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BACKGROUND: Dysphagia is common in Parkinson's disease (PD). The effects of antiparkinsonian drugs on dysphagia are controversial. Several treatments for dysphagia are available but there is no consensus on their efficacy in PD. OBJECTIVE: To conduct a systematic review of the literature and to define consensus statements on the treatment of dysphagia in PD and related nutritional management. METHODS: A multinational group of experts in the field of neurogenic dysphagia and/or Parkinson's disease conducted a systematic evaluation of the literature and reported the results according to PRISMA guidelines. The evidence from the retrieved studies was analyzed and discussed in a consensus conference organized in Pavia, Italy, and the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. RESULTS: The literature review retrieved 64 papers on treatment and nutrition of patients with PD and dysphagia, mainly of Class IV quality. Based on the literature and expert opinion in cases where the evidence was limited or lacking, 26 statements were developed. CONCLUSIONS: The statements developed by the Consensus panel provide a guidance for a multi-disciplinary treatment of dysphagia in patients with PD, involving neurologists, otorhinolaryngologists, gastroenterologists, phoniatricians, speech-language pathologists, dieticians, and clinical nutritionists. ispartof: JOURNAL OF THE NEUROLOGICAL SCIENCES vol:430 ispartof: location:Netherlands status: published

Aim: The novel primary end-point of the present study was to ascertain β-arrestin-1 expression in a cohort of consecutive patients with laryngeal squamous cell carcinoma (LSCC) with information available on their cigarette-smoking habits. A secondary end-point was to conduct a preliminary clinical and pathological investigation into the possible role of β-arrestin-1 in the epithelial-to-mesenchymal transition (EMT), identified by testing for E-cadherin, Zeb1, and Zeb2 expression, in the setting of LSCC. Methods: The expression of β-arrestin-1, E-cadherin, zeb1, and zeb2 was ascertained in 20 consecutive LSCCs. Results: Statistical analysis showed no significant associations between β-arrestin-1 and EMT (based on the expression of E-cadherin, Zeb1, and Zeb2). The combined effect of nicotine and β-arrestin-1 was significantly associated with a shorter disease-free survival ( P=0.01) in our series of LSCC. This latter result was also confirmed in an independent, publicly available LSCC cohort ( P=0.047). Conclusions: Further investigations on larger series (ideally in prospective settings) are needed before we can consider closer follow-up protocols and/or more aggressive treatments for patients with LSCC and a combination of nicotine exposure and β-arrestin-1 positivity in tumor cells at the time of their diagnosis. Further studies on how β-arrestin functions in cancer via different signaling pathways might reveal potential targets for the treatment of even advanced laryngeal malignancies.

Background When advanced, oral squamous cell carcinoma (OSCC) may involve adjacent non-epithelial structures, and the prognosis is worse for bone invasion. Human relaxin-2 is a peptide hormone that has recently been associated with cancer. It can induce human osteoclast differentiation and activation, suggesting a role in tumor-driven osteolysis. This study was a preliminary assessment of the prognostic role of relaxin-2 in surgical specimens of OSCC tissue and adjacent but uninvolved mandibular/maxillary bone. Methods Relaxin-2 immunohistochemical expression and reaction intensity were assessed in tumor and uninvolved adjacent mandibular/maxillary bone specimens from 23 operated OSCC patients. Results All OSCC specimens were positive for relaxin-2. The intensity of its reaction in OSCC correlated significantly with the pattern of the tumor's invasion front (p = 0.02), being higher with the infiltrative pattern. Mean relaxin-2 immunohistochemical expression was higher in patients whose OSCC recurred after treatment than those experiencing no recurrence (81.3% ± 22.6% vs. 59.5% ± 29.7%, respectively). A significant direct association emerged between relaxin-2 expression in OSCC specimens and recurrence rate (p = 0.049). Conclusions Relaxin-2 expression in OSCC should be further investigated as a potentially useful marker for identifying patients at higher risk of recurrence, who might benefit from closer follow-up and more aggressive adjuvant therapy. In other oncological settings, increasing evidence of relaxin being produced by cancer cells is prompting efforts to synthesize human relaxin-2 analogs capable of acting as antagonists and limiting tumor growth.

Background Adenosquamous carcinoma (ASC) of the head and neck is a rare malignancy characterized by loco-regional and distant aggressiveness. At histology, ASC reveals two distinct, juxtaposed components, squamous cell carcinoma (SCC), and true adenocarcinoma. Methods The immunohistochemical expression of AE3, CK19 and CAM5.2, and HPV infection was tested in a case of laryngeal ASC. Results The patient had no regional lymph node metastases, but developed a recurrence in neck soft tissues shortly after primary radical surgery. The laryngeal surgical specimen had the typical morphological features of ASC. The tumor's squamous and glandular components were both strongly and diffusely immunoreactive for AE3 and CK19, whereas CAM5.2 selectively stained only the gland-like part. We found no high- or low-risk HPV DNA (28 genotypes) in the specimens. The patient underwent salvage extended radical neck dissection and received postoperative radio-chemotherapy. At 4-month follow-up control, neck recurrence was found. Palliative chemotherapy was instituted. Conclusions An accurate histological and immunohistochemical diagnosis is mandatory to differentiate ASC from conventional SCC. Radical surgical excision is recommended for laryngeal ASC. Adjuvant postoperative therapy is administered in most cases, but there are no widely accepted indications for these treatments.

Olfactory receptors were found to be expressed also in human sperm giving rise to the hypothesis that they might play a role in fertility and sexual behavior. For instance, bourgeonal was demonstrated to be an agonist of sperm cells olfactory receptor, OR1D2. OR1D2 has been found to be expressed in human olfactory epithelium and to play a critical role in human sperm chemotaxis. Recent preliminary evidence showed that olfaction sensitivity (determined by n-butanol olfactory threshold) and sexual desire were associated in young adult males. It is reasonable to hypothesize that bourgeonal olfactory threshold could be related with human sexual behavior and desire. In 37 healthy young adult male volunteers (age range 20-36 years), the bourgeonal odor threshold and the intensity of sexual desire [the latter using the International Index of Erectile Function (IIEF) scale] were examined. In addition, samples of DNA were collected. Allele and genotype frequency of the OR1D2 single nucleotide polymorphisms (SNPs) were then evaluated in order to study the relationship between sexual desire and OR1D2 SNPs expression. The olfactory threshold was categorized as

The aim of this review is to summarise literature data on clinical aspects and traditional management of fungal malignant external otitis (FMEO), and to identify potential predictive factors of positive treatment outcome. Articles were initially selected based on their titles or abstracts. Full articles were then retrieved and further scrutinised according to predetermined criteria. Reference lists of selected articles were searched for any missed publications. The selected articles were methodologically evaluated. Of an initial 143 references, 14 were selected that focalised on the management of FMEO. The majority of studies demonstrated a correlation between treatment effectiveness, assessed as symptom resolution, and clinical and management variables: abstention from surgical debridement, absence of facial palsy, Aspergillus spp. as causative pathogen and absence of imaging findings at diagnosis and follow-up. The effectiveness of FMEO treatment depends on the assessment of cranial nerve state, the causative pathogen and imaging findings. Above all, absence of facial nerve palsy, Aspergillus spp. and absence of radiological signs at diagnosis and during follow-up correlate with symptom resolution. The fact that conservative treatment may be associated with a better outcome than surgical debridement could purely reflect that patients with more aggressive and advanced illness required debridement, whereas milder disease was treated conservatively. Thus, caution should be advised in the interpretation of data due to the need for further trials on the topic.Obiettivo dello studio è stato riassumere i dati della letteratura sugli aspetti clinici e la gestione abituale dell'otite esterna maligna fungina (OEMF), ed identificare possibili fattori predittivi di esito positivo del trattamento. Gli articoli sono stati inizialmente selezionati sulla base del titolo e degli abstract. Sono poi stati recuperati ed analizzati per intero seguendo criteri predeterminati. È stata stilata una lista di riferimento degli articoli selezionati per cercare eventuali pubblicazioni mancati. Gli studi raccolti sono stati infine valutati metodologicamente. Dei 143 articoli iniziali, ne sono stati selezionati 14 focalizzati sulla gestione dell'OEMF. La maggior parte di questi ha dimostrato una correlazione tra l'efficacia del trattamento, inteso come risoluzione dei sintomi, ed alcune variabili cliniche e di gestione della patologia quali l'astensione da procedure chirurgiche invasive, l'assenza di paralisi facciale, l'Aspergillus spp come patogeno causante e l'assenza di segni radiologici alla diagnosi e nel corso del follow-up. L'efficacia del trattamento dipende dalla valutazione dello stato dei nervi cranici, dal patogeno alla base e dai segni radiologici, più precisamente: l'assenza di paralisi facciale, l'Aspergillus spp e l'imaging negativo alla diagnosi e durante il follow-up correlano con la risoluzione dei sintomi. L'evidenza che il trattamento farmacologico possa associarsi ad un miglior outcome rispetto a procedure chirurgiche invasive potrebbe semplicemente riflettere il fatto che pazienti affetti da una patologia più avanzata richiedono un approccio più aggressivo mentre le forme più lievi possono essere trattate in modo conservativo. È necessario quindi prestare attenzione nell'interpretazione dei dati a causa della necessità di ulteriori studi sull'argomento.

Objective:To discover the anatomist who first identified the upper oesophageal sphincter.Method:The authors searched dozens of antique anatomy textbooks kept in the old section of the ‘Vincenzo Pinali’ Medical Library of Padua University, looking for descriptions of the upper oesophageal sphincter.Results:The oesophageal sphincter was drawn correctly only in 1601, by Julius Casserius, in the book De vocis auditusque organis historia anatomica… (which translates as ‘An Anatomical History on the Organs of Voice and Hearing …’), and was properly described by Antonio Maria Valsalva in 1704 in the book De aure humana tractatus… (‘Treatise on the Human Ear …’).Conclusion:Anatomists Casserius and Valsalva can be considered the discoverers of the ‘oesophageal sphincter’.

Objectives Before the widespread use of antibiotics, most deep neck infections (DNIs) stemmed from complicated pharyngeal infections. Nowadays, they seem to be due mainly to dental infections. In 2010, our group reported that DNIs originated from a major salivary gland in 14% of cases. The main endpoint of the present investigation was to review our experience of the diagnosis and treatment of DNIs of salivary gland origin. We also compared the characteristics of DNIs originating from salivary glands with those originating elsewhere. Methods Between 2000 and 2011, 44 patients were treated for DNIs of salivary origin at our institution. These patients were compared with 191 cases of DNI diagnosed as having other sites of origin. Results/conclusions In the present series, DNIs originating from a major salivary gland accounted for 19% of all cases of DNI of known origin. Patients with DNI of salivary gland origin were more likely to be elderly than those whose DNI originated from elsewhere (p = 0.000). Our multivariate statistical model showed that comorbidities (p = 0.051, statistical trend) and the need for surgical treatment (p = 0.028) independently predicted long-term hospitalization for DNIs originating from a major salivary gland.

Smoking is a self-destructive behavior that is known to induce remodeling of the lower airways, leading to squamous metaplasia, but little is known about its effects on the nose and paranasal sinuses. Nasal irrigations are often mentioned as measures for treating sinonasal inflammations. The purpose of our study was to compare the effects of nasal irrigations with sulfurous-arsenical-ferruginous thermal water or isotonic sodium chloride solution in smokers with nonallergic chronic rhinosinusitis, based on clinical and olfactory evidence.The present study was a prospective, randomized, double-blind study performed in a tertiary academic referral center. Seventy smokers with nonallergic chronic rhinitis were enrolled. Nasal endoscopy, rhinomanometry, nasal cytology, and odor threshold measurements were performed in subjects randomized to daily nasal irrigations with either thermal water or isotonic sodium chloride solution for 1 month.Immediately after the treatment, the thermal water irrigations revealed a positive pharmacologic action, judging from a tendency toward lower nasal resistances (P = .07) and larger numbers of ciliated cells in the patients treated (P = .003). Endoscopic findings in the thermal water group were still better than in the control group a further 2 months later (P = .03).Our results indicate that nasal irrigations with thermal water had a good effect on endoscopic objective signs, nasal resistances, and epithelial trophism.

There are currently no clinical or pathological parameters able to predict response to adjuvant radiotherapy (RT) in laryngeal squamous cell carcinoma (LSCC). Few studies have investigated the molecular pathways potentially capable of predicting said response. The mammalian target of rapamycin (mTOR) acts as a 'master switch' protein in cancer cells, modulating metabolism, the cell cycle, and apoptosis. Cancer treatment with mTOR inhibitors (rapamycin analogs, or rapalogs) has produced promising results in various malignancies (renal cell carcinoma, breast cancer, prostate cancer, leukemia, lymphoma, and melanoma). The novel aim of the present study was to ascertain the prognostic role of mTOR expression in a series of patients with LSCC treated with primary surgery followed by RT.The retrospective study involved 25 consecutive patients with LSCC given postoperative RT. Immunohistochemical mTOR expression was evaluated in primary LSCC by image analysis.The locoregional recurrence rate was significantly higher in patients with LSCC whose mTOR expression was2.5% (P = 0.013). After postoperative RT, the locoregional recurrence risk ratio was 3.25 in LSCCs with mTOR2.5%. The different disease-free survival was significantly shorter in cases of LSCC with mTOR2.5% (P = 0.029).mTOR should be studied as a potential predictor for identifying LSCCs at higher risk of early recurrence after postoperative RT. New therapeutic strategies should be investigated in LSCC, including the use of rapalogs associated with conventional chemotherapeutic regimens in combination with RT.

Objectives Nasal irrigations are mentioned among the adjunctive measures for treating several sinonasal conditions. Hyperchromatic supranuclear stria (HSS) in the ciliated cells (CCs) has recently been suggested as a potential cytological marker of the anatomofunctional integrity of nasal mucosa. The aim of this study was to compare the effects of nasal irrigations with sulfurous, salty, bromic, iodic (SSBI) thermal water or isotonic sodium chloride solution (ISCS) in patients with nonallergic chronic rhinosinusitis, considering the endoscopic, functional, microbiological, and cytological evidence (including the ratio of HSS-positive CCs to total CCs [the HSS+ rate]). Methods In a prospective, randomized, double-blind setting, 80 patients were recruited for nasal irrigations with SSBI water or ISCS for 1 month. Results An endoscopically assessed significant clinical improvement was seen after both SSBI thermal water and ISCS irrigations. Before treatment, Staphylococcus aureus was isolated in 5 patients in the SSBI thermal water group and 4 in the ISCS group. After the nasal irrigations, there was no sign of the bacteria in either group. Only the SSBI water irrigations significantly reduced total nasal resistance, as determined by rhinomanometry. Mild nasal irritation (6 cases) and episodes of extremely limited epistaxis (5 cases) were only reported after SSBI thermal water irrigations. Neither type of nasal irrigation significantly increased the mean HSS+ rate at cytological control after 1 month. Conclusions Both types of nasal irrigation improved the endoscopic and microbiological features of patients with nonallergic chronic rhinosinusitis, whereas only SSBI irrigations significantly reduced total nasal resistance. Further investigations are needed based on longer treatments and follow-up periods to establish whether the HSS+ rate is useful for monitoring clinical improvements in chronic rhinosinusitis treated with nasal irrigations.

It is known that 15-20% of oropharyngeal carcinomas develop distant metastases that involve most commonly lung, liver and bone. Clival metastasis from oropharyngeal squamous cell carcinoma has not been previously reported in the English literature. We describe the rare occurrence of clival metastasis from tonsillar carcinoma presenting with abducent paralysis and discuss diagnostic and therapeutic rational approaches. Despite neoadjuvant chemotherapy (cisplatinum/etoposide/epirubicin followed by taxotere), extended left tonsillectomy and ipsilateral radical neck dissection and external radiotherapy (60 Gy) for tonsillar carcinoma, the patient developed clival metastasis and died of disease. The overall prognosis of patients with clival metastases is extremely poor, with an overall median survival of about 2.5 years. Cranial nerve palsy occurrence is associated with a poorer prognosis with an average survival of only 5 months.

Laryngeal carcinoma is the 11th commonest form of cancer in men world-wide, with 121,000 new cases in 1985. More than 95% of all laryngeal malignancies are squamous cell carcinomas. Treatment indications in cancer of the larynx are often controversial, since there are few comparative studies of different available therapeutic approaches. Surgery and radiotherapy are both widely used, and the choice between these two procedures is the most common therapeutic decision which has to be taken. Laryngeal function preservation has gained more and more weight in the last decades and chemotherapy is also a significant component of several curative approaches. In the last decades, several organ-preserving surgical techniques have become available and consequently total laryngectomy results less applied. Regardless of the treatment modality, Tis, T1, T2 laryngeal carcinomas have an 80-90% probability of cure, whereas for more advanced tumours this is approximately 60%. The most effective approach to laryngeal cancer remains prevention and early diagnosis when this cancer is curable with function preserving treatments.

Cervical masses are a common clinical finding, but differential diagnosis is often challenging. Acute neck swellings are often due to deep cervical space infections that have originated at oral or oropharyngeal sites. Deep neck infections originating elsewhere are not rare; however, they are difficult to diagnose, and their origins remain obscure in 20% of cases. Neck swellings that originate in the middle ear are very rare, with only a few reported in the scientific literature. Here we report an atypical case of Bezold's abscess caused by the recurrence of a middle ear cholesteatoma. In patients with neck swelling and a history of primary cholesteatoma of the middle ear, otolaryngologists should consider regional recurrence of disease a possibility even several years after the primary surgery.

Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD. Objective To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients. Methods A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. Results Eighty-five papers were used to inform the Panel’s statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions. Conclusions The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD.

Background Obstructive sleep apnoea (OSA) is an independent risk factor of hypertension and cardiovascular diseases. Recurrent episodes of upper airways collapse during sleep causing blood oxygen desaturation, hypercapnia, and micro-arousals, are known to activate the sympathetic nervous system (SNS). However, whether changes in the renin-angiotensin-aldosterone system and endothelial activation also occur remains contentious. Methods Based on routine use of drug-induced sleep endoscopy (DISE) for the work-up of OSA patients in our centre, we designed a prospective study to investigate the haemodynamic and humoral changes occurring during the apnoeic episodes reproduced in vivo in the course of DISE. Specifically, plasma aldosterone concentration and renin activity, C-terminal fragment of proendothelin-1, as a marker of endothelial damage, and free plasma catecholamines, will be measured at fixed times during DISE. The activity of catechol-O-methyltransferase (COMT), a key catecholamine-inactivating enzyme that has been scantly investigated thus far owing to the lack of commercially available kits, will be also determined by a newly developed high performance liquid chromatography method, which is herein described. Results and conclusions The aim of this study is to provide novel information on the haemodynamic, hormonal, and SNS changes, and also on COMT activity modification concomitantly occurring during apnoea, thus contributing substantively to the understanding of the pathophysiology of OSA.