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Response to Comment on "Fluocinolone Acetonide Intravitreal Implant for Treating Recurrent Non-Infectious Uveitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal".
No full textNon-invasive Instrument-Based Tests for Quantifying Anterior Chamber Flare in Uveitis: A Systematic Review.
No full text: Anterior chamber (AC) flare is a key sign for anterior uveitis. New instrument-based techniques for measuring AC flare can offer automation and objectivity. This review aims to identify objective instrument-based measures for AC flare.: In this systematic review, we identified studies reporting correlation between instrument-based tests versus clinician AC flare grading, and/or aqueous protein concentration, as well as test reliability.: Four index tests were identified in 11 studies: laser-flare photometry (LFP), optical coherence tomography, ocular flare analysis meter (OFAM) and the double-pass technique. The correlation between LFP and clinician grading was 0.40-0.93 and 0.87-0.94 for LFP and protein concentration. The double-pass technique showed no correlation with clinician grading and insufficient information was available for OFAM.: LFP shows moderate to strong correlation with clinician grading and aqueous protein concentration. LFP could be a superior reference test compared to clinician AC flare grading for validating new index tests
High incidence of Hepatitis C virus infection observed in the PROUD study of HIV pre-exposure prophylaxis.
No full textHIV negative men who have sex with men (MSM) who access pre-exposure prophylaxis (PrEP) report sexual behaviours that could place them at high risk of hepatitis C virus infection (HCV). We report HCV prevalence and incidence from the PROUD trial of PrEP.PROUD was an open-label, wait-list design randomised trial of HIV PrEP for MSM.Participants were recruited between November 2012 and April 2014, and follow-up continued to October 2016. Initial HCV testing followed national guidelines, with screening "on indication", but was replaced by routine quarterly screening in the latter part of the study.We estimated HCV seroprevalence at enrolment and incidence overall and according to calendar year.544 participants were recruited to PROUD. 133 (24.4%) were screened for HCV at enrolment, and 490 (90.1%) were tested at least once during follow-up. Seroprevalence at enrolment was 2.1% (11/530; 95% CI: 1.0-3.7%). Median follow-up time was 2.6 (IQR: 2.1-3.0) years and total follow-up of 1188.8 person years (PY). Twenty-five participants had a new HCV infection during the trial, yielding an incidence rate of 2.1 per 100 PY (25/1188.8; 95% CI: 1.4-3.1), of which three were re-infections. There was some evidence that HCV incidence increased over calendar time (P-value for trend=0.09), reaching an estimated 4.0 per 100 PY (95% CI: 2.0-8.1)in 2016. In conclusion, participants in PROUD had a high, and possibly increasing, incidence of HCV infection. This high incidence of HCV supports the 2018 BHIVA/BASHH recommendation for quarterly HCV testing among HIV-negative MSM using PrEP in the UK
A review of retroperitoneal liposarcoma genomics.
No full textRetroperitoneal liposarcomas are rare tumours that carry a poorer prognosis than their extremity counterparts. Within their subtypes - well differentiated (WDL), dedifferentiated (DDL), myxoid (MLS) and pleomorphic (PLS) - they exhibit a diverse genomic landscape. With recent advances in next generation sequencing, the number of studies exploring this have greatly increased. The recent literature has deepened our understanding of the hallmark MDM2/CDK4 amplification in WDL/DDL and addressed concerns about toxicity and resistance when targeting this. The FUS-DDIT3 fusion gene remains the primary focus of interest in MLS with additional potential targets described. Whole genome sequencing has driven identification of novel genes and pathways implicated in WDL/DDL outside of the classic 12q13-15 amplicon. Due to their rarity; anatomical location and histologic subtype are infrequently mentioned when reporting the results of these studies. Reports can include non-adipogenic or extremity tumours, making it difficult to draw specific retroperitoneal conclusions. This narrative review aims to provide a summary of retroperitoneal liposarcoma genomics and the implications for therapeutic targeting
Endoscopy in inflammatory bowel diseases during the COVID-19 pandemic and post-pandemic period.
No full textThe coronavirus disease 2019 (COVID-19) pandemic is changing the management of many chronic diseases, including that of patients with inflammatory bowel diseases (IBD). In particular, the performance of routine endoscopy is temporarily suspended, and only emergency endoscopy is allowed in many countries where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread. We highlight different scenarios in which endoscopy should still be performed urgently in patients with IBD, as well as recommendations regarding the use of personal protective equipment. We suggest a pathway for performing safe endoscopy and discuss the potential risks of postponing endoscopy in IBD. Finally, we propose a post-pandemic plan for access to endoscopy
Natural history of adrenal steroidogenesis in autoimmune Addison's disease following diagnosis and treatment.
No full textCONTEXT
The natural history of adrenal function in autoimmune Addison's disease once diagnosed and treated has not been systematically studied, but several case reports of recovery from established adrenal failure suggest it may not be uniform.
OBJECTIVE
To ascertain steroidogenic function in autoimmune Addison's disease immediately following diagnosis and during prolonged treatment.
DESIGN
We studied peak serum cortisol in response to ACTH1-24 in 20 newly diagnosed autoimmune Addison's disease patients at first presentation and then again within a month. We also studied 37 patients with established Addison's disease (for between 7 months and 44 years) in a medication-free state, measuring peak serum cortisol responses to ACTH1-24 and the urine LC-MS steroid metabolome.
RESULTS
Adrenal steroidogenesis declined rapidly after steroid replacement treatment for newly diagnosed Addison's disease was started, with a peak serum cortisol falling from 138 ± 19nmol/l (SEM) at presentation to 63 ± 13nmol/L over 4 weeks (P<0.003).
CONCLUSION
Autoimmune Addison's disease is a heterogeneous condition, showing a rapid decline in adrenal steroidogenesis during the first few weeks following diagnosis, but low-level residual function in a minority of patients, which appears to persist for many years
Phenotypic and functional translation of IL1RL1 locus polymorphisms in lung tissue and asthmatic airway epithelium.
No full textThe IL1RL1 (ST2) gene locus is robustly associated with asthma; however, the contribution of single nucleotide polymorphisms (SNPs) in this locus to specific asthma subtypes and the functional mechanisms underlying these associations remain to be defined. We tested for association between IL1RL1 region SNPs and characteristics of asthma as defined by clinical and immunological measures and addressed functional effects of these genetic variants in lung tissue and airway epithelium. Utilizing 4 independent cohorts (Lifelines, Dutch Asthma GWAS [DAG], Genetics of Asthma Severity and Phenotypes [GASP], and Manchester Asthma and Allergy Study [MAAS]) and resequencing data, we identified 3 key signals associated with asthma features. Investigations in lung tissue and primary bronchial epithelial cells identified context-dependent relationships between the signals and IL1RL1 mRNA and soluble protein expression. This was also observed for asthma-associated IL1RL1 nonsynonymous coding TIR domain SNPs. Bronchial epithelial cell cultures from asthma patients, exposed to exacerbation-relevant stimulations, revealed modulatory effects for all 4 signals on IL1RL1 mRNA and/or protein expression, suggesting SNP-environment interactions. The IL1RL1 TIR signaling domain haplotype affected IL-33-driven NF-κB signaling, while not interfering with TLR signaling. In summary, we identify that IL1RL1 genetic signals potentially contribute to severe and eosinophilic phenotypes in asthma, as well as provide initial mechanistic insight, including genetic regulation of IL1RL1 isoform expression and receptor signaling
Synchronous primary lung and breast carcinoma removed via a single incision.
No full textWe describe a case of a middle-aged female who was diagnosed with synchronous primary lung and breast cancer following a bout of recurrent chest infections. Subsequent Multi Disciplinary Team (MDT) discussion proposed that in light of the patients' multiple comorbidities, both lesions should be resected simultaneously under one general anaesthetic. The patient underwent an initial left mastectomy and axillary node clearance. Through the same incision, a left anterolateral thoracotomy was created to complete a left lower lobectomy. Post-operatively she made an uncomplicated recovery and was discharged 7 days after the procedure. Despite undergoing a longer and more complex procedure, her length of stay was in keeping with the average length of stay for a patient undergoing a thoracotomy and lobectomy [1]. This case highlights the importance of a pre-planned multidisciplinary approach to deal with synchronous pathology in an efficiently synchronous manner to improve patient outcomes
