Erdheim-Chester disease with multisystemic involvement: a diagnostic challenge

Erdheim–Chester disease (ECD) is a rare, non-inherited, non- Langerhans form of histiocytosis of unknown origin, first described in 1930. This entity is defined by a mononuclear infiltrate consisting of lipid laden, foamy histiocytes that stain positively for CD68. Individuals affected by this disease are typically adults between their 4th and 6th decades of life. The multi systemic form of ECD is associated with significant morbidity, which may arise due to histiocytic infiltration of critical organ systems. Among the more common sites of involvement are the skeleton, central nervous system, cardiovascular system, lungs, kidneys (retroperitoneum) and skin. The most common presenting symptom of ECD is bone pain. Bilateral symmetric increased tracer uptake on 99mTc bone scintigraphy affecting the periarticular regions of the long bones is highly suggestive of ECD. However, definite diagnosis of ECD is established only once CD68(+), CD1a(−) histiocytes are identified within a biopsy specimen with aid of clinical and radiological data. Here we present a rare case of Erdheim-Chester disease in a 46 year male patient based on clinical data, radiological data, histopathological and immunohistochemistry findings

Pattern distribution of abnormal hemoglobin variants by cation exchange High Performance Liquid Chromatography: a study of 9,116 subjects

Background: The present study was conducted to identify pattern distribution of abnormal haemoglobin variants by using HPLC method in a tertiary care hospital, Surat, Gujrat, India.Methods: A cross sectional study of one-year duration was conducted including 9,116 patients screened for the presence of abnormal haemoglobin variants. Blood samples were initially tested for solubility test and run on automated haemoglobin analyzer for complete haemogram. All the suspected and family study cases were processed for HPLC (Bio-Rad Variant II) for conclusive diagnosis. Patients with a history of recent blood transfusion of less than 3 months duration were excluded from the study.Results: A total of 9,116 cases (1390 males, 7726 females) were included in the present study. The age group of patients ranged from 1 month to 95 years. Solubility test and complete haemogram were performed in all the cases. Out of the 9,116 cases, 8409(92.24%)cases had normal HPLC pattern. 492(5.40%)cases were diagnosed as sickle cell trait, 176(1.93%) cases as sickle cell disease, 29(0.32%) cases as β thalassaemia trait, 1(0.01%) case as β thalassaemia major, 2(0.02%)cases as Hb E heterozygous and 03 (0.07%) cases as Hb D Punjab heterozygous. One case of double heterozygous for Hb E-β thalassaemia was also found.Conclusions: HPLC is a rapid, accurate and useful method for diagnosing haemoglobinopathies. It serves as an reliable tool in diagnosing the presence of abnormal haemoglobin variants in suspected cases on routine haematology in developing countries like India, where the resources for detection of haemoglobinopathies are limited. Early diagnosis may help in proper management of patients

FGF Signalling Regulates Chromatin Organisation during Neural Differentiation via Mechanisms that Can Be Uncoupled from Transcription

Changes in higher order chromatin organisation have been linked to transcriptional regulation; however, little is known about how such organisation alters during embryonic development or how it is regulated by extrinsic signals. Here we analyse changes in chromatin organisation as neural differentiation progresses, exploiting the clear spatial separation of the temporal events of differentiation along the elongating body axis of the mouse embryo. Combining fluorescence in situ hybridisation with super-resolution structured illumination microscopy, we show that chromatin around key differentiation gene loci Pax6 and Irx3 undergoes both decompaction and displacement towards the nuclear centre coincident with transcriptional onset. Conversely, down-regulation of Fgf8 as neural differentiation commences correlates with a more peripheral nuclear position of this locus. During normal neural differentiation, fibroblast growth factor (FGF) signalling is repressed by retinoic acid, and this vitamin A derivative is further required for transcription of neural genes. We show here that exposure to retinoic acid or inhibition of FGF signalling promotes precocious decompaction and central nuclear positioning of differentiation gene loci. Using the Raldh2 mutant as a model for retinoid deficiency, we further find that such changes in higher order chromatin organisation are dependent on retinoid signalling. In this retinoid deficient condition, FGF signalling persists ectopically in the elongating body, and importantly, we find that inhibiting FGF receptor (FGFR) signalling in Raldh2−/− embryos does not rescue differentiation gene transcription, but does elicit both chromatin decompaction and nuclear position change. These findings demonstrate that regulation of higher order chromatin organisation during differentiation in the embryo can be uncoupled from the machinery that promotes transcription and, for the first time, identify FGF as an extrinsic signal that can direct chromatin compaction and nuclear organisation of gene loci

Ophthalmology research in the UK’s National Health Service: the structure and performance of the NIHR’s Ophthalmology research portfolio

Purpose- To report on the composition and performance of the portfolio of Ophthalmology research studies in the United Kingdom’s National Institute for Health Research (NIHR) Clinical Research Network (UK CRN). Methods- Ophthalmology studies open to recruitment between 1 April 2010 and 31 March 2018 were classified by: sub-specialty, participant age, gender of Chief Investigator, involvement of genetic investigations, commercial/ non-commercial, interventional/observational design. Frequency distributions for each covariate and temporal variation in recruitment to time and target were analysed. Results- Over 8 years, 137,377 participants were recruited (average of 15,457 participants/year; range: 5485–32,573) with growth by year in proportion of commercial studies and hospital participation in England (76% in 2017/18). Fourteen percent of studies had a genetic component and most studies (82%) included only adults. The majority of studies (41%) enrolled patients with retinal diseases, followed by glaucoma (17%), anterior segment and cataract (13%), and ocular inflammation (6%). Overall, 68% of non-commercial studies and 55% of commercial studies recruited within the anticipated time set by the study and also recruited to or exceeded the target number of participants. Conclusions- High levels of clinical research activity, growth and improved performance have been observed in Ophthalmology in UK over the past 8 years. Some sub-specialties that carry substantial morbidity and a very high burden on NHS services are underrepresented and deserve more patient-centred research. Yet the NIHR and its CRN Ophthalmology National Specialty Group has enabled key steps in achieving the goal of embedding research into every day clinical care

Sensitivity and specificity of time-domain versus spectral-domain optical coherence tomography in diabetic macular edema

Purpose: The purpose was to evaluate the sensitivity and specificity of measurements of central macular thickness (CMT) in diabetic macular edema using stratus time-domain and cirrus spectral-domain optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA). Materials and Methods: A total of 36 eyes from 19 patients with clinically significant diabetic macular edema (DME) were included. All participants underwent automated scanning patterns using cirrus HD-OCT and stratus OCT examinations on the same day. The sensitivity/specificity of retinal thickness measurements was calculated from published normative data. Agreement was calculated using Bland--Altman method. The receiver operating characteristic curves (ROC) and areas under the ROC were plotted. Results: The mean difference between the cirrus HD-OCT and stratus OCT in the central foveal zone was 49.89 μm. Bland--Altman analysis confirmed that the retinal thickness measurements had poor agreement in patients with DME. The areas under the ROC for retinal thickness measurements were 0.88 using cirrus HD-OCT and 0.94 with stratus. Conclusions: In patients with DME, the cirrus HD-OCT gives a higher reading than stratus OCT with poor agreement between the devices in most regions within the nine subfield zones. The sensitivity and specificity of the stratus OCT was comparable to the cirrus

Extracorporeal shock wave lithotripsy: Prematurely falling out of favour? A 7 year retrospective study from an Australian high‐volume centre

Abstract Objectives The aim of this study is to audit 7 years of data with a 3 year follow up from a high‐volume stone centre performing extracorporeal shock wave lithotripsy (ESWL) to evaluate efficacy in stone clearance compared to existing knowledge and understand reasons for this performance. Methods Patients who received ESWL treatment for renal or proximal ureteric stones at a single centre between January 2012 and January 2019 (to allow minimum 3 year follow up) were retrieved. A retrospective analysis was performed cross referencing for stone size, location, treatment and need for further procedures. Ethical approval was granted through Metro North HHS HREC, Queensland, Australia. Results A total of 1930 patients met inclusion criteria. Fifty‐seven percent (n = 1100) underwent left‐sided ESWL, compared to 43% (n = 830) on the right. Stone size and location were both statistically significant to treatment outcome. Small stones (2 cm) had a clearance rate of 31.3%. Small stones in an upper calyx had the highest clearance rate (87.5%, n = 120). Allowing for two procedures, 89% of stones were treated successfully. Conclusion ESWL remains a legitimate option for the treatment of small and medium sized renal calculi. ESWL stone clearance rates at our centre are higher than published elsewhere and serve as proof to its efficacy. X‐ray imaging on the day of the procedure, heavy consultant input and frequent intra‐operative imaging are cited as key reasons for success. Further research is warranted to elucidate factors affecting stone clearance rate and to enable more standardised outcomes. Further investment may be required into ESWL provisions in most Australian states and especially in Queensland to enable its continued use in contrast to developing endourological techniques

The effect of aqualase and phacoemulsification on the corneal endothelium.

PURPOSE: To compare corneal endothelial cell loss after cataract surgery by phacoemulsification and by Aqualase. METHODS: This was a prospective, randomized study of 75 eyes of 75 patients undergoing cataract surgery. Patients were randomly assigned to receive either phacoemulsification or Aqualase for cataract removal. Specular microscopy was used to calculate endothelial cell counts preoperatively and 3 weeks and 6 months afterwards. Best-corrected visual acuity was also measured. The t-test was used to detect statistical significance. RESULTS: The mean endothelial cell loss was 8.1% in the phacoemulsification group and 6.8% in the Aqualase group. There was no statistically significant difference in the amount of endothelial cell loss or in visual outcome between the 2 groups. The number of Aqualase pulses tended to increase with nuclear density while the phacoemulsification time showed little variation with nuclear subtype. CONCLUSION: Endothelial cell loss after cataract surgery is similar whether phacoemulsification or Aqualase is used. Aqualase can be considered to be as safe as phacoemulsification with regard to corneal trauma and is a useful alternative especially for soft cataracts

Correction: FGF Signalling Regulates Chromatin Organisation during Neural Differentiation via Mechanisms that Can Be Uncoupled from Transcription.

[This corrects the article DOI: 10.1371/journal.pgen.1003614.]