The Management of Inflatable Penile Prosthesis Erosion and Infection following Iatrogenic Aspiration.

This case report presents a unique and previously unreported case of malfunction, infection, and erosion of an inflatable penile prosthesis (IPP) resulting from iatrogenic injury during a priapism aspiration procedure performed by an emergency medicine physician. The patient, a 75-year-old male with a history of IPP placement for erectile dysfunction, presented with urinary retention and priapism, leading to inadvertent deflation of the IPP during aspiration. Subsequent evaluation revealed a pinhole opening on the scrotum, indicating infection and erosion of the prosthesis tubing. The patient underwent emergent explantation of the infected IPP, washout, cystoscopy, and insertion of a suprapubic tube. Intraoperative cultures identified Escherichia cloacae as the causative pathogen. This case highlights the importance of thorough chart review to identify patients with IPPs before aspiration procedures and emphasizes the need for healthcare provider education regarding potential complications in this patient population. Early recognition and management of such complications are crucial for optimal patient outcomes. While IPP placement remains a highly satisfactory treatment for erectile dysfunction, this case highlights the importance of vigilance to ensure the best care for patients with penile prostheses. It is noteworthy that ultimately, a new IPP was not placed in this patient due to the patient's significant medical comorbidities.

Robot-Assisted Repair of Bladder Rupture following Penile Ring Entrapment.

Penile rings have been used to help sustain erection and enhance sexual pleasure for centuries. Constriction of the penis reduces the outflow of blood from the cavernosal tissue. However, if left for an extended time period, a condition called penile ring entrapment can occur. This may result in severe edema, gangrene, necrosis, and even penile amputation. Penile ring entrapment is a very rare condition; complete urinary obstruction with concomitant bladder rupture as a result renders this case even more extraordinary. We discuss our experience in the management of a 64-year-old man, who presented with altered mental status and inability to urinate, found to have penile ring entrapment and intraperitoneal bladder rupture. Removal of the constricting ring was performed in the ED, and bladder injury and penile necrosis were subsequently repaired with robot-assisted laparoscopic cystorrhaphy, penectomy, and perineal urethrostomy.

Porous Silicon Nanoparticle Delivery of Tandem Peptide Anti-Infectives for the Treatment of Pseudomonas aeruginosa Lung Infections.

There is an urgent need for new materials to treat bacterial infections. In order to improve antibacterial delivery, an anti-infective nanomaterial is developed that utilizes two strategies for localization: i) a biodegradable nanoparticle carrier to localize therapeutics within the tissue, and ii) a novel tandem peptide cargo to localize payload to bacterial membranes. First, a library of antibacterial peptides is screened that combines a membrane-localizing peptide with a toxic peptide cargo and discovers a tandem peptide that displays synergy between the two domains and is able to kill Pseudomonas aeruginosa at sub-micromolar concentrations. To apply this material to the lung, the tandem peptide is loaded into porous silicon nanoparticles (pSiNPs). Charged peptide payloads are loaded into the pores of the pSiNP at ≈30% mass loading and ≈90% loading efficiency using phosphonate surface chemistry. When delivered to the lungs of mice, this anti-infective nanomaterial exhibits improved safety profiles over free peptides. Moreover, treatment of a lung infection of P. aeruginosa results in a large reduction in bacterial numbers and markedly improves survival compared to untreated mice. Collectively, this study presents the selection of a bifunctional peptide-based anti-infective agent and its delivery via biodegradable nanoparticles for application to an animal model of lung infection.

Neuron-Targeted Nanoparticle for siRNA Delivery to Traumatic Brain Injuries.

Traumatic brain injuries (TBIs) affect 2.5 million Americans per year, and survivors of TBI can develop long-term impairments in physical, cognitive, and psychosocial functions. Currently, there are no treatments available to stop the long-term effects of TBI. Although the primary injury can only be prevented, there is an opportunity for intervention during the secondary injury, which persists over the course of hours to years after the initial injury. One promising strategy is to modulate destructive pathways using nucleic acid therapeutics, which can downregulate "undruggable" targets considered difficult to inhibit with small molecules; however, the delivery of these materials to the central nervous system is challenging. We engineered a neuron-targeting nanoparticle which can mediate intracellular trafficking of siRNA cargo and achieve silencing of mRNA and protein levels in cultured cells. We hypothesized that, soon after an injury, nanoparticles in the bloodstream may be able to infiltrate brain tissue in the vicinity of areas with a compromised blood brain barrier (BBB). We find that, when administered systemically into animals with brain injuries, neuron-targeted nanoparticles can accumulate into the tissue adjacent to the injured site and downregulate a therapeutic candidate.

Self-Sealing Porous Silicon-Calcium Silicate Core-Shell Nanoparticles for Targeted siRNA Delivery to the Injured Brain.

Calcium ions react with silicic acid released from dissolving porous silicon nanoparticles to create an insoluble calcium silicate shell. The calcium silicate shell traps and protects an siRNA payload, which can be delivered to neuronal tissues in vitro or in vivo. Gene delivery is enhanced by the action of targeting and cell-penetrating peptides attached to the calcium silicate shell.

Porous silicon-graphene oxide core-shell nanoparticles for targeted delivery of siRNA to the injured brain.

We report the synthesis, characterization, and assessment of a nanoparticle-based RNAi delivery platform that protects siRNA payloads against nuclease-induced degradation and efficiently delivers them to target cells. The nanocarrier is based on biodegradable mesoporous silicon nanoparticles (pSiNPs), where the voids of the nanoparticles are loaded with siRNA and the nanoparticles are encapsulated with graphene oxide nanosheets (GO-pSiNPs). The graphene oxide encapsulant delays release of the oligonucleotide payloads in vitro by a factor of 3. When conjugated to a targeting peptide derived from the rabies virus glycoprotein (RVG), the nanoparticles show 2-fold greater cellular uptake and gene silencing. Intravenous administration of the nanoparticles into brain-injured mice results in substantial accumulation specifically at the site of injury.

Programmable probiotics for detection of cancer in urine.

Rapid advances in the forward engineering of genetic circuitry in living cells has positioned synthetic biology as a potential means to solve numerous biomedical problems, including disease diagnosis and therapy. One challenge in exploiting synthetic biology for translational applications is to engineer microbes that are well tolerated by patients and seamlessly integrate with existing clinical methods. We use the safe and widely used probiotic Escherichia coli Nissle 1917 to develop an orally administered diagnostic that can noninvasively indicate the presence of liver metastasis by producing easily detectable signals in urine. Our microbial diagnostic generated a high-contrast urine signal through selective expansion in liver metastases (10(6)-fold enrichment) and high expression of a lacZ reporter maintained by engineering a stable plasmid system. The lacZ reporter cleaves a substrate to produce a small molecule that can be detected in urine. E. coli Nissle 1917 robustly colonized tumor tissue in rodent models of liver metastasis after oral delivery but did not colonize healthy organs or fibrotic liver tissue. We saw no deleterious health effects on the mice for more than 12 months after oral delivery. Our results demonstrate that probiotics can be programmed to safely and selectively deliver synthetic gene circuits to diseased tissue microenvironments in vivo.