BackgroundIrisin is a recently discovered myokine, involved in the browning of white adipose tissue. To date, its function has been mainly associated with energy homeostasis and metabolism, and it has been proposed as a promising therapeutic target for obesity and metabolic diseases. This is the first study investigating the role of irisin in human breast cancer.MethodsParticipants included one hundred and one (101) female patients with invasive ductal breast cancer and fifty one (51) healthy women. Serum levels of irisin, leptin, adiponectin and resistin were quantified in duplicates by ELISA. Serum levels of CEA, CA 15–3 and Her-2/neu were measured on an immunology analyzer. The association between irisin and breast cancer was examined by logistic regression analysis. The feasibility of serum irisin in discriminating breast cancer patients was assessed by ROC curve analysis. Potential correlations with demographic, anthropometric and clinical parameters, with markers of adiposity and with breast tumor characteristics were also investigated.ResultsSerum levels of irisin were significantly lower in breast cancer patients compared to controls (2.47 ± 0.57 and 3.24 ± 0.66 μg/ml, respectively, p < 0.001). A significant independent association between irisin and breast cancer was observed by univariate and multivariate analysis (p < 0.001). It was estimated that a 1 unit increase in irisin levels leads to a reduction in the probability of breast cancer by almost 90 %. Irisin could effectively discriminate breast cancer patients at a cut-off point of 3.21 μg/ml, with 62.7 % sensitivity and 91.1 % specificity. A positive association with tumor stage and marginal associations with tumor size and lymph node metastasis were observed (p < 0.05, p < 0.01, p < 0.01, respectively).ConclusionsOur novel findings implicate irisin in breast cancer and suggest its potential application as a new diagnostic indicator of the presence of disease.

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PurposeTo compare treatment patterns of intravitreal ranibizumab and aflibercept for the management of neovascular age-related macular degeneration (nAMD) in a real-world setting over the first 12 months of treatment.MethodsA proprietary clinical database was used to identify treatment-naïve patients with nAMD in the USA with claims for ranibizumab or aflibercept between November 1, 2011 and November 30, 2013 and with follow-up of at least 12 months. Patients were considered treatment-naïve if they had no anti-VEGF treatment code for 6 months before the index date. Mean numbers of injections and of non-injection visits to a treating physician were compared between the two treatment cohorts (ranibizumab or aflibercept). In addition, the mean interval between doses was also investigated.ResultsPatient characteristics were similar for those receiving either ranibizumab (n = 5421) or aflibercept (n = 3506) at the index date. The mean (± standard deviation) numbers of injections received by patients treated with ranibizumab (4.9 ± 3.3) or aflibercept (5.2 ± 2.9) were not clinically different. The mean number of non-injection visits was 2.8 ± 2.8 and 2.1 ± 2.5 for ranibizumab and aflibercept, respectively. Mean dosing interval was 51.0 days (± 41.8 days) in patients receiving ranibizumab and 54.1 days (± 36.0 days) in those receiving aflibercept. Results were robust to sensitivity analyses for definition of treatment-naïve, length of follow-up and treatment in the index eye only.ConclusionsLimited data exist regarding real-world treatment patterns of aflibercept for the management of nAMD. Our results suggest that, in routine clinical practice, patients receive a comparable number of injections in the first year of treatment with ranibizumab or aflibercept.

Background/objectives To investigate the association between optical coherence tomography (OCT) markers of lesion activity and changes in visual acuity (VA) during anti-vascular endothelial growth factor (anti-VEGF) therapy of eyes diagnosed with neovascular age-related macular degeneration (nAMD); and how VA and OCT markers are considered in physicians' decision to retreat with anti-VEGFs. Subjects/methods Retrospective, non-comparative, non-randomised cohort study involving electronic medical record data collected from 1190 patient eyes with nAMD diagnosis at two sites in the United Kingdom. Two sub-cohorts consisting of 321 and 301 eyes, respectively, were selected for analyses. Results In 321 eyes, absence of IRF or SRF at ≥2 clinic visits resulted in a gain of five ETDRS letters from baseline, compared with two letters gained in eyes with <2 clinic visits with absence of IRF (p = 0.006) or SRF (p = 0.042). Anti-VEGF treatment was administered at 421 clinic visits, and 308 visits were without treatment. Comparing treatment visits with non-treatment visits, the maximum difference in frequency of OCT markers of lesion activity were for intraretinal fluid (IRF; 24% versus 5%) and subretinal fluid (SRF; 32% versus 5%). Pigment epithelial detachment (PED) was reported in 58% of treatment visits compared with 36% in non-treatment visits. VA loss was not a consistent trigger for retreatment as it was present in 63% of injection visits and in 49% of non-injection visits. Conclusions Retreatment decision making is most strongly influenced by the presence of IRF and SRF and less by the presence of PED or VA loss.

Objectives To study the effect of repeated retinal thickness fluctuations during the anti-VEGF therapy maintenance phase in neovascular age-related macular degeneration (nAMD). Methods Data were extracted from electronic medical records of 381 nAMD patients, aged ≥50 years; baseline VA ≥33 and ≤73 letters; ≥24 months’ follow-up and ≥2 optical coherence tomography (OCT) measurements. OCT scans were analysed using an artificial intelligence algorithm that quantified the volumes of intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED) and central subfield thickness (CSFT). IRF, SRF and PED were summed to obtain total fluid (TF). The standard deviation (SD) of IRF, SRF, PED, CSFT and TF was computed and categorised into quartiles (SD-Q). Relationships between SD-Qs for each OCT feature and VA change was tested using generalised estimating equations and linear regression. Results By Month 24, compared to SD-Q1, eyes in SD-Q2, SD-Q3, and SD-Q4 for IRF, SRF, PED, CSFT and TF showed greater VA losses. Eyes in SD-Q4 of TF were 9.4 letters worse compared to eyes in Q1 (95% Confidence Interval: −12.9 to −6.0). The frequency of clinic visits with IRF and SRF present on OCT scans by quartiles of CSFT was lower in eyes with least fluctuation (Q1) compared to eyes with the most fluid fluctuation (Q4) (median [IQR] IRF: 0.3 [0.0–0.7] versus 0.8 [0.5–1.0]; SRF: 0.0 [0.0–0.5] versus 0.6 [0.3–1.0]). Conclusions Greater fluctuations in retinal fluid volumes during the maintenance phase of anti-VEGF treatment in nAMD is associated with worse VA by 2 years.

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Treat and extend (T&E) is a standard treatment regimen for treating neovascular age-related macular degeneration (nAMD) with anti-vascular endothelial growth factors (anti-VEGFs), but the treatment intervals attained are not well documented. This retrospective, non-comparative, non-randomised study of eyes with nAMD classified treatment interval sequences in a T&E cohort in Australia using Electronic Medical Records (EMR) data. We analysed data from 632 treatment-naïve eyes from 555 patients injected with ranibizumab, aflibercept or unlicensed bevacizumab between January 2012 and June 2016 (mean baseline age 78.0). Eyes were categorised into non-overlapping clusters of interval sequences based on the first 12 months of follow-up. We identified 523 different treatment interval sequences. The largest cluster of 197 (31.5%) eyes attained an 8-week treatment interval before dropping to a shorter frequency, followed by 168 (26.8%) eyes that did not reach or attained a single 8-week interval at the end of the study period. A total of 65 (10.4%) and 83 (13.3%) eyes reached and sustained (≥2 consecutive injection intervals of the same length) an 8 and 12 weekly interval, respectively. This study demonstrates highly individualised treatment patterns in the first year of anti-VEGF therapy in Australia using T&E regimens, with the majority of patients requiring more frequent injections than once every 8 weeks.

Syringe preparation times for ranibizumab intravitreal injections are significantly shorter with the PFS than with the vial. The time saved by using the PFS may benefit physicians and nurses, and the simplicity of the injection preparation process with the PFS is advantageous.