First-in-Human Assessment of cRGD-ZW800-1, a Zwitterionic, Integrin-Targeted, Near-Infrared Fluorescent Peptide in Colon Carcinoma.

PURPOSE: Incomplete oncologic resections and damage to vital structures during colorectal cancer surgery increases morbidity and mortality. Moreover, neoadjuvant chemoradiotherapy has become the standard treatment modality for locally advanced rectal cancer, where subsequent downstaging can make identification of the primary tumor more challenging during surgery. Near-infrared (NIR) fluorescence imaging can aid surgeons by providing real-time visualization of tumors and vital structures during surgery. EXPERIMENTAL DESIGN: We present the first-in-human clinical experience of a novel NIR fluorescent peptide, cRGD-ZW800-1, for the detection of colon cancer. cRGD-ZW800-1 was engineered to have an overall zwitterionic chemical structure and neutral charge to lower nonspecific uptake and thus background fluorescent signal. We performed a phase I study in 11 healthy volunteer as well as a phase II feasibility study in 12 patients undergoing an elective colon resection, assessing 0.005, 0.015, and 0.05 mg/kg cRGD-ZW800-1 for the intraoperative visualization of colon cancer. RESULTS: cRGD-ZW800-1 appears safe, and exhibited rapid elimination into urine after a single low intravenous dose. Minimal invasive intraoperative visualization of colon cancer through full-thickness bowel wall was possible after an intravenous bolus injection of 0.05 mg/kg at least 2 hours prior to surgery. Longer intervals between injection and imaging improved the tumor-to-background ratio. CONCLUSIONS: cRGD-ZW800-1 enabled fluorescence imaging of colon cancer in both open and minimal invasive surgeries. Further development of cRGD-ZW800-1 for widespread use in cancer surgery may be warranted given the ubiquitous overexpression of various integrins on different types of tumors and their vasculature.

Prevention of Dental Caries by Silver Diamine Fluoride.

The use of silver diamine fluoride (SDF) for management of dental caries has gained considerable attention due to recent regulatory clearance in the United States. The primary focus of policies, presentations, and publications has been the arrest of caries lesions (cavities) because of the material's unique ability to non-invasively achieve this elusive and clinically important goal. However, SDF also has proven efficacy in prevention, ie, decreasing the incidence of new caries lesions. Analysis of nine clinical trials in children shows that SDF prevented 61% of new lesions compared to controls. To prevent one new caries lesion, clinicians need to treat four primary teeth (one patient) or 12.1 permanent molars (three patients) with SDF. The preventive effect appears to be immediate and maintains at the same fraction over time. Direct comparisons of SDF applied once per year with alternative treatments show that SDF is more effective than other topical fluorides placed two to four times per year and more cost-effective than dental sealants. Enamel lesions may be even more responsive than cavitated dentin lesions. Annual application of SDF to high-risk surfaces (eg, mesial surfaces of permanent first molars where the distal surface of the second primary molar is carious) in patients with any risk of new caries lesions appears to be the most cost-effective approach available to prevent dental caries. SDF is an underutilized evidence-based preventive agent for dental caries.

New proposal of silver diamine fluoride use in arresting approximal caries: study protocol for a randomized controlled trial.

BACKGROUND: Approximal surfaces are a challenge to caries lesions control. Silver diamine fluoride (SDF) is a simple,low-cost and promisor intervention for arresting caries lesions, but it has never been tested on approximal surfaces. Our aim is to evaluate the efficacy and cost-efficacy of SDF in arresting initial lesions compared to resin infiltration and exclusively flossing (control group). Our second aim is to assess discomfort and satisfaction regarding interventions. METHODS/DESIGN: This is a randomized clinical trial, double-blinded, placebo-controlled study. Children/adolescents presenting at least one approximal initial caries lesion in primary molars/permanent premolars and molars will be included. Surfaces with advanced dentine lesions identified by radiography and participants who refuse to participate or present negative behaviors will be excluded. A minimum sample size of 504 surfaces will be required for each subgroup. Individuals will be randomly allocated in three groups of interventions: SDF, resin infiltration, and control group. Depending on the allocation, the patients will receive the active treatment and respective placebo therapies. All patients will be oriented to daily flossing the included surfaces. Our primary outcome will be caries progression by clinical and radiographic examinations. Appointments will be timed and costs of materials will be considered to calculate cost-efficacy. Patient discomfort will be assessed after interventions. Parent and patient satisfaction with the treatment will be collected after treatment and in the last follow-up visit. Individuals will be assessed at 1 and 3 months after treatment to evaluate dental biofilm and at 6, 12, and 24 months to assess caries progression by visual examination and/or radiography. Multilevel analyses will be used to verify if the type of treatment influenced on the tested outcomes. Costs will be compared and analyses of cost-efficacy will be performed. Poisson analysis will test the association between intervention and reported discomfort and satisfaction. DISCUSSION: Our hypothesis is that SDF is the most cost-efficacious option from all tested interventions. If our hypothesis is confirmed, the use of SDF in private and public contexts could represent an easier and effective option in the treatment of enamel approximal caries in children/adolescents. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01477385), Initial release: 11/16/2011: last update: 06/02/2014.

Adverse reactions associated with respirator fit testing of healthcare workers in British Columbia, Canada: a review of compensation claim cases.

Thousands of healthcare workers in British Columbia are being fit tested for respirator use as a part of respiratory protection programs emanating from the SARS outbreak in 2003. The author reviews 8 claims submitted to the Workers' Compensation Board of British Columbia for adverse reactions related to denatonium benzoate fit testing. The adverse effects varied in severity. Most claims involved respiratory symptoms and 3 dermatitis or angioedema symptoms. One asthmatic required hospitalization for a severe asthmatic reaction. These cases indicate that there may be potentially significant health risks associated with denatonium benzoate-based fit testing at least for a small group of susceptible individuals. More systematic research is required.

Risk assessment of the occupational contact with ammonium.

The aim of the cohort retrospective study was to analyze and evaluate the influence of certain factors (age, profession, smoking) on the characteristics and the incidence rate of the upper respiratory tract diseases (URTDs) in the occupational contact with ammonium. Subjects were 180 men, divided into 3 professional groups. The average shift concentrations of ammonium were measured in the permanent work places and individually by personal passive dosemeters. The URTDs were classified into 15 groups according to localization and the stage of the inflammatory process. The relationships "time-response" and "dose (concentration)-response" were determined. The factor "cumulative exposure" was used in order to evaluate the actual noxious effect of NH3 on the mucose of the upper respiratory tract (URT). There was a statistically reliable difference found in the incidence rate of atrophic rhinitis, hypertrophic pharyngitis and laryngitis, and neoplasms of the URT in the workers with the highest cumulative exposure. For this group relative risk was 4.00, 2.22, 3.20 and 4.00, respectively, with 95% Cl. The "cumulative exposure" factor gives the best proofs for the toxic effect of ammonium and a possibility for assessment of the relative risk.