Lessons learnt and future directions in managing dialysis access during the COVID 19 pandemic: Patient and provider experience in the United States.

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.

PICC line management among patients with chronic kidney disease.

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.

Complications of Percutaneous Peritoneal Dialysis Catheter.

A functional peritoneal dialysis (PD) catheter is the cornerstone for the success of renal replacement therapy. This success is largely dependent on adhering to best practices during catheter insertion, which starts with a comprehensive preoperative evaluation that helps in determining the catheter configuration type and both entry and exit sites. Additionally, following the best practice guidelines during PD catheter insertion minimizes undesirable complications and provides a durable functional access for dialysis. However, adverse complications are still encountered despite abiding with these clinical guidelines. These complications are categorized into mechanical and infectious groups. The description and management of these adverse events are discussed in detail in this article with particular attention to the technical pitfalls that can occur during catheter insertion. Avoiding these pitfalls can minimize PD catheter complications and potentially improve clinical outcomes.

Fatty Acid Synthase Confers Tamoxifen Resistance to ER+/HER2+ Breast Cancer.

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.

Hemodialysis catheter locking solutions and the prevention of catheter dysfunction: a meta-analysis.

PURPOSE: Tunneled dialysis catheters (TDCs) continue to be utilized at an alarming rate despite having a higher rate of complications when compared to fistulas and grafts. One of the primary complications of TDCs involves catheter dysfunction resulting in reduced blood flow and poor dialysis adequacy, often requiring catheter removal in addition to thrombolytic therapy. Our objective was to compare the use of locking solutions containing heparin versus all other locking solutions for primary prevention of TDC dysfunction. METHODS: We searched Medline for English language literature from 1980 through December 2013, along with national conference proceedings and reference lists of all included publications to identify relevant studies. Inclusion criteria were a measure of incidence of catheter dysfunction, catheter exchange or use of thrombolytic therapy. Studies were excluded if they were not in English or if they included pediatric patients. Random effects models were used to derive the pooled risk ratios. RESULTS: Thirteen studies with a total of 1,883 subjects met the inclusion criteria. There was no significant difference in catheter patency in those receiving heparin versus those treated with other lock solutions (incidence rate ratio [IRR] 0.99; 95% confidence interval [CI] 0.66-1.48, p = 0.96). Catheter patency did not differ between treatments in experimental studies (n = 10; IRR = 0.89; 95% CI: 0.56-1.39, p = 0.60) or observational design (n = 3; IRR = 1.64; 95% CI 0.40-6.85, p = 0.50). Significant heterogeneity was detected across studies (I2 = 84.4%, p<0.001). CONCLUSIONS: Our results suggest that there is no substantial difference between heparin lock solutions versus all other types of catheter lock solutions for catheter dysfunction. Whether there are significant benefits of citrate or other novel lock solutions requires further robust studies. These findings have significant implications for future design of clinical trials in TDCs and the delivery of dialysis-related services.