108 Developing A Non-Biopsy Protocol for The Female Cohort 25-29 Years with Clinically Typical Fibroadenoma Conforming to Maxwell Criteria on Ultrasound – Our Peninsular Experience in Wirral

Introduction The aim of this study was to introduce a non –biopsy protocol in our department for benign breast lump referrals confirmed as typical U2/3 fibroadenoma on imaging. Current UK guidance is not to biopsy sonographically typical fibroadenoma in women under 25 years. We have studied our population extending the radiological Maxwell criteria reflecting benign outcomes in 25-29 years cohort. Method Retrospectively data was collected of all women between 25-29 years of age undergoing core biopsies for ultrasound confirmed fibroadenoma between 2014 and 2019 over a period of five years. The number of cancers picked up was compared with the number of referrals and the discordance between radiological diagnosis of fibroadenoma and histopathological confirmation of malignancy was recorded. Results A total of 1707 referrals were made across five years. n = 175 image guided core biopsies were carried out for U2, U3, U4 lesions appearing as fibroadenoma on ultrasound. Out of these (n = 175), all lesions coded U2/3 (n = 165) based on Maxwell criteria on ultrasound were negative for cancer. U4 lesions on ultrasound were confirmed as cancers mimicking fibroadenoma(n = 10). Conclusions This retrospective audit of 1707 patients provides sound evidence for non-biopsy of typical fibroadenoma in 25–29 years cohort sonographic features meet strict criteria.

Sex difference in the impact of smoking on Clinical outcomes following LVAD implantation

Background Smoking would have a negative impact on clinical outcomes following left ventricular assist device (LVAD) implantation. However, its impact on male and female cohorts separately remains uninvestigated. Purpose We aimed to investigate the association between smoking and post-LVAD outcomes among male and female cohorts separately. Methods Data of consecutive patients who received LVAD implantation at our institute between Jan 2013 and Sep 2018 were retrospectively reviewed. Clinical outcomes were compared between the never smokers and the current smokers among male and female cohorts separately. Those with former smoking were excluded. Results Of all, 85 male patients (median 56 years old) and 45 female patients (median 56 years old) were included. Among the male cohort, total readmission rate was higher in the current smokers than never smokers (incidence rate ratio 1.51, p=0.09). Rates of gastrointestinal bleeding, stroke, and hemolysis trended to be higher in current smokers (Figure 1A). Among the female cohort, these rates were not different irrespective of the smoking status (Figure 1B). Survival was not different irrespective of smoking status among both male and female cohorts. Conclusion The impact of smoking on post-LVAD outcomes seems to be different between males and females. Different therapeutic strategy might be required for the LVAD candidates with active smoking between male and female cohort. Figure 1 Funding Acknowledgement Type of funding source: None

Recapitulation of the Genetic Association of PLXNA2 with Bone Density and Osteoporosis via In Vitro Experiments Using a Korean Female Cohort

Osteoporosis is a bone disorder in which the imbalance of osteoclasts and osteoblasts leads to bone-destructive diseases especially among elderly women. Several factors, including genetic and environmental factors, contribute to the pathogenesis of these diseases. Bone mineral density (BMD) is a robust factor that influences osteoporosis; the development of osteoporosis in the elderly is estimated based on the BMD. Our previous microarray assay using murine preosteoblast cells revealed that Plexin A2 is associated with the differentiation and mineralization of bone-forming osteoblasts via bone morphogenetic protein 2 signaling. For our in vitro replication study using a Korean female cohort, we analyzed the genetic variation of PLEXIN A2 (PLXNA2) and its paralog genes (PLXNA1, A3, and A4) based on 125 single nucleotide polymorphisms (SNPs) associated with bone density and osteoporosis. In this study, the PLXNA2 gene was confirmed as a robust candidate gene associated with osteoporosis in Korean women. We have demonstrated that the SNPs rs4844649 (p = 9.3×10−3) and rs3748737 (p = 2.7×10−3) of PLXNA2 were the most significantly associated with bone density and osteoporosis, respectively. Consequently, this study demonstrates that the PLXNA2 gene is implicated in bone metabolism, further supporting the genetic association between polymorphisms in PLXNA2 and osteoporosis. Our current findings also suggest that polymorphisms in PLXNA2 may serve as feasible clinical targets for osteoporosis treatment in the future.

P72 Muscle weakness affects function differently in males and females in inclusion body myositis: providing results for focused clinical care and clinical trial design

Background Sporadic inclusion body myositis (IBM) is a muscle wasting disorder usually affecting those aged over 50 years, characterised by slowly progressive weakness of the distal upper limbs and proximal lower limbs. Particular weakness of pinch, knee extension and ankle dorsiflexion result in functional decline and disability. Weakness-associated functional decline differences between genders has not previously been investigated. This study aimed to investigate for differences of functional decline in men and women with IBM. Methods A cohort of verified adult IBM patients were followed at a single specialist neuromuscular clinic (Royal Victoria Infirmary, Newcastle-upon-Tyne, UK) between 2004-15, with data collected at each clinic visit. Strength of 11 movements was measured via dynamometry at each clinic visit. Patient-reported function was measured via the Neuromuscular Symptom Score (NSS). Generalised linear modelling, adjusted for disease duration, was carried out to identify associations between strength and function (NSS). Pinch, knee extension and ankle dorsiflexion strength measurements were analysed. Modelling was carried out separately for male and female cohorts. Results Data of 75 participants (47% female) was analysed. A total of 591 measurements were taken. Median age at time of IBM diagnosis was 68.8 years. Median baseline NSS score was 45 (IQR 37, 54) for the male cohort and 40 (IQR 29, 45) for the female cohort. The median disease duration of the study cohort was 2.6 years. Reduced function (NSS) was significantly associated with reduced pinch, knee extension and ankle dorsiflexion strength in the male cohort only (Table 1). No significant associations were observed in the female cohort. Conclusion This is the first study to demonstrate that the progression of weakness, in the characteristic muscle groups affected in IBM, impacts on function differently in men and women. These results illustrate the importance of functional assessment in patients with IBM and the importance of focused physiotherapy upon function-dependent muscle groups. Further, potential gender-based differences of weakness-related function in IBM should be considered when designing clinical trials. Disclosures J. Williams None. A. Oldroyd None. J. Lilleker None. H. Chinoy None. J. Miller None.

O33 Earlier cancer diagnosis after myositis onset is associated with improved long term survival: results from UK, French and Czech cohorts

Background The idiopathic inflammatory myopathies (IIMs) are associated with cancer. Cancer screening is advocated in new IIM cases; however no study has investigated if this confers improved long-term survival. This study aimed to investigate if a shorter time between IIM onset and cancer diagnosis is associated with improved survival. Methods Verified adult-onset IIM (dermatomyositis, polymyositis, anti-synthetase syndrome) cases, according to the International Myositis Classification Criteria, were recruited from three separate UK (UKMYONET), France and Czech-based cohort studies. Only cases with cancer diagnosis following IIM onset were included in analysis. The time between IIM onset and cancer diagnosis was calculated for each case. The relationship between survival at the end of follow up and time between IIM onset and cancer diagnosis was quantified via calculation of hazard ratios using a Cox-proportional hazard model, adjusted for age and gender. Results A total of 193 (66% female) IIM cases with a total of 1,395 person-years follow up were included in the analysis (Table 1). Data of 120 UK, 45 Czech and 28 French participants were analysed. Breast was the most common site of cancer (16%), followed by lung (9%) and bowel (6%). Forty six (24%) deaths occurred within the follow up period. The IIM onset to cancer diagnosis time was shorter for those that survived at the end of follow up, compared to those that died: 4.6 years (IQR 1.2, 10.7), vs 5.8 years (IQR 1.6, 13.8), respectively. Cox-proportional hazard modelling, indicated that a longer time between IIM onset and cancer diagnosis was significantly associated with death (HR 1.06 [95% CI 1.02, 1.10]). This significant relationship was only demonstrated in the female cohort when analysed separately: female HR 1.06 (95% CI 1.01, 1.10), male HR 1.08 (95% CI 0.98, 1.18). Conclusion Using data from three international cohorts, this study has, for the first time, identified that earlier cancer diagnosis after IIM onset is associated with improved long term survival. This finding was observed in the female cohort only. This study therefore indicate that cancer screening in newly diagnosed IIM cases without a preceding cancer history should be carried out, especially in female cases. Disclosures A. Oldroyd None. P. New None. J. Lamb None. W. Ollier None. R. Cooper None. K. Mariampillai None. O. Benveniste None. J. Vencovský None. H. Mann None. H. Chinoy None.