Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis.

Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of "too-sick-to-treat patients" to avoid futile treatments.

Fatal sclerosing peritonitis associated with primary effusion lymphoma after liver transplantation: a case report.

Sclerosing peritonitis (SP) after liver transplantation has been described in 10 cases in the literature. The etiology is still unknown; however, SP is considered a consequence of chronic irritation and inflammation. It can be classified as primary (idiopathic) or secondary form. Although pathologically benign, it has a negative course, resulting in unrelenting abdominal pain, small bowel obstruction, malnutrition, and death. Posttransplantation lymphoproliferative disease (PTLD) is one of the leading causes of late death. Its development is related to complex interactions between immunosuppressive drugs and environmental agents. Primary effusion lymphoma (PEL) as an onset presentation of PTLD is relatively uncommon. Most examples of effusion-based PTLD have been secondary to widespread solid organ involvement and associated with Human herpes virus 8 (HHV-8) recurrence. Here in, we report a case of a 55-year-old man who rapidly developed refractory ascites and bacterial peritonitis at 1-year after orthotopic liver transplantation (OLT) with a fatal clinical course at the beginning of the second follow-up year after an uncomplicated liver transplantation due to cryptogenic cirrhosis. The diagnosis of HHV-8-positive lymphoma was established by postmortem examination with multiple solid localizations and massive dense fibrotic adhesions encompassing the small intestine, colon, liver, and porta hepatis without any involvement of body cavities.

Measurement of numicro and nue events in an off-axis horn-focused neutrino beam.

We report the first observation of off-axis neutrino interactions in the MiniBooNE detector from the NuMI beam line at Fermilab. The MiniBooNE detector is located 745 m from the NuMI production target, at 110 mrad angle (6.3 degrees) with respect to the NuMI beam axis. Samples of charged-current quasielastic numicro and nue interactions are analyzed and found to be in agreement with expectation. This provides a direct verification of the expected pion and kaon contributions to the neutrino flux and validates the modeling of the NuMI off-axis beam.

Cryptococcal lymphadenitis as a manifestation of immune reconstitution inflammatory syndrome in an HIV-positive patient: a case report and review of the literature.

Cryptococcus neoformans infections are typically associated with T-cell deficiencies, including acquired immunodeficiency syndrome (AIDS). Although highly active antiretroviral therapy (HAART) has strongly reduced AIDS-related opportunistic infections, the restoration and reactivation of CD4+ cells can induce an immune reconstitution inflammatory syndrome (IRIS), consisting in a deregulated inflammatory response to latent infectious pathogens and/or to their residual antigens. Cryptococcal lymphadenitis has occasionally been documented in IRIS. Here we report a case of histology- and culture-negative cryptococcal lymphadenitis associated with IRIS in an adult AIDS patient with a history of disseminated cryptococcosis, after the start of fully adherent HAART. Appropriate diagnosis was established on nested-PCR and sequence analysis of the interspacer region 2 of C. neoformans ribosomal DNA, and detection of slow-growing blastospores in enrichment cultures of fine-needle lymph node aspirate. Review of recent literature and our case findings suggest that IRIS-associated cryptococcal lymphadenitis is more likely the flare up of a latent infection rather than an immunopathological response to residual antigen of unviable cryptococci.

Immunohistochemical expression of cyclin T1 in a case of AIDS-related cachexia.

The expression of cyclin T1 in an autoptic case of AIDS-related cachexia was investigated by immunohistochemistry. When contrasted with normal human tissues, a very similar pattern of expression was found. However, a peculiar distribution of cyclin T1 was noticed in the brown fat and in lymph nodes affected by AIDS-associated lymphadenopathy.

Ciprofloxacin versus chloramphenicol in the treatment of salmonella infection.

Strains of Salmonella typhi resistant to chloramphenicol and ampicillin have been isolated in several countries. This study compares treatment of Salmonella infection using ciprofloxacin (500 mg twice daily) for 10 days with chloramphenicol (50 mg/kg per day divided into four doses) for 14 days. The pathogen eradication rates for patients receiving ciprofloxacin was 18/20 (90%), compared with 25/28 (89%) for those who received chloramphenicol. Signs and symptoms in patients receiving chloramphenicol lasted longer and sometimes twice as long as patients treated with ciprofloxacin. In this study, ciprofloxacin was superior to cloramphenicol in the treatment of S. typhi infection and also had fewer side-effects and the convenience of a twice-a-day dosing

Molecular characterization of HCV 1b intra-familiar infection through three generations.

Vertical transmission is an uncommon route of hepatitis C virus (HCV) infection. Little is known about the way of virus spread between relatives. Furthermore, the nucleotide sequence variability studies that can be used for the definition of cases of HCV transmission still need accurate standardization. In this study, we analyzed the HCV positive sera from subjects belonging to one family. Five out of seven individuals were positive both for anti-HCV and HCV-RNA. The epidemiological data, in our knowledge, excluded the possible risk of parenteral exposure to HCV for the members of the family. The genetic relatedness of the viruses infecting the members of this family was demonstrated by the phylogenetic analysis of sequences from E1 genome region. The analysis included the calculation of the genetic divergence specific index, based on the ratio of synonymous/non-synonymous mutations. By the analysis of this genome region, we demonstrated the occurrence of HCV transmission among family members. In 2 cases out of 3, Mother-to-Infant transmission was demonstrated that involved three generations of the family. Transmission by sexual route was absent. A method of sequence analysis of E1 HCV genome region is proposed as molecular approach for the definition of transmission cases of HCV.

[Plasma HIV-1 RNA viral load up to one year of follow-up in 64 patients treated with HAART] / Follow up ad un anno della carica virale plasmatica di HIV in 64 soggetti trattati con HAART.

The aim of this study was to evaluate efficacy of highly active antiretroviral therapy (HAART) in 64 HIV-1 positive treatment-naive and previously treated patients, with different viral load at baseline. The HAART regimen consisted of one protease inhibitor and two reverse-transcriptase inhibitors. Plasma RNA viral load was measured by RT-PCR (Roche Amplicor Monitor kit) at enrolment and at months 3, 6, 9, and 12 of follow-up. The viral load fell below the threshold of 200 copies/ml in 46.9% of patients at month 6 and this result lasted up to month 12 of follow-up in 42.2% of patients. In these patients the CD4+ cell count increased from a baseline with a median of 194 cells/mmc at month 12. Treatment failure occurred in 35.9% of patients and the proportion was higher among previously treated patients. 7 patients stopped therapy because of poor compliance and 5 because of adverse drug effects. Also in our cases the HAART regimen showed more efficacy in treatment-naive patients, whereas baseline viral load >1x105 was the cause of less efficacy of therapy.

Hepatitis C virus infection in family setting.

To evaluate risk factors associated with intrafamiliar transmission of hepatitis C virus (HCV), 113 hepatitis C virus index subjects with chronic HCV infection and their 267 family contacts were studied from January 1994 to October 1995. Overall, 16 family contacts (6%) were positive for anti-HCV by ELISA II generation. The prevalence was 11.3% in spouses and 2.9% in other relatives (odds ratios: 4.2; 95% CI: 1.4-12.6). Spouses who had been married to the index cases longer than 20 years had a 7.5-fold risk (95% CI: 1.0-336.3) of HCV seropositivity as compared to those married less than 20 years. In univariate analysis HCV seropositivity was associated with surgical intervention, use of glass syringes and hospitalization. The results of multivariate logistic analysis showed that any parenteral exposure (odds ratios: 3.8; 95% CI: 1.2-12.8) and sexual contact with an anti-HCV index case (odds ratios: 3.0; 95% CI: 1.0-9.4) were both independent predictors of HCV seropositivity among household contacts of HCV positive index cases. These findings indicate that sexual contact and any parenteral exposure both play an independent role in the spread of HCV infection in the family setting.

Prevalence, risk factors, and genotype distribution of hepatitis C virus infection in the general population: a community-based survey in southern Italy.

In 1996 the prevalence, risk factors, and genotype distribution of hepatitis C virus (HCV) infection were assessed in the general population of a town in southern Italy. The sample was selected from the census by a systematic 1:4 sampling procedure. The participation rate was 96.6%. Among the 1,352 subjects enrolled, 195 (14.4%) tested reactive to antibody to HCV (anti-HCV) with enzyme immunoassay (EIA 3). When further tested with recombinant immunoblot assay (RIBA 3), 170 subjects (87.2%) tested positive, 23 subjects (11.8%) had indeterminate results, and 2 subjects (1%) tested negative. Thus, the overall anti-HCV EIA-positive RIBA-confirmed prevalence was 12.6% (170 of 1,352 subjects) and increased from 1.3% in subjects younger than 30 years to 33.1% in those > or =60 years of age. This latter age group accounted for 72.3% of all anti-HCV-positive subjects. Females tested positive more frequently than males (14.1% vs. 10.5%; P < .05). Alanine transaminase (ALT) concentrations were abnormal in only 4.1% (7/170) of anti-HCV EIA-positive RIBA-confirmed subjects. This suggests that ALT screening is not useful in the detection of anti-HCV-positive subjects in a general population. The results of multiple logistic regression analysis showed that an age of less than 45 years, the use of glass syringes, and dental therapy were all independent predictors of anti-HCV positivity. HCV RNA was detected by polymerase chain reaction in 75.9% of the 195 anti-HCV EIA-positive subjects: in 84.7% (144/170) of the RIBA-confirmed subjects; in 17.4% (4/23) tested as RIBA indeterminate; and in neither of the two subjects who tested RIBA negative. HCV type 1b was detected in 75 subjects (50.7%), type 2b in 1 subject (0.7%), type 2c in 66 subjects (44.6%), type 3a in 4 subjects (2.7%), and type 4 in two subjects (1.3%). These figures differ from those of Italian patients with chronic liver disease in whom genotype 2 is more rare. None of the individuals was infected with more than one genotype. The distribution of the two most common HCV viral types (1b and 2c) was not statistically different in terms of mean age, sex, or risk factors and suggests that they may have had a parallel spread in this community. These findings provide one of the highest overall anti-HCV prevalence rates in a general population with a likely cohort effect, i.e., decreased risk of infection along generations. These observations may indicate an epidemic or focus of hepatitis C that occurred several years earlier. The majority of anti-HCV-positive subjects in the oldest age group and with no clinical evidence suggests that HCV infection is a very prolonged and indolent disease.

Identification of HCV genotypes in the Calabria region.

The present work describes the distribution of HCV genotypes in Calabria. The data presented suggest that, in the sample of population investigated, genotype 1b is the most prevalent followed by the 2b and the 2a.. In addition it is important to note that in Calabria the prevalence of genotype 1b is strikingly high in respect to the other Italian pullulation. An Association between HCV type 1b and the more severe clinical course of the liver disease has been reported. Although the data presented indicate that in Calabria most of the subjects enrolled in the study are infected by a virulent HCV strain, no association has been found with more severe clinical manifestations.

Variability in the clinical skills of residents entering training programs in surgery.

BACKGROUND: Residents may have significant differences in clinical skills at the start of their surgical training. The purpose of this study was to investigate the variability in these skills by using an objective structured clinical examination. METHODS: A needs assessment was performed, and an objective structured clinical examination composed of 10, two-part stations was developed. Standardized patients (SPs) were trained, validated, and used as both simulated patients and evaluators to assess history taking, physical examination, and interpersonal skills of 10 first-year surgical residents. Structured patient notes (PNs) written by residents after the SP encounters were used to assess history and physical examination documentation skills. Data from one station were not used because more than 25% of the SP ratings were missing. RESULTS: The alpha-reliability was 0.78 for SP ratings, 0.91 for PN scores, and 0.91 for the combined scores. ANOVA revealed significant variation in individual residents' clinical skills as assessed by SPs (F = 4.56, p < 0.01), PNs (F = 11.09, p < 0.001), or both (F = 10.9, p < 0.001). Paired t tests showed that residents scored significantly higher on history taking than on physical examination and attained significantly lower scores on documentation as compared with performance of both history and physical examination (p < 0.001 for each comparison). CONCLUSIONS: The results showed significant variability in clinical skills of the group of residents and yielded detailed information on the performance of each resident. The data were shared with individual residents and are being used to make changes in the educational activities of the program.

Age determination of experimental venous thrombi by ultrasonic tissue characterization.

PURPOSE: The ability of ultrasonic tissue characterization based on radiofrequency signal processing to detect compositional differences in thrombi of varying ages was evaluated in vivo. METHODS: Thrombi were produced in 49 jugular veins of 26 anesthetized 18 to 20 kg pigs by partial ligation and application of direct electric current. Thrombi were imaged 30 minutes after formation and 1, 7, and 14 days later with a color Doppler ultrasound scanner that identified the thrombi, and acquired radio frequency data for ultrasonic tissue characterization analysis. Ultrasonic tissue characterization used two parameters from the normalized power spectrum, slope, and intercept, which are related to scatterer size, scatterer concentration, and acoustic-impedance differences between scatterers and surrounding medium. Previous in vitro studies demonstrated that lower slope and higher intercept values correlated with greater cellularity and more-dense fibrin mesh. Histologic examination was performed for each time period. The values of slope and intercept for each timed observation were compared by a multilinear discriminant analysis. RESULTS: There were no statistical differences between day 0 and day 1. Statistically-significant differences in ultrasonic tissue characterization parameters were seen between all other time intervals with p values < 0.01. Older thrombi tended to demonstrate higher slope and lower intercept values. These ultrasonic tissue characterization changes correlated with a red cell and fibrin-mesh density reduction, which was confirmed by histologic findings and was indicative of partial spontaneous thrombolysis. The degree of spontaneous thrombolysis provides an estimate of the age of thrombi. CONCLUSION: Ultrasonic tissue characterization is capable of distinguishing age differences in thrombi in an animal model and has the potential for noninvasive application in clinical diagnosis.

Ultrasonic detection of viscera slide as an indicator of abdominal wall adhesions.

Real-time ultrasonography can detect the movement of viscera immediately deep to the abdominal wall. This motion of abdominal contents is called viscera slide, and is produced by the force of respiratory motion (spontaneous viscera slide) or by manual ballottement of the abdomen (induced viscera slide). Viscera slide was observed in 18 "normal" subjects (no history of previous abdominal surgery or peritonitis) and in 24 subjects at "risk" for abdominal wall adhesions because of previous abdominal operations or past history of peritonitis. In 14 of the 24 "risk" group subjects, spontaneous and induced viscera slide was restricted to excursions of less than 1 cm (58.3%). Operations were performed on 18 patients, which confirmed the fact that restriction of ultrasonically detected viscera slide identified abdominal wall adhesions in all cases, but no adhesions were found in patients with normal viscera slide. This ultrasonic finding of restricted viscera slide may be useful in the preoperative discovery and localization of abdominal wall adhesions prior to laparoscopy or laparotomy.

Operative color Doppler imaging for vascular surgery.

Operative color Doppler imaging (CDI) was performed during 57 vascular operations (24 carotid, 24 lower extremity, six renal artery, and three other operations), and its benefits were assessed in comparison to B-mode imaging. Pre-reconstruction operative CDI was used selectively in 18 operations, and post-reconstruction operative CDI was used routinely in all operations. In 16 operations (28.6%), post-reconstruction CDI diagnosed vascular defects such as intimal flaps (n = 4), anastomotic stenoses (n = 7), and in situ bypass arteriovenous fistulas (n = 4). Vascular defects at eight operations required immediate repair. Operative CDI had advantages over B-mode imaging in (1) detection of preoperatively unknown vascular abnormalities before reconstruction, (2) faster recognition of vascular defects after reconstruction, (3) unique ability to detect problems (i.e., arteriovenous fistulas) that were unidentifiable by B-mode imaging, and (4) provision of supplemental blood flow information.

Cellularity and fibrin mesh properties as a basis for ultrasonic tissue characterization of blood clots and thrombi.

This in vitro study was designed to evaluate the ability of ultrasonic tissue characterization (UTC) based on power spectrum analysis of backscattered radio-frequency echo signals to distinguish two prominent variables of thrombi: cellularity (primarily red cell content) and fibrin-mesh density. Six types of clots simulating thrombus components were prepared by varying red-cell and platelet concentrations and shear forces during clotting. Data were acquired with a linear-array transducer, digitized, and analyzed in terms of slope and intercept parameters obtained from normalized power spectra of radio-frequency echo signals. Increased cellularity and fibrin-mesh density both produced lower slope and higher intercept values, which permitted statistically significant discrimination of cellularity and mesh density in the six types of clots analyzed. Shearing forces and (to a lesser degree) platelet concentrations increased fibrin-mesh density. This study suggests that UTC based upon the power spectrum of echo signals may be used to detect and follow compositional differences that have clinical relevance in the diagnosis and follow-up of thrombi.

Detection of preoperatively unrecognized multiple pancreatic pseudocysts by intraoperative ultrasonography. Report of two cases.

During two pancreatic operations, intraoperative ultrasonography detected multiple pancreatic pseudocysts that were unrecognized preoperatively. In each operation, a single pseudocyst was detected by preoperative ultrasonography, computed tomography, and intraoperative surgical exploration. In addition, high-resolution ultrasonography used during the operations also identified and precisely localized additional smaller pseudocysts. Also, the use of color Doppler imaging during the operations enabled the delineation of small blood vessels around the pseudocysts. The accurate diagnosis of multiple pseudocysts and the precise anatomic information provided by intraoperative ultrasonography permitted appropriate surgical treatment of the pancreatic pseudocysts which, in turn, might help prevent recurrence of the disease.

Technique of ultrasonic detection and mapping of abdominal wall adhesions.

A technique for noninvasive ultrasound examination to detect and map abdominal wall adhesions is described. The examination is based on the demonstration of movement of abdominal viscera during real-time imaging. This movement is called viscera slide and either occurs spontaneously as a result of respiratory movement or may be induced by manual compression. Abdominal wall adhesions produce a restriction of viscera slide. Ultrasonic demonstration of restricted viscera slide has been used for the precise localization and mapping of abdominal wall adhesions prior to abdominal surgery. The technique may be particularly useful in providing safe initial access in patients undergoing laparoscopy who are at increased risk for trocar injury of viscera due to abdominal wall adhesions resulting from previous surgery or peritonitis.