Surgical Delay-Associated Mortality Risk Varies by Subtype in Loco-Regional Breast Cancer Patients in SEER-Medicare.

Substantial evidence supports that delay of surgery after breast cancer diagnosis is associated with increased mortality risk, leading to the introduction of a new Commission on Cancer quality measure for receipt of surgery within 60 days of diagnosis for non-neoadjuvant patients. Breast cancer subtype is a critical prognostic factor and determines treatment options; however, it remains unknown whether surgical delay-associated breast cancer-specific mortality (BCSM) risk differs by subtype. This retrospective cohort study aimed to assess whether the impact of delayed surgery on survival varies by subtype (hormone [HR]+/HER2-, HR-/HER2-, and HER2+) in patients with loco-regional breast cancer who received surgery as their first treatment between 2010-2017 using the SEER-Medicare. Continuous time to surgery from diagnostic biopsy (TTS; days) in reference to TTS = 30 days. BCSM were evaluated as flexibly dependent on continuous time (days) to surgery from diagnosis (TTS) using Cox proportional hazards and Fine and Gray competing-risk regression models, respectively, by HR status. Inverse propensity score-weighting was used to adjust for demographic, clinical, and treatment variables impacting TTS. Adjusted BCSM risk grew with increasing TTS across all subtypes, however, the pattern and extent of the association varied. HR+/HER2- patients exhibited the most pronounced increase in BCSM risk associated with TTS, with approximately exponential growth after 42 days, with adjusted subdistribution hazard ratios (sHR) of 1.21 (95% CI: 1.06-1.37) at TTS = 60 days, 1.79 (95% CI: 1.40-2.29) at TTS = 90 days, and 2.83 (95% CI: 1.76-4.55) at TTS = 120 days. In contrast, both HER2 + and HR-/HER2- patients showed slower, approximately linear growth in sHR, although non-significant in HR-HER2-.

Using IV-Tubing "Bridge" from Splenic Artery to Superior Mesentery Artery to Create a Single Arterial Cannulation for Normothermic Machine Perfusion When Donor Liver Has Replaced Right Hepatic Artery.

BACKGROUND The presence of anatomical variations of the hepatic artery poses a challenge for normothermic machine perfusion (NMP). Here, we describe our experience of creating a single arterial cannulation for NMP in 3 donor livers with replaced right hepatic artery. CASE REPORT Three donor livers with replaced right hepatic artery were perfused using NMP (OrganOx® metra®) for liver transplantation. To maintain hepatic artery integrity and establish an intact arterial vascular inflow for NMP, a single vasculature was created to allow single arterial cannulation for NMP. A piece of intravenous-line tubing was used as a bridge from the splenic artery to the superior mesenteric artery during the back-table preparation. After 1 h of NMP, the lactate of 2 livers decreased from >10.0 to about 1.0 mmol/L, and the lactate of 1 liver decreased from >4.0 to <0.4 mmol/L. Three livers made >100 mL of bile after 4 h of NMP and were successfully implanted after >10 h of NMP. The recipients spent 2, 3, and 4 days in the Intensive Care Unit and were discharged home at 6, 7, and 9 days, respectively. None of the patients experienced early allograft dysfunction or any early technical complication or non-anastomotic biliary stricture. CONCLUSIONS Creating an intravenous-line tubing bridge from the splenic artery to the superior mesenteric artery prior to NMP of liver grafts associated with replaced right hepatic artery could reduce the cold ischemia time associated with vessel reconstruction and reduce bleeding risk during NMP. This is feasible, safe, and effective.

Nanotheranostics for Image-Guided Cancer Treatment.

Image-guided nanotheranostics have the potential to represent a new paradigm in the treatment of cancer. Recent developments in modern imaging and nanoparticle design offer an answer to many of the issues associated with conventional chemotherapy, including their indiscriminate side effects and susceptibility to drug resistance. Imaging is one of the tools best poised to enable tailoring of cancer therapies. The field of image-guided nanotheranostics has the potential to harness the precision of modern imaging techniques and use this to direct, dictate, and follow site-specific drug delivery, all of which can be used to further tailor cancer therapies on both the individual and population level. The use of image-guided drug delivery has exploded in preclinical and clinical trials although the clinical translation is incipient. This review will focus on traditional mechanisms of targeted drug delivery in cancer, including the use of molecular targeting, as well as the foundations of designing nanotheranostics, with a focus on current clinical applications of nanotheranostics in cancer. A variety of specially engineered and targeted drug carriers, along with strategies of labeling nanoparticles to endow detectability in different imaging modalities will be reviewed. It will also introduce newer concepts of image-guided drug delivery, which may circumvent many of the issues seen with other techniques. Finally, we will review the current barriers to clinical translation of image-guided nanotheranostics and how these may be overcome.

Performance of Renal Allografts Perfused With Verapamil-Treated Perfusion Solution.

Verapamil has been used in perfusion solution to improve kidney performance, but evidence was anecdotal, and no research has been reported on recipient outcomes. Our organization began a program to evaluate Verapamil's effect on pump performance, transplant rate, and recipient outcomes. One kidney in a pair was treated with Verapamil and one with standard perfusion. Donor inclusion criteria were age 18 or older and both kidneys were placed on the pump. The laterality of the treated kidney was changed every month to reduce bias. From January 1, 2020 to June 30, 2020, 88 kidneys were evaluated. Of those, 21 donors had both kidneys transplanted to different recipients, so for those 42 kidneys, recipient outcomes were evaluated. Small improvements in pump performance were observed in the Verapamil-treated kidneys and more were transplanted. No clinical differences were found in recipients between the Verapamil-treated and standard perfused kidneys. A larger cohort is needed to determine whether differences are significant.

The Impact and Implications of The COVID-19 Pandemic on Organ Procurement Outside of an Epicenter.

The COVID-19 pandemic has been well-documented to have a variable impact on individual communities and health care systems. We describe the experience of a single organ procurement organization (OPO), located in an area without a large cluster of cases during the initial phase of the COVID-19 pandemic. A review of community health data describing the impact of COVID-19 nationally and in Oklahoma was conducted. Additionally, a retrospective review of available OPO data from March 2019-May 2020 was performed. While the amount of donor referrals received and organs recovered by the OPO remained stable in the initial months of the pandemic, the observed organs transplanted vs. expected organs transplanted (O:E) decreased to the lowest number in the 15-month period and organs transplanted decreased as well. Fewer organs from Oklahoma donors were accepted for transplant despite staff spending more time allocating organs.

A prospective single-institution study of intraoperative radiotherapy (IORT) for early-stage breast cancer.

Intraoperative radiation therapy (IORT) is an option for breast-conserving therapy in early-stage breast cancer. IORT is given in one fraction at the time of surgery and eliminates the need for adjuvant external beam radiation therapy. However, previous trials indicate increased local failure rates compared with whole-breast irradiation, which engenders controversy around the appropriate use of IORT. We conducted a prospective study of patients diagnosed with early-stage breast cancer (T1-T2, N0-N1) at the University of Oklahoma Health Sciences Center (OUHSC) between 2013 and 2017 and treated with lumpectomy followed by intraoperative radiation therapy (IORT). Data collected included stage of disease, tumor location, histology, tumor markers, lymph node status, surgical margin size, recurrence, cosmetic outcomes, and length of follow-up. In-breast tumor recurrence rate (IBTR) in the 77 evaluable patients was 3.9% (3 patients). Margins were close (1 mm or less) in all three recurrent patients, and two were initially diagnosed with DCIS. Recurrence rates in our patients were comparable to prior reports. All recurrences were in patients with close margins indicating that this may represent a predictive feature for exclusion from IORT; additional studies are essential to determine the recurrence rates among patients treated with IORT and to identify potential predictors of IORT eligibility.

A call to action: Feasible strategies to reduce the discard of transplantable kidneys in the United States.

Changes to the United States kidney allocation system targeted at reducing organ discard have failed to improve organ utilization. High Kidney Donor Profile Index kidneys continue to be discarded at high rates as a result of the regulatory and financial barriers to widespread utilization of these organs. However, there are potential changes to clinical practice that could improve organ utilization. Expediting the time from initial offer to final organ acceptance would reduce cold ischemic time and should improve utilization. Implementation of procurement biopsy standards to avoid biopsy of low risk organs may prevent organ discards due to inaccurate data or excessive cold ischemia time. Further, standardization of procurement biopsy pathological interpretation coupled with electronic accessibility would enable early acceptance of difficult to transplant organs. These changes to allocation practice patterns are vital given proposals to expand the geographic sharing of deceased donor kidneys. Implementation of new allocation policies must be evaluated to ensure they result in higher transplant rates and acceptable post-transplant outcomes.

Do the CMS proposed breast cancer quality measures actually predict improved outcomes?

BACKGROUND: In 2007, professional collaborations developed a unified set of quality standards for breast cancer care. METHODS: This was an Institutional Review Board-approved, retrospective review of all breast cancer patients treated initially at University of Oklahoma Medical Center from 2000 to 2008. All tumor registry data were reviewed to test compliance with the Center for Medicare and Medicaid Services (CMS) (Medicare) quality standards. RESULTS: Overall and disease-free survival was better for patients meeting the radiation for breast conservation standard (P < .02). Whether estrogen receptor positive (ER+) or estrogen receptor negative, there were similar statistically significant benefits of combination chemotherapy in overall and disease-free survival rates for all patients with tumors greater than 1 cm in size (P < .05). Hormonal therapy was associated with an overall survival benefit (P < .005) but only a trend toward improvement in disease-free survival (P = .076). CONCLUSIONS: We believe the current CMS standards are a reasonable first step at monitoring breast cancer quality of care. Our data suggest that these may be improved by including combination chemotherapy in ER+ disease when data show a net survival benefit over hormonal therapy alone.

Tigecycline for the treatment of infections due to resistant Gram-positive organisms.

Tigecycline is a novel compound in the antimicrobial class known as the glycylcyclines. In vitro studies have shown it to have activity against the vast majority of Gram-positive pathogens, including multi-drug resistant Staphylococcus aureus and vancomycin-resistant enterococci. Tigecycline has also shown excellent in vitro activity against a broad range of Gram-negative enteric organisms including strains resistant to other antimicrobials as well as anaerobes. Tigecycline is not affected by the ribosomal protection and efflux mechanisms transmitted by the known tetracycline resistance genes. Tigecycline represents an exciting new class of glycylcycline antimicrobial agents for the treatment of multi-drug resistant Gram-positive bacteria. Although its broad spectrum of activity, which also includes Gram-negative enterics, makes it a candidate for empiric therapy for intra-abdominal infections, its spectrum against multi-drug resistant Gram-positive organisms makes it a very attractive choice for empiric treatment of Gram-positive infections in patients at risk for resistant strains. The two pivotal Phase II clinical trials involving complicated skin and soft tissue infections and intra-abdominal infections have shown the drug to be safe and effective.