Use of the 445-nm Blue Laser for Management of Early Glottic Carcinoma: Preliminary 1-Year Results.

OBJECTIVE: To analyze oncological efficacy and voice outcomes of the 445-nm blue laser (BL) in the treatment of early glottic carcinoma and compare results with the 532-nm potassium-titanyl-phosphate (KTP) laser. STUDY DESIGN: Single institution, retrospective chart review. METHODS: All patients who underwent microlaryngoscopic KTP or BL laser excision of early glottic carcinoma from 2018 to the present day with at least 1-year follow-up were included. Primary and recurrent disease, including radiation and surgical failures, were included. Demographic data, voice outcomes and oncologic outcomes were compared between the two laser groups. RESULTS: Forty-nine patients met the inclusion criteria for the BL group and 88 for the KTP group, with average follow-up of 635 and 1236 days, respectively. Oncologic outcomes were not significantly different, with disease-specific survival rates of 95.9% for BL and 100% for KTP (p = 0.13), organ preservation rates of 98.0% for BL and 95.6% for KTP (p = 0.39), and local control rates of 93.9% for BL and 92.1% for KTP (p = 0.81). Both BL and KTP groups showed significant improvement in CAPE-V (p = 0.04, 0.006 respectively) and VHI-10 scores (p = 0.003, <0.00001) following surgery. CONCLUSIONS: Photoangiolytic removal of early glottic carcinoma with BL appears to be equally safe and effective as with KTP laser at minimum one-year follow-up, and with excellent voice outcomes. Additional study will be warranted over time to assess long-term outcomes in BL patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Polysomnogram outcomes in patients with laryngomalacia and obstructive sleep apnoea treated surgically versus non-surgically.

OBJECTIVE: To compare supraglottoplasty versus non-surgical treatment in children with laryngomalacia and mild, moderate and severe obstructive sleep apnoea. METHODS: Patients were classified based on their obstructive apnoea hypopnoea index on initial polysomnogram, which was compared to their post-treatment polysomnogram. RESULTS: Eighteen patients underwent supraglottoplasty, and 12 patients had non-surgical treatment. The average obstructive apnoea hypopnoea index after supraglottoplasty fell by 12.68 events per hour (p = 0.0039) in the supraglottoplasty group and 3.3 events per hour (p = 0.3) in the non-surgical treatment group. Comparison of the change in obstructive apnoea hypopnoea index in the surgical versus non-surgical groups did not meet statistical significance (p = 0.09). CONCLUSION: All patients with laryngomalacia and obstructive sleep apnoea had a statistically significant improvement in obstructive apnoea hypopnoea index after supraglottoplasty irrespective of obstructive sleep apnoea severity, whereas patients who received non-surgical treatment had more variable and unpredictable results. Direct comparison of the change between the two groups did not find supraglottoplasty to be superior to non-surgical treatment. Larger prospective studies are recommended.

Porphyrin-based supramolecular nanofibres as a dynamic and activatable photosensitiser for photodynamic therapy.

Photodynamic therapy (PDT) represents a promising treatment modality for a range of cancers and other non-malignant diseases due to its non-invasive nature arising from the light-dependent activation. However, PDT has not been the first-line treatment of cancer thus far as a consequence of, among others, the lack of effective transport and activation strategies, and the undesired side effect caused by skin photosensitisation induced by the "always on" photosensitisers. To overcome this "Achilles' heel", we present herein a non-covalent approach to construct a one-component dynamic supramolecular nanophotosensitising system based on a carefully designed porphyrin. The control of the photoactivities of the resulting supramolecular fibres lies in the spatiotemporal control of the monomer-polymer equilibrium. Both the thermodynamics and kinetics of this nanosystem have been carefully studied by different techniques. Moreover, in vitro and in vivo studies have also been performed, showing that these supramolecular aggregates exhibit facile cell internalisation and progressive disassembly after being endocyted by targeted cells, leading to activation of the photosensitising units and eventually cell death and tumour eradication under photoirradiation.

Geographic disparities in head and neck cancer survival in Upstate New York 2011-2019.

PURPOSE: To examine the association between distance to care-center and urban-rural residence on 5-year overall survival (OS) from head and neck cancer (HNC). MATERIALS AND METHODS: Five-year OS was retrospectively measured from date of initial diagnosis for patients with HNC treated at a single tertiary care center. Distances were calculated based on ZIP code of patient's residence and care center. Multilevel Weibull regression was used to adjust for confounders and identify disparities in 5-year all-cause mortality. RESULTS: A total of 670 patients included in study. Multivariable analysis revealed older age or late-stage cancer at diagnosis, and HPV negative status were associated with poorer OS. Patients residing in isolated small rural town (HR = 2.20, p = 0.015) or small rural town (HR = 2.07, p = 0.015) had lower OS. Distance to care center was not associated with OS (HR = 0.996, p = 0.11). CONCLUSIONS: Greater rurality was associated with poorer OS among HNC patients in Upstate New York.

A self-assembled subphthalocyanine-based nanophotosensitiser for photodynamic therapy.

A subphthalocyanine substituted with nine tetra(ethylene glycol) chains on the periphery has been synthesised. This novel amphiphilic and cone-shaped compound can self-assemble in water into spherical nanoparticles with a hydrodynamic diameter of 154 nm. These nanoparticles can be taken up readily by cancer cells and localised predominately in lysosomes where they disassemble gradually, leading to activation in fluorescence emission and, photocytotoxicity, showing IC50 values of as low as 1.2 µM.

Elucidating dynamic behavior of synthetic supramolecular polymers in water by hydrogen/deuterium exchange mass spectrometry.

A comprehensive understanding of the structure, self-assembly mechanism, and dynamics of one-dimensional supramolecular polymers in water is essential for their application as biomaterials. Although a plethora of techniques are available to study the first two properties, there is a paucity in possibilities to study dynamic exchange of monomers between supramolecular polymers in solution. We recently introduced hydrogen/deuterium exchange mass spectrometry (HDX-MS) to characterize the dynamic nature of synthetic supramolecular polymers with only a minimal perturbation of the chemical structure. To further expand the application of this powerful technique some essential experimental aspects have been reaffirmed and the technique has been applied to a diverse library of assemblies. HDX-MS is widely applicable if there are exchangeable hydrogen atoms protected from direct contact with the solvent and if the monomer concentration is sufficiently high to ensure the presence of supramolecular polymers during dilution. In addition, we demonstrate that the kinetic behavior as probed by HDX-MS is influenced by the internal order within the supramolecular polymers and by the self-assembly mechanism.

Unveiling Polymerization Mechanism in pH-regulated Supramolecular Fibers in Aqueous Media.

An amine functionalized C3 -symmetric benzotrithiophene (BTT) monomer has been designed and synthetized in order to form pH responsive one-dimensional supramolecular polymers in aqueous media. While most of the reported studies looked at the effect of pH on the size of the aggregates, herein, a detailed mechanistic study is reported, carried out upon modifying the pH to trigger the formation of positively charged ammonium groups. A dramatic and reversible change in the polymerization mechanism and size of the supramolecular fibers is observed and ascribed to the combination of Coulombic repulsive forces and higher monomer solubility. Furthermore, the induced frustrated growth of the fibers is further employed to finely control the one-dimensional supramolecular polymerisation and copolymerization processes.

Resistive switching in an organic supramolecular semiconducting ferroelectric.

The combination of switchable dipolar side groups and the semiconducting core of the newly synthetized C3-symmetric benzotrithiophene molecule (BTTTA) leads to an ordered columnar material showing continuous tunability from injection- to bulk-limited conductivity modulation.

From isodesmic to highly cooperative: reverting the supramolecular polymerization mechanism in water by fine monomer design.

Two structurally-similar discotic molecules able to self-assemble in water, forming supramolecular fibers, are reported. While both self-assembled polymers are indistinguishable from a morphological point-of-view, a dramatic change in their polymerization mechanism is observed (i.e., one self-assemble via an isodesmic mechanism, while the other shows one of the highest cooperativity values).

Clinical characterization and mutation spectrum in Caribbean Hispanic families with Lynch syndrome.

Lynch syndrome (LS) is an inherited form of colorectal cancer (CRC) caused by germline mutations in the mismatch repair (MMR) genes. It accounts for approximately 5% of all CRCs. The prevalence of LS among US Hispanics is unknown. The objective of this study was to describe the germline mutations of LS in Caribbean Hispanics from Puerto Rico and Dominican Republic. A total of 89 subjects were recruited through the Puerto Rico Familial Colorectal Cancer Registry and were classified according to Amsterdam and Bethesda clinical guidelines. For those tumors with lack of expression of MMR protein, gene sequencing was ordered. A total of 35 individuals with deficient MMR system were identified: 22 had MMR mutations and 13 had tumors with absent MMR protein expression. Our results show that the mutation spectrum of Caribbean Hispanic LS patients was composed mostly of MSH2 (66.7%) mutations, followed by MLH1 (25.0%). One mutation was identified in MSH6 (8.3%). A previously unidentified mutation in MLH1 gene c.2044_2045del was found in one Caribbean Hispanic family. MMR mutation-positive individuals were found to be more likely to have a prominent family history of CRC and tumors located at the proximal colon. Compared to MSH2 mutation carriers, MLH1 mutation-positive individuals were more likely to have a strong family history of CRC and LS associated cancers. Furthermore, insurance coverage for genetic testing was found to be limited in the study population with 65.1% of the individuals recruited were denied coverage. This report presents the first description of the mutation spectrum and clinicopathologic characteristics of LS Caribbean Hispanics patients.