A Novel Technique to Improve Anastomotic Perfusion Prior to Esophageal Surgery: Hybrid Ischemic Preconditioning of the Stomach. Preclinical Efficacy Proof in a Porcine Survival Model

Esophagectomy often presents anastomotic leaks (AL), due to tenuous perfusion of gastric conduit fundus (GCF). Hybrid (endovascular/surgical) ischemic gastric preconditioning (IGP), might improve GCF perfusion. Sixteen pigs undergoing IGP were randomized: (1) Max-IGP (n = 6): embolization of left gastric artery (LGA), right gastric artery (RGA), left gastroepiploic artery (LGEA), and laparoscopic division (LapD) of short gastric arteries (SGA); (2) Min-IGP (n = 5): LGA-embolization, SGA-LapD; (3) Sham (n = 5): angiography, laparoscopy. At day 21 gastric tubulation occurred and GCF perfusion was assessed as: (A) Serosal-tissue-oxygenation (StO2) by hyperspectral-imaging; (B) Serosal time-to-peak (TTP) by fluorescence-imaging; (C) Mucosal functional-capillary-density-area (FCD-A) index by confocal-laser-endomicroscopy. Local capillary lactates (LCL) were sampled. Neovascularization was assessed (histology/immunohistochemistry). Sham presented lower StO2 and FCD-A index (41 ± 10.6%; 0.03 ± 0.03 respectively) than min-IGP (66.2 ± 10.2%, p-value = 0.004; 0.22 ± 0.02, p-value < 0.0001 respectively) and max-IGP (63.8 ± 9.4%, p-value = 0.006; 0.2 ± 0.02, p-value < 0.0001 respectively). Sham had higher LCL (9.6 ± 4.8 mL/mol) than min-IGP (4 ± 3.1, p-value = 0.04) and max-IGP (3.4 ± 1.5, p-value = 0.02). For StO2, FCD-A, LCL, max- and min-IGP did not differ. Sham had higher TTP (24.4 ± 4.9 s) than max-IGP (10 ± 1.5 s, p-value = 0.0008) and min-IGP (14 ± 1.7 s, non-significant). Max- and min-IGP did not differ. Neovascularization was confirmed in both IGP groups. Hybrid IGP improves GCF perfusion, potentially reducing post-esophagectomy AL

Real-time navigation by fluorescence-based enhanced reality for precise estimation of future anastomotic site in digestive surgery

Background: Fluorescence-based enhanced reality (FLER) is a technique to evaluate intestinal perfusion based on the elaboration of the Indocyanine Green fluorescence signal. The aim of the study was to assess FLER's performances in evaluating perfusion in an animal model of long-lasting intestinal ischemia. Materials and methods: An ischemic segment was created in 18 small bowel loops in 6 pigs. After 2h (n=6), 4h (n=6), and 6h (n=6), loops were evaluated clinically and by FLER to delineate five regions of interest (ROIs): ischemic zone (ROI 1), presumed viable margins (ROI 2a-2b), and vascularized areas (3a-3b). Capillary lactates were measured to compare clinical vs. FLER assessment. Basal (V 0 ) and maximal (V max) mitochondrial respiration rates were determined according to FLER. Results: Lactates (mmol/L) at clinically identified resection lines were significantly higher when compared to those identified by FLER (2.43±0.95 vs. 1.55±0.33 p=0.02) after 4h of ischemia. Lactates at 2h at ROI 1 were 5.45±2.44 vs. 1.9±0.6 (2a-2b; p<0.0001) vs. 1.2±0.3 (3a-3b; p<0.0001). At 4h, lactates were 4.36±1.32 (ROI 1) vs. 1.83±0.81 (2a-2b; p<0.0001) vs. 1.35±0.67 (3a-3b; p<0.0001). At 6h, lactates were 4.16±2.55 vs. 1.8±1.2 vs. 1.45±0.83 at ROI 1 vs. 2a--2b (p=0.013) vs. 3a-3b (p=0.0035). Mean V 0 and V max (pmolO2/second/mg of tissue) were significantly impaired after 4 and 6h at ROI 1 (V 0 4h =34.83±10.39; V max 4h =76.6±29.09; V 0 6h =44.1±12.37 and V max 6h =116.1±40.1) when compared to 2a--2b (V 0 4h =67.1±17.47 p=0.00039; V max 4h =146.8±55.47 p=0.0054; V 0 6h =63.9±28.99 p=0.03; V max 6h =167.2±56.96 p=0.01). V 0 and V max were significantly higher at 3a-3b. Conclusions: FLER may identify the future anastomotic site even after repetitive assessments and long-standing bowel ischemia

Probe-based confocal laser endomicroscopy and fluorescence-based enhanced reality for real-time assessment of intestinal microcirculation in a porcine model of sigmoid ischemia

Background and aim: Surgeons currently rely on visual clues to estimate the presence of sufficient vascularity for safe anastomosis. We aimed to assess the accuracy of endoluminal confocal laser endomicroscopy (CLE) and laparoscopic fluorescence-based enhanced reality (FLER), using near-infrared imaging and fluorescence from injected Indocyanine Green, to identify the transition from ischemic to vascular areas in a porcine model of mesenteric ischemia. Methods: Six pigs underwent 1-h sigmoid segmental ischemia. The ischemic area was evaluated by clinical assessment and FLER to determine presumed viable margins. For each sigmoid colon, 5 regions of interest (ROIs) were identified: ischemic (ROI 1), presumed viable margins ROI 2a (distal) and 2b (proximal), and vascular areas 3a (distal) and 3b (proximal). After injection of fluorescein, CLE scanning of the mucosa from the ischemic area toward viable margins was performed. Capillary blood samples were obtained by puncturing the serosa at the ROIs, and capillary lactates were measured with the EDGE® analyzer. Results: Capillary lactates were significantly higher at ROI 1 (4.91mmol/L) when compared to resection margins (2.8mmol/L; mean difference: 2.11; p<0.05) identified by FLER. There was no significant difference in lactates between ROI1 and resection margins identified by clinical evaluation. In 50% of cases, ROI 2aCLINIC-2bCLINIC were considered to match (<1cm distance) with ROI 2aFLER-2bFLER. Confocal analysis revealed specific clues to identify the transition from ischemic to viable areas corresponding to those assessed by FLER in 11/12 cases versus 7/12 for those identified by clinical evaluation. Conclusions: In this experimental model, FLER and CLE were more accurate than clinical evaluation to delineate bowel vascularization

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Automatic Liver Viability Scoring with Deep Learning and Hyperspectral Imaging.

Hyperspectral imaging (HSI) is a non-invasive imaging modality already applied to evaluate hepatic oxygenation and to discriminate different models of hepatic ischemia. Nevertheless, the ability of HSI to detect and predict the reperfusion damage intraoperatively was not yet assessed. Hypoxia caused by hepatic artery occlusion (HAO) in the liver brings about dreadful vascular complications known as ischemia-reperfusion injury (IRI). Here, we show the evaluation of liver viability in an HAO model with an artificial intelligence-based analysis of HSI. We have combined the potential of HSI to extract quantitative optical tissue properties with a deep learning-based model using convolutional neural networks. The artificial intelligence (AI) score of liver viability showed a significant correlation with capillary lactate from the liver surface (r = -0.78, p = 0.0320) and Suzuki's score (r = -0.96, p = 0.0012). CD31 immunostaining confirmed the microvascular damage accordingly with the AI score. Our results ultimately show the potential of an HSI-AI-based analysis to predict liver viability, thereby prompting for intraoperative tool development to explore its application in a clinical setting

Detection of Pneumocystis jirovecii in Patients with Severe COVID-19: Diagnostic and Therapeutic Challenges

Cases of Pneumocystis jirovecii pneumonia (PCP) in patients suffering from COVID-19 were described in patients with various comorbidities and outcomes. The diagnosis of PCP in these patients is difficult due to clinical and radiological similarities. We carried out this study in order to better describe potentially at-risk patients and their outcomes. We retrospectively analyzed all patients with a P. jirovecii PCR performed in bronchoalveolar lavage fluid, tracheal aspirate, or sputum within a month after the COVID-19 diagnosis. Fifty-seven patients with COVID-19 infection were tested for P. jirovecii. Among 57 patients with COVID-19, four patients had a concomitant positive P. jirovecii PCR. These four patients were elderly with a mean age of 78. Two patients were immunocompromised, and the two others presented only diabetes mellitus. Three patients presented an ARDS requiring transfer to the ICU and mechanical ventilation. All patients presented lymphocytopenia. Three patients had probable PCP, and one had proven PCP. All patients died within two months after hospital admission. These co-infections are rare but severe, therefore, PCP should be considered in case of worsening of the condition of patients with severe COVID-19

Unique Transcriptomic Profile of Collecting Duct Carcinomas Relative to Upper Tract Urothelial Carcinomas and other Kidney Carcinomas

International audienceCollecting duct carcinoma (CDC) is a kidney cancer subtype that is thought to arise from principal cells in distal parts of the collecting ducts. Some studies suggested an overlap of CDC with upper tract urothelial carcinoma (UTUC), making the pathological diagnosis challenging. Herein, we performed for the first time transcriptome sequencing of CDC and compared them to UTUC and renal cell carcinoma subtypes. We discovered that CDC displays a unique transcriptomic signature among kidney cancer subtypes, with a putative cell of origin in the distal convoluted tubules. Hierarchical unsupervised clustering reveals that the CDC signature is closer to that of other RCC subtypes than to UTUC, which is similar to that of bladder carcinoma. CDC is characterized by a metabolic shift, with impairment of oxidoreductase activity, pyruvate metabolism and the tricarboxlyic acid cycle, as well as an immunogenic response consistent with increased tumor infiltrating lymphocytes, particularly within metastatic cases. In addition, pathways differentially altered between CDC and UTUC point to a basal-like phenotype of CDC in contrast to the luminal-like signature of UTUC. We conclude that CDC harbors a pathognomonic transcriptomic signature characterized by immunogenic and a metabolic aberrations, indicating that targeting these processes might provide therapeutic options for patients