Thromboelastography to Monitor Clotting/Bleeding Complications in Patients Treated with the Molecular Adsorbent Recirculating System

Background. The Molecular Adsorbent Recirculating System (MARS) has been shown to clear albumin-bound toxins from patients with liver failure but might cause bleeding complications potentially obscuring survival benefits. We hypothesized that monitoring clotting parameters and bed-side thromboelastography allows to reduce bleeding complications. Methods. Retrospective analysis of 25 MARS sessions during which clotting parameters were monitored by a standardized protocol. Results. During MARS therapy median INR increased significantly from 1.7 to 1.9 platelet count and fibrinogen content decreased significantly from 57 fL−1 to 42 fL−1 and 2.1 g/L to 1.5 g/L. Nine relevant complications occurred: the MARS system clotted 6 times 3 times we observed hemorrhages. Absent thrombocytopenia and elevated plasma fibrinogen predicted clotting of the MARS system (ROC 0.94 and 0.82). Fibrinolysis, detected by thromboelastography, uniquely predicted bleeding events. Conclusion. Bed-side thromboelastography and close monitoring of coagulation parameters can predict and, therefore, help prevent bleeding complications during MARS therapy

Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study

Introduction: Critically ill cirrhosis patients awaiting liver transplantation (LT) often receive prioritization for organ allocation. Identification of patients most likely to benefit is essential. The purpose of this study was to examine whether the Sequential Organ Failure Assessment (SOFA) score can predict 90-day mortality in critically ill recipients of LT and whether it can predict receipt of LT among critically ill cirrhosis listed awaiting LT. Methods: We performed a multicenter retrospective cohort study consisting of two datasets: (a) all critically-ill cirrhosis patients requiring intensive care unit (ICU) admission before LT at five transplant centers in Canada from 2000 through 2009 (one site, 1990 through 2009), and (b) critically ill cirrhosis patients receiving LT from ICU (n = 115) and those listed but not receiving LT before death (n = 106) from two centers where complete data were available. Results: In the first dataset, 198 critically ill cirrhosis patients receiving LT (mean (SD) age 53 (10) years, 66% male, median (IQR) model for end-stage liver disease (MELD) 34 (26-39)) were included. Mean (SD) SOFA scores at ICU admission, at 48 hours, and at LT were 12.5 (4), 13.0 (5), and 14.0 (4). Survival at 90 days was 84% (n = 166). In multivariable analysis, only older age was independently associated with reduced 90-day survival (odds ratio (OR), 1.07; 95% CI, 1.01 to 1.14; P = 0.013). SOFA score did not predict 90-day mortality at any time. In the second dataset, 47.9% (n = 106) of cirrhosis patients listed for LT died in the ICU waiting for LT. In multivariable analysis, higher SOFA at 48 hours after admission was independently associated with lower probability of receiving LT (OR, 0.89; 95% CI, 0.82 to 0.97; P = 0.006). When including serum lactate and SOFA at 48 hours in the final model, elevated lactate (at 48 hours) was also significantly associated with lower likelihood of receiving LT (0.32; 0.17 to 0.61; P = 0.001). Conclusions: SOFA appears poor at predicting 90-day survival in critically ill cirrhosis patients after LT, but higher SOFA score and elevated lactate 48 hours after ICU admission are associated with a lower probability receiving LT. Older critically ill cirrhosis patients (older than 60) receiving LT have worse 90-day survival and should be considered for LT with caution

The impact of preexisting and post-transplant diabetes mellitus on outcomes following liver transplantation

Background: Diabetes mellitus (DM) is said to adversely affect transplant outcomes. The aim of this study was to investigate the impact of pre-existing and post-transplant DM on liver transplant (LT) recipients.Method: A single centre retrospective analysis of prospectively collected data of LT recipients (1990–2015) was undertaken.Results: Of the 2,209 patients, 13% (n=298) had Pre-DM, 16% (n=362) developed PTDM, 5% (n=118) developed transient hyperglycemia (t-HG) post-LT, and 65% (n=1,431) never developed DM (no DM). Baseline clinical characteristics of patients with PTDM was similar to that of patients with pre-DM. Incidence of PTDM peaked during first-year (87%) and plateaued thereafter. On multivariate analysis (Bonferroni-corrected), non-alcoholic fatty liver disease and the use of Tacrolimus and Sirolimus use were independently associated with PTDM development. Both Pre-DM and PTDM patients had satisfactory and comparable glycaemic control throughout the follow-up period. Those who developed t-HG seems to have a unique characteristic compared to others. Overall, 9%, 5%, and 8% developed end-stage renal disease (ESRD), major cardiovascular event (mCVE), and de novo cancer, respectively. Both Pre-DM and PTDM did not adversely affect patient survival, re-LT, or de novo cancer. The risks of ESRD and mCVE were significantly higher in patients with Pre-DM followed by PTDM and no DM.Conclusions: In this largest non-registry study, patients with pre-DM and PTDM share similar baseline clinical characteristics. Pre-DM increases the risk of ESRD and mCVE; however, patient survival was comparable to those with PTDM and without diabetes. Understanding the impact of PTDM would need prolonged follow-up

Outcomes of Radiofrequency Ablation as First-Line Therapy for Hepatocellular Carcinoma less than 3 cm in Potentially Transplantable Patients

© 2019 European Association for the Study of the Liver Background & Aims: Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3 cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy. Methods: We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3 cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged 2 cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria. Results: We included 301 patients (167 HCC ≤2 cm and 134 HCC >2 cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2 cm and the HCC >2 cm groups, respectively (p = 0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2 cm group vs. 93.3%, 77.6% and 70.9% in the HCC >2 cm group (p = 0.01). Tumor size >2 cm (hazard ratio 1.94; 95% CI 1.25–3.02) and alpha-fetoprotein levels at the time of ablation (100–1,000 ng/ml: hazard ratio 2.05; 95% CI 1.10–3.83) were found to be predictors of post-RFA recurrence outside Milan criteria. Conclusion: RFA for single HCC ≤3 cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA. Lay summary: Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC >2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients

Gelechiidae Moths Are Capable of Chemically Dissolving the Pollen of Their Host Plants: First Documented Sporopollenin Breakdown by an Animal

Background: Many insects feed on pollen surface lipids and contents accessible through the germination pores. Pollen walls, however, are not broken down because they consist of sporopollenin and are highly resistant to physical and enzymatic damage. Here we report that certain Microlepidoptera chemically dissolve pollen grains with exudates from their mouthparts. Methodology/Principal Findings: Field observations and experiments in tropical China revealed that two species of Deltophora (Gelechioidea) are the exclusive pollinators of two species of Phyllanthus (Phyllanthaceae) on which their larvae develop and from which the adults take pollen and nectar. DNA sequences placed the moths and plants phylogenetically and confirmed that larvae were those of the pollinating moths; molecular clock dating suggests that the moth clade is younger than the plant clade. Captive moths with pollen on their mouthparts after 2-3 days of starvation no longer carried intact grains, and SEM photographs showed exine fragments on their proboscises. GC-MS revealed cis-b-ocimene as the dominant volatile in leaves and flowers, but GC-MS analyses of proboscis extracts failed to reveal an obvious sporopollenindissolving compound. A candidate is ethanolamine, which occurs in insect hemolymphs and is used to dissolve sporopollenin by palynologists. Conclusions/Significance: This is the first report of any insect and indeed any animal chemically dissolving pollen

Characteristics of liver transplant candidates delisted following recompensation and predictors of such delisting in alcohol-related liver disease: a case-control study

Whether and when recovery beyond the need for transplant may occur in patients listed for decompensation remains unclear. This study aimed to investigate the characteristics of patients delisted following recompensation. Seventy-seven patients who were listed between 2005 and 2015 for decompensation, but later delisted following recompensation were included. Alcohol-related liver disease (ALD) was the underlying etiology in the majority (n=47, 61%). Listing characteristics of these patients were compared with those of decompensated ALD patients who either underwent deceased donor liver transplantation or died on the waiting list. The model for end-stage liver disease (MELD) score <20 and serum albumin ≥32g/l at listing were the only independent predictors of recompensation/delisting in ALD. The probability of recompensation was 70% when both factors were present at listing. Interestingly, about a tenth of decompensated ALD patients who died on the waiting list (median duration on waiting list 11 months) and a quarter of decompensated ALD patients who underwent living donor liver transplantation (median duration on waiting list 2 months) also had both factors at listing. In conclusion, ALD seems to be the most favorable etiology for recompensation beyond the need for transplantation. Both MELD and serum albumin at listing independently predict recompensation/delisting in ALD. It seems advisable to implement a period of observation for ALD patients with both favorable factors, before embarking on living donor liver transplantation

Liver transplantation is a preferable alternative to palliative therapy for selected patients with advanced hepatocellular carcinoma

Background: Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT). Materials & Methods: All patients listed in the Toronto liver transplant program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiological images were reviewed by two independent radiologists. The primary endpoint was patient survival. Results: Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p=0.02) and tumor burden (p <0.001). The majority of those listed underwent LT (n=69, 72%). Both tumor progression on waiting list (HR 4.973 [1.599 – 15.464], p=0.006) and peak AFP ≥400ng/ml (HR 4.604 [1.660 – 12.768], p=0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% (n=24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p=0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93%, 71%, and 66%. Conclusion: LT provides significantly better survival rates than palliation for patients with selected advanced HCC

Immunosurveillance of alveolar echinococcosis by specific humoral and cellular immune tests: long-term analysis of the Swiss chemotherapy trial (1976-2001).

BACKGROUND/AIMS Long-term chemotherapy with benzimidazoles is beneficial in non-resectable alveolar echinococcosis (AE). Criteria to track early therapeutic efficacy are lacking and the clinical impact of immunosurveillance is unsettled. We aimed to analyze this issue particularly for assessing the putative parasitocidal efficacy of chemotherapy. METHODS The present study is part of our prospective Swiss trial outlined previously and comprises 57 patients with a median follow-up of 18.5 (3-30) years and with repeated tests of humoral and cell-mediated immunity. The series was subdivided into group A (n=23; curative surgery) and group B (n=34: non-resectable AE). RESULTS Long-term survival was 87% (group A) and 76% (group B). The profiles of specific antibodies against EmII/3-10 antigen normalized within 3 years in most group A-patients, but remained above the cut-off value in 40% of group B-patients. This lack of normalization was associated with lower bioavailability of mebendazole. AE-recurrence after 'radical' surgery (up to 13 years) was associated with high anti-EmII/3-10 concentrations in 7 of 8 cases. Following abrogation of longterm chemotherapy in group B, no AE-recurrence occurred in 9/18 patients, suggestive of parasitocidal efficacy and documented by a normal EmII/3-10 profile. CONCLUSIONS The EmII/3-10 profile is of value in monitoring AE after surgery and/or chemotherapy