Combined exome and whole transcriptome sequencing identifies a de novo intronic SRCAP variant causing DEHMBA syndrome with severe sleep disorder.

Rare heterozygous variants in exons 33-34 of the SRCAP gene are associated with Floating-Harbor syndrome and have a dominant-negative mechanism of action. At variance, heterozygous null alleles falling in other parts of the same gene cause developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (DEHMBA) syndrome. We report an 18-year-old man with DEHMBA syndrome and obstructive sleep apnea, who underwent exome sequencing (ES) and whole transcriptome sequencing (WTS) on peripheral blood. Trio analysis prioritized the de novo heterozygous c.5658+5 G > A variant. WTS promptly demostrated four different abnormal transcripts affecting >40% of the reads, three of which leading to a frameshift. This study demonstrated the efficacy of a combined ES-WTS approach in solving undiagnosed cases. We also speculated that sleep respiratory disorder may be an underdiagnosed complication of DEHMBA syndrome.

Depression and Anxiety in Pediatric Patients with Beckwith-Wiedemann Syndrome: A Pilot Study.

The study's aim was to determine the prevalence of depression and anxiety in children with Beckwith-Wiedemann syndrome (BWS) and their effects on social relationships and family acceptance. The Pediatric Symptom Checklist-35 items (PSC-35), Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Vineland Adaptive Behavior Scale Second Edition (VABS-II) were administered to the children. The parental Acceptance Rejection/Control Questionnaire (PARQ/Control) and Zarit Burden Inventory (ZBI) were administered to parents. In total, 6 patients and 10 parents were included. Patients showed a significant presence of internalizing behavior in PSC-35 (mean, 7.66 ± 3.67), anxiety symptoms (SCARED: mean, 46.33 ± 17.50) and socialization difficulties (mean, 90.83 ± 10.09). Parents reported a perceived good acceptance (mean, 56.33 ± 1.03) and a moderate control (mean, 24.17 ± 1.83), but the burden level was ranked moderate to severe (mean, 59.33 ± 16.78). It was found that the severity of the burden level reported by parents was related to internalizing behavior (OR = 2.000; 95% CI = 0.479-3.521; p = 0.022) and anxiety symptoms (SCARED total score: OR = 3.000; 95% CI = 1.479-4.521; p = 0.005) of children. During psychological counseling in the context of BWS treatment, it is important to identify specific resources that can support patients and families in dealing with stress and identify any critical areas that could hinder the adaptation process.

Perioperative Management of a Pediatric Patient with Beckwith-Wiedemann Syndrome Undergoing a Partial Glossectomy According to Egyedi/Obwegeser.

Here, we report the perioperative management of a clinical case of a 6 year, 5 month old girl suffering from Beckwith-Wiedemann syndrome undergoing a partial glossectomy procedure in a patient with surgical indication for obstructive sleep apnea syndrome (OSAS), difficulty swallowing, feeding, and speech. On surgery day, Clonidine (4 µg/kg) was administered. Following this, a general anesthesia induction was performed by administering Sevoflurane, Fentanyl, continuous intravenous Remifentanil, and lidocaine to the vocal cords, and a rhinotracheal intubation with a size 4.5 tube was carried out. Before starting the procedure, a block of the Lingual Nerve was performed with Levobupivacaine. Analgosedation was maintained with 3% Sevoflurane in air and oxygen (FiO2 of 40%) and Remifentanil in continuous intravenous infusion at a rate of 0.08-0.15 µg/kg/min. The surgical procedure lasted 2 h and 32 min. At the end of the surgery, the patient was under close observation during the first 72 h. In the pediatric patient with Beckwith-Wiedemann syndrome submitted to major maxillofacial surgery, the difficulty in managing the airways in the preoperative phase during intubation and in the post-operative phase during extubation should be considered.

Is 2020 the golden year of Otolaryngology research? The impact of COVID-19 on the Italian academic production.

BACKGROUND AND AIM: The aim of this research was to review the articles published by the Otolaryngology (ORL) departments of the Italian University Hospitals in 2019 and in 2020 in order to analyze the impact of the COVID-19 pandemic on the academic production. METHODS: PubMed and Scopus were searched for the articles published by the ORL departments of the Italian Universities in 2019 and in 2020. The main eligibility criteria were English-language articles, while there were no exclusion criteria related to topic. The articles were classified into seven domains corresponding to the main ORL subspecialties. RESULTS: There was an overall increase in the number of articles by the 42.2% in 2020. Publications pertaining Rhinology and Laryngology increased more significantly in 2020, respectively by the 50.5% and 72.2%. Additionally, there was an increase in the number of articles concerning topics of general interest, by the 95.2% in 2020. Also, the citation trends of the articles published by the Italian University Hospitals increased remarkably in 2020. CONCLUSIONS: These results evidenced an overall increase in the number of ORL articles. Although 2020 is going to be remembered as a year to forget, it should be acknowledged for being the "golden year of research".

Managing head and neck cancer patients during the COVID-19 pandemic: the experience of a tertiary referral center in southern Italy.

BACKGROUND: The medical community has been deeply involved in fighting the Coronavirus disease 2019 (COVID-19) pandemic and, as a consequence, the care of non-COVID-19 patients has been impacted. However, the treatment of head and neck cancer patients is not deferrable, and an integrated strategy is required. The aim of the current article is to present the experience in the management of head and neck patients during the COVID-19 pandemic at the research hospital "Casa Sollievo della Sofferenza". This review contains replicable and widely usable instructions on how to avoid delays in the diagnosis and treatment of head and neck tumors and to ensure a gradual return to elective procedures. MAIN TEXT: The Head and Neck Department of the research hospital "Casa Sollievo della Sofferenza" includes an Otolaryngology and a Maxillofacial Surgery Unit, both of which deal with the diagnosis and treatment of benign and malignant pathologies of the head and neck, as well as urgent/emergent consultations and surgical procedures that necessitate time sensitive operative management, such as cochlear implantation (CI). Given these premises and the complexity of the Department, the "COVID-19 organizing protocol" of the research hospital "Casa Sollievo della Sofferenza" was divided into two phases in accordance with the different stages of the pandemic and the priority of treatment. Special attention was given to the medical surveillance of health care workers and hospitalized patients, to the organization of the outpatient clinic and the operating setting as well as to the implementation of telehealth systems. CONCLUSIONS: The COVID-19 pandemic is going to be a long-term situation with lasting effects on the public health and the entire society. Therefore, an efficient health care system has to adopt a double strategy: always being ready for a "new wave" of the pandemic and not forgetting non-COVID-19 patients, among whom head and neck cancer patients represent a priority. More than 1 year since the first outbreak in Wuhan, this review offers a unique and helpful perspective that incorporates awareness of the disease.

Adequacy of the Italian National Tariff for Orthognathic Surgery: A Cost Analysis Using the Activity Based Costing (ABC) Method.

ABSTRACT: The reduced economic resources in health care and the consequent spending review have brought great interest in surgical costs. The aim of the study is to determine direct hospital costs for Orthognathic procedures using the Activity based costing method and evaluate the adequacy of the refund provided by the Italian National Health Service. From January 2017 to December 2017 9 consecutive patients underwent the following Orthognathic procedures at IRCCS Casa Sollievo della Sofferenza (San Giovanni Rotondo, Italy): bimaxillary osteotomy (n = 7), Le Fort I osteotomy (n = 1) and Bilateral Sagittal Split Osteotomy (BSSO) (n = 1). Activity based costing was used to obtain costs of each single hospitalization split into surgery, instay, and services. The mean total cost for a bimaxillary osteotomy was 7596.40€. We observed a total cost of 3925.00€ for Le Fort I osteotomy and of 4334.50€ for BSSO. The refund of 4378.00€ provided by the Italian National Health Service system for Orthognathic surgery seems insufficient to cover costs of bimaxillary osteotomy but consistent for single osteotomy (Le Fort I or BSSO).

Italian cost analysis of free flap surgery in head and neck reconstruction using the activity-based costing (ABC).

The aim of the study is to evaluate costs of free flap surgery for head and neck (H & N) reconstructions using the time-driven activity-based costing (ABC) method and to compare them with the refund provided by the Italian National Health System (NHS) amounting to 11,891€. We retrospectively selected 29 consecutive patients underwent free flap reconstruction in 2013 at IRCCS Casa Sollievo della Sofferenza. Patients were divided into three groups: Group 1 (n = 10) included patients receiving radial forearm free flap (RFFF), Group 2 (n = 10) receiving anterolateral thigh (ALT) free flap, and Group 3 (n = 9) composed of patients having fibular free flap. For each patient, costs were calculated using the ABC and divided into instay, surgical, and services costs. We observed an overall mean total cost of 27,802.40€. The mean costs related to hospital stay were 9,800.70€. The mean costs for surgery were 13,097.60€ and amounted to 4,904.10€ for services. RFFF appears to be less costing (25,175.40€) compared with ALT (29,191.60€) and fibula free flap (29,040.20€). ABC is an appropriate method to determine actual costs of free flap surgery by correctly allocating the resources used. The Italian NHS tariff seems to be inadequate to cover the real cost of this type of surgery.

Reconstruction of Full-Thickness Defects of the Lower Lip With a Double Overlying Cervical Flap.

Reconstruction of full-thickness total or subtotal lower lip defects represents a challenge for the reconstructive surgeon because of the difficulty to create a functional and aesthetically good lip. Many surgical techniques, going from local to free flaps, have been reported, each of them having its own advantages and disadvantages. In particular, the free fascio-cutaneous flaps in most cases are the first reconstructive option, even though several disadvantages such as the complexity of the procedure, longer operative times, morbidity, longer hospitalization, and conspicuous donor-site scar. To avoid these problems, especially in aged patients and in presence of low compliance and/or comorbidities, the Authors propose a single stage reconstruction with a double overlying cervical flap.

Akt, protein kinase C, and mitogen-activated protein kinase phosphorylation status in head and neck squamous cell carcinoma.

BACKGROUND: To detect epigenetic changes in head and neck squamous cell carcinoma (HNSCC) and between metastatic and nonmetastatic tumors, we performed a systematic phosphorylation screening on different protein kinases. METHODS: The phosphorylation levels of the serine-threonine kinase Akt, of mitogen-activated protein kinase (MAPK), and of protein kinase C (PKC) beta and epsilon were measured in a series of 94 biopsy specimens, corresponding to 47 HNSCCs and paired controls taken from clinically uninvolved tissue of the same patients. RESULTS: Akt and MAPK were significantly underphosphorylated (two-sided p < .004) in tumors, whereas PKCs showed no differences from control samples.Second, although in control tissue there was a significant correlation between phosphorylation levels of Akt, MAPK, and PKC (all two-sided p < .05), many correlated activations were lost in tumors and even more in lymph node-positive tumors. Finally, p44 MAPK and Akt pThr308 were phosphorylated in a coordinated fashion only in lymph node-positive tumors (two-sided p < .01). CONCLUSIONS: This novel evidence documents important changes in the phosphorylation program during cancer progression of HNSCC.