Peelerasch0477

Objectives To examine survival endpoints in patients with tumor (T)4b oral cavity squamous cell carcinoma (OCSCC) with pathologically proven masticator space invasion treated with primary surgery followed by adjuvant therapy. Study design Retrospective review at an academic cancer center. Methods Twenty-five patients with T4b OCSCC with pathologic masticator space invasion were treated with primary surgery from May 2012 to December 2016. Only patients with ≥ 2 years follow-up from date of surgery were included. Sixteen patients received adjuvant chemoradiation. Results Median follow-up time was 39 months from date of surgery. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival at 24 months were 44.0%, 63.2%, and 52.6%, respectively. On univariate analyses, adjuvant chemoradiation was associated with improved OS. Advanced age and prolonged length of hospital stay was associated with worse OS. Conclusion For pT4b OCSCCA involving the masticator space, primary surgical resection followed by adjuvant chemoradiation demonstrates 24-month DSS of > 50% and OS of 44%. Level of evidence 4 Laryngoscope, 2020.Objectives During crizotinib clinical evaluation, visual disturbances, generally of grade 1 severity, were frequently reported adverse events (AE). Consequently, ophthalmologic assessments were included in a patient subgroup enrolled in PROFILE 1001 (NCT00585195), a phase 1, open-label, single-arm trial of crizotinib in patients with advanced non-small-cell lung cancer and are reported here. Materials and methods At least 30 patients were required to undergo ophthalmologic assessments, including best-corrected visual acuity (BCVA), refractive error, pupil size, slit-lamp anterior segment biomicroscopy, intraocular inflammation, intraocular pressure, retinal fundoscopic exams, fundus photography, ocular characteristics, and optical coherence tomography (OCT). Scheduled assessments included those at baseline, Cycle 1 Day 15, Cycle 3 Day 1 (C3D1), annually during treatment, and end of treatment (28 days after last crizotinib dose). Results Thirty-three patients completed all required ophthalmologic assessments t; and of 9 patients without an all-causality ocular TEAE, 4/9 (44.4 %) had ≥1 abnormal ophthalmologic finding and 5/9 (55.6 %) had none. Of the 18 patients with ≥1 abnormal ophthalmologic finding, 9 (50 %) had preexisting ocular conditions. Conclusion During crizotinib treatment, ophthalmologic changes from baseline did not appear to be associated with patient-reported ocular TEAEs. Abnormal ophthalmologic findings occurred in the context of preexisting conditions for a number of patients. No ophthalmologic changes from baseline or ocular all-causality TEAEs required permanent treatment discontinuation.Interleukin-31 (IL-31) is a major protein involved in severe inflammatory skin disorders. Its signaling pathway is mediated through two type I cytokine receptors, IL-31RA (also known as the gp130-like receptor) and the oncostatin M receptor (OSMR). Understanding molecular details in these interactions would be helpful for developing antagonist anti-IL-31 monoclonal antibodies (mAbs) as potential therapies. Previous studies suggest that human IL-31 binds to IL-31RA and then recruits OSMR to form a ternary complex. In this model, OSMR cannot interact with IL-31 in the absence of IL-31RA. In this work, we show that feline IL-31 (fIL-31) binds independently with feline OSMR using surface plasmon resonance, an enzyme-linked immunosorbent assay, and yeast surface display. Moreover, competition experiments suggest that OSMR shares a partially overlapping epitope with IL-31RA. We then used deep mutational scanning to map the binding sites of both receptors on fIL-31. In agreement with previous studies of the human homologue, the binding site for IL31-RA contains fIL-31 positions E20 and K82, while the binding site for OSMR comprises the "PADNFERK" motif (P103-K110) and position G38. However, our results also revealed a new overlapping site, composed of positions R69, R72, P73, D76, D81, and E97, between both receptors that we called the "shared site". FRAX486 concentration The conformational epitope of an anti-feline IL-31 mAb that inhibits both OSMR and IL-31RA also mapped to this shared site. Combined, our results show that fIL-31 binds IL-31RA and OSMR independently through a partially shared epitope. These results suggest reexamination of the putative canonical mechanisms for IL-31 signaling in higher animals.Introduction Oncoplastic breast conserving surgery (OBCS) can cause breast asymmetry. Although contralateral breast surgery to achieve symmetry was offered to these patients, the uptake of symmetrisation was variable. We aimed to determine the factors that deter patients with breast cancer undergoing OBCS from taking up symmetrisation. Methods All patients with breast cancer who underwent OBCS of displacement type but no symmetrisation were prospectively surveyed to explore social, economic, psychological and physical reasons against symmetrisation. Results 28 patients participated in a survey administered at a mean 21.6 (range 2-47) months after OBCS. A combination of factors, such as worry and desire to treat breast cancer first (67.9%), not being overly concerned about breast cosmesis (57.1%) and fear of pain from additional operation (28.6%) deterred patients from immediate symmetrisation. Worry and desire to treat breast cancer first was the most important single factor for 50% of patients. Reasons for no delayed symmetrisation included not being overly concerned about breast cosmesis (70.4%), fear of breast cancer recurrence (48.1%) and being happy with current breast cosmesis (33.3%), with the former two reasons equally cited as the single most important deterrent by 30% of patients each. Conclusion A combination of factors may deter patients from symmetrisation. The most significant factors deterring OBCS among patients were worry and desire to treat breast cancer first for immediate symmetrisation, and not being overly concerned about breast cosmesis and fear of breast cancer recurrence for delayed symmetrisation. Reassurance of these patients may increase their uptake of symmetrisation, thereby improving patient cosmesis and satisfaction.