Idiopathic erythrocytosis: a germline disease?

Polycythemia Vera (PV) is typically caused by V617F or exon 12 JAK2 mutations. Little is known about Polycythemia cases where no JAK2 variants can be detected, and no other causes identified. This condition is defined as idiopathic erythrocytosis (IE). We evaluated clinical-laboratory parameters of a cohort of 56 IE patients and we determined their molecular profile at diagnosis with paired blood/buccal-DNA exome-sequencing coupled with a high-depth targeted OncoPanel to identify a possible underling germline or somatic cause. We demonstrated that most of our cohort (40/56: 71.4%) showed no evidence of clonal hematopoiesis, suggesting that IE is, in large part, a germline disorder. We identified 20 low mutation burden somatic variants (Variant allelic fraction, VAF, < 10%) in only 14 (25%) patients, principally involving DNMT3A and TET2. Only 2 patients presented high mutation burden somatic variants, involving DNMT3A, TET2, ASXL1 and WT1. We identified recurrent germline variants in 42 (75%) patients occurring mainly in JAK/STAT, Hypoxia and Iron metabolism pathways, among them: JAK3-V722I and HIF1A-P582S; a high fraction of patients (48.2%) resulted also mutated in homeostatic iron regulatory gene HFE-H63D or C282Y. By generating cellular models, we showed that JAK3-V722I causes activation of the JAK-STAT5 axis and upregulation of EPAS1/HIF2A, while HIF1A-P582S causes suppression of hepcidin mRNA synthesis, suggesting a major role for these variants in the onset of IE.

Smell and taste dysfunction during the COVID-19 pandemic: an infodemiological analysis.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause smell and taste dysfunction. We aimed to investigate the general community's interest in smell dysfunction (SD) and taste dysfunction (TD) using Google Trends to compare results with more common symptoms associated with SARS-CoV-2 infection, such as fever and cough. MATERIALS AND METHODS: Relative Search Volumes (RSVs) for the English terms "Smell", "Taste", "Fever" and "Cough", filtered by the category "Health", were collected from 2018 through 2020. Moreover, RSVs using synonyms of "Taste" and "Smell" in 5 European languages were analyzed. RESULTS: The worldwide mean RSVs for "Fever", "Cough", "Smell", and "Taste" during 2020 were 49%, 34%, 8% and 9%, respectively. RSVs associated with the search terms "Fever" and "Cough" showed a peak between February and March 2020, as did "Smell" and "Taste". Even though RSVs were much lower, they were highly correlated (r=0.890). RSVs obtained from "Smell" and "Taste" in five European languages (German, English, French, Italian and Spanish) had similar temporal trends. CONCLUSIONS: Our findings show the level of the general population's interest for early symptoms, suggesting that their interest in SARS-CoV-2 infection symptoms, such as SD and TD, was scarce but peaked during the pandemic outbreak.

Ion concentrations in nasal airway surface liquid: a prediction model for the identification of cystic fibrosis carriers.

BACKGROUND: Cystic fibrosis (CF) carriers seem to have a higher risk to develop chronic rhino-sinusitis (CRS), although the full underlying mechanisms are unknown. Ion concentrations in nasal airway surface liquid (ASL) may be influenced by the heterozygosity for CF gene mutation, with possible impacts on the development of CRS. METHODS: A cheap and feasible standardized technique was designed to measure the ion levels in nasal ASL. With this purpose we collected, under basal conditions, samples from the nasal cavity of 165 adults: 14 homozygous for CF, 83 carriers and 68 healthy controls. Sodium (Na) and Chlorine (Cl) concentrations were then evaluated among different groups. RESULTS: Statistical analysis revealed a significant difference of Na and Cl values between controls and carriers and between controls and homozygotes. Receiver operating characteristic (ROC) curves and derived indicators (Youden's index and Area Under the Curve, AUC) were used to further evaluate the diagnostic capability of Na and Cl concentrations to differentiate heterozygotes from controls. ROC curves demonstrated that the optimal diagnostic cut-off value of Na is at 124, and the optimal cut-off value of Cl is at 103,2. CONCLUSION: ASL sampling can be considered a new diagnostic tool for providing quantitative information on nasal ion composition. According to our findings, Na and Cl concentrations of nasal ASL could represent a useful tool to assess heterozygotes and healthy controls.

Surgical management of acquired anterior glottic web: a systematic review.

BACKGROUND: Acquired anterior glottic web poses a significant challenge to laryngologists given its propensity to recur following treatment, and there are a wide variety of described techniques. METHODS: A systematic review of the medical literature was undertaken in order to identify all articles pertaining to the management of acquired anterior glottic web. RESULTS: Thirteen studies meeting the inclusion criteria were identified and analysed. All were retrospective series, with varying surgical techniques and outcome measures. Only two studies reported on the use of topical mitomycin C. CONCLUSION: Mucosal graft techniques and keel placement appear to improve success rates, but both carry risks and disadvantages. Based on the available evidence, the use of topical agents such as mitomycin C cannot be recommended in the management of acquired anterior glottic web.

Transoral robotic surgery for hilo-parenchymal submandibular stones: step-by-step description and reasoned approach.

The conservative transoral approach to hilo-parenchymal submandibular stones has been proposed as an alternative to traditional sialadenectomy. The main purpose is to preserve the gland and eliminate the risk of a cervical scar and damage to the marginal mandibular branch of the facial nerve. The spread of transoral robotic surgery has favoured its application not only in the oropharynx, but also in the anterior oral cavity. This article describes a transoral robotic approach for hilo-parenchymal submandibular stones. In January 2019, two patients with a right and a left hilo-parenchymal submandibular stone of 15mm and 8mm, respectively, underwent removal of the stone with transoral robotic surgery using the Si Da Vinci surgical robot. The procedure was performed successfully and tolerated well, with a one-night hospitalization. There were no complications such as lingual nerve damage, painful gland swelling, infection, or ranula. The patients were followed up clinically and ultrasonographically for the first 3 months to verify symptom relief and persistence of stones; no symptoms or stones were found. The transoral robotic surgical approach seems to be safe and adequate for the conservative management of large hilo-parenchymal submandibular stones. An adequate diagnosis together with proper docking and an appropriate approach to the oral floor is mandatory.

Transnasal endoscopic management of anterior cerebrospinal fluid (CSF) leak: experience from a large case series.

Transnasal endoscopic management of anterior cerebrospinal fluid (CSF) leak: experience from a large case series. OBJECTIVES: Anterior cerebrospinal fluid (CSF) leak is a consequence described after head trauma, skull base surgery or inflammatory diseases, but may also occur spontaneously. Prompt recognition and management is crucial in order to avoid complications and to achieve successful surgical repair. The purpose of this study is to present the clinical features of a large group of patients with anterior CSF leak and the results of their surgical management. METHODOLOGY: The study approach was a retrospective review of 110 consecutive patients treated by the same surgeon for CSF leak of the anterior skull base via a transnasal endoscopic approach between 2003 and 2013. Patients with anterior skull base surgery due to cancer or pituitary adenoma were excluded from this study. The diagnostic workup included nasal endoscopy, beta2-transferrin and -trace protein assay in the rhinoliquorrhoea and radiological imaging. The intrathecal fluorescein test was performed in selected cases. The surgical techniques used to repair dural defects were primarily middle turbinate placement and fascia lata grafting. RESULTS: Primary endoscopic repair of the CSF fistula was successful in 106/110 (96.4%) patients. Four patients (3.6%) required a revision procedure due to early failure of the repair. After a minimum follow-up of 24 months, no recurrent CSF leaks were observed in the study group. None of the patients developed meningitis as a surgical complication. CONCLUSIONS: The endoscopic transnasal approach is a reliable technique for treating CSF leaks. The intrathecal fluorescein test is safe and helpful in locating the defect. The fascia lata proved the best graft available in our experience.

Post-operative pain management in head and neck cancer patients: predictive factors and efficacy of therapy.

There is increasing interest about all aspects of pain sensation for patients undergoing head and neck surgery, and efforts have been made to better assess, monitor and reduce the occurrence of pain. The aetiology of pain is considered to be "multifactorial", as it is defined by several features such as personal experience, quality perception, location, intensity and emotional impact. The aim of this paper is: (i) to evaluate the efficacy of analgesic treatment in patients with head and neck cancer treated by surgery, and (ii) to study the variables and predictive factors that can influence the occurrence of pain. A total of 164 patients, affected by head and neck cancer and surgically treated, between December 2009 and December 2013, were included in this study. Data collected include age, gender, assessment of anaesthetic risk, tumour localisation, pathological cancer stage, TNM stage, type of surgery performed, complexity and duration of surgery, post-operative complications, postoperative days of hospital stay and pain evaluation on days 0, 1, 3 and 5 post-surgery. We studied the appropriateness of analgesic therapy in terms of incidence and prevalence of post-operative pain; we also related pain to patient characteristics, disease and surgical treatment to determine possible predictive factors. The population studied received adequate pain control through analgesic therapy immediately post-surgery and in the following days. No associations between gender, age and post-operative pain were found, whereas pathological cancer stage, complexity of surgery and tumour site were significantly associated with the risk of post-operative pain. Adequate pain control is essential in oncological patients, and particularly in head and neck cancer patients as the prevalence of pain in this localisation is reported to be higher than in other anatomical sites. Improved comprehension of the biological and psychological factors that characterise pain perception will help to enhance its control in the future.

Listeria Monocytogenes: an uncommon pathogen of cervical necrotizing fasciitis.

The aim of this paper is to present a unique case of neck-necrotizing fasciitis caused by Listeria Monocytogenes in a young woman, successfully treated by surgery and IV antibiotic therapy. Necrotizing fasciitis is a rare, rapidly progressing and potentially life-threatening infection that infrequently occurs in the head and neck region. Pathogens involved in necrotizing fasciitis are heterogeneous and include aerobic and anaerobic bacteria. To the best of our knowledge, this is the only case of neck necrotizing fasciitis caused by Listeria Monocytogenes studied in literature so far.

Simultaneous nasopharyngeal and parotid gland Warthin's tumour: a case report.

Herein, a rare case of synchronous cystoadenolymphoma (Warthin's tumour) of the right parotid gland and the nasopharyngeal space is described. Although Warthin's tumour (WT) of the parotid gland is a common benign pathology, the occurrence of extra-parotid cystoadenolymphoma is rare. Extra-parotid WT have been mainly localised in the submandibular gland, periparotid region and occasionally in other sites, such as the oral cavity, hard palate and nasopharynx. The simultaneous occurrence of an intra-parotid and extra-parotid WT localisation, as in the case presented, is extremely uncommon.

Analysis of Il-10 gene sequence in patients with sinonasal polyposis.

Sinonasal polyposis (SNP) is a chronic inflammatory disease of nasal and paranasal cavities. Human leukocyte antigen-G molecules (HLA-G) are non-classic HLA-I molecules with anti-inflammatory and tolerogenic properties. HLA-G production is mainly induced by interleukin (IL)-10. IL-10 is an anti-inflammatory cytokine that inhibits the production of proinflammatory cytokines and induces HLA-class II down-modulation. Recent studies suggest that HLA-G could play a role in SNP pathogenesis; in SNP patients physiological levels of IL-10 (produced by activated peripheral blood CD14+ monocytes) are not able to induce production of HLA-G. Different mechanisms could justify these findings: genomic or amino-acidic sequence alterations in IL-10 lower IL-10 receptor expression, lower IL-10 receptor affinity, or alterations of the intracellular signal transmission. This study analyzes nucleotidic sequence of IL-10 gene in SNP patients. Sequencing of IL-10 gene shows that the lack of HLA-G production by peripheral blood CD14+ monocytes is not related to alterations in IL-10 gene nucleotidic sequence.

Orofacial pain and Eagle Syndrome: cues from a clinical series.

AIM: Watt Eagle, firstly described the Elongated Stylohyoid Process Syndrome (ESPS), or Eagle Syndrome, in 1937. Since then, several authors have further studied this syndrome and some classifications have been proposed in relation to signs, symptoms and etiopathogenesis. Aim of this paper was to present the clinical features of a cohort of patients affected by Eagle syndrome that underwent surgical treatment. METHODS: Retrospective study. A cohort of ten patients that underwent surgical intervention for Eagle syndrome from January 2000 to December 2012 has been selected. For each subject, medical history, clinical features, treatment and follow-up after surgery were evaluated. RESULTS AND CONCLUSIONS: The surgical treatment resulted effective in 8 of 10 patients. Two patients are still complaining neck pain, although the discomfort has a lower grade and is pharmacologically controllable. Although rare, Eagle's Syndrome should be always considered in the differential diagnosis in patients with chronic orofacial pain refractory to conventional treatments.

Patients' survival after free flap reconstructive surgery of head and neck squamous cell carcinoma: a retrospective multicentre study.

Head and neck squamous cell carcinoma of the (HNSCC) represents approximately 5% of malignant tumours in Italy. HNSCC are commonly treated with surgery or radiotherapy, or a combination of such therapies. The objectives of treatment are maximum cure rate balanced with organ preservation, restoration of form and function, reduction of morbidities and improvement or maintenance of the patient's quality of life. Immediate reconstructive surgery: local, regional or free flaps are now widely advised in the treatment of these patients. Microsurgical transfer requires expertise, is time and resource consuming, and as a whole requires substantial costs. These considerations introduce some concerns about the wide or indiscriminate use of free flap reconstructive surgery. When considering cost-benefit outcomes of such treatment, the main objective is undoubtedly, survival. This data is underreported in the current literature, whereas functional outcomes of free flaps have been largely diffused and accepted. This study collects data from 1178 patients treated with free flap reconstructive surgery following ablation of HNSCC in a group of Italian tertiary hospitals, all members of the Head & Neck Group affiliated with the Italian Society of Microsurgery. According to many authors, free flap surgery for HNSCC seems to be a beneficial option for treatment even in terms of survival.

Preoperative assessment of salivary gland neoplasms with fine needle aspiration cytology and echography: a retrospective analysis of 357 cases.

Fine-needle aspiration cytology (FNAC) is a minimally invasive procedure usually well tolerated, easy to perform, quick, cheap and easy to repeat in case of doubts or non-diagnostic results. Echography is also a fast, cheap and non-invasive tool; however, the role of FNAC and echography in the diagnosis of salivary gland pathology is not universally recognised. Three hundred and fifty-seven patients with a cytological diagnosis at FNAC, and 247 of these who were also studied with echography, were enrolled for this retrospective study. The final histopathological diagnoses, obtained after surgery, were then compared to the preoperative FNAC diagnoses and echographic findings. From the analysis of our data, the overall FNAC specificity resulted 93 percent, sensitivity 83 percent, and diagnostic accuracy 92 percent. Echography sensibility was 57.1 percent specificity 98.2 percent, while positive and negative predictive value were respectively 80 percent and 94.8 percent. While echography can be useful in order to provide a better characterization of salivary gland lesions, FNAC can then be considered a safe diagnostic tool with reliable sensitivity and specificity for the assessment of salivary gland pathology and thus for selecting patients and indicating the best surgical treatment.

Comparison of subjective and objective tools in transoral laser cordectomy for early glottic cancer: importance of voice handicap index.

Several studies in recent years have already reported good oncologic results with laser microsurgery in the treatment of early glottic carcinoma. We conducted a longitudinal voice evaluation, in patients with early glottic cancer who underwent transoral laser cordectomy, in order to assess the voice quality outcome and its relationship with objective and subjective (voice handicap index questionnaire and GIRBAS scale) means. Twenty-four previously untreated patients underwent transoral laser cordectomy for early glottic cancer. All patients underwent subjective and objective voice assessment according to the multidimensional voice protocol recommended by the European Laryngological Society including acoustic, perceptual and stroboscopic analysis combined to patient self assessment of voice (voice handicap index-VHI). These evaluations were performed before treatment and 6 months after the treatment. Vocal fold healing was complete in all cases by 6 months following surgery. Main voice parameters (subjective and objective) resulted improved at the 6-month control after surgery. In particular, voice handicap index (VHI) and GIRBAS scale resulted reliable for voice assessment and for the postoperative follow-up. In conclusion, VHI, GIRBAS, multidimensional voice program (MDVP) and spectroacoustic parameters showed a close trend in the present study, and this confirms the validity of the voice analysis performed by each tool.

Transnasal endoscopic management of petrous apex and clivus selected lesions.

The objective of this study was to report a series of selected primary skull base benign lesions midline located by transnasal endoscopic transsphenoidal approach. A retrospective review of 5 cases is presented: four cholesterol granuloma of the petruos apex and one of the clivus. All patients have been successfully treated via transnasal endoscopic transsphenoidal approach. The mean duration of follow-up was 27 months (range 12-50 months). No postoperative complication such as CSF leak, meningitis, or encephalocele and no signs of recurrence have been noticed. The transnasal route is a minimally invasive, safe, and efficient technique to approach the petrous apex and clivus for selected midline skull base lesions removal.

Subcutaneous sarcoidosis: a rare involvement of the paralateral nasal region.

A case of subcutaneous sarcoidosis involving the paralateral nasal region is described and a brief review of the literature is made. Subcutaneous sarcoidosis without systemic disease is a rare entity and has seldom been reported on the trunk and face. Diagnosis is always difficult as it can only be confirmed by histological studies.

Osteogenic potential of cells derived from nasal septum.

BACKGROUND: The research addressed to detect new molecular targets in the development of therapeutic strategies aimed to repair bone tissues. The AIM OF THIS STUDY was to determine the potential osteogenic activity of bone cells from the nasal septum and their use to perform accurate molecular analysis from a single sample. METHODOLOGY: The cells, after nasal septum surgery, were subjected to gene silencing, Reverse Transcriptase - Polymerase Chain reactions, immunocytochemistry and chromatin immunoprecipitation. RESULTS: Cells from the nasal septum can give rise to mature osteoblasts that express osteogenic markers (ALP, Runx2, Slug) and are able to mineralize. We demonstrated that Runx2, a transcription factor critical in early osteospecific differentiation, interacts in vivo with the promoter of the SLUG gene, a marker of osteoblast maturation. CONCLUSIONS: We demonstrated that nasal septum-derived osteoblasts represent an interesting alternative source for bone forming cells, and a promising material to be utilized in bone cellular therapy.

Total iron-overload measurement in the human liver region by the magnetic iron detector.

An accurate assessment of body iron accumulation is essential for the diagnosis and therapy of iron overload in diseases, such as hemochromatosis, thalassemia and other forms of severe anemias. The magnetic iron detector (MID) is a room-temperature susceptometer, which measures the total iron overload in the liver. Since February 2005, about 600 patients have been assessed using this device. The iron overload is obtained by calculating the difference between the measured magnetization signal of the patient and the patient's background signal. The latter is the magnetization signal that the patient would generate with normal iron content. This study presents the method for calculating the background signal of healthy volunteers and the application of the same method to patients with iron burden in order to evaluate their overload. The present MID sensitivity is 0.8 g and the reproducibility of the iron overload measurement of the same patients is lower than 0.5 g. The MID does not require calibration with liver biopsies. We correlated the MID measurements with the results of 26 biopsies (R = 0.62), 64 superconducting quantum interference device susceptometer measurements (R = 0.79), 666 serum ferritin concentration measurements (R = 0.72), and 41 MRI- R2* measurements (R = 0.71).

Genetic and metabolic factors are associated with increased hepatic iron stores in a selected population of p.Cys282Tyr heterozygotes.

Heterozygosity for p.Cys282YTyr is not ordinarily associated with a hemochromatosis phenotype, unless associated in the compound heterozygous state with other HFE mutations. The aims of the study were to identify factors responsible for iron overload in patients who were only heterozygous for p.Cys282Tyr at first genetic testing. Since 2001, twelve p.Cys282Tyr heterozygous patients with iron overload, defined by increased transferrin saturation, serum ferritin and hepatic iron stores, were identified. Four patients showed rare nonsense or missense HFE mutations in the compound heterozygous state with p.Cys282Tyr. One mutation (p.Gln233X) was never described before. The other 8 patients did not carry any other causal mutations in iron-related genes, but showed a very high prevalence of hepatic steatosis and steato-hepatitis, and metabolic alterations. Serum ferritin levels did not differ between the two groups, but transferrin saturation, hepatic iron amount and distribution significantly did. These last indices should be then strongly considered to decide for additional genetic characterization in p.Cys282Tyr heterozygotes. Our results also highlights the influence of metabolic alterations on serum iron indices and pattern of hepatic iron accumulation.