Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal.

CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant or continue mycophenolate mofetil + standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: -7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m2 ). Mean changes (z-score) in height (0.72 vs 0.39; P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR + rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: NCT01544491.

Wide-field individual retinal layer thickness in healthy eyes.

PURPOSE: To report the individual retinal layer thickness in healthy subjects using wide-field optical coherence tomography. METHODS: This was a prospective, cross-sectional study involving healthy subjects. A custom-designed semiautomated segmentation algorithm was used to split the retinal layers in seven bands, and individual retinal layer thicknesses were measured in horizontal (nasal, macular, and temporal segments) and vertical meridians (superior, macular, and inferior segments). The variation in retinal thickness was analyzed in different segments at an interval of 1 mm from reference points. Regression analysis was performed to identify the factors affecting retinal thickness. RESULTS: Twenty eyes of 20 healthy subjects with mean age of 28.9 ± 6.3 years were analyzed. Overall, nasal and superior segments (mean ± standard deviation: 279.6 ± 17.0 and 234.4 ± 19.2 µm) had maximum and minimum retinal thicknesses, respectively. A total of seven bands were delineated in each optical coherence tomography b scan in each segment. Retinal nerve fiber layer was thickest immediately nasal to optic disk margin in horizontal scan (72.4 ± 32.4 µm) and near the vascular arcades in vertical meridian. Outer plexiform layer, external limiting membrane-ellipsoid zone and interdigitation zone-retinal pigment epithelium-Bruch's complex showed significant variation in both horizontal and vertical meridians (all p values <0.05). Macular segment in both meridians showed the highest coefficient of variation. Age was the only significant factor affecting retinal thickness in multiple regression analysis (p = 0.001). CONCLUSIONS: Wide-field optical coherence tomography shows significant regional variation in overall and individual retinal layer thicknesses in macular and peripheral areas in healthy eyes with the highest variation in macular segment.

Comparison of Loading Doses of Ziv-Aflibercept and Aflibercept in Neovascular Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to compare outcomes of 3 loading doses of ziv-aflibercept and aflibercept in treatment-naïve neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective, nonrandomized, comparative study. METHODS: This was a retrospective chart review which included cases with treatment-naïve nAMD. The patients were divided into 2 groups (group 1, ziv-aflibercept; group 2, aflibercept). Groups 1 and 2 received 1.25 mg/0.05 mL of intravitreal ziv-aflibercept and 2 mg/0.05 mL aflibercept, respectively every month for 3 months. Best-corrected visual acuity (BCVA) in Snellen and logarithm of minimum angle of resolution (logMAR), central subfoveal thickness (CSFT), subretinal hyperreflective material height, neurosensory detachment height, and pigment epithelial detachment height were recorded at baseline and 3 monthly follow-up. RESULTS: Twenty-three eyes of 23 patients were included (males 14, females 9). Twelve and 11 eyes were included in group 1 and group 2, respectively. Group 1 showed statistically significant improvement in BCVA (P < 0.001) and CSFT (P=0.007) through 3 months compared with baseline. There was significant change in BCVA from baseline at 1st month (P = 0.007), 2nd month (P = 0.002) and 3rd month (P = 0.008). In group 2, there was no significant improvement in BCVA, CSFT, subretinal hyperreflective material height, neurosensory detachment, and pigment epithelial detachment height from baseline through 3 months. CONCLUSIONS: After 3 loading doses, ziv-aflibercept showed efficacy in terms of improved BCVA and reduction of CSFT from baseline whereas aflibercept did not show such improvement. Considering the cost- effectiveness and the proven safety of ziv-aflibercept, it is a viable option for the crucial, initial 3 doses in the treatment of nAMD.

Telbivudine vs tenofovir in hepatitis B e antigen-negative chronic hepatitis B patients: OPTIMA roadmap study.

AIM: To make efficacy and safety comparison of telbivudine-raodmap and tenofovir-roadmap in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. METHODS: This was the first prospective, randomised, two-arm, open-label, non-inferiority study in HBeAg-negative CHB patients that compared telbivudine and tenofovir administered as per roadmap concept. Patients were treated up to 24 wk and, depending on virologic response, continued the same therapy or received add-on therapy up to 104 wk. Eligible patients received an additional 52 wk of treatment in the extension period (i.e., up to 156 wk). Patients who developed virologic breakthrough (VB) while on monotherapy also received add-on therapy. The primary efficacy endpoint was the rate of patients achieving hepatitis B virus (HBV) DNA < 300 copies/mL at week 52. Secondary efficacy endpoints included the rates of HBV DNA < 300 and < 169 copies/mL, HBV DNA change from baseline, alanine aminotransferase normalisation, hepatitis B surface antigen (HBsAg) loss, HBsAg seroconversion, VB, and emergence of resistance at various timepoints throughout the study. Safety and estimated glomerular filtration rate (eGFR) were also analysed. RESULTS: A total of 241 patients were randomised. Non-inferiority of telbivudine arm to tenofovir arm was demonstrated at week 52 (± 7 d window), with over 91% of patients in each treatment arm achieving HBV DNA level < 300 copies/mL. Both arms were similar in terms of key secondary efficacy variables at weeks 104 and 156. The percentage of patients achieving HBV DNA < 300 copies/mL remained high and was similar in the telbivudine and tenofovir arms at both weeks 104 and 156. Over 82% of patients in both arms achieved alanine aminotransferase normalisation at week 52, and this percentage remained high at weeks 104 and 156. Telbivudine treatment progressively reduced serum HBsAg levels from baseline while no change was reported in quantitative HBsAg during therapy with tenofovir. Both treaments showed acceptable safety profiles. The telbivudine arm showed eGFR improvement unlike the tenofovir arm. CONCLUSION: Efficacy was shown for both telbivudine-roadmap and tenofovir-roadmap regimens in HBeAg-negative CHB patients over 156 wk. Telbivudine arm was associated with renal improvement.

Anal anatomy and normal histology.

The focus of this article is the anatomy and histology of the anal canal, and its clinical relevance to anal cancers. The article also highlights the recent histological and anatomical changes to the traditional terminology of the anal canal. The terminology has been adopted by the American Joint Committee on Cancer, separating the anal region into the anal canal, the perianal region and the skin. This paper describes the gross anatomy of the anal canal, along with its associated blood supply, venous and lymphatic drainage, and nerve supply. The new terminology referred to in this article may assist clinicians and health care providers to identify lesions more precisely through naked eye observation and without the need for instrumentation. Knowledge of the regional anatomy of the anus will also assist in management decisions.

Medical students' learning of anatomy: memorisation, understanding and visualisation.

INTRODUCTION: There is much subjective discussion, but few empirical data that explore how students approach the learning of anatomy. AIMS: Students' perceptions of successful approaches to learning anatomy were correlated with their own approaches to learning, quality of learning and grades. METHODS: First-year medical students (n = 97) studying anatomy at an Australian university completed an online survey including a version of the Study Process Questionnaire (SPQ) that measures approaches to learning. The quality of students' written assessment was rated using the Structure of Observed Learning Outcomes (SOLO) taxonomy. Final examination data were used for correlation with approaches and quality of learning. RESULTS: Students perceived successful learning of anatomy as hard work, involving various combinations of memorisation, understanding and visualisation. Students' surface approach (SA) scores (mean 30 +/- 3.4) and deep approach (DA) scores (mean 31 +/- 4.2) reflected the use of both memorisation and understanding as key learning strategies in anatomy. There were significant correlations between SOLO ratings and DA scores (r = 0.24, P < 0.01), between SA scores and final grades (r = - 0.30, P < 0.01) and between SOLO ratings and final grades (r = 0.61, P < 0.01) in the subject. CONCLUSIONS: Approaches to learning correlate positively with the quality of learning. Successful learning of anatomy requires a balance between memorisation with understanding and visualisation. Interrelationships between these three strategies for learning anatomy in medicine and other disciplines require further investigation.

Synthesis and evaluation of antimicrobial activity of novel hydrazino and N-benzylidinehydrazino-substituted 4,8-dihydro-1H,3H-pyrimido[4,5-d]pyrimidin-2,7-dithiones.

A number of novel pyrimido[4,5-d]pyrimidine-2,7-dithone derivatives bearing hydrazino and N-benzylidinehydrazino substitution were efficiently synthesized and screened for in vitro antibacterial activities against the representative panel of three Gram-positive and two Gram-negative bacteria. All the synthesized compounds showed the potent inhibitory action against Gram-positive bacteria. Particularly, N-benzylidinehydrazino-substituted compounds imparted profound effect. Furthermore, the Connolly-accessible surface area values were also calculated for the target compounds and correlated with the expressed biological activity.

Role of Dietary Intake and Biomarkers in Risk of Breast Cancer: A Case Control Study.

Reproductive factors are not considered to play a significant role in the aetiology of breast cancer in low incidence regions like Gujarat, although it is well established that they exert a major influence on such tumours in the western developed world. Women in the western Indian region have a very low prevalence of smoking, alcohol consumption but a high prevalence of vegetarianism. Noting the changes in the life style practices with increasing affluence is likely to yield several interesting findings in such a population. Physical activity and dietary factors have emerged as important parameters and their lack may contribute significantly to the risk of breast cancers. The breast cancer risk significantly increased with higher consumption of total fat (>25% of total calories), frequent intake of fried foods and sweets. A significant protection was offered by frequent consumption of green yellow leafy vegetables, foods rich in b-carotene and isoflavonoids. The present study demonstrated a good protective effect of dietary intake of antioxidant vitamins. The breast cancer risk increases with elevation of circulating lipid components except HDL-cholesterol.