Prior male sling does not affect outcomes of artificial urinary sphincter.

OBJECTIVE: To investigate the outcomes of artificial urinary sphincter (AUS) placement in patients with post-prostatectomy urinary incontinence (PPUI) with or without a prior male sling. PATIENTS AND METHODS: We performed a retrospective chart review of patients who underwent AUS for PPUI from 2007 to 2022. The primary endpoint was to determine the proportion of patients who achieved social continence, defined as self-reported use of 0-1 pad/day. The secondary endpoints were device failure rates and device failure-free survival. RESULTS: The analysis included 210 patients, with 30 (14.3%) having had prior slings and 180 (85.7%) without prior slings. After AUS insertion, 80.0% of patients with prior slings and 76.7% of those without prior slings achieved continence (0-1 pad/day). There were six (20.0%) and 53 (29.4%) device failures in patients with and without prior slings, respectively. The median device failure-free survival was not reached in patients with prior slings and was 8.9 years in patients without prior slings (P = 0.048). Limitations include retrospective nature and small sample size. CONCLUSIONS: The efficacy and safety of AUS in patients with prior slings are similar to those without. Prior sling is associated with a longer device failure-free survival. AUS remains a viable option in patients who have persistent PPI after prior slings.

Is it Safe to Continue Aspirin in Patients Undergoing Percutaneous Nephrolithotomy?

OBJECTIVE: To evaluate peri-operative outcomes in patients on chronic aspirin therapy undergoing percutaneous nephrolithotomy (PCNL), with and without discontinuation of aspirin. Anti-coagulation and anti-platelet therapy are contraindications for PCNL per American Urological Association guidelines due to bleeding risk. However, there is potentially increased cardiovascular risk with peri-procedural aspirin withdrawal. METHODS: Patients on chronic aspirin undergoing PCNL between January 2014 and May 2019 were retrospectively reviewed and stratified by continued or discontinued aspirin >5 days preoperatively. Hematologic complications, transfusions, and thrombotic complications were assessed with logistic regression model. RESULTS: Three hundred twenty-five patients on chronic aspirin therapy underwent PCNL-85 continued and 240 discontinued aspirin. There were no significant differences in hemoglobin change, estimated blood loss, transfusions, creatinine change, thrombotic complications, 30-days re-admissions, complications, or 30-day emergency department visits. Patients who continued aspirin had longer length of stay (1.6 vs 1.9 days, P = .03). American Society of Anesthesiologists (ASA) score of 3 (OR 3.2, P = .02, 95% confidence intervals (CI) [1.2-8.4]), ASA score of 4 (OR 4.0, P = .02, 95% CI [1.2-13.1]), Black race, and previous smoking (OR 2.1, P = .02, 95% CI [1.1-3.9]) was associated with continued aspirin. Body mass index ≥30 was associated with aspirin discontinuation (OR 0.9, P = .004, 95% CI [0.9-1.0]). Increased postoperative hematologic complications were associated with additional anticoagulation medication (OR 2.9, P = .04, 95% CI [1.0-4.4]). CONCLUSION: Continued aspirin use did not increase in postoperative complications in patients undergoing PCNL. Patients who are on additional anticoagulation medication are at risk of hematologic complications.

Effects of natural products on cisplatin ototoxicity and chemotherapeutic efficacy.

INTRODUCTION: Cisplatin is a very effective chemotherapeutic agent against a variety of solid tumors. Unfortunately, cisplatin causes permanent sensorineural hearing loss in at least two-thirds of patients treated. There are no FDA approved drugs to prevent this serious side effect. AREAS COVERED: This paper reviews various natural products that ameliorate cisplatin ototoxicity. These compounds are strong antioxidants and anti-inflammatory agents. This review includes mostly preclinical studies but also discusses a few small clinical trials with natural products to minimize hearing loss from cisplatin chemotherapy in patients. The interactions of natural products with cisplatin in tumor-bearing animal models are highlighted. A number of natural products did not interfere with cisplatin anti-tumor efficacy and some agents actually potentiated cisplatin anti-tumor activity. EXPERT OPINION: There are a number of natural products or their derivatives that show excellent protection against cisplatin ototoxicity in preclinical studies. There is a need to insure uniform standards for purity of drugs derived from natural sources and to ensure adequate pharmacokinetics and safety of these products. Natural products that protect against cisplatin ototoxicity and augment cisplatin's anti-tumor effects in multiple studies of tumor-bearing animals are most promising for advancement to clinical trials. The most promising natural products include honokiol, sulforaphane, and thymoquinone.

Designing a Dyad-Based Digital Health Intervention to Reduce Sedentary Time in Black Breast Cancer Survivors and Their First-degree Relatives: Human-Centered Design Study.

BACKGROUND: Breast cancer, the most commonly diagnosed cancer and second leading cause of cancer-related death in women in the United States, disproportionately affects women from minoritized or low socioeconomic backgrounds. The average woman has an approximately 12% lifetime risk of developing breast cancer. Lifetime risk nearly doubles if a woman has a first-degree relative with breast cancer, and the risk increases as multiple family members are affected. Decreasing sedentary behaviors through moving more and sitting less reduces breast cancer risk and improves outcomes for cancer survivors and healthy adults. Digital health solutions, such as mobile apps that are culturally appropriate, designed with input from the target audience, and include social support, are effective at improving health behaviors. OBJECTIVE: This study aimed to develop and evaluate the usability and acceptability of a prototype app designed with a human-centered approach to promote moving more and sitting less in Black breast cancer survivors and their first-degree relatives (parent, child, or sibling). METHODS: This 3-phase study consisted of app development, user testing, and evaluation of user engagement and usability. Key community stakeholders were engaged in the first 2 (qualitative) phases to provide input into developing the prototype app (MoveTogether). After development and user testing, a usability pilot was conducted. Participants were adult breast cancer survivors who identified as Black and agreed to participate with a relative. Participants used the app and a step-tracking watch for 4 weeks. App components included goal setting and reporting, reminders, dyad messaging, and educational resources. Usability and acceptability were assessed with a questionnaire that included the System Usability Scale (SUS) and semistructured interviews. Data were analyzed with descriptive statistics and content analysis. RESULTS: Participants in the usability pilot (n=10) were aged 30 to 50 years (6/10, 60%), not married (8/10, 80%), and college graduates (5/10, 50%). The app was used on average 20.2 (SD 8.9) out of 28 days-SUS score of 72 (range 55-95)-and 70% (7/10) agreed that the app was acceptable, helpful, and gave them new ideas. Additionally, 90% (9/10) found the dyad component helpful and would recommend the app to friends. Qualitative findings suggest that the goal-setting feature was helpful and that the dyad partner (buddy) provided accountability. Participants were neutral regarding the cultural appropriateness of the app. CONCLUSIONS: The MoveTogether app and related components were acceptable for promoting moving more in dyads of breast cancer survivors and their first-degree relatives. The human-centered approach, which involved engaging community members in the development, is a model for future technology development work. Future work should be done to further develop the intervention based on the findings and then test its efficacy to improve sedentary behavior while considering culturally informed strategies for adoption and implementation within the community. TRIAL REGISTRATION: ClinicalTrials.gov NCT05011279; https://clinicaltrials.gov/ct2/show/NCT05011279.

Targeting CXCL1 chemokine signaling for treating cisplatin ototoxicity.

Cisplatin is chemotherapy used for solid tumor treatment like lung, bladder, head and neck, ovarian and testicular cancers. However, cisplatin-induced ototoxicity limits the utility of this agent in cancer patients, especially when dose escalations are needed. Ototoxicity is associated with cochlear cell death through DNA damage, the generation of reactive oxygen species (ROS) and the consequent activation of caspase, glutamate excitotoxicity, inflammation, apoptosis and/or necrosis. Previous studies have demonstrated a role of CXC chemokines in cisplatin ototoxicity. In this study, we investigated the role of CXCL1, a cytokine which increased in the serum and cochlea by 24 h following cisplatin administration. Adult male Wistar rats treated with cisplatin demonstrated significant hearing loss, assessed by auditory brainstem responses (ABRs), hair cell loss and loss of ribbon synapse. Immunohistochemical studies evaluated the levels of CXCL1 along with increased presence of CD68 and CD45-positive immune cells in cochlea. Increases in CXCL1 was time-dependent in the spiral ganglion neurons and organ of Corti and was associated with progressive increases in CD45, CD68 and IBA1-positive immune cells. Trans-tympanic administration of SB225002, a chemical inhibitor of CXCR2 (receptor target for CXCL1) reduced immune cell migration, protected against cisplatin-induced hearing loss and preserved hair cell integrity. We show that SB225002 reduced the expression of CXCL1, NOX3, iNOS, TNF-α, IL-6 and COX-2. Similarly, knockdown of CXCR2 by trans-tympanic administration of CXCR2 siRNA protected against hearing loss and loss of outer hair cells and reduced ribbon synapses. In addition, SB225002 reduced the expression of inflammatory mediators induced by cisplatin. These results implicate the CXCL1 chemokine as an early player in cisplatin ototoxicity, possibly by initiating the immune cascade, and indicate that CXCR2 is a relevant target for treating cisplatin ototoxicity.

Evaluation of prior authorizations in transplant recipients at an urban institution.

BACKGROUND: Increasing prior authorization (PA) requirements for immunosuppression remain a burden for solid organ transplant (SOT) recipients and transplant staff. The objective of this study was to evaluate the number of PAs required and the approval rates at an academic, urban transplant center. METHODS: This was a retrospective study of SOT recipients at the University of Illinois Hospital and Health Sciences System (UI Health) that required PAs between 11/1/2019 and 12/1/2020. Inclusion criteria were SOT recipients greater than 18 years of age and prescribed a medication by the transplant team that required PA. Duplicate PA requests were excluded from the analysis. RESULTS: A total of 879 PAs were included in the study. Of these PAs, 85% (747/879) were approved. Seventy-four percent of the denials were overturned by an appeal. Most PAs were in black (45.4%), kidney transplant (62%), Medicare (31.7%), and Medicaid recipients (33.2%). The median approval time was 1 day for PAs and 5 days for appeals. Tacrolimus extended release (XR) (35.4%), tacrolimus immediate release (IR) (9.7%),and mycophenolic acid (7%) required most PAs. Black recipients and immunosuppression were identified as predictors of eventual PA approval, whereas recipients with Medicaid were less likely to obtain approval. CONCLUSIONS: At our transplant center, there was a high approval rate of PAs for immunosuppression, which calls into question the utility of PAs in this patient population, where these medications are standard of care. More black recipients and patients with Medicare and Medicaid had increased PA requirements, highlighting further disparities within the current system.

The Significance and Impact of Screening Preservation Fluid Cultures in Renal Transplant Recipients.

INTRODUCTION: Infectious complications can be a major cause of morbidity and mortality in solid organ transplant recipients. Preservation fluid is necessary to maintain organ viability but may serve as a vector or infection. The utility of screening preservation fluid routinely for microbial growth and the impact of culture-positive preservation fluid is controversial. Research Question: What is the clinical impact of a culture positive preservation fluid in a kidney transplant recipient? DESIGN: This retrospective study was performed to define the incidence of post-operative infection related to PF and examine the negative sequelae of culture-positive PF. One hundred and fifty-two deceased donor renal transplant recipients from January 2015 to December 2017 were included for analysis. RESULTS: Overall, 67% of patients (102/152) received an allograft from a culture-positive PF. Nearly 80% of microbial growth was consistent with skin flora, and coagulase-negative staphylococci was the most frequently isolated organism (56%). Sixty-seven percent of patients (68/102) with culture-positive PF received antimicrobial treatment for an average duration of 5 days. There was no difference in the incidence of infection between patients with culture positive PF compared to culture-negative PF. Furthermore, there were no cases of infection related to PF regardless of whether culture-positive PF was treated or untreated. The incidence of subsequent C. difficile infection and multidrug-resistant organisms was similar. DISCUSSION: This study suggests antimicrobial treatment for culture positive PF may not be necessary with pathogens that are common contaminants and of low virulence. Interventional studies are needed to validate this strategy.

A randomized, open-label pharmacokinetic trial of tacrolimus extended-release dosing in obese de novo kidney transplant recipients.

PURPOSE: Tacrolimus extended-release (TAC-ER; Astagraf XL® ) is utilized in many immunosuppressive regimens post-renal transplantation. Current dosing recommendation for the TAC-ER in renal transplant is 0.15-0.2 mg/kg/day administered once daily. The purpose of this study was to determine the best method of dosing TAC-ER in obese renal transplant recipients. METHODS: De novo obese kidney transplant recipients were randomized to receive TAC-ER 0.15 mg/kg/day based on either adjusted body weight (aBW) or ideal body weight (IBW). Post-transplant patients underwent three pharmacokinetic assessments over 14 days. The primary endpoint was the difference in TAC-ER exposure (AUC0-24) in obese patients dosed using aBW compared with IBW. RESULTS: A total of 20 obese renal transplant recipients were randomized to participate in the study (10 aBW and 10 IBW). Results of the primary outcome (AUC0-24) on Study Day 1, 7, and 14 were not statistically different between the two groups. There was no difference in the number of days to therapeutic trough concentration between the two dosing weights (aBW = 5.1, IBW = 4.9, days; P = 0.90). CONCLUSION: In a population of obese renal transplant recipients, comparable trough concentrations and overall exposure in both groups indicate that IBW may be preferred, as less initial drug was needed to attain adequate exposure.

Targeted disruption of the extracellular polymeric network of Pseudomonas aeruginosa biofilms by alginate oligosaccharides.

Acquisition of a mucoid phenotype by Pseudomonas sp. in the lungs of cystic fibrosis (CF) patients, with subsequent over-production of extracellular polymeric substance (EPS), plays an important role in mediating the persistence of multi-drug resistant (MDR) infections. The ability of a low molecular weight (Mn = 3200 g mol-1) alginate oligomer (OligoG CF-5/20) to modify biofilm structure of mucoid Pseudomonas aeruginosa (NH57388A) was studied in vitro using scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) with Texas Red (TxRd®)-labelled OligoG and EPS histochemical staining. Structural changes in treated biofilms were quantified using COMSTAT image-analysis software of CLSM z-stack images, and nanoparticle diffusion. Interactions between the oligomers, Ca2+ and DNA were studied using molecular dynamics (MD) simulations, Fourier transform infrared spectroscopy (FTIR) and isothermal titration calorimetry (ITC). Imaging demonstrated that OligoG treatment (≥0.5%) inhibited biofilm formation, revealing a significant reduction in both biomass and biofilm height (P < 0.05). TxRd®-labelled oligomers readily diffused into established (24 h) biofilms. OligoG treatment (≥2%) induced alterations in the EPS of established biofilms; significantly reducing the structural quantities of EPS polysaccharides, and extracellular (e)DNA (P < 0.05) with a corresponding increase in nanoparticle diffusion (P < 0.05) and antibiotic efficacy against established biofilms. ITC demonstrated an absence of rapid complex formation between DNA and OligoG and confirmed the interactions of OligoG with Ca2+ evident in FTIR and MD modelling. The ability of OligoG to diffuse into biofilms, potentiate antibiotic activity, disrupt DNA-Ca2+-DNA bridges and biofilm EPS matrix highlights its potential for the treatment of biofilm-related infections.