Minimizing and managing needle and instrument loss during pediatric robotic surgery.

INTRODUCTION: Lost objects and equipment malfunctions during robotic and laparoscopic cases can lead to an increase in operating time and potential risk to the patient. The literature on the management of foreign bodies during pediatric robotic-assisted surgery is limited. The purpose of the video is to review proper instrument handling to prevent loss of an object and to propose our technique for retrieving lost objects through two pediatric case examples. MATERIALS AND METHODS: The first case is a robotic-assisted laparoscopic left pyeloplasty in a 6-week-old male with congenital uteropelvic junction obstruction during which a needle was lost. In the video, we describe our techniques for safe needle passage, proper suturing technique, and recovering a lost needle. The second case is a robotic-assisted right upper pole heminephrectomy in a 14-month-old female with a duplicated renal collecting system and hydroureteronephrosis. We present the management of a rare case during which a harmonic scalpel jaw malfunctioned leading to a lost foreign body. We describe our technique for retrieving the lost fragment. RESULTS: All objects were safely removed, and patients were discharged post-op day one without complication. CONCLUSION: Our video presents two case examples of foreign bodies lost during pediatric robotic surgeries and approaches to manage each of these incidents.

Severe penile necrotizing infection with subsequent glandular gangrene after distal corporal aspiration and irrigation procedure for ischemic priapism.

Necrotizing penile infection following ischemic priapism takedown is a rare complication. A 60-year-old man presented with 1-week history of green and pink purulent discharge, penile swelling, and inability to void. Computed tomography demonstrated gas and fluid accumulation within the corporal bodies, suggestive for bilateral penile necrotizing corporal infection with possibility of intra-corporal abscesses. The patient underwent extensive serial surgical debridement of the penile and corporal tissues which was complicated with poly-microbial tissue cultures, growing Candida albicans and Staphylococcus epidermidis. Despite maximal penile drainage, glans penis gangrene was developed to level of mid penile shaft necessitating a partial penectomy.

Effects of Music Therapy on Quality of Life in Adults with Sickle Cell Disease (MUSIQOLS): A Mixed Methods Feasibility Study.

PURPOSE: To investigate the feasibility, acceptability, and preliminary efficacy of a 6-session music therapy protocol on self-efficacy, quality of life, and coping skills in adults with sickle cell disease (SCD). PATIENTS AND METHODS: Using a mixed-methods intervention design, adults with SCD (ages 21-57; mean age 32.33) were randomized (1:1) to either 1) a 6-session music therapy (MT) intervention (n = 12) or 2) waitlist control (WLC) (n = 12) using stratified randomization where factors were age in years (≤30 vs >30), and sex (male, female). All participants completed two weeks of daily electronic pain diary entries and self-efficacy, quality of life, and coping skills measures before and after their assigned study condition to explore preliminary efficacy. MT participants were taught music exercises accessed via smartphone and subsequently interviewed to determine feasibility and acceptability. RESULTS: The enrollment rate was 89%. All study measures were completed, with high rates of electronic pain diary completion at baseline (70%) and 2-week follow-up (66%). Interviews revealed two overall themes related to MT participants' experience: 1) participants learned new self-management skills and 2) MT improved participants' ability to cope with pain. MT participants demonstrated 100% attendance. In preliminary analyses, MT participants demonstrated significant improvements (means ± SD) in self-efficacy (5.42 ± 5.43, p = 0.008, d = 1.20), PROMIS sleep disturbance (-1.49 ± 6.68, p = 0.023, d = -0.99), PROMIS pain interference (-2.10 ± 4.68, p = 0.016, d = -1.06), and ASCQ-Me social functioning impact scores (2.97 ± 6.91, p = 0.018, d = 1.05) compared to WLC participants. CONCLUSION: Preliminary findings support the feasibility and acceptability of music therapy for home use in adults with SCD. While music therapy may assist adults with SCD in improving self-efficacy and quality of life, subsequent, fully-powered clinical research is needed to determine its efficacy.

Race, Decisional Regret and Prostate Cancer Beliefs: Identifying Targets to Reduce Racial Disparities in Prostate Cancer.

PURPOSE: African American men are more likely to be diagnosed with, die of and experience decisional regret about their prostate cancer than nonAfrican American men. Although some clinical discrepancies may be attributed to genetic risk and/or access to care, explanations for racial discrepancies in decisional regret remain largely speculative. We aim to identify sources of prostate cancer decisional regret with a focus on racial disparities. MATERIALS AND METHODS: A cohort of 1,112 patients with localized prostate cancer treated at the Cleveland Clinic between 2010 and 2016 were matched by race, Gleason score, treatment (external beam radiation, brachytherapy, prostatectomy, active surveillance), prostate specific antigen at diagnosis, age at treatment and time since treatment. All patients received 4 surveys, including the Expanded Prostate Cancer Index Composite (EPIC) 26, the Decisional Regret Scale, our novel Prostate Cancer Beliefs Questionnaire and a modified EPIC demographics form. Descriptive and comparative statistics and multivariable logistic regression were used to compare survey outcomes by race and treatment method. RESULTS: Of 1,048 deliverable surveys 378 (36.07%) were returned. African American men had worse decisional regret than nonAfrican American men even after adjusting for relevant covariates (OR 2.46, p <0.0001). African American men also had higher Prostate Cancer Beliefs Questionnaire medical mistrust and masculinity scores, both of which predicted worse decisional regret independent of race (1.415 and 1.350, p=0.0001, respectively). CONCLUSIONS: African American men suffer worse decisional regret than nonAfrican American men, which may be partially explained by higher medical mistrust and concerns about masculinity as captured by the Prostate Cancer Beliefs Questionnaire. This novel survey may facilitate identifying targets to reduce racial disparities in prostate cancer.

A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging.

Despite the immense potential of existing photocaging technology, its application is limited by the paucity of advanced caging tools. Here, we report on the design of a novel thioacetal ortho-nitrobenzaldehyde (TNB) dual arm photocage that enabled control of the simultaneous release of two payloads linked to a single TNB unit. By using this cage, which was prepared in a single step from commercial 6-nitroverataldehyde, three drug-fluorophore conjugates were synthesized: Taxol-TNB-fluorescein, Taxol-TNB-coumarin, and doxorubicin-TNB-coumarin, and long-wavelength UVA light-triggered release experiments demonstrated that dual payload release occurred with rapid decay kinetics for each conjugate. In cell-based assays performed in vitro, dual release could also be controlled by UV exposure, resulting in increased cellular fluorescence and cytotoxicity with potency equal to that of unmodified drug towards the KB carcinoma cell line. The extent of such dual release was quantifiable by reporter fluorescence measured in situ and was found to correlate with the extent of cytotoxicity. Thus, this novel dual arm cage strategy provides a valuable tool that enables both active control and real-time monitoring of drug activation at the delivery site.

Light-controlled active release of photocaged ciprofloxacin for lipopolysaccharide-targeted drug delivery using dendrimer conjugates.

We report an active delivery mechanism targeted specifically to Gram(-) bacteria based on the photochemical release of photocaged ciprofloxacin carried by a cell wall-targeted dendrimer nanoconjugate.

Mechanism of Cooperativity and Nonlinear Release Kinetics in Multivalent Dendrimer-Atropine Complexes.

Despite extensive studies on drug delivery using multivalent complexation systems, the biophysical basis for release kinetics remains poorly defined. The present study addresses this aspect involved in the complexation of a fifth generation poly(amidoamine) (PAMAM) dendrimer with atropine, an essential antidote used for treating organophosphate poisoning. First, we designed (1)H NMR titration studies for determining the molecular basis of the drug complexation with a glutarate-modified anionic dendrimer. These provide evidence pointing to a combination of electrostatic and hydrophobic interactions as the driving forces for dendrimer complexation with the alkaloid drug molecule. Second, using LC-MS/MS spectrometry, we determined the dissociation constants (KD) at steady state and also measured the drug release kinetics of atropine complexes with four negatively charged dendrimer types. Each of these dendrimers has a high payload capacity for up to ∼ 100 atropine molecules. However, the affinity of the atropine to the carrier was highly dependent on the drug to dendrimer ratio. Thus, a complex made at a lower loading ratio (≤ 0.1) displayed greater atropine affinity (KD ≈ µM) than other complexes prepared at higher ratios (>10), which showed only mM affinity. This negative cooperative variation in affinity is tightly associated with the nonlinear release kinetics observed for each complex in which drug release occurs more slowly at the later time phase at a lower loading ratio. In summary, the present study provides novel insights on the cooperativity as the mechanistic basis for nonlinear release kinetics observed in multivalent carrier systems.

A lipopolysaccharide binding heteromultivalent dendrimer nanoplatform for Gram negative cell targeting.

We report on the practicality of a heteromultivalent design strategy for a nanoplatform that targets lipopolysaccharide molecules (LPS) present on the surface of Gram-negative bacteria. This design is based on the conjugation of a poly(amido amine) (PAMAM) dendrimer with two types of ligands, each having distinct affinities: (i) polymyxin B (PMB) as a primary high affinity ligand; (ii) a PMB-mimicking dendritic branch as an auxiliary low affinity ligand. Co-conjugation of these two ligands maximizes the efficiency of the primary ligand even when the primary ligand is present at a low valency on the nanoplatform (mean nPMB≈ 1). By performing surface plasmon resonance studies using a LPS-immobilized cell wall model, we identified an ethanolamine (EA)-terminated branch as the auxiliary ligand that promotes binding avidity via heteromultivalent association. PMB conjugation of the dendrimer with excess EA branches led to LPS avidity two orders of magnitude greater than unconjugated PMB. Such tight binding observed by SPR corresponded well with adsorption to E. coli cells and with potent bactericidal activity in vitro.