Detection of hepatitis B virus (HBV) genotype E carried--even in the presence of high titers of anti-HBs antibodies--by an Argentinean patient of African descent who had received vaccination against HBV

Genotype E hepatitis B virus (HBV) was detected in two Argentine sisters exhibiting an African mitochondrial lineage. One of them (who had been vaccinated against HBV) exhibited anti-HBs cocirculating antibodies without HBsAg escape mutants, while her unvaccinated sister showed a D144A HBsAg escape mutant without anti-HBs antibodies. Both sisters carried an unusual L209V substitution within HBsAg.     

Tamoxifen vs. non-tamoxifen treatment for advanced melanoma: a meta-analysis

Although tamoxifen (TAM) is routinely used in advanced melanoma, it is still uncertain whether evidence exists to support this practice. This review assesses the benefits and harms of systemic therapy with TAM vs. without TAM on response and mortality in patients with advanced melanoma. MEDLINE, The Cochrane Database of Systemic Reviews, The Cochrane Central Register of Controlled Trials, EMBASE and LILACS were searched for randomized controlled trials comparing chemotherapy using and not using TAM in any dose, in patients of any age with advanced melanoma. References lists, databases of ongoing trials and conference proceedings were hand-searched. All included trials were evaluated for quality assessment. Primary outcomes were response and mortality. Secondary outcomes were hematologic and non hematologic toxicity, treatment-related mortality and quality of life. A meta-analysis was performed and results were presented as relative risk with 95% confidence interval. Nine randomized controlled trials met the inclusion criteria. Patients treated with TAM were more likely to respond, with a relative risk 1.36 (95% CI: 1.04-1.77, P = 0.02). However, there was no improvement in 1-year mortality. The incidence of hematologic toxicity was higher in the TAM group. Subgroup analyses showed that female patients were more likely to respond. Chemotherapies with TAM improve overall and partial response, but do not improve mortality in 1 year in advanced melanoma. Further use of TAM in melanoma should be done only in the context of clinical trials.     

In vitro binding of simian immunodeficiency virus matrix protein to the cytoplasmic domain of the envelope glycoprotein

Incorporation of the envelope (Env) glycoprotein into budding virions is a key step in the replication cycle of lentiviruses. Previously, we provided genetic and biochemical evidence indicating that Env packaging into simian immunodeficiency virus (SIV) particles is mediated by the association of the Env cytoplasmic domain (CD) with the matrix (MA) domain of Gag. In this study, we developed an in vitro binding assay that, based on recombinant proteins expressed in bacteria, allowed us to demonstrate the physical interaction between the SIV Env CD and the MA in the absence of other viral or cellular proteins. We show that this association is blocked by mutations in each of the interacting domains that have been reported to interfere in vivo with the incorporation of Env into SIV virions. Moreover, we determined that the binding of SIV MA to the Env CD is saturable with a dissociation constant of 7x10(-7) M. Interestingly, the SIV MA is capable of specifically interacting in vitro with the human immunodeficiency virus type 1 Env CD, but not with that of the distantly related feline immunodeficiency virus. Our results strongly support the notion that the association between the SIV MA and Env CD plays a central role in the process of SIV Env incorporation into Gag-made particles.     

Utility of the Thin Prep Imaging System® in the detection of squamous intraepithelial abnormalities on retrospective evaluation: Can we trust the imager?

Prospective studies analyzing the ThinPrep Imaging System (TIS) have demonstrated a significant decrease in screening time and detection rates comparable or better than manual screening. We retrospectively analyzed the accuracy of the TIS in detecting cervical abnormalities. Our study included all new HSIL diagnoses in 2007 with previous negative (NIL) pap tests screened with TIS. The original 22 fields of view (FOV) were reviewed by 2 blinded screeners followed by manual screening of all slides. Any ASC-US or above was considered "abnormal." Of a total of 111,080 pap tests performed in 2007, 180 were reported as HSIL. Of these, 45 cases had a previous NIL pap diagnosed within the last year, screened with TIS. Following re-examination of the NIL pap, 31 diagnoses remained unchanged and 9 were reclassified as abnormal on the basis of cells present within the original FOV. When manually reviewed, all nine cases were confirmed as abnormal. Four cases were reclassified as abnormal on the basis of the manual screen (abnormal cells absent in the FOV). The sensitivity of TIS for the detection of abnormality was 99.95% (false-negative rate FNR: 0.05%) and the sensitivity for detection of HSIL was 99.07% (FNR: 0.92%). When analyzing the cytotechnologist interpretation of the FOV, the sensitivity for detection of abnormality and HSIL was 99.89% (FNR: 0.1%), and 99.53% (FNR: 0.4%), respectively. On retrospective analysis based on newly diagnosed HSIL cases, the sensitivity of TIS was comparable to that of manual screening with a slightly decreased rate of false negatives.     

Outcome of males with high anorectal malformations treated with laparoscopic-assisted anorectal pull-through: preliminary results of a comparative study with the open approach in a single institution

Objective

The aim of this study was to analyze the outcome of males with HARM treated with a laparoscopic-assisted anorectal pull-through compared with the open posterior sagittal approach in a single institution.

Methods

This study includes 32 patients: 17 (9 with a rectoprostatic fistula [RPF] and 8 with a rectovesical fistula [RVF]) who underwent laparoscopic-assisted anorectal pull-through from October 2001 onward and 15 (8 with an RPF and 7 with an RVF) treated by posterior sagittal approach before that date. Patients were reviewed retrospectively but were operated on by the authors and had longitudinal follow-up. Parameters analyzed included associated anomalies, sacral ratio (SR) index, age at surgery, operative time, complications, presence of voluntary bowel movements, constipation, and soiling. A good outcome was determined by absent or grade 1 soiling and a poor outcome result by soiling grades 2 and 3.

Results

Mean age at surgery was 22 and 37.5 months for patients with RPF and RVF, respectively, in the laparoscopic group and 29.2 and 25.7 months in the open group. Operative time was significantly shorter (P < .0036) for the laparoscopic RVF repair compared with the open approach. In patients with RPF, 50% in the laparoscopic (L) and 37.5% in the open (O) approach had an SR below 0.6. Fifty percent of all patients with RVF had an SR below 0.6, making groups comparable in terms of evaluating bowel function. Four patients were excluded in the analysis of functional results. Voluntary bowel movements with previous defecatory sensation were present in 83.l3% (5/6) in L vs 87.5% (7/8) in O patients with RPF and 62.5% (5/8) L vs 50% (3/6) in O patients with RVF. Grade 1 soiling was present in 50% (3/6) vs 62.5% (5/8) of patients with RPF and 37.5% (3/8) vs 16% (1/6) of patients with RVF in the L and O groups, respectively. Soiling grade 2 or 3 was present in 50% (3/6) vs 12.5% (1/8) of patients with RPF and 37.5% (3/8) vs 50% (3/6) of patients with RVF in the L and O groups, respectively. The risk of poor outcome was 61% in the group with SR lower than 0.6 vs 13% in the group with a higher ratio. By stratifying the groups according to type of surgery or anatomical type, these results were maintained.

Conclusion

The laparoscopic approach is a reasonable surgical option for the management of HARM. Laparoscopic approach was less time consuming in patients with RVF without impairing functional results.     

Development and validation of a pediatric laparoscopic surgery simulator

Background

Although a validated simulator exists for adult laparoscopy, there is no pediatric counterpart. The objective of this study is to develop and validate a pediatric laparoscopic surgery (PLS) simulator.

Methods

A PLS simulator was developed. Participants were stratified according to level of expertise and tested on the fundamentals of laparoscopic surgery (FLS) and PLS simulators. A subsequent group was tested exclusively on the PLS simulator.

Results

The PLS intracorporeal suturing score was lower than its adult counterpart (P = .02). The PLS pattern-cutting score was higher than in the FLS simulator (P < .001). If the latter was eliminated from the calculation, the revised total FLS score was significantly better than the revised PLS score. When all participants were combined, total PLS scores as well as performance on 3 of 5 tasks allowed differentiation between novice, intermediate, and expert.

Conclusions

The PLS simulator was able to discriminate between the novice, intermediate, and expert using the total PLS score and the performance on 3 of the 5 tasks, thus providing evidence for construct validity. The other 2 tasks will require formal modification or a change in the scoring metrics to establish their independent construct validity.     

Estimating the number of fractions by tumour site for European countries in 2012 and 2025: An ESTRO-HERO analysis

Background and purpose

The optimal number of radiotherapy fractions is a relevant input for planning resource needs. An estimation of the total number of fractions by country and tumour site is assessed for 2012 and 2025.