The Connective Tissue Disorder Associated with Recessive Variants in the SLC39A13 Zinc Transporter Gene (Spondylo-Dysplastic Ehlers-Danlos Syndrome Type 3): Insights from Four Novel Patients and Follow-Up on Two Original Cases.

Recessive loss-of-function variants in SLC39A13, a putative zinc transporter gene, were first associated with a connective tissue disorder that is now called "Ehlers-Danlos syndrome, spondylodysplastic form type 3" (SCD-EDS, OMIM 612350) in 2008. Nine individuals have been described. We describe here four additional affected individuals from three consanguineous families and the follow up of two of the original cases. In our series, cardinal findings included thin and finely wrinkled skin of the hands and feet, characteristic facial features with downslanting palpebral fissures, mild hypertelorism, prominent eyes with a paucity of periorbital fat, blueish sclerae, microdontia, or oligodontia, and-in contrast to most types of Ehlers-Danlos syndrome-significant short stature of childhood onset. Mild radiographic changes were observed, among which platyspondyly is a useful diagnostic feature. Two of our patients developed severe keratoconus, and two suffered from cerebrovascular accidents in their twenties, suggesting that there may be a vascular component to this condition. All patients tested had a significantly reduced ratio of the two collagen-derived crosslink derivates, pyridinoline-to-deoxypyridinoline, in urine, suggesting that this simple test is diagnostically useful. Additionally, analysis of the facial features of affected individuals by DeepGestalt technology confirmed their specificity and may be sufficient to suggest the diagnosis directly. Given that the clinical presentation in childhood consists mainly of short stature and characteristic facial features, the differential diagnosis is not necessarily that of a connective tissue disorder and therefore, we propose that SLC39A13 is included in gene panels designed to address dysmorphism and short stature. This approach may result in more efficient diagnosis

Patients Enrolled in Large Randomized Clinical Trials of Antiplatelet Treatment for Prevention After Transient Ischemic Attack or Ischemic Stroke Are Not Representative of Patients in Clinical Practice: the Netherlands Stroke Survey

Background and Purpose—Many randomized clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of new vascular events in patients with a recent transient ischemic attack or ischemic stroke. Evidence from these trials forms the basis for national and international guidelines for the management of nearly all such patients in clinical practice. However, abundant and strict enrollment criteria may limit the validity and the applicability of results of randomized clinical trials to clinical practice. We estimated the eligibility for participation in landmark trials of antiplatelet drugs of an unselected group of patients with stroke or transient ischemic attack from a national stroke survey. Methods—Nine hundred seventy-two patients with transient ischemic at

The reliability of the patellotrochlear index on magnetic resonance imaging for measuring patellofemoral height

Background: The purpose of this study was to determine the inter-and intra-observer reliability of the patellotrochlear index (PTI) on magnetic resonance images (MRI) in patients with patellofemoral pain. The correlation between the PTI measured on MRI and the modified Insall-Salvati (MIS) ratio measured on radiographs was also assessed. Methods: The PTI was assessed on MRI images and the MIS ratio on radiographs of 66 knees of 62 patients. Assessment was performed by two orthopaedic surgeons, one orthopaedic surgery registrar, two radiologists and one radiology registrar. Correlation coefficients, standard errors of measurement and limits of agreement were calculated for the PTI. To assess the association between the PTI and the MIS ratio, the Pearson's correlation coefficient was calculated. Results: The PTI showed good interobserver reliability (intraclass correlation coefficient (ICC) 0.79; 95% confidence interval (CI) 0.73-0.85) and excellent intra-observer reliability (ICC 0.90; 95% CI 0.89-0.91). The standard error of measurement was 0.05 and limits of agreement with the mean +/- 0.09. A very weak and not significant correlation was found between the PTI and the MIS (r = 0.02; P = 0.77). Conclusions: The PTI showed good interobserver reliability and excellent intra-observer reliability. In order to conclude which measurement method of assessing patellar height is truly the most reliable, future studies should investigate agreement parameters (standard error of measurement, limits of agreement) besides solely correlation coefficients. We found a very weak correlation between the PTI and the MIS which suggests that at least one index has poor validity. Future validity studies on indices to assess patellar height are necessary. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Patch: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect.</p> <p>Methods/Design</p> <p>The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included.</p> <p>Discussion</p> <p>To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.</p> <p>Trial registration</p> <p>The Netherlands National Trial Register (NTR1303)</p

Effect of apomorphine on cognitive performance and sensorimotor gating in humans

Contains fulltext : 88792.pdf (publisher's version ) (Closed access)INTRODUCTION: Dysfunction of brain dopamine systems is involved in various neuropsychiatric disorders. Challenge studies with dopamine receptor agonists have been performed to assess dopamine receptor functioning, classically using the release of growth hormone (GH) from the hindbrain as primary outcome measure. The objective of the current study was to assess dopamine receptor functioning at the forebrain level. METHODS: Fifteen healthy male volunteers received apomorphine sublingually (2 mg), subcutaneously (0.005 mg/kg), and placebo in a balanced, double-blind, cross-over design. Outcome measures were plasma GH levels, performance on an AX continuous performance test, and prepulse inhibition of the acoustic startle. The relation between central outcome measures and apomorphine levels observed in plasma and calculated in the brain was modeled using a two-compartmental pharmacokinetic-pharmacodynamic analysis. RESULTS: After administration of apomorphine, plasma GH increased and performance on the AX continuous performance test deteriorated, particularly in participants with low baseline performance. Apomorphine disrupted prepulse inhibition (PPI) on high-intensity (85 dB) prepulse trials and improved PPI on low intensity (75 dB) prepulse trials, particularly in participants with low baseline PPI. High cognitive performance at baseline was associated with reduced baseline sensorimotor gating. Neurophysiological measures correlated best with calculated brain apomorphine levels after subcutaneous administration. CONCLUSION: The apomorphine challenge test appears a useful tool to assess dopamine receptor functioning at the forebrain level. Modulation of the effect of apomorphine by baseline performance levels may be explained by an inverted U-shape relation between prefrontal dopamine functioning and cognitive performance, and mesolimbic dopamine functioning and sensorimotor gating. Future apomorphine challenge tests preferentially use multiple outcome measures, after subcutaneous administration of apomorphine.1 januari 201