Long-term follow-up of laryngeal Rhinosporidium seeberi diagnosed by PCR and treated with laser ablation and voriconazole nebulization in a retired thoroughbred polo horse.

A 21-year-old retired polo Argentinian thoroughbred horse from a teaching herd was presented for a routine bronchoalveolar lavage demonstration, during which an incidental finding of a granulomatous mass on the dorsal aspect of the epiglottis was made. Rhinosporidium seeberi was suspected from a histological section obtained from an initial biopsy, and the mass was removed via laser surgery for cytology and PCR. Sequencing of the PCR amplicons confirmed the diagnosis of R. seeberi. A treatment protocol of nebulized voriconazole for 10 d postoperatively was used. Long-term follow-up required 2 more laser surgeries plus oral fluconazole to resolve the remaining fungal spores. However, 2.5 y later, there was no evidence of remaining fungal spores. Key clinical message: Horses from endemic regions can potentially be exposed to R. seeberi. Based on its travel history, this horse may have contracted the infection in South America, California, or Alberta. Treatments administered, including diode laser resection, voriconazole antifungal nebulization, and oral fluconazole administration, were successful but required repeated interventions.

Suivi à long terme du Rhinosporidium seeberi laryngé diagnostiqué par PCR et traité par ablation au laser et nébulisation au voriconazole chez un cheval de polo thoroughbred pur-sang à la retraiteUn cheval thoroughbred argentin de polo retraité de 21 ans, issu d'un troupeau d'enseignement, a été présenté pour une démonstration de lavage broncho-alvéolaire de routine, au cours de laquelle une découverte fortuite d'une masse granulomateuse sur la face dorsale de l'épiglotte a été faite. Rhinosporidium seeberi a été suspecté à partir d'une coupe histologique obtenue à partir d'une biopsie initiale, et la masse a été retirée par chirurgie au laser pour cytologie et PCR. Le séquençage des amplicons PCR a confirmé le diagnostic de R. seeberi. Un protocole de traitement au voriconazole nébulisé pendant 10 jours après l'opération a été utilisé. Le suivi à long terme a nécessité 2 autres interventions chirurgicales au laser et du fluconazole oral pour éliminer les spores fongiques restantes. Cependant, 2,5 ans plus tard, il n'y avait aucune trace de spores fongiques restantes.Message clinique clé:Les chevaux des régions endémiques peuvent potentiellement être exposés à R. seeberi. D'après ses antécédents de voyage, ce cheval pourrait avoir contracté l'infection en Amérique du Sud, en Californie ou en Alberta. Les traitements administrés, notamment la résection au laser à diode, la nébulisation antifongique au voriconazole et l'administration orale de fluconazole, ont été efficaces mais ont nécessité des interventions répétées.(Traduit par Dr Serge Messier).

A case of epiglottic entrapment in a cat.

OBJECTIVE: The objective of this study was to describe a case of epiglottic entrapment in a cat. CASE SUMMARY: A 5-month-old male neutered Russian Blue cat was evaluated for progressive stertorous upper airway sounds, acute onset vestibulopathy and abnormal laryngeal anatomy. Endotracheal intubation was only able to be achieved using videoscopic guidance and identified concern for severe nasopharyngeal stenosis. A computerized tomography scan revealed otitis interna, narrowed nasopharynx and no definitive cause for the stertorous breathing. The cat recovered very slowly from anaesthesia due to concern for airway obstruction following extubation. It was discharged the following day and then passed away at home 2 weeks later. Necropsy revealed that the epiglottis was obscured by 2 cm of redundant mucosal tissue extending from the base of the tongue to the larynx resulting in epiglottic entrapment. Also noted was chronic, severe otitis interna and externa. Upper airway obstruction is suspected to be the cause of sudden death. NEW OR UNIQUE INFORMATION: To the authors' knowledge, this is the first report of these oropharyngeal anatomic abnormalities in a cat.

Retrospective study of 1050 dogs with respiratory symptoms in Japan (2005-2020).

BACKGROUND: Few studies have investigated the incidence of respiratory diseases based on anatomical sites or the relationship between breed and these diseases. OBJECTIVE: The objective of this study was to investigate the prevalence of canine respiratory diseases among dogs in Japan, with relationship to the breed. METHODS: We retrospectively reviewed the medical records of dogs with respiratory symptoms and calculated the odds ratio (OR) to evaluate the relationship between breed and disease. RESULTS: A total of 1050 dogs with respiratory symptoms were included in this study. Miniature dachshunds were the most common breed affected by respiratory diseases. Among tracheobronchial diseases, there was a significant association between some small breeds and tracheobronchial collapse, miniature dachshunds (OR: 4.44, 8.43, 95% confidence interval [CI]: 3.17-6.22, 4.33-16.0) and chronic bronchitis and bronchiectasis. Among nasal diseases, miniature dachshunds (OR: 27.2, 95% CI: 16.8-44.8) and golden retrievers (OR: 21.0, 95% CI: 6.43-69.3) were the most affected by non-infectious rhinitis and nasal aspergillosis, respectively. Brachycephalic obstructive airway syndrome was the most common disease among pharyngeal and laryngeal diseases, with a relationship with breed being found in some brachycephalic breeds, and Pomeranians (OR: 2.7, 95% CI: 1.42-5.17). CONCLUSIONS: Respiratory diseases in dogs are strongly correlated with popular breeds in Japan. Miniature dachshunds, in particular, are associated with many respiratory diseases, which may differ from international reports. Thus, this result may help in the early detection, prevention, treatment, and elucidation of the pathophysiology of canine respiratory diseases.

Sealing peri-cuff leak of a small endotracheal tube passing through laryngeal web in five dogs (2015-2019).

CASE DESCRIPTION: 5 dogs with a history of ventriculocordectomy were anesthetized with isoflurane for ovariohysterectomy, dental prophylaxis, or intracapsular lens extraction. CLINICAL FINDINGS: No remarkable, abnormal clinical signs such as exercise intolerance, respiratory distress, or stridor were found in 4 dogs. However, 1 dog had cough after drinking, which had started after the ventriculocordectomy. During intubation, laryngeal web, suspected to be a complication of ventriculocordectomy, was accidentally discovered. TREATMENT AND OUTCOME: Laryngeal web was observed during intubation, necessitating the use of a smaller-diameter endotracheal tube (ETT) for intubation. However, the smaller cuff volume of the smaller ETT did not prevent the air leak. Therefore, the ETT with the inflated cuff was pulled cranially until the narrowed laryngeal lumen was plugged with the cuff behind the vocal cords. The ETT was secured to prevent slippage. No air leakage around the ETT cuff or complications related to the ETT placement were observed in the peri-anesthetic period in any dog. CLINICAL RELEVANCE: Laryngeal web can be found in patients with a history of larynx-related surgeries and may allow only a small-diameter ETT to pass through. The sealing technique used for peri-cuff air leak using a small ETT described here that can pass through a laryngeal web could be useful to seal an air leak around the cuff without complications.

Updates in Upper Respiratory Surgery.

This article discusses updates in brachycephalic and other upper respiratory surgery of dogs and cats, including schemata for classifying brachycephalic dogs in terms of severity of disease and indications for monitoring and treatment, new characterizations of the primary and secondary components of brachycephalic obstructive airway syndrome (BOAS), and updates to traditional brachycephalic airway surgical procedures as well as novel surgeries to treat BOAS, including laser-assisted turbinectomy, the cardiopulmonary effects of brachycephaly on some feline breeds, epiglottic entrapment and retroversion, and upper airway syndrome in Norwich terriers.

Development of a constant pressure perfused ex vivo model of the equine larynx.

Distal axonopathy is seen in a broad range of species including equine patients. In horses, this degenerative disorder of the recurrent laryngeal nerve is described as recurrent laryngeal neuropathy (RLN). The dysfunctional innervation of the cricoarytenoideus dorsalis muscle (CAD) leads to a loss of performance in affected horses. In general, ex vivo models of the larynx are rare and for equine patients, just one short report is available. To allow for testing new therapy approaches in an isolated organ model, we examined equine larynges in a constant pressure perfused setup. In order to check the vitality and functionality of the isolated larynx, the vessels´ reaction to norepinephrine (NE) and sodium nitroprusside (NP) as vasoactive agents was tested. Additionally, the contractility of the CAD was checked via electrical stimulation. To determine the extent of hypoxic alterations, lactate dehydrogenase (LDH) and lactate were measured and an immunofluorescent analysis of hypoxia-inducible factor (HIF-1α), a key transcription factor in hypoxia, was performed. For this, a hypoxia-induced cell culture for HIF-1α was developed. The application of NE led to an expected vasoconstriction while NP caused the expected vasodilation. During a perfusion period of 352 ±20.78 min, LDH values were in the reference range and lactate values slightly exceeded the reference range at the end of the perfusion. HIF-1α nuclear translocation could reliably be detected in the hypoxia-induced cell cultures, but not in sections of the perfused CAD. With the approach presented here, a solid basis for perfusing equine larynges was established and may serve as a tool for further investigations of equine larynx disorders as well as a transferrable model for other species.

Infiltrative laryngeal disease in dogs.

OBJECTIVES: To describe the clinical features and outcome of neoplastic and inflammatory infiltrative laryngeal disease in dogs. MATERIALS AND METHODS: Medical records at a single referral centre were retrospectively reviewed for dogs diagnosed with infiltrative laryngeal disease by CT or laryngoscopy. RESULTS: Fifteen dogs were included, with a median age of 6 years (range 1-14 years). Thirteen dogs were diagnosed with inflammatory disease including granulation tissue (n = 4) and neutrophilic (n = 2), septic neutrophilic (n = 2), eosinophilic (n = 1) lymphocytic/plasmacytic (n = 1) and mixed/unclassified (n = 3) inflammation. One dog was diagnosed with large cell lymphoma and one dog was diagnosed with mast cell tumour. Twelve dogs survived to discharge. Follow-up was available for 10 dogs diagnosed with inflammatory disease. Four had fully recovered (7, 10, 23 and 32 months) and one dog developed acute leukaemia and was euthanased at 2 months. Five dogs had recurrence of clinical signs at 1, 1, 5, 17 and 26 months. The dog with lymphoma was euthanased at 8 months and the dog with mast cell tumour died at 5 months. CLINICAL SIGNIFICANCE: In this cohort, infiltrative inflammatory lesions of the larynx were more common than neoplastic infiltration. For dogs that survived to discharge, outcome was fair although relapse was common.

A laryngeal inflammatory polyp in a miniature dachshund.

A 15-year old, female miniature dachshund was presented for a 5-year history of progressive dyspnoea. A laryngeal mass was detected on cervical radiographs. Surgery was performed 5 days later to reduce the volume of the mass and to obtain biopsy samples; the dyspnoea improved. Based on the histopathological findings, the mass was diagnosed as inflammatory polyp. This case of inflammatory polyp in the larynx suggests that it should be listed in the differential diagnoses for laryngeal masses in dogs and that surgical treatment may be curative.

Laryngeal chondritis as a differential for upper airway diseases in German sheep.

BACKGROUND: Ovine laryngeal chondritis is a rare entity of sheep in the USA, Great Britain, New Zealand and Iceland, but has not been reported in Germany so far. Here, two German cases are reported. CASE PRESENTATION: Two rams showed severe and progressive signs of dyspnea. Endoscopically, a severe bilateral swelling of the larynx was identified in both rams. Due to poor prognosis and progression of clinical signs one ram was euthanized, while the other ram died overnight. In both cases, a necrosuppurative laryngitis and chondritis of arytenoid cartilages was found at necropsy. Fusobacterium necrophorum and Streptococcus ovis were isolated from the laryngeal lesion in one animal. CONCLUSIONS: This is the first report of ovine laryngeal chondritis in continental Europe. This entity should be considered a differential diagnosis for upper airway disease in sheep.

Upper Airway Obstruction Due to Primary Laryngeal Blastomycosis in a Dog.

A 9 yr old female spayed Labrador retriever presented for progressive dyspnea. Inspiratory stridor and inspiratory and expiratory dyspnea were present, consistent with an upper airway obstruction. A laryngeal exam revealed severe thickening of the arytenoid cartilages and masses associated with the arytenoids. A tracheostomy tube was placed, and the masses were biopsied. Histopathology showed pyogranulomatous inflammation secondary to Blastomyces dermatitidis. The dog was initially treated with amphotericin B and terbinafine in the hospital until the airway obstruction resolved and the tracheostomy tube could be removed. The dog experienced complete recovery after long-term treatment with itraconazole and terbinafine. This is the first report of laryngeal obstruction secondary to primary laryngeal blastomycosis in a dog. Blastomycosis should be considered for cases of obstructive laryngeal disease, and a good outcome can be achieved with antifungal treatment.

Race performance following epiglottic entrapment surgery in Thoroughbred yearlings.

BACKGROUND: Epiglottic entrapment can occur in yearling Thoroughbreds (TB); however, race performance following surgical correction is unknown. OBJECTIVES: To determine the race performance of horses treated surgically for epiglottic entrapment as yearlings as compared to an untreated cohort. A second objective was to identify risk factors for treated horses not racing post-operatively. STUDY DESIGN: Retrospective cohort and case-control studies. METHODS: Medical (1989-2014) and race records of 66 treated TB racehorses were reviewed. Observed abnormalities on pre- and post-operative endoscopic images and surgical method were recorded. Race records (EquineLine) were recorded. Racing performance of treated yearling TBs and two of their maternal half-siblings, which were used as the untreated cohort, was evaluated in a cohort study. A case-control study was used to investigate risk factors for not racing post-operatively among treated horses. Quarterly starts and earnings were compared to an untreated cohort. Survival analysis was used to assess career longevity. Rates of racing and earnings were compared between groups using Poisson and negative binomial regression respectively. Associations between clinical variables and not racing post-surgery were evaluated using logistic regression. RESULTS: Sixty-six treated horses were identified, 65 of which had at least one half-sibling. Proportions of horses that raced were similar for treated and maternal cohorts (70.0 vs. 70.8%, P = 0.9). Treated horses performed similarly to untreated horses. In treated horses, epiglottic entrapment with abnormal right arytenoid movement was associated with never racing (OR 15.40, 95% CI 1.64-144.23, P = 0.02). More females were affected by epiglottic entrapment than males (47/66 vs. 19/66 respectively, P<0.001). MAIN LIMITATIONS: The retrospective design over a prolonged period of time with cases obtained from a single hospital population. Low case numbers likely influenced the outcome of the multivariable analysis. CONCLUSIONS: Thoroughbred racehorses treated in their yearling year for epiglottic entrapment had no differences in performance variables compared to their untreated cohort. Epiglottic entrapment with abnormal right arytenoid movement might decrease odds of racing post-operatively.

Laryngeal Disease in Dogs and Cats: An Update.

Laryngeal diseases are manifested by obstructive breathing patterns reflecting functional or mechanical upper airway obstruction. Laryngeal paralysis is the most common disease of the larynx. Diagnosis requires close attention to anesthetic plane and coordination of respiratory effort with laryngeal motion. Surgical arytenoid lateralization improves clinical signs and quality of life in dogs; however, aspiration pneumonia is a recognized complication, and generalized neuropathy can progress. Laryngeal collapse can result from any cause of chronic upper airway obstruction but is most often associated with brachycephalic obstructive airway syndrome. Although uncommon, laryngeal neoplasia has a guarded to grave prognosis regardless of treatment.

Dynamic laryngeal collapse associated with poll flexion as a complication of laryngeal tie-forward surgery in three harness racehorses.

OBJECTIVE: To report dynamic laryngeal collapse (DLC) associated with poll flexion as a potential complication of the laryngeal tie-forward procedure (LTFP) in harness racehorses. STUDY DESIGN: Short case series. ANIMALS: Three harness racehorses. METHODS: Preoperative and postoperative medical records of all harness racehorses that underwent the LTFP were reviewed, as were high-speed treadmill videoendoscopy recordings of 35 horses that returned for upper airway evaluation postoperatively. RESULTS: One standardbred and two Norwegian coldblooded trotters in which dorsal displacement of the soft palate had been initially diagnosed were found to have bilateral arytenoid cartilage and vocal fold collapse associated with poll flexion after the LTFP. These three horses were otherwise clinically normal when exercised in free head carriage. CONCLUSION: Dynamic laryngeal collapse associated with poll flexion can occur as a complication after the LTFP in harness racehorses and should be considered as a differential in horses with persistence of airway problems after surgery. CLINICAL SIGNIFICANCE: Postoperative DLC may be underdiagnosed in harness racehorses because this complication is obvious only when horses are driven with bit and reins during high speed treadmill or overground videoendoscopy.

Pharyngeal contraction secondary to its collapse in dogs with brachycephalic airway syndrome.

Brachycephalic airway syndrome (BAS) is a common disease in certain "flat-faced" dog breeds. This syndrome includes stenotic nares, elongated and thickened soft palate, laryngeal collapse, and tracheal hypoplasia. Pharyngeal collapse is also commonly observed, but it is unclear if laryngopharynx motions are merely sequelae or actually contribute to BAS respiratory symptoms. Laryngopharynx motion was imaged using dynamic four-dimensional computed tomography (4D-CT) during spontaneous respiration in four dogs with different BAS types. Dynamic 4D-CT showed laryngopharynx motion in the following order during inspiration: pharyngeal collapse, contraction, and laryngospasm. We concluded that dynamic 4D-CT is a highly-detailed diagnostic approach for detecting laryngopharynx motion. Pharyngeal contraction during inspiration appears to contribute toward the worsening of clinical respiratory signs of BAS.

Transendoscopic correction of epiglottic entrapment with a silicone-covered laser guide and diode laser in 29 horses.

OBJECTIVE: To describe the use of a silicone-covered laser guide and diode laser for surgical correction of epiglottic entrapment and report postoperative outcomes in horses with epiglottic entrapment. STUDY DESIGN: Retrospective case series. ANIMALS: Thoroughbred and standardbred racehorses (n = 29) with epiglottic entrapment. METHODS: A silicone-covered laser guide was placed endoscopically to direct the diode laser cutting action during transection of the entrapping subepiglottic membrane and to act as a physical barrier between the membrane and the epiglottic cartilage. Postoperative complications and trainer satisfaction were recorded via use of a follow-up questionnaire. Race records were reviewed to determine return to racing and detect differences in the number of starts, wins, or earnings before and after surgery. RESULTS: The entrapping membrane was successfully released in all horses. Mild postoperative complications such as swelling of the surgical site (12 horses) and coughing or mild nasal discharge (5 horses) were recorded during the first few days after surgery. Ninety-six percent of trainers were satisfied with the outcome of the procedure; 93% of horses returned to racing. CONCLUSION: Laser guide-assisted transection of the subepiglottic membrane corrected epiglottic entrapment in standing horses. CLINICAL SIGNIFICANCE: Ease of surgical technique, mild postoperative complications, and a good prognosis to return to racing make this a suitable alternative to the traditional laser procedure.

Race-day performance of horses with epiglottic entrapment, and following surgical correction using intra-oral curved bistoury hook in anaesthetised horses.

Epiglottic entrapment is a condition in racing horses, associated with abnormal respiratory noises and exercise intolerance. Epiglottic entrapment has been linked to both poor and superior athletic performance, leading to concerns regarding whether surgery is indicated, and whether surgical correction may have a deleterious effect on future race performance. The objective of the current study was to assess the race-day performance of horses racing with epiglottic entrapment and the effect of surgical correction on performance outcomes using an intra-oral technique in anaesthetised horses. A case-control study was conducted at the Singapore Turf Club from 2008 to 2011. Controls were selected 1:1 to cases, based on Malaysian Racing Authority number. The performance of horses racing with epiglottic entrapment was recorded and post-surgery race performance was described. Further, post-surgery race performance was compared between cases and with non-case controls. Twenty horses raced with epiglottic entrapment were retrospectively enrolled. There was a significant difference in racing performance in case horses racing with and without epiglottic entrapment (P < 0.001). Fourteen horses finished in the top three post-surgery, compared to one horse finishing in the top three when running with epiglottic entrapment present. There was no significant difference between the performance of case horses (n = 33) post-surgery and controls (number of wins P = 0.20; and places P = 0.62). The intra-oral release of epiglottic entrapment is a suitable technique to resolve epiglottic entrapment. This study may assist veterinarians advising clients in the decision-making process when epiglottic entrapment is diagnosed in a racehorse.

Epiglottopexy for the treatment of epiglottic retroversion in 2 horses.

OBJECTIVE: To report an epiglottopexy technique for the treatment of epiglottic retroversion (ER) in 2 horses. STUDY DESIGN: Case report. ANIMALS: A 2-year-old thoroughbred gelding and a 6-year-old standardbred gelding, both with ER. METHODS: Epiglottic retroversion was diagnosed via exercising endoscopic examination in both horses. Epiglottopexy technique was performed in both cases. RESULTS: Both horses returned to previous racing class within 1 year after surgery. Repeat exercising endoscopy of 1 horse 6 months postoperatively revealed resolution of the ER. CONCLUSION: Epiglottopexy should be considered for treatment of ER in the equine athlete. CLINICAL SIGNIFICANCE: Previously reported surgical techniques for ER in the equine athlete have not resulted in horses returning to previous performance level. The technique reported here resulted in both horses achieving athletic status.

Intraoperative and major postoperative complications and survival of dogs undergoing surgical management of epiglottic retroversion: 50 dogs (2003-2017).

OBJECTIVE: To report intraoperative and major postoperative complications in dogs treated surgically for epiglottic retroversion (ER), compare the incidence of major postoperative complications between procedures, and report survival of surgically treated dogs. STUDY DESIGN: Multi-institutional retrospective study. SAMPLE POPULATION: Fifty dogs treated with 78 procedures. METHODS: Medical records of dogs diagnosed and surgically treated for ER from 2003 to 2017 at 11 institutions were reviewed. Complications were divided into intraoperative and major postoperative complications. RESULTS: Intraoperative complications occurred during 2 of 78 (2.6%) procedures. Thirty-six major postoperative complications were documented in 22 dogs after 36 of 74 (48.7%) procedures. Postoperative complications occurred after 7 of 12 (58.3%) nonincisional epiglottopexy, 23 of 43 (53.5%) incisional epiglottopexy, 2 of 4 (50%) partial epiglottectomy, 2 of 12 (16.7%) subtotal epiglottectomy, and 2 of 3 (66.7%) other surgical procedures. Epiglottopexy failure was the most common major postoperative complication. The incidence of major postoperative complications did not differ between procedures (P = .1239), although, when combined, epiglottopexy procedures (30/55) had a higher incidence of complications than epiglottectomy procedures (4/16; P = .048). Thirty (60%) dogs were alive at a median of 928 days (range, 114-2805), 8 (16%) were lost to follow-up after 411 days (range, 43-1158), and 12 (24%) were dead/euthanized after 301.5 days (range, 3-1212). Median survival time was not reached after a median of 716 days. CONCLUSION: Although intraoperative complications were uncommon, major postoperative complications were common, especially after epiglottopexy procedures. CLINICAL SIGNIFICANCE: Although surgical treatment of ER is associated with a high rate of major postoperative complications, especially epiglottopexy procedures, long-term survival can be achieved.

Exercising upper respiratory videoendoscopic findings of 50 competition draught horses with abnormal respiratory noise and/or poor performance.

BACKGROUND: Upper respiratory tract (URT) endoscopy at rest is commonly used to evaluate competition draught horses with URT conditions. Overground endoscopy might be preferred for draught horse URT evaluation as it allows the horses to be driven with harness, overcheck and cart-load under similar conditions to those experienced in the show ring where airway conditions are most prominent. OBJECTIVE: To describe the exercising URT findings of competition draught horses with abnormal respiratory noise and/or poor performance. STUDY DESIGN: Case series. METHODS: Medical records of competition draught horses undergoing overground endoscopic evaluation between January 2013 and January 2018 with a presenting complaint of abnormal respiratory noise and/or poor performance were reviewed. Video recordings of resting and overground endoscopy were evaluated in all horses. Spearman's rank correlation coefficient was calculated between laryngeal function at rest and at exercise. RESULTS: Fifty competition draught horses were examined. Thirteen had previously undergone URT surgery. There was significant correlation between resting and exercising laryngeal function (ρ = 0.77, P<0.01). Abnormalities were detected in 46 horses and included arytenoid cartilage collapse (n = 31), vocal fold collapse (n = 27), palatal dysfunction (n = 14), epiglottic disorders (n = 11), dynamic laryngeal collapse (n = 1), rostral deviation of the palatopharyngeal arch (n = 3) and medial deviation of the aryepiglottic folds (n = 16). The majority of horses had a complex of abnormalities (n = 31) or required exercising examination for identification (n = 41). Incidental upper oesophageal incompetence was observed in nine horses. MAIN LIMITATIONS: Retrospective collection of data. CONCLUSIONS: Overground endoscopic evaluation was a useful technique for identifying URT disorders in competition draught horses. The spectrum of upper airway conditions identified in exercising draught horses supports the use of overground endoscopy as a diagnostic technique and could influence treatment considerations. The Summary is available in Portuguese - see Supporting Information.