Oral Losartan After Limited Mandibulectomy for Treatment of Desmoid-Type Fibromatosis.

Desmoid-type fibromatosis (DF) is a rare soft tissue lesion with an annual incidence of 2 to 4 per million population and peak incidence occurring at approximately 4.5 years of age. While benign, the tumor has a locally aggressive infiltrative growth pattern and a high rate of recurrence. Given the functional and aesthetic implications of excision and reconstruction in the facial skeleton, novel medical treatment options are highly desirable. We describe the case of a 3-year-old boy who presented with an enlarging, asymptomatic mass involving the left mandible. Biopsy revealed an immunohistochemical profile consistent with DF. Despite the high likelihood of recurrence, conservative, mandible-sparing en bloc resection and limited mandibulectomy were performed. Pathological and immunohistochemical analysis of the resection specimen revealed DF with grossly positive margins and elevated expression of angiotensin II type 1 receptor. Postoperative medical treatment with the angiotensin receptor blocker losartan was initiated. The patient remains medically stable and disease progression-free on repeat imaging at 20 months post-resection. We describe for the first time the successful use of the angiotensin blocker losartan following conservative surgery for management of DF.

Degradable multifunctional gold-liposomes as an all-in-one theranostic platform for image-guided radiotherapy.

To improve tumor destruction and minimize adverse effects to healthy tissues, image-guided radiation therapy (IGRT) has been developed to allow for the accurate delivery of radiation energy to tumor sites facilitated by real-time imaging. Nevertheless, the current IGRT platform still suffers from the limitation of poor tissue contrast, resulting in the incidental irradiation of healthy tissue. Gold nanoparticles (GNPs) have been identified as promising candidates to simultaneously improve both radiotherapy and imaging, thereby improving both the accuracy and safety of IGRT. However, despite much preclinical study, little clinical progress has been made due to uncertainty over GNP toxicity. Herein, we demonstrate the great potential of using GNP-coated liposomes, i.e., Lipogold, which combine the advantages of both large and small nanoparticles into one multifunctional formulation, as an ideal platform for IGRT. When irradiated with low doses (<2 Gy) of therapeutic X-rays, Lipogold induced a significant radiosensitization effect for PC-3 prostate cancer cells, which are moderately radiation-resistant. When imaged with computed tomography (CT), Lipogold was also found to possess consistent X-ray contrast of âˆ¼ 18-23 HU/mg across tube X-ray voltages (70-140 kVp), which could be boosted via the encapsulation of a small-molecule contrast agent containing iodine.

Oncological and functional outcomes following treatment of T1a glottic squamous cell carcinoma with transoral laser microsurgery.

BACKGROUND: Laryngeal cancers of glottic origin comprise a large proportion of head and neck malignancies. Transoral laser microsurgery (TLM) and radiation therapy are mainstays in the treatment of early stage glottic cancer, but debate persists as to which modality is functionally superior. Furthermore, there is a paucity of North American data related to functional and oncological outcomes in T1a glottic cancer. Here, we assessed oncological and functional outcomes of T1a glottic squamous cell carcinoma (SCC) with TLM to supplement evidence from jurisdictions outside North America. METHODS: This study is a retrospective cohort study performed from a prospectively collected tertiary center institutional TLM database. Patients who were diagnosed with T1a glottic SCC and underwent TLM as their primary treatment were included. Functional outcomes were analyzed using the Voice Handicap Index-10 (VHI-10) questionnaire. Ultimate control with TLM only was considered to be those patients with locoregional control with repeat TLM procedures, but without addition of other modalities. Student's t-test was used to test significance and Kaplan-Meier survival analysis was used to assess oncological outcomes. RESULTS: 48 patients met study criteria. The mean follow-up time was 74 months. The 5-year locoregional, ultimate control with TLM only and laryngeal preservation rates were 83.2%, 90.4% and 100%, respectively. The overall survival and disease-specific survival were 87.2% and 100%, respectively. VHI-10 scores were available for 13/48 patients and mean scores improved non-significantly from pre-op (mean: 11.23; range: 2 to 30; median: 10) and post op (mean: 7.92; range: 0 to 18; median: 8) scoring (p-value = 0.15). Sub-stratification of voice data revealed a significant improvement between pre and post-operative scores (mean difference - 10.6, 95% CI: - 0.99 to - 20.21, p-value = 0.035) for patients with abnormal pre-operative scores (VHI > 11). CONCLUSION: To our knowledge, the current work represents one of the first North American studies to report both functional and oncologic outcomes for TLM treatment of T1a glottic SCC. The oncologic and functional outcomes presented here add to existing evidence in favor of TLM as a safe and effective primary treatment option for early staged T1a glottic cancer.

Massive Saddle Pulmonary Embolism in a Preterm Neonate With Successful Emergent Open Embolectomy.

Pulmonary embolism in the neonate is a rare, life-threatening emergency. Risk factors for neonatal pulmonary embolism (PE) include sepsis, asphyxia, prematurity, and vascular catheterisation. We report the case of a preterm neonate with a massive saddle pulmonary thrombosis of unidentified etiology. Prompt diagnosis by cardiology allowed an emergent lifesaving open surgical thrombectomy, underscoring the importance of efficient multidisciplinary teamwork. Pediatric health-care professionals must be aware of this rare entity when initial oxygen desaturation management fails, even when obvious risk factors for PE are not apparent. We emphasise the importance of seamless multidisciplinary communication and proactive surgical consultation.

L'embolie pulmonaire chez le nouveau-né est une urgence rare qui met la vie en danger. Les facteurs de risque d'embolie pulmonaire néonatale comprennent la septicémie, l'asphyxie, la prématurité et le cathétérisme vasculaire. Nous rapportons le cas d'un nouveau-né prématuré présentant une thrombose pulmonaire en selle massive d'origine indéterminée. Un diagnostic rapide par le service de cardiologie a permis la réalisation d'urgence d'une thrombectomie chi-rurgicale ouverte salvatrice, soulignant ainsi l'importance d'un travail d'équipe multidisciplinaire efficace. Les professionnels de la santé en pédiatrie doivent être au fait de cette entité rare lorsque la prise en charge initiale de la désaturation en oxygène échoue, même quand les facteurs de risque évidents d'une embolie pulmonaire ne sont pas apparents. Nous insistons sur l'importance d'une communication multidisciplinaire en continu et d'une consultation chirurgicale proactive.

Treatment Choices in Managing Bethesda III and IV Thyroid Nodules: A Canadian Multi-institutional Study.

OBJECTIVE: Patient-centered decision making is increasingly identified as a desirable component of medical care. To manage indeterminate thyroid nodules, patients are offered the options of surveillance, diagnostic hemithyroidectomy, or molecular testing. Our objective was to identify factors associated with decision making in this population. STUDY DESIGN: This is a retrospective cross-sectional study of patients with Bethesda III and IV thyroid nodules. SETTING: Multi-institutional. METHODS: Factors of interest included age, sex, socioeconomic status (SES), nodule size, institution, attending surgeon, surgeon payment model, and hospital type. Our outcome of interest was the initial management decision made by patients. RESULTS: A total of 956 patients were included. The majority of patients had Bethesda III nodules (n = 738, 77%). A total of 538 (56%) patients chose surgery, 413 (43%) chose surveillance, and 5 (1%) chose molecular testing. There was a significant variation in management decision based on attending surgeon (proportion of patients choosing surgery: 15%-83%; P≤.0001). Fee-for-service surgeon payment models (odds ratio [OR], 1.657; 95% CI, 1.263-2.175; P < .001) and community hospital settings (OR, 1.529; 95% CI, 1.145-2.042; P < .001) were associated with the decision for surgery. Larger nodule size, younger patients, and Bethesda IV nodules were also associated with surgery. CONCLUSION: While it seems appropriate that larger nodules, younger age, and higher Bethesda class were associated with decision for surgery, we also identified attending surgeon, surgeon payment model, and hospital type as important factors. Given this, standardizing management discussions may improve patient-centered shared decision making.

Medical Intervention Alone vs Surgical Drainage for Treatment of Peritonsillar Abscess: A Systematic Review and Meta-analysis.

OBJECTIVE: Peritonsillar abscesses (PTAs) are common emergency consultations for otolaryngologists. Medical management alone may offer satisfactory treatment without the risk associated with surgical drainage. Therefore, we performed a systematic review of medical treatment alone compared to surgical drainage for the treatment of PTA. DATA SOURCES: MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov. REVIEW METHODS: Studies comparing the outcomes of medically treated to surgically treated patients were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. All screening and data extraction were completed by 2 independent reviewers. Meta-analysis was performed using a random-effects model. Subgroup and sensitivity analyses were performed. RESULTS: Ten cohort studies and 2 randomized studies were included (ntotal = 33,468). Study quality was low, with only 1 study providing multivariable analysis. The combined rate of treatment failure in patients initially treated with medical management alone was 5.7% compared to 5.5% in the surgical group. There was no statistically significant difference in the odds of treatment failure between interventions through random-effects meta-analysis (odds ratio [OR], 1.10; 95% CI, 0.53-2.26; I 2 = 41%; P = .13). Subgroup analysis excluding pediatric-specific studies revealed similar odds of treatment failure when initially managed with medical intervention (OR, 0.92; 95% CI, 0.56-1.50; P = .39; I 2 = 0%). CONCLUSION: Meta-analysis of available studies demonstrated no difference in odds of treatment failure for patients with PTA managed through medical intervention alone compared to surgical intervention. These findings should be interpreted with caution due to high probability of bias and overall low quality of studies.

Regenerative nanobots based on magnetic layered double hydroxide for azo dye removal and degradation.

A highly regenerative multifunctional nanobot system, using Fe3O4@SiO2@MgFe-LDH nanoparticles, is developed for efficient removal of waterborne azo dyes and pharmaceuticals. Efficient capture of pollutants, powerful Fenton degradation, and superior materials regeneration lead to a simple and cost-effective wastewater remediation solution.

Chloride-accelerated Cu-Fenton chemistry for biofilm removal.

Biofilms present challenges to numerous industries. Herein, a simple approach was developed based on chloride-accelerated Fenton chemistry, where copper oxide nanoparticles facilitate efficient generation of reactive chlorine species for biofilm removal.

Highly Hybridizable Spherical Nucleic Acids by Tandem Glutathione Treatment and Polythymine Spacing.

Gold nanoparticle (AuNP)-templated spherical nucleic acids (SNAs) have been demonstrated as an important functional material in bionanotechnology. Fabrication of SNAs having high hybridization capacity to their complementary sequences is critical to ensure their applicability in areas such as antisense gene therapy and cellular sensing. The traditional salt-aging procedure is effective but tedious, requiring 1-3 days to complete. The rapid low-pH assisted protocol is efficient, but causes concerns related to nonspecific DNA adsorption to the AuNP core. To address these issues, we systematically compared the SNAs prepared by these two methods (salt-aging method and low-pH protocol). In terms of the number of complementary DNA that each SNA can bind and the average binding affinity of each thiolated DNA probe to its complementary strand, both methods yielded comparable hybridizability, although higher loading capacity was witnessed with SNAs made using the low-pH method. Additionally, it was found that nonspecific DNA binding could be eliminated almost completely by a simple glutathione (GSH) treatment of SNAs. Compared to conventional methods using toxic mercapto-hexanol or alkanethiols to remove nonspecific DNA adsorption, GSH is mild, cost-effective, and technically easy to use. In addition, GSH-passivated SNAs minimize the toxicity concerns related to AuNP-induced GSH depletion and therefore offer a more biocompatible alternative to previously reported SNAs. Moreover, rational design of probe sequences through inclusion of a polythymine spacer into the DNA sequences resulted in enhanced DNA loading capacity and stability against salt-induced aggregation. This work provides not only efficient and simple technical solutions to the issue of nonspecific DNA adsorption, but also new insights into the hybridizability of SNAs.

Chemisorption Mechanism of DNA on Mg/Fe Layered Double Hydroxide Nanoparticles: Insights into Engineering Effective SiRNA Delivery Systems.

Layered double hydroxide nanoparticles (LDH NPs) have attracted interest as an effective gene delivery vehicle in biomedicine. Recent advances in clinic trials have demonstrated the efficacy of Mg/Fe LDHs for hyperphosphatemia treatment, but their feasibility for gene delivery has not been systematically evaluated. As a starting point, we aimed to study the interaction between oligo-DNA and Mg/Fe LDH NPs. Our investigation revealed the chemisorption mechanism of DNA on Mg/Fe LDH surfaces, wherein the phosphate backbone of the DNA polymer coordinates with the metal cations of the LDH lattice via the ligand-exchange process. This mechanistic insight may facilitate future gene delivery applications using Mg/Fe LDH NPs.

Driving Adsorbed Gold Nanoparticle Assembly by Merging Lipid Gel/Fluid Interfaces.

Surface forces between inorganic nanoparticles and lipid bilayer is of great relevance to biophysics, medicine, and nanobiotechnology. Adsorbed nanoparticles may influence the fluidity of the underlying lipids, which may in turn influence nanoparticle assembly. Herein three types of lipids (DOPC, Tc = -20 °C; DMPC, Tc = 23 °C; and DPPC, Tc = 41 °C) are used, all with the same phosphocholine (PC) headgroup. Gold nanoparticle (AuNP) color change is monitored as a function of lipid phase transition temperature (Tc), surface ligands on AuNPs, and temperature. Liposomes with higher fluidity induce much faster aggregation of AuNPs. Aside from the kinetic aspect of faster diffusion on fluid bilayers, this faster color change is attributed to the local lipid gelation and merging of gelled regions to eliminate the interface between different lipid phases.

Adsorption of doxorubicin on citrate-capped gold nanoparticles: insights into engineering potent chemotherapeutic delivery systems.

Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates.