Mixed Brain Pathologies in Dementia: The BrainNet Europe Consortium Experience

Background: Dementia results from heterogeneous diseases of the brain. Mixed disease forms are increasingly recognized. Methods: We performed a survey within brain banks of BrainNet Europe to estimate the proportion of mixed disease forms underlying dementia and age- and gender-specific influences. Results: Data collected in 9 centres from 3,303 individuals were analysed. The proportion of patients with mixed diagnoses among all cases with Alzheimer disease (AD), vascular pathology (VP), argyrophilic grain dementia (AGD), and synucleinopathies, such as Lewy body dementia (LBD), Parkinson disease (PD) and synuclein pathology only in the amygdala, was 53.3%. Mixed pathology was more frequently reported with LBD, PD, AGD, and VP than with AD. The percentage of mixed diagnoses for AGD and VP significantly differed between centres. In patients younger than 75 years, synucleinopathies, and pure forms of AD, VP, and AGD were more frequent in men. Above 75 years of age, more women had pure AD and pure AGD. Conclusions: The most obvious neuropathological alteration should not terminate the diagnostic procedure since copathology is likely to be found. Neuropathological interpretation of AGD and VP has not been sufficiently established in a consensus. Pure forms of synucleinopathies are unlikely sole substrates for dementia. Copyright (C) 2008 S. Karger AG, Base

Origin of Minority Drug-Resistant HIV-1 Variants in Primary HIV-1 Infection

Background. Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants (MVs) are present in some antiretroviral therapy (ART)-naive patients. They may result from de novo mutagenesis or transmission. To date, the latter has not been proven. Methods. MVs were quantified by allele-specific polymerase chain reaction in 204 acute or recent seroconverters from the Zurich Primary HIV Infection study and 382 ART-naive, chronically infected patients. Phylogenetic analyses identified transmission clusters. Results. Three lines of evidence were observed in support of transmission of MVs. First, potential transmitters were identified for 12 of 16 acute or recent seroconverters harboring M184V MVs. These variants were also detected in plasma and/or peripheral blood mononuclear cells at the estimated time of transmission in 3 of 4 potential transmitters who experienced virological failure accompanied by the selection of the M184V mutation before transmission. Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001). Third, the prevalence of less-fit M184V MVs is significantly higher in acutely or recently than in chronically HIV-1-infected patients (8.2% vs 2.5%; P = .004). Conclusions. Drug-resistant HIV-1 MVs can be transmitted. To what extent the origin—transmission vs sporadic appearance—of these variants determines their impact on ART needs to be further explore

Treatment-Naive Individuals Are the Major Source of Transmitted HIV-1 Drug Resistance in Men Who Have Sex With Men in the Swiss HIV Cohort Study

A molecular epidemiologic analysis of a highly representative population found that the majority of patients who transmit drug-resistant subtype B HIV-1 to men who have sex with men in Switzerland had never been treated with antiretroviral

360° fixation with modern instrumentations of segment separation cervical spine injury in a 23 –month-old

In this case report clinical and technical lessons including seven years follow up learned from a flexion-distraction, highly unstable cervical spine injury causing a complete separation of C6-7 cervical segment with qaudriparesis in a 23 –month-old boy, are presented. To our knowledge this is the only documented case in medical literature where adult size implants (cage, plate and lateral mass screw-rod system) were utilized for cervical combined anterior and posterior internal fixation in a child under the age of two years without implant-size related problem. Seven years after the injury the child attends elementary school, can operate a wheelchair manually, and can eat and write. Computed tomography control showed no failure of the hardware and fusion was later observed in the intervertebral space of the stabilized cervical segment, however adjacent segment syndrome occurred without deterioration of the patient’s status. The decision on the mode of realignment and fixation to be made in such a case is difficult because there is no standard procedure for infants

Transpedicular direct osteosynthesis of hangman's fracture from a mini-open exposure as a less invasive procedure: A technical note

This surgical technical case report presents initial clinical experience and preliminary results with a less invasive surgical solution for selected hangman's fracture. A well-known stabilization technique (i.e. direct transpedicular osteosynthesis) was applied through a minimally invasive small incision transmuscular posterior approach guided by a standard C-arm fluoroscopy. This mini-open approach to C2 vertebra allows similar dissection, visualization of the bony landmarks, visual control of the transpedicular screw path drilling, tapping and screw insertion to the standard posterior cervical spine approach. At the same time it has the benefits of less invasive procedures

Initial experience with the treatment of concomitant aortic pseudoaneurysm and thoracolumbar spinal fracture: Case report

One blunt abdominal aortic disruption (BAAD) and one blunt thoracic aortic injury (BTAI) case are presented. Both aortic injuries were combined with spinal fractures. In the BAAD case the aortic pseudoaneurysm manifested just above the lumbar fracture while in the BTAI case the aortic injury appeared several vertebras below the thoracal fracture site, suggesting different mechanisms in the aortic wall damage. In both cases the aortic wall first was sealed, successfully, by endovascularly-placed stents, meaning the risks of open aortic reconstructive surgery could be avoided. The adjacent crucial vessel's preservation, despite the stent covering the left subclavian artery and the left common carotid artery in one of the cases was verified by post-operative computed tomography angiography (CTA) examination. In second stage those spinal fractures which were deemed unstable were stabilized by the fixateur interne (a transpedicular screw-rod system). With this treatment sequence we wanted to avoid the unnecessary risk of a possible rupture of the unsealed aortic wall during positioning for the spinal procedure and during the spinal surgery. Both patients recovered from their aortic and spinal injuries

Comparison of Single-Level Open and Minimally Invasive Transforaminal Lumbar Interbody Fusions Presenting a Learning Curve

Background. Comparison of single-level open and minimally invasive transforaminal lumbar interbody fusions (O-TLIF and MI-TLIF) of a single surgeon and presentation of his MI-TLIF learning curve in a retrospective observational cohort study. Methods. 27 MI-TLIF and 31 O-TLIF patients, performed between 03/01/2013 and 03/31/2018, were compared regarding the operative time, blood loss, blood transfusion frequency, postoperative length of stay (LOS), and adverse events. An overall comparison of pre- and postoperative Oswestry Disability Index (ODI) results and Visual Analog Score (VAS) results of low back and leg pain was performed in the case of the two techniques. For a learning curve presentation, the MI-TLIF cases were compared and the optimal operative time was determined. Results. The gender ratio and age did not differ in the groups. Operative time showed no difference (P=0.88) between the MI-TLIF (161.2 ± 33.7 minutes) and O-TLIF groups (160 ± 33.6 minutes). Intraoperative blood loss was less (P≤0.001) in the MI-TLIF group (288.9 ± 339.8 mL) than in the O-TLIF group (682.3 ± 465.4 mL) while the incidence of blood transfusion was similar (P=0.64). The MI-TLIF group had shorter LOS (2.7 ± 1.1 days vs. 5 ± 2.7, P≤0.001). The frequencies of the surgical site infections (SSI), durotomy, new motor, and sensory deficit were not significantly different (P=0.17, 0.5, 0.29, 0.92). All the ODI, the VAS low back pain, and the VAS leg pain scores improved in both groups significantly (P≤0.001, P≤0.001, and P≤0.001 in the MI-TLIF group and P≤0.001, P≤0.001, and P≤0.001 in the O-TLIF group). The comparison of the pre- and postoperative results of the ODI and VAS questionnaires of the two techniques showed no significant difference regarding the improvement of these scores (MI-TLIF versus O-TLIF pre- and postoperative ODI difference p=0.64, VAS low back pain P=0.47, and VAS leg pain P=0.21). Assessing the MI-TLIF learning curve, operative time was shortened by 63 minutes (P=0.04). After the 14th MI-TLIF case, the surgical duration became relatively constant. Comparing the 14th and previous MI-TLIF cases to the later cases, LOS showed reduction by 1.03 days (P=0.01), while the other parameters did not show significant changes. Conclusions. Similar operative time and postoperative quality of life improvement can be achieved by MI-TLIF procedure as with O-TLIF, and additionally LOS and blood loss can be reduced. When comparing parameters, MI-TLIF can be an alternative option for O-TLIF with a similar complication profile. The learning curve of MI-TLIF can be steep, although it depends on the circumstances

Viral suppression rates in salvage treatment with raltegravir improved with the administration of genotypic partially active or inactive nucleoside/tide reverse transcriptase inhibitors

BACKGROUND: Nucleoside reverse transcriptase inhibitors (NRTIs) are often administered in salvage therapy even if genotypic resistance tests (GRTs) indicate high-level resistance, but little is known about the benefit of these additional NRTIs. METHODS: The effect of <2 compared with 2 NRTIs on viral suppression (HIV-1 RNA < 50 copies/mL) at week 24 was studied in salvage patients receiving raltegravir. Intent-to-treat and per-protocol analyses were performed; last observation carried forward imputation was used to deal with missing information. Logistic regressions were weighted to create a pseudopopulation in which the probability of receiving <2 and 2 NRTIs was unrelated to baseline factors predicting treatment response. RESULTS: One-hundred thirty patients were included, of whom 58.5% (n = 76) received <2 NRTIs. NRTIs were often replaced by other drug classes. Patients with 2 NRTIs received less additional drug classes compared with patients with <2 NRTIs [median (IQR): 1 (1-2) compared with 2 (1-2), P Wilcoxon < 0.001]. The activity of non-NRTI treatment components was lower in the 2 NRTIs group compared with the <2 NRTIs group [median (IQR) genotypic sensitivity score: 2 (1.5-2.5) compared with 2.5 (2-3), P Wilcoxon < 0.001]. The administration of <2 NRTIs was associated with a worse viral suppression rate at week 24. The odds ratios were 0.34 (95% confidence interval: 0.13 to 0.89, P = 0.027) and 0.19 (95% confidence interval: 0.05 to 0.79, P = 0.023) when performing the last observation carried forward and the per-protocol approach, respectively. CONCLUSIONS: Our findings showed that partially active or inactive NRTIs contribute to treatment response, and thus the use of 2 NRTIs in salvage regimens that include raltegravir seems warranted