Assessment of Right-Sided Heart Failure in Patients with Dilated Cardiomyopathy using Magnetic Resonance Relaxometry of the Liver.

In non-ischemic dilated cardiomyopathy (DC) patients at risk of developing right heart failure (RHF), early depiction of congestive heart failure (CHF) is pivotal to inform about the hemodynamic status and tailor medical therapy. We hypothesized increased liver relaxation times measured at routine cardiovascular magnetic resonance (CMR), reflecting passive hepatic congestion, may be a valuable imaging biomarker to depict congestive heart failure. The study cohort consisted of DC patients with LV dysfunction (i.e., ejection fraction <35%) with (n = 48) and without (n = 46) right ventricular dysfunction (RVD), defined as a right ventricular ejection fraction <35%, and >45%, respectively, and a control group (n = 40). Native T1, T2, and extracellular volume (ECV) liver values were measured on routinely acquired cardiac maps. DC+RVD patients had higher C-reactive protein, troponin I and NT-pro BNP values, and worse LV functional parameters than DC-RVD patients (all p <0.001). T1, T2 and ECV Liver values were significantly higher in DC+RVD compared to DC-RVD patients and controls, that is, T1: 675 ± 88 ms verses 538 ± 39 ms and 540 ± 34 ms; T2: 54± 8 ms versus 45 ± 5 ms and 46 ± 4 ms; ECV: 36 ± 7% versus 29 ± 4% and 30 ± 3% (all p <0.001). Gamma-glutamyltranspeptidase (GGT) correlated moderately but significantly with native T1 (r2 = 0.34), T2 (r2 = 0.27), and ECV liver (r2 = 0.23) (all p <0.001). Using right atrial (RA) pressure, as surrogate measure of RHF (i.e., RA pressure >5 mm Hg), native T1 liver yielded at ROC analysis the highest area under the curve (0.906), significantly higher than ECV liver (0.813), GGT (0.806), T2 liver (0.797), total bilirubin (0.737) and alkaline phosphatase (0.561)(p = 0.04). A T1 value of 617 ms yielded a sensitivity of 79.5% and specificity of 91.0% to depict RHF. Excellent intra-/inter-observer agreement was found for assessment of native T1/T2/ECV liver values. In conclusion, in DC patients, assessment of liver relaxation times acquired on a cardiovascular magnetic resonance exam, may provide valuable information with regard to the presence of RHF.

Assessment of pretreatment albumin-bilirubin grade in pancreatic cancer patients with liver metastasis.

PURPOSE: This study aimed to assess the effect of pretreatment albumin-bilirubin (ALBI) score on treatment outcomes in pancreatic cancer (PC) patients with liver metastasis at the time of diagnosis treated with chemotherapy (CT) in the first-line setting. METHODS: This was a retrospective study of 273 PC patients ≥18 years of age who had liver metastasis at the time of diagnosis and received CT in the first-line. ALBI score was calculated through the following formula; [(log10 bilirubin (µmol/L)×0.66)+[albumin(g/l)×-0.0852]. Patients were stratified into 3 categories based on the ALBI score as follows; grade I:ALBI ≤-2.60, grade II:-2.60-1.39. RESULTS: A total of 273 patients, [180 (65.9%) men and 93 (34.1%) women], were evaluated. The median age was 60 years. ALBI grade was I in 45 (16.4%) patients, II in 156 (57.1%) patients, and III in 72 (26.5%) patients. Based on the ALBI grade, median progression-free survival (mPFS) was 9 months in grade I patients, 6 months in grade II patients, and 4 months in grade III patients (p=0.002), with median overall survival (mOS) durations of 12 months vs. 8 months vs. 5 months, respectively (p<0.001). Multivariate analysis showed that ALBI grade II (HR,1.543) or III (HR,2.260) negatively affected survival. CONCLUSION: A higher pretreatment ALBI grade is related to worse OS and PFS in PC patients with liver metastasis treated with a first-line CT, and therefore it can help predict the treatment outcomes in these patients.

In vitro and in vivo toxicity assessment of biologically synthesized silver nanoparticles from Elaeodendron croceum.

Background The cytotoxic properties of nanoparticles have attracted a great deal of attention in the field of nanoscience and nanotechnology due to their small size and ability to penetrate cellular membranes. Methods The silver nanoparticles were synthesized using Elaeodendron croceum stem bark and characterized. The oral acute toxicity studies were carried out by administration of 500, 1000, 2000 mg/kg body weight to Wister rats in respective groups. An in vitro cytotoxicity assay was evaluated in MDA-MB-231 breast cancer cells using the WST-1 Cell Proliferation assay. The percentage of cell viability after treatment with aqueous extracts of Elaeodendron croceum (ECE) and Elaeodendron croceum silver nanoparticles (ECAgNPs) was compared with that of paclitaxel. Results The in vivo studies revealed that the LD50 was higher than 2000 mg/kg and there was no significant difference (p>0.05) between the treatment groups compared with the control group for mean organ-to-body weight ratio except in the liver and in all hematological parameters except WBC and hematocrit. Similarly, there was no significant difference (p>0.05) for serum electrolytes (Na+, Mg2+ K+, Cl-, and Ca2+), total protein, urea, É£-glutamyl transferase (GGT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), albumin, total and conjugated bilirubin between the treatment and the control group. However, there were changes in creatinine, urea, and cholesterol. In the in vitro assays, ECE and ECAgNPs showed IC50 values of 70.87±2.99 and 138.8±3.98 µg/mL respectively against MDA-MB-231 cells compared to paclitaxel, which showed an IC50 value of 80 ng/mL. Conclusion The results showed that the LD50 of the ECE and ECAgNPs in Wister rats was determined to be greater than 2000 mg/kg body weight. The aqueous extract also showed more cytotoxic than the ECAgNPs suggesting that the toxic compounds in aqueous extract were involved in the capping of the AgNPs.

Serum and Hepatic Autofluorescence as a Real-Time Diagnostic Tool for Early Cholestasis Assessment.

While it is well established that various factors can impair the production and flow of bile and lead to cholestatic disease in hepatic and extrahepatic sites, an enhanced assessment of the biomarkers of the underlying pathophysiological mechanisms is still needed to improve early diagnosis and therapeutic strategies. Hence, we investigated fluorescing endogenous biomolecules as possible intrinsic biomarkers of molecular and cellular changes in cholestasis. Spectroscopic autofluorescence (AF) analysis was performed using a fiber optic probe (366 nm excitation), under living conditions and in serum, on the livers of male Wistar rats submitted to bile duct ligation (BDL, 24, 48, and 72 h). Biomarkers of liver injury were assayed biochemically. In the serum, AF analysis distinctly detected increased bilirubin at 24 h BDL. A continuous, significant increase in red-fluorescing porphyrin derivatives indicated the subversion of heme metabolism, consistent with an almost twofold increase in the serum iron at 72 h BDL. In the liver, changes in the AF of NAD(P)H and flavins, as well as lipopigments, indicated the impairment of mitochondrial functionality, oxidative stress, and the accumulation of oxidative products. A serum/hepatic AF profile can be thus proposed as a supportive diagnostic tool for the in situ, real-time study of bio-metabolic alterations in bile duct ligation (BDL) in experimental hepatology, with the potential to eventually translate to clinical diagnosis.

Initial assessment of the infant with neonatal cholestasis-Is this biliary atresia?

INTRODUCTION: Optimizing outcome in biliary atresia (BA) requires timely diagnosis. Cholestasis is a presenting feature of BA, as well as other diagnoses (Non-BA). Identification of clinical features of neonatal cholestasis that would expedite decisions to pursue subsequent invasive testing to correctly diagnose or exclude BA would enhance outcomes. The analytical goal was to develop a predictive model for BA using data available at initial presentation. METHODS: Infants at presentation with neonatal cholestasis (direct/conjugated bilirubin >2 mg/dl [34.2 µM]) were enrolled prior to surgical exploration in a prospective observational multi-centered study (PROBE-NCT00061828). Clinical features (physical findings, laboratory results, gallbladder sonography) at enrollment were analyzed. Initially, 19 features were selected as candidate predictors. Two approaches were used to build models for diagnosis prediction: a hierarchical classification and regression decision tree (CART) and a logistic regression model using a stepwise selection strategy. RESULTS: In PROBE April 2004-February 2014, 401 infants met criteria for BA and 259 for Non-BA. Univariate analysis identified 13 features that were significantly different between BA and Non-BA. Using a CART predictive model of BA versus Non-BA (significant factors: gamma-glutamyl transpeptidase, acholic stools, weight), the receiver operating characteristic area under the curve (ROC AUC) was 0.83. Twelve percent of BA infants were misclassified as Non-BA; 17% of Non-BA infants were misclassified as BA. Stepwise logistic regression identified seven factors in a predictive model (ROC AUC 0.89). Using this model, a predicted probability of >0.8 (n = 357) yielded an 81% true positive rate for BA; <0.2 (n = 120) yielded an 11% false negative rate. CONCLUSION: Despite the relatively good accuracy of our optimized prediction models, the high precision required for differentiating BA from Non-BA was not achieved. Accurate identification of BA in infants with neonatal cholestasis requires further evaluation, and BA should not be excluded based only on presenting clinical features.

Pre-operative labs: Wasted dollars or predictors of post-operative cardiac and septic events in orthopaedic trauma patients?

PURPOSE: As US healthcare expenditures continue to rise, there is significant pressure to reduce the cost of inpatient medical services. Studies have estimated that over 70% of routine labs may not yield clinical benefits while adding over $300 in costs per day for every inpatient. Although orthopaedic trauma patients tend to have longer inpatient stays and hip fractures have been associated with significant morbidity, there is a dearth of data examining pre-operative labs in predicting post-operative adverse events in these populations. The purpose of this study was to assess whether pre-operative labs significantly predict post-operative cardiac and septic complications in orthopaedic trauma and hip fracture patients. METHODS: Between 2006 and 2013, 56,336 (15.6%) orthopaedic trauma patients were identified and 27,441 patients (7.6%) were diagnosed with hip fractures. Pre-operative labs included sodium, BUN, creatinine, albumin, bilirubin, SGOT, alkaline phosphatase, white count, hematocrit, platelet count, prothrombin time, INR, and partial thromboplastin time. For each of these labs, patients were deemed to have normal or abnormal values. Patients were noted to have developed cardiac or septic complications if they sustained (1) myocardial infarction (MI), (2) cardiac arrest, or (3) septic shock within 30 days after surgery. Separate regressions incorporating over 40 patient characteristics including age, gender, pre-operative comorbidities, and labs were performed for orthopaedic trauma patients in order to determine whether pre-operative labs predicted adverse cardiac or septic outcomes. RESULTS: 749 (1.3%) orthopaedic trauma patients developed cardiac complications and 311 (0.6%) developed septic shock. Multivariate regression demonstrated that abnormal pre-operative platelet values were significantly predictive of post-operative cardiac arrest (OR: 11.107, p=0.036), and abnormal bilirubin levels were predictive (OR: 8.487, p=0.008) of the development of septic shock in trauma patients. In the hip fracture cohort, abnormal partial thromboplastin time was significantly associated with post-operative myocardial infarction (OR: 15.083, p=0.046), and abnormal bilirubin (OR: 58.674, p=0.002) significantly predicted the onset of septic shock. CONCLUSIONS: This is the first study to demonstrate the utility of pre-operative labs in predicting perioperative cardiac and septic adverse events in orthopaedic trauma and hip fracture patients. Particular attention should be paid to haematologic/coagulation labs (platelets, PTT) and bilirubin values. LEVEL OF EVIDENCE: Prognostic Level II.

[The assessment of metabolism of bone tissue as changes in concentration of biochemical markers of bone turnover in inpatient alcohol dependent women]. / Ocena metabolizmu tkanki kostnej u kobiet uzaleznionych od alkoholu z zastosowaniem markerów obrotu kostnego - osteokalcyny i ctx.

AIM: The aim of this study was the assessment to of metabolism of bone tissue as changes in concentration of biochemical markers of bone turnover in inpatient alcohol dependent women. METHODS: The studied group consisted of 50 alcohol dependent female patients who were divided in two groups: one with an activity ofAST or ALT above referential values and level of bilirubin and the second one with the activity oftransaminases and level ofbilirubin within referential values. The level of sex hormones and markers of bone turnover such as osteocalcin and collagen cross laps (ctx) were indicated. RESULTS: In the group with an AST, ALT or BIL above referential values, the concentration of FSH in the ovulation phase and luteal phase as well as LH in luteal phase was significantly higher, while ctx and osteocalcin was lower compared to the group with AST, ALT or BIL within referential values. The mean concentrations ofFSH in follicular phase and luteal phase as well as LH in the luteal phase and progesterone in the follicular phase were increased in the group of patients with AST, ALT or BIL above referential values. The positive correlation between levels ofctx and osteocalcin was found which suggests a balance between processes. of bone formation and bone resorption in the whole group while a lack of such correlation was observed in patients with AST, ALT or BIL above referential values. CONCLUSIONS: The results obtained indicate the multidirectional and mutual relations between the alcohol abuse, liver function, bone turnover and activity of endocrine system.

Surgical stress after robot-assisted distal gastrectomy and its economic implications.

BACKGROUND: There is a lack of reports evaluating the outcomes of robotic gastrectomy and conventional laparoscopic surgery. The aim of this study was to compare the surgical stress response and costs of robot-assisted distal gastrectomy (RADG) with those of laparoscopy-assisted distal gastrectomy (LADG). METHODS: This prospective study compared a cohort of patients who had RADG with a cohort that underwent conventional LADG for early gastric cancer between March 2010 and May 2011. The surgical outcomes including Eastern Cooperative Oncology Group performance status and complications, surgical stress response and overall costs were compared between the two groups. RESULTS: Thirty patients were enrolled in the RADG group and 120 in the LADG group. There were no conversions. Median duration of operation was longer in the RADG group (218 (interquartile range 200-254) versus 140 (118-175) min; P < 0·001). Postoperative abdominal drain production was less (P = 0·001) and postoperative performance status was worse (P < 0·001) in the RADG group. C-reactive protein (CRP) levels on postoperative days 1 and 3, and interleukin (IL) 6 level on the third postoperative day, were lower in the LADG compared with the RADG group (CRP: P = 0·002 and P = 0·014 respectively; IL-6: P < 0·001). Costs for robotic surgery were much higher than for laparoscopic surgery (difference €3189). CONCLUSION: RADG did not reduce surgical stress compared with LADG. The substantial RADG costs due to robotic system expenses may not be justified.

Reflectance spectrometry of normal and bruised human skins: experiments and modeling.

A stochastic photon transport model in multilayer skin tissue combined with reflectance spectroscopy measurements is used to study normal and bruised skins. The model is shown to provide a very good approximation to both normal and bruised real skin tissues by comparing experimental and simulated reflectance spectra. The sensitivity analysis of the skin reflectance spectrum to variations of skin layer thicknesses, blood oxygenation parameter and concentrations of main chromophores is performed to optimize model parameters. The reflectance spectrum of a developed bruise in a healthy adult is simulated, and the concentrations of bilirubin, blood volume fraction and blood oxygenation parameter are determined for different times as the bruise progresses. It is shown that bilirubin and blood volume fraction reach their peak values at 80 and 55 h after contusion, respectively, and the oxygenation parameter is lower than its normal value during 80 h after contusion occurred. The obtained time correlations of chromophore concentrations in developing contusions are shown to be consistent with previous studies. The developed model uses a detailed seven-layer skin approximation for contusion and allows one to obtain more biologically relevant results than those obtained with previous models using one- to three-layer skin approximations. A combination of modeling with spectroscopy measurements provides a new tool for detailed biomedical studies of human skin tissue and for age determination of contusions.

Quantitative assessment of liver function after ischemia-reperfusion injury and partial hepatectomy in rats.

BACKGROUND: Liver function after hepatic ischemia-reperfusion (I/R) injury and partial liver resection (PHx) is influenced by the extent of PHx, hepatocellular damage, and liver regeneration. This study investigates the effect of minor PHx with increasing degrees of I/R-induced damage on postoperative liver function parameters and compares the indocyanine green (ICG) clearance test with (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) for quantitative measurement of hepatic function in a standardized rat model. METHODS: Rats were subjected to 70% partial liver I/R combined with resection of the nonischemic lobes. Various degrees of hepatic damage were induced by 0, 15, 30, 45, and 60 min ischemia. Prothrombin time and bilirubin were used as indirect parameters of liver function. (99m)Tc-mebrofenin HBS and ICG clearance were used as dynamic quantitative liver function tests. RESULTS: After 24 h reperfusion hepatocellular damage increased with prolonged ischemia times. Hepatocellular damage and liver regeneration were closely interrelated. Moderate I/R-induced damage enhanced regeneration, while extensive damage debilitates the regenerative capacity. PHx alone resulted in no significant decrease in liver uptake function measured by HBS or ICG. Increasing severity of hepatic I/R injury had a differential effect on ICG clearance and (99m)Tc-mebrofenin uptake and excretion. CONCLUSIONS: The specific impact of 30% PHx combined with progressive ischemia times is different for each liver function test. Albeit (99m)Tc-mebrofenin HBS and the ICG clearance test provide complementary quantitative information to biochemical parameters, they only quantify one or two components of liver function. ICG and (99m)Tc-mebrofenin uptake profiles differed significantly, suggesting that the specific hepatic transporters may be distinct.

Multicenter study of plasma diafiltration in patients with acute liver failure.

Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. A prospective, multicenter study was undertaken to evaluate the changes in bilirubin, IL-18, and cystatin C, as well as the 28-day and 90-day survival rates, with the use of PDF according to the level of severity as measured by the Model for End-Stage Liver Disease (MELD) score. Twenty-one patients with liver failure were studied: 10 patients had fulminant hepatitis and PDF therapies were performed 28 times; 11 had acute liver failure with the therapy performed 96 times. Levels of total bilirubin, IL-18, and cystatin C decreased significantly after treatment. The 28-day survival rate was 70.0% and that at 90 days was 16.7%. According to the severity of the MELD score, each of the results compared well with the use of Molecular Adsorbent Recirculating System or Prometheus therapy. In conclusion, PDF appears to be one of the most useful blood purification therapies for use in cases of acute liver failure in terms of medical economics and the removal of water-soluble and albumin-bound toxins.

Effective use of FibroTest to generate decision trees in hepatitis C.

AIM: To assess the usefulness of FibroTest to forecast scores by constructing decision trees in patients with chronic hepatitis C. METHODS: We used the C4.5 classification algorithm to construct decision trees with data from 261 patients with chronic hepatitis C without a liver biopsy. The FibroTest attributes of age, gender, bilirubin, apolipoprotein, haptoglobin, alpha2 macroglobulin, and gamma-glutamyl transpeptidase were used as predictors, and the FibroTest score as the target. For testing, a 10-fold cross validation was used. RESULTS: The overall classification error was 14.9% (accuracy 85.1%). FibroTest's cases with true scores of F0 and F4 were classified with very high accuracy (18/20 for F0, 9/9 for F0-1 and 92/96 for F4) and the largest confusion centered on F3. The algorithm produced a set of compound rules out of the ten classification trees and was used to classify the 261 patients. The rules for the classification of patients in F0 and F4 were effective in more than 75% of the cases in which they were tested. CONCLUSION: The recognition of clinical subgroups should help to enhance our ability to assess differences in fibrosis scores in clinical studies and improve our understanding of fibrosis progression.

The joint use of human and electronic eye: visual assessment of jaundice and transcutaneous bilirubinometry.

Our aim was to study the usefulness of jaundice visual assessment combined with skin bilirubin determination in 517 healthy newborns. Yellowness assessment was made and babies were included in three different bilirubin classes. Skin bilirubin and total serum bilirubin were determined within 10 minutes from the visual assessment. This latter led to underestimation of serum bilirubin in 16.7-40.4% and overestimation in 4.9-35.7% of newborns. Skin bilirubin measurement after the visual assessment decreased the risk of underestimation to 0-9.2% and the risk of overestimation to 2.1-11.1%. The majority of visual assessment errors were performed in the more lighted hours of the morning (75%), while the smallest number (39%) occurred during the afternoon. Skin bilirubin measurement significantly corrected these diagnostic errors (p < 0.001, p < 0.02) without differences during the day. Clinical estimate is unreliable for evaluating the need for serum bilirubin assay. Using the addition of skin bilirubin determination is a more advisable approach.

A case report of pediatric fulminant hepatitis treated with plasma diafiltration.

Plasma diafiltration (PDF) is blood purification therapy in which simple plasma exchange is performed with a membrane plasma separator while dialysate flows outside the hollow fibers. A 14-year-old boy with fulminant hepatitis underwent two sessions of PDF and one session of hemodiafiltration. We infused filtered replacement fluid for artificial kidneys at a dialysate flow rate of 600 mL/h and a replacement flow rate of 450 mL/h. We infused fresh frozen plasma (1200 mL) and 25% albumin solution (50 mL) intravenously over 8 h. Each PDF session lasted 8 h. The patient's total bilirubin, interleukin-18, and cystatin C levels decreased with treatment, and he recovered from hepatic failure. PDF may be an extremely useful blood purification therapy for pediatric fulminant hepatitis in terms of both medical economics and cytokine removal.

[Assessment of duodenogastric reflux 24h variability in subjects with functional dyspepsia]. / Ocena zmiennosci dobowej refluksu dwunastniczo-zoladkowego u osób z dyspepsja czynnosciowa.

Symptoms of functional dyspepsia demonstrate significant variability, among others dependently on the time of the day and on consumed meals. The aim of the study was to find out whether duodenogastric reflux is observed in subjects with nonulcer (NUD) and dysmotor dyspepsia (DD) and whether its intensification changes within 24 h. Investigations comprised 25 subjects with NUD and 25 with DD, aged 19-43 years after exclusion of other diseases and H. pylori infection. The gastric content of bilirubin was registered with Bilitec 2000 Synectics Medical. Duodenogastric reflux episodes were observed in both groups but their intensification and 24h dynamics were differentiated. In subjects with DD total reflux index was significantly higher than in those with NUD (mean=18.0+/-9.5% and mean=6.3+/-4.1%; p<0.05). These differences were particularly visible in after meal (mean=21.2+/-7.9% and mean=10.4+/-6.6%; p<0.01) and night time (mean=8.7+/-3.6% and mean=2.9+/-0.9%; p<0.01). The results of the study indicate that bilimetry may be useful in differentiation of the form of dyspepsia and in selection of rational therapy.

Noninvasive transcutaneous bilirubin as a screening test to identify the need for serum bilirubin assessment.

Hyperbilirubinemia is a common problem in the newborn infant. It can progress to develop kernicterus unless intervention is initiated. Severity and decision for management are usually based on serum bilirubin (TsB) which needs blood sampling. Transcutaneous bilirubin measurement is a noninvasive technique and the result correlates closely with TsB. A new transcutaneous bilirubinometer, Minolta AirShields Jaundice Meter, JM103, has been introduced The objectives of this study were: 1) To evaluate the accuracy of transcutaneous bilirubin (TcB) measured by JM 103, when compared to TsB, used clinically in a hospital setting (Leica Unistat Bilirubinometer) and 2) To develop a cut-off point of TcB level which indicated the need for serum bilirubin assessment. Three hundred and eighty eight term and near-term newborn infants with 460 paired TcB-TsB specimens were studied from August to November 2003. Birth weight was 3117.57 +/- 424.82 grams. TsB ranged from 4 to 19.6 mg/dL (x 10.5, SD 2.46). The correlation coefficient between TcB and TsB was significant (r 0.8, p < 0.001). TcB showed a tendency to underestimate TsB, with mean difference of 0.7 mg/dL, SD 1.6 mg/dL, and 95% confidence interval 0.85 and 0.55 mg/dL. TcB values of 8, 9, 10, 12 mg/dL were chosen as cut-off points that indicated the need for blood sampling for TsB (corresponded to hour-specific levels of 10, 12, 13 and 15 mg/dL, respectively when phototherapy should be initiated). In conclusion, noninvasive TcB assessment demonstrates significant accuracy, compared to TsB. It can be used as a screening test to identify the need for blood sampling for serum bilirubin level.