addiction follow up to limit the severe alcohol relapses rate. This information should be further investigated in prospective studies to validate these data.

Development and validation of a composite score to predict severe forms of ischemic colitis.

OBJECTIVE: To develop a simple scoring system in order to predict the risk of severe (death and/or surgery) ischemic colitis METHODS: In this retrospective study, 205 patients diagnosed with ischemic colitis in a tertiary hospital were consecutively included over a 6-year period. The study sample was sequentially divided into a training cohort (n = 103) and a validation cohort (n = 102). In the training cohort, multivariable analysis was used to identify clinical, biological, and CT variables associated with poor outcome and to build a risk scoring system. The discriminative ability of the score (sensitivity, specificity, positive predictive value, negative predictive value) was estimated in the two cohorts to externally validate the score, and a receiver operating characteristic curve was established to estimate the area under the curve of the score. Bootstrapping was used to validate the score internally. RESULTS: In the training cohort, four independent variables were associated with unfavorable outcome: hemodynamic instability (2 pts), involvement of the small bowel (1 pt), paper-thin wall pattern (3 pts), no stratified enhancement pattern (1 pt). The score was used to categorize patients into low risk (score: 0, 1), high risk (score: 2-3), and very high risk (score: 4-7) groups with sensitivity and specificity of 97% and 67%, respectively, and a good discriminating capability, with a C-statistic of 0.94. Internal and external validation showed good discrimination capability (C-statistics of 0.9 and 0.84, respectively). CONCLUSION: A simple risk score can stratify patients into three distinct prognosis groups, which can optimize patient management. CLINICAL TRIAL NUMBER: NCT04662268 KEY POINTS: • Simple scoring system predicting the risk of severe ischemic colitis • First study to include CT findings to the clinical and biological data used to determine a severity score.

Use of speckle tracking echocardiography to detect late anthracycline-induced cardiotoxicity in childhood cancer: A prospective controlled cross-sectional study.

BACKGROUND: This study aimed to detect late sub-clinical patterns of cardiac dysfunction using speckle tracking echocardiography (STE) in children with cancer remission more than 12 months after the end of anthracycline treatment. METHODS: This prospective controlled study enrolled 196 children, 98 of which had been treated with anthracyclines (mean age 10.8 ± 3.6 years; 51% female) and 98 were age- and gender-matched healthy subjects in a 1:1 case-control design. Conventional echocardiographic variables were collected for left ventricle (LV) and right ventricle (RV). STE analyses were performed in the LV longitudinal, radial, and circumferential displacements and in the RV free wall longitudinal displacement. The association between LV global longitudinal strain (GLS) and the main clinical and biological parameters was evaluated. RESULTS: After a mean time interval of 5.1 ± 3.2 years since the end of chemotherapy (mean cumulative anthracycline dose of 192 ± 96 mg/m2), conventional echocardiographic measures were normal. GLS was significantly decreased in the anthracycline group (-19.1% vs. -21.5%, P < 0.0001), with a higher proportion of children with abnormal values (Z-score < -2 in 18.6% vs. 1.0%, P < 0.0001). No association was found between GLS and clinical or biological parameters. Circumferential strain was significantly worse in the anthracycline group (-16.8% vs. -19.4%, P < 0.0001), and radial strain significantly better (+51.4% vs. +35.9%, P < 0.0001). RV conventional echocardiography and STE parameters were normal and not different between anthracycline and control groups. CONCLUSIONS: The existence of a modified LV strain despite normal LV function in children treated with anthracyclines represents an important perspective for cardiomyopathy surveillance in childhood cancer survivors. Clinical Trial Registration -ClinicalTrials.gov Identifier: NCT02893787.

Complication and lung function impairment prediction using perfusion and computed tomography air trapping (CLIPPCAIR): protocol for the development and validation of a novel multivariable model for the prediction of post-resection lung function.

BACKGROUND: Recent advancements in computed tomography (CT) scanning and post processing have provided new means of assessing factors affecting respiratory function. For lung cancer patients requiring resection, and especially those with respiratory comorbidities such as chronic obstructive pulmonary disease (COPD), the ability to predict post-operative lung function is a crucial step in the lung cancer operability assessment. The primary objective of the CLIPPCAIR study is to use novel CT data to develop and validate an algorithm for the prediction of lung function remaining after pneumectomy/lobectomy. METHODS: Two sequential cohorts of non-small cell lung cancer patients requiring a pre-resection CT scan will be recruited at the Montpellier University Hospital, France: a test population (N=60) on which predictive models will be developed, and a further model validation population (N=100). Enrolment will occur during routine pre-surgical consults and follow-up visits will occur 1 and 6 months after pneumectomy/lobectomy. The primary outcome to be predicted is forced expiratory volume in 1 second (FEV1) six months after lung resection. The baseline CT variables that will be used to develop the primary multivariable regression model are: expiratory to inspiratory ratios of mean lung density (MLDe/i for the total lung and resected volume), the percentage of voxels attenuating at less than ‒950 HU (PVOX‒950 for the total lung and resected volume) and the ratio of iodine concentrations for the resected volume over that of the total lung. The correlation between predicted and real values will be compared to (and is expected to improve upon) that of previously published methods. Secondary analyses will include the prediction of transfer factor for carbon monoxide (TLCO) and complications in a similar fashion. The option to explore further variables as predictors of post-resection lung function or complications is kept open. DISCUSSION: Current methods for estimating post-resection lung function are imperfect and can add assessments (such as scintigraphy) to the pre-surgical workup. By using CT imaging data in a novel fashion, the results of the CLIPPCAIR study may not only improve such estimates, it may also simplify patient pathways. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03885765).

Shear Wave Elastography, a New Tool for Diaphragmatic Qualitative Assessment: A Translational Study.

Rationale: Prolonged mechanical ventilation is often associated with either a decrease (known atrophy) or an increase (supposed injury) in diaphragmatic thickness. Shear wave elastography is a noninvasive technique that measures shear modulus, a surrogate of tissue stiffness and mechanical properties. Objectives: To describe changes in shear modulus (SM) during the ICU stay and the relationship with alterations in muscle thickness. To perform a comprehensive ultrasound-based characterization of histological and force production changes occurring in the diaphragm. Methods: Translational study using critically ill patients and mechanically ventilated piglets. Serial ultrasound examination of the diaphragm collecting thickness and SM was performed in both patients and piglets. Transdiaphragmatic pressure and diaphragmatic biopsies were collected in piglets. Measurements and Main Results: We enrolled 102 patients, 88 of whom were invasively mechanically ventilated. At baseline, SM was 14.3 ± 4.3 kPa and diaphragm end-expiratory thickness was 2.0 ± 0.5 mm. Decrease or increase by more than 10% from baseline was reported in 86% of the patients for thickness and in 92% of the patients for SM. An increase in diaphragmatic thickness during the stay was associated with a decrease in SM (ß = -9.34 ± 4.41; P = 0.03) after multivariable analysis. In the piglet sample, a decrease in SM over 3 days of mechanical ventilation was associated with loss of force production, slow and fast fiber atrophy, and increased lipid droplets accumulation. Conclusions: Increases in diaphragm thickness during critical illness is associated with decreased tissue stiffness as demonstrated by shear wave ultrasound elastography, consistent with the development of muscle injury and weakness. Clinical trial registered with www.clinicaltrials.gov (NCT03550222).

Integration of an Addiction Team in a Liver Transplantation Center.

Up to 50% of liver transplantation (LT) recipients with known or clandestine alcohol-use disorder (AUD) before surgery return to alcohol use after LT. However, only severe alcohol relapse, which varies in frequency from 11% to 26% of patients, has an impact on longterm survival and significantly decreases survival rates after 10 years. Therefore, it is crucial to identify patients with the highest risk of severe relapse in order to arrange specific, standardized monitoring by an addiction team before and after LT. The aims of this study were to describe the effects of combined management of AUD on the rate of severe alcohol relapse and to determine the risk factors before LT that predict severe relapse. Patients transplanted between January 2008 and December 2014 who had met with the LT team's addiction specialist were included in the study. Patients who exhibited alcohol-related relapse risk factors received specific addiction follow-up. A total of 235 patients were enrolled in the study. Most of them were men (79%), and the mean age at the time of the LT was 55.7 years. Severe relapse occurred in only 9% of the transplant recipients. Alcohol-related factors of severe relapse were a pretransplant abstinence of 6 months and family, legal, or professional consequences of alcohol consumption, whereas the nonalcohol-related factors were being single and being eligible for a disability pension. In conclusion, the integration of an addiction team in a LT center may be beneficial. The addiction specialist can identify patients at risk of severe relapse in the pretransplantation period and hence arrange for specific follow-up.