Constant Transmission Properties of Variant Creutzfeldt-Jakob Disease in 5 Countries

Variant Creutzfeldt-Jakob disease (vCJD) has been reported in 12 countries. We hypothesized that a common strain of agent is responsible for all vCJD cases, regardless of geographic origin. To test this hypothesis, we inoculated strain-typing panels of wild-type mice with brain material from human vCJD case-patients from France, the Netherlands, Italy, and the United States. Mice were assessed for clinical disease, neuropathologic changes, and glycoform profile; results were compared with those for 2 reference vCJD cases from the United Kingdom. Transmission to mice occurred from each sample tested, and data were similar between non-UK and UK cases, with the exception of the ranking of mean clinical incubation times of mouse lines. These findings support the hypothesis that a single strain of infectious agent is responsible for all vCJD infections. However, differences in incubation times require further subpassage in mice to establish any true differences in strain properties between cases

Telemedicine and international disaster response: Medical consultation to Armenia and Russia via a telemedicine spacebridge

The Telemedicine Spacebridge, a satellite mediated audio-video-fax link between four U.S. and two Armenian and Russian medical centers, permitted remote American consultants to assist Armenian and Russian physicians in the management of medical problems following the December 1988 earthquake in Armenia and the June 1989 gas explosion near Ufa. During 12 weeks of operations, 247 Armenian and Russian and 175 American medical professionals participated in 34 half-day clinical conferences. 209 patients were discussed, requiring expertise in 20 specialty areas. Telemedicine consultations resulted in altered diagnoses for 54, new diagnostic studies for 70, altered diagnostic processes for 47, and modified treatment plans for 47 of 185 Armenian patients presented. Simultaneous participation of several U.S. medical centers was judged beneficial; quality of data transmission was judged excellent. These results suggest that interactive consultation by remote specialists can provide valuable assistance to onsite physicians and favorably influence clinical decisions in the aftermath of major disasters

Generalized cerebral atrophy seen on MRI in a naturally exposed animal model for creutzfeldt-jakob disease

<p>Abstract</p> <p>Background</p> <p>Magnetic resonance imaging has been used in the diagnosis of human prion diseases such as sCJD and vCJD, but patients are scanned only when clinical signs appear, often at the late stage of disease. This study attempts to answer the questions "Could MRI detect prion diseases before clinical symptoms appear?, and if so, with what confidence?"</p> <p>Methods</p> <p>Scrapie, the prion disease of sheep, was chosen for the study because sheep can fit into a human sized MRI scanner (and there were no large animal MRI scanners at the time of this study), and because the USDA had, at the time of the study, a sizeable sample of scrapie exposed sheep, which we were able to use for this purpose. 111 genetically susceptible sheep that were naturally exposed to scrapie were used in this study.</p> <p>Results</p> <p>Our MRI findings revealed no clear, consistent hyperintense or hypointense signal changes in the brain on either clinically affected or asymptomatic positive animals on any sequence. However, in all 37 PrP^Scpositive sheep (28 asymptomatic and 9 symptomatic), there was a greater ventricle to cerebrum area ratio on MRI compared to 74 PrP^Scnegative sheep from the scrapie exposed flock and 6 control sheep from certified scrapie free flocks as defined by immunohistochemistry (IHC).</p> <p>Conclusions</p> <p>Our findings indicate that MRI imaging can detect diffuse cerebral atrophy in asymptomatic and symptomatic sheep infected with scrapie. Nine of these 37 positive sheep, including 2 one-year old animals, were PrP^Scpositive only in lymph tissues but PrP^Scnegative in the brain. This suggests either 1) that the cerebral atrophy/neuronal loss is not directly related to the accumulation of PrP^Scwithin the brain or 2) that the amount of PrP^Scin the brain is below the detectable limits of the utilized immunohistochemistry assay. The significance of these findings remains to be confirmed in human subjects with CJD.</p

Biochemical Properties of Highly Neuroinvasive Prion Strains

Infectious prions propagate from peripheral entry sites into the central nervous system (CNS), where they cause progressive neurodegeneration that ultimately leads to death. Yet the pathogenesis of prion disease can vary dramatically depending on the strain, or conformational variant of the aberrantly folded and aggregated protein, PrPSc. Although most prion strains invade the CNS, some prion strains cannot gain entry and do not cause clinical signs of disease. The conformational basis for this remarkable variation in the pathogenesis among strains is unclear. Using mouse-adapted prion strains, here we show that highly neuroinvasive prion strains primarily form diffuse aggregates in brain and are noncongophilic, conformationally unstable in denaturing conditions, and lead to rapidly lethal disease. These neuroinvasive strains efficiently generate PrPSc over short incubation periods. In contrast, the weakly neuroinvasive prion strains form large fibrillary plaques and are stable, congophilic, and inefficiently generate PrPSc over long incubation periods. Overall, these results indicate that the most neuroinvasive prion strains are also the least stable, and support the concept that the efficient replication and unstable nature of the most rapidly converting prions may be a feature linked to their efficient spread into the CNS

Periprocedural Complications After Transcatheter Aortic Valve Replacement and Their Impact on Resource Utilization

To examine the incidence and trends of peri-procedural complications after TAVR and their impact on resource utilization. The incidence of complications by type [acute kidney injury (AKI), permanent pacemaker (PPM), vascular, paravalvular leak, in-hospital mortality, others] was calculated for TAVR patients at a high-volume center between 2012 and 2018. Clinical data were matched with hospital-billing data of patients. Trends in high resource utilization (discharge to a rehabilitation facility or PLOS >7 days) (HRU) and complication rates were assessed. Multivariable logistic regression models were used to determine predictors of HRU. Out of 1163 patients, 966 (83%) had no complications, others in 95 (8%), PPM in 56 (5%), AKI alone in 32 (3%), vascular in 31 (3%), in-hospital mortality in 28 (2%) and PVL in 10 (1%). A significant decreasing trend in the incidence of complications (29% vs 10%; p trend <0.001) and HRU (75% vs 12%; p trend <0.001) was observed between 2012 and 2018 respectively. Mean ± SD direct procedure cost of having a complication was $58,234 ±$24,568, was associated with an incremental cost of $10, 649 and a prolonged stay of 3-days. On multivariable logistic regression analysis, PPM, vascular complications, high STS risk score, NYHA class III/IV, frailty and ≥ moderate tricuspid regurgitation were significantly associated with HRU. TAVR year was protective against HRU. We established that, post-TAVR resource utilization and morbidity is high among frail and patients with higher STS risk scores. However, these rates decrease over time with experience