The identification of clinically important molecular mechanisms driving endocrine resistance is a priority in estrogen receptor-positive (ER+) breast cancer. Although both genomic and non-genomic cross-talk between the ER and growth factor receptors such as human epidermal growth factor receptor 2 (HER2) has frequently been associated with both experimental and clinical endocrine therapy resistance, combined targeting of ER and HER2 has failed to improve overall survival in endocrine non-responsive disease. Herein, we questioned the role of fatty acid synthase (FASN), a lipogenic enzyme linked to HER2-driven breast cancer aggressiveness, in the development and maintenance of hormone-independent growth and resistance to anti-estrogens in ER/HER2-positive (ER+/HER2+) breast cancer. The stimulatory effects of estradiol on FASN gene promoter activity and protein expression were blunted by anti-estrogens in endocrine-responsive breast cancer cells. Conversely, an AKT/MAPK-related constitutive hyperactivation of FASN gene promoter activity was unaltered in response to estradiol in non-endocrine responsive ER+/HER2+ breast cancer cells, and could be further enhanced by tamoxifen. Pharmacological blockade with structurally and mechanistically unrelated FASN inhibitors fully impeded the strong stimulatory activity of tamoxifen on the soft-agar colony forming capacity—an in vitro metric of tumorigenicity—of ER+/HER2+ breast cancer cells. In vivo treatment with a FASN inhibitor completely prevented the agonistic tumor-promoting activity of tamoxifen and fully restored its estrogen antagonist properties against ER/HER2-positive xenograft tumors in mice. Functional cancer proteomic data from The Cancer Proteome Atlas (TCPA) revealed that the ER+/HER2+ subtype was the highest FASN protein expressor compared to basal-like, HER2-enriched, and ER+/HER2-negative breast cancer groups. FASN is a biological determinant of HER2-driven endocrine resistance in ER+ breast cancer. Next-generation, clinical-grade FASN inhibitors may be therapeutically relevant to countering resistance to tamoxifen in FASN-overexpressing ER+/HER2+ breast carcinomas.

More than 1 million peripherally inserted central catheters (PICC) are placed annually in the US and are used to provide convenient vascular access for a variety of reasons including long term antibiotic treatment, chemotherapy, parenteral nutrition, and blood draws. Although they are relatively easy to place and inexpensive, PICC line use is associated with many complications such as phlebitis/thrombophlebitis, venous thrombosis, catheter-related infection, wound infection, and central vein stenosis. These complications are far more deleterious for patients with chronic kidney disease (CKD) whose lives depend on a functioning hemodialysis access once they reach end stage kidney disease (ESKD). Despite recent guidelines to avoid PICC lines in CKD and ESKD patients, clinical use remains high. There is an ongoing urgency to educate and inform health care providers and the CKD patients themselves in preserving their venous real estate. In this article, we review AV access and PICC line background, complications associated with PICC lines in the CKD population, and recommendations for alternatives to placing a PICC line in this vulnerable patient population.

Background: The COVID 19 pandemic adversely impacted delivery of preventive, routine, urgent, and essential care worldwide. Dialysis access care was particularly affected due to the lack of specific guidelines regarding procedures for its creation and maintenance. Early guidance by Centers for Medicare and Medicaid was inadvertently interpreted as guidance to stop dialysis access procedures. Prompt action by professional societies was needed to furnish detailed guidance to establish essential nature of these procedures. Methods: The American Society of Diagnostic and Interventional Nephrology (ASDIN) issued a joint statement with Vascular Access Society of the Americas (VASA) – “Maintaining Lifelines for ESKD Patients” to clearly establish the role of vascular access as a lifeline for ESKD (End Stage Kidney Disease) patients and the importance and urgency of its timely management. ASDIN also conducted a survey in mid-2020, that was administered to the ASDIN database as well as shared with the general public via the organization’s social media platforms. The respondents reported their experiences in the care of dialysis access, practice patterns and the utility of the ASDIN-VASA statement during the COVID 19 pandemic. Results: Of the 2030 individual surveys sent, 581 were opened and 53 (9.1%) responses were received from different parts of the country and from different practice settings. ASDIN COVID 19 triage document was frequently utilized and 83% of respondents found the document valuable. The survey also revealed multiple obstacles, including logistical and financial issues that led to significant disruption of services. Conclusions: The care of dialysis access was significantly affected in the United States during the COVID 19 pandemic due to multiple reasons. ASDIN actions provided valuable specific guidance regarding and explored barriers to dialysis access care. We describe those results and discuss strategies to prevent COVID 19 transmission with innovative strategies of providing access care. Individualized decision making is of essence when considering dialysis access procedures.

Key Points: Hands-on training is crucial for vascular access training. A multidisciplinary approach to vascular access training is paramount. Creation of a multifaceted vascular access curriculum is needed in all training programs. Background: This study seeks to provide insights into the current state of vascular access education in adult nephrology fellowship programs in the United States and to identify areas for improvement. Methods: A total of 63 adult nephrology programs and 71 second-year adult nephrology fellows were randomly selected for participation in a roundtable. Virtual roundtable discussions preceded by a survey were conducted to gather information on the delivery of vascular access education. Descriptive statistics were used for analysis. Results: Among the respondents invited to the roundtable discussions, 42 individuals (30 faculty and 12 fellows) completed the survey, while 21 individuals (13 faculty and eight fellows) also participated in the roundtable discussion. Of these respondents, most (67%) didactic lectures on vascular access in fellowship programs were delivered by general nephrologists, with 57% provided by interventional nephrologists, 36% by surgeons, and 17% by interventional radiologists (respondents were able to select multiple disciplines). The respondents reported limited exposure to proceduralists, including interventional nephrologists and vascular access surgeons during fellowship training. Faculty and fellows were less comfortable with physical examination skills related to vascular access, particularly in using point-of-care ultrasound and interpreting vascular imaging as compared with naming and identification of vascular access. Both groups emphasized the importance of hands-on modalities in vascular access education. Conclusion: Roundtable discussions highlighted the need for enhanced hands-on training, multidisciplinary collaboration, and standardized curricula in vascular access education. Recommendations were formulated in alignment with the three levels of competency outlined by the American Society of Nephrology Task Force on the Future of Nephrology, aiming to address gaps and improve the quality of vascular access education in nephrology fellowship programs. This study underscores the importance and need for a comprehensive vascular access education in nephrology fellowship training. By implementing the identified recommendations, programs can better prepare fellows to manage vascular access-related challenges in clinical practice.