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In this paper, we investigate the effect of sedation using low-dose propofol on patient reported outcome measures (PROMS) in patients undergoing cataract surgery. This is a randomised, single-blinded observational prospective study. Patients undergoing elective cataract surgery using peribulbar anaesthesia over consecutive cataract lists were selected for this trial. Patients were randomised to receive either no sedation or low-dose propofol (20 to 30 mg followed by 10 mg increments until the patient developed slurred speech alone) prior to the administration of local anaesthesia. Pain, satisfaction, anxiety, needle recall, pulse, and blood pressure (BP) were measured. A total of 97 patients were included, 50 of whom received propofol. There were 4 senior surgeons and anaesthetists. There were no ocular or systemic complications and all patients had uncomplicated surgery. Anxiety (p = 0.026), needle recall (p < 0.001), difference in systolic BP (p = 0.043), and pulse (p = 0.046) were dependent on patient age (p < 0.001) and the use of propofol (p = 0.007). Lower pain was associated with propofol (p = 0.008), as well as lower anxiety (p = 0.002), and increased patient age (p = 0.014). The administration of propofol was significantly associated with lower needle recall (p < 0.001), pre- to post-operative difference in systolic BP (p = 0.029), and mean BP (p = 0.044). Low-dose propofol given immediately prior to administration of local anaesthesia was associated with reduced pain and needle recall, as well as lower BP.

Purpose: To determine liver screening frequency and modality in UM patients following primary treatment, and the characteristics of detected metastases. Methods: A 10-year retrospective study of 615 UM patients undergoing liver surveillance in Liverpool. Information was collected from liver scan reports of these patients. Results: Of 615 UM patients analyzed, there were 337 men (55%) and 278 women (45%). Median age at primary treatment was 61 years (range, 22–94). At study end, median follow-up was 5.1 years, with 375 patients (61%) alive and 240 deceased (39%). Of the deceased patients, 187 (78%) died due to metastatic UM; 24 (10%) deaths were due to other causes; and 29 (12%) patients died of unknown conditions. In total, 3854 liver scans were performed in the 615 UM patients, with a median of 6.2 scans per patient (range, 1–40). Liver MRI was most frequently performed (62.8%). In total, 229 (37%) UM patients developed metastases during the study period: 150 were detected via liver surveillance and 79 were observed post-mortem. Conclusions: Metastatic UM onset is related to the size and genetic profiles of the primary UM, and can be predicted using the model LUMPO3. Regular liver surveillance allowed for timely detection of metastases, and through metastasectomy can lead to prolongation of life in some patients.

Medical device vigilance is concerned about device problems (incidents) their analysis and mitigation to ensure that device performance is good and that patient safety are maintained. The main aim of this is to outline the criteria of the medical device vigilance program and to highlight the requirements that still remain in the state laws of regulated markets (US and EU) and to increase access to safe, reliable and therapeutic benefits. The severity of the Subject, risk assessment should carried out by the manufacturer prior to marketing. In US, Medical Device surveillance deals with post-marketing monitoring where the manufacturer or importer is required submit reports to regulatory authorities; same as in the EU. US medical device tracking system involved with different sections to update adverse event. The user or manufacturer has to report incidents to member states where necessary actions are to be taken as early as possible to protect or reduce hazard of casualty or severe decline in terms of safety and quality by implementing the CAPA for risk analysis.

Primary sinonasal neuroendocrine carcinoma (SNEC) is a rare aggressive sinonasal malignancy which typically occurs in the ethmoidal or maxillary sinuses, with or without nasal cavity involvement, of middle-aged patients (median age 53 years), with a slight male preponderance. No risk factors have been identified. Most patients present at advanced stages due to the lack of significant symptoms.1,4,5,8 Advanced tumours may invade the skull, orbit or brain. Staging is of limited value in predicting prognosis and recent literature clearly highlights the importance of histological diagnosis, particularly differentiation grade, in determining the prognosis and predicting treatment response. Nomenclature has been ambiguous, but broadly SNECs can be classified as well-, moderately- or poorly differentiated. The latter group includes sinonasal undifferentiated carcinoma and sinonasal small cell carcinoma. On histological examination, well-to-moderately differentiated tumours show medium-sized cells with large nuclei containing stippled or ‘salt/pepper’ chromatin and scant cytoplasm. Nuclear moulding, increased mitoses and apoptotic bodies are commonly seen. Immunohistochemistry reveals expression of neuroendocrine markers.1,4–7 Poorly-differentiated tumours may lose expression of neuroendocrine markers and differentiation from other poorly differentiated malignancies can be extremely difficult.1,4–7 Due to the limited number of reported cases, there is no clear consensus on management, although oncologists now advocate multimodal therapy. Combined surgery and radiotherapy is thought to beneficial in moderately and poorly-differentiated subtypes.1,4–8 We describe a classical case of SNEC with secondary orbital involvement, with a review of the current literature.

Hemorrhoids or piles are typically where swollen veins inside the rectum or outside the anus can cause pain, anal itching, and rectal bleeding. Hemorrhoids can be affected by any age group of people. It affects people most often at the age of 45 and 65 years. Management of hemorrhoid disease ranging from conservative treatment to office-based procedure and surgical treatment. For the majority of patients simple dietary, lifestyle modification, topical and over-the-counter drugs, and sitz bath will provide symptomatic relief. The surgical and office-based procedure should be done for patients who do not respond to conservative treatment. However, it is clearly stated that treatment option is based on patient choice, convenience, and degree of hemorrhoids. Key words: Hemorrhoids, Piles, Management, Hemorrhoidectomy

Metastatic uveal melanoma (mUM) to the liver is incurable. Transcriptome profiling of 40 formalin-fixed paraffin-embedded mUM liver resections and 6 control liver specimens was undertaken. mUMs were assessed for morphology, nuclear BAP1 (nBAP1) expression, and their tumour microenvironments (TME) using an &ldquo, immunoscore&rdquo, (absent/altered/high) for tumour-infiltrating lymphocytes (TILs) and macrophages (TAMs). Transcriptomes were compared between mUM and control liver, intersegmental and intratumoural analyses were also undertaken. Most mUM were epithelioid cell-type (75%), amelanotic (55%), and nBAP1-ve (70%). They had intermediate (68%) or absent (15%) immunoscores for TILs and intermediate (53%) or high (45%) immunoscores for TAMs. M2-TAMs were dominant in the mUM-TME, with upregulated expression of ANXA1, CD74, CXCR4, MIF, STAT3, PLA2G6, and TGFB1. Compared to control liver, mUM showed significant (p &lt, 0.01) upregulation of 10 genes: DUSP4, PRAME, CD44, IRF4/MUM1, BCL2, CD146/MCAM/MUC18, IGF1R, PNMA1, MFGE8/lactadherin, and LGALS3/Galectin-3. Protein expression of DUSP4, CD44, IRF4, BCL-2, CD146, and IGF1R was validated in all mUMs, whereas protein expression of PRAME was validated in 10% cases, LGALS3 stained TAMs, and MFGEF8 highlighted bile ducts only. Intersegmental mUMs show differing transcriptomes, whereas those within a single mUM were similar. Our results show that M2-TAMs dominate mUM-TME with upregulation of genes contributing to immunosuppression. mUM significantly overexpress genes with targetable signalling pathways, and yet these may differ between intersegmental lesions.

Uveal melanoma (UM) is a rare aggressive intraocular tumour with a propensity for liver metastases, occurring in ∼50% of patients. The tumour suppressor BAP1 is considered to be key in UM progression. Herein, we present the largest study to date investigating cellular expression patterns of BAP1 protein in 165 UMs, correlating these patterns to prognosis. Full clinical, histological, genetic, and follow-up data were available for all patients. BAP1 gene sequencing was performed on a subset of 26 cases. An independent cohort of 14 UMs was examined for comparison. Loss of nuclear BAP1 (nBAP1) protein expression was observed in 54% (88/165) UMs. nBAP1 expression proved to be a significant independent prognostic parameter: it identified two subgroups within monosomy 3 (M3) UM, which are known to have a high risk of metastasis. Strikingly, nBAP1-positiveM3 UMs were associated with prolonged survival compared to nBAP1-negative M3 UMs (Log rank, p = 0.014). nBAP1 protein loss did not correlate with a BAP1 mutation in 23% (6/26) of the UMs analysed. Cytoplasmic BAP1 protein (cBAP1) expression was also observed in UM: although appearing 'predominantly diffuse' in most nBAP1-negative UM, a distinct 'focal perinuclear' expression pattern - localized immediately adjacent to the cis Golgi - was seen in 31% (18/59). These tumours tended to carry loss-of-function BAP1 mutations. Our study demonstrates loss of nBAP1 expression to be the strongest prognostic marker in UM, confirming its importance in UM progression. Our data suggest that non-genetic mechanisms account for nBAP1 loss in a small number of UMs. In addition, we describe a subset of nBAP1-negative UM, in which BAP1 is sequestered in perinuclear bodies, most likely within Golgi, warranting further mechanistic investigation.

Current treatments for metastatic uveal melanoma (mUM) are limited and rarely prolong patient survival. Immunotherapy trials for mUM are few and to date have demonstrated only marginal success. High densities of tumor-associated macrophages (TAMs) and infiltrating T lymphocytes (TILs) in primary UM are associated with poor prognosis. Little is known about the immune microenvironment of mUM. Our aim was to examine the presence and distribution of TAMs and TILs in mUM within the liver. Whole-tissue sections of liver mUM (n=35) were examined by immunohistochemistry. For TAMs, monoclonal antibodies against CD68 and CD163 were used. Macrophage density and morphology were scored using previous established systems. Density and spatial distribution of TILs were highlighted using antibodies against CD3 (pan-lymphocyte marker), CD4 (T-helper cells), and CD8 (T-cytotoxic cells). CD68+ and CD163+ TAMs were seen within the tumor in all 35 specimens; their density was "moderate" in 50% of cases and "few" in 43%, and the majority showed an "indeterminate" phenotype. CD3+ TILs were noted both within mUMs and surrounding the tumor. Of these, CD8+ TILs were "few" in number within mUM but were predominantly seen peritumorally at the tumor/normal liver interface, whereas CD4+ TILs showed a high perivascular density within mUM. CD68+ and CD163+ TAMs of "indeterminate" morphology were observed in mUM, suggesting a tendency toward the protumorigenic M2 phenotype. CD4+ TILs were seen within the mUM, whereas CD8+ TILs tended to be peritumoral. The biological and functional roles of inflammatory cells in mUM require further investigation to determine if they represent potential targets for future therapies in mUM.

Background: Lymphomas of the lacrimal sac are rare, accounting for less than 10% of lacrimal sac malignant tumours. They may present with symptoms typical of secondary acquired nasolacrimal duct obstruction and are thus often misdiagnosed. Methods: Case series and literature review. Results: Herein we describe 3 cases of chronic lymphocytic leukaemia (CLL)/small-cell lymphocytic lymphoma (SLL) of the lacrimal sac with immunohistochemical and in 1 case molecular confirmation. Conclusion: Lymphomas of the lacrimal sac should be suspected in patients with known CLL presenting with epiphora and dacryocystitis. During dacryocystorhinostomy, an incisional biopsy of the lacrimal sac is essential for confirming CLL/SLL involvement and may guide treatment.

Tumors of the lacrimal sac are rare but their recognition and early management are imperative, as they are locally invasive and potentially life-threatening. Because of their rarity, large clinical studies with statistically significant data on the natural course, management, and prognosis of these neoplasms are unavailable. Current practices are therefore based on a few case series and a small number of isolated case reports. Most tumors are primary and of epithelial origin (60-94%), of which 55% are malignant. Lacrimal sac tumors typically present with epiphora and a palpable mass over the medial canthus and are thus often erroneously diagnosed as chronic dacryocystitis. A full history with clinical and diagnostic workup is essential to plan treatment, which is often multi-disciplinary. Statistically significant associations have been shown with higher tumor staging and size with increased metastatic risk and lower survival rates. Management usually involves complete surgical resection with adjuvant radiotherapy and/or chemotherapy for malignant lesions. Long-term follow-up is required, as recurrences and metastases can occur many years after initial treatment.

Subretinal transplantation of functioning retinal pigment epithelial (RPE) cells grown on a synthetic substrate is a potential treatment for age-related macular degeneration (AMD), a common cause of irreversible vision loss in developed countries. Plasma polymers give the opportunity to tailor the surface chemistry of the artificial substrate whilst maintaining the bulk properties. In this study, plasma polymers with different functionalities were investigated in terms of their effect on RPE attachment and growth. Plasma polymers of acrylic acid (AC), allyl amine (AM) and allyl alcohol (AL) were fabricated and characterised using X-ray photoelectron spectroscopy (XPS) and water contact angle measurements. Octadiene (OD) hydrocarbon films and tissue culture polystyrene were used as controls. Wettability varied from hydrophobic OD to relatively hydrophilic AC. XPS demonstrated four very different surfaces with the expected functionalities. Attachment, proliferation and morphological examination of an RPE cell line and primary RPE cells were investigated. Both cell types grew on all surfaces, with the exception of OD, although the proliferation rate of primary cells was low. Good epithelial morphology was also demonstrated. Plasma polymerised films show potential as cell carrier surfaces for RPE cells in the treatment of AMD. Refereed/Peer-reviewed

Transplantation of cultured retinal pigment epithelial (RPE) cells under the failing macular is a potential treatment for age related macular degeneration. An important step in the development of this procedure is the identification of a suitable membrane on which to grow and transplant the cells. This paper evaluates the potential of using polyurethanes in this application since they possess several of the required properties, such as, flexibility, robustness, biostability and good biocompatiblilty although their hydrophobicity can limit cell adhesion. Three commercially available polyether urethanes (Pellethane®, Tecoflex® and Zytar®) were evaluated in terms of their wettability using dynamic contact angle analysis and their ability to support a monolayer of functioning RPE cells (ARPE-19) . Furthermore Pellethane® and Tecoflex® were treated with a simple air plasma treatment and analysed as above. In the “as received condition" only a few RPE cells attached to the Pellethane® and Tecoflex® and remained clumped. RPE cells grew to confluence on the Zytar® substrate by 7 days without further surface modification. Air gas plasma treatment of both Pellethane® and Tecoflex® increased the wettability of the surfaces and this resulted in the growth of a monolayer of well-spread RPE cells on both materials. Morphologically these cells grew with a normal 'cobblestone' phenotype. These results demonstrate the potential of these polyurethanes for this application.

The aim of this study was to produce a heavy tamponade with a specific gravity greater than 1.06 g/mL that was optically transparent, could be manufactured using simple processing, could be injected using standard clinical equipment, and would have appropriate biocompatibility.Aerosil silica was added to a phenyl trimethicone and mixed via a roller, overhead stirring, and ultrasonics. The refractive index, visible absorbance, and shear viscosity were measured. The injectability of the solutions was evaluated using the Accurus Viscous Fluid Injection system. The tamponade efficiency was assessed using a model eye chamber and compared with that of Densiron 68, Oxane HD, and F6H8. The biocompatibility was evaluated in vitro and in vivo in rabbits.Tamponade agents were produced with specific gravities of 1.10, 1.11, 1.13, and 1.16 g/mL that had good optical clarity. Mixing using overhead stirring was sufficient to produce tamponade agents with shear viscosities in the range 1000 to 5000 mPa·s that were reproducible and stable during storage. The solutions were easier to inject using the Accurus Viscous Fluid Injection system than silicone oil 1000 mPa·s. The 11% silica solution had greater tamponade efficiency than Densiron 68 or Oxane HD. There was no evidence of cytotoxicity in vitro. Silica solution 11% induced cataract earlier than Polydimethylsiloxane 1000 (PDMS 1000). Silica solution 11% and phenyl trimethicone reduced the a-wave value at 1 week after vitrectomy, but recovery was observed at later time points. Silica solution 11% caused inner nuclear layer (INL) nuclei dropdown in inferior retina from 4 weeks postoperation. Polydimethylsiloxane 1000 induced a similar phenomenon in superior retina 12 weeks postoperation.We have produced a heavy tamponade with good clarity that has appropriate shear viscosity, injectibility, enhanced tamponade efficiency, and biocompatibility similar to that of PDMS 1000.