Evidence of Partial Seniority Conservation in the πg_{9/2} Shell for the N=50 Isotones.

The reduced transition probabilities for the 4_{1}^{+}→2_{1}^{+} and 2_{1}^{+}→0_{1}^{+} transitions in ^{92}Mo and ^{94}Ru and for the 4_{1}^{+}→2_{1}^{+} and 6_{1}^{+}→4_{1}^{+} transitions in ^{90}Zr have been determined in this experiment making use of a multinucleon transfer reaction. These results have been interpreted on the basis of realistic shell-model calculations in the f_{5/2}, p_{3/2}, p_{1/2}, and g_{9/2} proton valence space. Only the combination of extensive lifetime information and large scale shell-model calculations allowed the extent of the seniority conservation in the N=50 g_{9/2} orbital to be understood. The conclusion is that seniority is largely conserved in the first πg_{9/2} orbital.

Pseudospin Symmetry and Microscopic Origin of Shape Coexistence in the

Lifetime measurements of excited states of the light N=52 isotones ^{88}Kr, ^{86}Se, and ^{84}Ge have been performed, using the recoil distance Doppler shift method and VAMOS and AGATA spectrometers for particle identification and gamma spectroscopy, respectively. The reduced electric quadrupole transition probabilities B(E2;2^{+}→0^{+}) and B(E2;4^{+}→2^{+}) were obtained for the first time for the hard-to-reach ^{84}Ge. While the B(E2;2^{+}→0^{+}) values of ^{88}Kr, ^{86}Se saturate the maximum quadrupole collectivity offered by the natural valence (3s, 2d, 1g_{7/2}, 1h_{11/2}) space of an inert ^{78}Ni core, the value obtained for ^{84}Ge largely exceeds it, suggesting that shape coexistence phenomena, previously reported at N≲49, extend beyond N=50. The onset of collectivity at Z=32 is understood as due to a pseudo-SU(3) organization of the proton single-particle sequence reflecting a clear manifestation of pseudospin symmetry. It is realized that the latter provides actually reliable guidance for understanding the observed proton and neutron single particle structure in the whole medium-mass region, from Ni to Sn, pointing towards the important role of the isovector-vector ρ field in shell-structure evolution.

Individual particle SEM-EDS analysis of atmospheric aerosols in rural, urban, and industrial sites of Central Italy.

PM10 samples were collected simultaneously at three representative areas (urban, industrial, and rural areas). Their morphology and elemental composition were determined by scanning electron microscopy coupled with energy-dispersive analysis (SEM-EDS). Twenty-four chemical parameters (C, O, Na, Mg, Al, Si, P, Cd, Cl, K, Ca, S, Sn, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, W, and Pb) were determined and three morphological parameters (area, roundness, and fractal dimension) were measured by Image Pro Analyzer 6.3. The particles were classified into ten groups based on morphology and elemental composition: Ca-rich and metal particles, soot aggregates, cenosphere, alumosilicates, sea salt, calcium sulfate, spherical particles of iron, biological carbonaceous particles, and various. Particles of natural origin were predominantly found in the coarse size fraction and particles of anthropogenic origin in the fine size fraction. The greatest contribution to particulate matter belonged to aluminum-silicates and calcium-rich particles. The cenosphere were recognized only in the coastal urban site, while all the other particles were present in each site. The coastal industrial site was characterized by the prevalence of alumosilicates and Ca-rich particles, due to construction activity in this site during the sampling period (movement of vehicles, transport of terrigenous materials, and use of construction products). The coastal urban site was characterized by a higher amount of soot and by the presence of cenosphere, due to the presence of vehicular traffic.

HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels.

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Anxiety in Multiple Sclerosis: psychometric properties of the State-Trait Anxiety Inventory.

OBJECTIVE: The aims of the present study were to examine psychometric properties of the Spielberger State-Trait Anxiety Inventory (STAI-Y-1 and STAI-Y-2, respectively) in a Multiple Sclerosis (MS) population and to identify a cut-off score to detect those MS patients with high level of state and/or trait anxiety who could be more vulnerable to development of depression and/or cognitive defects. MATERIAL AND METHODS: The STAI-Y-1 and STAI-Y-2 was completed by a group of patients (n = 175) affected by MS and a group of healthy subjects (n = 150) matched for age, educational level, and gender. In MS patients internal consistency, divergent and discriminant validities were evaluated. Construct validity was examined by exploratory factor analysis for each scale. RESULTS: There was no missing data, no floor or ceiling effects for both scales. The two scales showed high internal consistency, good divergent, and Known-groups validities. To identify high levels of state and trait anxiety in a patient with MS, we proposed three gender specific screening cut-off values (1, 1.5, 2 SD) for the STAI-Y-1 and the STAI-Y-2. CONCLUSIONS: The findings showed that the STAI-Y-1 and the STAI-Y-2 are a valid tool for clinical use in MS patients and can be useful to measure the severity of anxiety and to identify those patients with high anxiety to introduce them in specific non-pharmacological intervention.

Psychometric properties of the Italian version of the multifactorial memory questionnaire for adults and the elderly.

Reliable and valid metamemory measures are needed to assess subjective memory complaints that can be distinct from objective memory performance. The Multifactorial Memory Questionnaire (MMQ) evaluates dimensions of subjective memory functioning such as frequency of memory problems (Ability), affect related to memory abilities (Contentment), and strategy use in everyday life (Strategy). To examine the psychometric properties of the Italian version of the MMQ, six hundred Italian healthy individuals (aged 25-91 years) completed MMQ, a questionnaire assessing metacognition (Cognitive Failures Questionnaire, CFQ) and two batteries assessing cognitive global status (Montreal Cognitive Assessment, MoCA; Mini Mental State Examination, MMSE). MMQ was easy to administer, acceptable, and had good test-retest reliability (r for the total MMQ score 0.95), and internal consistency (Cronbach's α for the total MMQ score = 0.83). An exploratory factor analysis provided a four-factor solution: "Ability" (α = 0.99), "Contentment" (α = 0.91), "External Strategies" (α = 0.85) and "Internal Strategies" (α = 0.78) factors. MMQ total score and MMQ-Ability factor score showed good convergent validity when compared to CFQ score (r rho ≥ 0.51), whereas MMQ total score and the four MMQ factors showed good divergent validity when compared to MoCA and MMSE score (r rho ≤ 0.27). Demographic variables significantly influenced MMQ total score and most subscale scores. From the derived linear equations, we computed correction factors for raw scores and percentile distribution of adjusted scores. The Italian version of MMQ is reliable and valid to assess dimensions of metamemory in adult and elderly subjects.

Single-step multimodal locoregional treatment for unresectable hepatocellular carcinoma: balloon-occluded percutaneous radiofrequency thermal ablation (BO-RFA) plus transcatheter arterial chemoembolization (TACE).

PURPOSE: This study was undertaken to evaluate the feasibility, safety and efficacy of a new combined single-step therapy in patients with unresectable multinodular unilobar hepatocellular carcinoma (HCC), with at least one lesion >3 cm, with balloon-occluded radiofrequency ablation (BO-RFA) plus transcatheter arterial chemoembolization (TACE) of the main lesion and TACE of the other lesions. The second purpose of our study was to compare the initial effects in terms of tumour necrosis of this new combined therapy with those obtained in a matched population treated with TACE alone in a singlestep treatment in our centre in the previous year. METHODS AND MATERIALS: This pilot study was approved by the institutional review board, and informed consent was obtained from all patients. Ten consecutive patients with multinodular (two to six nodules) unilobar unresectable HCC and with a main target lesion >3 cm (range, 3.5-6 cm) not suitable for curative therapy were enrolled in our single-centre multidisciplinary pilot study. The schedule consisted of percutaneous RFA (single 3-cm monopolar needle insertion) of the target lesion during occlusion of the hepatic artery supplying the tumour, followed by selective TACE, plus lobar TACE for other lesions (450-mg carboplatin and lipiodol plus temporary embolisation with SPONGOSTAN). Adverse events and intra- and periprocedural complications were clinically assessed. Early local efficacy was evaluated on 1-month follow-up multiphasic computed tomography (CT) on the basis of the Modified Response Evaluation Criteria in Solid Tumors (m-RECIST). A separate evaluation of target lesions in terms of enhancement, necrotic diameter and presence and distribution of lipiodol uptake was also performed. RESULTS: No major complications occurred. Overall technical success, defined as complete devascularisation of all nodules during the arterial phase, was achieved in seven of 10 patients, with three cases of partial response (persistence of small hypervascular nodules). When considering only target lesions, technical success was obtained in all patients, with a nonenhancing area corresponding in shape to the previously identified HCC (necrotic diameter, 3.5-5 cm) and with circumferential peripheral lipiodol uptake (safety margin) of at least 0.5 cm (0.5-1.3cm). CONCLUSIONS: TACE and BO-RFA, plus TACE in a singlestep approach seems to be a safe and effective combined therapy for treating advanced, unresectable HCC lesions, allowing a high rate of complete local response to be achieved in large lesions also.

Hypermutable myotonic dystrophy CTG repeats in transgenic mice.

Myotonic dystrophy (DM) is one of a growing number of inherited human disorders associated with the expansion of triplet repeat DNA sequences. Expanded alleles are highly unstable in both the germline and soma, accounting in large part for the unusual genetics of this disorder, its phenotypic variability and probably, the progressive nature of the symptoms. However, the molecular mechanisms and the genetic factors modulating repeat stability in DM and the other human disorders associated with expanded repeats are not well understood. To provide a model system in which the turnover of triplet repeats could be studied throughout mammalian development, we have generated five transgenic mouse lines incorporating expanded CTG/CAG arrays derived from the human DM locus. Transgene analysis has revealed germline hypermutability, including expansions, deletions and parent-of-origin effects, somatic and early embryonic instability and segregation distortion. Mutational differences between lines and sexes demonstrate that stability, as in humans, is modulated by as yet unidentified cis and trans acting genetic elements.

Efficacy and safety of first-line checkpoint inhibitors-based treatments for non-oncogene-addicted non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Frontline immune checkpoint inhibitors (ICI)-based regimens in non-oncogene-addicted non-small-cell lung cancer (NSCLC) have been deeply investigated. To rank the available therapeutic options, we carried out a systematic review and Bayesian meta-analysis. METHODS: A comprehensive search for randomized controlled trials (RCTs) of ICI regimens, and a pairwise and a network meta-analysis (NMA) with an all-comers and a stratified strategy were conducted. Endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (TRAEs). RESULTS: Nineteen RCTs involving 17 treatment regimens were included. For the all-comers population, pembrolizumab/chemotherapy (CT) and cemiplimab were most likely the best treatments. For programmed death-ligand 1 (PD-L1) <1% nivolumab/ipilimumab with/without CT, for PD-L1 >1% and 1%-49% pembrolizumab/CT and for PD-L1 >50% cemiplimab ranked first for OS. In non-squamous (NSQ), pembrolizumab with/without CT ranked first for OS; cemiplimab ranked worse than the unselected population. In squamous (SQ), pooled hazard ratio (HR) showed a better chance in improving efficacy for combination strategy, while monotherapy did not, except for cemiplimab that ranked second. Atezolizumab/CT/bevacizumab ranked first in most subgroups for PFS. Direct comparison showed a non-statistically significant benefit of ICI regimens for the liver metastases cohort in OS, with a good ranking for pembrolizumab/CT and atezolizumab/bevacizumab/CT. Regarding brain metastases, all ICI regimens demonstrated an improvement in OS and PFS compared to CT. Nivolumab/ipilimumab/CT ranked better in this subset. CONCLUSIONS: Our meta-analysis updated on the most recent findings demonstrates that different ICI treatments rank differently in specific NSCLC settings (histology, biomarker and clinical presentation) offering a novel challenging scenario for clinical decision making and research planning.

EBV persistence in gastric cancer cases conventionally classified as EBER-ISH negative.

BACKGROUND: The Epstein-Barr virus (EBV) causes various B-cell lymphomas and epithelial malignancies, including gastric cancer (GC) at frequencies ranging from 5 to 10% in adenocarcinomas (ADK) to 80% in GC with lymphoid stroma (GCLS). Using high-sensitivity methods, we recently detected EBV traces in a large cohort of EBV-negative B-cell lymphomas, suggesting a hit-and-run mechanism. METHODS: Here, we used routine and higher-sensitivity methods [droplet digital PCR (ddPCR) for EBV segments on microdissected tumour cells and RNAscope for EBNA1 mRNA] to assess EBV infection in a cohort of 40 GCs (28 ADK and 12 GCLS). RESULTS: ddPCR documented the presence of EBV nucleic acids in rare tumour cells of several cases conventionally classified as EBV-negative (ADK, 8/26; GCLS, 6/7). Similarly, RNAscope confirmed EBNA1 expression in rare tumour cells (ADK, 4/26; GCLS, 3/7). Finally, since EBV induces epigenetic changes that are heritable and retained after complete loss of the virus from the host cell, we studied the methylation pattern of EBV-specifically methylated genes (Timp2, Eya1) as a mark of previous EBV infection. Cases with EBV traces showed a considerable level of methylation in Timp2 and Eya1 genes that was similar to that observed in EBER-ISH positive cases and greater than cases not featuring any EBV traces. CONCLUSIONS: These findings suggest that: (a) EBV may contribute to gastric pathogenesis more widely than currently acknowledged and (b) indicate the methylation changes as a mechanistic framework for how EBV can act in a hit-and-run manner. Finally, we found that the viral state was of prognostic significance in univariate and multivariate analyses.

"Say Ninetynine": It's Never too Late to Recover from COVID-19.

COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, showed higher severity and lethality in male older adults . There are currently no specific treatments. Studies are evaluating the efficacy of monoclonal antibodies against interleukin-6 receptor. Here we present the case of a 98-years old man admitted to our COVID-Hospital with acute respiratory failure. Comprehensive geriatric assessment showed no signs of frailty. First-line therapy with hydroxychloroquine and anticoagulants was not effective. Patient was administered intravenous monoclonal antibodies, and he showed remarkable clinical improvement. This case suggests that age alone should not preclude access to new therapeutic approaches. Comprehensive, multisciplinary, multidomain approaches are needed to develop patient-tailored treatments against COVID-19.

Cloning and characterization of 5E6(Ly-49C), a receptor molecule expressed on a subset of murine natural killer cells.

5E6 is a cell surface molecule expressed on a subpopulation of murine natural killer (NK) cells that are involved in the specific rejection of H-2d or H-2f (hemopoietic histocompatibility determinant 2) bone marrow cell grafts. Here, we isolated and cloned the gene encoding 5E6 and determined the nucleotide sequence of the cDNA. 5E6 is nearly identical to Ly-49C; the deduced amino acid sequence reveals a polypeptide of 266 amino acids with a molecular weight of 31,284 that contains multiple cysteine residues to explain its disulfide-linked homodimer structure and five potential N-linked glycosylation sites. 5E6 is a type II integral membrane protein with an extracellular carbohydrate recognition domain characteristic of C-type (Ca(2+)-dependent) animal lectins. Chromosomal mapping indicates that 5E6 is located within the NK gene complex on chromosome 6. The sequence of 5E6 mRNA and the degree of glycosylation of 5E6 protein are under genetic control. Immunoprecipitation before removal of N-linked sugars reveals different size molecules. There are several nucleotide differences among BALB/c, B6, and NZB mRNAs; however, none of them would be expected to affect N-glycosylation. Of particular interest are two findings: (a) BALB/c, B6, and (BALB/c x B6)F1 5E6 reduced molecules are approximately 65, 54, and 54 kD, and (b) the cDNA sequence of (BALB/c x B6)F1 is identical to B6. Thus, there appears to be allelic exclusion of 5E6 expression that may be related to the ability of F1 hybrid mice to reject parental H-2d bone marrow cell grafts.

Seroconversion of HBsAg in HBeAg positive and HBeAg negative patients with chronic HBV treated with entecavir: a case series.

We report a case series of three HBeAg positive and five HBeAg negative patients (7 males, mean age 50.6 +/- 14.6 years) with chronic HBV infection experiencing seroconversion after treatment with entecavir (0.5 mg/day or 1 mg/day), initiated in 2007. Overall, the mean time to HBsAg clearance was 9.4 +/- 4.5 months. Seroconversion occurred in all patients, after a mean time of 8.0 +/- 3.7 months. In HBeAg negative patients, mean time to HBsAg clearance and to seroconversion were 9.2 +/- 5.9 and 6.8 +/- 4.0 months, respectively. In HBeAg positive patients, mean time to HBsAg clearance and to seroconversion were 9.7 +/- 0.6 months and 10.0 +/- 2.6 months, respectively. In this case series, seroconversion was maintained and was observed both in HBeAg positive patients and in HBeAg negative patients. Therefore, it may be preliminarily suggested that treatment with entecavir could be associated to HBsAg seroconversion in a short period of time, in both HBeAg positive and HBeAg negative HBV patients.

Predictors of fatigue severity in early, de novo Parkinson disease patients: A 1-year longitudinal study.

INTRODUCTION: Fatigue is one of the most common and disabling nonmotor symptom in Parkinson's disease (PD). The aim of the present study was to investigate the 1-year course of fatigue in a consecutive sample of de novo drug-naïve patients with PD, and at systematically searching for baseline motor and nonmotor predictors associated with fatigue severity over time. METHODS: Fifty-five consecutive de novo PD patients (age: 64.71 ± 7.74 years) underwent a comprehensive examination, including Parkinson Fatigue Scale, Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, Beck Depression Inventory, Parkinson's Anxiety Scale, Apathy Evaluation Scale, and an extensive neuropsychological evaluation. Bivariate and multiple regression analyses were performed to identify baseline predictors independently related to fatigue severity at 1-year follow-up. RESULTS: Prevalence rate of fatigue (defined by PFS cut-off) increased from 22% at baseline to 38% at 1-year follow-up. A similar increase in prevalence was observed for excessive daytime sleepiness, and apathy. Among patients with fatigue at baseline, 91% had fatigue at follow-up too (i.e., persistent fatigue). Multivariate regression analysis identified fatigue (p < 0.01), daytime sleepiness (p < 0.01), and emotional apathy (p < 0.01) as the main baseline variables significantly predicting fatigue severity at 1-year follow-up. CONCLUSION: In early PD, fatigue increases and persists over time, and its severity is related to higher baseline levels of fatigue, excessive daytime sleepiness, and emotional apathy. These results warrant to monitor fatigue since the early stage of disease, and suggest that treating excessive daytime sleepiness and emotional apathy might prevent its worsening.

Isolation of human transcribed sequences from human-rodent somatic cell hybrids.

A method was developed for selectively isolating genes from localized regions of the human genome that are contained in interspecific hybrid cells. Complementary human DNA was prepared from a human-rodent somatic cell hybrid that contained less than 1% human DNA, by using consensus 5' intron splice sequences as primers. These primers would select immature, unspliced messenger RNA (still retaining species-specific repeat sequences) as templates. Screening a derived complementary DNA library for human repeat sequences resulted in the isolation of human clones at the anticipated frequency with characteristics expected of exons of transcribed human genes--single copy sequences that hybridized to discrete bands on Northern (RNA) blots.

Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia.

The pericentric inversion of chromosome 16 [inv(16)(p13q22)] is a characteristic karyotypic abnormality associated with acute myeloid leukemia, most commonly of the M4Eo subtype. The 16p and 16q breakpoints were pinpointed by yeast artificial chromosome and cosmid cloning, and the two genes involved in this inversion were identified. On 16q the inversion occurred near the end of the coding region for CBF beta, also known as PEBP2 beta, a subunit of a heterodimeric transcription factor regulating genes expressed in T cells; on 16p a smooth muscle myosin heavy chain (SMMHC) gene (MYH11) was interrupted. In six of six inv(16) patient samples tested, an in-frame fusion messenger RNA was demonstrated that connected the first 165 amino acids of CBF beta with the tail region of SMMHC. The repeated coiled coil of SMMHC may result in dimerization of the CBF beta fusion protein, which in turn would lead to alterations in transcriptional regulation and contribute to leukemic transformation.

Fatigue in Parkinson's disease: Italian validation of the Parkinson Fatigue Scale and the Fatigue Severity Scale using a Rasch analysis approach.

INTRODUCTION: The Fatigue Severity Scale (FSS-9) and the Parkinson Fatigue Scale (PFS-16) are commonly used for assessing fatigue in Parkinson's disease (PD). Here we validated the Italian version of these scales, assessed their psychometric properties by Rasch analysis, and computed their optimal cut-off scores using clinical diagnosis of PD-related fatigue as the gold standard. METHODS: PD patients (n = 167) completed the Italian versions of FSS-9 and PFS-16. Each item of PFS-16 was scored both on a 5-point (PFS-16polytomous) and on a 2-point scale (PFS-16dichotomous). RESULTS: All scales showed an adequate overall Rasch model fit, high reliability, and good discriminant, convergent, and concurrent validity, but were less accurate in measuring very high and very low fatigue levels. No evidence of differential item functioning with respect to age, sex, and severity of parkinsonian symptoms was found. Some items of FSS-9 (item 1), PFS-16polytomous (items 1 and 13), and PFS-16dichotomous (items 1, 8, and 13) showed misfit, possibly due to their content concerning sleep and motivation disorders. When FSS-9 and PFS-16polytomous' responses were rescored on a 3-point scale, the discriminability across response categories improved. The optimal cut-off score in detecting clinically-diagnosed fatigue (observed in 20% of the sample) was 3.09 for PFS-16polytomous, 8.00 for PFS-16dichotomous, and 4.67 for FSS-9. CONCLUSIONS: The Italian version of PFS-16 and FSS-9 showed sound psychometric properties and can be confidently used to quantify fatigue symptoms in PD, although clinical diagnosis of fatigue should rely on validated criteria. The PFS-16polytomous exhibited advantages with respect to PFS-16dichotomous.

Donor risk index and organ patient index as predictors of graft survival after liver transplantation.

In liver transplantation the identification of risk factors and the risk quantification for each single case represent a field of great interest. There are donor-related and recipient-related risk factors. Donor risk index (DRI) was retrospectively calculated in 223 liver transplant cases. We did not include patients with preoperative diagnosis of hepatocarcinoma and retransplants. The cases were stratified into two classes according to the DRI (low risk, DRI<1.7, and high risk, DRI >or= 1.7). A new index, namely the organ patient index (OPI) was calculated adding the Model for End-stage Liver Disease (MELD) score to the DRI. Patients were stratified into two classes according to the OPI (low risk, OPI 2.85). The cases with low DRI (n=144) showed better survival than the cases with high DRI (n=82; P< .02). The cases with low OPI (n=173) showed better survival than cases with high OPI (n=50; P< .01). The OPI predicted outcomes better than DRI, increasing the gap in the long-term graft survival between the low- and the high-risk class. The inclusion of the MELD in the new index allowed better prediction of graft survival.

Treatment of chronic hepatitis C virus infection with pegylated interferon and ribavirin in cirrhotic patients awaiting liver transplantation.

Successful treatment of chronic hepatitis C virus (HCV) infection can prevent reinfection after orthotopic liver transplantation (OLT). Pegylated interferon (PEG-IFN) may ameliorate virological response (VR), making the risk-to-benefit ratio of therapy favorable in waiting list patients. From January 2001 to April 2006, we treated 15 HCV cirrhotics with PEG-IFN alpha-2b (1.5 microg/kg/week) and ribavirin (RIBA; >or=10.6 mg/kg/d). Their mean age was 51.5 years. There were 9 men. In 6 cases the genotype was 1b. With Child-Pugh scores >or=9 (range 9-12) and Model for End-Stage Liver Disease (MELD) scores >or=14 (range, 14-22). Adverse events occurred in all subjects: thrombocytopenia (<40,000/microL) in 8; neutropenia (<700/microL) in 10; anemia (Hb <8.5 g/dL) in 1; grade III hepatic encephalopathy in 2; pelvic infection in 1; variceal hemorrhage in 1; and hepatocellular carcinoma (HCC) recurrence in 1. Adverse events caused treatment withdrawal in 6 (40.0%) and RIBA and/or PEG-IFN dose reduction in 10 (66.6%). Early VR (EVR) was obtained in 9 subjects (60.0%), end-of-treatment (EOT) VR in 7 (46.6%), and sustained VR (SVR) in 3 (20.0%). Three subjects--2 nonresponder and 1 breakthrough--were transplanted at 25, 23, and 16 months after the EOT, respectively. Three subjects died at 6, 8, and 15 months after the EOT due to HCC, spontaneous bacterial peritonitis, and liver failure. Nine patients are awaiting OLT. The risk-to-benefit ratio is against PEG-INF and RIBA treatment of severely decompensated cirrhotics infected with genotype 1 awaiting OLT, but therapy is probably beneficial in genotype 2 subjects, due to an expected SVR rate of more than 40%. However, one must carefully consider the high risk for severe adverse events.