Overall survival, disease-free survival and quality of life in patients affected by HPV mediated p16+ oropharyngeal squamous cell carcinoma treated with upfront trans-oral robotic surgery vs radiotherapy or chemoradiotherapy.

PURPOSE: Treatment de-intensification for p16 + oropharyngeal squamous cell carcinoma (OPSCC) is an area of active research to reduce the side effects and improve patients' quality of life (QoL). In this paper we evaluated the Overall Survival (OS), the Disease-Free Survival (DFS) and the QoL of patients affected by p16 + OPSCC according to their prognostic stage group (PSG) and different treatments. METHODS: Patients were selected retrospectively through our Electronic Tumor Board Database according to prespecified inclusion criteria. Basic data of eligible patients were recorded and analyzed. Then, OS and DFS were evaluated according to the PSG and the treatments performed. Patients alive completed three questionnaires: the QoL Questionnaire Core 30 (QLQ-C30), the QoL Questionnaire Head & Neck 43 (QLQ-HN43) and the MD Anderson Dysphagia Inventory (MDADI) questionnaire. RESULTS: Sixty-one patients were included in this study. Eight patients died from the disease and the remaining 53 patients completed the 3 questionnaires. Fifteen (25%) patients were treated with upfront surgery, 6 (10%) patients with definitive radiotherapy and 40 (65%) patients with concomitant chemoradiotherapy. Comparing the DFS and the OS of PSG I patients by the different treatments performed, no statistically significant difference was identified. Patients treated with upfront surgery showed better outcomes in some aspects of their QoL. CONCLUSION: For p16 + OPSCC PSG I patients, upfront surgery can be considered a valid alternative to radiotherapy or chemoradiotherapy while maintaining a comparable DFS and OS and giving patients better results in terms of specific aspects of their QoL.

Acute Otitis Media and Facial Paralysis in Children: A Systemic Review and Proposal of an Operative Algorithm.

Acute otitis media (AOM) is one of the most common ENT diseases in children. In the antibiotic/post-antibiotic era, facial paralysis is a very rare complication of AOM (0.004-0.005%). Despite the rarity of this complication, it should be known by all physicians for proper therapeutic management to avoid serious sequelae. The aim of this review is to provide a management guide based on the current literature. MATERIALS AND METHODS: Fifteen studies published between 2000 and 2022 were selected, including 120 patients (62 M/58 F) with an average age of 4.96 years old (range = 4 months-16 years; SD: 4.2). The paralysis frequently has a sudden onset and is of a severe grade (medium House-Brackmann (HB) score at onset: 4.68; SD: 0.5); however, it tends to have an almost complete recovery in most patients (88.49% HB 1 at follow-up). RESULTS: Its first-line treatment must be based on the use of antibiotics (beta-lactam antibiotics as penicillins or cephalosporins). Corticosteroids should be used concomitantly for their anti-inflammatory and neuroprotective actions; however, there is no unanimity between authors about their application. Myringotomy, with or without ventilation tube insertion, is indicated in cases where the tympanic membrane is intact. Other kinds of surgery should be performed only in patients who have a worsening of their AOM symptoms or a worsening in HB score even with clinical treatment. CONCLUSIONS: The obtained data show that a conservative treatment can be sufficient for complete recovery in most patients, and it is preferred as the first-line therapy. Mastoidectomy should be performed only in patients with acute mastoiditis and without symptom improvement after a conservative approach. There are insufficient data in the current literature to provide clear selection criteria for patients who need to undergo mastoidectomy with facial nerve decompression. The choice of this treatment is based on an individual center expertise. Further studies are needed to clarify the role of corticosteroids and the role of facial nerve decompression in this clinical scenario.

Extrusion and Dislocation in Titanium Middle Ear Prostheses: A Literature Review.

Titanium middle ear (ME) prostheses are widely used in surgical practice due to their acoustic properties. However, they present a significant drawback shared by all synthetic materials currently in use for ME reconstruction: they can be rejected by the organism of the host. In this study, we aim to review the current literature on titanium partial ossicular replacement prostheses (PORPs) and total ossicular replacement prostheses (TORPs) extrusion and dislocation. Eighty articles were analysed after a full article review based on the inclusion and exclusion criteria. The most common indication for reconstruction was chronic otitis media with cholesteatoma. The average extrusion or dislocation rate was 5.2%, ranging from 0 to 35%. The average improvements in the air-bone gap were 12.1 dB (1.6 dB to 25.1 dB) and 13.8 (-0.5 dB to 22.7 dB) for the PORP and TORP groups, respectively. The data reported on this topic are highly variable, demonstrating that functional outcomes are difficult to predict in clinical practice. We believe that the current limitations could be overcome with technological developments, including bioengineering research focused on promoting prosthesis adaptation to the ME environment.

Current trends on subtotal petrosectomy with cochlear implantation in recalcitrant chronic middle ear disorders.

Objective: To establish the safety and effectiveness of subtotal petrosectomy with cochlear implantation in patients affected by chronic middle ear disorders to refractory to previous surgical treatments. Methods: A multicentre, retrospective study was conducted on patients affected by recalcitrant chronic middle ear disorders who underwent cochlear implantation in combination with subtotal petrosectomy. Patients' details were collected from databases of 11 Italian tertiary referral centres. Additionally, a review of the most updated literature was carried out. Results: 55 patients were included with a mean follow-up time of 44 months. Cholesteatoma was the most common middle ear recurrent pathology and 50.9% of patients had an open cavity. 80% of patients underwent a single stage surgery. One case of explantation for device failure was reported among the 7 patients with post-operative complications. Conclusions: Subtotal petrosectomy with cochlear implantation is a benchmark for management of patients with recalcitrant chronic middle ear disorders. A single stage procedure is the most recommended strategy. Optimal follow-up is still debated. Further studies are required to investigate the role of this surgery in paediatric patients.

Surgical Treatment of an Endolymphatic Sac Tumor.

Endolymphatic sac tumors (ELST) are low-grade papillary adenocarcinoma originating from the endolymphatic sac. Usually slow-growing, with local aggressiveness and a low risk of distant metastases, ELST can be sporadic but also frequently associated with von Hippel Lindau disease. The current treatment of ELST is primarily surgical resection. A 55-year-old woman accessed our otologic tertiary level referral center for a sudden worsening of hearing loss in her left ear and vertigo. A magnetic resonance (MRI) and computer tomography scan study subsequently showed a mass in the petrous bone; hence, the presence of an ELST was hypothesized. After embolization of the mass, the patient underwent surgical removal of the lesion. The resection of the mass was done through a translabirinthine approach, with an uneventful procedure. No residual disease remained after surgery. After 24 months of radiologic follow up with MRI, there are no signs of recurrence disease. This paper reports the management of this sporadic ELST, as well as the follow up results, providing clinicians this protocol for the handling of such a challenging otologic skull base surgery and rare disease.

Incidence and types of laryngotracheal sequelae of prolonged invasive ventilation in COVID-19 patients.

PURPOSE: The COVID-19 outbreak has led to an increasing number of acute laryngotracheal complications in patients subjected to prolonged mechanical ventilation, but their incidence in the short and mid-term after ICU discharge is still unknown. The main objective of this study is to evaluate the incidence of these complications in a COVID-19 group of patients and to compare these aspects with non-COVID-19 matched controls. METHODS: In this cohort study, we retrospectively selected patients from November 1 to December 31, 2020, according to specific inclusion and exclusion criteria. The follow-up visits were planned after 6 months from discharge. All patients were subjected to an endoscopic evaluation and completed two questionnaires (VHI-10 score and MDADI score). RESULTS: Thirteen men and three women were enrolled in the COVID-19 group while nine men and seven women were included in the control group. The median age was 60 [56-66] years in the COVID-19 group and 64 [58-69] years in the control group. All the patients of the control group showed no laryngotracheal lesions, while five COVID-19 patients had different types of lesions, two located in the vocal folds and three in the trachea. No difference was identified between the two groups regarding the VHI-10 score, while the control group showed a significantly worse MDADI score. CONCLUSIONS: COVID-19 patients subjected to prolonged invasive ventilation are more likely to develop a laryngotracheal complication in the short and medium term. A rigorous clinical follow-up to allow early identification and management of these complications should be set up after discharge.

Nasopharyngeal sarcoidosis: case reports and literature review.

Sarcoidosis is a multisystemic inflammatory chronic disease characterized by the presence of noncaseating granulomas most frequently in lungs and in intrathoracic lymph nodes. The nasopharyngeal form is unusual and noncommon in the ENT practice. Background and objectives: In order to establish a correct knowledge about this rare disease, we report two different cases of nasopharyngeal sarcoidosis moreover all the available literature is reviewed. Materials and Methods: A systematic literature review was made through PubMed databases, according to the PRISMA guidelines (1), combining the following key words: Nasopharyngeal, Rhinopharynx, Sarcoidosis, in publications between 1951 and 2020. In addition, we reported our personal experience on the disease by describing two clinical cases that occurred at our clinic in November 2018 and June 2019. Results: 16 articles reported 27 cases of nasopharyngeal sarcoidosis. The number of males was 13 (48,2%) and the number of females was 14 (51,8%) with a mean age at the diagnosis of 35,28 ± 13.05 years old (range 5 - 64). In 16 (59,3%) cases nasopharyngeal sarcoidosis was associated with lungs and/or intrathoracic lymph nodes involvement; nasal obstruction was the most frequently reported symptom (51,8% of subjects). Conclusions: Nasopharyngeal sarcoidosis can mimic several disorders of the upper airway respiratory tract and it must therefore be considered in the differential diagnosis. A biopsy of nonspecific lesions in the nasopharynx is advisable to permit several early diagnosis of upper airway respiratory tract disorders including sarcoidosis.

Component-Resolved Diagnosis for Endotyping Patients with Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammation-mediated disease of the nasal mucosa and paranasal sinuses that often coexists with asthma. The role of atopy in the development and severity of CRSwNP is still a controversial issue. OBJECTIVE: The aim of our study was to propose a systematic allergy workup to identify atopic patients in the context of CRSwNP and to characterize their allergen sensitization profile (sources/molecules). METHODS: Patients with a diagnosis of CRSwNP (n = 97) were studied in the otorhinolaryngologist and allergy settings. Demographic and clinical data were collected for each patient. Different allergen sensitization profiles (sources/molecules) were evaluated in atopic CRSwNP patients by using component-resolved diagnosis (CRD). RESULTS: In our cohort of patients, the CRSwNP was frequently diagnosed during adulthood with significant impact on health-related quality of life. Asthma and atopy were the most common comorbidities with a prevalence of asthma in the atopic group. In CRSwNP patients sensitized to grass pollens and/or to house dust mites, the CRD analysis revealed a prevalence of sensitization to species-specific allergens of Phleum pratense (Phl p1, Phl p2, and Phl p5) or Dermatophagoides pteronyssinus (Der p1 and Der p2) rather than to cross-reactive ones. CONCLUSION: To define the allergen sensitization profile in atopic CRSwNP patients by CRD, it may be useful to better characterize type 2 inflammation, thus providing a personalized endotype-driven treatment.

Complications during Fiberoptic Endoscopic Evaluation of Swallowing in 5,680 Examinations.

OBJECTIVE: To evaluate retrospectively the incidence of complications during fiberoptic endoscopic evaluation of swallowing (FEES) in 5,680 examinations. PATIENTS AND METHODS: 5,680 patients were evaluated at the Department of Otorhinolaryngology, Audiology and Phoniatrics of Pisa University Hospital between January 2014 and December 2018, involving both inpatients and outpatients. Most common comorbidities included neurological pathologies such as stroke (11.8%), neurodegenerative diseases (28.9%) and a history of previous head and neck surgery (24.6%). The evaluation was conducted by clinicians with experience in swallowing for a minimum of 10 years with the assistance of one or more speech-language pathologists. RESULTS: In all patients studied the endoscope insertion was tolerated, and it was possible to visualize the pharyngolaryngeal structures. Three subjects refused to undergo the procedure after being informed regarding the protocol and were therefore not included in this study. Most patients reported discomfort (70.1%) and gagging (20.8%). In a minority of patients complications were recorded, such as anterior epistaxis (0.1%), posterior epistaxis (0.02%), vasovagal crises (0.08%) and laryngospasm (0.04%). Especially laryngospasm was recorded in patients affected by amyotrophic lateral sclerosis. Multivariate binary logistic regression showed that discomfort (OR 9.944; CI 7.643-12.937), chronic gastrointestinal diseases (OR 2.003; CI 1.518-2.644), neurodegenerative diseases (OR 1.550; CI 1.302-1.846) and brain tumors (OR 1.577; CI 1.179-2.111) were risk factors associated with minor complications. CONCLUSIONS: FEES proved to be easy to perform, well tolerated by the patients and cost-effective. It can be performed at the patient's bedside, and it is characterized by a low rate of complications. As a matter of fact, normally only discomfort, gagging and/or vomiting are reported. Complications occurred only rarely, such as anterior or posterior epistaxis episodes or vasovagal crises, but these are still easily managed. Exceptionally, more severe complications are reported: adverse drug reactions to substances such as blue dye (methylene blue) and local anesthetics (not used in our protocol), and laryngospasm.

Evaluation of the Electroglottographic Signal Variability in Organic and Functional Dysphonia.

OBJECTIVES: To confirm the data reported in our previous studies on the analysis of the variability of the electroglottographic signal in the pathological voice; to evaluate possible differences in variability between organic and functional pathologies; to identify any distinctive/typical EGG patterns for these pathologies. METHODS: One hundred twenty-five subjects were enrolled (36 euphonic and 89 pathological: 24 functional dysphonia, 21 bilateral vocal nodules, 23 unilateral polyps and 21 unilateral cysts). All subjects were studied with videolaryngostroboscopy, spectrographic analysis of voice and electroglottography (EGG). The EGG signal variability was then investigated using amplitude-speed combined analysis, by means of a proprietary software algorithm. Amplitude and Speed variation were expressed as a new parameter, the Variability Index (VI), calculated both for the whole EGG signal recorded (VI-tot) and in each phase of the glottic cycle (VI-Q, absolute value; VI-Q%, percentage value). RESULTS: In the comparison of VI values between pathological and normal groups, VI-tot and VI-Q2% (which corresponds to the final phase of vocal fold contact) were significantly greater in pathological subjects (P= 0.002). The comparison of VI values among subgroups of the various pathologies showed a difference for VI-tot (P< 0.0001) and VI-Q2% (P= 0.001); this difference was more marked in the cysts than in the functional dysphonia. The cut-off values of VI-tot and VI-Q2% were 0.191 and 18.17%, respectively (sensitivity and specificity 65.2% and 66.7% for VI-tot and 84.3% and 77.8% for VI-Q2%). CONCLUSIONS: The variability of the EGG signal investigated through the combined analysis of the amplitude and the speed of vibration using a proprietary algorithm software has proved useful not only to distinguish the normal voice from the pathological voice, but also to characterize which phases are more altered in the various voice pathologies studied, both functional and organic. Furthermore, the analysis of the VI parameter allowed to propose cut-off values characterized by a good sensitivity and specificity to discriminate dysphonia from the euphonic voice. Larger groups of patients will be needed to confirm these results.

Piezoelectric Signals in Vascularized Bone Regeneration.

The demand for bone substitutes is increasing in Western countries. Bone graft substitutes aim to provide reconstructive surgeons with off-the-shelf alternatives to the natural bone taken from humans or animal species. Under the tissue engineering paradigm, biomaterial scaffolds can be designed by incorporating bone stem cells to decrease the disadvantages of traditional tissue grafts. However, the effective clinical application of tissue-engineered bone is limited by insufficient neovascularization. As bone is a highly vascularized tissue, new strategies to promote both osteogenesis and vasculogenesis within the scaffolds need to be considered for a successful regeneration. It has been demonstrated that bone and blood vases are piezoelectric, namely, electric signals are locally produced upon mechanical stimulation of these tissues. The specific effects of electric charge generation on different cells are not fully understood, but a substantial amount of evidence has suggested their functional and physiological roles. This review summarizes the special contribution of piezoelectricity as a stimulatory signal for bone and vascular tissue regeneration, including osteogenesis, angiogenesis, vascular repair, and tissue engineering, by considering different stem cell sources entailed with osteogenic and angiogenic potential, aimed at collecting the key findings that may enable the development of successful vascularized bone replacements useful in orthopedic and otologic surgery.

Human papillomavirus-related head and neck adenosquamous carcinoma: A systematic review and individual patient data meta-analysis.

This work examined published papers of patients affected by human papillomavirus-related head and neck adenosquamous carcinoma. Demographic data, tumor site and sub-site, TNM stage, HPV status (positive VS negative) and the technique used for its identification, the treatments performed, follow-up time and patient's status at follow-up were assessed. Three papers including 26 patients resulted eligible for the study. The incidence of HPV-positive Adenosquamous Carcinomas located in the oropharynx was significantly higher than HPV-negative tumors (p = 0.01), especially if the origin of primary unknown tumors was considered within this anatomical site (p < 0.0001). HPV-positive Adenosquamous Carcinomas had a higher incidence of small primary tumor (Tx + T1) (p = 0.03) and bulky cervical lymph node metastasis (N2) at presentation (p = 0.02). HPV-positive and HPV-negative tumors had similar OS and DFS. Head & Neck HPV-positive Adenosquamous Carcinoma seems to act like HPV-positive conventional Squamous Cell Carcinoma, thus we suggest to determine the HPV status of Adenosquamous Carcinoma during the diagnostic phase.

Functional and aesthetic outcomes of pedicled temporalis muscle flap for mesostructure reconstruction.

The purpose of this work is to analyse the soundness of the Temporalis Muscle Flap as a safe and reliable flap to restore the aesthetic and functions of the facial mesostructure after its partial resection. Subjects were selected retrospectively and were invited to come to our outpatient clinic. Here, subjects completed a clinical evaluation in which the medical examiners evaluated the aesthetic outcome, the phonation, the ocular motility and the swallowing. Twenty-two subjects were enrolled in this study and completed the clinical evaluation. The mean value of the score obtained for the aesthetic outcome was 2.91 ± 0.92, slightly less than good. The VHI-30 questionnaire for voice evaluation obtained a mean score of 22.5 ± 11.5, pointing out minor voice problems. The mean value of the P-score evaluated during Fiberoptic Endoscopic Evaluation of Swallowing was 4.64 ± 0.95, highlighting the near absence of endoscopic signs of dysphagia. On the evaluation of ocular function, only one subject showed an inferior displacement of his right eyeball without vertical diplopia. The Temporalis Muscle Flap is a safe and reliable flap that can be used to reconstruct numerous surgical defects of the maxilla, giving an excellent recovery of physical aspect, phonation, and swallowing.

Binaural hearing restoration with a bilateral fully implantable middle ear implant.

AIM: The fully implantable middle ear implant (C-FI-MEI) is designed for patients with moderate-to-severe sensorineural hearing loss or those with mixed hearing loss. To analyze the audiological post-operative results of subjects bilaterally implanted with C-FI-MEI. MATERIALS AND METHODS: Retrospective study: 14 patients with bilateral, moderate-to-severe, sensorineural or mixed hearing loss were treated. This clinical sample included 14 cases bilaterally implanted (13 sequentially, 1 simultaneously). The evaluation at each follow-up after surgery included otologic examination, a structured interview, and different audiological tests composed of pure tone audiometry, speech in quiet and in noise test, and localization task. The mean follow-up was 67.2 ± 33 months. RESULTS: There were no significant differences between pre and post-operative pure tone averages. The patients showed no significant differences between pre-operatively aided and C-FI-MEI implant-aided conditions in terms of word recognition score. Speech perception in noise under different loudspeaker arrangements and localization tests demonstrated a binaural advantage in bilaterally implanted patients. The mean daily use time was 17.4 and 16.7 h, respectively, for right and left side. CONCLUSION: The results for the 14 patients, bilaterally implanted with C-FI-MEI, suggest that bilateral implantation of fully implantable middle ear hearing devices is an effective procedure. LEVEL OF EVIDENCE: 4.

Evaluation of the Incidence and Potential Mechanisms of Tracheal Complications in Patients With COVID-19.

Importance: Full-thickness tracheal lesions and tracheoesophageal fistulas are severe complications of invasive mechanical ventilation. The incidence of tracheal complications in ventilated patients with coronavirus disease 2019 (COVID-19) is unknown. Objective: To evaluate whether patients with COVID-19 have a higher incidence of full-thickness tracheal lesions and tracheoesophageal fistulas than matched controls and to investigate potential mechanisms. Design, Setting, and Participants: This is a retrospective cohort study in patients admitted to the intensive care unit in a tertiary referral hospital. Among 98 consecutive patients with COVID-19 with severe respiratory failure, 30 underwent prolonged (≥14 days) invasive mechanical ventilation and were included in the COVID-19 group. The control group included 45 patients without COVID-19. Patients with COVID-19 were selected from March 1 to May 31, 2020, while the control group was selected from March 1 to May 31, 2019. Exposures: Patients with COVID-19 had severe acute respiratory syndrome coronavirus 2 infection diagnosed by nasopharyngeal/oropharyngeal swabs and were treated according to local therapeutic procedures. Main Outcomes and Measures: The primary study outcome was the incidence of full-thickness tracheal lesions or tracheoesophageal fistulas in patients with prolonged invasive mechanical ventilation. Results: The mean (SD) age was 68.8 (9.0) years in the COVID-19 group and 68.5 (14.1) years in the control group (effect size, 0.3; 95% CI, -5.0 to 5.6). Eight (27%) and 15 (33%) women were enrolled in the COVID-19 group and the control group, respectively. Fourteen patients (47%) in the COVID-19 group had full-thickness tracheal lesions (n = 10, 33%) or tracheoesophageal fistulas (n = 4, 13%), while 1 patient (2.2%) in the control group had a full-thickness tracheal lesion (odds ratio, 38.4; 95% CI, 4.7 to 316.9). Clinical and radiological presentations of tracheal lesions were pneumomediastinum (n = 10, 71%), pneumothorax (n = 6, 43%), and/or subcutaneous emphysema (n = 13, 93%). Conclusions and Relevance: In this cohort study, almost half of patients with COVID-19 developed full-thickness tracheal lesions and/or tracheoesophageal fistulas after prolonged invasive mechanical ventilation. Attempts to prevent these lesions should be made and quickly recognized when they occur to avoid potentially life-threatening complications in ventilated patients with COVID-19.

Bone Anchored Hearing Aids for the Treatment of Asymmetric Hearing Loss.

OBJECTIVES: Asymmetric hearing loss is generally defined as a moderate-to-profound hearing loss in the poorer ear and a mild-to-moderate hearing loss in the better ear. Application of a bone conduction hearing aid is one of the possible treatments for the poorer ear in asymmetric hearing loss. However, the device essentially stimulates the contralateral better ear, precluding true binaural hearing. The aim of this paper is to evaluate the application and utility of bone-anchored hearing aids in the treatment of asymmetric hearing loss. MATERIALS AND METHODS: We retrospectively evaluated 215 implanted subjects in our clinic and extracted a series of 27 patients affected by asymmetric hearing loss and treated with bone-anchored hearing aids. All 27 subjects had a mixed hearing loss after middle ear surgery. The preoperative and postoperative audiological data of these patients were collected and analyzed. RESULTS: The audiological tests showed an improvement in the performance of hearing perception of sound and speech in quiet and noise. Moreover, the subjects have positively answered the questionnaires administered to evaluate subjective benefits. All subscales of the abbreviated profile of hearing aid benefit and speech, spatial, and qualities of hearing scale showed a significant improvement with the device. CONCLUSION: Bone-anchored hearing aids are a suitable treatment for asymmetric hearing loss. When other devices cannot be utilized or are not indicated, the bone conduction devices may allow good audiological results.

Overview of different modified full-face snorkelling masks for intraoperative protection.

OBJECTIVE: The COVID-19 pandemic has caused significant impact on healthcare systems worldwide. The rate of infected healthcare workers is > 10% in Italy. Within this dramatic scenario, the development of new personal protective equipment (PPE) devices is mandatory. This study focuses on validation of modified full-face snorkel masks (MFFSM) as safe and protective equipment against SARS-CoV-2 infection during diagnostic and therapeutic procedures on the upper aerodigestive tract. METHODS: Five different MFFSM were tested during otolaryngological surgery and in anaesthesia procedures. Data were collected through an online survey to assess the feedback of operators. pO2 and pCO2 monitoring values during procedures were recorded in selected cases. RESULTS: All five MFFSM tested were easy to use and gave all operators a sound "feeling" of protection. All clinicians involved had common agreement regarding safety and the user-friendly format. CONCLUSIONS: In the future, specific development of different type of masks for protection in the operating room, intensive care units and/or office will be possible as a joint venture between clinicians and developers. Goals for clinicians include better definition of needs and priorities, while developers can devote their expertise to produce devices that meet medical requirements.