Measuring femoral lesions despite CT metal artefacts: a cadaveric study

Objective Computed tomography is the modality of choice for measuring osteolysis but suffers from metal-induced artefacts obscuring periprosthetic tissues. Previous papers on metal artefact reduction (MAR) show qualitative improvements, but their algorithms have not found acceptance for clinical applications. We investigated to what extent metal artefacts interfere with the segmentation of lesions adjacent to a metal femoral implant and whether metal artefact reduction improves the manual segmentation of such lesions. Materials and methods We manually created 27 periprosthetic lesions in 10 human cadaver femora. We filled the lesions with a fibrotic interface tissue substitute. Each femur was fitted with a polished tapered cobalt-chrome prosthesis and imaged twice—once with the metal, and once with a substitute resin prosthesis inserted. Metalaffected CTs were processed using standard back-projection as well as projection interpolation (PI) MAR. Two experienced users segmented all lesions and compared segmentation accuracy. Results We achieved accurate delineation of periprosthetic lesions in the metal-free images. The presence of a metal implant led us to underestimate lesion volume and introduced geometrical errors in segmentation boundaries.MediamaticsElectrical Engineering, Mathematics and Computer Scienc

Defects in tRNA Modification Associated with Neurological and Developmental Dysfunctions in Caenorhabditis elegans Elongator Mutants

Elongator is a six subunit protein complex, conserved from yeast to humans. Mutations in the human Elongator homologue, hELP1, are associated with the neurological disease familial dysautonomia. However, how Elongator functions in metazoans, and how the human mutations affect neural functions is incompletely understood. Here we show that in Caenorhabditis elegans, ELPC-1 and ELPC-3, components of the Elongator complex, are required for the formation of the 5-carbamoylmethyl and 5-methylcarboxymethyl side chains of wobble uridines in tRNA. The lack of these modifications leads to defects in translation in C. elegans. ELPC-1::GFP and ELPC-3::GFP reporters are strongly expressed in a subset of chemosensory neurons required for salt chemotaxis learning. elpc-1 or elpc-3 gene inactivation causes a defect in this process, associated with a posttranscriptional reduction of neuropeptide and a decreased accumulation of acetylcholine in the synaptic cleft. elpc-1 and elpc-3 mutations are synthetic lethal together with those in tuc-1, which is required for thiolation of tRNAs having the 5′methylcarboxymethyl side chain. elpc-1; tuc-1 and elpc-3; tuc-1 double mutants display developmental defects. Our results suggest that, by its effect on tRNA modification, Elongator promotes both neural function and development

Small-Animal PET Imaging of Amyloid-Beta Plaques with [11C]PiB and Its Multi-Modal Validation in an APP/PS1 Mouse Model of Alzheimer's Disease

In vivo imaging and quantification of amyloid-β plaque (Aβ) burden in small-animal models of Alzheimer's disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of Aβ in mouse brain with [11C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure Aβ at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [11C]PiB uptake in individual brain regions with Aβ deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of Aβ pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [11C]PiB imaging of Aβ in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal Aβ imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice

Polymorphism of brain derived neurotrophic factor influences β amyloid load in cognitively intact apolipoprotein E ε4 carriers.

Aside from apolipoprotein E (APOE), genetic risk factors for β amyloid deposition in cognitively intact individuals remain to be identified. Brain derived neurotrophic factor (BDNF) modulates neural plasticity, which has been implicated in Alzheimer's disease. We examined in cognitively normal older adults whether the BDNF codon 66 polymorphism affects β amyloid burden and the relationship between β amyloid burden and cognitive scores, and how this relates to the effect of APOE. Amyloid load was measured by means of (18)F-flutemetamol PET in 64 community-recruited cognitively intact individuals (mean age 66, S.D. 5.1). Recruitment was stratified according to a factorial design with APOE (ε4 allele present vs absent) and BDNF (met allele at codon 66 present vs absent) as factors. Individuals in the four resulting cells were matched by the number of cases, age, and gender. Among the APOE ε4 carriers, BDNF met positive subjects had a significantly higher amyloid load than BDNF met negative subjects, while BDNF met carrier status did not have an effect in APOE ε4 noncarriers. This interaction effect was localized to precuneus, orbitofrontal cortex, gyrus rectus, and lateral prefrontal cortex. In the APOE ε4/BDNF met carriers, a significant inverse relationship existed between episodic memory scores and amyloid burden but not in any of the other groups. This hypothesis-generating experiment highlights a potential role of BDNF polymorphisms in the preclinical phase of β amyloid deposition and also suggests that BDNF codon 66 polymorphisms may influence resilience against β amyloid-related effects on cognition

Low rates of serious complications but high rates of hardware removal after high tibial osteotomy with Tomofix locking plate

© 2020, European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA). Purpose: The purpose of this study was to analyse adverse events encountered in medial opening wedge high tibial osteotomy (MOWHTO) utilizing contemporary surgical techniques with the Tomofix locking plate (DePuy Synthes, Raynham, MA, USA) and categorize them by their severity and need for further medical/surgical management. It was hypothesized that there would be low rates of serious complications after medial opening wedge high tibial osteotomy utilizing an internal locking plate fixator. Methods: This study included 169 consecutive patients (200 knees) who underwent MOWHTO with a Tomofix locking plate at a single center, completing a minimum 2-year follow-up. Types of intra- and post-operative adverse events were retrospectively identified by an independent observer and categorized by their severity and further need of management. Additional surgery due to elective hardware removal was not included in the adverse event classification. Results: There were in total 58 (29%) adverse events, the majority (13.5%) of which required no additional treatment (class 1). Class 1 events included lateral cortex hinge fractures that were observed in 8.5% (17 knees) and delayed wound healing 2% (4/200). Adverse events requiring additional or extended nonoperative management (class 2) were 9%. These included post-operative stiffness in 1% (2/200), low grade infection in 1.5% (3/200), delayed union in 5.4% (11/200), deep vein thrombosis 0.5% (1/200). One hundred and four knees (52%) underwent elective hardware removal. Serious adverse events requiring unplanned additional or revision surgery and/or long-term medical care (class 3) were the least reported (6.5%). Aseptic non-union was reported in 2.5%, deep infection requiring revision in 2% and limited hardware failure 1%. Conclusion: A low rate of serious complications (6.5%) requiring unplanned additional surgery (class 3) was found. The overall rate of complications following MOWHTO with Tomofix locking plate was 29% and the majority (13.5%) required no additional treatment (class 1). Lateral hinge fractures were the most common complication (8.5%) and these were associated with corrections over 12 mm. However, 52% knees required a further operation for elective hardware removal. Level of evidence: Level IV, prospective study without control group

Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR

Endothelin 1 (ET-1), a potent vasoconstrictor, pro-mitogenic and pro-inflammatory peptide, may promote development of endothelial dysfunction and arterial remodeling. ET-1 can be formed through cleavage of big-ET-1 by endothelin-converting enzyme (ECE) or neutral endopeptidase (NEP). We investigated whether chronic treatment with the novel dual NEP/ECE inhibitor SOL1 improves functional and structural properties of resistance-sized arteries of 32-week-old male spontaneously hypertensive rats (SHR). SHR received a chronic 4-week treatment with SOL1, losartan or hydralazine. We then compared effects of inhibition of NO synthase (NOS) (100 mu M L-NAME), blockade of ETA-and ETB-receptors (10 mu M bosentan) and stimulation of the endothelium with 0.001-10 mu M acetylcholine (ACh) in isolated third-order mesenteric resistance arteries. Losartan and hydralazine significantly lowered blood pressure. Losartan decreased the media-to-lumen ratio of resistance arteries. L-NAME (1) increased arterial contractile responses to K+ (5.9-40 mM) in the losartan, SOL1 and vehicle group and (2) increased the sensitivity to phenylephrine (PHE; 0.16-20 mu M) in the SOL1 group but not in the losartan, hydralazine and vehicle group. Relaxing responses to ACh in the absence or presence of L-NAME during contractions induced by either 10 mu M PHE or 40 mM K+ were not altered by any in vivo treatment. Acute treatment with bosentan did, however, significantly improve maximal relaxing responses involving endothelium-derived nitric oxide and -hyperpolarizing factors in the SOL1 group but not in the losartan, hydralazine or vehicle group. Thus, chronic inhibition of NEP/ECE improved basal endothelial function but did not alter blood pressure, resistance artery structure and stimulated endothelium-dependent relaxing responses in 32-week-old SH

Opening wedge tibial osteotomy for large varus deformity with CeraverTM resorbable beta tricalcium phosphate wedges

The results in 53 knees that had been treated by proximal tibial opening-wedge osteotomy for large varus deformity and osteoarthritis of the medial compartment were evaluated after a mean length of follow-up of ten years (range, 8–12 years). We used a porous beta-tricalcium phosphate (β-TCP) wedge because it is resorbable and osteoinductive. All osteotomies were completely consolidated and complete osseointegration of the remnant of the β-TCP wedge took place. However, after a mean maximum follow-up of ten years none of the cases showed complete resorption. After ten years, 40 (81%) of the 53 knees had an excellent or good result, and in 13 knees there was recurrent pain for which six had an arthroplasty. Although the results deteriorated with time, time was not the only determinant of the result. Alignment, measured as the hip-knee-ankle angle on radiographs of the whole limb that were made with the patient bearing weight, was also a determinant of long-term results. The best results were obtained in the knees that had a hip-knee-ankle angle of 183–186 degrees. In these knees, there was no pain and no progression of the arthrosis in either the medial or the lateral tibiofemoral compartment. Of the three knees that had an angle of more than 186 degrees, all five had progressive degenerative changes in the lateral compartment. In the undercorrected knees (an angle of less than 183 degrees), the results were less satisfactory, and there was a tendency toward recurrence of the varus deformity and progression of the arthritis of the medial compartment. However, when the correction was insufficient the deterioration was slow. Therefore, proximal tibial osteotomy is a very suitable operation even for patients who have gonarthrosis of the medial compartment and a large varus deformity. Although, a rigidly standardised and precise operative technique is required as well as accurate radiographic measurements of the mechanical axis of the limb because exact postoperative alignment is the prerequisite for the longest possible period of relief of symptoms after osteotomy, and this exact alignment is difficult to obtain for patients with large varus deformity