Splicing Machinery Is Impaired in Oral Squamous Cell Carcinomas and Linked to Key Pathophysiological Features.

Alternative splicing dysregulation is an emerging cancer hallmark, potentially serving as a source of novel diagnostic, prognostic, or therapeutic tools. Inhibitors of the activity of the splicing machinery can exert antitumoral effects in cancer cells. We aimed to characterize the splicing machinery (SM) components in oral squamous cell carcinoma (OSCC) and to evaluate the direct impact of the inhibition of SM-activity on OSCC-cells. The expression of 59 SM-components was assessed using a prospective case-control study of tumor and healthy samples from 37 OSCC patients, and the relationship with clinical and histopathological features was assessed. The direct effect of pladienolide-B (SM-inhibitor) on the proliferation rate of primary OSCC cell cultures was evaluated. A significant dysregulation in several SM components was found in OSCC vs. adjacent-healthy tissues [i.e., 12 out of 59 (20%)], and their expression was associated with clinical and histopathological features of less aggressiveness and overall survival. Pladienolide-B treatment significantly decreased OSCC-cell proliferation. Our data reveal a significantly altered expression of several SM-components and link it to pathophysiological features, reinforcing a potential clinical and pathophysiological relevance of the SM dysregulation in OSCC. The inhibition of SM-activity might be a therapeutic avenue in OSCC, offering a clinically relevant opportunity to be explored.

Mathematical Modeling of Vessel Geometry and Circumference in Microvascular Surgery.

Introduction: Microvascular anastomosis has traditionally been executed with a perpendicular transection through the vessel at the widest diameter to increase circumference and thus increase blood flow while decreasing resistance. In Chen's 2015 article, it was suggested that an "open Y" would improve vessel size match, and Wei and Mardini discuss angled transections of the vessels. This project aims to explore the geometric configurations feasible at the anastomotic transection and mathematically model the resulting hypothetical increases in circumference. Materials and Methods: The mathematical models were theoretically developed by our team. The formulas model increases in circumference of the transection at different distances in relation to the bifurcation of a blood vessel, as well as changes in circumference at different transection angulations. An in vitro exploration as to the anastomotic feasibility of each geometric cut was completed on ten poultry tissue specimens. Results: The mathematical models demonstrated the change in vessel circumference, with multiple geometric designs calculated, best shown through diagrams. For example, if the vessel width is 1 mm, the distance from the increasing vessel diameter to the final bifurcation is 1 mm, and the bifurcation angle is 45°, the circumference of the transected vessel increases by 82.8%. Models of transections at different angulations, for instance 30°, 45°, and 60°, yield an increase in elliptical circumference of 8.0%, 22.5%, and 58.1%, respectively. Additional derivations calculate the elliptical circumference at any angle in a single vessel, and at any angle in a bifurcating vessel. Conclusion: The theoretical and clinical aim of this project is to increase awareness of the anastomotic creativity and mathematically demonstrate the optimal anastomotic geometry, which has not been objectively explored to our knowledge. An in vivo study would further support clinical improvements, with the aim to map postoperative fluid dynamics through the geometric anastomoses.

Does Transcervical Styloidectomy for Eagle Syndrome Improve Quality of Life?

PURPOSE: Eagle syndrome is an uncommon disorder that significantly impacts the quality of life (QoL) of patients. No formal QoL study has been carried out on a population of Eagle syndrome patients treated via transcervical approach. We aim to evaluate and analyze the outcomes of the patients with Eagle syndrome treated with transcervical styloidectomy via our modified QoL survey. METHODS: A retrospective cohort study was utilized for patients with Eagle syndrome who underwent transcervical styloidectomy at our institution from January 2008 until December 2018. Two QoL surveys were sent to subjects. Patients were asked preoperatively and postoperatively about the presence and intensity of pain, alteration of speech, diet or chewing, limitations of daily activity, mobility or recreation, and the presence of anxiety or mood disturbances related to the disease. The styloid length on preoperative computed tomography scans and the length of the surgical specimen were obtained, and correlations with the Numeric Pain Rating Scale (NPRS) were analyzed. Spearman's rank correlation coefficient was used to determine numerical correlation. Data are expressed as mean ± standard deviation, and P value less than .05 was considered statistically significant. RESULTS: The study sample comprised 10 patients with Eagle syndrome who underwent transcervical styloidectomy. Eight patients underwent unilateral styloidectomy, and 2 patients were bilateral. Most patients were female (80%) with a mean age of 46.0. Preoperative NPRS score averaged 5.5 ± 2.7 (range 1 to 10) and postoperative NPRS was 2.1 ± 1.4 (range 0 to 4) (P = .008). No correlation was found between preoperative or postoperative NRPS score and preoperative styloid length and length of styloid resected. QoL survey showed a significant improvement in neck mobility and the anxiety felt by the patients. The survey showed that all patients would recommend surgery to a friend or family member with similar symptoms. Seven patients (70%) would recommend the operation as primary treatment, and the rest would recommend it after conservative options fail. CONCLUSIONS: Transcervical styloidectomy was associated with a statistically significant decrease in NPRS and positive QoL changes for patients operated for Eagle syndrome at our institution.

Molecular and Clinical Implications of Somatostatin Receptor Profile and Somatostatin Analogues Treatment in Oral Cavity Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) incidence has increased by 50% over the last decade. Unfortunately, surgery and adjuvant radiotherapy and chemotherapy are still the mainstream modality of treatment, underscoring the need for alternative therapies. Somatostatin-analogues (SSA) are efficacious and safe treatments for a variety of tumors, but the presence of somatostatin-receptors (SSTs) and pharmacological effects of SSA on OSCC are poorly known. In this study, we demonstrated that SST2 and SST3 levels were significantly higher in OSCC, compared to adjacent healthy control tissues. SST2 expression was associated with less regional metastasis and a lower recurrence rate. Moreover, SST2 was elevated in OSCC and associated with histopathological good prognosis factors, such as high peritumoral inflammation, smaller depth of invasion, and expansive vs. infiltrative front of tumor invasion. Importantly, treatment with different SSA (octreotide, lanreotide, and pasireotide) significantly reduced cell-proliferation in OSCC primary cell cultures. Altogether, this study demonstrated that SST2 is overexpressed in OSCC vs. healthy tissues and could represent a novel prognostic biomarker, since its expression is associated with tumors that show better prognostic factors and less recurrent rate. Moreover, our data unveil clear antitumoral effects of SSAs on OSCC, opening new avenues to explore their potential as targeting therapy to OSCC.

COVID-19 pneumonia treated with ultra-low doses of radiotherapy (ULTRA-COVID study): a single institution report of two cases.

INTRODUCTION: Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic, healthcare systems have focused their efforts into finding a treatment to avoid the fatal outcomes of severe acute respiratory syndrome due to coronavirus­2 (SARS-CoV-2). Benefits and risks of systemic treatments remain unclear, with multiple clinical trials still ongoing. Radiotherapy could play a role in reducing the inflammatory response in the lungs and relieve life-threatening symptoms. METHODS: We designed a prospective study of Ultra-Low Doses of Therapy with Radiation Applied to COVID-19 (ULTRA-COVID) for patients who suffer pneumonia, are not candidates for invasive mechanical ventilation and show no improvement with medical therapy. RESULTS: We present the preliminary results of two patients diagnosed with COVID-19 pneumonia treated with ULTRA-COVID. After one radiotherapy session, significant clinical response and a good radiological response was observed in both cases, resulting in both patients being discharged from hospital in less than 2 weeks after radiation treatment. CONCLUSION: Preliminary clinical and radiological results suggest a potential benefit of treating COVID-19 pneumonia with ULTRA-COVID. ClinicalTrials.gov Identifier: NCT04394182.

Chimeric profunda artery perforator - gracilis flap: A computed tomographic angiography study and case report.

BACKGROUND: The possibility of harvesting the profunda artery perforator (PAP) flap in a chimeric configuration together with the innervated gracilis muscle may be a good option for dynamic reconstruction following total glossectomies. In this paper, we present a retrospective radiological study, which evaluates the presence and characteristics of the anatomical variation of the chimeric PAP - gracilis flap. METHODS: The study sample comprised 66 patients (132 legs), 38 men, and 28 women with an average age of 56 ± 2 years old, who underwent head and neck reconstruction with a free flap. Preoperative computed tomographic angiography (CTA) was used for morphologic analysis. We present a case report of a patient with a total glossectomy reconstructed with this flap. RESULTS: A perforator in the PAP area joining with the main pedicle of the gracilis muscle was found in 38 legs (28.8%). Mean length of the pedicle from the profunda femoral artery to the point where the perforator in the PAP area and the pedicle of the gracilis joined was 3.0 ± 0.3 cm. Differences in the existence of this vascular configuration were not significant comparing groups by sex, BMI, height, side or source vessel. Motion of the new tongue was documented clinically and with electromyography. The patient achieved an intelligible speech and normal diet. CONCLUSIONS: Preoperative evaluation is necessary to assess the existence of a perforator in the PAP area joining with the main pedicle of the gracilis muscle. This chimeric flap has been demonstrated useful for dynamic reconstruction of a patient with a total glossectomy.