Hyaluronic acid carrier-based photodynamic therapy for head and neck squamous cell carcinoma.

PURPOSE: Conventional photosensitizers for photodynamic therapy (PDT) typically have wide tissue distribution and poor water solubility. A hyaluronic acid (HA) polymeric nanoparticle with specific lymphatic uptake and highly water solubility was developed to deliver pyropheophorbide-a (PPa) for locally advanced head and neck squamous cell carcinoma (HNSCC) treatment. METHODS AND RESULTS: PPa was chemically conjugated to the HA polymeric nanoparticle via an adipic acid dihydrazide (ADH) linker. The conjugates were injected subcutaneously in a region near the tumor. Near-infrared (NIR) imaging was used to monitor distribution, and diode laser was used to activate PPa. The singlet oxygen generation efficiency of PPa was not affected by conjugation to HA nanoparticles at a PPa loading degree of 1.89 w.t.%. HA-ADH-PPa inhibited human HNSCC MDA-1986 cell growth only when photo-irradiation was applied. After HA-ADH-PPa treatment and radiation, NU/NU mice bearing human HNSCC MDA-1986 tumors showed reduced tumor growth and significantly enhanced survival time compared with an untreated group (p < 0.05). CONCLUSIONS: These results demonstrate that HA-ADH-PPa could be useful for in vivo locoregional photodynamic therapy of HNSCC.

Use of an adherent fenestrated drape to anchor an adjacent vertical sterile surgical towel.

Vertical surgical sites or those on reclining patients often present a challenge when establishing and securing a sterile field. The drape or towel most proximal to the physician is often vertically oriented. The forces of gravity and movements of surgery can shift or detach this vertical drape. Sterile clamps are not always available or are needed for securing other instruments. We present a method to secure this vulnerable drape using a central fenestrated adherent drape.

Formulation and preclinical evaluation of a toll-like receptor 7/8 agonist as an anti-tumoral immunomodulator.

The toll-like receptor 7 and 8 (TLR7/8) agonist Resiquimod (R848) has been recognized as a promising immunostimulator for the treatment of cutaneous cancers in multiple clinical trials. However, systemic administration of R848 often results in strong immune-related toxicities while having limited therapeutic effects to the tumor. In the present study, a prodrug-based nanocarrier delivery system was developed that exhibited high therapeutic efficiency. R848 was conjugated to α-tocopherol to constitute an R848-Toco prodrug, followed by formulating with a tocopherol-modified hyaluronic acid (HA-Toco) as a polymeric nano-suspension. In vitro evaluation showed that the delivery system prolonged the release kinetics while maintaining TLR agonist activities. When administered subcutaneously, the nano-suspension formed a depot at the injection site, inducing localized immune responses without systemic expansion. This formulation also suppressed tumor growth and recruited immune cells to the tumor in a murine model of head and neck cancer. In a preclinical canine study of spontaneous mast cell tumors, the treatment led to a 67% response rate (three partial remissions and one complete remission).

CELLULITIS: A mnemonic to increase accuracy of cellulitis diagnosis.

Cellulitis, a bacterial infection of the skin and subcutaneous tissue, is often misdiagnosed. Cellulitis accounts for a large number of all infectious disease-related hospitalizations in the U.S. Cellulitis can be challenging to diagnose since it lacks pathognomonic findings. We reviewed all articles on cellulitis within the last 20 years that included a statistical analysis, with odds ratios (OR), of specific clinical features of cellulitis. We then constructed a mnemonic encompassing the features with the highest odds ratios. Our mnemonic is CELLULITIS for cellulitis history, edema, local warmth, lymphangitis, unilateral, leukocytosis, injury, tender, instant onset, and systemic signs. The first characteristic has the highest OR and may be the easiest to recall: past episode(s) of cellulitis.