Management of patients with extensive locally advanced thyroid cancer: results of multimodal treatments.

PURPOSE: Surgery plays a key role in the treatment of thyroid cancer (TC) patients. Locally advanced cases, however, can require an extensive surgical approach with technical issues and a high risk of complications. In these cases, a multidisciplinary evaluation should be carried out to evaluate pros and cons. The aim of this study was to share our experience, as a multidisciplinary team, in the management of patients with locally advanced TC with a particularly extensive local disease, whose surgical approach could be challenging and part of a multimodal treatment. METHODS: We retrospectively evaluated clinical, surgical, and oncologic features of all patients with locally advanced TC who had undergone multidisciplinary surgery from January 2019 to June 2020. RESULTS: Six patients (two cases each of poorly differentiated, papillary, and medullary TC) were included. Four out of six were suffering from symptoms related to the advanced disease. At pre-surgical evaluation, a multidisciplinary team proposed extended surgery with radical intent via cervicotomy and sternotomy, considering other therapies not feasible or probably ineffective without it. No one passed away in intra- or perioperative time. At the end of follow-up (median 2.6 years), all patients presented a remission of symptoms due to the advanced disease, four patients were submitted to adjuvant therapies and only one patient died for a cause unrelated to the disease. CONCLUSION: This series of very advanced TCs shows the effectiveness of a surgery performed by a multidisciplinary team in controlling symptoms, allowing adjuvant therapies, and improving the survival of patients whose cases would otherwise be very difficult to manage.

Sequential bilateral cochlear implant: long-term speech perception results in children first implanted at an early age.

PURPOSE: The study aims to assess the benefit of sequential bilateral cochlear implantation in children with congenital bilateral profound hearing loss, submitted to the first implant at an early age. METHODS: We enrolled all the bilateral sequential cochlear implanted children who received the first implant within 48 months and the second within 12 years of age at our Institution. The children were submitted to disyllabic word recognition tests and Speech Reception Threshold (SRT) assessment using the OLSA matrix sentence test with the first implanted device (CI1), with the second implanted device (CI2), and with both devices (CIbil). Furthermore, we measured the datalogging of both devices. Then we calculated the binaural SRT gain (b-SRTgain) and checked the correlations between speech perception results and the b-SRTgain with the child's age at CI1 and CI2, DELTA and the datalogging reports. RESULTS: With the bilateral electric stimulation, we found a significant improvement in disyllabic word recognition scores and in SRT. Moreover, the datalogging showed no significant differences in the time of use of CI1 and CI2. We found significant negative correlations between speech perception abilities with CI2 and age at CI2 and DELTA, and between the SRT with CI1 and the b-SRTgain. CONCLUSIONS: From this study we can conclude that in a sequential CI procedure, even if a short inter-implant delay and lower ages at the second surgery can lead to better speech perception with CI2, children can benefit from bilateral stimulation independently of age at the second surgery and the DELTA.

Enlarged vestibular aqueduct and Mondini Malformation: audiological, clinical, radiologic and genetic features.

PURPOSE: When referring to enlarged vestibular aqueduct (EVA) we should differentiate between nonsyndromic enlarged vestibular aqueduct (NSEVA) and Pendred Syndrome (PDS), a disease continuum associated with pathogenic sequence variants of Pendrin's Gene (SLC26A4) in about half of the cases. The study was aimed to analyse the clinical and audiological features of a monocentric cohort of Caucasian patients with NSEVA/PDS, their genetic assessment and morphological inner ear features. METHODS: We retrospectively reviewed the audiologic, genetic and anamnestic data of 66 patients with NSEVA/PDS followed by our audiology service. RESULTS: SLC26A4 mutations was significantly correlated with the presence of PDS rather than NSEVA (p < 0.019), with the expression of inner ear malformations (p < 0.001) and with different severity of hearing loss (p = 0.001). Furthermore, patients with PDS showed significantly worse pure tone audiometry (PTA) than patients with NSEVA (p = 0.001). Anatomically normal ears presented significantly better PTA than ears associated with Mondini Malformation or isolated EVA (p < 0.001), but no statistically significative differences have been observed in PTA between patients with Mondini Malformation and isolated EVA. CONCLUSION: NSEVA/PDS must be investigated in all the congenital hearing loss, but also in progressive, late onset, stepwise forms. Even mixed or fluctuating hearing loss may constitute a sign of a NSEVA/PDS pathology. Our findings can confirm the important role of SLC26A4 mutations in determining the phenotype of isolated EVA/PDS, both for the type/degree of the malformation, the hearing impairment and the association with thyroid dysfunction.

Comparison of a purely endoscopic three-layer technique versus pericranial flap for reconstruction of anterior skull base defects after sino-nasal tumor resection: assessment of postoperative frontal lobe sagging and frontal lobe falling.

BACKGROUND: The evolution of endoscopic skull base approaches has enabled surgeons to manage selected skull base tumors through a transnasal endoscope-assisted approach. On the other side, more extensive lesions may require a combined cranioendoscopic approach. In this paper, we analysed and compared the incidence of frontal lobe sagging after endoscopic multilayer (EM) reconstruction versus pericranial flap (PF) reconstruction. METHODOLOGY: Subjects were selected retrospectively according to specific inclusion and exclusion criteria. The degree of frontal lobe sagging after surgery was calculated based on the most inferior position of the frontal lobe relative to the nasion-sellar line defined on preoperative and postoperative imaging. A positive value signified upward displacement, and a negative value represented frontal lobe sagging. RESULTS: Twenty subjects were enrolled in our study. In the EM technique group the average frontal lobe displacement was -2,34 ± 1,55 mm. The average postoperative frontal lobe sagging was -0,45 ± 8,92 mm in subjects reconstructed with the PF. The skull base defect size correlated with the degree of frontal lobe sagging in subjects reconstructed with the PF, but not in the other group and when merging the two groups. CONCLUSIONS: In conclusion, the EM technique and the PF reconstruction showed a good reliability for the closure of anterior skull base defects. Moreover the PF seemed to prevent frontal lobe sagging but, for larger skull base defects, it could be useful to be combined with other autologous or heterologous materials to avoid the frontal lobe falling.

A new technique to investigate vestibulo-spinal reflexes.

Vestibulospinal reflexes can be elicited in humans by low amplitudes direct (galvanic) currents lasting tens of milliseconds and applied across the two mastoids bones, which can be delivered by particular stimulators. The stimulus induces a perception of body sway and a postural response appropriate to counteract the perceived sway. Both the direction of the perceived and induced body sway are modulated by the orientation of the head with respect to the body. This phenomenon is due to the fact that integration of vestibular and neck signals allows to correctly infer the direction of body sway from the labyrinthine input, which is instead related to direction of head motion. The modulation of stimulus-elicited body sway by neck rotation could be utilised for testing the effectiveness of neck proprioceptive signals in modifying the reference frame for labyrinthine signals from the head to the body. In the present experiments we showed that labyrinthine stimulation can be performed also by using train of pulses of 1 msec duration, which can be delivered by virtually all stimulators allowed for human use. Moreover, we developed a simple technique for visualising the time course of the changes in the direction of the postural response, based on the evaluation of the velocity vector of subject's centre of pressure. This method could be exploited in order to the test the efficacy of neck proprioceptive information in modifying the reference frame for processing vestibular signals in both physiological and pathological condition.

Cochlear implantation in patients affected by superficial hemosiderosis of the central nervous system.

The objectives of the study were to: report three more cases of cochlear implantation (CI) in patients affected by superficial hemosiderosis of the central nervous system (SH-CNS); assess whether CI may be a viable option in this disease. The study was conducted in a tertiary referral center. Pre-operative and post-operative clinical notes of three patients with SH-CNS were reviewed. Two out of three cases showed very good results with CI in sentence perception in noise over 90%. For the other case, hearing performance was very low. He showed only disyllabic word identification abilities in a closed set (40%). Cochlear implantation may be a viable option for patients with severe to profound sensorineural hearing loss due to SH-CNS. In these cases, an adequate pre-operative counseling, explaining the possibility of poor post-operative results and/or the worsening of the outcomes in the following years, is important.

Cochlear implantation in patients with asymmetric hearing loss: reporting and discussing the benefits in speech perception, speech reception threshold, squelch abilities, and patients' reported outcomes.

OBJECTIVES: This study presents the results obtained in a group of patients with asymmetric hearing loss undergoing cochlear implantation at our institution. Prognostic factors are discussed in relation to different rehabilitative approaches for asymmetric hearing loss remediation. The current literature is also discussed. METHODS: Nineteen adult patients with post-verbal asymmetric hearing loss were enrolled. The results were assessed by means of a speech perception test, completed in silence and with background noise, and a speech reception threshold test (Oldenburg Sentence Test). The subjectively perceived benefits were assessed using the Speech, Spatial and Qualities of Hearing Scale. RESULTS: Statistically significant improvements were achieved by all patients in terms of speech perception and speech reception threshold, and in subjective benefits. CONCLUSION: The results confirm the literature findings which suggest that patients with asymmetric hearing loss generally gain substantial benefit from cochlear implantation because of the binaural input, with significant improvement in speech perception abilities in noise, speech reception threshold, and squelch abilities.

Unexpected delayed death after manual strangulation: need for careful examination in the emergency room.

The aim of this case report was to demonstrate the importance of detailed clinical assessment in victims of attempted manual strangulation, to prevent the occurrence of delayed death due to an airway collapse; and to provide an update on clinical management of these patients. An elderly male patient presented with a sore throat and speech impairment after attempting manual strangulation. Physical examination showed reddish skin of the neck, an extensive haematoma of the hard palate and anterior tongue. Flexible laryngoscopy failed to show any swelling of the hypopharynx or larynx. A few hours after presentation, the patient developed acute dyspnoea and died. Autopsy and post-mortem CT scan showed a haematoma in the thyro-epiglottal space. In conclusion, victims of manual strangulation can survive despite internal neck injury which can lead to delayed fatal airway collapse. This is because often there are few or no signs of assault, therefore medical evaluation should be thorough and timely. Sometimes immediate tracheotomy can be life saving.

Transtympanic Hearing Aid: exploratory study on a new device.

SUMMARY: In this paper, we present the preliminary results achieved with a transtympanic hearing aid (THA). This is a modified digital, open-fit external hearing aid (HA) designed for acute study only, which allows coupling with a pre-implanted ventilation tube. The THA conveys amplified sound directly onto the round window, bypassing the ossicular chain, in contrast with traditional HAs that convey sound onto the second or third portion of the external auditory canal. The THA has been developed as an alternative to standard HAs and active middle ear implants for patients who are unsatisfied with traditional HA outcomes and want to avoid middle-ear implantation. The results achieved using the THA were compared to those obtained with an equivalent device, the Latitude 8 Moxi 13 (Moxi), uncoupled from the ventilation tube, and placed onto the outer ear. For this purpose, 12 patients with conductive (1/12), sensorineural (3/12), or mixed (8/12) hearing loss from moderate to severe, with a pre-implanted ventilation tube, underwent audiological evaluation with both the THA and the Latitude 8 Moxi 13 (Moxi). Our initial results showed that the THA provided significant improvement in the warble tone results in comparison to the Moxi. Moreover, patients with a PTA between 41 and 90 also achieved better results in terms of speech recognition using the THA in comparison to the Moxi. In conclusion, these outcomes provide the first evidence of the potential benefits of the THA over standard open-fit HAs. Nevertheless, these preliminary outcomes require further confirmation.

Ultra-slow mechanical stimulation of olfactory epithelium modulates consciousness by slowing cerebral rhythms in humans.

The coupling between respiration and neural activity within olfactory areas and hippocampus has recently been unambiguously demonstrated, its neurophysiological basis sustained by the well-assessed mechanical sensitivity of the olfactory epithelium. We herein hypothesize that this coupling reverberates to the whole brain, possibly modulating the subject's behavior and state of consciousness. The olfactory epithelium of 12 healthy subjects was stimulated with periodical odorless air-delivery (frequency 0.05 Hz, 8 s on, 12 off). Cortical electrical activity (High Density-EEG) and perceived state of consciousness have been studied. The stimulation induced i) an enhancement of delta-theta EEG activity over the whole cortex mainly involving the Limbic System and Default Mode Network structures, ii) a reversal of the overall information flow directionality from wake-like postero-anterior to NREM sleep-like antero-posterior, iii) the perception of having experienced an Altered State of Consciousness. These findings could shed further light via a neurophenomenological approach on the links between respiration, cerebral activity and subjective experience, suggesting a plausible neurophysiological basis for interpreting altered states of consciousness induced by respiration-based meditative practices.

Paradoxical vocal cord dysfunction: clinical experience and personal considerations.

Paradoxical vocal cord dysfunction is a nosographic entity that remains to be fully elucidated as far as concerns criteria required for diagnosis and underlying aetiopathogenesis. The disorder manifests with repeated episodes of acute dyspnoea associated with a series of symptoms that may include hoarseness, globus, chest pain and "shortness of breath". A retrospective analysis of cases with acute dyspnoea referred to our Department between June 2004 and June 2005 revealed 3 patients with paradoxical vocal cord dysfunction. In 2 of these 3 cases, concomitant psychiatric morbidity was observed and the third also presented gastro-oesophageal reflux. In one patient, the episodes of dyspnoea were triggered by inspiration of irritating substances. Diagnosis of the condition requires a high level of suspicion, which is confirmed by a laryngoscopic investigation that demonstrates hyperadduction of the true vocal cords and a reduction of at least 50% in the breathing space. From a therapeutic point of view, patients with paradoxical vocal cord dysfunction require, in our opinion, a multidisciplinary approach; in fact, only a team comprising otorhinolaryngologists, phoniatricians, pulmonologists, neurologists, allergologists, psychotherapists and speech therapists is capable of defining the appropriate treatment according to the clinical and psychological characteristics of each individual patient. Our results with speech therapy, focused on respiratory and speech retraining, are reported.

Cochlear implant in prelingually deafened oralist adults: speech perception outcomes, subjective benefits and quality of life improvement.

The aim of this study is to report our results in a group of prelingually deafened adults, who followed an oralist rehabilitation programme, and submitted to cochlear implant at our institution. We evaluated 30 prelingually deafened adult patients, 18 males and 12 females, median age 35 years, of a group of 36 prelingually deafened adult patients consecutively submitted to unilateral cochlear implantation at the ENT Unit of the University of Pisa. After implantation, patients achieved significant benefits in terms of speech perception skills, including the ability to have telephone conversations in some cases, quality of life and their own perception of disability. According to literature data, the results herein reported are quite variable but generally satisfactory. Procedures other than traditional speech perception measures should be used to evaluate the benefits of cochlear implant in such patients, to compressively evaluate the global benefits, not only in terms of speech perception, but also in terms of quality of life and daily life.

Responses of Purkinje-cells of the cerebellar anterior vermis to stimulation of vestibular and somatosensory receptors.

In decerebrate cats, sinusoidal rotation of the forepaw around the wrist modifies the activity of the ipsilateral forelimb extensor triceps brachii (TB) and leads to plastic changes of adaptive nature in the gain of vestibulospinal (VS) reflexes (VSRs). Both effects are depressed by functional inactivation of the cerebellar anterior vermis, which also decreases the gain of VSRs. In order to better understand the mechanisms of these phenomena, the simple spike activity of Purkinje (P-) cells was recorded from the vermal cortex of the cerebellar anterior lobe during individual and/or combined stimulation of somatosensory wrist, neck and vestibular receptors. About one third of the recorded units were affected by sinusoidal rotation of the ipsilateral forepaw around the wrist axis (0.16 Hz, +/-10 degrees ). Most of these neurons ( approximately 60%) increased their activity during ventral flexion of the wrist and decreased it during the oppositely directed movement, with an average phase lag of -141 degrees with respect to the position of maximal dorsiflexion. The remaining cells ( approximately 40%) were excited during dorsiflexion of the wrist, with an average phase lead of 59 degrees with respect to the extreme dorsal flexion. Both populations showed comparable response gains, with an average value of 0.42+/-0.52, S.D., imp/s/deg. About half of the recorded units were also tested during sinusoidal roll tilt of the animal around the longitudinal axis (0.16 Hz, +/-10 degrees ), leading to stimulation of labyrinthine receptors. When both stimuli were applied simultaneously, the responses to combined stimulation usually corresponded to the sum of individual responses. While the phase distribution of somatosensory responses was clearly bimodal, vestibular responses showed phase angle values uniformly scattered between +/-180 degrees and 0 degrees , so that, during combined stimulation, each neuron could be maximally activated by coupling the two stimuli with a particular phase relation. Finally, a proportion of the recorded neurons was also tested during sinusoidal rotation of the body around its longitudinal axis, with the head fixed in space, leading to stimulation of neck receptors. The proportion of neurons affected by individual stimulation of vestibular or neck receptors (81% and 72%, respectively) was larger than that of wrist-driven neurons. Convergence of signals from vestibular, somatosensory wrist and neck receptors was found in 18% of the neurons analyzed. In conclusion, the results of this study show that somatosensory signals from the forelimb: i) modulate the activity of a sizeable proportion of neurons located within the cerebellar anterior vermis and ii) interact widely with labyrinthine and neck signals at this level. Moreover, iii) this corticocerebellar region is largely dominated by vestibular and neck signals that may be utilized to build up a neuronal representation of the position of body in space. These findings suggest that: 1) the modulation of TB activity induced by rotation of the ipsilateral wrist may at least partially depend upon the simultaneous changes in P-cell activity and 2) the interaction of vestibular and somatosensory wrist signals at P-cell level may represent the substrate of the plastic changes that affect the VSR when animal tilt and wrist rotation are driven together. A preliminary report of these data has been presented [ Responses of cerebellar Purkinje cells to forepaw rotation in decerebrate cat. Pflügers Arch 440:R31].

Transtympanic steroids in refractory sudden hearing loss. Personal experience.

The treatment of choice for sudden sensorineural hearing loss is still lacking. Many drugs have been used over the years, with varying results and steroids have proven to be effective in clinical trials, albeit systemic administration is associated with untoward side-effects and cannot be used in all patients. The transtympanic approach presents two main advantages: first, it allows higher concentrations in the inner ear environment and, second, it minimizes systemic absorption. Aim of the present investigation was to establish the effectiveness of transtympanic steroid treatment for sudden sensorineural hearing loss in patients in whom conventional treatment had failed. For this purpose, a prospective, non-randomized study was designed to evaluate hearing improvement in sudden sensorineural hearing loss patients treated with transtympanic steroids. A solution of methyl-prednisolone and sodium bicarbonate was administered, via a transtympanic injection, in 10 patients. Hearing levels were evaluated before treatment and on days 1, 7 and 30, thereafter. Improvement in hearing was observed in 70% of patients, moreover, in patients not usually considered amenable to this kind of treatment. Transtympanic steroid treatment is an effective and safe option for patients with sudden sensorineural hearing loss when conventional treatment regimens have failed. Further studies are needed to define the optimal dosage, route of administration and type of steroids.

Aetiologic diagnosis of hearing loss in children identified through newborn hearing screening testing.

With the implementation of universal newborn hearing screening (UNHS) programmes and early diagnosis and treatment of hearing problems, the need has clearly emerged to implement and carry out a systematic and coordinated protocol for the aetiological diagnosis of permanent hearing impairment (PHI). Within the framework of the Italian Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for early Identification, Intervention and Care of Hearing Impaired Children", it has been decided to consider the problems relative to aetiological diagnosis of child PHI within UNHS programmes. The specific objective was to apply a shared diagnostic protocol that can identify the cause in at least 70% of cases of PHI. For this part of the project, four main recommendations were identified that can be useful for an efficient aetiological diagnosis in children affected by PHI and that can offer valid suggestions to optimise resources and produce positive changes for third-level audiologic centres.

Idiopathic sensorineural hearing loss in the only hearing ear.

A retrospective chart review was used for 31 patients with sudden, progressive or fluctuating sensorineural hearing loss (SHL) in the only hearing ear who had been consecutively evaluated at the ENT, Audiology and Phoniatrics Unit of the University of Pisa. The group of patients was evaluated with a complete history review, clinical evaluation, imaging exam (MRI, CT), audiologic tests (tone and speech audiometry, tympanometry, study of stapedial reflexes, ABR and otoacoustic emission) evaluation. In order to exclude genetic causes, patients were screened for CX 26 and CX30 mutations and for mitochondrial DNA mutation A1555G. Patients with sudden or rapidly progressive SHL in the only hearing ear were treated with osmotic diuretics and corticosteroids. In patients who did not respond to intravenous therapy we performed intratympanic injections of corticosteroid. Hearing aids were fitted when indicated and patients who developed severe to profound SHL were scheduled for cochlear implant surgery. The aim of this study is to report and discuss the epidemiology, aetiopathogenesis, therapy and clinical characteristic of patients affected by SHL in the only hearing hear and to discuss the issues related to the cochlear implant procedure in some of these patients, with regard to indications, choice of the ear to implant and results.

Early care in children with permanent hearing impairment.

The implementation of regional protocols for newborn hearing screening and early audiologic diagnosis represent the first step of the entire diagnostic, rehabilitative and prosthetic programme for children with permanent hearing impairment. The maximum benefit of early diagnosis can indeed be obtained only by prompt rehabilitation aimed at fostering the child's communicative, linguistic and cognitive development. Within the framework of the CMM 2013 project of the Ministry of Health entitled "Preventing Communication Disorders: a Regional Program for Early Identification, Intervention and Care of Hearing Impaired Children", the problems concerning the promotion of the global development of children with PHI through an early rehabilitation project based on shared knowledge and scientific evidence. In this project, our specific aim was to define the features and modes of access to a precise and specialised rehabilitation project for the small hearing-impaired child within three months from audiologic diagnosis. Three main recommendations relative to assessment and rehabilitation aspects of early care emerged from the study.

Drop attacks and vertical vertigo after transtympanic gentamicin: diagnosis and management.

Drop attacks represent a significant problem during the natural course of Meniere's disease. They are characterized by a sudden fall to the ground without loss of consciousness. Diagnosis is clinical and based on the typical description of the patient. Involvement of vertical canal is possible during Meniere's disease and also after gentamicin application. Treatment of drop attacks is still a matter of discussion; most cases have a benign course with spontaneous remission and no treatment is necessary. In severe cases, aggressive treatment (surgical or pharmacological) is necessary. A case of drop attack associated with vertical vertigo is presented. Vestibular tests were performed in order to assess the involvement of inner ear. Caloric test and ice water test reveal no response. Vestibular Evoked Myogenic Potentials are present even after high doses of gentamicin. Drop attacks and vertical vertigo can occur after transtympanic gentamicin and can be well managed with high doses of local gentamicin.

Neck input modifies the reference frame for coding labyrinthine signals in the cerebellar vermis: a cellular analysis.

The activity of 68 neurons, mainly Purkinje cells, was recorded from the cerebellar anterior vermis of decerebrate cats during wobble of the whole animal (at 0.156 Hz, 5 degrees), a mixture of tilt and rotation, leading to stimulation of labyrinth receptors. Most of the neurons (65/68) were affected by both clockwise and counterclockwise rotations. Twenty-four units showing responses of comparable amplitude to these stimuli (narrowly tuned cells) were represented by a single vector (Smax), whose preferred direction corresponded to the direction of stimulation giving rise to the maximal response. The remaining 41 units, however, showed different amplitude responses to these rotations (broadly tuned cells) and were characterized by two spatially and temporally orthogonal vectors (Smax and Smin), suggesting that labyrinthine signals with different spatial and temporal properties converged on these cells. All these units were tested while the body was aligned with the head (control position), as well as after static displacement of the body under a fixed head by 15 degrees and/or 30 degrees around a vertical axis passing through C1-C2, thus leading to stimulation of neck receptors. The orientation component of the response vector of the Purkinje cells to vestibular stimulation changed following body-to-head displacement. Moreover, the amplitude of vector rotation corresponded, on the average, to that of body rotation. Changes in temporal phase, gain and tuning ratio of the responses were also observed. We propose that information from neck receptors regulates the convergence of labyrinthine signals with different spatial and temporal properties on corticocerebellar units. Due to their strict relationship with the motor system, these units may give rise to appropriate responses in the limb musculature, by modifying the spatial organization of the vestibulospinal reflexes according to the requirements of body stability. The cerebellar vermis may thus represent an important structure, where frames of reference can be altered to account for changes in position of trunk, head and neck.