PRDX3 is associated with metastasis and poor survival in uveal melanoma.

AIMS: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and 40% develop fatal metastatic disease. Overexpression of thioredoxin-dependent peroxidase reductase (PRDX3) has been implicated in several cancers, including prostate, breast, colorectal and lung cancer. The aim of this study was to compare the immunohistochemical expression of PRDX3 in formalin-fixed, paraffin-embedded (FFPE) primary UM tissues of patients who did and did not develop metastatic disease. METHODS: Immunohistochemical staining of PRDX3 was performed on FFPE tissue microarray samples of 92 primary UM tumours from patients who did and did not develop metastatic disease. The immunohistochemical staining was assessed by two observers who were blinded to all clinicopathological and cytogenetic details including metastatic/non-metastatic information. Based on a scoring system, expression of PRDX3 was graded as high or low. RESULTS: There were 55 tumours (59.8%) from patients who developed metastatic disease, while 37 (40.2%) were from patients who did not develop metastasis. A statistically significant difference in PRDX3 expression was observed in patients who did and did not develop metastasis (p=0.001). A significant positive correlation between high PRDX3 expression and metastasis was observed (p=0.001). A significant negative correlation between PRDX3 expression and survival was found (p=0.005). Kaplan-Meier survival analysis showed a statistically significant difference in overall survival between tumours that demonstrated low and high expression of PRDX3 (67.61 vs 130.64 months, respectively, p=0.013). CONCLUSIONS: High immunohistochemical expression of PRDX3 in primary UM tissue is associated with metastasis and poor survival.

Australia-wide point prevalence survey of the use and appropriateness of antimicrobial prescribing for children in hospital.

OBJECTIVES: To describe antimicrobial use in hospitalised Australian children and to analyse the appropriateness of this antimicrobial use. DESIGN: Multicentre single-day hospital-wide point prevalence survey, conducted in conjunction with the Antimicrobial Resistance and Prescribing in European Children study. SETTING: Eight children's hospitals across five Australian states, surveyed during late spring and early summer 2012. PATIENTS: Children and adolescents who were inpatients at 8 am on the day of the survey. MAIN OUTCOME MEASURES: Quantity and quality of antimicrobial prescribing. RESULTS: Of 1373 patients, 631 (46%) were prescribed at least one antimicrobial agent, 198 (31%) of whom were < 1 year old. The highest antimicrobial prescribing rates were in haematology and oncology wards (76% [95/125]) and paediatric intensive care units (55% [44/80]). Of 1174 antimicrobial prescriptions, 550 (47%) were for community-acquired infections, 175 (15%) were for hospital-acquired infections and 437 (37%) were for prophylaxis. Empirical treatment accounted for 72% of antimicrobial prescriptions for community-acquired infections and 58% for hospital-acquired infections (395 and 102 prescriptions, respectively). A total of 915 prescriptions (78%) were for antibacterials; antifungals and antivirals were predominantly used for prophylaxis. The most commonly prescribed antibacterials were narrow-spectrum penicillins (18% [164 prescriptions]), ß-lactam-ß-lactamase inhibitor combinations (15% [136]) and aminoglycosides (14% [128]). Overall, 957 prescriptions (82%) were deemed appropriate, but this varied between hospitals (range, 66% [74/112]) to 95% [165/174]) and specialties (range, 65% [122/187] to 94% [204/217]). Among surgical patients, 65 of 187 antimicrobial prescriptions (35%) were deemed inappropriate, and a common reason for this was excessive prophylaxis duration. CONCLUSION: A point prevalence survey is a useful cross-sectional method for quantifying antimicrobial use in paediatric populations. The value is significantly augmented by adding assessment of prescribing quality.

Proteomics in uveal melanoma.

Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

Balamuthia mandrillaris Encephalitis: Survival of a Child With Severe Meningoencephalitis and Review of the Literature.

Balamuthia mandrillaris causes granulomatous amoebic encephalitis, which is frequently fatal. There are few reports of survival in children. A 4-year-old child developed severe meningoencephalitis with multiple intracranial ring-enhancing lesions. Empiric therapy was commenced after a biopsy was performed, and the patient had a good clinical response. Molecular testing and indirect immunofluorescence later confirmed the diagnosis of Balamuthia encephalitis. Diagnosis of Balamuthia encephalitis is often delayed. The literature is reviewed with particular reference to reported survival. Prompt tissue diagnosis and initiation of therapy are common features among survivors. In previous reports, miltefosine was not used to treat children, but it was well tolerated in this case and should be considered as a therapeutic option.

Differential expression of fourteen proteins between uveal melanoma from patients who subsequently developed distant metastases versus those who did Not.

PURPOSE: To compare the proteomic profiles of two categories of primary uveal melanoma tissue samples; those from patients who have subsequently developed metastatic disease and those who have not. METHODS: Two-dimensional difference gel electrophoresis (2D DIGE) was performed on 25 uveal melanoma tissue specimens (minimum follow-up of 7 years) comparing nine uveal melanoma tumors from patients who developed metastatic disease and 16 from those who did not. Most of the tumors which metastasized also exhibited chromosome 3 monosomy. Selected differentially expressed proteins were further followed up by immunohistochemistry and functional validation in vitro using siRNA. RESULTS: Proteomic analysis revealed 14 statistically significant differentially expressed proteins, with nine showing increased expression (PDIA3, VIM/HEXA, SELENBP1, ENO1, CAPZA1, ERP29, TPI1, PARK7, and FABP3) and five showing decreased expression (EIF2S, PSMA3, RPSA, TUBB, and TUBA1B) in uveal melanomas that subsequently metastasized compared with those that did not. Immunohistochemical analysis was performed for six of the differentially expressed proteins and gave similar results to the 2D DIGE study for two of these proteins, fatty acid-binding protein, heart-type (FABP3) and triosephosphate isomerase (TPI1). siRNA knockdown in the 92.1 uveal melanoma cell line confirmed a functional role for FABP3 and TPI1 in invasion in vitro. CONCLUSIONS: Proteomic analysis identified proteins differentially expressed in uveal melanoma that will subsequently metastasize, some of which appear to have a functional role in invasion. These results may contribute to better predictive tests (along with genetic analysis) and to the identification of new therapeutic targets.

Beware the empty curette!

BACKGROUND AND OBJECTIVE: Chalazions are a common occurrence in the eyelids due to chronic inflammation in the tarsal plate. Treatment of non-resolving cases may involve incision and curettage. Chalazions that are recurrent should arouse suspicion. We present a case of a pleomorphic adenoma of the palpebral portion of the lacrimal gland, which was misdiagnosed as a chalazion. PATIENT AND METHODS: A 41-year-old Caucasian lady initially presented with a swelling in the outer part of her right upper eyelid. A diagnosis of chalazion was made and two attempts at incision and curettage failed to resolve the lesion. She was then referred to the oculoplastics/adnexal unit. A more detailed examination revealed involvement of the palpebral part of her lacrimal gland. A CT-scan confirmed this and she proceeded to have a lateral orbitotomy to remove the tumour. RESULTS: Histological confirmation of a pleomorphic adenoma of the palpebral portion of the lacrimal gland was obtained. The lacrimal gland had been completely excised. CONCLUSION: Persistent or recurrent meibomian cyst should be treated with suspicion. A careful orbital examination including lid eversion should always be performed to outrule a more sinister pathology.