Combination of anti-CGRP/CGRP-R mAbs with onabotulinumtoxin A as a novel therapeutic approach for refractory chronic migraine: a retrospective study of real-world clinical evidence and a protocol for a double-blind, randomized clinical trial to establish the efficacy and safety.

Chronic migraine is a disabling neurovascular disorder that ranks amongst the top causes of years lived with disability worldwide. The duration and the frequency of migraine affect cognitive and affective domains, inducing worsening of memory, executive functions, orientation and causing anxiety. Population-based studies report a worrying level of resistance to treatments. Therefore, this study aims: 1) to assess efficacy of monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) or its receptor (CGRP-R) for chronic migraine resistant to current preventatives; 2) to design a clinical trial protocol to evaluate the efficacy and safety of combination therapy utilizing anti-CGRP/CGRP-R together with onabotulinumtoxin A in patients suffering from resistant chronic migraine; 3) to provide a molecular rationale for combination therapy. A controlled trial is warranted as pooled analysis of real-world data from our group highlighted that combined treatment provides ≥50% reduction vs. baseline (onabotulinumtoxin A) of monthly headache days (MHDs) in up to 58.8% of patients, but there has been only sparse application of this combined therapy to date. The mAbs chosen are: erenumab, because its combination effect with onabotulinumtoxin A improved symptoms in 65% of patients; eptinezumab, due to its faster action. The results highlight that early diagnosis of migraine improves therapeutic outcomes with mAbs alone, confirming their effectiveness and the need for an adequately powered clinical trial evaluating the safety and potential superior effectiveness of eptinezumab/erenumab and onabotulinumtoxin A together.

Prosthetically guided mandibular reconstruction using a fibula free flap: three-dimensional Bologna plate, an alternative to the double-barrel technique.

The fibula free flap represents the gold standard for mandibular reconstruction. However, when harvested as a single barrel, this flap does not allow the native mandibular height to be restored, which is required for implant-supported dental rehabilitation of the patient. The aim of this study was to present a new design for a patient-specific three-dimensionally printed reconstructive plate (3DBO-PSI) that positions the fibula bone at the height of the resected mandibular alveolar bone while restoring the mandibular profile to ensure a correct morphological outcome. Twenty patients were enrolled prospectively between January 2019 and May 2022. All patients underwent a segmental mandibular resection and prosthetically guided reconstruction making use of a fibula free flap supported by the 3DBO-PSI. The mean follow-up period was 20 months. All microvascular and implant-related complications were recorded. Microvascular failure occurred in two patients. No PSI-related complications were recorded during the postoperative follow-up. The proposed reconstructive method was found to be reliable and reproducible. In all treated patients, the bony flap appeared to be adequately positioned to maintain the preoperative intermaxillary relationship, as planned. To date, dental rehabilitation has been completed in seven patients.

3D planning of ear prosthesis and navigated flapless surgery for craniofacial implants: A pilot study.

New 3D digital technologies can be applied to implant-supported ear prostheses to restore anatomical structures damaged by cancer, dysplasia, or trauma. However, several factors influence the accuracy of implant positioning using a cranial template. This pilot study describes an innovative navigated flapless surgery for craniofacial implants, prosthetically guided by 3D planning of the ear prosthesis. Laser surface scanning of the face allowed for mapping of the healthy ear onto the defect site, and projection of the volume and position of the final prosthesis. The projected ear volume was superimposed on the skull bone image obtained by cone-beam computed tomography (CBCT), performed with the navigation system marker plate positioned in the patient's mouth. The craniofacial implants were fitted optimally to the ear prosthesis. After system calibration, real-time navigated implant placement based on the virtual planning was performed with minimally invasive flapless surgery under local anesthesia. After 3 months of healing, digital impressions of the implants were made, and the digital manufacturing workflow was completed to manufacture the ear prosthesis anchored to the craniofacial implants. The proposed digital method facilitated implant positioning during flapless surgery, improving the ear prosthesis manufacturing process and reducing operation time, patient morbidity, and related costs. This protocol avoids the need for a reference tool fixed in the cranial bone, as is usually required for maxillofacial surgery, and confirmed that surgical navigation is useful for guiding the insertion of craniofacial implants during flapless surgery.

Impact of COVID-19 epidemic on maxillofacial surgery in Italy.

Maxillofacial departments in 23 surgical units in Italy have been increasingly involved in facing the COVID-19 emergency. Elective surgeries have been progressively postponed to free up beds and offer human and material resources to those infected. We compiled an inventory of 32 questions to evaluate the impact of the SARS-COV2 epidemic on maxillofacial surgery in 23 selected Italian maxillofacial departments. The questionnaire focused on three different aspects: the variation of the workload, showing both a reduction of the number of team members (-16% among specialists, -11% among residents) due to reallocation or contamination and a consistent reduction of elective activities (the number of outpatient visits cancelled during the first month of the COVID-19 epidemic was about 10 000 all over Italy), while only tumour surgery and trauma surgery has been widely guaranteed; the screening procedures on patients and physicians (22% of maxillofacial units found infected surgeons, which is 4% of all maxillofacial surgeons); and the availability of Personal Protective Equipment, is only considered to be partial in 48% of Maxillofacial departments. This emergency has forced those of us in the Italian health system to change the way we work, but only time will prove if these changes have been effective.

Tapentadol prolonged release and the long-term management of chronic musculoskeletal pain in the elderly - focus on anxiety, depression, cognitive status and life quality: the TaPE study.

OBJECTIVE: The use of long-term opioids for the management of chronic musculoskeletal pain is a hot topic in the scientific community, especially when it concerns the elderly. This paper aimed at assessing the efficacy and tolerability of tapentadol prolonged release (PR), a molecule with a unique mechanism of action combining µ-opioid-receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI), administered to patients aged ≥80 years with chronic persistent pain. The effect of this molecule on anxiety, depression, cognitive status, and overall quality of life were investigated. PATIENTS AND METHODS: This was a spontaneous, observational, open-label, prospective study, in 80 older patients aged ≥80 years, naïve to strong opioids, presenting moderate-to-severe chronic pain from different etiologies. Tapentadol PR was initially prescribed at the dose of 25-50 mg/day and increased gradually in case of insufficient analgesia. Pain intensity was assessed by a 10-point Numeric Rating Scale (NRS). Other endpoints were as follows: DN4 questionnaire for the evaluation of the neuropathic component of pain, SF12, HADS, and MMSE questionnaires to evaluate the quality of life, anxiety, and cognitive impairment, respectively. Safety evaluations were also performed through the assessment of the frequency and severity of adverse events. RESULTS: At T45, NRS score reduction was achieved in 86.0% of patients. On average, pain decreased by 55% from a mean of 8.2 to a mean of 3.6. At T90, tapentadol PR did not affect the psychophysical and cognitive abilities of older patients. CONCLUSIONS: The benefits with tapentadol PR in controlling pain have improved the quality of life of our patients, also showing a favorable effect on their cognitive performance.

Design of a customised bridging mandibular prosthesis for complex reconstruction: a pilot study.

The gold standard for mandibular reconstruction is universally recognised and consists of the replacement of the bony part of the mandible with a bony microvascular free flap supported by a reconstructive plate. Although this procedure is feasible and reproducible in most patients, at times poor oncological prognosis or poor performance status force surgeons to consider other reconstructive solutions. In these cases, the main alternative in reconstructing a mandibular defect is represented by bridging plates combined with soft tissue flaps. However, repairing a mandibular defect with a reconstructive plate only can lead to a series of diverse complications. The most frequent complications reported are rupture and oral exposure of the plate. In this paper, we describe a new method for mandibular reconstruction using a customised bridging mandibular prosthesis (CBMP) without bone free flap.

Clonal analysis as a prognostic factor in multiple oral squamous cell carcinoma.

OBJECTIVES: A novel classification based on molecular methods to assess clonality defines three types of secondary oral squamous cell carcinoma (OSCC): second primary tumour (SPT) independent from the index tumour, local recurrence (LR), clonally related to the primary tumour, and second field tumour (SFT), derived from the same genetically altered mucosal field as the primary tumour. The present study applied mtDNA analysis in a group of patients experiencing a second loco-regional neoplastic manifestation. The purpose was to differentiate secondary tumours into LRs, SPTs and SFTs and evaluate the prognostic impact in terms of survival rate. MATERIAL AND METHODS: The study population comprised 23 patients who experienced a second neoplastic lesion after a surgical resection of primary OSCC. mtDNA D-loop analysis was applied in paired neoplastic lesions and in clinically and histologically normal mucosa. On the basis of mtDNA results, the second OSCC was classified as LR or SPT or SFT. Disease-free survival was defined as the duration between the appearance of the second neoplastic lesion and death of disease, or last follow-up visit. RESULTS: Seven secondary tumours were classified as LR, 12 as SFT, 4 as SPT. An altered mucosal field proved a variable significantly related to a better survival rate (p<0.05); 2/12 (16.6%) SFT events failed as compared to 5/7 LRs (71.4%) and 3/4 SPTs (75%). CONCLUSION: mtDNA analysis may be considered a useful tool to differentiate secondary tumours and might influence the choice of the most appropriate treatment in patients with multiple OSCCs.

Mandibular reconstruction using fibula free flap harvested using a customised cutting guide: how we do it.

Free fibula flap is routinely used for mandibular reconstructions. For contouring the flap, multiple osteotomies should be shaped to reproduce the native mandibular contour. The bone segments should be fixed using a reconstructive plate. This plate is usually manually bent by the surgeon during surgery. This method is efficient, but during reconstruction it is complicated to reproduce the complex 3D conformation of the mandible and recreate a normal morphology with a mandibular profile as similar as possible to the original; any aberration in its structural alignment may lead to aesthetic and function alterations due to malocclusion or temporomandibular disorders. In order to achieve better morphological and functional outcomes, we have performed a customised flap harvest using cutting guides. This study demonstrates how we have performed customised mandibular reconstruction using CAD-CAM fibular cutting guides in 20 patients undergoing oncological segmental resection.

Giant pleomorphic adenoma of the parotid gland: an unusual case presentation and literature review.

Pleomorphic adenoma is the most common type of all salivary gland tumours. Although uncommon, cases of giant pleomorphic adenomas have been described in the medical literature, the majority involving the parotid gland. This paper describes an unusual case of a giant adenoma arising in the parotid gland. The patient underwent surgical resection of the giant tumour, which was one of the largest pleomorphic adenoma reported in recent literature. This case has prompted us to evaluate the behaviour of those benign tumours, which suggested that aesthetic and social morbidity is sufficient to justify, when possible, early tumour excision, despite the relatively low risk of malignant transformation. Management of this unusual tumour is discussed, and the literature on giant parotid tumours is reviewed.

3D computed tomographic evaluation of the upper airway space of patients undergoing mandibular distraction osteogenesis for micrognathia.

Mandibular distraction osteogenesis (MDO) is currently an accepted method of treatment for patients requiring reconstruction of hypoplastic mandibles. To date one of the unsolved problems is how to assess the quantitative increase of mandible length needed to achieve a significant change in the volume of the posterior airway space (PAS) in children with mandibular micrognathia following distraction osteogenesis. The purpose of this study is to present quantitative volumetric evaluation of PAS in young patients having distraction osteogenesis for micrognathia using 3D-CT data sets and compare it with pre-operative situation. In this observational retrospective study, we report our experience in five consecutive patients who underwent MDO in an attempt to relieve severe upper airway obstruction. Each patient was evaluated before treatment (T0) and at the end of distraction procedure (T1) with computer tomography (CT) in axial, coronal, and sagittal planes and three-dimensional CT of the facial bones and upper airway. Using parameters to extract only data within anatomic constraints, a digital set of the edited upper airway volume was obtained. The volume determination was used for volumetric qualification of upper airway. The computed tomographic digital data were used to evaluate the upper airway volumes both pre-distraction and post-distraction. The mean length of distraction was 23 mm. Quantitative assessment of upper airway volume before and after distraction demonstrated increased volumes ranging from 84% to 3,087% with a mean of 536%. In conclusion, our study seems to show that DO can significantly increase the volume of the PAS in patients with upper airway obstruction following micrognathia, by an average of 5 times. Furthermore, the worse is the starting volume, the greater the increase in PAS to equal distraction.

Ki-67 and p53 expression in ghost cell odontogenic carcinoma: a case report and literature review.

Ghost cell odontogenic carcinomas are rare neoplasms that arise in the maxillary bones either from a calcifying odontogenic cyst or de novo. They are aggressive locally and can metastasize. We report herein a case of a ghost cell odontogenic carcinoma arising in the mandible of a Caucasian male 86 years of age. We have described the clinical and radiographic features, histological characteristics, immunohistochemistry findings, and surgical treatment. We especially focused on how Ki-67 expression guides the treatment choice. Finally, we reviewed 32 cases described in the literature and compared them with the cases described up until 2014 to help clinicians identify the diagnostic characteristics of and select appropriate treatment modalities for ghost cell odontogenic carcinomas.

Functional results of microvascular reconstruction after hemiglossectomy: free anterolateral thigh flap versus free forearm flap.

The aim of the present study is to assess functional outcomes after hemiglossectomy and microvascular reconstruction. Twenty-six patients underwent primary tongue microvascular reconstruction after hemiglossectomy. Twelve patients were reconstructed using a free radial forearm flap and 14 with an anterolateral thigh flap. Speech intelligibility, swallowing capacity and quality of life scores were assessed. Factors such as tumour extension, surgical resection and adjuvant radiotherapy appeared to be fundamental to predict post-treatment functional outcomes. The data obtained in the present study indicate that swallowing capacity after hemiglossectomy is better when an anterolateral thigh flap is used. No significant differences were seen for speech intelligibility or quality of life between free radial forearm flap and anterolateral thigh flap.

Vascular pedicle ossification of free fibular flap: is it a rare phenomenon? Is it possible to avoid this risk?

Free fibula flap is the most common free tissue transfer for maxillary and mandibular reconstructions. The distal part of the harvested bone is transferred, while the proximal part is removed by sub-periosteum dissection. The vascularized periosteum attached to the vascular pedicle has osteogenic potential. 61 patients reconstructed with free fibula flaps were divided in 2 groups: 41 flaps performed with a standard technique and 20 flaps performed by dissecting the periosteum from the pedicle. Patients were followed up with orthopantomography and CT scan at 6, 12, 18 and 24 months after surgery. The minimum follow-up time was 18 months. With retrospective analysis of the first group we diagnosed 7 pedicle ossifications on 41 reconstructions (17%). In the second group, no pedicle ossification was observed (p < 0.05). The dissection of periosteum from the vascular pedicle of free fibula flaps avoids the risk of ossification.

Unusual presentation of obstructive sleep apnoea syndrome due to a giant mandible osteoma: case report and literature review.

Osteomas are benign lesions composed of mature compact and/or cancellous bone that grow continuously. Their pathogenesis is unknown. It has been considered to be a neoplasm, a developmental or reactive osteogenic lesion resulting from muscle traction on the periosteum, or due to trauma. Herein, we report an unusual case of giant osteoma of the mandible depressing the lateral pharyngeal wall, interfering with normal respiration during the night. The uniqueness of this case is related to snoring and sleep apnoea symptoms. In fact, he presented to our Department because daytime sleepiness hindered his work, and not for the evident facial swelling. We reported our experience in diagnosis, treatment and follow-up of this uncommon disease. Polysomnography, CT scan and 3-D PAS volume analysis are useful tools to study in detail the aetiology of apnoea and assess outcomes.

Head and neck cancer in elderly patients: is microsurgical free-tissue transfer a safe procedure?

The safety and success of microvascular transfer have been well documented in the general population, but the good results achieved with the use of free flaps in elderly patients have received little attention. This study sought to identify differences in complications, morbidity and functional outcomes between elderly (≥ 75 years) and younger (< 75 years) patients treated surgically for advanced head and neck cancer using the Head and Neck 35 module of the European Organisation for Research and Treatment of Cancer quality of life questionnaire. Patient treatment consisted of composite resection, including excision of the primary tumour with ipsilateral or bilateral neck dissection and microvascular reconstruction. Eighty-five microvascular tissue transfers were performed to reconstruct major surgical defects. Postoperative radiation therapy was performed when indicated. Total flap loss occurred in three cases in elderly patients and two cases in younger patients. The rates of major surgical complication were 9% in young patients and 11% in elderly patients. No significant difference was observed between the two groups in the rates of major and minor flap complications, morbidity or long-term functional outcome. The results of the present analysis indicate that free-flap microvascular reconstruction can be considered a safe procedure in elderly patients with head and neck cancer.