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.

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.

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.

The thin profunda femoral artery perforator flap for tongue reconstruction.

BACKGROUND: With the ongoing global epidemic of obesity in the Western countries, thigh flaps such as the profunda artery perforator (PAP) free flap, have been less favorable for glossectomy reconstruction due to large bulk of adipose tissue associated with traditional subfascial harvest. In this article, we present a series of 10 patients who underwent reconstruction with suprafascial PAP free flaps following oncologic tongue resection. METHODS: Our series included six men and four women with an average age of 53.9 years old (range, 28-71 years). All patients underwent preoperative computed tomographic angiography (CTA) for selection of the most suitable perforator and preoperative design of its customized thickness. Flap elevation was performed at the superficial fascia layer while modifying the plane of dissection according to the specific bulk needs in each case. RESULTS: Flaps survived in nine patients; one flap failed due to vasospasm. Mean pedicle length was 7.4 cm (range, 6-8 cm). Skin paddle dimensions varied between 8 × 6 and 15 × 9 cm. Flaps thicknesses ranged from 0.4 to 3 cm. Functional outcome was evaluated at 6 months follow up: good speech and deglutition functional outcomes relative to extent of resection were observed. CONCLUSIONS: The dissection above the superficial fascia layer represents an important refinement to the traditional fasciocutaneous PAP flap. Flap thickness can be tailored to avoid excess of bulk in the medial thigh observed in larger BMI populations.

Customized Soft Tissue Free Flaps in Head and Neck Reconstruction.

The integration of imaging technologies such as computed tomography angiography and color Doppler ultrasonography are transforming soft tissue free flap reconstruction. The search for thinner and more refined flaps has expanded indications for flaps harvested from donor sites that were not commonly used in head and neck reconstruction. This article explores how these tools and techniques facilitate precise flap selection, thickness, and design customization based on detailed patient preoperative perforator anatomy and vascular configuration mapping. Optimizing outcomes with tailored flap designs improves surgical accuracy and patient-specific results in soft tissue reconstruction.

Surgical Navigation and CAD-CAM-Designed PEEK Prosthesis for the Surgical Treatment of Facial Intraosseous Vascular Anomalies.

Background: Intraosseous vascular anomalies in the facial skeleton present significant diagnostic and therapeutic challenges due to complex anatomy. These anomalies represent about 0.5-1% of bony neoplastic and tumor-like lesions, usually presenting as a firm, painless mass. Most described intraosseous vascular malformations are venous malformations (VMs) and, more rarely, arteriovenous malformations. Objectives: The objectives of this work are to show our experience, protocol and the applications of computer planning, virtual surgery, CAD-CAM design, surgical navigation, and computer-assisted navigated piezoelectric surgery in the treatment of facial intraosseous vascular anomalies and to evaluate the advantages and disadvantages. Methods: Three females and one male with periorbital intraosseous vascular anomalies were treated using en-block resection and immediate reconstruction with a custom-made PEEK prosthesis. One lesion was in the supraorbital rim and orbital roof, one in the frontal bone and orbital roof, and two in the zygomatic region. We accomplished the resection and reconstruction of the lesion using virtual planning, CAD-CAM design, surgical navigation and piezoelectric device navigation. Results: There were no complications related to the surgery assisted with navigation. With an accuracy of less than 1 mm, the procedure may be carried out in accordance with the surgical plan. The surgeon's degree of uncertainty during deep osteotomies and in locations with low visibility was decreased by the use of the navigated piezoelectric device. Conclusions: Resection and reconstruction of facial intraosseous vascular anomalies benefit from this new surgical strategy using CAD-CAM technologies, computer-assisted navigated piezoelectric surgery, and surgical navigation.

Increased Reliability in Medial Canthal Tendon Reposition in Nasoorbitoethmoidal Fractures with Computer-assisted Surgery and Surgical Navigation.

Avulsion of the medial canthal tendon secondary to nasoorbitoethmoidal fractures leads to severe aesthetic and functional impairments. The tendon should be repositioned at the posterior lacrimal crest. Owing to the complexity of nasoorbitoethmoidal fractures, accurate location of this point during surgery can be challenging. With the aid of computer-assisted planning and surgical navigation, the point at which the medial canthal tendon should be repositioned can be easily and precisely located. We have developed an innovative navigation-assisted technique that increases the reliability and safety of internal canthus repositioning. We performed a case series of three consecutive patients who underwent medial canthal tendon repositioning using computer-assisted planning and surgical navigation. We believe that this innovation provides a new and useful application of computer-assisted planning and surgical navigation in craniomaxillofacial surgery.

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.

Computer-assisted and navigated piezoelectric surgery: A new technology to improve precision and surgical safety in craniomaxillofacial surgery.

Background: Computer-assisted navigated piezoelectric surgery (CANPS) is a surgical technique that combines the surgical navigation with a piezoelectric device. This association multiplies the advantages of both technologies, taking the best of each one providing a synergistic association. Objective: To describe and assess the indications, advantages, disadvantages, and complications of this association of surgical techniques. Methods: CANPS was used in 32 patients. The clinical diagnosis was facial trauma, tumors, orthognathic surgeries, temporomandibular joint ankylosis, pathology of the frontal sinus, and alveolar distraction. Nineteen patients were men and 13 were women. Planning software iPlan 3.05 of Brainlab, and Elements of Brainlab were used for planning and the Kolibri and Kurve of Brainlab for surgical navigation. The piezoelectric device used was a "Vercelotti" type in all patients. Results: CAPNS could be performed successfully in all cases without complications and reduced the surgeon's uncertainty during the osteotomies. There is continuous control of the position of the surgical instrument. The use of the navigated piezoelectric device allowed the surgeon's uncertainty to be reduced during the performance of the osteotomies in depth, in poorly visible areas, with little access or reduced visibility. It also increases the safety of bone resections near important anatomical structures. Conclusions: CANPS combines the advantages of piezoelectric surgery and navigation. CANPS affords real-time control of the position of the cutting tip and allows semiburied approaches. CANPS allows surgery to be precise, safer, and minimally invasive.

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.

Fibula free flap in maxillomandibular reconstruction. Factors related to osteosynthesis plates' complications.

The aim of this paper is to identify risk factors associated with the development of osteosynthesis plates' related complications in fibula free flap reconstructions. This is a case series study of consecutive fibula free flaps. Clinical and radiological variables were recorded. Patient outcomes were evaluated with special attention to osteosynthesis plates' related complications; these included plate exposure, plate fracture, loosening of screws, non-union, bone resorption, oro-cutaneous fistulas, and bone exposure. We have done a descriptive analysis, univariate analysis, and multivariate logistic regression model to explore possible risk factors for osteosynthesis plates' related complications. Data analysis was performed using R software (version 3.5.0). 111 fibula free flaps were studied. 29 patients (26.1%) developed osteosynthesis plates' related complications. The mean time to osteosynthesis plates' related complications was 22 months; range (1-120); the median and mode were 12 months. Patients with preoperative radiotherapy (34% vs 14%, p = 0.021), and secondary reconstruction (31% vs 15%, p = 0.053) had a higher incidence of osteosynthesis plates' related complications. In the univariate analysis, "preoperative radiotherapy" (OR 3.07, 95%CI = 1.139-8.242, p = 0.025) and "extraoral soft-tissue defect" (OR 2.907, 95%CI = 1.032-8.088, p = 0.042) were risk factors for osteosynthesis plates' related complications. We have observed an interaction effect: patients with mandibular Brown's classes III + IV and "secondary reconstruction" have a higher risk for osteosynthesis plates' related complications; more than 47.30 times compared to Brown's class I and "primary reconstruction" (p = 0.026). Different factors may contribute to the development of osteosynthesis plates' related complications. Our study adds important information about these. Patients with higher risk of developing complications should be informed that a second intervention to remove the plates might be necessary.

Condylar intramedullary intraosseous lipoma: Contribution of a new case and review of the literature.

BACKGROUND: Lipoma is the most common benign tumour of the human body, being intraosseous involvement very rare. Just 1 to 4% of all cases of lipoma are located in the oral cavity, only 0.1% being intraosseous. The jaw is its most uncommon bone location. Etiology of intraosseous lipoma (IOL) is unknown, although several theories have been proposed. Usually asymptomatic, the symptoms, when present, will depend on its location and size. Its origin may be intraosseous or juxtacortical. A biopsy is essential for diagnosis, and definitive treatment involves resection or curettage of the lesion. The aim of this paper is to present a new case of intramedullary intraosseous lipoma of the mandible with involvement of the left mandibular ramus and condylar neck. MATERIAL AND METHODS: A case of intramedullary intraosseous lipoma (IOL) on the left mandibular ramus and condyle is presented. No history of trauma in temporomandibular joint existed. The radiology showed a radiolucent multi-lobulated lesion with values of attenuation in the range of fat. Curettage is performed and the histopathology showed a conglomerate of adipocytes without trabeculae, calcifications or atypia. RESULTS: According to the bibliography 24 cases of mandibular IOL have been described. This is the second reported case of condylar involvement and the first with cortical expansion. CONCLUSIONS: Lipoma intraosseous is a very rare benign bone neoplasm. Histology is required for the differential diagnosis from other radiolucent lesions. The IOL treatment is the curettage with a good prognosis, although malignant transformation to liposarcoma has been reported in other locations. It is a disease with a difficult differential diagnosis, therefore the publication of new cases is important. Key words:Intraosseous lipoma, lipoma, jaw tumour, condylar tumour.

Electromyography assisted application of botulinum toxin in pterygoid musculature for the treatment of masticatory myofascial pain / Aplicación de toxina botulínica en musculatura pterigoidea asistida con electromiografía para tratamiento del dolor miofascial

AIM: To evaluate the efficacy of botulinum toxin A injection (BTA) in the lateral pterygoid muscles assisted by electromyography (EMG) for the treatment of masticatory myofascial pain (MMP). MATERIAL AND METHODS: We conducted a retrospective study of 31 patients diagnosed of MMP who were treated by infiltration of botulinum toxin A in 1, 2 or 3 times, in the lateral and medial pterygoid muscles by electromyographic control of the puncture site. We assessed the treatment effectiveness in pain intensity decrease by numerical scales (NS) and categorical scales (CS). The impact of pathology on its quality of life, the decrease of demand for analgesic drugs, and the duration of BTA effect and its side effects were also valued. RESULTS: The mean decrease in pain after treatment was 4.9 +/- 2.9 points in NS. A statistical decrease of the pain (p = 0.01) can be shown after treatment. There is no statistical relationship between greater improvement after the administration of a greater number of injections. However, there is a significant improvement in the decrease of the pain in CS (p = 0.028) after the administration of several injections. There is also a significant decrease (p = 0.012) of the use of analgesic medication post-treatment. CONCLUSIONS: EMG assisted pterygoid muscles infiltration of BTA is effective in the treatment of MMP; it improves quality of life and decreases the consumption of health resources

OBJETIVO: Evaluar la eficacia de la inyección de toxina botulínica A (TBA) en los músculos pterigoideos guiada por electromiografía (EMG) para el tratamiento del dolor miofascial masticatorio. MATERIAL Y MÉTODOS: Realizamos un estudio retrospectivo de 31 pacientes diagnosticados de dolor miofascial de origen masticatorio a los que se le administró TBA en los músculos pterigoideos laterales y mediales guiada por EMG. Se evaluó la efectividad por disminución de intensidad del dolor mediante escalas numéricas (EN) y escalas categóricas (EC). Además, se determinó el impacto de esta patología en su calidad de vida, la duración del tratamiento y la disminución de la demanda de analgésicos. RESULTADOS: La disminución media del dolor en la EN tras tratamiento fue de 4,9 +/- 2,9 puntos. Se observó una disminución estadística del dolor (p < 0,01) después del tratamiento. No existe una relación estadística entre una mejoría mayor después de la administración de un mayor número de inyecciones. Sin embargo, hay una mejora significativa en la disminución del dolor en la CS (p = 0,028) después de la administración de varias inyecciones; así como una disminución significativa del uso de medicación analgésica posttratamiento (p = 0,012). CONCLUSIONES: La administración de TBA guiada por EMG en los músculos pterigoideos es eficaz en el tratamiento del dolor miofascial masticatorio, mejor la calidad de vida y se consigue una disminución del consumo de analgésicos postratamiento

Teratoma quístico maduro benigno parotídeo: una entidad extremadamente rara / Benign cystic teratoma mature parotid: an extremely rare entity

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Estudio preoperatorio de colgajo peroneo: ecografía doppler color versus angiografía o angio-TC / Pre-operative study of a fibula free flap: Colour flow doppler versus angiography or angio-CT

Objetivo. Valorar el uso de la ecografía doppler color (EDC) en el estudio preoperatorio del colgajo de peroné. Material y métodos. Realizamos un estudio retrospectivo de 78 piernas con EDC y angiografía por tomografía computarizada (angio-TC) o arteriografía. Se obtienen y comparan los resultados sobre el flujo y la morfología vascular de cada vaso infrapoplíteo. Se calcula la sensibilidad y especificidad de la EDC con respecto a angio-TC/angiografía y el índice kappa. Resultados. La EDC presentó una especificidad del 100%, una sensibilidad del 77% y un índice kappa del 0,84. Se obtuvieron 3 resultados falsos negativos en la EDC con respecto a la angio-TC, que fueron desestimados para cirugía. Conclusiones. La sensibilidad de la EDC en nuestra serie implica que esta prueba por sí sola no puede sustituir a la angio-TC/arteriografía, a no ser que se combine con una correcta anamnesis y exploración física vascular. El uso de la EDC de manera rutinaria permite identificar alteraciones vasculares que contraindican la elevación del colgajo libre de peroné y evita la necesidad de pruebas radiológicas adicionales (AU)

Aim. To evaluate the use of colour flow doppler (CFD) in the pre-operative study of a fibula flap. Material and methods. A retrospective study was conducted on 78 lower limbs with CFD and angio-CT and/or angiography. The results of arterial flow and vessel morphology of infrapopliteal vessels were obtained and compared. CFD sensitivity, CFD specificity, and kappa index were calculated. Results. CFD showed 100% specificity, 77% sensitivity, and a kappa index of 0.84. Three false negative results of CFD according to angio-CT were excluded from surgery. Conclusions. The CFD sensitivity in our series implies that this test alone cannot replace CT angiography/arteriography, unless it is combined with a correct anamnesis and physical examination. The routine use of the CFD identifies vascular disorders that contraindicate the fibula free flap elevation, avoiding the need for additional radiological tests (AU)