Prognostic factors after acute mesenteric ischemia: which patients require specific management?

PURPOSE: Diagnosis and treatment of AMI are a real issue for implicating physicians. In the literature, only one AMI stroke center has reported its results so far, with increasing survival rates. Our aim was to analyze acute mesenteric ischemia (AMI) related mortality and predictive factors, in a single academic center, before creating a dedicated intestinal stroke center. METHODS: All the patients with an AMI, between January 2015 and December 2020, were retrospectively included. They were divided into 2 groups according to the early mortality: death during the first 30 days and alive. The 2 groups were compared. RESULTS: 173 patients (57% of men), were included, with a mean age of 68 ± 16 years. Overall mortality rate was 61%. Mortality occurred within the first 30 days in 78% of dead cases. Dead patients were significantly older, more frequently admitted from intensive care, with more serious clinical, laboratory and radiological characteristics. We have identified 3 protective factors - history of abdominal surgery (Odd Ratio = 0.1; 95%CI = 0.01-0.8, p = 0.03), medical management with curative anticoagulation (OR = 0.09; 95%CI = 0.02-0.5, p = 0.004) and/or antiplatelets (OR = 0.04; 95%CI = 0.006-0.3, p = 0.001)-, and 2 predictive factors of mortality - age > 70 years (OR = 7; 95%CI = 1.4-37, p = 0.02) and previous history of coronaropathy (OR = 13; 95%CI = 1.7-93, p = 0.01). CONCLUSIONS: AMI is a severe disease with high morbidity and mortality rates. Even if its diagnosis is still difficult because of non-specific presentation, its therapeutic management needs to be changed in order to improve survival rates, particularly in patients older than 70 years with history of coronaropathy. Developing a dedicated organization would improve the diagnosis and the management of patients with AMI.

Impact of Hyperoxia after Graft Reperfusion on Lactate Level and Outcomes in Adults Undergoing Orthotopic Liver Transplantation.

BACKGROUND: Hyperoxia is common during liver transplantation (LT), without being supported by any guidelines. Recent studies have shown the potential deleterious effect of hyperoxia in similar models of ischemia-reperfusion. Hyperoxia after graft reperfusion during orthotopic LT could increase lactate levels and worsen patient outcomes. METHODS: We conducted a retrospective and monocentric pilot study. All adult patients who underwent LT from 26 July 2013 to 26 December 2017 were considered for inclusion. Patients were classified into two groups according to oxygen levels before graft reperfusion: the hyperoxic group (PaO2 > 200 mmHg) and the nonhyperoxic group (PaO2 < 200 mmHg). The primary endpoint was arterial lactatemia 15 min after graft revascularization. Secondary endpoints included postoperative clinical outcomes and laboratory data. RESULTS: A total of 222 liver transplant recipients were included. Arterial lactatemia after graft revascularization was significantly higher in the hyperoxic group (6.03 ± 4 mmol/L) than in the nonhyperoxic group (4.81 ± 2 mmol/L), p < 0.01. The postoperative hepatic cytolysis peak, duration of mechanical ventilation and duration of ileus were significantly increased in the hyperoxic group. CONCLUSIONS: In the hyperoxic group, the arterial lactatemia, the hepatic cytolysis peak, the mechanical ventilation and the postoperative ileus were higher than in the nonhyperoxic group, suggesting that hyperoxia worsens short-term outcomes and could lead to increase ischemia-reperfusion injury after liver transplantation. A multicenter prospective study should be performed to confirm these results.

Liver transplantation and hepatocellular carcinoma: is TIPS deleterious? A multicentric retrospective study of the ARCHET research group with propensity score matching.

PURPOSE: A transjugular intrahepatic portosystemic shunt (TIPS) before the liver transplantation (LT) has been considered a contraindication in cases of hepatocellular carcinoma (HCC) because of the risk of tumour growth. We aimed to assess the impact of TIPS on incidental HCC and oncological outcomes in transplanted patients with pre-existing HCC. METHODS: All consecutive transplanted patients for cirrhosis who had a previous TIPS with or without HCC were included. Between 2007 and 2014, 1912 patients were transplanted. We included 122 (6.3%) patients having TIPS before LT. A 1:3 matched cohort of 366 patients (18.9%) having LT without previous TIPS was selected using a propensity score. Incidental HCC rate and risk factor of HCC recurrence were evaluated using multivariate analysis with a competing risk model. RESULTS: Before LT, in the TIPS group, 27 (22.1%) had an HCC vs. 81 (22.1%) in the control group (p = 1). The incidental HCC rate was similar: 10.5% (10/95) in the TIPS group vs. 6.3% (18/285) in the control group (p = 0.17). Recurrence occurred in 1/27 (3.7%) patient in the TIPS group and in 7/81 (8.6%) patients in the control group, without significant difference (p = 0.51). After multivariate regression, patient's gender (p < 0.01) was significantly associated with HCC recurrence while a tumour within Milan criteria (p = 0.01, sHR: 0.17 [0.04; 0.7]) and an incidental HCC (p<0.01) were found to be protector factors against HCC recurrence. CONCLUSION: TIPS did not worsen the prognosis of transplanted patients for HCC. TIPS should no longer be contraindicated for oncological reasons in patients with HCC waiting for an LT.

Liver Transplantation Using Allografts With Recent Liver Blunt Trauma: A Nationwide Audit From the French CRISTAL Biomedicine Agency Registry.

BACKGROUND: In the current setting of organ shortage, brain-dead liver donors with recent liver trauma (RLT) represent a potential pool of donors. Yet, data on feasibility and safety of liver transplantation (LT) using grafts with RLT are lacking. METHODS: All liver grafts from brain-dead donors with RLT proposed for LT between 2010 and 2018 were identified from the nationwide CRISTAL registry of the Biomedicine Agency. The current study aimed at evaluating 1-y survival as the primary endpoint. RESULTS: Among 11 073 LTs, 142 LTs (1.3%) using grafts with RLT were performed. These 142 LTs, including 23 split LTs, were performed from 131 donors (46.1%) of 284 donors with RLT proposed for LT. Transplanted grafts were procured from donors with lower liver enzymes levels ( P < 0.001) and less advanced liver trauma according to the American Association for the Surgery of Trauma liver grading system ( P < 0.001) compared with not transplanted grafts. Before allocation procedures, 20 (7%) of 284 donors underwent damage control intervention. During transplantation, specific liver trauma management was needed in 19 patients (13%), consisting of local hemostatic control (n = 15), partial hepatic resection on back-table (n = 3), or perihepatic packing (n = 1). Ninety-day mortality and severe morbidity rates were 8.5% (n = 12) and 29.5% (n = 42), respectively. One-year overall and graft survival rates were 85% and 81%, and corresponding 5-y rates were 77% and 72%, respectively. CONCLUSIONS: Using liver grafts from donors with RLT seems safe with acceptable long-term outcomes. All brain-dead patients with multiorgan trauma, including liver injury, should be considered for organ allocation.

Impact of Dexamethasone and Inhaled Nitric Oxide on Severe Acute Kidney Injury in Critically Ill Patients with COVID-19.

Background: Acute kidney injury (AKI) is the second most frequent condition after acute respiratory distress syndrome (ARDS) in critically ill patients with severe COVID-19 and is strongly associated with mortality. The aim of this multicentric study was to assess the impact of the specific treatments of COVID-19 and ARDS on the risk of severe AKI in critically ill COVID-19 patients. Methods: In this cohort study, data from consecutive patients older than 18 years admitted to 6 ICUs for COVID-19-related ARDS requiring invasive mechanical ventilation were included. The incidence and severity of AKI, defined according to the 2012 KDIGO definition, were monitored during the entire ICU stay until day 90. Patients older than 18 years admitted to the ICU for COVID-19-related ARDS requiring invasive mechanical ventilation were included. Results: 164 patients were included in the final analysis; 97 (59.1%) displayed AKI, of which 39 (23.8%) had severe stage 3 AKI, and 21 (12.8%) required renal replacement therapy (RRT). In univariate analysis, severe AKI was associated with angiotensin-converting enzyme inhibitors (ACEI) exposure (p = 0.016), arterial hypertension (p = 0.029), APACHE-II score (p = 0.004) and mortality at D28 (p = 0.008), D60 (p < 0.001) and D90 (p < 0.001). In multivariate analysis, the factors associated with the onset of stage 3 AKI were: exposure to ACEI (OR: 4.238 (1.307−13.736), p = 0.016), APACHE II score (without age) (OR: 1.138 (1.044−1.241), p = 0.003) and iNO (OR: 5.694 (1.953−16.606), p = 0.001). Prone positioning (OR: 0.234 (0.057−0.967), p = 0.045) and dexamethasone (OR: 0.194 (0.053−0.713), p = 0.014) were associated with a decreased risk of severe AKI. Conclusions: Dexamethasone was associated with the prevention of the risk of severe AKI and RRT, and iNO was associated with severe AKI and RRT in critically ill patients with COVID-19. iNO should be used with caution in COVID-19-related ARDS.

Partial splenectomy in children undergoing liver transplantation or venous shunt for severe hypersplenism: A case control comparative study.

BACKGROUND AND AIM: Hypersplenism is a consequence of portal hypertension and splenomegaly secondary to cirrhosis or portal cavernoma in children. In order to avoid persistent hypersplenism and splenomegaly after liver transplantation (LT) or venous shunt (VS), partial splenectomy (PS) may represent a relevant therapeutic option. The aim of this retrospective study was to evaluate the results of PS performed in children presenting hypersplenism. METHODS: The following end-points were evaluated: (1) reversion of hypersplenism and its durability over time, (2) postoperative outcome, (3) courses of spleen size and volume and (4) comparison to a control group in which PS was not performed. RESULTS: Between 1996 and 2020, 16 children underwent PS associated with LT (8 cases) for cirrhosis or VS (8 cases) for portal cavernoma. From Day 0 to 1 month, mean platelet and white blood cell counts (WBC) dramatically improved from 48 ±â€¯19 at day 0 to 176 ±â€¯70 × 109/L (P < 0.0001) and from 2469 ±â€¯853 to 7198 ±â€¯3982/L (P = 0.001) respectively. PS allowed significant reduction of splenic length and volume from 176 ±â€¯33 to 112 ±â€¯24 cm (P < 0.0001) and from 1228 ±â€¯464 to 450 ±â€¯297 cm3 (P = 0.0003) respectively. After a mean follow-up of 92.6 ±â€¯84.7 months (range: 4.1-210.7), 14 patients are alive with normal platelet and WBC counts and persistent spleen size reduction. Compared to control group, PS was associated with a significant platelet count rise from baseline to one year. CONCLUSIONS: PS appears to be effective for treatment of hypersplenism and splenomegaly in combination with LT or VS without compromising outcome.

Upfront and Repeated Gamma-Knife Radiosurgery for Small (≤5 mL) Unruptured Brain Arteriovenous Malformation: A Cohort of 249 Consecutive Patients.

OBJECTIVE: According to A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), conservative treatment seems to be superior to any intervention for unruptured brain arteriovenous malformations (AVMs). This study aims to evaluate safety and efficacy of upfront and repeated Gamma-Knife Radiosurgery (GKRS) in patients harboring small AVMs fulfilling the inclusion criteria of ARUBA. METHODS: A retrospective study was conducted to evaluate outcomes of unruptured naive brain AVM with a volume ⩽ 5 mL eligible to ARUBA treated by GKRS with at least 3 years of follow-up. RESULTS: From 1992 to 2014, 249 patients fulfilled the inclusion criteria of this study. The median age was 36 years (range: 18-78 years). The median treated volume of the nidus was 1.3 mL (range: 0.4-5 mL) and 63% of the AVM were in eloquent areas. Radiosurgery-based AVM score was 1-1.8 (76%), the Spetzler-Martin grade was II-III (73%), and the Virginia Radiosurgery AVM scale was ≤1 point (75%). The overall AVM obliteration rate was 77.1% after up to 3 GKRS sessions. The median dose at the margin was 24 Gy (15-25 Gy) and the median follow-up was 45 months (range: 36-205 months). Eight patients (3.2%) experienced hemorrhage after GKRS, corresponding to a post-GKRS hemorrhage annual rate of 1.03%. Permanent symptomatic radio-induced changes rate was 2% (4 increased seizures, 1 neurologic deficit). CONCLUSIONS: The very low toxicity rate and the high occlusion rate suggest in favor of upfront and repeated GKRS for unruptured small AVMs (⩽5 mL).

Peri-operative risk factors of chronic kidney disease after liver transplantation.

BACKGROUND: Chronic kidney disease (CKD) is a frequent long-term complication after liver transplantation (LT) and is associated with poor long-term survival. The aim of our study was to identify the risk factors of developing post-transplant CKD at 1 year, during the pre-operative, peri-operative, and post-LT phases. METHODS: All consecutive patients who underwent primary LT between July 2013 and February 2018 were analyzed. To assess the impact of peri- and post-operative factors on renal function at 1 year we performed a propensity score matching on gender, age of the recipient, Model for End-Stage Liver Disease (MELD) score, etiology of the hepatic disease, and estimated Glomerular Filtration Rate (eGFR) at baseline. RESULTS: Among the 245 patients who underwent LT, 215 had available data at one year (Y1), and 46% of them had CKD. Eighty-three patients in the CKD group and 83 in the normal renal function group were then matched. The median follow-up was 35 months (27-77). Patients with CKD at Y1 had a decreased 5-year survival compared to patients with normal renal function at one year: figures were 62% and 90%, respectively, p = 0.001. The independent predictors of CKD at Y1 were major complications (OR = 2.2, 95% CI [1.2-4.2]), p = 0.015, intensive care unit (ICU) stay > 5 days (OR = 2.2, 95% CI [1.3-5.1]), p = 0.046, ICU serum lactate level at 24 h ≥ 2.5 mmol/L (OR = 3.8 95% CI [1.1-8]), p = 0.034, need for post-LT renal replacement therapy (OR = 6.4 95% CI [1.4-25]), and MELD score ≥ 20 (OR = 2.1 95% CI [1.1-3.9]), p = 0.019. CONCLUSIONS: The peri-operative period has a major impact on CKD incidence. Early recognition of patients at high risk of CKD may be critical for implementation of nephroprotective measures.

Acquired diaphragmatic hernia after hepatectomy and liver transplantation in adults and children: A case series and literature review.

BACKGROUNDS/AIMS: Acquired diaphragmatic hernia is a rare complication following liver surgery in adult and pediatric patients. This study aims to describe main features occurring in adult and pediatric patients after liver surgery and report an up-date review of the literature. METHODS: All adult and pediatric patients who were diagnosed with postoperative acquired diaphragmatic hernia in Lyon and Marseille University Hospitals were included in this study. Diagnosis, clinical, radiologic, and therapeutic data were analysed retrospectively from medical papers and/or electronic records. RESULTS: Thirteen adults with a median age of 50 years (range, 30-67 years) and 5 children aged 2.4 years (range, 0.9-4 years) were diagnosed with acquired diaphragmatic hernia after a median time of 65.1 (range, 1.8-244.7) and 2 (range, 0.33-10.9) months, respectively, following surgeries (5 live-donor right hepatectomies, 5 right and 1 left hepatectomies for tumors and cysts, and 2 whole liver transplantations in adults; and 5 liver transplantations with left lateral section in children). Eleven patients presented digestive and/or thoracic symptoms whereas seven were asymptomatic and diagnosed by routine imaging follow-up. All patients were re-operated with a median delay of 2.4 months (range, 0-25.3 months) for adults and 1 day (range, 0-2 days) for children. Two recurrences resulted in a secondary surgical repair. CONCLUSIONS: Acquired diaphragmatic hernia is a rare and potentially serious event after liver surgery. Recognition and surgical repair of this particular complication should be considered in the setting of unexplained abdominal and/or thoracic symptoms. Preventive measures should be taken intraoperatively.

The white test for intraoperative screening of bile leakage: a potential trigger factor for acute pancreatitis after liver resection-a case series.

BACKGROUND: Acute pancreatitis after liver resection is a rare but serious complication, and few cases have been described in the literature. Extended lymphadenectomy, and long ischemia due to the Pringle maneuver could be responsible of post-liver resection acute pancreatitis, but the exact causes of AP after hepatectomy remain unclear. CASES PRESENTATION: We report here three cases of AP after hepatectomy and we strongly hypothesize that this is due to the bile leakage white test. 502 hepatectomy were performed at our center and 3 patients (0.6%) experienced acute pancreatitis after LR and all of these three patients underwent the white test at the end of the liver resection. None underwent additionally lymphadenectomy to the liver resection. All patient had a white-test during the liver surgery. We identified distal implantation of the cystic duct in these three patients as a potential cause for acute pancreatitis. CONCLUSION: The white test is useful for detection of bile leakage after liver resection, but we do not recommend a systematic use after LR, because severe acute pancreatitis can be lethal for the patient, especially in case of distal cystic implantation which may facilitate reflux in the main pancreatic duct.

Percutaneous lung and liver CT-guided ablation on swine model using microwave ablation to determine ablation size for clinical practice.

PURPOSE: Microwave ablation (MWA) provides an effective treatment of lung and liver tumors but suffers from a lack of reproducibility of ablation size among currently available technologies. In-vitro evaluations are far removed from clinical practices because of uninfused tissue. This study is in-vivo preclinical testing of a new MWA system on swine lungs and liver. MATERIALS AND METHODS: All ablations were performed under CT guidance and multiple algorithms were tested with a power of 50, 75, and 100 W for durations of 3, 5, 8, 10, and 15 min. A 3 D-evaluation of the ablation zone was carried out using enhanced-CT. The sphericity index, coefficients of variation, and energy efficiency (which corresponds to the volume yield according to the power supplied) were calculated. RESULTS: Fifty liver and 48 lung ablations were performed in 17 swine. The sphericity index varies from 0.50 to 0.80 for liver ablations and from 0.40 to 0.69 for lung ablations. The coefficient of variation was below 15% for 4/5 and 4/8 protocols for lung and liver ablations, respectively. The energy efficiency seems to decrease with the duration of the ablation from 0.60 × 10-3 cm3/J (75 W, 3 min) to 0.26 × 10-3 cm3/J (100 W, 15 min) in the liver and from 0.57 × 10-3 cm3/J (50 W, 10 min) to 0.42 × 10-3 cm3/J (100 W, 12 min) in the lungs. CONCLUSION: A shorter treatment time provides the best energy efficiency, and the best reproducibility is obtained for a 10 min treatment duration. The system tested provides an interesting reproducibility in both lung and liver measurements. Our results may help interventional radiologists in the optimal selection of treatment parameters.

Long-term outcomes following resection of hepatocellular adenomas with small foci of malignant transformation or malignant adenomas.

BACKGROUND & AIMS: Malignant transformation of hepatocellular adenoma (MT-HCA) may occur in up to 5% of tumours. However, the prognostic value of this event remains poorly described. In this study, we aimed to analyse the long-term outcomes of patients undergoing liver resection (LR) for MT-HCA compared to those of patients resected for hepatocellular carcinoma (HCC) occurring on normal liver parenchyma (NP-HCC). METHODS: This single-centre retrospective study included all patients who underwent LR for MT-HCA at Beaujon Hospital between 2001 and 2019. MT-HCAs were classified as small foci of malignant transformation HCA (SF-HCA) and as malignant HCA (M-HCA) in cases of predominant HCC foci. Recurrence-free survival (RFS) of MT-HCA was compared with that of NP-HCC after propensity score matching. RESULTS: Forty patients (24 men, 16 women) underwent LR for MT-HCA, including 23 with SF-HCA and 17 with M-HCA. Of these cases, 16/40 (40%) had ß-catenin mutations, 19/40 (47.5%) were inflammatory, 1 was HNF1α-mutated HCA and 4 (10%) were unclassified HCA. Microvascular invasion (12% vs. 0%, p = 0.091) and satellite nodules (25% vs. 4%, p = 0.028) were more frequently observed in M-HCA than in SF-HCA. After a median follow-up of 67 months, 10 (25%) patients with MT-HCA had tumour recurrence, including 9 with M-HCA and 1 with SF-HCA (p = 0.007). M-HCA was linked to significantly poorer 1-, 3-, 5- and 10-year RFS rates than SF-HCA (76%, 63%, 39%, 37% vs. 100%, 100%, 100%, 91%, p = 0.003). Multivariate analysis showed that SF-HCA was independently associated with improved RFS (hazard ratio 0.064; 95% CI 0.008-0.519; p = 0.01). After propensity score matching, NP-HCC was associated with significantly poorer 1-, 3-, 5- and 10-year RFS rates than MT-HCA (p = 0.01). CONCLUSIONS: HCA with malignant transformation yields a better long-term prognosis than NP-HCC. Among MT-HCA, SF-HCA is associated with a better prognosis than M-HCA. LAY SUMMARY: The prognostic relevance of malignant transformation of hepatocellular adenoma (HCA) remains unknown. Thus, the aim of our study was to compare the outcomes of patients undergoing liver resection for malignant transformation to those of patients undergoing liver resection for hepatocellular carcinoma (HCC). The main long-term risk after resection for carcinoma is recurrence. In this study, 10/40 patients with malignant transformation of HCA relapsed after resection and we identified age >55 years, presence of satellite nodes, and microvascular invasion as risk factors for long-term recurrence. Compared to patients with HCC, patients who underwent liver resection for HCA with malignant transformation had better long-term survival.

Diagnostic performance of pulmonary ultrasonography and a clinical score for the evaluation of fluid overload in haemodialysis patients.

INTRODUCTION: There is no feasible benchmark in daily routine to estimate the hydration status of haemodialysis patients, which is essential to their management. OBJECTIVE: We performed a study in haemodialysis patients to assess the diagnostic performance of pulmonary ultrasound and clinical examination for the evaluation of fluid overload using transthoracic echocardiography as a gold standard. METHODS: Thirty-one patients receiving chronic haemodialysis patients were included. Evaluation of hydration status was assessed weekly before haemodialysis sessions using clinical and Echo Comet Score from pulmonary ultrasound and transthoracic echocardiography (reference method). RESULTS: Five patients had a transthoracic echocardiography overload. Compared with transthoracic echocardiography, the diagnostic performance of the clinical overload score has a sensitivity of 100%, a specificity of 77%, a positive predictive value of 50% and a negative predictive value of 100% with a κ of 0.79. Only orthopnoea (P=0.008), jugular turgor (P=0.005) and hepatic-jugular reflux (P=0.008) were significantly associated with transthoracic echocardiography overload diagnosis. The diagnostic performance of Echo Comet Score by pulmonary ultrasound has a sensitivity of 80%, a specificity of 58%, a positive predictive value of 26% and a negative predictive value of 94%. Ten patients (32.3%) had an increase of extravascular pulmonary water without evidence of transthoracic echocardiography or clinical overload. CONCLUSIONS: Our clinical score has a convincing diagnostic performance compared to transthoracic echocardiography and could be easily used in daily clinical routine to adjust dry weight. The evaluation of the overload using pulmonary ultrasound seems poorly correlated with the overload evaluated by transthoracic echocardiography. Extravascular pulmonary water undetected by clinical examination and transthoracic echocardiography remains a parameter that requires further investigation.

Renal SPECT/CT with 99mTc-dimercaptosuccinic acid is a non-invasive predictive marker for the development of interstitial fibrosis in a rat model of renal insufficiency.

BACKGROUND: Chronic kidney disease (CKD) increases cardiovascular risk and mortality. Renal fibrosis plays a major role in the progression of CKD but, to date, histology remains the gold standard to assess fibrosis. Non-invasive techniques are needed to assess renal parenchymal impairment and to perform the longitudinal evaluation of renal structure. Thus we evaluated renal isotopic imaging by single-photon emission computed tomography/computed tomography (SPECT/CT) with technetium-99m (99mTc)-dimercaptosuccinic acid (DMSA) to monitor renal impairment during renal insufficiency in rats. METHODS: Renal insufficiency was induced by an adenine-rich diet (ARD) at 0.25 and 0.5% for 28 days. Renal dysfunction was evaluated by assaying biochemical markers and renal histology. Renal parenchymal impairment was assessed by SPECT/CT isotopic imaging with 99mTc-DMSA on Days 0, 7, 14, 21, 28, 35 and 49. RESULTS: Compared with controls, ARD rats developed renal dysfunction characterized by increased serum creatinine and blood urea nitrogen, fibrosis and tubulointerstitial damage in the kidneys, with a dose-dependent effect of the adenine concentration. 99mTc-DMSA SPECT-CT imaging showed a significant decrease in renal uptake over time in 0.25 and 0.5% ARD rats compared with control rats (P = 0.011 and P = 0.0004, respectively). 99mTc-DMSA uptake on Day 28 was significantly inversely correlated with Sirius red staining evaluated on Day 49 (r = 0.89, P < 0.0001, R2 = 0.67). CONCLUSIONS: 99mTc-DMSA renal scintigraphy allows a longitudinal follow-up of risk of renal fibrosis in rats. We found that the reduction of renal parenchyma in ARD rats is inversely proportional to newly formed fibrous tissue in the kidney. Our results suggest that 99mTc-DMSA renal scintigraphy may be a useful non-invasive prognostic marker of the development of renal fibrosis in animals and should be tested in humans.

Combination of Alcohol and EVOH as a New Embolic Agent: Midterm Tissue and Inflammatory Effects in a Swine Model.

OBJECTIVE: To evaluate the vascular occlusion and midterm tissue toxicity properties of a combination of ethylene-vinyl alcohol (EVOH) (Squid 18®) (75%) and alcohol (25%)-Alco-Squid 18-in a swine model. MATERIALS AND METHODS: Alco-Squid 18 (75% Squid 18® mixed with 25% alcohol) (AS18) was compared to embolization with 96% alcohol alone and to embolization with Squid 18® (S18®) alone. An arteriovenous malformation (AVM) model was created in group 1 (n = 2). Each AVM model was then embolized with AS18 or S18® alone with evaluation of a ratio between the volume of embolic agent divided by the volume of the AVM (evaluated by CT). For group 2 (n = 5), each agent was tested on three different kidneys (upper pole kidney artery). Pre- and postinterventional CTs, angiographies, blood alcohol content dosages, and histological studies (3 months postintervention) were performed. RESULTS: AS18 has better distal distribution than S18® alone, both in the kidneys (mean capsule-S18® distance: 3.9 mm (±0.23) and mean capsule-AS18 distance: 2.3 mm (±0.11) (p=0.029) and in the AVM model. Histological exploration found a higher rate of tubular necrosis with AS18 compared with S18® alone and alcohol alone (3.78 ± 0.44 compared to 2.33 ± 1.22 (p = 0.012) and 1.22 ± 0.67 (p < 0 .0001)). The blood alcohol content was negligible in all cases. CONCLUSION: AS18 can suggest a better distal sclerotic and embolic character as compared with S18® alone without systemic toxicity.

Uremic Toxic Blood-Brain Barrier Disruption Mediated by AhR Activation Leads to Cognitive Impairment during Experimental Renal Dysfunction.

BACKGROUND: Uremic toxicity may play a role in the elevated risk of developing cognitive impairment found among patients with CKD. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AhR), which is widely expressed in the central nervous system and which we previously identified as the receptor of indoxyl sulfate in endothelial cells. METHODS: To characterize involvement of uremic toxins in cerebral and neurobehavioral abnormalities in three rat models of CKD, we induced CKD in rats by an adenine-rich diet or by 5/6 nephrectomy; we also used AhR-/- knockout mice overloaded with indoxyl sulfate in drinking water. We assessed neurologic deficits by neurobehavioral tests and blood-brain barrier disruption by SPECT/CT imaging after injection of 99mTc-DTPA, an imaging marker of blood-brain barrier permeability. RESULTS: In CKD rats, we found cognitive impairment in the novel object recognition test, the object location task, and social memory tests and an increase of blood-brain barrier permeability associated with renal dysfunction. We found a significant correlation between 99mTc-DTPA content in brain and both the discrimination index in the novel object recognition test and indoxyl sulfate concentrations in serum. When we added indoxyl sulfate to the drinking water of rats fed an adenine-rich diet, we found an increase in indoxyl sulfate concentrations in serum associated with a stronger impairment in cognition and a higher permeability of the blood-brain barrier. In addition, non-CKD AhR-/- knockout mice were protected against indoxyl sulfate-induced blood-brain barrier disruption and cognitive impairment. CONCLUSIONS: AhR activation by indoxyl sulfate, a uremic toxin, leads to blood-brain barrier disruption associated with cognitive impairment in animal models of CKD.