The effects and effectiveness of electromotive drug administration and chemohyperthermia for treating non-muscle invasive bladder cancer

Introduction

Preliminary studies show that device assisted intravesical therapies appear more effective than passive diffusion intravesical therapy for the treatment of non-muscle invasive bladder cancer (NMIBC) in specific settings, and phase III studies are now being conducted. Consequently, we have undertaken a non-systematic review with the objective of describing the scientific basis and mechanisms of action of electromotive drug administration (EMDA) and chemohyperthermia (CHT).

Methods

PubMed, ClinicalTrials.gov and the Cochrane Library were searched to source evidence for this non-systematic review. Randomised controlled trials, systematic reviews and meta-analyses were evaluated. Publications regarding the scientific basis and mechanisms of action of EMDA and CHT were identified, as well as clinical studies to date.

Results

EMDA takes advantage of three phenomena: iontophoresis, electro-osmosis and electroporation. It has been found to reduce recurrence rates in NMIBC patients and has been proposed as an addition or alternative to bacillus Calmette–Guérin (BCG) therapy in the treatment of high risk NMIBC. CHT improves the efficacy of mitomycin C by three mechanisms: tumour cell cytotoxicity, altered tumour blood flow and localised immune responses. Fewer studies have been conducted with CHT than with EMDA but they have demonstrated utility for increasing disease-free survival, especially in patients who have previously failed BCG therapy.

Conclusions

It is anticipated that EMDA and CHT will play important roles in the management of NMIBC in the future. Techniques of delivery should be standardised, and there is a need for more randomised controlled trials to evaluate the benefits of the treatments alongside quality of life and cost-effectiveness.     

Alveolar soft part sarcoma of the head and neck

Alveolar soft part sarcoma (ASPS) of the head and neck region has been a rarely reported entity. These lesions have a high propensity for distant metastasis. A retrospective study of the medical records at our institute, revealed thirty-eight cases of ASPS. Six of these were of primary head and neck origin. The article highlights the aggressive nature of the tumour and the need to arrive at a consensus on the treatment protocol.     

Specific Retrograde Transduction of Spinal Motor Neurons Using Lentiviral Vectors Targeted to Presynaptic NMJ Receptors

To understand how receptors are involved in neuronal trafficking and to be able to utilize them for specific targeting via the peripheral route would be of great benefit. Here, we describe the generation of novel lentiviral vectors with tropism to motor neurons that were made by coexpressing onto the lentiviral surface a fusogenic glycoprotein (mutated sindbis G) and an antibody against a cell-surface receptor (Thy1.1, p75^NTR, or coxsackievirus and adenovirus receptor) on the presynaptic terminal of the neuromuscular junction. These vectors exhibit binding specificity and efficient transduction of receptor positive cell lines and primary motor neurons in vitro. Targeting of each of these receptors conferred to these vectors the capability of being transported retrogradely from the axonal tip, leading to transduction of motor neurons in vitro in compartmented microfluidic cultures. In vivo delivery of coxsackievirus and adenovirus receptor-targeted vectors in leg muscles of mice resulted in predicted patterns of motor neuron labeling in lumbar spinal cord. This opens up the clinical potential of these vectors for minimally invasive administration of central nervous system-targeted therapeutics in motor neuron diseases.     

Novel uses of intracardiac echocardiography with a phased-array imaging catheter.

A newer phased-array ultrasound imaging catheter (AcuNav, Siemens, Moutainview, Calif) provides comprehensive anatomic and physiologic data during cardiac interventions. The role of this catheter in percutaneous closure procedures, transseptal ablative procedures, and valvular interventions has been reported. We describe an expanded role of intracardiac echocardiography using AcuNav imaging catheter (Siemens) in 2 clinical situations.     

Marked QT prolongation and torsades de pointes secondary to acute ischemia in an elderly man taking dofetilide for atrial fibrillation: a cautionary tale

Dofetilide has been shown to be effective and safe in maintaining sinus rhythm in patients with persistent atrial fibrillation and congestive heart failure. Because of serious side effects of an increase in the QT interval causing torsades de pointes, dofetilide must be initiated with close monitoring of the QT interval in an inpatient setting. However, little has been reported about conditions surrounding the change in QT interval after the steady state is achieved that may have implications in the safety and efficacy of the drug. We report marked QT prolongation and torsades de pointes in a setting of flash pulmonary edema resulting from acute myocardial ischemia in a patient who was being treated with dofetilide for atrial fibrillation. Our case reminds the clinicians that the adverse and proarrhythmic effects of dofetilide can occur due to changes in the arrhythmic substrate during acute severe ischemia.     

Do Gerontology Nurse Specialists Make a Difference in Hospitalization of Long‐Term Care Residents? Results of a Randomized Comparison Trial

Residents of long‐term care facilities have highly complex care needs and quality of care is of international concern. Maintaining resident wellness through proactive assessment and early intervention is key to decreasing the need for acute hospitalization. The Residential Aged Care Integration Program (RACIP) is a quality improvement intervention to support residential aged care staff and includes on‐site support, education, clinical coaching, and care coordination provided by gerontology nurse specialists (GNSs) employed by a large district health board. The effect of the outreach program was evaluated through a randomized comparison of hospitalization 1 year before and after program implementation. The sample included 29 intervention facilities (1,425 residents) and 25 comparison facilities (1,128 residents) receiving usual care. Acute hospitalization rate unexpectedly increased for both groups after program implementation, although the rate of increase was significantly less for the intervention facilities. The hospitalization rate after the intervention increased 59% for the comparison group and 16% for the intervention group (rate ratio (RR) = 0.73, 95% confidence interval (CI) = 0.61–0.86, P < .001). Subgroup analysis showed a significantly lower rate change for those admitted for medical reasons for the intervention group (13% increase) than the comparison group (69% increase) (RR = 0.67, 95% CI = 0.56–0.82, P < .001). Conversely, there was no significant difference in the RR for surgical admissions between the intervention and comparison groups (RR = 1.0, 95% CI = 0.68–1.46, P = .99). The integration of GNS expertise through the RACIP intervention may be one approach to support staff to provide optimal care and potentially improve resident health.     

Toxicity induced by nanoparticles

Nanoparticle research is currently an area of intense scientific interest due to a wide variety of potential applications. Human beings have been exposed to airborne nanosized particles throughout their evolutionary stages, and such exposures have increased dramatically over the last century. Nanoparticle can modify the physicochemical properties of the material as well as create the opportunity for increased uptake and interaction with biological tissues through inhalation, ingestion, and injection. This combination of effects can generate adverse biological effects in living cells. Nanoparticles have proved toxic to human once in the blood stream, nanoparticles, spleen, bone marrow and nervous system can be transported around the body and be taken up by organs tissue and cell cultures, resulting in increased oxidative stress, inflammatory cytokine production and cell death. Unlike larger particles, nanoparticles may be taken up by cell mitochondria and the cell nucleus studies demonstrate the potential for nanoparticles to cause DNA mutation and induce major structural damage to mitochondria, even resulting in cell death. Size is therefore a key factor in determining the potential toxicity of a particle. How these nanoparticles behave inside the body is still a major question that needs to be resolved. There is a responsibility to test and optimize these new nanomaterials early during the development process to eliminate or ameliorate identified toxic characteristics.