Levelling the playing field through the London Network of the UK clinical trials accelerator platform.

Cystic fibrosis (CF) is a multisystem, genetic disease with a significantly reduced life expectancy. Despite substantial progress in therapies in the last 10-15 years, there is still no cure. There are dozens of drugs in the development pipeline and multiple clinical trials are being conducted across the globe. The UK Cystic Fibrosis Trust's (CFT) Clinical Trials Accelerator Platform (CTAP) is a national initiative bringing together 25 UK based CF centres to support the CF community in accessing and participating in CF clinical trials. CTAP enables more CF centres to run a broader portfolio of trials and increases the range of CF studies available for UK patients. There are four large specialist CF centres based in London, all within a small geographical region as well as two smaller centres which deliver CF care. At the launch of CTAP, these centres formed a sub-network in a consortium-style collaboration. The purpose of the network was to ensure equity of access to trials for patients across the UK's capital, and to share experience and knowledge. Four years into the programme we have reviewed our practices through working group meetings and an online survey. We sought to identify strengths and areas for improvement. We share our findings here, as we believe they are relevant to others delivering research in regions outside of London and in other chronic diseases.

Community Health Care Providers' Perspectives on Human Immunodeficiency Virus Pre-Exposure Prophylaxis Use Among Black Women in Eastern Virginia.

The most at-risk population among women for human immunodeficiency virus (HIV) diagnosis in the United States are Black women, accounting for 61% of all new HIV cases. Pre-exposure prophylaxis (PrEP) is a safe and effective HIV prevention method for people at risk of HIV acquisition. Although disproportionately affected by HIV, Black women's knowledge, perceived benefits, and uptake of PrEP remain low. The socioecological model (SEM) may be useful for understanding why there is a low uptake of PrEP among Black women. The current study used the SEM to explore provider perspectives on the barriers and facilitators of PrEP uptake among Black women in Eastern Virginia. Semistructured interviews were conducted with a total sample of 15 community health care providers. Barriers of PrEP uptake at the societal (e.g., PrEP advertisements focus on gay men), community/organizational (e.g., time constraints in the workplace), interpersonal (e.g., perceived monogamy), and individual (e.g., unmet basic needs) levels were identified. Providers also identified facilitators of PrEP uptake at the societal (e.g., PrEP advertisements that target women), community/organizational (e.g., PrEP education), interpersonal (e.g., HIV-positive partner), and individual (e.g., PrEP awareness and perceived susceptibility to HIV) levels. These findings highlight unique barriers to accessing and taking PrEP for Black women in the United States, and potential factors that could facilitate PrEP use. Both barriers and facilitators may be important targets for interventions to improve PrEP uptake. Future research focused on improving PrEP uptake among Black women in the United States should consider multi-level interventions that target barriers and facilitators to reduce rates of HIV infections.

Glucagon-like peptide-1 analogues in monogenic syndromic obesity: Real-world data from a large cohort of Alström syndrome patients.

AIM: To examine the real-world efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in monogenic obesity in patients with Alström syndrome (ALMS). METHODS: We screened 72 UK adult patients with ALMS and offered treatment to 34 patients meeting one of the following criteria: body mass index of 25 kg/m2 or higher, insulin resistance, suboptimal glycaemic control on antihyperglycaemic medications or non-alcoholic fatty liver disease. RESULTS: In total, 30 patients, with a mean age of 31 ± 11 years and a male to-female ratio of 2:1, completed 6 months of treatment with GLP-1 RAs either in the form of semaglutide or exenatide. On average, treatment with GLP-1 RAs reduced body weight by 5.4 ± 1.7 (95% confidence interval [CI] 3.6-7) kg and HbA1c by 12 ± 3.3 (95% CI 8.7-15.3) mmol/mol, equating to 6% weight loss (P < .01) and 1.1% absolute reduction in HbA1c (P < .01). Significant improvements were also observed in serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and alanine aminotransferase. The improvement of metabolic variables in our cohort of monogenic syndromic obesity was comparable with data for polygenic obesity, irrespective of weight loss. CONCLUSIONS: Data from our centre highlight the non-inferiority of GLP-1 RAs in monogenic syndromic obesity to the available GLP-1 RA-use data in polygenic obesity, therefore, these agents can be considered as a treatment option in patients with ALMS, as well as other forms of monogenic obesity.

Membrane binding properties of plant defensins.

The membrane interaction characteristics of five antifungal plant defensin peptides: NaD1, and the related HXP4 and L5, as well as NaD2 and the related ZmD32 were studied. These peptides were chosen to cover a broad range of cationic charges with little structural variations, allowing for assessment of the role of charge in their membrane interactions. Membrane permeabilizing activity against C. albicans was confirmed and quantified for benchmarking purposes. Viscoelastic characteristics of the membrane interactions were studied in typical neutral and charged model membranes using quartz crystal microbalance with dissipation (QCM-D. Frequency-dissipation fingerprinting analysis of the QCM-D results revealed that all of the peptides were able to bind to all studied model membranes albeit with slightly different viscoelastic character for each membrane type. However, characteristic disruption patterns were not observed suggesting that the membrane disrupting activity of these defensins is mostly specific to fungal membranes, and that increasing the peptide charge does not enhance their action. The results also show that the presence of specific sterols has a profound effect on the ability of the peptides to disrupt the membrane.

Homocystinuria diagnosis and management: it is not all classical.

Homocystinuria (HCU) refers to a group of inherited disorders of homocysteine metabolism associated with high blood homocysteine concentration, thromboembolic tendency and neurocognitive symptoms. The most common causes of a high blood homocysteine relate to underlying vitamin B12 or folate deficiency which must be excluded first. Thereafter, an inherited metabolic condition can be considered.The most prevalent inherited disorder of homocysteine metabolism is classical HCU caused by deficiency of the pyridoxine-dependent enzyme, cystathione beta-synthase, which converts homocysteine to cystathionine in the transsulphuration pathway. An alternative route for homocysteine metabolism is its remethylation to methionine by the cobalamin-dependent enzyme, methionine synthase, using the folate derivative, methyltetrahydrofolate, as a methyl donor. Remethylation defects are caused by impaired activity of methionine synthase itself, of an enzyme required to generate its methylcobalamin cofactor from dietary vitamin B12, or of the enzyme methyltetrahydrofolate reductase (MTHFR), which generates the methyl donor.The correct diagnosis can be inferred from additional laboratory investigations including a complete blood count and quantitation of methionine and methylmalonic acid. Methionine is high/normal in HCU and low in the remethylation disorders. In the latter, cobalamin defects are readily distinguished from MTHFR by a coexisting macrocytic anaemia and further delineated by presence or absence of methylmalonic acid in urine or plasma.Lowering homocysteine reverses thromboembolic risk. In HCU, this may be achieved with pyridoxine alone or with betaine as an alternative methyl donor. Some patients additionally follow a methionine-restricted diet. Betaine is the primary treatment for MTHFR and cobalamin disorders are managed with high-dose hydroxocobalamin.

Subcellular Transcriptomics and Proteomics: A Comparative Methods Review.

The internal environment of cells is molecularly crowded, which requires spatial organization via subcellular compartmentalization. These compartments harbor specific conditions for molecules to perform their biological functions, such as coordination of the cell cycle, cell survival, and growth. This compartmentalization is also not static, with molecules trafficking between these subcellular neighborhoods to carry out their functions. For example, some biomolecules are multifunctional, requiring an environment with differing conditions or interacting partners, and others traffic to export such molecules. Aberrant localization of proteins or RNA species has been linked to many pathological conditions, such as neurological, cancer, and pulmonary diseases. Differential expression studies in transcriptomics and proteomics are relatively common, but the majority have overlooked the importance of subcellular information. In addition, subcellular transcriptomics and proteomics data do not always colocate because of the biochemical processes that occur during and after translation, highlighting the complementary nature of these fields. In this review, we discuss and directly compare the current methods in spatial proteomics and transcriptomics, which include sequencing- and imaging-based strategies, to give the reader an overview of the current tools available. We also discuss current limitations of these strategies as well as future developments in the field of spatial -omics.

Acute Confusion as an Initial Presentation of SARS-CoV-2 Infection.

BACKGROUND AND PURPOSE: The respiratory manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been extensively documented. There is emerging evidence that coronavirus disease 2019 (COVID-19) has number of other presenting features which might not be related to the severity of the respiratory disease. We have previously described a case of hypoactive delirium as the first manifestation of COVID-19 without profound lung disease. Here we present five cases of elderly patients, without a prior history of dementia and had no overt COVID-19-related pneumonia, who presented with the acute onset of delirium as the primary manifestation of COVID-19. METHODS: This retrospective, single-center study performed a health informatics search to produce a list of patients who were admitted with acute confusion and tested positive for the SARS-CoV-2 virus between March 1 and June 30, 2020. The electronic medical admission notes were screened for all patients with confusion who tested positive for SARS-CoV-2. Patients with a history of dementia and a high risk of delirium were excluded, such as severe COVID-19-related pneumonia or any other infection, malignancy, drugs, or severe illness of any kind. RESULTS: During the first wave of the COVID-19 pandemic our hospital experienced just over 3,000 SARS-CoV-2 positive patients, and 45 of them had documented confusion upon admission. Secondary causes for their acute confusion were excluded. Five patients were identified as having delirium as the initial presentation of COVID-19-related illness without significant COVID-19-related pneumonitis. None of them had overt chest symptoms or a previous history of confusion, and the 3 patients who underwent head CT scans had normal findings. CONCLUSIONS: This case series illustrates the importance of recognizing acute confusion as the first manifestation of COVID-19 in susceptible individuals.

Comparison of two protocols for insulin administration and fasting time in diabetic dogs anaesthetised for phacoemulsification: A prospective clinical trial.

BACKGROUND: There is a lack of evidence-based guidelines on perioperative insulin administration and fasting time in diabetic dogs. The aim of this study was to compare two protocols with respect to intraoperative changes in blood glucose (BG) concentrations compared to preoperative values. METHODS: Thirty-two dogs were included. Dogs of group AM (n = 15) underwent anaesthesia in the morning after 12 hours fasting and received half their usual insulin dose, while dogs of group PM (n = 17) had surgery in the afternoon after 6 hours fasting and received their usual insulin dose; BG was measured before premedication (baseline), after anaesthetic induction, every 30 minutes throughout surgery, at extubation and after anaesthetic recovery. The occurrence of intraoperative complications was recorded. RESULTS: There were no differences between groups in perioperative changes in BG over time, and in the proportion of dogs experiencing complications. Common complications were hypotension (53 per cent of dogs in either groups), hyperglycaemia (67 and 65 per cent in groups AM and PM) and hyperkalaemia (20 and 11 per cent in groups AM and PM). CONCLUSIONS: Either protocols may be used in diabetic dogs undergoing anaesthesia. The occurrence of hyperkalaemia in the study population supports routine intraoperative monitoring of blood potassium concentration.

A multicenter retrospective study into endogenous causes of uveitis in cats in the United Kingdom: Ninety two cases.

PURPOSE: The purpose of this study was to investigate the most common causes of endogenous feline uveitis in a UK referral population and to investigate associations based on signalment. METHODS: Retrospective multicenter cross-sectional study from 2010 to 2019 including cats presented to the Animal Health Trust and the Royal Veterinary College with clinical signs consistent with uveitis. Cats were included in analyzes if they had a full physical examination including an ophthalmic examination, complete blood count, serum biochemistry, and infectious disease testing for at least two diseases unless the diagnosis was found on clinical examination (eg, neoplasia). RESULTS: A total of 92 cats were included in the study. The majority of cats presenting with uveitis were male (66.3%). The most common causes of endogenous uveitis were idiopathic uveitis (42/92 45.7%), feline infectious peritonitis (FIP) 15/92 16.3%), and lymphoma (10/92 10.9%). Fisher's exact test showed differences in breed across diagnosis groups (p = .002) with purebred cats being overrepresented in the lymphoma and FIP groups. Kruskal-Wallis test showed differences in median age across diagnosis groups (p < .001) with cats in the FIP group having the youngest age (median 1.4 years, interquartile range (IQR) 0.4-1.8 years) and cats in the neoplasia (primary or paraneoplastic) group having the oldest age (median 12.8 IQR 10.8-13.8). Idiopathic uveitis was unilateral in 56.1% of cases, and infectious causes were unilateral in 47.8% of cases. CONCLUSIONS: The most common cause of endogenous uveitis in a population of cats in the UK was idiopathic uveitis, followed by FIP and lymphoma.

Corneo-limbo-conjunctival transposition to treat deep and perforating corneal ulcers in dogs: A review of 418 eyes and corneal clarity scoring in 111 eyes.

PURPOSE: To report surgical and corneal clarity scores (CCSs) of corneo-limbo-conjunctival transpositions (CLCTs) in a large number of canine cases. METHODS: Retrospective review of records that underwent CLCT to repair deep ulcers or perforations between 2002 and 2018. Signalment, concurrent eye disease, additional procedures, pathogenesis, medication, graft orientation, follow-up, and CCSs were recorded. RESULTS: 418 eyes of 399 dogs were included. Brachycephalics were most commonly affected, comprising 325/418 (77.75%) of the eyes. The most commonly affected breeds were Pugs, Shih Tzus, Cavalier King Charles Spaniels, and French Bulldogs, with 116/418 (27.75%), 64/418 (15.31%), 34/418 (8.13%), and 34/418 (8.13%) ulcerated eyes, respectively. Mean age at surgery was 5.5 years (range 59 days-17.7 years), and median follow-up time was 100 days (range 3 days-7.64 years). The most common etiopathogenesis was spontaneous ulceration in 205/418 eyes (49.04%) of which 191 (93.17%) occurred in brachycephalics. Primary keratoconjunctivitis sicca affected 122/418 eyes (29.19%) and injury 39/418 eyes (9.33%). Mean ulcer width was 3.5 mm (0.5-10 mm). Success rate was 97.13% (406/418 eyes). Failure end points recorded included no menace response, secondary glaucoma, and endophthalmitis. Pre-existing perforation was found in 101/418 (24.16%) of the eyes and significantly increased failure rate (P < .001). The median CCS was G3 (G0-G4), which was lower for Pugs (G2). Graft orientation affected CCS, but did not reach statistical significance. CONCLUSION: The high success rate and CCS for CLCT in dogs make it a good technique to treat deep ulcers but a less desirable outcome is anticipated when treating perforations and Pugs.

Severe neurological crisis in adult patients with Tyrosinemia type 1.

We report six adult patients with Tyrosinaemia type 1 (HT-1) who presented with recurrent porphyria-like neurological crises after discontinuation/interruption of 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione (NTBC) treatment. The crises were life-threatening for some of the patients, with respiratory muscle paralysis requiring ventilatory support, hemodynamic disturbance due to autonomic changes requiring resuscitation, acute progressive ascending motor neuropathy causing profound impairment, recurrent seizures, and neuropathic pain. Our patients' porphyria-like presentations were variably misdiagnosed, with delay to diagnosis resulting in more severe recurrent attacks. We report the first series of neurological crises in adult patients with HT-1. These crises, which may be fatal, can be prevented and treated effectively with neurologist/physician awareness and patient education.

The clinical utility of total concentration of urinary globotriaosylsphingosine plus its analogues in the diagnosis of Fabry disease.

BACKGROUND: Fabry disease (FD) is a genetic disorder caused by defective α-galactosidase-A enzyme due to mutations in the GLA gene. A reliable diagnosis in classical FD males can be made by measuring the enzyme activity while diagnosing classical FD females and non-classical FD patients requires mutation analysis. Plasma globotriaosylsphingosine (Lyso-Gb3) has progressively gained more importance as a diagnostic biomarker for FD in recent years. Having another biomarker to complement plasma Lyso-Gb3 will increase the diagnostic accuracy in the era of mass screening, and also precision medicine. This study aims to highlight the clinical utility of the total concentration of urinary Lyso-Gb3 plus its analogues in diagnosing FD. METHOD: Random urine samples collected from 42 FD patients and 48 healthy individuals. Lyso-Gb3 and its analogues were enriched by solid phase extraction and analysed by liquid chromatography tandem mass spectrometry. RESULTS: The total concentration of Lyso-Gb3 plus its analogues in classical FD male and female patients were 1124.4 ±â€¯181.2 and 308.6 ±â€¯78.6 pmol/mmol creat., respectively. The levels in non-classical FD male and female patients were 229.2 ±â€¯169.4 and 314.4 ±â€¯156.4 pmol/mmol creat., respectively. Urinary Lyso-Gb3 and its analogues were virtually undetectable in healthy volunteers making it 100% specific for FD diagnosis. For FD male and female patients, total concentration of urinary Lyso-Gb3 plus its analogue levels ≥0.25 pmol/mmol creat. yielded a diagnostic sensitivity and specificity of 100% (AUC = 1, p < 0.00001). CONCLUSIONS: Our study findings support that the total concentration of Lyso-Gb3 plus its analogues in urine is specific to FD and may provide extra diagnostic utility for both classical and non-classical FD patients.

Outcome of phacoemulsification in 71 cats: A multicenter retrospective study (2006-2017).

PURPOSE: To assess outcome of phacoemulsification in cats. METHODS: Records of 71 cats (82 eyes) from five referral centers were reviewed. Groups were divided by cause of cataract (congenital/juvenile [n = 32], traumatic [n = 33], and secondary to uveitis [n = 6]), and group comparisons were performed for the most common complications: postoperative ocular hypertension (POH), uveitis, corneal ulceration, synechia/dyscoria, and posterior capsular opacity (PCO) in three different time periods: immediately postoperatively, at 1-90 days, and at >90 days. RESULTS: Median follow-up was 198 days (interquartile range 64-518 days). The overall visual success rate of the cats with a 12-month follow-up was 92.6% (25/27 eyes). POH occurred in 35/82 (42.6%) eyes. Immediately postoperatively, uveitis was the most common complication in 28/82 eyes (34.1%) followed by corneal ulceration in 22/82 eyes (26.8%). At 1-90 days, uveitis in 41/81 eyes (50.6%) remained the most common complication, followed by synechia/dyscoria in 21/81 eyes (25.9%), corneal ulceration in 16/81 eyes (19.7%), and PCO in 15/81 eyes (18.5%). At >90 days, PCO in 17/47 eyes (36.1%), followed by synechia/dyscoria in 16/47 eyes (34%), was the most common complications. The number of eyes with synechia/dyscoria in the trauma group was higher (13/33 [39.3%]) than in the congenital/juvenile group (5/31 [16.1%]) at 1-90 days (P = .039). No statistical difference was found for the other group comparisons. Three eyes in total were enucleated owing to endophthalmitis, post-traumatic ocular sarcoma, and secondary glaucoma. CONCLUSION: Uveitis in the short-term and PCO and synechia/dyscoria in the long-term were the most common complications following phacoemulsification in cats.

Defining renal phenotype in Alström syndrome.

BACKGROUND: Alström syndrome (AS) is a rare autosomal recessive ciliopathy with a wide spectrum of clinical features, including cone-rod retinal dystrophy, neuronal deafness, severe insulin resistance and major organ failure. The characteristics of renal disease in the syndrome have not been systematically described. The aim of this study is to define the onset and progression of renal disease in AS. METHOD: Prospective observational cohort study. SETTING AND PARTICIPANTS: Thirty-two adult subjects from a national specialist clinic in UK and 86 subjects from an international AS registry were studied. OUTCOMES: First, an international registry cross-sectional study across all age groups to determine change in kidney function was performed. Secondly, a detailed assessment was carried out of adult AS patients with serial follow-up to determine incidence, aetiology and progression of renal disease. ANALYTICAL APPROACH: Generalized estimating equations were used to evaluate the relationship between age and estimated glomerular filtration rate (eGFR). Associations between patient factors and eGFR levels were then assessed in the adult AS cohort. RESULTS: The international registry study of the renal function of 118 subjects with AS (median age 21 years) showed a rapid decline with age, at an average of -16.7 and -10.9 mL/min/1.73 m2 per decade in males and females, respectively. In a UK national cohort of 32 patients with AS (median age 22 years), 20/32 (63%) had chronic kidney disease (CKD) Stage 3 or above based on eGFR <60 mL/min/1.73 m2 or evidence of albuminuria. Hyperuricaemia was noted in 25/32 (79%). Structural abnormalities such as nephrocalcinosis without hypercalcaemia and cysts were observed in 20/32 (63%) subjects. Lower urinary tract symptoms were frequent in 17/19 (70%) of AS patients. Histological evidence showed mixed tubulo-interstitial and glomerular disease. CONCLUSIONS: This is the first study to demonstrate that renal disease is the hallmark of AS, which starts early and progresses with age, leading to a high prevalence of advanced CKD at young age. AS should be considered in the differential diagnosis of rare genetic renal diseases.

Visual outcome following phacoemulsification in English Cocker Spaniels with suspected progressive retinal atrophy: A retrospective multicenter study of 54 cases (2002-2017).

OBJECTIVE: To describe the visual outcome following phacoemulsification in English Cocker Spaniels (ECS) affected by cataracts and suspected progressive retinal atrophy (PRA). ANIMALS STUDIED: Fifty-four client-owned dogs. PROCEDURES: A multicenter, retrospective study was performed including ECS with suspected PRA which underwent phacoemulsification. PRA was suspected on ophthalmic examination before and after surgery, and/or after electroretinography (ERG) was performed. Visual outcome was assessed by menace response per eye at seven time periods post-surgery (P1= 25-90 days, P2 = 91-180 days, P3 = 181-364 days, P4 = 365-549 days, P5 = 550-729 days, P6 = 730-1094 days, and P7 ≥ 1095 days). Descriptive statistics were performed. Generalized estimating equations were used to identify predictors associated with vision after surgery. Odds ratio and confidence intervals were reported. Significance was set at P < 0.05. Owners were invited to participate in a questionnaire. RESULTS: Phacoemulsification was performed in 85 eyes. Median age at surgery was 9.09 years (min. 2.17 years, max. 13.49 years). At all re-examinations, up to and including P5, significantly more eyes were visual than before surgery (P ≤ 0.003). Odds for vision were significantly increased for eyes that underwent surgery. Electroretinograms were performed in 75/85 eyes that underwent surgery, demonstrating low b-wave amplitudes. There was no significant effect of the age, gender, vision before surgery, presence of dazzle reflex, cataract stage or abnormality on gonioscopy on visual outcome. The questionnaire response rate was 48.2%. Most participants (92.5%) felt that cataract surgery led to improvement of the dog's quality of life. CONCLUSIONS: English Cocker Spaniels with suspected PRA may benefit from phacoemulsification with vision up to 2 years following surgery.

Bilateral enucleation in dogs: A review of owner perceptions and satisfaction.

PURPOSE: To evaluate owner perceptions of the quality of life of their dogs before and after bilateral enucleation and to assess owner satisfaction with the procedure. METHODS: Medical records of 72 dogs from the Willows Veterinary Centre and Referral Service (49 dogs) and the Royal Veterinary College (RVC, 23 dogs) that had undergone bilateral enucleation, either in one procedure or at different times, between April 2008 (Willows) or 2012 (RVC) and April 2017, were reviewed. Owners were initially telephoned to determine owner satisfaction, followed by a postal visual analogue scale (VAS) questionnaire evaluating perceptions of their dog's quality of life before and after the bilateral enucleation. Statistical evaluation included Wilcoxon signed-rank tests and Chi-squared analysis. RESULTS: Of the 72 cases identified, 63 owners (88%) were contacted by telephone and 60 owners (83%) also completed the VAS questionnaire. The mean age at the time of the second or bilateral enucleation was 8.47 years (range 7.1 months-14.5 years). Cross-breeds (n = 12, 17%) and Jack Russell Terriers (n = 7, 10%) were the two most represented breeds. Glaucoma was the most common reason for enucleation (139/144 eyes, 97%). Most owners (57/63, 90%) were satisfied with the surgery and would consent to the procedure again. Statistically significant improvements in owner perceptions of their dog's pain level, reaction to facial/ocular palpation, activity levels, and quality of life were identified post-enucleation. CONCLUSIONS: Following bilateral enucleation, owners were satisfied with the procedure and perceived their dogs to have a good quality of life.

Rhomboid blepharoplasty and cryotherapy for the treatment of a squamous cell carcinoma on the lower eyelid in a horse.

A rhomboid blepharoplasty can be used to achieve functional and cosmetic eyelid reconstruction at the medial canthus in the horse. Combination of a rhomboid blepharoplasty with cryotherapy is a treatment option for eyelid ocular squamous cell carcinomas.

The investigation of histopathology and locations of excised eyelid masses in dogs.

BACKGROUND: Eyelid masses are the most common ocular diseases in dogs. However, there are no studies specifically investigating the location of eyelid masses. METHODS: 118 dogs with 119 eyelid masses were included. Medical records and pathology reports were retrospectively reviewed at National Taiwan University veterinary hospital and Vision Eyecare Centre for Animals between 2012 and 2017. RESULTS: Mean age of dogs was 9.4±2.5 years. Female spayed dogs had significantly higher prevalence of eyelid mass than female intact dogs (p<0.01). Prevalence of upper eyelid mass was significantly higher than lower eyelid mass (p<0.01). The upper lateral eyelid was the significantly more common location compared with the upper medial eyelid. Mean mass volume was 258.2±661.0 mm3. The most common eyelid mass type was meibomian epithelioma (34.5%), followed by meibomian adenoma (29.4%) and meibomian hyperplasia (18.5%). Non-tumours comprised 25.2%, benign tumours comprised 67.2% and malignant tumours comprised 7.6% of all eyelid masses. Malignant tumours were significantly larger than benign lesions (p<0.01). All dogs underwent surgical excision without any complications. CONCLUSION: The majority of eyelid masses were benign. Surgical intervention can prevent further ocular irritation and provide good prognosis.

Globotriaosylsphingosine (Lyso-Gb3) as a biomarker for cardiac variant (N215S) Fabry disease.

Fabry disease (FD) is a multi-systemic X-linked lysosomal disorder caused by the deficient activity of α-galactosidase-A enzyme, which leads to accumulation of glycosphingolipids in various body tissues. The N215S mutation is a known variant of FD, with a late onset cardiac phenotype. Consensus guidelines acknowledged the use of globotriaosylsphingosine (Lyso-Gb3) as a diagnostic marker for classical FD but its utility for cardiac variant FD is not clear. We aim to characterize the clinical features and evaluate the diagnostic accuracy of plasma and urinary Lyso-Gb3 levels in N215S cardiac variant FD patients. Thirty-four FD patients with the late-onset N215S cardiac variant mutation were enrolled along with 62 classical FD patients and 109 healthy controls. Plasma and urinary Lyso-Gb3 and its analogues were analyzed by LC-MS/MS. Both FD males and females with N215S mutation showed Lyso-Gb3 levels of (mean ± SEM) 9.7 ± 1.0 and 5.4 ± 0.8 nM, respectively. These levels were significantly higher than healthy control and lower than classical FD patients (p < 0.0001). Plasma Lyso-Gb3 levels equal to or higher than 2.7 nM yielded a diagnostic sensitivity and specificity of 100% (AUC = 1, p < 0.0001). Cardiac involvement was frequent with 16/34 (47%) developing left ventricular hypertrophy. Three patients who underwent renal biopsy had the characteristic sphingolipid deposition in the podocytes while 6/19 (32%) had evidence of white matter changes or infarct on brain MRI. Taken together, cardiac variant N215S mutation is rather an attenuated form of classical FD. Plasma Lyso-Gb3 is a diagnostic hallmark to differentiate N215S variant phenotype from subjects with no FD.

Rabbits with naturally occurring cataracts referred for phacoemulsification and intraocular lens implantation: a preliminary study of 12 cases.

OBJECTIVE: To describe the presentation of 15 rabbits with naturally occurring cataracts referred for phacoemulsification surgery, the procedure in 13 cases and the follow-up in 12. ANIMALS INCLUDED: Fifteen rabbits (30 eyes), nine of which stopped following visual cues in association with cataract progression. MATERIALS AND METHODS: Rabbits underwent preoperative ophthalmic and ocular ultrasound examination. RESULTS: Thirteen rabbits (22 eyes) had mature cataracts. Ten were bilateral and three unilateral. Two rabbits had an anterior chamber abscess. The cataract in one of these was incipient. One rabbit had bilateral immature cataracts. One rabbit had a subluxated lens, and one had a retinal detachment. Thirteen rabbits (22 eyes) underwent phacoemulsification. Eighteen, 13.5-mm capsular tension rings (CTRs) and seventeen, 13-mm IOLs (Acrivet® , Berlin, Germany) were fitted including one 41D 60V-model, and three 49D and thirteen 58D 20S-models. Intraoperative complications included one unilateral posterior-capsular tear, one lens subluxation, and one expulsive choroidal hemorrhage. One rabbit died during anesthetic recovery. Nine cases were PCR-tested for Encephalitozoon cuniculi, and only three were positive. The median follow-up time was 12 months (4-24 months). Rabbits that were not following visual cues preoperatively did so postoperatively, and surgery resulted in a clear visual axis for the follow-up period in every case except in two, due to reasons other than the surgery. CONCLUSIONS: Phacoemulsification with CTR and IOL implantation offers good long-term results and can improve the quality of life of pet rabbits. Retinal detachment, lens luxation, expulsive choroidal hemorrhage, and anesthetic death are potential complications.