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Subacute sclerosing panencephalitis (SSPE) is a lethal neurological disorder occurring several years after measles. Reconstruction of the evolution of the measles virus (MeV) genome in an SSPE case suggested that the matrix (M) protein mutation M-F50S, when added to other mutations, drove neuropathogenesis. However, whether and how M-F50S would promote spread independently from other mutations was in question. We investigated here the cell specificity of MeV spread in this brain and documented that both neurons and astrocytes were heavily infected. We then generated recombinant MeV with individual mutations in the three proteins of the viral membrane fusion apparatus, M, fusion (F), and hemagglutinin (H). These viruses reached similar titers as the parental wild-type virus, kept the respective mutations upon passage, and infected cells expressing the tissue-specific MeV receptors SLAM and nectin-4 with similar efficiencies. However, after inoculation of receptor-negative neurons and astrocytes differentiated from human induced pluripotent stem cells, only MeV M-F50S spread with moderate efficiency; the parental virus and its derivatives coding for a hyperfusogenic F protein, or for a cytoplasmic tail-mutated H protein, did not spread. When delivered to primary mouse neurons by cell-mediated neurite overlay, MeV M-F50S frequently reached the cell bodies and occasionally formed small infectious centers, while the other MeV reached the cell bodies only sporadically. These results demonstrate that, in neuronal cell cultures, M-F50S can enable receptor-independent spread in the absence of other mutations, and validate the inference that this single amino acid change initiated ubiquitous MeV brain spread.IMPORTANCEMeasles virus (MeV), a non-integrating negative-strand RNA virus, rarely causes subacute sclerosing panencephalitis (SSPE) several years after acute infection. During brain adaptation, the MeV genome acquires multiple mutations reducing the dependence of its membrane fusion apparatus (MFA) from an activating receptor. It was proposed that one of these mutations, matrix protein F50S, drove neuropathogenesis in an SSPE case. We report here that, in two types of neuronal cultures, a recombinant MeV with only this mutation gained receptor-independent spread, whereas viruses expressing MFA proteins with other mutations acquired during brain adaptation did not. Our results validate the inference that M-F50S initiated ubiquitous MeV brain spread resulting in lethal disease. They also prompt studies of the impact of analogous amino acid changes of the M proteins of other nonsegmented negative-strand RNA viruses on their interactions with membrane lipids and cytoskeletal components., Competing Interests: The authors declare no conflict of interest.

Competing Interests: Declaration of Competing Interest None.

Orthotopic neobladder (ONB) reconstruction is a continent urinary diversion procedure increasingly used in patients with muscle-invasive bladder cancer following radical cystectomy (RC). It represents a valid alternative to the ileal duct in suitable patients who do not prefer a stoma and are motivated to undergo adequate training of the neobladder. Careful patient selection, taking into account the absolute and relative contraindications for ONB as well as an adequate recovery protocol after surgery are integral to the success of this procedure and the oncological and functional outcomes. The objective of this review is to summarize the current data on RC with ONB in terms of patient selection, preoperative preparation, surgical techniques and functional (continence and sexual activity) and oncological outcomes, with particular attention to the management of complications and the impact on quality of life (QoL)., Competing Interests: The authors have stated that they have no conflict of interest.

Purpose: To investigate the clinical performance of a new mRNA-based urine test, aiming to avoid unnecessary follow-up cystoscopy in patients under active surveillance (AS) for recurrent NMIBC., Methods: This is a prospective cohort study enrolling patients with history of low-grade (LG) NMIBC, who developed a recurrence during the follow-up and underwent AS. Their urinary samples were analyzed by Xpert BC Monitor (Cepheid, Sunnyvale, CA, USA). The primary endpoint was to investigate if Xpert BC Monitor could avoid unnecessary cystoscopy during the follow-up period. Its sensitivity, specificity, PPVs and NPVs were calculated. A cutoff of 0.4 "linear discriminant analysis" (LDA) was optimized for the AS setting., Results: The cohort consisted of 106 patients with a mean age of 72 ± 9.52 and a median follow-up from AS start of 8.8 (range 0-56.5) months. No statistically significant difference was found for the mean age, smoker status, lesion size, and number of lesions with a cutoff of 0.4. Of 106 patients, 22 (20.8%) were deemed to require treatment because of cystoscopic changes in size and/or number of lesions during the follow-up period. Using a cutoff value of < 0.4, 34 (33.7%) cystoscopies could be avoided due to low LDA value, missing 2/22 (9%) failures, none with high-grade (HG) NMIBC. Further research on larger population remains mandatory before its clinical use., Conclusion: Xpert BC Monitor seems to be a reliable assay, which might avoid unnecessary cystoscopies without missing HG NMIBC when its cutoff is optimized for the AS setting.

Background: The aim of this study was to identify the predictive factors for progression defined as any event that shifted the management of the disease from a bladder sparing approach, by comparing patients with pure versus non-pure carcinoma in situ (CIS) of the bladder., Methods: A retrospective analysis was carried out in consecutive patients affected by newly-diagnosed pure CIS and non-pure CIS (excluding cases with concomitant muscle invasive cancer). All patients were enrolled a in our institution from 1998 to 2010. Data was prospectively collected. Main end point was progression-free survival., Results: Overall, 149 patients with CIS were identified for the analysis. A total of 98 patients had pure CIS (66%). Median follow-up was 103 months (range: 40-206 months). Progression occurred in 29 patients (19%). A total of 30 patients died during the follow-up (20%). In 13 cases (9%), the death was cancer specific. Progression-free survival estimate was 181 months (95% CI: 169-193 months) and 154 months (95% CI: 133-176 months) respectively for pure and non-pure CIS population (P=0.03). Among examined variables (age, gender, symptoms, smoking habit, ASA score, number of bacillus Calmette-Guérin [BCG] instillations), multivariate analysis disclosed that only CIS type was an independent predictor of progression (P=0.03) with a relative risk of 0.37 in favor of pure CIS., Conclusions: Pure and non-pure CIS are efficiently treated by BCG therapy combined with trans-urethral resection and/or radical cystectomy, with relatively low rate of progression. CIS type was the only significant predictor of progression.

Background: There is an unmet clinical need for more biochemical specific tests that may detect clinically significant recurrent PCa at an early stage after radical prostatectomy (RP). Our purpose is to test the hypothesis that p2PSA (Index test) detects prostate cancer relapse (BCR) earlier than the current Reference Standard Test (total prostate-specific antigen [tPSA]) in patients who underwent RP for localized PCa., Methods: This is an observational, prospective, cohort, follow-up study in patients subjected to RALP (robotic assisted laparoscopic radical prostatectomy) for clinically localized PCa from January 2013 to July 2013 at a high-volume Institution (450 average RP/year). A blood sample, for tPSA and p2PSA, was prospectively drawn after 3, 6, and 12 months and then every 6 months during the following two years. The primary outcome is to determine whether or not kinetics in rising of p2PSA significantly anticipates the tPSA kinetics. Exploratory data analysis was used to identify relationship between different variables., Results: Over 134 patients 20 BCRs were detected according to tPSA cut-off. Five patients showed a contemporary increase of tPSA and p2PSA, 11 presented a p2PSA increase earlier than tPSA increase (13.9 months ±9.7). In four patients, the increase of PSA was not associated with a p2PSA>0.8 pg/mL. The correlation between tPSA and p2PSA according to Sperman's rho coefficient was statistically significant at 3, 6, 18 and 30 months: 0.416 (P<0.01), 0.255 (P<0.01), 0.359 (P<0.01) and 0.413 (P<0.01) respectively. When subjects were stratified according to stage/grade and margins (positive vs. negative), patients with higher stage and positive surgical margins could be considered the target categories. The low rate of observed BCR and high rate of p2PSA false positive are the main limitations., Conclusions: The current findings showed that p2PSA might be more sensitive than tPSA in detecting earlier BCR within 3-year follow-up. Further studies with a longer follow-up and larger population remain mandatory before considering p2PSA for clinical decision-making.

Background: El Camino Hospital is a leader in the use of health information technology to promote patient safety, including bar coding, computerized order entry, electronic medical records, and wireless communications., Overall Approach to Quality and Safety: Each year, El Camino Hospital's board of directors sets performance expectations for the chief executive officer, which are tied to achievement of local, regional, and national safety and quality standards, including the six Institute of Medicine quality dimensions. He then determines a set of explicit quality goals and measurable actions, which serve as guidelines for the overall hospital. The goals and progress reports are widely shared with employees, medical staff, patients and families, and the public., Addressing the Six Iom Quality Aims: For safety, for example, the medication error reduction team tracks and reviews medication error rates. The hospital has virtually eliminated transcription errors through its 100% use of computerized physician order entry. Clinical pathways and standard order sets have reduced practice variation, providing a safer environment., Challenges: Many projects focused on timeliness, such as emergency department wait time, lab turnaround time, and pneumonia time to initial antibiotic. Results have been mixed, with projects most successful when a link was established with patient outcomes, such as in reducing time to percutaneous transluminal coronary angioplasty for patients with acute myocardial infarction.

Through their shared service organization, six hospitals conducted a study that showed that they had similar practical needs and legal requirements for medical record retention but widely varying retention policies. Written policies that were developed for and jointly adopted by the hospitals have ensured consistent, cost-effective retention practices.