Clinical relevance of lung transplantation for COVID-19 ARDS: a nationwide study.

BACKGROUND: Although the number of lung transplantations (LTx) performed worldwide for COVID-19 induced acute respiratory distress syndrome (ARDS) is still low, there is general agreement that this treatment can save a subgroup of most severly ill patients with irreversible lung damage. However, the true proportion of patients eligible for LTx, the overall outcome and the impact of LTx to the pandemic are unknown. METHODS: A retrospective analysis was performed using a nationwide registry of hospitalised patients with confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-Cov-2) infection admitted between January 1, 2020 and May 30, 2021 in Austria. Patients referred to one of the two Austrian LTx centers were analyzed and grouped into patients accepted and rejected for LTx. Detailed outcome analysis was performed for all patients who received a LTx for post-COVID-19 ARDS and compared to patients who underwent LTx for other indications. RESULTS: Between January 1, 2020 and May 30, 2021, 39.485 patients were hospitalised for COVID-19 in Austria. 2323 required mechanical ventilation, 183 received extra-corporeal membrane oxygenation (ECMO) support. 106 patients with severe COVID-19 ARDS were referred for LTx. Of these, 19 (18%) underwent LTx. 30-day mortality after LTx was 0% for COVID-19 ARDS transplant recipients. With a median follow-up of 134 (47-450) days, 14/19 patients are alive. CONCLUSIONS: Early referral of ECMO patients to a LTx center is pivotal in order to select patients eligible for LTx. Transplantation offers excellent midterm outcomes and should be incorporated in the treatment algorithm of post-COVID-19 ARDS.

Cardiopulmonary response to high-altitude mountaineering in lung transplant recipients-The Jebel Toubkal experience.

OBJECTIVES: Only a small proportion of lung transplant recipients achieve a physical status comparable to healthy individuals in the long term. It is reasonable to hypothesize that the necessary cardiopulmonary adaptation required for strenuous physical exercise may be impaired. Exposure to high altitude provides an optimal platform to study the physiological cardiopulmonary adaptation in lung transplant recipients under aerobic conditions. To gain a deeper understanding, 14 healthy lung transplant recipients and healthcare professionals climbed the highest peak in North Africa (Mount Jebel Toubkal; 4167 m) in September 2019. METHODS: Monitoring included daily assessment of vital signs, repeated transthoracic echocardiography, pulmonary function tests, and capillary blood sampling throughout the expedition. RESULTS: Eleven out of fourteen lung transplant recipients reached the summit. All recipients showed a stable lung function and vital parameters and physiological adaptation of blood gases. Similar results were found in healthy controls. Lung transplant recipients showed worse results in the 6-minute walk test at low and high altitude compared to controls (day 1: 662 m vs. 725 m, p < 0.001, day 5: 656 m vs. 700 m, p = 0.033) and a lack of contractile adaptation of right ventricular function with increasing altitude as measured by tricuspid plane systolic excursion on echocardiography (day 2: 22 mm vs. 24 mm, p = 0.202, day 5: 23 mm vs. 26 mm, p = 0.035). CONCLUSIONS: Strenuous exercise in healthy lung transplant recipients is safe. However, the poorer cardiopulmonary performance in the 6-minute walk test and the lack of right ventricular cardiac adaptation may indicate underlying autonomic dysregulation.

Performing central venous catheters in neonates and small infants undergoing cardiac surgery using a wireless transducer for ultrasound guidance: a prospective, observational pilot study.

BACKGROUND: Neonates and small infants with congenital cardiac disease undergoing cardiac surgery represent major challenges facing paediatric anaesthesia and perioperative medicine. AIMS: We here aimed to investigate the success rates in performing ultrasound (US) guided central venous catheter insertion (CVC) in neonates and small infants undergoing cardiac surgery, and to evaluate the practicability and feasibility of thereby using a novel wireless US transducer (WUST). METHODS: Thirty neonates and small infants with a maximum body weight of 10 kg and need for CVC before cardiac surgery were included in this observational trial and were subdivided into two groups according to their weight: < 5 kg and ≥ 5 kg. Cannulation success, failure rate, essential procedure related time periods, and complications were recorded and the clinical utility of the WUST was assessed by a 5-point Likert scale. RESULTS: In total, CVC-insertion was successful in 27 (90%) of the patients and the first attempt was successful in 24 (78%) of patients. Success rates of CVC were 80% < 5 kg and 100% ≥5 kg. Comparing the two groups we found a clear trend towards longer needle insertion time in patients weighing < 5 kg (33 [28-69] vs. 24 [15-37]s, P = .07), whereas, the total time for catheter insertion and the duration of the whole procedure were similar in both groups (199 [167-228] vs. 178 [138-234] and 720[538-818] vs. 660 [562-833]s. In total, we report 3 (10%) cases of local hematoma as procedure-related complications. Assessments of the WUST revealed very good survey results for all parameters of practicability and handling (all ratings between 4.5 and 5.0). CONCLUSION: Although difficulties in CVC-placement seem to relate to vessel size and patient's weight, US guided CVC-insertion represents a valuable, fast, and safe intervention in neonates and small children undergoing cardiac surgery. Using the WUST is feasible for this clinical application and may aid in efforts aiming to optimize perioperative care. TRIAL REGISTRATION: Wireless US-guided CVC placement in infants; Clinicaltrials.gov: NCT04597021 ; Date of Registration: 21October, 2020; retrospectively registered.

Urinary [TIMP-2] × [IGFBP-7] for predicting acute kidney injury in patients undergoing orthotopic liver transplantation.

BACKGROUND: The product of the concentrations of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein-7 (urinary [TIMP-2] × [IGFBP-7]) has been suggested as biomarker for early detection of acute kidney injury (AKI) in various clinical settings. However, the performance of urinary [TIMP-2] × [IGFBP-7] to predict AKI has never been assessed in patients undergoing orthotopic liver transplantation (OLT). Thus, the aim of this study was to assess the early predictive value of urinary [TIMP-2] × [IGFBP-7] for the development of AKI after OLT. METHODS: In this observational study, urinary [TIMP-2] × [IGFBP-7] was measured in samples from adult OLT patients. AKI was diagnosed and classified according to KDIGO criteria. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of urinary [TIMP-2] × [IGFBP-7] for the development of AKI. RESULTS: Forty patients (mean age 55 ± 8 years) were included. Twenty-eight patients (70%) developed AKI stage 1, 2, or 3 within 48 h after OLT. Urinary [TIMP-2] × [IGFBP-7] was not predictive for AKI at the end of OLT (AUC: 0.54, CI [0.32-0.75], P = 0.72), at day 1 (AUC: 0.60, CI [0.41-0.79], P = 0.31), or day 2 after OLT (AUC: 0.63, CI [0.46-0.8], P = 0.18). CONCLUSION: Based on our results, routine clinical use of urinary [TIMP-2] × [IGFBP-7] cannot be recommended for risk assessment of AKI in patients undergoing OLT.

D-dopachrome tautomerase predicts outcome but not the development of acute kidney injury after orthotopic liver transplantation.

BACKGROUND: Elevated concentrations of D-dopachrome tautomerase (D-DT) were associated with adverse outcome in various clinical settings. However, no study assessed D-DT concentrations in patients requiring orthotopic liver transplantation (OLT). The aim of this observational study was to measure serum D-DT concentrations in patients undergoing OLT and associate D-DT with survival and acute kidney injury (AKI). METHODS: Forty-seven adults with end-stage liver disease undergoing OLT were included. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of D-DT for outcome and AKI after OLT. Survival was analyzed by Kaplan-Meier curves. RESULTS: Serum D-DT concentrations were greater in non-survivors than in survivors prior to OLT (86 [50-117] vs. 53 [31-71] ng/ml, P = 0.008), and on day 1 (357 [238-724] vs. 189 [135-309] ng/ml, P = 0.001) and day 2 (210 [142-471] vs. 159 [120-204] ng/ml, P = 0.004) following OLT. Serum D-DT concentrations predicted lethal outcome when measured preoperatively (AUC = 0.75, P = 0.017) and on postoperative day 1 (AUC = 0.75, P = 0.015). One-year survival of patients with preoperative D-DT concentrations >85 ng/ml was 50%, whereas that of patients with preoperative D-DT concentrations <85 ng/ml was 83% (Chi2 = 5.83, P = 0.016). In contrast, D-DT was not associated with AKI after OLT. CONCLUSION: In patients undergoing OLT, serum D-DT might predict outcome after OLT.

Graft-derived macrophage migration inhibitory factor correlates with hepatocellular injury in patients undergoing liver transplantation.

Experimental studies suggest that macrophage migration inhibitory factor (MIF) mediates ischemia/reperfusion injury during liver transplantation. This study assessed whether human liver grafts release MIF during preservation, and whether the release of MIF is proportional to the extent of hepatocellular injury. Additionally, the association between MIF and early allograft dysfunction (EAD) after liver transplantation was evaluated. Concentrations of MIF, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) were measured in effluents of 38 liver grafts, and in serum of recipients. Concentrations of MIF in the effluent were greater than those in the recipients' serum before and after reperfusion (58 [interquartile range, IQR:23-79] µg/mL vs 0.06 [IQR:0.03-0.07] µg/mL and 1.3 [IQR:0.7-1.8] µg/mL, respectively; both P<.001). Effluent MIF concentrations correlated with effluent concentrations of the cell injury markers ALT (R=.51, P<.01), AST (R=.51, P<.01), CK (R=.45, P=.01), and LDH (R=.56, P<.01). Patients who developed EAD had greater MIF concentrations in effluent and serum 10 minutes after reperfusion than patients without EAD (Effluent: 80 [IQR:63-118] µg/mL vs 36 [IQR:20-70] µg/mL, P=.02; Serum: 1.7 [IQR:1.2-2.5] µg/mL vs 1.1 [IQR:0.6-1.7] µg/mL, P<.001). CONCLUSION: Human liver grafts release MIF in proportion to hepatocellular injury. Greater MIF concentrations in effluent and recipient's serum are associated with EAD after liver transplantation.

Patients Undergoing Orthotopic Liver Transplantation Require Lower Concentrations of the Volatile Anesthetic Sevoflurane.

BACKGROUND: Sevoflurane is a volatile anesthetic commonly used to maintain anesthesia in patients with end-stage liver disease (ESLD) undergoing orthotopic liver transplantation (OLT). Growing evidence suggests that patients with ESLD have decreased anesthetic requirements compared to patients with preserved liver function. The potency of volatile anesthetics is expressed as the minimum alveolar concentration (MAC). In this prospective, blinded study, we compared the MAC of sevoflurane among patients with ESLD undergoing OLT and patients with normal liver function undergoing major abdominal surgery. METHODS: After propofol-induced anesthesia, the MAC of sevoflurane was assessed by evaluating motor response to initial skin incision in patients undergoing OLT and in patients with normal liver function undergoing major abdominal surgery. The MAC was determined using Dixon "up-and-down" method and compared between groups. In addition, the bispectral index was documented immediately before and after skin incision. RESULTS: Twenty patients undergoing OLT and 20 control patients were included in the study. The MAC of sevoflurane in patients undergoing OLT was 1.3% (95% confidence interval [CI], 1.1-1.4). In comparison, the MAC of sevoflurane in patients with normal liver function was 1.7% (95% CI, 1.6-1.9), equal to a relative reduction of the MAC in patients with ESLD of 26% (95% CI, 14-39). The bispectral index was higher in patients with ESLD than in control patients at 3 minutes before (47 [95% CI, 40-53] vs 35 [95% CI, 31-40], P = .011), 1 minute before (48 [95% CI, 42-54] vs 37 [95% CI, 33-43], P = .03), and 1 minute after skin incision (57 [95% CI, 50-64] vs 41 [95% CI, 36-47], P < .001). CONCLUSIONS: Our results suggest that the MAC of sevoflurane is lower in patients with ESLD than in patients with normal liver function after propofol-induced anesthesia. However, as we did not measure propofol concentrations at the time of skin incision, the difference in MAC should be interpreted with caution given that residual propofol may have been present at the time of skin incision.

Macrophage migration inhibitory factor as a potential predictor for requirement of renal replacement therapy after orthotopic liver transplantation.

Acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is associated with a poor clinical outcome. Because there is no specific treatment for postoperative AKI, early recognition and prevention are fundamental therapeutic approaches. Concentrations of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) are elevated in patients with kidney disease. We hypothesized that plasma MIF concentrations would be greater in patients developing AKI after OLT compared with patients with normal kidney function. Twenty-eight patients undergoing OLT were included in the study. Kidney injury was classified according to AKI network criteria. Fifteen patients (54%) developed severe AKI after OLT, 11 (39%) requiring renal replacement therapy (RRT). On the first postoperative day, patients with severe AKI had greater plasma MIF concentrations (237 ± 123 ng/mL) than patients without AKI (95 ± 63 ng/mL; P < 0.001). The area under the receiver operating characteristic (ROC) curve for predicting severe AKI was 0.87 [95% confidence interval (CI), 0.69-0.97] for plasma MIF, 0.61 (95% CI, 0.40-0.79) for serum creatinine (sCr), and 0.90 (95% CI, 0.72-0.98) for delta serum creatinine (ΔsCr). Plasma MIF (P = 0.02) and ΔsCr (P = 0.01) yielded a better predictive value than sCr for the development of severe AKI. Furthermore, the area under the ROC curve to predict the requirement of RRT was 0.87 (95% CI, 0.68-0.96) for plasma MIF, 0.65 (95% CI, 0.44-0.82) for sCr, and 0.72 (95% CI, 0.52-0.88) for ΔsCr. Plasma MIF had a better predictive value than sCr for the requirement of RRT (P = 0.02). In conclusion, postoperative plasma MIF concentrations were elevated in patients who developed severe AKI after OLT. Furthermore, plasma MIF concentrations showed a good prognostic value for identifying patients developing severe AKI or requiring postoperative RRT after OLT.

Extracorporeal liver support.

PURPOSE OF REVIEW: The mortality in patients suffering from liver failure decreased in line with medical progress over the past decades. However, it still remains unacceptably high and liver transplantation still provides the only definite treatment for many patients. The goal of extracorporeal liver support systems is to improve the clinical condition of patients waiting for liver transplantation and/or enhance the regeneration of native injured liver. Nonbiological liver support systems with pure detoxification and biological liver support systems with assumed synthesis and metabolism in addition to detoxification are currently under clinical investigation. Since patient survival is the most significant outcome parameter, we focus in this review on prospective randomized trials with survival rate as primary outcome parameter. RECENT FINDINGS: Although a short-term outcome benefit in patients with acute-on-chronic liver failure was shown in some of these trials, long-term outcome has not been improved significantly with either of the support systems. In spite of more favourable but yet limited data in patients with acute liver failure, it is too early to draw definite conclusions. SUMMARY: The future development of liver support systems may provide different combinations of new adsorbents, integrated regional citrate anticoagulation and eventual substitution of irreversibly damaged albumin.

Incidence and outcomes of AKI in postoperative patients admitted to ICU using full KDIGO criteria - a cohort study.

STUDY OBJECTIVE: Acute kidney injury (AKI) is a serious complication in postoperative ICU patients. The incidence of AKI varies substantially based on the type of surgery and definition used. This study focuses on the incidence of AKI in postoperative ICU patients using full KDIGO criteria and related outcomes regarding to different types of surgery. DESIGN: Retrospective cohort study. SETTING: Tertiary level university hospital, eight anaesthesiological/surgical ICUs, between 2016 and 2018. PATIENTS: 6261 adult patients. MEASUREMENTS: Primary outcome was 28-day all-cause mortality in different stages of AKI according to complete KDIGO criteria. MAIN RESULTS: We found 3497 (55.9%) postoperative ICU patients with AKI. The severity distribution of AKI stage 1 to 3 was 19.7%, 28.4% and 7.8%, respectively, and 235 (4%) patients received RRT. The 28-day mortality was 3% (n = 205). Increasing AKI severity was associated with increased 28-day mortality when adjusted for other variables (AKI 2°: OR 2.81; 95% CI 1.55 to 5.24; p < 0.001 and AKI 3°: OR 11.37.; 95% CI 5.91 to 22.55; p < 0.001). Besides AKI stages 2 and 3, age (OR 1.02; 95% CI 1.01 to 1.04, p < 0.001), NYHA IV (OR 2.23; 95% CI 1.03 to 4.43, p = 0.042), need for surgical reintervention within 48 h (OR 2.92; 95% CI 1.76 to 4.72, p = 0.001), urgent surgery (OR 1.78; 95% CI 1.15 to 2.71, p = 0.01), emergency surgery (OR 2.63; 95% CI 1.58 to 4.31, p = 0.001), vascular surgery (OR 2.01; 95% CI 1.06 to 3.98, p = 0.033), and orthopedic and trauma surgery (OR 3.79; 95% CI 1.98 to 7.09, p < 0.001) versus cardiac surgery was significantly associated with increased risk for 28-days mortality in multivariate analysis. CONCLUSION: AKI based on full KDIGO criteria is very common in postoperative ICU patients and it is associated with stepwise increase in 28-days mortality.

The Effect of Prone Positioning After Lung Transplantation.

BACKGROUND: Prone positioning has become a standard therapy in acute respiratory distress syndrome to improve oxygenation and decrease mortality. However, little is known about prone positioning in lung transplant recipients. This large, singe-center analysis investigated whether prone positioning improves gas exchange after lung transplantation. METHODS: Clinical data of 583 patients were analyzed. Prone position was considered in case of impaired gas exchange Pao2/fraction of oxygen in inhaled air (<250), signs of edema after lung transplantation, and/or evidence of reperfusion injury. Patients with hemodynamic instability or active bleeding were not proned. Impact of prone positioning (n = 165) on gas exchange, early outcome and survival were determined and compared with patients in supine positioning (n = 418). RESULTS: Patients in prone position were younger, more likely to have interstitial lung disease, and had a higher lung allocation score. Patients were proned for a median of 19 hours (interquartile range,15-26) hours). They had significantly lower Pao2/fraction of oxygen in inhaled air (227 ± 96 vs 303 ± 127 mm Hg, P = .004), and lower lung compliance (24.8 ± 9.1 mL/mbar vs 29.8 ± 9.7 mL/mbar, P < .001) immediately after lung transplantation. Both values significantly improved after prone positioning for 24 hours (Pao2/fraction of oxygen ratio: 331 ± 91 mm Hg; lung compliance: 31.7 ± 20.2 mL/mbar). Survival at 90 days was similar between the 2 groups (93% vs 96%, P = .105). CONCLUSIONS: Prone positioning led to a significant improvement in lung compliance and oxygenation after lung transplantation. Prospective studies are needed to confirm the benefit of prone positioning in lung transplantation.

Copeptin: Prognostic Relevance as a Perioperative Marker in Pediatric Cardiac Surgery.

BACKGROUND: Copeptin is a cleavage product of vasopressin. This study aimed to figure out if copeptin would be a suitable biomarker in patients with congenital heart disease in the postoperative course. METHODS: The primary outcome endpoint of this study was the change in copeptin concentration perioperatively in patients with congenital heart disease after surgery, with the use of a cardiopulmonary bypass. Three blood samples were taken from 81 patients up to 6 years of age in order to evaluate changes in copeptin concentration. RESULTS: Significant increase of copeptin concentration was shown between the first and second blood draws as well as between the first and third blood draws (Ps < .001). Additionally, positive and significant correlations (r ≥ .27) between the cardiopulmonary bypass times, The Society of Thoracic Surgeons and European Association for Cardio-Thoracic Surgery mortality category, the inotropic score, the duration of mechanical ventilation, the length of stay at the intensive care unit (ICU), the length of stay at the hospital, and the preoperative as well as the ICU copeptin levels were found. CONCLUSIONS: Copeptin showed a tendency to predict the clinical outcome of patients after congenital heart surgery. Patients with higher copeptin levels underwent more complex procedures, had longer cardiopulmonary bypass times, required more catecholamine support, needed longer time of invasive ventilation, and had longer overall stay and ICU stay.

Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS.

BACKGROUND: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. METHODS: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. RESULTS: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the 'SSC' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of 'SSC' patients was severely impaired compared to 'no SSC' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). CONCLUSIONS: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing.

Regional citrate anticoagulation in patients with liver failure supported by a molecular adsorbent recirculating system.

OBJECTIVE: Regional citrate anticoagulation has emerged as a promising method in critically ill patients at high risk of bleeding. However, in patients with liver failure, citrate accumulation may lead to acid-base and electrolyte imbalances, notably of calcium. The aim of this study was to evaluate the feasibility and safety of regional citrate anticoagulation during liver support using a molecular adsorbent recirculating system as well as its effects on electrolyte and acid-base balance in patients with liver failure. DESIGN: Prospective observational study. SETTING: University hospital. PATIENTS: Twenty critically ill patients supported by molecular adsorbent recirculating system resulting from liver failure between January 2007 and May 2009. MEASUREMENTS AND MAIN RESULTS: The median duration of molecular adsorbent recirculating system treatment was 20 hrs (interquartile range, 18-22 hrs). Two of 77 molecular adsorbent recirculating system treatments (2%) were prematurely discontinued as a result of filter clotting and bleeding, respectively. The median citrate infusion rate, necessary to maintain the postfilter ionized calcium between 0.2 and 0.4 mmol/L, was 3.1 mmol/L (interquartile range, 2.3-4 mmol/L) blood flow. The median calcium chloride substitution rate was 0.9 mmol/L (0.3-1.7 mmol/L) dialysate. Total serum calcium remained stable during molecular adsorbent recirculating system treatments. There was a statistically significant increase of the ratio of total calcium to systemic ionized calcium (2.04 ± 0.32 mmol/L to 2.17 ± 0.35; p = .01), which reflected citrate accumulation resulting from liver failure. Under close monitoring, no clinically relevant electrolytes or acid-base disorders were observed. CONCLUSIONS: Our results suggest that regional citrate anticoagulation is a safe and feasible method to maintain adequate circuit lifespan without increasing the risk of hemorrhagic complications while maintaining a normal acid-base as well as electrolyte balance in patients with liver failure supported by molecular adsorbent recirculating system.

Evaluation of chemotherapy-associated liver injury in patients with colorectal cancer liver metastases using indocyanine green clearance testing.

BACKGROUND: Systemic chemotherapy may render initially unresectable colorectal cancer liver metastases resectable. Histopathologic examinations of resected nontumoral liver tissue revealed chemotherapy-associated liver injuries, which was recognized to impair the function of the remnant liver. We therefore evaluated whether indocyanine green (ICG) plasma clearance helps to assess chemotherapy-induced liver damage. METHODS: Data of 101 liver resections performed between 2006 and 2008 for colorectal liver metastases were analyzed for this study. Eighteen patients had liver resection without preoperative treatment, whereas 83 patients underwent neoadjuvant chemotherapy before surgery. ICG clearance was assessed by pulse densitometry before surgery. RESULTS: Comparison of ICG retention clearances demonstrated that patients pretreated with systemic chemotherapy had a significantly lower plasma disappearance rate (ICG-PDR; 19.3 ± 5.9 vs. 23.1 ± 3.8%/min; P = 0.002) and a significantly elevated ICG retention rate at 15 min (7.9 ± 6.6 vs. 3.8 ± 1.9%; P < 0.001). The percentage of subjects with an abnormal ICG-PDR (≤18%/min) was significantly higher in the pretreated group (48.2% vs. 5.6%; P = 0.001). Patients with an ICG-PDR of ≤18 had a prolonged postoperative hospital stay and experienced four times more complications in their postoperative course. CONCLUSIONS: ICG clearance helps to identify patients with impaired liver function after neoadjuvant chemotherapy and aids in the estimation of the postoperative risk of morbidity after liver resection for colorectal liver metastases.

Up-regulation of interleukin 33 and soluble ST2 serum levels in liver failure.

BACKGROUND: IL-33, a member of the IL-1 family, induces the production of pro-inflammatory and Th2-associated cytokines and may also serve as an 'alarmin' similar to HMGB1. Soluble ST2 has been implicated as a decoy receptor, to attenuate Th2 inflammatory responses. The relevance of both molecules in hepatic failure is unknown. MATERIALS AND METHODS: The trial was a prospective preliminary study in a university hospital surgical ICU; 11 patients with acute liver failure (ALF) and 12 patients with acute-on-chronic liver failure (ACLF), who were admitted to the ICU; 14 patients with chronic hepatic failure (CHF) awaiting liver transplantation; 13 healthy individuals served as controls. IL-33 and soluble ST2 concentrations were determined by enzyme linked immunosorbent assay (ELISA). RESULTS: The concentration of IL-33 and soluble ST2 was significantly higher in ALF, ACLF, and CHF patients compared with the controls. Soluble ST2 serum concentration was significantly elevated in ALF and ACLF compared with CHF; moreover, soluble ST2 was significantly higher in CHF compared with healthy controls. IL-33 and soluble ST2 serum levels correlated significantly (r = 0.6117, P < 0.0001). Moreover, there was a correlation between IL-33 serum levels and alanine aminotransferase (ALT) activity in CHF, ALF, and ACLF patients (r = 0.4321, P = 0.0171). CONCLUSION: Our data provide evidence for elevated levels of IL-33 and soluble ST2 in liver failure, which could a sign of immune hyperactivation, and/or a mechanism to down-regulate inflammation. Especially, soluble ST2 maybe useful to discern acute from chronic hepatic failure or to monitor the course and the severity of the disease.

Unexpected complete recovery of a patient with severe tick-borne encephalitis treated with favipiravir.

We report a case of tick-borne encephalitis (TBE) in a 22-year-old man, who was admitted to the Medical University of Vienna hospital with severe meningoencephalitis, unresponsive and dependent on a respirator. He had given a history of a recent tick bite, but because he had previously received a full course of vaccination against TBE, West Nile virus infection was suspected. Because the antiviral drug favipiravir has been reported to be active against WNV, therapy was initiated, and continued even after a diagnosis of TBE was confirmed, due to significant improvement of symptoms. Within days, the patient's symptoms resolved, and he was discharged after complete recovery at 15 days after onset. Although this single case does not permit any conclusion as to the role of favipiravir in the favorable outcome, it suggests that the drug should be further evaluated in laboratory animal models and in appropriate clinical settings.

Glycocalyx Damage Within Human Liver Grafts Correlates With Graft Injury and Postoperative Graft Function After Orthotopic Liver Transplantation.

BACKGROUND: Destruction of the endothelial glycocalyx has been observed within lung and kidney grafts during ischemic organ preservation. We aimed to quantify glycocalyx damage within human liver grafts after organ preservation and correlate the results with graft injury and postoperative graft function in patients undergoing orthotopic liver transplantation (OLT). METHODS: Syndecan-1 (Sdc-1) was measured as indicator of glycocalyx degradation in effluents of 38 liver grafts and serum of patients undergoing OLT. Effluent Sdc-1 concentrations were correlated with hepatic injury markers from the effluent. Furthermore, we assessed the association of Sdc-1 with early allograft dysfunction (EAD), 1-year graft survival, and 1-year patient survival. RESULTS: Effluent Sdc-1 concentrations correlated with effluent concentrations of hepatocellular injury markers, including alkaline phosphatase (R = 0.543, P = 0.003), aspartate aminotransferase (R = 0.420, P = 0.029), and lactate (R = 0.574, P = 0.002). Sdc-1 effluent concentrations were greater in patients who developed EAD compared with those without EAD (4720 [4374-5133] vs 3838 [3202-4240] ng/mL, P = 0.015). Furthermore, receiver operating characteristics analyses revealed that effluent Sdc-1 concentrations (AUC = 0.82, P = 0.017) and serum Sdc-1 concentrations (AUC = 0.84, P = 0.006) were associated with the development of EAD. These results were confirmed by regression analyses. No association was found between Sdc-1 and 1-year graft survival or 1-year patient survival. CONCLUSIONS: Our data suggest that the glycocalyx is damaged within human liver grafts during preservation and the extent of glycocalyx damage correlates with the severity of hepatocellular injury. Recipients of livers grafts with greater glycocalyx damage might be at higher risk for development of EAD after OLT.

Regulation of histamine and diamine oxidase in patients undergoing orthotopic liver transplantation.

Increased concentrations of the vasodilator histamine have been observed in patients undergoing abdominal surgery. The role of histamine during orthotopic liver transplantation (OLT) has only been studied in animals. The aim of this study was to measure plasma concentrations of histamine and its degrading enzyme diamine oxidase (DAO) in patients undergoing orthotopic liver transplantation, and assess whether histamine or DAO correlate with intraoperative noradrenaline requirements. Histamine and DAO concentrations were measured in 22 adults undergoing liver transplantation and 22 healthy adults. Furthermore, norepinephrine requirements during liver transplantation were recorded. Baseline concentrations of histamine and DAO were greater in patients, who underwent liver transplantation, than in healthy individuals (Histamine: 6.4 nM, IQR[2.9-11.7] versus 4.3 nM, IQR[3.7-7.1], p = 0.029; DAO: 2.0 ng/mL, IQR[1.5-4.1] versus <0,5 ng/mL, IQR[<0.5-1.1], p < 0.001). During liver transplantation, histamine concentrations decreased to 1.8 nM, IQR[0.5-4.9] in the anhepatic phase (p < 0.0001 versus baseline), and to 1.5 nM, IQR[0.5-2.9] after reperfusion (p < 0.0001 versus baseline). In contrast, DAO concentrations increased to 35.5 ng/ml, IQR[20-50] in the anhepatic phase (p = 0.001 versus baseline) and to 39.5 ng/ml, IQR[23-64] after reperfusion (p = 0.001 versus baseline), correlating inversely with histamine. Norepinephrine requirements during human liver transplantation correlated significantly with DAO concentrations in the anhepatic phase (r = 0.58, p = 0.011) and after reperfusion (r = 0.56; p = 0.022). In patients undergoing orthotopic liver transplantation, histamine concentrations decrease whereas DAO concentrations increase manifold. Diamine oxidase correlates with intraoperative norepinephrine requirements in patients undergoing OLT.

MCP-1 and MIP3-alpha serum levels in acute liver failure and molecular adsorbent recirculating system (MARS) treatment: a pilot study.

OBJECTIVE: The CC chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-3 alpha (MIP3-alpha) may be involved in the pathogenesis of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). In ALF and ACLF, the molecular adsorbent recirculating system (MARS) has been used to support liver function. Enhancement of MCP-1, as seen in other extracorporeal support systems such as haemodialysis, might thus have mitigated the beneficial effects of the MARS system in acute hepatic failure. MATERIAL AND METHODS: Serum concentrations of MCP-1 and MIP3-alpha were measured in 10 patients with ALF or ACLF treated with MARS. Thirteen patients suffering from chronic hepatic failure (CHF) and 15 healthy individuals served as controls. RESULTS: Baseline MCP-1 serum concentrations were significantly increased in ALF and ACLF patients as compared to patients with CHF (p=0.0027 and p=0.0046, respectively) and controls (p=0.0006 and p=0.0012, respectively). MIP3-alpha serum concentrations were also significantly enhanced in the ALF and ACLF groups as compared with those in CHF patients (p=0.0002 and p=0.0003, respectively) and controls (p<0.0001 and p<0.0001, respectively). Moreover, MIP3-alpha levels were significantly increased in CHF patients as compared to controls (p=0.0002). MCP-1 and MIP3-alpha concentrations did not change significantly during MARS treatment in ALF and ACLF patients. CONCLUSIONS: The CC chemokines MCP-1 and MIP3-alpha are increased in ALF and ACLF patients. MARS had no effect on MCP-1 and MIP3-alpha serum concentrations in patients with ALF and ACLF, and yielded no evidence of any harmful effects of the increase of these potentially hepatocidal chemokines.