Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5?mg/kg i.v. 3 weekly for 1?year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56?years (range 18-88?years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5?years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P?=?0.78). At 5?years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P?=?0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P?=?0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P?=?0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P?=?0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64

EFFECT OF NON-SURGICAL THERAPY ON SALIVARY NITRIC OXIDE AND LIPID PEROXIDATION LEVELS IN TYPE II DIABETIC AND NON DIABETIC PATIENTS WITH PERIODONTAL DISEASE

Objective: Reactive oxygen species have been identified as potential factors causing periodontal tissue destruction. Elevated levels of these in patients with chronic periodontitis and diabetes may aggravate the oxidative stress burden thereby accelerating the tissue damage associated with diabetes. The present study aimed to assess the effect of diabetes and periodontal disease on the oxidative stress markers and the effect of non-surgical therapy on these markers.Methods: A total of 50 participants were divided into four groups based on the selection criteria. In addition to clinical parameters and biochemical parameters (salivary nitric oxide [NO] and malondialdehyde [MDA] levels) were assessed using spectrophotometric method at baseline and 3 months after non-surgical periodontal therapy.Result: There was a statistically significant difference in the clinical parameters as well as NO and MDA levels in patients with type 2 diabetes and chronic periodontitis than other three groups at baseline and at 3 months after non- surgical periodontal therapy.Conclusion: Diabetes mellitus and periodontitis have a compounding effect on the oxidative stress. Periodontal therapy is essential for diabetic patients as it can lower the levels of oxidative damage

Stonewall and Brickwall: Two Partially Redundant Determinants Required for the Maintenance of Female Germline in Drosophila

Proper specification of germline stem cells (GSCs) in Drosophila ovaries depends on niche derived non-autonomous signaling and cell autonomous components of transcriptional machinery. Stonewall (Stwl), a MADF-BESS family protein, is one of the cell intrinsic transcriptional regulators involved in the establishment and/or maintenance of GSC fate in Drosophila ovaries. Here we report identification and functional characterization of another member of the same protein family, CG3838/ Brickwall (Brwl) with analogous functions. Loss of function alleles of brwl exhibit age dependent progressive degeneration of the developing ovarioles and loss of GSCs. Supporting the conclusion that the structural deterioration of mutant egg chambers is a result of apoptotic cell death, activated caspase levels are considerably elevated in brwl- ovaries. Moreover, as in the case of stwl mutants, on several instances, loss of brwl activity results in fusion of egg chambers and misspecification of the oocyte. Importantly, brwl phenotypes can be partially rescued by germline specific over-expression of stwl arguing for overlapping yet distinct functional capabilities of the two proteins. Taken together with our phylogenetic analysis, these data suggest that brwl and stwl likely share a common MADF-BESS ancestor and they are expressed in overlapping spatiotemporal domains to ensure robust development of the female germline

Supplemental Material for Shukla et al., 2018

Supplementary Figures for Manuscript "Stonewall and Brickwall: Two partially redundant determinants required for the maintenance of female germline in <i>Drosophila"</i

Residency evaluation and adherence design study: Young ophthalmologists' perception of their residency programs – Clinical and surgical skills

Background: Residency training is the basis of good clinical and surgical practice. Purpose: The aim is to know the demographics, training experience, and perception of young ophthalmologists to improve the present residency programs in India. Setting: Young ophthalmologists trained in India. Methods: A survey was conducted by the Academic and Research Committee of the All India Ophthalmology Society, in 2014–2016 of young ophthalmologists (those trained between 2002 and 2012, with 2–10 years' postresidency experience) to gauge teaching of clinical and surgical skills during the postgraduate residency program. Statistical Analysis: Statistical Package for Social Sciences version 16. Results: Of the 1005 respondents, 531 fulfilled inclusion criteria. Average age was 32.6 years (standard deviation [SD] 4). On a scale of 0–10, clinical skills teaching was graded as (mean, SD): Slit lamp examination (7.2, SD 2.8), indirect ophthalmoscopy (6.2, SD 3.3), gonioscopy (5.7, SD 3.4), perimetry (6.2, SD 3.2), optical coherence tomography (4.6, SD 4), and orthoptic evaluation (4.3, SD 3.1). The mean (SD) and median of surgeries performed independently was intracapsular cataract extraction 3.0 (14.9), 0; extracapsular cataract extraction 39.9 (53.2), 18; small incision cataract surgery 75.3 (64.4), 55; phacoemulsification 30 (52.6), 1; pterygium excision 31.5 (43.5), 15; dacryocystectomy 20.3 (38.1), 4; dacryocystorhinostomy 11.7 (26.2), 2; chalazion 46.4 (48.3), 30; trabeculectomies 4 (14.9), 0; strabismus correction 1.4 (4.9), 0; laser-assisted in situ Keratomileusis 1.5 (12.2), 0; retinal detachment 1.5 (12.5), 0; vitrectomy 3.0 (17.0), 0; keratoplasty 5.2 (17.8), 0; eyelid surgery 8.6 (18.9), 2 and ocular emergencies 41.7 (52.4), 20. Observed and assisted surgeries were more common. However, the range of grading was 0–10 in all categories. Conclusion: Residency training in India varies considerably from program to program. Standardization is needed to assure all graduates are competent and render consistent quality of service