Hepatic Comorbidities Research Articles

Exclusion criteria and adverse events in perioperative trials of tranexamic acid in cardiac surgery: a systematic review and meta-analysis.

Tranexamic acid (TXA) reduces perioperative blood loss and transfusion requirement following cardiac surgery. Nevertheless, TXA remains underutilized because of concerns regarding development of adverse events. We conducted a systematic review to determine which patients are commonly excluded from TXA cardiac surgery clinical trials to determine if there are patient groups lacking safety data on TXA. The databases Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until September 2017. Eligible studies were randomized-controlled trials (RCTs) administering systemic TXA perioperatively to patients undergoing any cardiac surgery. Our primary outcome was the exclusion criteria for each RCT, and the secondary endpoint was TXA safety. A descriptive synthesis was performed to analyze the exclusion criteria. TXA safety was assessed with meta-analysis. Seventy eligible RCTs were included. The most common reasons for excluding patients from TXA cardiac surgery trials were major hepatic, renal, or cardiac comorbidities (76% of studies). Meta-analysis showed that TXA did not increase the risk of adverse events compared with placebo or no intervention (risk ratio, 0.97; 95% confidence interval, 0.88 to 1.07), including thrombosis and seizure. We found that systemic TXA is safe to use in cardiac surgery. Certain patient groups are frequently excluded from TXA cardiac surgery trials, and may consequently have limited efficacy and safety data on TXA. Further research in these patient groups may be needed; nevertheless, for many patient populations there are sufficient data to inform evidence-based guidelines for TXA use in cardiac surgery. PROSPERO (CRD42017060971); registered 4 April, 2017.

Can Physical Activity Help in Hepatitis C Treatment? A Mini Review

Hepatitis C (HCV) is a major public health problem worldwide and can lead in many cases to liver transplants. The liver condition of the patient is multifactorial, with genetic, biochemical profile immune system and lifestyle as a protagonist of such a process which has as one of the clinical outcomes hepatic fibrosis, increasing the progression of the cell subject to hepatocellular carcinoma. These parameters directly influence the fibrous framework of HCV patients that may be worsened by maintaining physical inactivity frame and biochemical profile disruption, since it favors the inflammatory and fibrogenic process. Since studies with patients with HCV and physical activity are quite scarce, they demonstrate the efficacy of physical activity on the fibrotic and hepatic condition of patients with hepatitis C virus, since this requires a prescriptive planning with quality and adequate for these individuals. Thus defining the best type of physical activity or exercise that will bring the best effects to patients with hepatitis C and other hepatic comorbidities, which can condition the lifestyle of these individuals and thus lead to better pathophysiological stages, avoiding the progression of the disease, providing an improvement of their health, and psychosocial since the physical activity and / or exercise guarantee the activation of elements linked to the neuroendocrine axis activating the secretion of endorphins guaranteeing the well-being of the patients with this pathology. Thus the objective of this review is to describe the main benefits of physical activity within the pathophysiological processes found in patients with HCV.

Characterization of Frontline Treatment Patterns and Attrition Rates According to Subsequent Lines of Therapy in Non-Transplant Patients with Newly Diagnosed Multiple Myeloma

Background: Each additional line of therapy is associated with lower rates of deeper responses, shorter durations of treatment-free intervals, and increased rates of toxicities/comorbidities in patients with multiple myeloma (MM; Yong K, et al. Br J Haematol 2016. 175[2]:252-264), all of which are factors that contribute to treatment discontinuation. In order to characterize the newly diagnosed MM (NDMM) patient population in the United States not treated with a stem-cell transplant based on the number of subsequent lines of therapy (LOT) received, we examined baseline patient characteristics and pre-existing comorbidities, frontline treatment patterns, and attrition rates for these patients according to whether subsequent LOT was received or not received.Methods: NDMM patients were identified from 3 US patient-level data sources: the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked database (from January 2007 through December 2014), the OPTUM™ Commercial Claims database (from January 2000 through March 2017), and the OPTUM™ Electronic Medical Records (EMR) database (from January 2007 through March 2016). Patients included in the assessment had 1) an index diagnosis of MM on or after 1 January 2007, 2) known gender, 3) medical prescription coverage in place at diagnosis, 4) a 1-year look-back period prior to the index diagnosis, 5) no prior malignancies in the 1-year period prior to index diagnosis, and 6) received ≥1 LOT. The analysis was limited to patients who did not receive stem cell transplantation at any time during their follow-up. Descriptive and logistic regression analyses were conducted to characterize and compare patients who received or did not receive a subsequent LOT.Results: The analysis included a total of 7,724 patients (1 LOT only: n = 3,906; 2+ LOT: n = 3,818). A summary of baseline patient characteristics and pre-existing comorbidities by LOT is summarized in Table 1. Patients who received a subsequent LOT vs those that did not were significantly younger (median age 72.0 vs 74.0 years; P <0.0001) and had significantly lower mean Charleston Comorbidity Index (CCI) score due to lower occurrence of renal, cardiac, and hepatic comorbidities (Table 1). Older age at diagnosis and presence of renal, congestive heart failure (CHF), hepatic, and pulmonary comorbidities were associated with higher attrition.The regimens used in frontline treatment included bortezomib/dexamethasone (26%), lenalidomide/dexamethasone (21%), bortezomib/lenalidomide/dexamethasone (11%), a bortezomib/alkylator ± steroid combination (6%), bortezomib monotherapy (10%), lenalidomide monotherapy (6%), thalidomide monotherapy (4%), and other (17%).The proportions of patients progressing to each subsequent line of therapy are shown in Table 2. In total, 49% of patients went on to receive a second line of therapy, and 55% of patients receiving a second line of therapy went on to receive a third line of therapy. The incidence of patients not receiving subsequent lines of therapy due to death or being lost to follow up by LOT is summarized in Table 2.Conclusions: A majority of non-transplant patients with NDMM in the study did not progress to subsequent lines of therapy, with attrition as high as 50% per line of therapy and only <8% of patients reaching LOT 5. This high level of attrition is associated with older age and poor comorbidity status of non-transplant patients with NDMM. Therefore, utilizing the most optimal regimens upfront (rather than reserving them for later lines) is warranted. [Display omitted] DisclosuresFonseca:Mayo Clinic: Employment; Amgen: Consultancy. Usmani:Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy; Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding. Mehra:Janssen Global Services, LLC: Employment. Slavcev:Janssen Global Services, LLC: Employment. Ukropec:Janssen Scientific Affairs, LLC: Employment. Lam:Janssen Global Services, LLC: Employment. Potluri:SmartAnalyst Inc.: Employment.

Impact of Individual Comorbidities on Treatment Outcomes in Chronic Lymphocytic Leukemia

Introduction: Chronic lymphocytic leukemia (CLL) is a common leukemia which tends to occur late in life. Comorbidities are common, and the iwCLL guidelines recommend their assessment in patients (pts) enrolled on clinical trials. The Cumulative Illness Rating Scale (CIRS) is a rigorous tool designed to evaluate the burden of comorbidities, which has been employed in therapeutic studies. Our group and others demonstrated that CIRS score predicts survival in pts with CLL treated with either chemo-immunotherapy (CIT) or novel kinase inhibitors (KI; ibrutinib) (Manda et al, 2016 & Gordon et al, 2018). However, CIRS has not become part of common clinical practice, in part due to complexities in scoring. It is also unknown whether all of the 14 organ systems included in the score carry equal weight to determine prognosis. Here we report the impact of specific comorbidities from a multicenter retrospective cohort of CLL pts treated with either CIT or KI. Methods: We conducted a retrospective analysis of pts with CLL treated at five US academic medical centers between 2000 and 2017. CIRS score was calculated as in Salvi et al, 2008. Random forest (RF) was used to assess specific comorbidities9 impact on overall survival (OS) and event-free survival (EFS, defined as time to new therapy, disease progression or death). We adapted two separate approaches to investigate the RF variable selection process: variable Importance (VIMP), a property related to variable misspecification, and Minimal Depth (MD), a property derived from the construction of trees within the forest. Best variables were those selected consistently as top 3 in both VIMP and MD on the 500 RF repetitions. Because hepatic and renal comorbidities were rare they were excluded. OS and EFS were assessed by Kaplan-Meier estimates and Cox proportional hazard model adjusted for performance status and age. Significance was assessed with log-rank test. Results: 398 pts were included in the final analysis. The median age was 63 years (range, 30-93). 50% of pts (n=198) had a high CIRS score (≥7). 184 pts (46%) had comorbidities assessed in relapsed setting. For all pts, the most common treatments included ibrutinib (n=145; 37%), fludarabine-containing regimens (n=104; 26%) and bendamustine (n=39; 10%). Complex karyotype was observed in 3.5% (n=14) and 10.6% (n=42) of pts had del(17p). Pts with comorbidities (CIRS ≥7) demonstrated shortened survival following therapy, with 5-year OS of 64% vs 89% (p Random forest variable selections identified vascular comorbidities (e.g. DVT/PE) as the most influential risk factor for OS with CIT treatment, while HEENT and cardiac comorbidities were most impactful to OS for patients treated with KI. For EFS, the most influential comorbidities were cardiac and vascular for the CIT treatment group and endocrine and HEENT for patients treated with KI. Across EFS and OS, the most frequently selected variables in CIT were cardiac, hypertension, vascular and neurologic. We constructed a simplified scoring system assigning 1 point for each category. Comparing scores of 0, 1 and 2-4 (n=100, n=82, n=60), 5-year OS was 87%, 82% and 66%, respectively (p Conclusion: Comorbidities impact survival in CLL whether treated with CIT or KI. Which comorbidities are most prognostic may vary by treatment type. Vascular and cardiac comorbidities appear to be the most relevant in CLL pts treated with CIT. Meanwhile, cardiac, endocrine and HEENT had greater impact when pts were treated with KI. A simplified CIRS score is predictive of outcomes in both treatment subgroups. Disclosures Choi:Gilead: Speakers Bureau; AbbVie, Inc: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Rigel: Consultancy; Genentech: Speakers Bureau. Cohen:Takeda: Research Funding; Pharmacyclics: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; AbbVie: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity9s Board of Directors or advisory committees; BioInvent: Consultancy. Persky:Genentech: Honoraria; Morphosys (IDMC): Consultancy; Spectrum: Research Funding; Merck: Research Funding. Danilov:Aptose Biosciences: Research Funding; Verastem: Consultancy, Research Funding; Astra Zeneca: Consultancy; Gilead Sciences: Consultancy, Research Funding; Takeda Oncology: Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Bayer Oncology: Consultancy, Research Funding.

Prognostic significance of serum γ-glutamyltransferase in patients with advanced urothelial carcinoma

ObjectivesSerum γ-glutamyltransferase (GGT) is reportedly associated with prognosis in patients with various malignancies. However, the prognostic role of GGT is unknown among patients with advanced urothelial carcinoma (aUC). This study was designed to examine the prognostic role of serum GGT in patients with aUC. Materials and methodsCharts of 125 consecutive aUC patients (inoperable cT4 and/or metastasis to lymph nodes/distant organs) managed at a single cancer center between 2004 and 2016 were retrospectively reviewed. Variables collected included age, sex, body mass index, Karnofsky performance status, primary site, clinical tumor stage, lymph node/visceral metastasis, hepatic comorbidities, the presence of curative treatment before the diagnosis of aUC, white blood cell count, neutrophil-to-lymphocyte ratio, hemoglobin, albumin, lactate dehydrogenase, alkaline phosphatase, GGT, C-reactive protein, and treatments given after the diagnosis of aUC. Associations of variables with overall survival (OS) were analyzed using the Cox proportional hazard model. ResultsSerum GGT was elevated (≥60 U/l) at the diagnosis of aUC in 16 patients (13%). During follow-up period (median 12.1 months), 101 patients died (2-year OS rate, 32%). Patients with elevated GGT at the diagnosis of aUC had a significantly poorer prognosis than those with normal GGT with respective 2-year OS rates of 0% and 37% (P < 0.001). On multivariate analysis, elevated GGT was a significant and independent risk factor for shorter OS (hazard ratio, HR = 2.97; P < 0.001) as were poorer Karnofsky performance status (HR = 3.47; P < 0.001), elevated lactate dehydrogenase (HR = 1.86; P = 0.033), advanced age (HR = 1.82; P = 0.013), elevated neutrophil-to-lymphocyte ratio (HR = 1.80; P = 0.015), elevated C-reactive protein (HR = 1.73; P = 0.018), the absence of systemic chemotherapy (HR = 1.71; P = 0.035), and primary site of upper urinary tract (HR = 1.71; P = 0.014) in descending order by HR. The prognostic significance of elevated GGT was also observed in a subset of 101 patients who had been diagnosed with aUC at their first presentation. ConclusionThe present study for the first time demonstrated that elevated serum GGT was an independent adverse prognostic factor in aUC patients.

Treating Hepatic Steatosis and Fibrosis by Modulating Mitochondrial Pyruvate Metabolism.

A hepatic comorbidity of metabolic syndrome, known as nonalcoholic fatty liver disease (NAFLD), is increasing in prevalence in conjunction with the pandemics of obesity and diabetes. The spectrum of NAFLD ranges from simple hepatic fat accumulation to a more severe disease termed nonalcoholic steatohepatitis (NASH), involving inflammation, hepatocyte death, and fibrosis. Importantly, NASH is linked to a much higher risk of cirrhosis, liver failure, and hepatocellular carcinoma, as well as an increased risk for nonhepatic malignancies and cardiovascular disease. Interest in the understanding of the disease processes and search for treatments for the spectrum of NAFLD-NASH has increased exponentially, but there are no approved pharmacologic therapies. In this review, we discuss the existing literature supporting insulin-sensitizing thiazolidinedione compounds as potential drug candidates for the treatment of NASH. In addition, we put these results into new context by summarizing recent studies suggesting these compounds alter mitochondrial metabolism by binding and inhibiting the mitochondrial pyruvate carrier.

Long Term Mortality in Young Patients (&lt;40 y/o) With Alcoholic Liver Cirrhosis After First Hospitalization: Carilion Clinic Experience

Introduction: Long term mortality in young patients after their first hospitalization for alcoholic liver disease (ALC) is not well established. We aimed to evaluate the long term outcomes among young subjects with ALC after their first related hospitalization in a tertiary referral academic center. Methods: We searched the EPIC EMR and identified all patients hospitalized for ALC at Carilion Clinic, Roanoke from 2008-2016, and review outcomes through 6/2018. Information on demographics, comorbidities, lab values, procedures, and mortality were extracted. Cumulative risks of long-term mortality after the first hospitalization were estimated using Kaplan-Meier curves and compared between two groups; those 40 years of age. Demographic data, lab values, and comorbidities associated with cirrhosis were assessed using multivariate Cox proportional hazard analysis to determine risk factors associated with long-term mortality. Results: We identified Sixty-five young patients out of a total of 325 patients admitted for the first time for ALC (mean age, 34.6±4.7 years; 72.3% males, 48.4% current alcohol use, 67.2% current smokers, 15.8% current illicit drugs use). Seven (10.8%) had biopsy-proven ALC, others were diagnosed clinically. Over a mean follow-up of 1.3±2.0 years, twenty patients (30.8%) died. The mean number of hospitalizations was 2.3±2.2. The 1-, 3- and 5-years cumulative mortality was 21.1 %, 31.1% and 49.7% respectively. The median survival for young patients was longer as compared old patients (p<0.001); this was likely related to extra hepatic comorbidities. Mortality in those younger than 40 was lower than in older patients (P less than 0.001). On multivariate Cox proportional hazard analysis (HR), increased age (HR 1.04; 95% CI, 1.02-1.06), neutrophils-to-lymphocytes ratio (NLR) (HR 1.02; 95% CI, 1.001-1.038), and initial MELD score (HR 1.14; 95% CI, 1.08-1.21) were found to be associated with long-term mortality. Current tobacco (HR 1.07, p=0.08) and alcohol use (HR 1.23, p=0.09) were not found to be risk factors for long-term mortality. Conclusion: 5-year cumulative mortality for patients younger than 40 years of age with ALC after their first hospitalization is 49.7% despite quitting drinking in about 50% of the patients. Old age, most recent NLR, and initial MELD score were associated with increased risk for late mortality.

Short Term Mortality in Young Patients (&lt;40 y/o) With Alcoholic Liver Cirrhosis After First Hospitalization: Carilion Clinic Experience

Introduction: Alcoholic liver cirrhosis (ALC) is increasingly diagnosed in young patients. Liver transplantation (LT) in these cases remains highly controversial, while the mortality of young patients after their first hospitalization for ALC is not well established. we aimed to evaluate the short term outcomes among young subjects with ALC after their first related hospitalization in a tertiary referral academic center. Methods: We searched the EPIC EMR and identified all patients hospitalized for ALC at Carilion Clinic, Roanoke from 2008-2016. All available data was analyzed looking at 3-month outcomes. Information on demographics, comorbidities, lab values, procedures, and mortality were extracted. The cumulative risk of mortality in the first 3 ± 1 months after hospitalization were estimated using Kaplan-Meier curves and compared between two groups; those 40 years of age. Demographic data, lab values, and associated comorbidities were assessed using multivariate Cox proportional hazard analysis (HR) to determine risk factors associated with short-term mortality. Results: We identified Sixty-five young patients out of a total of 325 patients admitted for the first time for ALC (mean age 34.6±4.7 years; 72.3% males, 48.4% current alcohol use, 67.2% current smokers, 15.8% current illicit drugs users). Seven (10.8%) had biopsy-proven ALC and the rest were diagnosed clinically. Over a median (interquartile range) follow-up of 2.4 months (0.24-3.24), nine (13.8%) died. The 1 and 3 months cumulative mortality after first hospitalization was 3.1 %, and 14.6% respectively. Mortality in those younger 40 years old was lower than in older patients (P less than 0.001); this was likely related to extra hepatic comorbidities in older patients. On multivariate Cox proportional hazard analysis, hepatic encephalopathy (HR 2.53; 95% CI, 1.36-4.89), and the presence of ascites (HR 2.07; 95% CI, 1.12-3.96) were associated with increased risk of early mortality. Current tobacco (HR 1.07, p=0.08), drug use (HR 1.66, p=0.197), alcohol use (HR 1.23, p=0.09), older age (HR 1.03; 95% CI, 1.01-1.06) and MELD score on admission (HR 1.07; CI, 1.01-1.12) were not found to be risk factors for short-term mortality. Conclusion: Short-term mortality for patients younger than 40 years of age with ALC after their first hospitalization is 14%, which is lower than the mortality for older patients. Hepatic encephalopathy and ascites seem to significantly impact mortality.

Biomarkers in follow-up treatment of alcoholism with hepatic comorbidity. An observational study

The aim of this paper is the evolution of the biological markers and of alcoholism when the patient diagnosed with alcoholism is undergoing detox treatment. After detox, the biological markers of alcoholism undergo changes as the patient undergoes treatment. As a result of the successive visits for the detox treatment from alcohol, correlations were identified between GGT, GPT and GOT values in the group of patients diagnosed with alcoholism, as well as in the group of the patients with alcoholism and associated hepatopathy. The study aims to investigate a group of patients diagnosed with alcoholism that undergo the detox treatment and the manner in which the biological markers evolve in the case of the patients with alcoholism and associated hepatopathy. The results of the study will be capitalized in the form of a statistical and mathematical model so that clinicians can establish strategies for therapeutic approach for patients with relapses in alcoholism and hepatopathy associated to alcoholism.

Depression, fatigue and neurocognitive deficits in chronic hepatitis C.

Patients with chronic hepatitis C virus (HCV) infection experience a range of symptoms including depression, fatigue and neurocognitive deficits, impairing quality of life. Depression, in particular, may be reactive to increased psychosocial stress, and the physical symptoms of advanced HCV or associated comorbidities. However, even patients at an early stage of HCV infection, with minimal hepatic inflammation or comorbidities, report more depressive symptoms and fatigue than the general population. Similarly, specific neurocognitive deficits occur in early stage HCV infection and are independent of the presence of depression or encephalopathy. Therefore, intracerebral neurobiological changes associated with HCV may potentially explain these symptoms. These changes may arise from infiltration of the brain by peripherally induced cytokines, as well as direct neuropathic effects of HCV viral particles penetrating the blood-brain barrier. These phenomena parallel those reported in human immunodeficiency virus (HIV) infection. HCV-associated intracerebral changes include upregulated inflammatory responses, altered neurotransmitter levels, hormonal dysregulation, and release of neurotoxic substances. These may subsequently lead to abnormal neuronal conduction and function in areas of the brain governing affective responses, emotional processing, motivation, attention and concentration. Although direct-acting antiviral medications lead to high rates of HCV clearance, intracerebral changes may not be subsequently reversed and symptoms of depression, fatigue and neurocognitive deficits may persist. There is an ongoing role for multidisciplinary care and pharmacotherapy to manage these symptoms in HCV patients. Furthermore, there may be opportunities for future therapies to specifically target and ameliorate HCV-associated intracerebral changes.

FRI-523 - Independent cohort validation of hepatic metabolism, daily dose and comorbidities as features associated with delayed symptom onset in drug-induced liver injury

FRI-523 - Independent cohort validation of hepatic metabolism, daily dose and comorbidities as features associated with delayed symptom onset in drug-induced liver injury

Acute Complications After High-Dose Chemotherapy and Stem-Cell Rescue in Pediatric Patients With High-Risk Neuroblastoma Treated in Countries With Different Resources.

PurposeHigh-dose chemotherapy with autologous stem-cell rescue (SCR) is a key component of high-risk neuroblastoma (HRNB) therapy. Carboplatin, etoposide, and melphalan (CEM) or busulfan and melphalan (Bu/Mel) are the most evaluated, effective high-dose chemotherapy for HRNB on the basis of results from major cooperative group studies. Toxicity profiles vary between these regimens, and practice variation exists regarding the preferred high-dose therapy (HDT). We sought to evaluate the safety of HDT and autologous SCR for HRNB in a resource-limited country (Egypt) compared with the resource-rich United States.Patients and MethodsWe performed a retrospective comparative review of single CEM-based HDT/SCR outcomes through day 100 for HRNB at the Fred Hutchinson Cancer Research Center (FH) in the United States (2005 to 2015) versus Bu/Mel-based HDT at El-Sheikh Zayed Specialized Hospital (SZ) in Egypt (2009 to 2015).ResultsForty-four patients at FH and 77 patients at SZ were reviewed. Pretransplant hepatic comorbidities were significantly higher at SZ (29 of 77 v nine of 44; P = .05), with 19 of 77 patients at SZ having hepatitis infection. Engraftment was delayed after SZ-Bu/Mel therapy compared with FH-CEM therapy for neutrophils (median 12 days v 10 days, respectively; P < .001) and platelets (median 20 days v 18 days, respectively; P < .001). Sinusoidal obstruction syndrome occurred later, after SZ-Bu/Mel therapy (median 19 days v 7 days; P = .033), and four of eight cases were fatal (six of eight patients had underlying hepatitis infection), whereas three of three cases after FH-CEM therapy were moderately severe. Resource utilization associated with the number of days with fever, antibiotic use, and the number of transfusions administered was significantly higher after FH-CEM therapy than after SZ-Bu/Mel therapy.ConclusionUse of autologous stem-cell transplantation is feasible in the context of a resource-limited country.

Computational Modeling in Liver Surgery.

The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.

Effects of cyclic parenteral nutrition on parenteral-associated liver dysfunction parameters

IntroductionOne of the most common complications of parenteral nutrition (PN) is liver dysfunction (LD). Therapeutic approaches for LD include, among others, administering cyclic parenteral nutrition (cPN), allowing some hours for metabolic rest. The purpose of this study was to evaluate the effectiveness of cPN in treating PN-associated LD.Materials and methodsA retrospective observational study was carried out at the Costa del Sol Hospital in Spain between 2013 and 2014. The study involved inpatients ≥18 years old prescribed with cPN due to the development of PN-associated LD. The hepatic biochemical parameters measured at baseline and after completion of cPN included aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP) and total bilirubin (TB). Quantitative values (age, biochemical parameters) were compared using matched Student’s t-test; the mean change in qualitative variables (sex, indication of PN, hepatic comorbidities, presence of insulin in cPN, infection during cPN, management of LD prior to cPN administrarion) was estimated using Mann-Whitney U test, and bivariate correlation between quantitative variables was determined by Spearman’s coefficient of correlation.ResultsThirty-seven patients met inclusion criteria. All hepatic function parameters except ALP improved after the administration of cPN, with statistically significant differences (p < 0.05) in AST GGT and TB.ConclusioncPN improves PN-associated LD by restoring abnormal AST, GGT, and BT levels to normal, and reducing ALT levels close to normal. The results obtained suggest that the administration of cPN is effective in reverting PN-associated LD.

Hepatic comorbidity in psychiatry. A case report

IntroductionComorbidity between mental and physical illnesses is very common and their possible interactions must always be taken into account. Hepatic disorders in particular, can affect the blood levels of antipsychotic drugs altering their effects on patients. Therefore, it is very important to assess in each case which treatment might be the most beneficial for the patient to avoid iatrogenic complications.AimTo review articles in Pub-Med and UpToDate about the possible iatrogenic complications that can arise using antipsychotic drugs in patients with hepatic disorders.MethodsWe describe the case of a 52-year-old male with Schizophrenia who was diagnosed of HCV infection ten years ago, for which he rejected any kind of treatment due to delirious ideation. In the past he was treated with oral Paliperidone with good tolerance, which he discontinued because of pour insight and stopped attending Psychiatric consultation. In April 2016 the patient was hospitalised suspecting a hepatocellular carcinoma.ResultsDuring hospitalization he began treatment with long-acting injectable formulation of Paliperidone Palmitate that improved his insight. The patient agreed to perform the necessary tests to verify the suspected diagnosis, which was sadly confirmed. He achieved psychopathological stability, but unfortunately the patient died 6 months later because of his hepatocellular carcinoma.ConclusionsPaliperidone is a good therapeutic option in patients with hepatic disorders because it is not metabolised by the liver. It also has a depot formulation that improves adherence in patients with low insight, reducing the danger of future psychotic decompensation and improving the long-term prognosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Diagnosis of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) with or without Multi-Organ Dysfunction (MOD) after Hematopoietic Stem Cell Transplantation (HSCT): Analysis of a Multicenter Chart Review

Background: VOD/SOS, a potentially life-threatening complication of HSCT conditioning, has historically been diagnosed using modified Seattle criteria (≥2 of: bilirubin >2 mg/dL, hepatomegaly, or >2% weight gain [sometimes >5%]) or Baltimore criteria (bilirubin ≥2 mg/dL and ≥2 of: hepatomegaly, ascites, ≥5% weight gain); the European Society for Blood and Marrow Transplantation proposed new adult criteria in 2016. VOD/SOS with multi-organ dysfunction (MOD) may be associated with >80% mortality. This chart review characterizes VOD/SOS diagnosis patterns.Methods: Physicians performed ≥5 transplants/year in accredited centers listed by the Center for International Blood and Marrow Transplant Research, and provided data from the most recent 1-3 patients with VOD/SOS (with or without MOD) post-HSCT diagnosed in the past 3 years. MOD was defined by renal failure (creatinine clearance 3´ baseline), pulmonary failure (mechanical ventilation, oxygen requirement, or saturation <90%), or heart failure.Results: 200 charts were identified, most at centers participating in a VOD/SOS drug-treatment protocol. 8 charts had missing data, leaving 192 (125 adults and 67 pediatric patients [≤17 years]). Prespecified VOD/SOS risk factors (most common: ≥2 chemotherapy regimens, Karnofsky score <85, second remission, and hepatic comorbidity) were generally more frequent in adults than pediatric patients. Most adult and pediatric patients were reported to have had myeloablative conditioning (MAC; 74% and 65%, respectively) vs reduced-intensity conditioning/autologous HSCT (RIC; 26% and 35%, respectively). In adults, diagnostic ultrasound was used in 90% and biopsy in 29%, typically on the day of VOD/SOS diagnosis. However, patients were diagnosed with VOD/SOS even though 31% and 19% of the respective tests did not confirm VOD/SOS.At diagnosis, 48% of adult and 51% of pediatric patients exceeded minimums for both ≥5% weight gain and ≥2 mg/dL bilirubin components of Baltimore criteria; by modified Seattle criteria, 62% of adults and 51% of pediatric patients exceeded >2% weight and >2 mg/dL bilirubin components (Figure). Adults had higher laboratory values at diagnosis, while pediatric patients generally had more clinical symptoms (Table).MOD was identified in 54% of adult and 69% of pediatric VOD/SOS patients, and these patients generally had greater clinical and laboratory burden than patients without MOD. MOD was more common among patients receiving RIC (65%) than MAC (57%). Bilirubin and weight gain at diagnosis and at peak were higher in patients with vs without MOD (Table). The increase in bilirubin level between the day before diagnosis and day of diagnosis was generally higher in patients with MOD, although rate of weight gain was similar between adult MOD and non-MOD groups.Conclusion: In this study, many patients' signs at diagnosis had progressed beyond VOD/SOS diagnostic criteria. Overall, adults were diagnosed later in disease progression than pediatric patients. Patients with MOD generally had earlier occurrence and higher, more rapidly rising levels of markers at diagnosis: an observation that may aid early identification of MOD. Interestingly, patients with VOD/SOS who received RIC vs MAC had higher rates of MOD. Together, these findings may help in prompt diagnosis of VOD/SOS, which may improve patient outcomes.Support: Jazz Pharmaceuticals [Display omitted] [Display omitted] DisclosuresDoede:Jazz Pharmaceuticals: Employment, Equity Ownership. Viddam:Jazz Pharmaceuticals: Employment, Equity Ownership. Villa:Jazz Pharmaceuticals: Employment, Equity Ownership. Hannah:Jazz Pharmaceuticals: Consultancy. Weaver:Jazz Pharmaceuticals: Consultancy. Tappe:Jazz Pharmaceuticals, Inc.: Employment, Other: stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc.

PRM71 - Prediction Of Costs Associated With The Hospital Management Of Hiv Patients In France Using An Advanced Data Mining Approach On The French Medical Information System Database

The PMSI (medical information system database) is the French national administrative database containing medical information and patients’ features for millions of hospital stays. Most medical studies only use descriptive methods to analyze patient cohorts. The objective of this study is to assess the capability of an innovative Data Mining algorithm to discover hidden values in health data and to bring a better understanding of diseases. We applied the approach to predict the costs associated to HIV patients’ hospital management. We only selected hospital stays with an HIV code, HIV being the principal cause of hospitalization or not. Patients hospitalized with an HIV code in 2013 were extracted and followed up for one year. 10 groups of comorbidities and 5 types of opportunistic infections (OIs) linked to HIV were also identified, and their presence was tracked among these patients. Data were analyzed with an Enhanced Decision Tree technique, in order to explain HIV hospitalization costs depending on non-linear combinations of age, gender and the presence of comorbidities or OIs. 30,294 patients with 70,180 hospital stays were included, for a total cost of 180 million euros. Our Enhanced Decision Tree was able to determine 165 different patient profiles, created automatically to maximize the gathering of patients with similar features. The most discriminative variables for the cost of hospitalization were infections not associated to HIV, bacterial OI, cancer, fungal infections and endocrino-metabolic complications, whereas age, psychiatric or hepatic comorbidities were not discriminative. The annual average cost per patient profiles ranged from €1,680 to €42,650. This exploratory study shows that Enhanced Decision Trees are relevant to identify patient profiles from big databases and may have predictive capabilities. It could help identifying leverages to prevent hospitalizations costs. Further research should be done, adding therapeutic and biological parameters.

Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study.

BackgroundApproval of drugs in chronic hepatitis C is supported by registration trials. These trials might have limited generalizability through use of strict eligibility criteria. We compared effectiveness and safety of real world hepatitis C patients eligible and ineligible for registration trials.MethodsWe performed a nationwide, multicenter, retrospective cohort study of chronic hepatitis C patients treated in the real world. We applied a combined set of inclusion and exclusion criteria of registration trials to our cohort to determine eligibility. We compared effectiveness and safety in eligible vs. ineligible patients, and performed sensitivity analyses with strict criteria. Further, we used log binomial regression to assess relative risks of criteria on outcomes.ResultsIn this cohort (n = 467) 47% of patients would have been ineligible for registration trials. Main exclusion criteria were related to hepatic decompensation and co-morbidity (cardiac disease, anemia, malignancy and neutropenia), and were associated with an increased risk for serious adverse events (RR 1.45–2.31). Ineligible patients developed significantly more serious adverse events than eligible patients (27% vs. 11%, p< 0.001). Effectiveness was decreased if strict criteria were used.ConclusionsNearly half of real world hepatitis C patients would have been excluded from registration trials, and these patients are at increased risk to develop serious adverse events. Hepatic decompensation and co-morbidity were important exclusion criteria, and were related to toxicity. Therefore, new drugs should also be studied in these patients, to genuinely assess benefits and risk of therapy in the real world population.

Myeloid-derived suppressor cells are elevated in patients with psoriasis and produce various molecules

Psoriasis is a debilitating chronic inflammatory disease. In addition to the characteristic effects on the skin, chronic inflammation associated with the disease is recognized to contribute to cardiovascular, hepatic and renal comorbidities. Immature myeloid regulatory cells, known as myeloid-derived suppressor cells (MDSCs), have been demonstrated to accumulate in various diseases and chronic inflammatory states, including inflammatory bowel disease and various types of cancer. The results of the present study, obtained using flow cytometry and cell culture analysis of peripheral blood mononuclear cells from psoriasis and healthy patients, revealed that MDSC levels are significantly increased in the blood of patients with psoriasis compared with healthy controls. Furthermore, these cells are capable of producing various molecules, including matrix metalloproteinase-9 and-1, interleukin-8, growth-related oncogene, and monocyte chemoattractant protein 1. These molecules may recruit additional immune cells involved in the pathogenesis of the disease, and contribute to the chronic inflammatory state in these patients. Therefore, MDSCs, which have various immune regulatory functions, may contribute to the pathogenesis of psoriasis as a systemic inflammatory disease.

Bradycardia Associated with Steroid Use for Laryngeal Edema in an Adult: A Case Report and Literature Review.

Steroids are used for specific indications in the perioperative period to reduce laryngeal or spinal cord edema, or for prophylaxis and treatment of postoperative nausea and vomiting. Given the other potential causes for hemodynamic alterations in the perioperative setting, it is important for physicians to be aware of cardiovascular side effects of short term steroids. Changes in blood pressure and heart rate, cardiac dysrhythmias, and even death have been described in patients receiving short term intravenous steroids. Bradycardia has been reported following short term methylprednisolone and dexamethasone therapy in both adult and pediatric patients. There are only two case reports in the literature of bradycardia following short term intravenous dexamethasone use in adult patients. This is the first case report that describes bradycardia following the use of dexamethasone in the postoperative setting for management of laryngeal edema in an adult. Telemetry and twelve lead electrocardiograms revealed sinus bradycardia and correlated directly with administration of dexamethasone in our patient. Bradycardia resolved following discontinuation of dexamethasone. We advocate for hemodynamic monitoring in patients receiving more than one dose of intravenous steroid therapy in the perioperative period, especially those with known cardiac and hepatic comorbidities and those taking medications with negative chronotropic effects.