A highly sensitive molecular structural probe applied to in situ biosensing of metabolites using PEDOT:PSS.

A large amount of research within organic biosensors is dominated by organic electrochemical transistors (OECTs) that use conducting polymers such as poly(3,4-ethylene dioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS). Despite the recent advances in OECT-based biosensors, the sensing is solely reliant on the amperometric detection of the bioanalytes. This is typically accompanied by large undesirable parasitic electrical signals from the electroactive components in the electrolyte. Herein, we present the use of in situ resonance Raman spectroscopy to probe subtle molecular structural changes of PEDOT:PSS associated with its doping level. We demonstrate how such doping level changes of PEDOT:PSS can be used, for the first time, on operational OECTs for sensitive and selective metabolite sensing while simultaneously performing amperometric detection of the analyte. We test the sensitivity by molecularly sensing a lowest glucose concentration of 0.02 mM in phosphate-buffered saline solution. By changing the electrolyte to cell culture media, the selectivity of in situ resonance Raman spectroscopy is emphasized as it remains unaffected by other electroactive components in the electrolyte. The application of this molecular structural probe highlights the importance of developing biosensing probes that benefit from high sensitivity of the material's structural and electrical properties while being complimentary with the electronic methods of detection.

Immunotherapy for the treatment of perineural spread in cutaneous head and neck squamous cell carcinoma: Time to rethink treatment paradigms.

BACKGROUND: Immune checkpoint inhibitors have shown promising antitumour activity. Application in head and neck cutaneous squamous cell carcinoma (cSCC) large nerve perineural spread (PNS) is limited. METHODS: Retrospective review of 13 patients with PNS receiving anti-PD-1 therapy from September 2017 to May 2021 is presented. Primary endpoints were objective response (complete or partial response) and median time to progression, determined by Head and Neck Multi-Disciplinary Team (MDT) and independent radiology review of magnetic resonance imaging (MRI) and/or computed tomography/positron emission tomography (CT/PET). RESULTS: Objective response was observed in 9/13 patients (69%), with complete response in 6 (46%) and partial response in 3 patients (23%). Median time to response was 2.1 months (IQR 1.8-2.7 months). There were 3 (23%) patients with progressive disease, with median time to progression of 3.5 months. There were no grade 3-4 treatment related adverse events. CONCLUSIONS: This case series supports developing evidence for anti-PD-1 checkpoint inhibitor therapy for perineural spread, supporting future prospective clinical trials in this patient population.

Adenoid cystic carcinoma: a review of clinical features, treatment targets and advances in improving the immune response to monoclonal antibody therapy.

The natural history of adenoid cystic carcinoma (ACC) is relentless, defined by treatment failure heralded by locoregional recurrence and distant metastatic disease. In this review, we present an update of clinical features, molecular classification, current targeted therapies, immune landscapes and novel treatment targets with their respective clinical trials. The presented results are defined by a lack of overall response rate and limited progression free survival, with restriction to stable disease. In addition, ACC is resistant to immune checkpoint inhibition due to low tumour immunogenicity and lack of PD-L1 expression. Here we present a new prospective research paradigm for ACC, including the potential to target prostate specific membrane antigen (PSMA) and the potential for manipulation of target receptors in the clinic. The presentation of this review aims to promote future research to improve response rates and outcomes for therapeutics undergoing clinical trial in ACC.

Trans-oral robotic surgery: a safe and effective tool in head and neck surgery in an Australian rural setting.

BACKGROUND: Trans-oral robotic surgery (TORS) facilitates surgical resection of tumours as an alternative to open surgery and has demonstrated favourable oncological results. Given the novelty of TORS and the paucity of evidence on TORS-specific complications in a rural setting, we report our experience with TORS at an Australian rural head and neck centre. METHODS: A retrospective review of all robotic cases performed at a regional head and neck centre in Queensland was undertaken from 2014 to 2019. Patient demographics, pre-operative surgical risk, complications and outcomes such as margins and cancer recurrence were recorded. Complications were graded based on the Clavien-Dindo grading system. Descriptive statistics were used to present patient characteristics and statistical analyses were performed using Stata. RESULTS: Forty-two TORS surgeries were performed. Twenty-one had histology confirming malignancy. There were no adverse intraoperative effects. Overall, seven patients (16.7%) had at least one complication. Four were recorded as a Clavien-Dindo 3b (post-operative bleed, wound infection and drain dislodgment). Of two cases with residual positive margins, one declined further surgery, and another received chemoradiotherapy. One patient recurred with distant metastatic disease, and another had locoregional nodal recurrence. The distribution of complications was significant across the pre-operative risk categories for both American Society of Anaesthesiologists and surgical risk score (P = 0.02). CONCLUSION: TORS in a rural head and neck centre is a safe and viable treatment option for patients so long as this is undertaken with appropriate training, mentorship and teamwork.

Outpatient surgical management of non-melanoma skin cancers of the head and neck in a regional centre: an analysis of costs and outcomes.

BACKGROUND: Non-melanoma skin cancer is the most commonly diagnosed malignancy in Australia. Lesions of the head and neck are often outside the scope of primary care providers. The challenges of cancer care in regional Australia necessitate careful resource planning. This study presents an outpatient model that minimizes health service cost with local general practitioner follow-up. METHODS: A retrospective review of 105 patients with 122 skin lesions in a dedicated Facial Lesion Assessment Management and Excision clinic was performed from July 2018 to 2019. Clinical outcomes, patient travel and cost analysis/comparison were recorded. RESULTS: There were 85 malignant cases with 59 basal cell carcinomas and 25 squamous cell carcinomas. For basal cell carcinoma, clear margins (≥3 mm), close margins (<3 mm) and positive margins were achieved in 24 (48%), 23 (46%) and three (6%) cases, respectively. For squamous cell carcinoma, clear margins (≥5 mm), close margins (<5 mm) and positive margins were achieved in seven (38.8%), 11 (61.1%) and none (0%) of the cases, respectively. Complications included one haematoma and two wound infections. For 37% of patients living >100 km from the department, 72.3% had local general practitioner follow-up. Inpatient cost was $2870, $5697 and $9300 for primary closure, local flap and full-thickness skin graft, respectively, and outpatient cost was $746 for a single facial lesion. CONCLUSION: This study presents a cost-effective model for the management of non-melanoma skin cancers with improved departmental efficiency and streamlined patient care in an outpatient skin cancer management model in a regional centre.

Utility of hydroxypropylmethylcellulose acetate succinate (HPMCAS) for initiation and maintenance of drug supersaturation in the GI milieu.

PURPOSE: To identify materials and processes which effect supersaturation of the GI milieu for low solubility drugs in order to increase oral bioavailability. METHODS: A variety of small and polymeric molecules were screened for their ability to inhibit drug precipitation in supersaturated solutions. The best polymeric materials were utilized to create spray-dried dispersions (SDDs) of drug and polymer, and these were tested for drug form and homogeneity. Dispersions were tested in vitro for their ability to achieve and maintain drug supersaturation, for a variety of drug structures. RESULTS: Of the 41 materials tested, HPMCAS was the most effective at maintaining drug supersaturation. Drug/HPMCAS SDDs were consistently more effective at achieving and maintaining drug supersaturation in vitro than were SDDs prepared with other polymers. Drug/HPMCAS SDDs were effective in vitro for eight low solubility drugs of widely varying structure. Drug/HPMCAS SDDs were more effective at achieving and maintaining supersaturation than were rotoevaporated Drug/HPMCAS dispersions or physical mixtures of Drug and HPMCAS. The degree of achievable drug supersaturation increased with increasing polymer content in the SDD. The drug in Drug /HPMCAS SDDs was amorphous, and the dispersions were demonstrated to have a single glass transition and were thus homogeneous. CONCLUSION: HPMCAS has been identified as a uniquely effective polymer for use in SDDs of low solubility drugs, with broad applicability across a variety of drug structures and properties.