Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the “Epigenetic Clock,” a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012). Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.

Introduction: Both conservative and liberal transfusion thresholds, in regard to hematocrit and hemoglobin levels, have been widely studied with varying outcomes. The aim of this study was to evaluate if transfusion administered peri- (anytime during the admission), pre-, intra-, or postoperatively an its association with morbidity and mortality in the geriatric population undergoing hip surgery. Methods: This study was an institutional review board approved retrospective analysis of data collected from 841 patients at a single urban institution who underwent surgical repairs for hip fractures from 2008 to 2010. Results: Our analysis included data from 841 surgical patients. Mean patient age was 83, 74% were female, 48% received spinal anesthesia while 52% underwent general anesthesia. Out of 841 patients, 425 were transfused during the perioperative period. Most transfusions occurred postoperatively. Perioperative, intraoperative and postoperative transfusion was associated with an increase in post-operative AKI. Intraoperative blood transfusion was associated with an increase in morbidity (11.6% increased to 22.2%) by 1.9 fold, AKI (3.9% increased to 11.1%) by 2.8 fold, as well as an increase in mortality (5.2 increased to 15.6%) within 60 days by 3 fold. Conclusions: This may suggest that patients transfused prior to surgery, despite having met a specific trigger hemoglobin level earlier, may have been treated before deteriorating to a point that would cause future systemic implications.

Currently, there is no reliable method of discerning between low-risk and high-risk intraductal papillary mucinous neoplasms (IPMNs). Operative resection is utilized in an effort to resect those lesions with high-grade dysplasia (HGD) prior to the development of invasive disease. The current guidelines recommend resection for IPMN that involve the main pancreatic duct. Resecting lesions with HGD before their progression to invasive disease and the avoidance of resection in those patients with low-grade dysplasia is the optimal clinical scenario. Therefore, the importance of developing preoperative models able to discern HGD in IPMN patients cannot be overstated. Low-risk patients should be managed with nonsurgical treatment options (typically MRI surveillance), while high-risk patients would undergo resection, hopefully prior to the formation of invasive disease. Current research is evolving in multiple directions. First, there is an ongoing effort to identify reliable markers for predicting malignant transformation of IPMN, mainly focusing on genomic and transcriptomic data from blood, tissue, and cystic fluid. Also, multimodal models of combining biomarkers with clinical and radiographic data seem promising for providing robust and accurate answers of risk levels for IPMN patients.

A premenopausal woman having a totally occlusive distal urethral stricture, with suprapubic catheter (SPC) in situ, was referred to us for a definitive procedure. On discussion of the treatment options, the patient refused for a buccal or vaginal flap procedure. Thus, a local W-V flap was fashioned from the periurethral vestibular mucosa with seemingly excellent results, both in terms of resolution of her symptoms and a forwardly directed stream of urine without incontinence.