Efficacy of dual carbapenem treatment in a murine sepsis model of infection due to carbapenemase-producing Acinetobacter baumannii.

OBJECTIVES: To evaluate the in vivo efficacy of a dual carbapenem combination containing imipenem plus meropenem against carbapenem-resistant Acinetobacter baumannii producing carbapenemases OXA-23 or OXA-58. METHODS: An experimental model of peritonitis using C57BL/6J female mice was developed and the minimum lethal doses were calculated for infections due to OXA-23 or OXA-58 producers of A. baumannii clinical isolates. The efficacies of the carbapenems in monotherapy and in combination were tested. RESULTS: Meropenem was better than imipenem in mice infected with either of the carbapenem-resistant A. baumannii (CRAb) strains. The combination of meropenem plus imipenem significantly improved the clearance of CRAbs from spleen compared with non-treated groups. The carbapenem-containing combination was better than imipenem for treating mice infected with both carbapenemase producers. In blood, the carbapenem combination significantly decreased the bacterial load of the OXA-23 producers compared with imipenem or meropenem used in monotherapy. CONCLUSIONS: These results suggest that dual carbapenem combination could be an option for the treatment of infections due to carbapenemase-producing A. baumannii such as OXA-23 and OXA-58 producers.

Sequential pretreatment to recover carbohydrates and phosphorus from Desmodesmus sp. cultivated in municipal wastewater.

This study focused on the simultaneous recovery of carbohydrates (CHO) and phosphorus (P) from Desmodesmus sp. biomass cultivated in municipal wastewater, through a sequential pretreatment. The pretreatment consisted first of ultrasound to trigger cell disruption followed by ozonation to recover CHO and P. For ozone pretreatment, three different parameters were considered: ozone concentration (9, 15, 21, 27, 36, and 45 mg O3/L), contact time (15, 25 and 35 min), and pH (8 and 11). The maximum simultaneous release of 84% of CHO and 58% of P was achieved at the experimental parameters of ozone concentration of 45 mg O3/L, contact time of 35 min, and pH of 11. Also, P was concentrated in solution by 8- to 14-fold with respect to municipal wastewater. The sequential pretreatment was conducted at alkaline pH of 11 and atmospheric conditions, which may considerably reduce energy demand and reagents, in comparison to a traditional hydrolysis pretreatment. The results found suggest that the sequential pretreatment could be feasible on a large scale.

Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann-Pick disease.

Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane of neurons. Using ASM knockout (ASMko) mice as a NPA disease model, we investigated how high SM levels contribute to neural pathology in NPA. We found high levels of oxidative stress both in neurons from these mice and a NPA patient. Impaired activity of the plasma membrane calcium ATPase (PMCA) increases intracellular calcium. SM induces PMCA decreased activity, which causes oxidative stress. Incubating ASMko-cultured neurons in the histone deacetylase inhibitor, SAHA, restores PMCA activity and calcium homeostasis and, consequently, reduces the increased levels of oxidative stress. No recovery occurs when PMCA activity is pharmacologically impaired or genetically inhibited in vitro. Oral administration of SAHA prevents oxidative stress and neurodegeneration, and improves behavioral performance in ASMko mice. These results demonstrate a critical role for plasma membrane SM in neuronal calcium regulation. Thus, we identify changes in PMCA-triggered calcium homeostasis as an upstream mediator for NPA pathology. These findings can stimulate new approaches for pharmacological remediation in a disease with no current clinical treatments.

Electrochemical removal of carbamazepine in water with Ti/PbO2 cylindrical mesh anode.

Carbamazepine (CBZ) is one of the most frequently detected organic compounds in the aquatic environment. Due to its bio-persistence and toxicity for humans and the environment its removal has become an important issue. The performance of the electrochemical oxidation process and in situ production of reactive oxygen species (ROS), such as O3 and H2O2, for CBZ removal have been studied using Ti/PbO2 cylindrical mesh anode in the presence of Na2SO4 as supporting electrolyte in a batch electrochemical reactor. In this integrated process, direct oxidation at anode and indirect oxidation by in situ electrogenerated ROS can occur simultaneously. The effect of several factors such as electrolysis time, current intensity, initial pH and oxygen flux was investigated by means of an experimental design methodology, using a 2(4) factorial matrix. CBZ removal of 83.93% was obtained and the most influential parameters turned out to be electrolysis time, current intensity and oxygen flux. Later, the optimal experimental values for CBZ degradation were obtained by means of a central composite design. The best operating conditions, analyzed by Design Expert(®) software, are the following: 110 min of electrolysis at 3.0 A, pH = 7.05 and 2.8 L O2/min. Under these optimal conditions, the model prediction (82.44%) fits very well with the experimental response (83.90 ± 0.8%). Furthermore, chemical oxygen demand decrease was quantified. Our results illustrated significant removal efficiency for the CBZ in optimized condition with second order kinetic reaction.

Acquisition of Competencies by Medical Students in Neurological Emergency Simulation Environments Using High Fidelity Patient Simulators.

The training of medical students demands practice of skills in scenarios as close as possible to real ones that on one hand ensure acquisition of competencies, and on the other, avoid putting patients at risk. This study shows the practicality of using high definition mannequins (SimMan 3G) in scenarios of first attention in neurological emergencies so that medical students at the Faculty of Medicine of the University of Salamanca could acquire specific and transversal competencies. The repetition of activities in simulation environments significantly facilitates the acquisition of competencies by groups of students (p < 00.5). The greatest achievements refer to skills whereas the competencies that demand greater integration of knowledge seem to need more time or new sessions. This is what happens with the competencies related to the initial diagnosis, the requesting of tests and therapeutic approaches, which demand greater theoretical knowledge.

Lower-normal TSH is associated with better metabolic risk factors: A cross-sectional study on Spanish men.

BACKGROUND AND AIMS: Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic syndrome and cardiovascular risk. This work studies the linearity of the relationship between metabolic syndrome and TSH across the euthyroid range. METHODS AND RESULTS: We studied 3533 male participants of the Aragon Workers' Health Study (AWHS) with normal TSH and free T4 levels, across quintiles of these variables, after adjusting for age, alcohol intake, and smoking. Compared with the lowest TSH quintile, the odds ratios for metabolic syndrome at the higher quintiles, which indicate lower thyroid function, were 1.34 (1.04, 1.73), 1.56 (1.21, 2.01), 1.57 (1.22, 2.03), and 1.71 (1.32, 2.21). The lowest free T4 quintile also showed an odds ratio of 1.49 (1.16, 1.90) with respect to the highest quintile. In addition, spline models showed departures from linearity: the risk of metabolic syndrome mostly increases at TSH values below the median (sample half-closest to subclinical hyperthyroidism). Interestingly, glucose also increases with TSH primarily below the median TSH, diastolic blood pressure shows similar changes across the entire TSH range, whereas body mass index, triglycerides, and high-density lipoprotein (HDL)-cholesterol change only at the highest normal TSH values, which are associated with lower free T4 concentration. CONCLUSIONS: TSH and free T4 within the normal range are associated with the metabolic syndrome. The sample half-below the TSH median (with probably higher functional thyroid status) exhibited better metabolic and cardiovascular profiles.

Diagnosis of lesions of the acetabular labrum, of the labral-chondral transition zone, and of the cartilage in femoroacetabular impingement: Correlation between direct magnetic resonance arthrography and hip arthroscopy.

OBJECTIVE: To determine the sensitivity and accuracy of direct MR arthrography in the diagnosis of intra-articular lesions associated with femoroacetabular impingement. MATERIAL AND METHODS: We used direct MR arthrography to study 51 patients with femoroacetabular impingement who underwent arthroscopic hip surgery. Surgery demonstrated 37 labral tears, 44 lesions in the labral-chondral transitional zone, and 40 lesions of the articular cartilage. We correlated the findings at preoperative direct MR arthrography with those of hip arthroscopy and calculated the sensitivity, specificity, positive predictive value, negative predictive value, and validity index for direct MR arthrography. RESULTS: The sensitivity and specificity of MR arthrography were 94.5% and 100%, respectively, for diagnosing labral tears, 100% and 87.5%, respectively, for diagnosing lesions of the labral-chondral transition zone, and 92.5% and 54.5%, respectively, for diagnosing lesions of the articular cartilage. The negative predictive value of MR arthrography for lesions of the labral-chondral transitional zone was 100%. MR arthrography accurately defined extensive lesions of the cartilage and the secondary osseous changes (the main factor in poor prognosis), although its diagnostic performance was not so good in small chondral lesions. CONCLUSION: In patients with femoroacetabular impingement, direct MR arthrography can adequately detect and characterize lesions of the acetabular labrum and of the labral-chondral transitional zone as well as extensive lesions of the articular cartilage and secondary osseous changes.

Hepatitis B virus depicts a high degree of conservation during the immune-tolerant phase in familiarly transmitted chronic hepatitis B infection: deep-sequencing and phylogenetic analysis.

When intrafamilial transmission of hepatitis B virus (HBV) occurs, a virus with the same characteristics interacts with diverse hosts' immune systems and may thus result in different mutations to escape immune pressure. In this study, the HBV genomic characterization was assessed longitudinally after intrafamilial transmission using nucleotide sequence data of phylogenetic and mutational analyses, including those obtained by deep-sequencing for the first time. Furthermore, HBeAg-anti-HBe profile and variability of HBV core-derived epitopes were also evaluated. Strong evidence was obtained from intrafamilial transmission of HBV genotype D1 by phylogenetic inferences. HBV isolates exhibited high degree (~99%) of genomic conservation for almost 20 years, when patients were persistently HBeAg positive with normal amino transferase levels. This identity remained high among immune-tolerant siblings. In contrast, it diminished significantly (P = 0.02) when the mother cleared HBeAg (immune clearance phase). By deep-sequencing, the quantitative analysis of the dynamics of basal core promoter (BCP) (A1762T, G1764A; A1766C; T1773C; 8-bp deletion; and other) and precore (G1896A) variants among HBV isolates from family members exhibited differences during the follow-up. However, only those from the mother showed amino acid variations at core protein that would impair their MHC-II binding. Hence, when intrafamilial transmission occurs, HBV was highly conserved under the immune-tolerant phase, but it exhibited mutations more frequently during the immune clearance phase. The analysis of the HBV BCP and precore mutants after intrafamilial HBV transmission contributes to a better understanding of how they evolve over time.

Characterization and description of a multiple sex chromosome system in Potamotrygon motoro (Chondrichthyes, Myliobatiformes) from the Paraná River, Argentina.

The Potamotrygonidae family represents the only freshwater group of specialized elasmobranchs and is composed of 4 genera: Plesiotrygon, Paratrygon, Potamotrygon, and Heliotrygon. Individuals of Potamotrygon motoro were collected from the Paraná River at Ituzaingó (Province of Corrientes) in Argentina. Mitotic preparations were obtained using direct techniques and lymphocyte cultures. Chromosomes were studied with conventional Giemsa, C-band and nucleolus organizer region stainings. The diploid number and karyotype formulae were 2n = 66 with 33 homomorphic pairs (14M + 16SM + 22ST + 14A) in females and 2n = 65 with 31 homomorphic pairs plus 3 heteromorphic chromosomes (13M + 15SM + 23ST + 14A) in males. Heterochromatin was distributed at the pericentromeric regions of almost all chromosomes and in the telomeric and interstitial positions of some chromosomes. nucleolus organizer regions were multiple and located at telomeric regions. Because of the clear karyotype differences between the 2 sexes and the presence of 3 unpaired chromosomes in males, it is possible to suggest the occurrence of a multiple sex chromosome system, with male heterogamety (X1X1X2X2/X1X2Y). Further cytogenetic studies are required to develop a hypothesis about the origin of the multiple sex chromosome system in P. motoro.

Imported and autochthonous dengue in Spain.

Dengue is globally the most important arboviral infection. It is caused by the dengue virus and it is generally transmitted by Aedes mosquitoes' bites (Ae aegypti or Ae albopictus). In Spain it was initially eradicated in the 20th century, together with the Ae aegypti vector, and currently most of the cases reported in Spain are imported by travelers from countries with dengue transmission (imported dengue). However, in recent years, cases of dengue have been described in people residing in Spain who had not traveled to areas with known transmission (autochthonous dengue), transmitted by Aedes albopictus (the so-called tiger mosquito), present especially in the Mediterranean basin. Therefore, a good knowledge of this potentially severe disease is required, so that it can be diagnosed early, and managed correctly, thus reducing its mortality, as well as its eventual autochthonous transmission.

Real-life experience of hepatitis C treatment in a Spanish prison.

OBJECTIVE: Hepatitis C virus (HCV) infection is a major public health problem that causes multiple comorbidities. People in prisons who inject intravenous drugs are at increased risk of HCV infection, and HCV infection is 15-fold more prevalent among prisoners compared with the community. The objective of this study was to analyse the clinical and epidemiological characteristics of residents of a Spanish prison with HCV infection who received antiviral treatment. METHODS: An observational, descriptive and retrospective study was performed. All patients with HCV infection diagnosed or followed up in an Infectious Diseases attached to a penitentiary were included in this study. RESULTS: Of 81 patients analysed, sixty-nine (83.1%) patients were male. The mean age was 50.1 (SD8.8) years, and 70% of the inmates had a history of injection drug use. Coinfection with HIV was detected in 30%. In up to 25% of the sample, there were data on chronic liver disease in the degree of liver cirrhosis. The diagnosis of HCV infection had been made more than 15 years earlier in 28% of those studied. Decompensations from liver disease, hepatocellular carcinoma, or hospital admissions were exceptional. Most of the inmates with HCV accepted treatment, and approximately 94% of the patients who completed treatment achieved a sustained virological response without interactions or complications of interest. CONCLUSIONS: The availability of direct-acting antivirals and their exceptional side effects constitute an opportunity to reduce the burden of HCV infection in Spain, particularly in these high-risk populations.

[Comorbidity, discapacity and mortality in patients with multiple conditions and chronic obstructive pulmonary disease]. / Comorbilidad, discapacidad y mortalidad en pacientes pluripatológicos con enfermedad pulmonar obstructiva crónica.

AIMS: To determine the association between different comorbidities and other clinical conditions with mortality in patients with multiple diseases (PMD) suffering from chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: Patients with COPD and PMD criteria were included in an observational, prospective and multicentrer study. Data on age, gender, Charlson index, Barthel index, Lawton-Brody index, Pfeiffer test, sociofamilial Gijon scale, education level, hospitalizations during the previous 3 and 12 months and survival at one year were collected. The relationship between the variables and mortality were established by means of a univariate analysis and logistic regression model. RESULTS: A total of 688 PMD with COPD and mean age of 77.9 years were included. The mean score one the Charlson index was 3.99 (2.07). The most frequent comorbidities were heart failure (59%), diabetes (48%), myocardial infarction (29%), moderate kidney failure (22%), cerebrovascular disease (19%), hypertension (71%), anemia (62%), atrial fibrillation (34%), dyslipidemia (28%) and obesity (21%). A total of 26% of patients were dependent for activities of daily living, 47% needed a caregiver and 54% were at risk of having social problems. At one year, 258 patients (37%) had died. The Charlson index, dependency for activities of daily living and anemia were associated with mortality and hypertension and capacity for reading and writing were associated with survival. CONCLUSIONS: Comorbidity and discapacity are two prognostic factors in COPD patients.

Intensified recovery of lipids, proteins, and carbohydrates from wastewater-grown microalgae Desmodesmus sp. by using ultrasound or ozone.

This study evaluates the effect of ultrasound and ozone pretreatments for the subsequent recovery of Desmodesmus sp. biocomponents-lipids, proteins, and carbohydrates-using a response surface methodology. Both pretreatments impact on the recovered lipids quality, solvent waste production and extraction time is analysed for process intensification purposes. For ultrasound pretreatment, independent parameters were energy applied (50-200 kWh/kg dry biomass), biomass concentration (25-75 g/L), and ultrasonic intensity (0.32 and 0.53 W/mL). While for ozone pretreatment, independent parameters were ozone concentration (3-9 mg O3/L), biomass concentration (25-75 g/L), and contact time (5-15 min). In the case of ultrasound pretreatment, recovery yield reached 97 ±â€¯0.4%, 89 ±â€¯3%, and 73 ±â€¯0.6% for proteins, carbohydrates and lipids respectively. Given process required: energy applied of 50 kWh/kg dry biomass, 75 g/L of biomass concentration, 0.32 W/mL of ultrasonic intensity, and 56 min of time process. Ultrasound caused high cell disruption releasing all proteins, thereby obviating downstream processing for its recovery. Ozone pretreatment recovery yield was 85 ±â€¯2%, 48 ±â€¯1.4%, and 25 ±â€¯1.3%, for carbohydrates, lipids and proteins respectively, under the following conditions: 9 mg O3/L of ozone concentration, 25 g/L of biomass concentration, and 5 min of contact time that depicts an energy consumption of 30.64 kWh/kg dry biomass. It was found that ultrasound and ozone pretreatments intensified the lysis and biocomponents recovery process by reducing solvent consumption by at least 92% and extraction time between 80% and 90% compared with extraction of untreated biomass biocomponents. Both pretreatments improve the composition of the recovered lipids. It was noted that the yield of neutral lipids increased from 28% to 67% for ultrasound pretreatment while for ozone pretreatment from 49% to 63%. The method used for lipid extraction may also have an effect but here it was kept constant.

[Vagus nerve stimulation for the treatment of refractory epilepsy. State of the art]. / Estimulación eléctrica vagal en el tratamiento de la epilepsia rebelde. Situación actual.

The vagus nerve stimulation (VNS) therapy is a new neurostimulation technique used for treating pharmacoresistant epilepsy. It can be considered an effective and safe alternative for the treatment of refractory epilepsy patients. In the present review, we describe the surgical implantation technique, its indications and results achieved until now. We will also summarize the possible mechanisms of action of VNS therapy. Finally, we will comment on the difficulties and inconveniences that did not allow this antiepileptic surgical technique to become more widely used.

Efficacy of primary systemic chemotherapy regimen containing anthracyclines with/without taxanes in comparison to CMF in women with early breast cancer.

Neoadjuvant chemotherapy is the treatment of choice for locally-advanced breast cancer and leads to down staging and improved breast-conserving therapy (BCT) rates. While its efficacy is well established, considerably less is known about the most effective regimen. We have performed a retrospective analysis of 132 breast cancer patients who had undergone neoadjuvant chemotherapy at our institution. Patients had either received a) anthracyclines ("A", n=35), b) anthracyclines and taxanes ("AT", n=55), or c) neither of the two compounds ("NoA/T", n=42). Clinical response, pathological response and survival were evaluated in each arm. While all three regimens resulted in significant tumor regression, AT was most effective with a mean tumor shrinkage of 39% (ultrasound) and 41% (mammography) (Kruskal-Wallis, p=0.004, and p=0.027). Breast conservation was achieved in 75% by AT, in 49% by A, and in 19% by NoA/T (Kruskal-Wallis, p<0.001). The treatment groups did not differ in respect to pathological complete response (pCR) (chi2-test, p=0.068), although higher cumulative anthracycline doses were predictive of pCR in multivariate analyses (p=0.022). While the mammographic but not the ultrasound-determined tumor diameter determined whether a woman underwent BCT, only an ultrasound-determined size reduction was predictive for disease-free survival (DFS) and overall survival (OS) (log rank, p=0.0093, and p=0.044, respectively). Other parameters that affected BCT rates were age (p= 0.003), year of diagnosis (p=<0.001), presence of multifocal disease (p= 0.032) and the cumulative anthracycline dose (p= <0.001). While the combination of anthracyclines and taxanes is most effective in achieving clinical remission and BCT, the cumulative anthracycline dose appears most important for achieving pCR.

A description of cattle movements in two departments of Buenos Aires province, Argentina.

We present a descriptive analysis of cattle movement information retrieved from the Argentinean animal movement database for two departments in the province of Buenos Aires during 2004. For each quarter of the year (January to March, April to June, July to September, and October to December) we report the number of on- and off-farm movement events for the purpose of finishing. Our analyses show that the distribution of the number of finishing-related movement events per farm was skewed, with the majority of farms reporting at least 1 and less than 5% of farms of reporting greater than 15 finishing related movement events throughout the year. The frequency of finishing-related movement events varied over time, with a 1.2-1.8-fold increase in reported movement events from April to September, compared with the rest of the year. These analyses indicate that cattle movement patterns in these departments are dependent on the relative mix of constituent cattle enterprise types. Departments with a mixture of breeding and finishing enterprises behave as potential recipients and distributors of infectious disease, whereas departments comprised of primarily finishing enterprises are predominantly recipients of infectious disease, rather than distributors. Data integrity audits of the Argentinean animal movement database, on a regular or intermittent basis, should allow the presence of bias in these data to be quantified in greater detail.

[Neurohormonal blockade in patients with heart failure at discharge from hospital]. / Bloqueo neurohormonal al alta en pacientes con insuficiencia cardiaca.

With the objective to value the degree of fulfillment of the pharmacological processing in patients with heart failure was designed the study of therapeutic adherence in heart failure (ATICA). During the period of inclusion educational, social, demographic data have been obtained, personal antecedents, analytic and physical exploration of the patients. These data mentioned are the ones that are reflected in the present pilot study. The total of patients included is 554, the majority of which are women, the middle ages is advanced and they present a fraction of eyección conserved in more than the half. In the therapeutic plan only was collected information of groups with neurohormonal action and of great recognition in the processing of the heart failure. The most utilized pharmacological group are the IECA, nevertheless medicines as the espirolactona or the betablocker continue showing a worrying degree of infrautilización, although they present a greater prescription that in other series.

Theoretical and experimental studies of phenol oxidation by ruthenium complex with N,N,N-tris(benzimidazol-2yl-methyl)amine.

The ruthenium complex with (N,N,N-tris(benzimidazol-2yl-methyl)amine, L(1)) was prepared, and characterized. Fukui data were used to localize the reactive sites on the ligand. The structural and electronic properties of the complex were analyzed by DFT in different oxidation states in order to evaluate its oxidant properties for phenol oxidation. The results show that the hard Ru(IV) cation bonds preferentially with a hard base (Namine = amine nitrogen, or axial chloride ion), and soft Ru(II) with a soft base (Nbzim = benzimidazole nitrogen or axial triphenyl phosphine). Furthermore, the Jahn-Teller effect causes an elongation of the axial bond in the octahedral structure. The bonding nature and the orbital contribution to the electronic transitions of the complex were studied. The experimental UV-visible bands were interpreted by using TD-DFT studies. The complex oxidizes phenol to benzoquinone in the presence of H2O2 and the intermediate was detected by HPLC and (13)C NMR. A possible mechanism and rate law are proposed for the oxidation. The adduct formation of phenol with [Ru(O)L(1)](2+) or [Ru(OH)L(1)](+) is theoretically analyzed to show that [Ru(OH)L(1)-OPh](+) could produce the phenol radical.

Increased risk for hepatocellular carcinoma in NAT2-slow acetylators and CYP2D6-rapid metabolizers.

The arylamine N-acetyltransferase (NAT2) is a polymorphic enzyme which is expressed in the liver in a genotype-determined manner. NAT2 is involved in activation and inactivation of carcinogens through N-acetylation. We studied the role of this polymorphism in the development of hepatocellular carcinoma (HCC). One hundred consecutive patients diagnosed for HCC and 258 healthy volunteers were studied for NAT2 genotype. The occurrence of seven enzyme-inactivating and silent point mutations in the coding region of the NAT2 gene was studied by mutation-specific PCR amplification. An excess of subjects homozygous for NAT2 loss of function alleles was observed among patients with HCC (68% vs 53.9% controls). The relationship between the slow acetylator NAT2 genotype and HCC risk is more pronounced in patients lacking serum HBV and HCV markers. The additional determination of alleles of the cytochrome P450 2D6 (CYP2D6) gene in the same subjects confirmed our previous findings that subjects with two active CYP2D6 genes are at increased risk of developing HCC. The genetic polymorphism of NAT2 is a relevant factor in the risk for developing HCC (inverse odds ratio slow vs rapid = 1.8; 95% CI 1.1-3.0). The inverse odds ratio for subjects with two risk genotypes (two defect NAT2 genes and two or more active CYP2D6 genes) is 2.6 (95% CI 1.6-4.4) for all patients with HCC, and 5.6 (95% CI 1.4-33.3) for patients without serum viral markers.