The Predictors study: Development and baseline characteristics of the Predictors 3 cohort

Introduction

The Predictors study was designed to predict the length of time to major disease outcomes in Alzheimer's disease (AD) patients. Here, we describe the development of a new, Predictors 3, cohort.

Volumetric Misfit in CAD/CAM and Cast Implant Frameworks: A University Laboratory Study

Purpose: To compare the volumetric misfit between implant restorative platforms of implants and implant frameworks manufactured with two different technologies. One set of implant frameworks was made with a CAD/CAM protocol and a tactile probe; the second protocol consisted of frameworks made with the lost‐wax technique and conventional casting technology. Materials and Methods: In this laboratory study, an acrylic resin model with five “inter‐foraminal” implants was used as the “patient” model. Implant level impressions were made, and 10 definitive master casts were fabricated. The casts were verified using an index made on the patient model. Five cast high palladium noble alloy and five CAD/CAM titanium alloy frameworks were fabricated. The patient's implants and the frameworks’ implant restorative platforms were scanned with a tactile probe, and the data were digitized. The digitized implant restorative platforms of the frameworks were fit onto the patient's digitized implants via a software program, in a process called “lofting.” This computerized procedure simulated a 1‐screw test; the process was performed on both sides. The volumetric misfit between the implant restorative platforms of the frameworks and the patient's implants were measured. A Welch's t‐test was used to determine significant differences (p < 0.05) between the misfit of the two technologies. Wilcoxon Signed‐Rank tests were used to evaluate differences between the right and left sides. Results: On average, the volumetric misfit of the CAD/CAM frameworks was 1.8 mm³ less than the volumetric misfit of the cast alloy frameworks (p < 0.05). The Wilcoxon Signed‐Rank tests showed no significant differences between the right and left sides within both systems (p > 0.05). Conclusions: The scanning technology and computer software program used in this study demonstrated that the CAD/CAM implant frameworks had statistically significantly less volumetric misfit when compared with the cast implant frameworks. There were no significant differences between the right and left 1‐screw tests within the same type of frameworks.     

Native nephrectomy for autosomal dominant polycystic kidney disease: before or after kidney transplantation?

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? The indications and timing of native nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) is controversial, especially for those undergoing renal transplantation. Post‐transplant unilateral native nephrectomy appears to be the preferred intervention compared to pre‐transplant native nephrectomy. There seems to be substantial additive risk to bilateral over unilateral nephrectomy, especially prior to transplantation. Pre‐transplant native nephrectomy should only be carried out when there are clear indications such as massive size preventing allograft placement, severe pain, early satiety, recurrent bleeding and infections, or suspected malignancy.

OBJECTIVE

To analyse indications, timing and outcomes of native nephrectomy in autosomal dominant polycystic kidney disease (ADPKD) patients listed for kidney transplantation.

PATIENTS AND METHODS

A retrospective analysis of all ADPKD patients who had a native nephrectomy prior to or following transplantation between January 2003 and December 2009 at a single centre, including those undergoing the sandwich technique (removal of the most severely affected native kidney prior to transplantation, and the other afterwards), was undertaken.

RESULTS

There were 35 individuals in our cohort (M : F = 16 : 19), with a median age of 51.5 years (range 43–65). Twenty patients were in the pre‐transplant nephrectomy group, 12 in the post‐transplant group, and three underwent the sandwich technique. Indications for nephrectomy varied but were most commonly pain/discomfort, space for transplantation, ongoing haematuria, recurrent infections, and gastrointestinal pressure symptoms (early satiety). Seven individuals in the pre‐transplant group and three in the post‐transplant group required critical care admission after nephrectomy. Transient renal graft dysfunction occurred in two post‐transplant bilateral nephrectomy patients. Two patients in the bilateral nephrectomy pre‐transplant group and one in the bilateral nephrectomy post‐transplant group died in the immediate post‐operative period. No complications were noted in the sandwich technique group.

CONCLUSION

Native nephrectomy in ADPKD is a major undertaking associated with significant morbidity especially in the pre‐transplant group. Post‐transplant unilateral nephrectomy appears to be the safest approach with fewest complications.     

Un syndrome néphrotique chez un patient porteur d’une polyarthrite rhumatoïde : à propos d’un cas

A fifty-one years-old patient with a history of rheumatoid arthritis of recent diagnosis is hospitalized for exploration of a rapidly progressive anasarca state. First analysis discovered an impure nephrotic syndrome (acute renal failure, hematuria) and massive glomerular proteinuria. Auto-medication by nonsteroidal anti-inflammatory drug was revealed. Renal biopsy showed minimal glomerular disease and acute tubular necrosis. Corticosteroid use permitted a normalization of proteinuria and renal recovery was obtained. Literature review showed renal impairment occurring in rheumatoid polyarthritis. Minimal glomerular disease is rare but can be associated with rheumatoid arthritis. This disease, associated with the use of nonsteroidal anti-inflammatory drug, may be responsible of the patient condition.     

Independent risk factors for early urologic complications after kidney transplantation

Urologic complications are the most frequent technical adverse events following kidney transplantation (KTX). We evaluated traditional and novel potential risk factors for urologic complications following KTX. Consecutive KTX recipients between December 1, 2006 and December 31, 2010 with at least six‐month follow‐up (n = 635) were evaluated for overall urologic complications accounting for donor, recipient, and transplant characteristics using univariate and multivariate logistic regression. Urologic complications occurred in 29 cases (4.6%) at a median of 40 d (range 1–999) post‐transplantation and included 17 ureteral strictures (2.6%), five (0.8%) ureteral obstructions due to donor‐derived stones or intraluminal thrombus, and seven urine leaks (1.1%). All except two complications occurred within the first year of transplantation. Risk factors for urologic complications on univariate analysis were dual KTX (p = 0.04) and renal artery multiplicity (p = 0.02). On multivariate analysis, only renal artery multiplicity remained significant (aHR 2.4, 95% confidence interval 1.1, 5.1, p = 0.02). Donation after cardiac death, non‐mandatory national share kidneys, donor peak serum creatinine > 1.5 mg/dL or creatinine phosphokinase > 1000 IU/L, and donor down time were not associated with urologic complications. Our data suggest that donor artery multiplicity is an independent risk factor for urologic complications following KTX.     

The dual dopamine‐glutamate phenotype of growing mesencephalic neurons regresses in mature rat brain

Coexpression of tyrosine hydroxylase (TH) and vesicular glutamate transporter 2 (VGLUT2) mRNAs in the ventral tegmental area (VTA) and colocalization of these proteins in axon terminals of the nucleus accumbens (nAcb) have recently been demonstrated in immature (15‐day‐old) rat. After neonatal 6‐hydroxydopamine (6‐OHDA) lesion, the proportion of VTA neurons expressing both mRNAs and of nAcb terminals displaying the two proteins was enhanced. To determine the fate of this dual phenotype in adults, double in situ hybridization and dual immunolabeling for TH and VGLUT2 were performed in 90‐day‐old rats subjected or not to the neonatal 6‐OHDA lesion. Very few neurons expressed both mRNAs in the VTA and substantia nigra (SN) of P90 rats, even after neonatal 6‐OHDA. Dually immunolabeled terminals were no longer found in the nAcb of normal P90 rats and were exceedingly rare in the nAcb of 6‐OHDA‐lesioned rats, although they had represented 28% and 37% of all TH terminals at P15. Similarly, 17% of all TH terminals in normal neostriatum and 46% in the dopamine neoinnervation of SN in 6‐OHDA‐lesioned rats were also immunoreactive for VGLUT2 at P15, but none at P90. In these three regions, all dually labeled terminals made synapse, in contradistinction to those immunolabeled for only TH or VGLUT2 at P15. These results suggest a regression of the VGLUT2 phenotype of dopamine neurons with age, following normal development, lesion, or sprouting after injury, and a role for glutamate in the establishment of synapses by these neurons. J. Comp. Neurol. 517:873–891, 2009. © 2009 Wiley‐Liss, Inc.     

Echo Doppler parameters predict response to cardiac resynchronization therapy

Background  Cardiac resynchronization therapy (CRT) has been shown to reduce heart failure related morbidity and mortality. However, approximately 30% of patients do not respond to CRT. We investigated the usefulness of Echo Doppler parameters to predict reverse remodelling, functional improvement and mortality following CRT.
Materials and methods  Our population consists of 200 consecutive heart failure patients evaluated for ventricular dyssynchrony by echocardiography between February 1999 and May 2007 who subsequently received CRT. Patients were reassessed for signs of reverse remodelling after a mean follow-up of 10 months. Information on vital status was obtained from local registration authorities.
Results  Three parameters significantly predicted reverse remodelling in the logistic regression analysis: the Q-to-E-wave-delay (QED) at a cutoff of 550 ms (odds ratio 4·5, P -value 0·001), the interventricular mechanical delay (IVMD) at a cutoff of 60 ms (odds ratio 2·4, P -value 0·02), and the aortic electromechanical delay (A-EMD) at a cutoff of 140 ms (odds ratio 2·9, P -value 0·004). Furthermore, the QED and the IVMD also predicted all-cause mortality (hazard ratio 0·36, P -value 0·02 and 0·21, P -value 0·004, respectively). Adjustment for confounders did not alter the results.
Conclusions  The QED and IVMD predict reverse remodelling and survival following CRT. These parameters are easy to obtain, provide valuable prognostic information, and should thus be measured in CRT candidates evaluated by echocardiography.     

Regional expression and ultrastructural localization of EphA7 in the hippocampus and cerebellum of adult rat

EphA7 is expressed in the adult central nervous system (CNS), where its roles are yet poorly defined. We mapped its distribution using in situ hybridization (ISH) and immunohistochemistry (IHC) combined with light (LM) and electron microscopy (EM) in adult rat and mouse brain. The strongest ISH signal was in the hippocampal pyramidal and granule cell layers. Moderate levels were detected in habenula, striatum, amygdala, the cingulate, piriform and entorhinal cortex, and in cerebellum, notably the Purkinje cell layer. The IHC signal distribution was consistent with ISH results, with transport of the protein to processes, as exemplified in the hippocampal neuropil layers and weakly stained pyramidal cell layers. In contrast, in the cerebellum, the Purkinje cell bodies were the most strongly immunolabeled elements. EM localized the cell surface‐expression of EphA7 essentially in postsynaptic densities (PSDs) of dendritic spines and shafts, and on some astrocytic leaflets, in both hippocampus and cerebellum. Perikaryal and dendritic labeling was mostly intracellular, associated with the synthetic and trafficking machineries. Immunopositive vesicles were also observed in axons and axon terminals. Quantitative analysis in EM showed significant differences in the frequency of labeled elements between regions. Notably, labeled dendrites were ～3–5 times less frequent in cerebellum than in hippocampus, but they were individually endowed with ～10–40 times higher frequencies of PSDs, on their shafts and spines. The cell surface localization of EphA7, being preferentially in PSDs, and in perisynaptic astrocytic leaflets, provides morphologic evidence that EphA7 plays key roles in adult CNS synaptic maintenance, plasticity, or function. J. Comp. Neurol. 524:2462–2478, 2016. © 2016 Wiley Periodicals, Inc.