An image-based eyelid lesion management service—evaluation of a pilot

Background/aimsOculoplastics is a predominantly visual specialty and many of the pathologies can be diagnosed based on external appearance. An image-based eyelid lesion management service was piloted to reduce the number of patients who would require outpatient clinic review. The aim of this study was to determine its accuracy and feasibility, both as a hospital-based and community optometrist-based service. If successful, the service was envisaged to significantly reduce the number of patients that require face-to-face (F2F) review, in accordance with current post-COVID-19 principles of social distancing.MethodsPatients with lid lesions attending an oculoplastics clinic were assessed by consultant oculoplastic surgeons in an F2F consultation (Arm A). The lesions were photographed by a professional clinical photographer (Arm B) and by an optometrist with a handheld digital camera (Arm C). These images were reviewed by independent consultants masked to the outcome of the F2F clinical encounter. Data were collected prospectively including patient demographics, diagnosis, suspicion of malignancy and management. The image-based clinic results were compared to the F2F clinic results.ResultsNinety-five patients were included. Clinical diagnoses were compared for intra-observer variability and substantial agreement was demonstrated between gold-standard F2F clinic visit (Arm A) and Arm B (Ƙ = 0.708) and C (Ƙ = 0.776). There was no statistically significant difference in the rate of discharge and all cases of malignancy were either identified or flagged for F2F review in the image-based arms.ConclusionThis pilot demonstrated substantial diagnostic agreement of image-based diagnoses with F2F consultation and image review alone did not miss any cases of malignancy.Subject terms: Physical examination, Eyelid diseases     

Correction to: Serum microRNA is a biomarker for post-operative monitoring in glioma

Journal of Neuro-Oncology - We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS). Primary outcomes were...     

A Homozygous PDE6D Mutation in Joubert Syndrome Impairs Targeting of Farnesylated INPP5E Protein to the Primary Cilium

Joubert syndrome (JS) is characterized by a distinctive cerebellar structural defect, namely the « molar tooth sign ». JS is genetically heterogeneous, involving 20 genes identified to date, which are all required for cilia biogenesis and/or function. In a consanguineous family with JS associated with optic nerve coloboma, kidney hypoplasia, and polydactyly, combined exome sequencing and mapping identified a homozygous splice‐site mutation in PDE6D, encoding a prenyl‐binding protein. We found that pde6d depletion in zebrafish leads to renal and retinal developmental anomalies and wild‐type but not mutant PDE6D is able to rescue this phenotype. Proteomic analysis identified INPP5E, whose mutations also lead to JS or mental retardation, obesity, congenital retinal dystrophy, and micropenis syndromes, as novel prenyl‐dependent cargo of PDE6D. Mutant PDE6D shows reduced binding to INPP5E, which fails to localize to primary cilia in patient fibroblasts and tissues. Furthermore, mutant PDE6D is unable to bind to GTP‐bound ARL3, which acts as a cargo‐release factor for PDE6D‐bound INPP5E. Altogether, these results indicate that PDE6D is required for INPP5E ciliary targeting and suggest a broader role for PDE6D in targeting other prenylated proteins to the cilia. This study identifies PDE6D as a novel JS disease gene and provides the first evidence of prenyl‐binding‐dependent trafficking in ciliopathies.     

Dentinal candidiasis in cancer patients

Two examples of an unusual presentation of oropharyngeal candidiasis in cancer patients are offered. The light and scanning electron microscopic appearances of candidiasis involving the dentin of teeth are described. The potential significance of recognition of this form of candidiasis in cancer patients is discussed.     

Barium and strontium leaching from aged glass particle/resin matrix dental composites.

OBJECTIVES: This study characterizes the loss of Ba and Sr from glass particle/resin-matrix dental composites during simulated aging. METHODS: X-ray wavelength dispersive spectrometry and secondary ion mass spectrometry were used to analyze the Ba and Sr content from the surfaces of three commercial dental composites after aging for 4 and 8 months in humid air, artificial saliva, water, and 50% ethanol. RESULTS: Aging in artificial saliva caused the greatest leaching of Ba or Sr for all the specimens, compared with either lesser or no leaching for aging in ethanol and water. Differences in leaching were observed between the different composites. Composites aged in artificial saliva also picked up elements in the saliva solution and displayed crystallite formation on the surface. Samples aged in ethanol displayed cracking which was not observed for water or artificial saliva. SIGNIFICANCE: Dental composites display ion leaching from their surfaces over periods of four to eight months. Three mechanisms are proposed to explain differences in leaching for the various composites and aging solutions. Surface mineralization is also proposed to occur as a self-repair mechanism in artificial saliva.     

Novel dental anomalies associated with congenital contractural arachnodactyly: a case report

Congenital contractural arachnodactyly (CCA) is an inherited disorder of connective tissue similar to Marfan's syndrome. The craniofacial and oral features of a young girl with CCA are described. The patient has the typical features of CCA as well as some additional dental anomalies which have not previously been reported with this syndrome. These include banded pitted enamel hypoplasia and hypomineralization, long, spindly tapered roots, and pulp canal obliteration with multiple pulp stones. Dentists must be aware of the clinical features of a patient's syndrome to determine whether there are implications for dental treatment such as a need for antibiotic prophylaxis. It is important to exclude Marfan's syndrome as a differential diagnosis for CCA because the former has more associated complications and a less favorable prognosis.     

An EU-wide approach to HTA: An irrelevant development or an opportunity not to be missed?

An EU-wide cooperation on HTA has been proposed recently by the European Commission, focusing on relative effectiveness assessment (REA) for pharmaceuticals and medical devices. This cooperation is operationalised through a proposal for a regulation. While a good step in the right direction, this HTA cooperation framework needs to be more explicit and pragmatic about clinical value definition, what constitutes quality of evidence, how real-world evidence is handled, whether the same assessment requirements will apply for medical devices as they do for pharmaceuticals, and how to safeguard consistency in REA interpretation. If demand-rather than supply-driven, this initiative can deliver wider benefits: Europe can improve its power in global drug design and development, while Member States will have at their disposal more resources to assess performance of interventions in their healthcare systems.

     

Validity,potential clinical utility and comparison of a consumer activity tracker and a research‐grade activity tracker in insomnia disorder II: Outside the laboratory

Accurate assessment of sleep can be fundamental for monitoring, managing and evaluating treatment outcomes within diseases. A proliferation of consumer activity trackers gives easy access to objective sleep. We evaluated the performance of a commercial device (Fitbit Alta HR) relative to a research‐grade actigraph (Actiwatch Spectrum Pro) in measuring sleep before and after a cognitive behavioural intervention in insomnia disorder. Twenty‐five individuals with DSM‐5 insomnia disorder (M = 50.6 ± 15.9 years) wore Fitbit and Actiwatch and completed a sleep diary during an in‐laboratory polysomnogram, and for 1 week preceding and following seven weekly sessions of cognitive‐behavioural intervention for insomnia. Device performance was compared for sleep outcomes (total sleep time, sleep latency, sleep efficiency and wake after sleep onset). The analyses assessed (a) agreement between devices across days and pre‐ to post‐treatment, and (b) whether pre‐ to post‐treatment changes in sleep assessed by devices correlated with clinical measures of change. Devices generally did not significantly differ from each other on sleep variable estimates, either night to night, in response to sleep manipulation (pre‐ to post‐treatment) or in response to changes in environment (in the laboratory versus at home). Change in sleep measures across time from each device showed some correlation with common clinical measures of change in insomnia, but not insomnia diagnosis as a categorical variable. Overall, the Fitbit provides similar estimates of sleep outside the laboratory to a research grade actigraph. Despite the similarity between Fitbit and Actiwatch performance, the use of consumer technology is still in its infancy and caution should be taken in its interpretation.     

Attenuation of axon reflexes to compound 48/80 after repeated iontophoresis of compound 48/80 in skin of the human forearm

The aim of this study was to determine whether the iontophoretic administration of the mast cell degranulator compound 48/80 influences axon reflex vasodilatation in the skin of the human forearm. In stage 1, compound 48/80 was administered by iontophoresis to a circular site in the forearm of 9 healthy men and 8 healthy women on four occasions spread over 24 h. Two control sites were also prepared by passing the iontophoretic current through 0.9% saline. Large wheals initially developed at the compound 48/80 site in 8 of the males and in 2 of the females, but wheals were minimal in all subjects by the fourth administration. In stage 2, compound 48/80 iontophoresis provoked substantial flaring at the first control site, whereas saline iontophoresis induced only minor flaring at the second control site, indicating that compound 48/80 induced axon reflex vasodilatation. However, prior treatment with compound 48/80 inhibited flaring to compound 48/80 in subjects who initially developed wheals, consistent with mast cell degranulation. In stage 3, flaring after iontophoresis of histamine was investigated at the site of compound 48/80 pretreatment and at the second control site in 12 subjects. Flaring was impaired only slightly in 6 subjects who initially developed wheals to compound 48/80. The persistence of flaring indicates that repeated administrations of compound 48/80 did not abolish neurogenic inflammation. Transcutaneous iontophoresis of compound 48/80 may be an attractive alternative to intradermal injection in studies that aim at clarifying the function of mast cells in healthy and diseased skin.     

Induction of endothelial NO synthase by hydrogen peroxide via a Ca(2+)/calmodulin-dependent protein kinase II/janus kinase 2-dependent pathway

We have recently demonstrated that hydrogen peroxide (H(2)O(2)) is an extremely potent stimulus of endothelial NO synthase (eNOS) gene expression. The present study was designed to identify the signaling mechanisms mediating this response. Induction of eNOS expression by H(2)O(2) was found to be Ca(2+) dependent, inasmuch as it was blocked by BAPTA-AM. Further studies have indicated that Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) plays a critical role in mediating this response. Immunocytochemical staining with an anti-CaM kinase II antibody confirmed the expression of CaM kinase II in cultured bovine aortic endothelial cells. H(2)O(2) induced autophosphorylation of CaM kinase II and increased the activity of the enzyme, as assessed by an in-gel kinase assay. A specific inhibitor for CaM kinase II, KN93, and a calmodulin antagonist, W-7, attenuated eNOS induction by H(2)O(2). Further studies have indicated that janus kinase 2 is important in mediating increased eNOS expression in response to H(2)O(2) and likely is downstream from CaM kinase II. In conclusion, these data provide the first evidence that CaM kinase II plays a critical role in endothelial redox signaling. Regulation of eNOS via this pathway may represent an important vascular adaptation to oxidant stress.