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Objective To identify the appropriate treatment in the tonsillar region's infections, a distinction between tonsillitis with or without abscess formation is essential. Ultrasound proved to be a valuable method in identifying abscess formation in the head and neck region. However, no report described the assessment of the tonsil region. This study aims to determine the feasibility of transcervical ultrasound for abscess visualization in the palatal tonsillar region. Methods Retrospective analysis of 354 patients presenting with clinical suspicion of tonsillar abscess to a tertiary referral center and university hospital. All patients received a transcervical ultrasound to establish a primary diagnosis. The existence of an abscess was confirmed by puncture and incision, or final tonsillectomy. If no abscess could be delineated, non-abscessing tonsillitis was supposed, and conservative primary therapy and closed follow-up examinations were performed. Results After the first diagnostic ultrasound examination, in 257 cases (72.59%), the diagnosis of an abscess could be established, but in 97 cases (27.40%), due to missing abscess formation criteria, non-abscessing tonsillitis was documented. Overall, ultrasonography demonstrated an overall accuracy of 78.8% in this selected cohort. The sensitivity, specificity, PPV, and NPV after the first ultrasound examination were calculated with 75.1%, 88.6%, 94.6%, and 57.3%, respectively. Conclusion The presented data confirm that an abscess formation due to tonsillitis can be detected by transcervical ultrasound, enabling prompt, adequate management. As transcervical ultrasound can be conducted fast and is not associated with radiation, it can be regarded as a first-line diagnostic tool in this condition.

ZusammenfassungTraditionell besteht das multimodale Therapiekonzept bei den differenzierten Schilddrüsenkarzinomen in der Thyreoidektomie mit Neck-Dissection (bei cN+-Halsstatus) und adjuvanten Radiojodablation mit abschließender risikoadaptierter TSH-Suppression. Das Ausmaß der Radiojodaufnahme beim metastasierten Schilddrüsenkarzinom spielt eine signifikante Rolle bei der Einschätzung der Prognose. Das fehlende Jodspeicherungsvermögen einer Läsion in Zusammenschau mit dem fehlenden Abfall des Tumormarkers Thyreoglobulin sowie radiologische Zeichen einer Tumorprogression charakterisieren den Radiojod-refraktären Patienten. Aufgrund des meistens über einen langen Zeitraum indolenten Verlaufs erscheint in den meisten Fällen ein abwartendes Verhalten in Kombination mit lokaler Metastasenbehandlung sowie Symptomlinderung primär sinnvoll zu sein. Der Nachweis einer Veränderung der Tumordynamik ist der Zeitpunkt, um eine Systemtherapie zu evaluieren. Diese beruht auf Multi-Tyrosinkinase-Inhibitoren (Sorafenib, Lenvatinib). Diese Substanzen sind größtenteils mit einem ungünstigen Nebenwirkungsprofil assoziiert (Diarrhö, Hautauschläge, arterielle Hypertonie mit hypertensiver Entgleisung, lokale Wundheilungsstörungen), welches zu einer nicht vernachlässigbaren Rate einer therapieassoziierten Morbidität sowie einer hohen Anzahl an Therapieunterbrechungen führt. Daher sind im Jahr 2020 2 selektive RET-Inhibitoren (Selpercatinib, Pralsetinib) für die differenzierten Schilddrüsenkarzinome von der FDA zugelassen worden. Eine neue Perspektive für die Zukunft wären die unterschiedlichen Redifferenzierungsstrategien, welche auf die Steigerung der Sensitivität der Tumorzellen auf Radiojod abzielen.

Liver failure causes blood-brain-barrier (BBB) breakdown leading to central nervous system damage, however the mechanisms whereby the liver influences BBB-integrity remain elusive. One possibility is that the liver secretes an as-yet to be identified molecule(s) that circulate in the serum to directly promote BBB integrity. We developed light-sheet imaging for three-dimensional study of BBB function. We show that liver- or muscle-specific knockout of Hfe2 induces BBB breakdown, leading to accumulation of toxic-blood-derived fibrinogen in the brain, lower cortical neuron numbers, and behavioral deficits. In healthy animals, soluble Hfe2 competes with its homologue RGMa for binding to Neogenin, thereby blocking RGMa-induced downregulation of PDGF-B and Claudin-5 in endothelial cells and the ensuing BBB disruption. Hfe2 administration in an animal model of multiple sclerosis prevented paralysis and immune cell infiltration by inhibiting RGMa-mediated BBB alteration. This study has implications for the pathogenesis and potential treatment of diseases associated with BBB dysfunction such as multiple sclerosis.

BACKGROUND Firefighting has been associated with posttraumatic stress disorder (PTSD) and other mental health conditions. We previously found that among Fire Department of the City of New York (FDNY) responders to the World Trade Center (WTC) disaster, higher-intensity WTC-exposure predicted PTSD symptoms, depressive symptoms, and subjective cognitive concerns. The present study aims to compare these symptoms in the FDNY WTC-exposed cohort versus a comparison cohort of non-FDNY, non-WTC-exposed firefighters. METHODS The study population included WTC-exposed male firefighters from FDNY (N = 8466) and non-WTC-exposed male firefighters from Chicago (N = 1195), Philadelphia (N = 770), and San Francisco (N = 650) fire departments who were employed on 9/11/2001 and completed a health questionnaire between 3/1/2018 and 12/31/2020. Current PTSD symptoms, depressive symptoms, and subjective cognitive concerns were assessed via validated screening instruments. Multivariable linear regression analyses stratified by fire department estimated the impact of covariates on each outcome. RESULTS Adjusted mean PTSD symptom scores ranged from 23.5 ± 0.6 in Chicago firefighters to 25.8 ± 0.2 in FDNY, and adjusted mean depressive symptom scores ranged from 7.3 ± 0.5 in Chicago to 9.4 ± 0.6 in Philadelphia. WTC-exposure was associated with fewer subjective cognitive concerns (β = -0.69 ± 0.05, p

Objective This pilot study aimed to assess the feasibility of intraoperative assessment of safe margins with Confocal Laser Endomicroscopy (CLE) during planned partial or total laryngectomy. Methods Eight patients with confirmed larynx squamous cell carcinoma (SCC) and planned partial or total laryngectomy were included in this study in March 2020. Two head and neck surgeons and one pathologist were asked to classify carcinoma or healthy epithelium in a sample of 94 representative sequences (5.640 images), blinded to the histological results (H&E staining). Results Healthy mucosa areas showed epithelium with cells of uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE optical biopsy of SCC demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 80.1%, 72.3%, 87.9%, 85.7%, and 76.1%, respectively. A distinct transition between healthy appearing tissue and suspicious lesions could also be detected. Conclusion CLE can be easily integrated into the intraoperative setting, generate real-time, in-vivo microscopic images of the larynx for evaluation and demarcation of cancer. If validated in further studies, CLE could eventually contribute to a less radical approach by enabling a more precise evaluation of the cancer margin.

Purpose The aim of this study was to investigate the feasibility and reliability of transcutaneous ultrasound for the detection of complications after cochlear implantation. Methods In a single center retrospective cohort study, 115 consecutive cases of suspected complications after cochlear implantation (intervention group) were examined. The rate of pathologic ultrasound findings for specific leading symptoms and diagnoses was compared to a control group comprising twenty consecutive cochlear implants in symptom-free patients. Results Diagnostic ultrasound showed distinctly more pathologic findings in the intervention group (n = 67; 58.3%; p n = 1; 5%). Ultrasound revealed significantly more pathologic findings in haematoma or seroma around the implant (n = 17; 100%; p ϕ = 0.94) and magnet dislocation (n = 44; 97.7%; p ϕ = 0.92) confirmed by a strong effect. Ultrasound examination showed a medium to high effect size in patients presenting with local infections (n = 3; 21.4%; p = 0.283; ϕ = 0.25) and skin flap oedema (n = 2; 50%; p = 0.061; ϕ = 0.51). In contrast, ultrasound examinations displayed a low effect size in undefined cephalgia (0%; p = 0.444; ϕ = 0.17) and device malfunction or failure (0%; p > 0.999; ϕ = 0.13). Conclusion Transcutaneous ultrasound can be advocated as a feasible and effective method in the diagnostic work-up of magnet dislocation and haematoma or seroma around the implant following cochlear implantation. Contrary, ultrasound findings can be expected to be inconspicuous in patients presenting with undefined cephalgia and device malfunction or failure.

The main route of transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus is airborne. The objective of this study is to analyze the aerosol dispersion and potential exposure to medical staff within a typical medical examination room during classical airway procedures. The multiphase simulation of the aerosol particles in the airflow is based on a Lagrangian-Eulerian approach. All simulation cases with surgical mask show partially but significantly reduced maximum dispersion distances of the aerosol particles compared to the cases without a surgical mask. The simulations have shown that medical examiners are exposed to a large amount of aerosol particles, especially during procedures such as laryngoscopy where the examiner's head is directly in front of the patient's face. However, exposure can be drastically reduced if the patient wears a mask which is possible for most of the procedures studied, such as otoscopy, sonography, or anamnesis.

Human papillomavirus (HPV)+ and HPV- oropharyngeal squamous cell carcinomas (OPSCC) are separate tumor entities.The aim of this study was to examine if the p16 status influences the need and outcome of a salvage neck dissection (SND) after primary radiochemotherapy (pRCT).Retrospective study of 164 patients (Of the 56 p16+ patients, 17 (30.4%) patients were given an indication for a SND after pRCT with 4 (23.5%) patients showing persistent malignant nodes. Of the 108 p16- patients, 24 (22.2%) patients underwent a SND with 8 (33.3%) patients showing persistent malignant nodes. There was no significant association of the p16 status and neither the indication for SND (p(ChiThere was neither a significant association between the p16 status and the indication for a SND nor for persistent malignant nodal disease after pRCT.

A 50-year-old patient was admitted with symptoms of intracranial hypotension. MRI revealed a cervical myelomalacia caused by engorged epidural veins leading to a stenosis of the spinal canal. This condition is rarely described in patients with hydrocephalus and ventricular shunts suffering from chronic overdrainage. However, the reason in this patient was a CSF leak caused by an intradural disc herniation at T12/L1. After surgery, symptoms resolved and the cervical myelomalacia and the swollen epidural veins disappeared on postoperative MRI. In patients with engorged cervical epidural veins without a ventricular shunt, a CSF leak has to be considered.

Zusammenfassung Hintergrund Die Kupplungsvorrichtung für mikrovaskuläre Anastomosen hat in der freien Gewebetransplantation weite Verbreitung gefunden. Ziel der Arbeit ist der Vergleich der Thromboserate und des Transplantatversagens in Abhängigkeit von der Anastomosentechnik an einem großen Kopf-Hals-Tumorzentrum. Material und Methoden Retrospektive Auswertung von allen Patienten, die im Zeitraum von 2001–2019 eine freie Lappenrekonstruktion erhalten haben. Rekonstruktionstyp, Empfängergefäße, Anzahl an Venenanastomosen, Coupler-Größe und Operationszeit wurden untersucht. Wir verglichen die Raten an Venenthrombosen zwischen handgenähten und gekoppelten Anastomosen sowie die Rate des Transplantatversagens. Ergebnisse Insgesamt wurden 403 freie Lappenrekonstruktionen über einen Zeitraum von 17 Jahren durchgeführt. Die venöse Anastomose wurde bei 113 Lappen in Einzelknopftechnik genäht und in 290 Fällen mittels Coupler durchgeführt. Die Rate der Venenthrombosen, die eine umgehende chirurgische Revision erforderten, betrug in der genähten Gruppe 6,2 % (7/113), verglichen mit 7,6 % in der gekoppelten Gruppe (22/290; p = 0,627). Bei einer allgemeinen Erfolgsrate von 95,0 % (383/403) lag die Rate des Transplantatversagens jeweils bei 3,6 % (4/113) und 5,5 % (16/290; p = 0,421). Die Operationszeit war mit 680 ± 144 Minuten in der handgenähten Gruppe und 688 ± 167 Minuten in der Coupler-Gruppe vergleichbar (p = 0,678). Schlussfolgerungen Bei ähnlichen Erfolgsraten ist der Coupler als wirksame Alternative zur venösen Anastomose in Einzelnahttechnik zu sehen. Aufgrund der allgemein niedrigen Rate an Stielthrombosen in beiden Gruppen können wir den Einfluss der Anastomosentechnik nicht von möglichen Störvariablen trennen.

Introduction: During the COVID-19 pandemic, worldwide over 600,000 human beings died due to the cause of the disease. In order to deescalate the transmission rate and to avoid crush loading the countries medical health systems social distancing, face masks, and lockdowns have been considered essential by the majority of governments. Whereas some countries have highly reduced or completely stopped otorhinolaryngological procedures, other countries have continued selected surgeries. The objective of this study was to analyze procedures and outcomes of continuing semielective and emergency surgeries during the COVID-19 pandemic. Methods: Retrospective analysis of n = 750 patients who received semi-elective or emergency surgery between March 26 and June 16, 2020, in the Otolaryngology Department of the Friedrich-Alexander-University of Erlangen-Nürnberg. All patients were screened for COVID symptoms and swabbed for SARS-CoV-2 prior to surgery. Results: Of the n = 750 patients, n = 699 patients received semielective surgery and n = 51 emergency surgery. For 27 patients, the swab result could not be awaited due to a life-threatening condition. In these cases, surgery was performed in full protective equipment. No patient was tested positive during or after the surgery (follow-up 45 to 127 days). No member of the medical personnel showed symptoms or was tested positive after contact with patients. Due to the continuation of surgeries, patients’ lives were saved and improvement of long-term quality-of-life and outcomes is anticipated. Conclusions: Continuing selected otorhinolaryngological surgeries is crucial for patients’ health, survival, and long-time quality of life, yet, the protection of the medical personnel has to be granted.

BACKGROUND: Interhospital transfer (IHT) is often performed to provide patients with specialized care. Racial/ethnic disparities in IHT have been suggested but are not well-characterized. OBJECTIVE: To evaluate the association between race/ethnicity and IHT. DESIGN: Cross-sectional analysis of 2016 National Inpatient Sample data. PATIENTS: Patients aged ≥ 18 years old with common medical diagnoses at transfer, including acute myocardial infarction, congestive heart failure, arrhythmia, stroke, sepsis, pneumonia, and gastrointestinal bleed. MAIN MEASURES: We performed a series of logistic regression models to estimate adjusted odds of transfer by race/ethnicity controlling for patient demographics, clinical variables, and hospital characteristics and to identify potential mediators. In secondary analyses, we estimated adjusted odds of transfer among patients at community hospitals (those more likely to transfer patients) and performed subgroup analyses by region and primary medical diagnosis. KEY RESULTS: Of 5,774,175 weighted hospital admissions, 199,015 (4.5%) underwent IHT, including 4.7% of White patients, compared with 3.9% of Black patients and 3.8% of Hispanic patients. Black (OR 0.83, 95% CI 0.78–0.89) and Hispanic (OR 0.81, 95% CI 0.75–0.87) patients had lower crude odds of transfer compared with White patients, but this became non-significant after adjusting for hospital-level characteristics. In secondary analyses among patients hospitalized at community hospitals, Hispanic patients had lower adjusted odds of transfer (aOR 0.89, 95% CI 0.79–0.98). Disparities in IHT by race/ethnicity varied by region and medical diagnosis. CONCLUSIONS: Black and Hispanic patients had lower odds of IHT, largely explained by a higher likelihood of being hospitalized at urban teaching hospitals. Racial/ethnic disparities in transfer were demonstrated at community hospitals, in certain geographic regions and among patients with specific diseases.

Objective Repair of cerebrospinal fluid (CSF) leaks of the lateral recess of the sphenoid (LRS) sinus can be challenging to accomplish via an endoscopic transphenoidal approach. The endoscopic transpterygoid approach can improve surgical access to the lateral recess but requires more extensive surgical dissection. We review our experience with LRS CSF leak repair via both techniques to determine whether preoperative radiologic data can help predict the most appropriate surgical approach. Methods Electronic medical records of patients with LRS CSF leaks were retrospectively reviewed at a single tertiary referral center. Radiographic measurements from preoperative computed tomography images were reviewed. Results Twenty‐two LRS CSF leaks were identified. The transphenoidal and transpterygoid approach were used in 6 (27.3%) and 16 (72.7%) cases, respectively. The mean vidian canal to foramen rotundum angle of the repairs accessed transphenoidally as compared to the transptyergoid approach were not significantly different (41.93° ±10.91, 40.72° ±19.49, respectively; P = .63). However, the mean volume of the LRS accessed by the transpterygoid approach was significantly greater compared to those accessed through the transphenoidal approach (0.97 cm3 ± 0.48, 0.39 cm3 ± 0.40, respectively; P = .04). A LRS volume of 0.400 cm3 or greater predicted the use of the transpterygoid approach with 93.3% sensitivity and 60.0% specificity. Conclusion This study demonstrated that LRS CSF leaks that necessitated repair by the transpterygoid approach, rather than transphenoidal approach, were in the context of significantly larger lateral recess. Assessment of the LRS volume is a quantifiable parameter to aid in preoperative surgical planning. Level of Evidence Level 4., The endoscopic endonasal surgical approach is the gold standard in these repairs, however, the LRS sinus is particularly challenging due to anatomical constraints. Another method, known as the endoscopic endonasal transpterygoid (ETTP) approach has been used, but requires a more invasive process. Depending on the location of the CSF leak, maneuverability limitations and risks are important to consider. Our goal is to define a quantifiable parameter that will be useful in preoperative surgical planning to determine the safest, most effective approach on a case‐by‐case basis.

Since emergence of the new coronavirus in China in December 2019, many countries have been struggling to control skyrocketing numbers of infections, including among healthcare personnel. It has now been clearly demonstrated that SARS-CoV‑2 resides in the upper airways and transmits easily via aerosols and droplets, which significantly increases the risk of infection when performing upper airway procedures. Ventilated COVID-19 patients in a critical condition in the intensive care unit may require tracheotomy for long-term ventilation and to improve weaning. However, the risk of secondary infection of medical personnel performing subsequent tracheostomy care remains unclear.This study aimed to evaluate the risk of droplet dispersion during tracheostomy tube change and overview tracheostomy tube change in COVID-19 patients.The current literature was reviewed, quantitative and qualitative analyses of droplet formation during tracheostomy tube change in n = 8 patients were performed, and an overview of and checklist for tracheostomy tube change were compiled.This study demonstrates that tracheostomy tube change, in particular insertion of the new tube, may cause significant droplet formation. The aerosolization of particles smaller than 5 µm was not analyzed.Our data, together with the current literature, clearly emphasize that tracheostomy care is associated with a high infection risk and should only be performed by a small group of well-trained, maximally protected healthcare personnel.HINTERGRUND: Seit dem Auftreten des neuen Coronavirus im Dezember 2019 in China haben viele Länder Schwierigkeiten, die ansteigende Zahl der Infektionen, auch innerhalb des medizinischen Personals, zu kontrollieren. Es hat sich mittlerweile deutlich gezeigt, dass das neue SARS-CoV-2-Virus insbesondere über Aerosole und Tröpfchen der oberen Atemwege übertragen wird und die Infektionsgefahr bei oberen Atemwegsprozeduren deutlich erhöht ist. Ein Anteil der schwererkrankten beatmungspflichtigen Patienten benötigt ab einem gewissen Zeitpunkt eine Tracheotomie zur langfristigen Beatmung und einfacheren Entwöhnung von der Beatmungsmaschine. Diese Patienten erfordern jedoch im Anschluss eine nicht unerhebliche Betreuung durch medizinisches Pflegepersonal, und es ist bislang unklar, inwieweit die Tracheostomapflege ein Risiko für sekundäre Infektionen darstellt.Evaluierung der Gefahr der Tröpfchenbildung bei Trachealkanülenwechsel, Überblick zum Kanülenwechsel bei COVID-19-Patienten.Literaturrecherche, quantitative und qualitative Analyse der Tröpfchenfreisetzung bei Kanülenwechsel an n = 8 Patienten, Übersicht und Checkliste für Kanülenwechsel.Diese Studie demonstriert, dass beim Kanülenwechsel, insbesondere bei Einführen der neuen Kanüle, eine nicht unbeträchtliche Menge an Tröpfchen entstehen kann. Eine Aerosolbildung von Partikeln kleiner als 5 µm wurde nicht untersucht.Unsere Ergebnisse im Zusammenhang mit der aktuellen Literatur verdeutlichen, dass die Pflege nach Tracheotomie eine hoch risikoreiche Prozedur darstellt und nur von einer kleinen Gruppe von geschultem und gut geschütztem Personal durchgeführt werden sollte.

Low intensity transcranial focused ultrasound (LIFU) is a promising method of non-invasive neuromodulation that uses mechanical energy to affect neuronal excitability. LIFU confers high spatial resolution and adjustable focal lengths for precise neuromodulation of discrete regions in the human brain. Before the full potential of low intensity ultrasound for research and clinical application can be investigated, data on the safety of this technique is indicated. Here, we provide an evaluation of the safety of LIFU for human neuromodulation through participant report and neurological assessment with a comparison of symptomology to other forms of non-invasive brain stimulation. Participants (N = 120) that were enrolled in one of seven human ultrasound neuromodulation studies in one laboratory at the University of Minnesota (2015–2017) were queried to complete a follow-up Participant Report of Symptoms questionnaire assessing their self-reported experience and tolerance to participation in LIFU research (Isppa 11.56–17.12 W/cm2) and the perceived relation of symptoms to LIFU. A total of 64/120 participant (53%) responded to follow-up requests to complete the Participant Report of Symptoms questionnaire. None of the participants experienced serious adverse effects. From the post-hoc assessment of safety using the questionnaire, 7/64 reported mild to moderate symptoms, that were perceived as ‘possibly’ or ‘probably’ related to participation in LIFU experiments. These reports included neck pain, problems with attention, muscle twitches and anxiety. The most common unrelated symptoms included sleepiness and neck pain. There were initial transient reports of mild neck pain, scalp tingling and headache that were extinguished upon follow-up. No new symptoms were reported upon follow up out to 1 month. The profile and incidence of symptoms looks to be similar to other forms of non-invasive brain stimulation.

Highlights • Pedicled flap reconstruction in the head and neck is still an alternative if free flaps are not possible. • Angiography of the subclavian artery is not a standard procedure in the surgical planning of pedicle flap harvesting. • In exceptional cases, we recommend angiography of the neck and thoracic vessels. • The application of a temporary pharyngostoma is still an option in extraordinary circumstances., Introduction Pedicled flap reconstruction still plays an essential role in head and neck surgery as an alternative to free grafts. Two standard methods are the pectoralis major and the deltopectoral flap, which are generally characterized by their reliable perfusion. This case describes bilateral arteriosclerosis of the subclavian artery as a possible cause of flap failure. Presentation of case We report on a 65-year-old patient with a multilevel carcinoma of the right pharynx. Due to the unique patient history, a free flap reconstruction was not possible. After resection of the primary, we performed reconstruction with a pedicled pectoralis major flap. Discussion Postoperatively, we observed necrosis of the pectoralis major flap. Secondary defect reconstructions were performed with a deltopectoral flap first from the right and then, in the case of necrosis, from the left side. Stenosing arteriosclerotic plaques of the subclavian artery on both sides were the cause of flap failure. Conclusion Preoperative angiography of the subclavian artery is not a standard diagnostic procedure in the surgical planning of pedicled flap reconstruction in the head and neck region. In exceptional cases, we recommend angiographic imaging of the supplying vessels to make a more precise flap selection and avoid complications.

Surgical resection remains the first line treatment for salivary gland cancer (SGC). In the case of locally advanced disease, surgery is followed by adjuvant radiotherapy. Surgical resection should be favored in resectable locoregional recurrent disease as well, and even the complete resection of all distant oligometastases has clinical benefit for the patients. For inoperable and disseminated metastatic disease, a multitude of systemic therapies including chemotherapy, targeted therapy, and immunotherapy are available. In this review, the current therapeutic options for inoperable recurrent or metastatic SGCs are summarized. Systemic treatment can achieve prolonged progression-free and overall survival, while the overall prognosis remains poor. Current clinical trials include only a limited number of patients and mostly combine different histologic subtypes. Additionally, no randomized controlled trial comparing different therapeutic options has been performed. In the future, further studies with a larger patient cohort and ideally only one histologic subtype are needed in order to improve the outcome for SGC patients. However, this may be difficult to accomplish due to the rarity and diversity of the disease. Additionally, molecular analyses need to be performed routinely in order to individualize treatment and to go one step further towards precision medicine.

HNO 70(1), 44-50 (2022). doi:10.1007/s00106-021-01029-w, Published by Springer, New York

Endomicroscopia confocale laser tramite sonda nel rilevamento delle lesioni maligne delle corde vocali.L’endomicroscopia confocale laser (CLE) tramite sonda è una tecnica innovativa per l’analisi in tempo reale non invasiva dell’epitelio di superficie. Mentre il suo uso diagnostico ha avuto successo tra gli specialisti, questo metodo non si è ancora affermato nella routine clinica, in parte anche per la mancanza di regole e criteri per la classificazione delle varie lesioni. Il nostro obiettivo era quello di determinare il valore diagnostico e l’affidabilità tra valutatori CLE nel rilevamento delle lesioni maligne delle corde vocali. Sono state estratte 58 sequenze video dagli esami CLE tramite sonda (sonda GastroFlex con un sistema laser CellvizioProbe-based confocal laser endomicroscopy (CLE) is an innovative technique for real-time, non-invasive analysis of the surface epithelium. While being successfully used for diagnosis by experts, this method has not yet been established in clinical routine, partly due to the lack of standards and criteria for classifying various lesions. Our aim was to determine the diagnostic value and inter-rater reliability of CLE in detecting malignant lesions of the vocal cords. 58 video sequences were extracted from the probe-based CLE (GastroFlex probe with a Cellvizio

Repulsive guidance molecule A (RGMa) is a potent inhibitor of axonal growth and a regulator of neuronal cell death. It is up-regulated following neuronal injury and accumulates in chronic neurodegenerative diseases. Neutralizing RGMa has the potential to promote neuroregeneration and neuroprotection. Previously we reported that a rat anti-N terminal RGMa (N-RGMa) antibody r5F9 and its humanized version h5F9 (ABT-207) promote neuroprotection and neuroregeneration in preclinical neurodegenerative disease models. However, due to its cross-reactivity to RGMc/hemojuvelin, ABT-207 causes iron accumulation in vivo, which could present a safety liability. Here we report the generation and characterization of a novel RGMa-selective anti-N-RGMa antibody elezanumab, which is currently under Phase 2 clinical evaluation in multiple disease indications. Elezanumab, a human monoclonal antibody generated by in vitro PROfusion mRNA display technology, competes with ABT-207 in binding to N-RGMa but lacks RGMc cross-reactivity with no impact on iron metabolism. It neutralizes repulsive activity of soluble RGMa in vitro and blocks membrane RGMa mediated BMP signaling. In the optic nerve crush and optic neuritis models, elezanumab promotes axonal regeneration and prevents retinal nerve fiber layer degeneration. In the spinal targeted experimental autoimmune encephalomyelitis (EAE) model, elezanumab promotes axonal regeneration and remyelination, decreases inflammatory lesion area and improves functional recovery. Finally, in the mouse cuprizone model, elezanumab reduces demyelination, which is consistent with its inhibitory effect on BMP signaling. Taken together, these preclinical data demonstrate that elezanumab has neuroregenerative and neuroprotective activities without impact on iron metabolism, thus providing a compelling rationale for its clinical development in neurodegenerative diseases.

Definitive radiochemotherapy of locally advanced head and neck squamous cell cancer (HNSCC) achieves high locoregional tumor control rates, but is frequently associated with long-term toxicity. A future direction could be a de-escalation strategy focusing on treated volume rather than radiotherapy dose. This analysis evaluates radiotherapy dose and volume parameters of patients treated with a standard contouring approach in a clinical trial context compared with a revised volume-reduced contouring approach. In this case, 30 consecutive patients from the CheckRad-CD8 trial treated at a single study center were included in this analysis. Treatment toxicity and quality of life were assessed at the end of radiotherapy. Standard treatment plans (ST) following state of the art contouring guidelines that were used for patient treatment and volume reduced treatment plans (VRT) according to a revised simulated approach were calculated for each patient. Planning target volumes (PTV) and mean doses to 38 organs-at-risk structures were compared. At the end of radiotherapy patients reported high rates of mucositis, dysphagia and xerostomia. In addition, patient reported quality of life as assessed by the EORTC QLQ-HN35 questionnaire deteriorated. Comparing the two contouring approaches, the elective PTV_56 Gy and the high risk PTV_63 Gy (shrinking field) were significantly smaller in the VRT group. Significant reduction of mean dose to structures of the oral cavity, the larynx as well as part of the swallowing muscles and the submandibular glands was achieved in the simulated VRT-plan. Treatment de-intensification by reduction of the irradiated volume could potentially reduce treatment volume and mean doses to organs at risk. The proposed contouring approach should be studied further in the context of a clinical trial.

Traditionally, sinonasal adenocarcinomas have been subdivided into intestinal (ITAC) and non-intestinal (non-ITAC) categories. The latter encompasses salivary-type adenocarcinomas originating from the seromucinous glands of the sinonasal mucosa and non-salivary adenocarcinomas. The non-salivary adenocarcinoma category is further subdivided into low-and high-grade variants. Among salivary-type sinonasal adenocarcinomas, tumors recapitulating salivary duct carcinoma (SDC) are exceedingly rare, but some might have been lumped into the high-grade non-ITAC category. To date, only three primary SDCs originating in the sinonasal tract have been reported. We herein describe 7 cases of SDC including one previously reported case (4 primary sinonasal, 3 metastatic/ extension from parotid gland SDC). The primary tumors affected 3 males and one female aged 60 – 75. Different sites were involved by the primary tumors while the secondary tumors affected the sphenoidal (2) and the frontal + maxillary (1) sinuses. Three primary tumors were de novo high-grade SDC and one was confined to contours of a pre-existing pleomorphic adenoma. All 3 secondary tumors were SDC ex pleomorphic adenoma of the parotid with a long history of recurrences, ultimately involving the sinonasal tract. Androgen receptor was positive in 7/7 cases. Four of 6 cases were strongly HER2/neu + (either score 3 + or with verified amplification). This small case series adds to the delineation of primary sinonasal SDC highlighting that almost half of invasive SDC presenting within sinonasal tract indeed represents extension or metastasis from a parotid gland primary. There is a tendency towards overrepresentation of HER2/neu-positive cases in both categories (primary and metastatic), but this needs clarification in larger studies.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Objective: Companion animals are an important feature of the family system, and human-animal interaction is increasingly being recognized as an important social determinant of health. However, there is a need for more nuanced assessment of not only who owns pets, but how pet ownership is related to various health outcomes, and which sociodemographic and contextual factors moderate these associations. Design: Secondary analysis of cross-sectional data collected from an online, probability-based panel to generate a nationally representative sample of adults in the United States (n = 1267). Data were analyzed using hierarchical and logistic regression models. Results: Results suggested that pet owners are systematically different from non-pet owners on a number of key demographic and contextual characteristics, and these differences vary somewhat when looking at dog owners and cat owners. When controlling for individual and family-level covariates, pet ownership was not associated with overall health status or Body Mass Index, but dog ownership was associated with higher levels of physical activity. Pet ownership was associated with higher odds of having an anxiety disorder with gender moderating this relationship, but this association was not present for dog or cat owners, suggesting this relationship is limited to other types of pets. Higher odds of depression were associated with pet ownership (for both dog and cat owners), with employment status significantly moderating the relationship between dog ownership status and depression. Conclusions: These findings suggest that pet ownership is a complex and context specific phenomenon. Future research should carefully consider and control for sociodemographic predictors and use measurement and analysis approaches sensitive to the variations in human-animal relationships to fully understand how pets contribute to individual and family health and well-being.

Background Recurrent and residual laryngeal cancer after organ-preserving radio- or radiochemotherapy is associated with a poor prognosis. Salvage surgery is the most important therapeutic option in these cases. Objective The study assessed rates of recurrence and residual tumor as well as survival and complication rates after salvage laryngectomy at the authors’ academic cancer center. Materials and methods A retrospective examination of all patients receiving laryngectomy between 2001 and 2019 due to tumor residuals or recurrence after primary radio- and radiochemotherapy was conducted. Results A total of 33 salvage procedures were performed. Defect reconstruction was performed by free flap surgery in 30.3% (n = 10) and regional flap surgery in 15.2% (n = 5) . One patient received regional flap surgery and free flap surgery simultaneously. Overall survival after 1, 2, and 5 years was 68.7, 47.9, and 24.2%, and disease-free survival was 81.6, 47.8, and 24.2%, respectively, with 48.5% (n = 16) postoperative tumor recurrences overall. Disease-free survival was significantly shorter for tumor extension into or onto the hypopharynx (p = 0.041). Postoperatively, 72.7% of patients developed a pharyngocutaneous fistula, of which 24.2% required surgical treatment. The hospital stay was 28.0 ± 16.1 days. Conclusion Salvage laryngectomy is associated with a high rate of treatable complications and high morbidity. Nevertheless, considering the advanced tumor stages treated, it allows for respectable oncological results.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is treated using oral/topical steroids and surgery. Despite maximal medical therapy, some patients remain recalcitrant. Mucus cystatin 2, pappalysin-A, and periostin can predict the presence of CRSwNP and correlate with disease severity. This study was designed to determine whether prospective sampling of these mucus proteins could predict medical failure and the need for revision surgery. Methods This investigation was an institutional review board‒approved, prospective study of 66 patients with CRSwNP. All patients underwent surgery, administration of topical/oral steroids, and outpatient mucus sampling at 10 time-points over 2 years. Five proteins, including cystatin 2 (CST2), pappalysin-A (PAPP-A), and periostin (PST), were analyzed and correlated with subjective parameters (including scores on the 22-item Sino-Nasal Outcomes Test [SNOT-22]). Variables were then analyzed and compared between those requiring revision surgery within 2 years (n = 5) and those with stable disease (n = 61). Results All patients demonstrated a significant decline in CST2, PAPP-A, and periostin after their initial surgery. The recalcitrant group demonstrated escalations in all proteins despite steroids, with levels higher than those of the stable group at 1 year (CST2: 258.1 ± 205.2 pg/mL vs 235.3 ± 275.7 pg/mL, p = 0.86; PAPP-A: 170.3 ± 150.4 pg/mL vs 74.6 ± 106.7 pg/mL, p < 0.05; periostin: 188.8 ± 192.4 ng/mL vs 54.5 ± 47.6 ng/mL, p < 0.001). Escalation in all proteins correlated significantly with worsening SNOT-22 score at each time-point (domain 1: 8.2 ± 1.3 vs 5.5 ± 1.1; p < 0.05). Conclusion Early recurrences and medical recalcitrance in CRSwNP may be predicted noninvasively through the serial, prospective sampling of mucus CST2, PAPP-A, and periostin levels. These biosignatures may help to predict disease course and guide individualized therapy.

BACKGROUND Cystatins are epithelial protease inhibitors that participate in sinonasal immunity and inflammation. Nasal mucus-derived exosomes (NMDEs) are small vesicles secreted by epithelial cells that carry protein cargo reflective of their host cell. NMDEs have been used as a noninvasive biomarker source to study chronic rhinosinusitis with nasal polyps (CRSwNP) proteomics with superior sensitivity to whole mucus. The purpose of this study was to noninvasively quantify exosomal cystatins in a heterogenous population to determine their utility in predicting phenotype and disease severity. METHODS This was an Institutional Review Board-approved study in which NMDEs were purified from 105 patients undergoing sinonasal surgery by ultracentrifugation. Demographic and clinical variables were collected and phenotypes were assigned a priori. Linear discriminant analysis was executed based on normalized Cystatin values as phenotype predictor variables. Unsupervised cluster analysis was performed using Ward's linkage followed by Duda/Hart Je(2)/Je(1) index cluster stopping rules. Analysis of variance (ANOVA), Welch's test, and Fisher's exact tests were used for continuous and categorical variables. RESULTS NMDE Cystatin-2 expression segregated by phenotype (mean ± standard error [SEM]): control (23.4 ± 4.2 pg/µg, n = 32); CRS without NP (CRSsNP) (56.6 ± 8.3 pg/µg, n = 33); and CRSwNP (130.5 ± 16.7 pg/µg, n = 40) (p < 0.0001). Seven clusters were identified among patients where the highest NMDE Cystatin-2 levels clustered with asthma, tissue eosinophilia, and aspirin-exacerbated respiratory disease (AERD). CONCLUSION Cystatin levels in NMDEs predict CRS phenotype and disease severity. As a "liquid biopsy," noninvasive NMDE collection offers a promising opportunity to study disease pathophysiology, discriminate disease states, and potentially reveal novel therapeutic targets.

Objectives The aim of this study was to investigate the hypothesis of whether extracapsular dissection (ED) of the parotid gland increases the need for revision surgery for benign tumours in comparison to traditional surgical modalities. A further aim of this study was to evaluate and compare the functional outcome of revision procedures after primary ED with other modalities involving the parotid gland in our department. Materials and methods All patients who underwent revision parotid surgery after a primary surgical procedure at a tertiary care hospital (University of Erlangen-Nurnberg) between 2000 and 2016 were included in our study. Data concerning the indication for revision surgery as well as the functional postsurgical outcome were obtained. Results 2465 cases formed our study sample. In total, revision surgery was necessary in 30/2465 cases (1.2%). 1532 patients underwent primary ED, with 17 cases requiring revision (1.1%), whereas 933 cases were managed by means of other facial nerve dissecting surgical modalities, with the indication for revision surgery in 13 cases (1.4%). Our analysis did not reveal a statistically significantly higher need for revision surgery or a higher rate of facial nerve palsies after revision surgery in the group of patients after primary ED. Conclusion The argument in favour of a greater need for revision surgery after primary parenchyma-sparing modalities was not sustained from our data. Due to the low revision rate and the acceptable functional results after revision surgery, we believe that extracapsular dissection is justified in cases where a benign lesion is suspected preoperatively.

Objective The transfer of patients between acute care hospitals (interhospital transfer [IHT]) is a common but nonstandardized process leading to variable quality and safety. The goal of this study was to survey accepting physicians regarding problems encountered in the transfer process. Methods A cross-sectional survey of residents and inpatient attendings from internal medicine, neurology, and surgery services at a large tertiary care referral hospital was undertaken to identify problematic aspects of the IHT process as perceived by accepting frontline providers. The frequency that specific scenarios were encountered in caring for transferred patients and whether these processes impacted patient safety were determined using 5- and 3-point Likert scales, respectively. The frequency of responses to each question were measured using proportions. Results Approximately 51% of the 284 physicians surveyed responded. Pertinent findings included the following: physician subject surveys found that transferred patients sometimes, frequently, or always arrived without requiring specialized care in 56% of responses, arrived with unrealistic expectations of care in 77.2% of responses, arrived more than 24 hours after accepted for transfer in 80.1% of responses, and arrived without necessary transfer records in 86.9% of responses. Most respondents felt that lack of availability of transfer records and the time of day of arrival frequently posed a risk to transferred patients (57.2% and 53.1%, respectively). Response variation was noted between resident and attending physician respondents. Conclusions Expectations of care, delays and timing of transfer, and information exchange at time of transfer were identified as all too common problems in IHT, which creates a risk for patient safety. These areas are important targets for investigation and the development of interventions to improve patient safety.

Background Caregiver burden is present in many clients managing illness in a companion animal, but current assessment tools are time‐consuming and lack normative reference values. Objectives Statistical reduction of items in a measure of caregiver burden to create an abbreviated version, validation of the abbreviated version, and calculation of reference values. Animals None. Methods This study was conducted using observational methods. Owners of an ill cat or dog were recruited through social media (n = 429). Veterinary clients with an ill (n = 459) or healthy (n = 961) cat or dog were recruited through a general veterinary and an academic hospital with multiple specialties. The study was conducted in 3 stages: (a) reduction of the Zarit Burden Interview (ZBI) adapted for use in pets via factor and item analyses, (b) psychometric validation of the abbreviated instrument, and (c) standardization of the abbreviated (7 items) and full (18 items) measures. Results A 7‐item measure showed high correlations with the full measure (r = 0.88‐0.93) and good internal consistency (α = .71‐.75) across samples of veterinary clients with an ill cat or dog. This abbreviated measure correlated significantly (P

Background Renal cell carcinomas (RCC) represent a heterogeneous group of hypo- and hypervascularized malignancies. Using contrast-enhanced ultrasound (CEUS) specific imaging features of clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC) subtypes have been demonstrated. However, some RCCs show atypical imaging features making it difficult to distinguish between the subtypes. Objective This study was performed to evaluate the observed enhancement features of pRCC in CEUS and to assess the sensitivity in the diagnosis of suspected renal malignancies in a 10 year retrospective analysis at our institution. Methods The study population consisted of 60 patients with histologically confirmed pRCC. All patients underwent CEUS imaging between 2005 and 2015 as part of their diagnostic workup. Results In 45 out of 60 (75%) cases the examined pRCC showed typical hypoenhancement and wash-out. 15 out of 60 (25%) pRCC showed atypical enhancement features; in 14 cases the contrast enhancement indicated a ccRCC. 1 complex cyst was falsely reported as IIF lesion. 59 out of 60 malignancies were reported as malignant using CEUS resulting in a sensitivity of 98.4%. Conclusions CEUS is an eligible imaging technique to visualize the contrast enhancement features of pRCC. However, up to 25% of pRCCs show an atypical enhancement pattern making it difficult to distinguish it from other renal lesions.

Research on the impact of companion animals in the lives of older adults is considered from two perspectives: pet ownership and in animal-assisted interventions (AAI). This paper first presents a d...

Targeted noninvasive control of the nervous system and end-organs may enable safer and more effective treatment of multiple diseases compared to invasive devices or systemic medications. One target is the cholinergic anti-inflammatory pathway that consists of the vagus nerve to spleen circuit, which has been stimulated with implantable devices to improve autoimmune conditions such as rheumatoid arthritis. Here we report that daily noninvasive ultrasound (US) stimulation targeting the spleen significantly reduces disease severity in a mouse model of inflammatory arthritis. Improvements are observed only with specific parameters, in which US can provide both protective and therapeutic effects. Single cell RNA sequencing of splenocytes and experiments in genetically-immunodeficient mice reveal the importance of both T and B cell populations in the anti-inflammatory pathway. These findings demonstrate the potential for US stimulation of the spleen to treat inflammatory diseases., Modulation of the cholinergic pathway and spleen function can reduce inflammation with invasive implants. Here, the authors show that non-invasive ultrasound stimulation of the spleen reduces disease severity in a mouse model of inflammatory arthritis, partly via altering B and T cell function.

BACKGROUND Much of the literature examining chronic rhinosinusitis with nasal polyps (CRSwNP) immunopathology has been predicated on messenger RNA (mRNA) analysis with the assumption that transcriptional changes would reflect end-effector protein expression. The purpose of this study was to test this hypothesis using matched transcriptomic and proteomic data sets. METHODS Matched tissue proteomic and transcriptomic arrays were quantified in CRSwNP polyp tissue and control inferior turbinate tissue (n = 10/group). Mucus samples were additionally collected in 6 subjects from each group. Proteins were grouped into functional categories by bioinformatics and differential expression analyses. Log-log regression and Pearson correlations were performed to determine the level of agreement between data sets. RESULTS Of the 1310 proteins examined, 393 were significantly differentially expressed in CRSwNP. On regression analysis, differences in protein expression were poorly predicted by differences in mRNA expression (R2 = 0.020, p < 0.05). Several genes canonically thought to be overexpressed in CRSwNP, including IL-5, IL-13, TSLP, CCL13, and CCL26, showed substantial increases in mRNA transcription, but had minimally or unchanged protein expression. Others, including IgE, periostin, CCL18, and CST1/2, were increased at both the transcriptomic and proteomic levels. Among differentially regulated proteins, tissue and mucus protein levels showed weak correlation (r = 0.26, p < 0.0001). CONCLUSION Proteomic analysis in CRSwNP has revealed novel disease-associated proteins and pathways, yet correlates poorly with transcriptomic data. The increasing availability of proteomic arrays opens the door to new potential explanatory mechanisms in CRSwNP and suggests that mRNA based studies should be validated with protein analysis.

European archives of oto-rhino-laryngology and head & neck 279(4), 2029-2037 (2022). doi:10.1007/s00405-021-06954-8, Published by Springer, Heidelberg

The majority of salivary gland carcinomas are characterized by recurrent gene fusions that proved highly valuable diagnostically, but only rarely of therapeutic impact. Most of these fusion-positive carcinomas belong to the low-grade or intermediate-grade biological category. To date, only 5 cases of salivary gland carcinomas carrying an oncogenic ALK fusion have been reported in 4 recent studies, but their phenotypic spectrum and their nosological classification remain uncharacterized. We herein describe in detail the clinicopathologic and molecular features of 4 ALK-fusion-positive salivary carcinomas and review previously reported cases to assess if they could be classified into a defined World Health Organization (WHO) category. Patients were 3 men and 1 woman aged from 67 to 79 years (median: 70 y). All tumors originated in the parotid gland. Their size ranged from 1.1 to 3 cm (mean, 2 cm). Three tumors were de novo high-grade salivary duct carcinomas (SDCs) and 1 was a low-grade intercalated-type intraductal carcinoma. Histologically, high-grade tumors were predominantly solid, composed of intimately admixed basal (CK5+, androgen-) and luminal (CK5-, androgen+) components. The remarkable basal component showed squamoid basophilic pattern imparting an adenosquamous-like appearance in all cases. Conventional apocrine intraductal high-grade carcinoma was noted in 1 case. Prominent intraductal growth of the solid basal component (highlighted by p63 staining) was seen in all cases. The tumor cells expressed CK7 (3/3), mammaglobin (3/3, 1 focal), GATA3 (3/3, 1 focal), variably CK5 (3/3), and focally the androgen receptor (1/3), but lacked expression of HER2/neu, SOX10, MUC4, TTF1, S100, and Napsin A. The low-grade tumor showed classic histologic and immunophenotypic features of intercalated-type noninvasive intraductal carcinoma. Molecular profiling showed rearrangements involving exon 20 of ALK in all cases, confirmed by ALK immunohistochemistry (IHC and FISH). The fusion partner was EML4 (n=2) and STRN (n=1) in high-grade tumors and EML4 in the intraductal carcinoma. Two patients with high-grade tumors developed progressive disease (1 died at 9 mo; 1 alive under palliative therapy at 5 mo). This series and a review of 5 published cases indicate that ALK rearrangements characterize 2 distinct subsets of salivary gland carcinomas in the spectrum of high-grade androgen-poor, basal-like SDC (total reported: 5 cases) and low-grade intercalated-type intraductal carcinomas (4 cases). Given the therapeutic relevance of ALK fusions, inclusion of ALK IHC in any atypical-looking or androgen-poor SDC and in high-grade adenocarcinoma-not otherwise specified is recommended. Absence of aberrant ALK expression in genetically characterized secretory (n=15) and intraductal (n=9) carcinomas lacking ALK fusions underlines the value of ALK IHC as a diagnostic screening method for identifying potential cases.

BACKGROUND AND OBJECTIVES: Animal-assisted interventions (AAIs) are increasingly popular as treatments to reduce anxiety. However, there is little empirical evidence testing the mechanisms of action in AAIs, especially among adolescents. We examined whether two possible mechanisms, social interaction and/or physical contact with a therapy dog, might reduce anxiety during a social stressor. DESIGN AND METHODS: To test these mechanisms, we randomly assigned 75 adolescents with low, middle, and high levels of social anxiety to complete a laboratory-based social evaluative stressor in one of three conditions: social interaction with a therapy dog (no physical interaction), social plus physical interaction with a therapy dog, or no interaction with a therapy dog. We measured self-reported anxiety and autonomic reactivity during the social stressor to assess the effects of contact with a therapy dog. RESULTS AND CONCLUSIONS: We found no evidence that the presence of a real dog, with or without the opportunity to touch it, reduced anxiety or autonomic reactivity or improved cognitive performance relative to the presence of a stuffed dog in the control condition, regardless of levels of preexisting social anxiety.

Simple Summary This study assessed the relationship between pet ownership, pet attachment, loneliness, and coping with stress before and during the COVID-19 pandemic. Contrary to our hypotheses, results did not support the presence of a buffering effect of pet ownership on loneliness, with pet ownership predicting increases in loneliness from pre-pandemic to during the pandemic. Dog owners showed lower levels of loneliness prior to the pandemic as well as higher levels of attachment, suggesting possible species-level differences in these relationships. Pet owners also reported spending time with their pet as a highly used strategy for coping with stress, suggesting that future research should explore the role of pets in coping with stress and social isolation during the pandemic. These results indicate that the relationship between pet ownership and adolescent loneliness during the pandemic is complex and warrants further research. Abstract The pandemic associated with the emergence of the novel coronavirus (COVID-19) is an unprecedented historical event with the potential to significantly impact adolescent loneliness. This study aimed to explore the role of companion animals and attachment to pets in the context of the pandemic. We used longitudinal quantitative survey data collected prior to and during the pandemic to assess the role of pets in predicting adolescent loneliness. Pet ownership was not a significant predictor of loneliness before the pandemic, but did predict higher levels of loneliness during COVID-19 as well as higher increases in loneliness from before to during the pandemic. Dog ownership predicted lower levels of loneliness prior to, but not during the pandemic, and dog owners were significantly more attached to their pets than non-dog pet owners. Adolescents with pets reported spending more time with their pets during the pandemic, and frequently reported pet interactions as a strategy for coping with stress. Overall, the results from this study did not support the presence of a buffering effect of companion animals on loneliness for adolescents and indicate complexity in the relationships between pet ownership, attachment, loneliness, and coping with stress. These results suggest a need for additional research further assessing how features of the relationship such as species and relationship quality might contribute to adolescent mental health outcomes.

Confocal laser endomicroscopy is an optical imaging technique that allows in vivo, real-time, microscope-like images of the upper aerodigestive tract's mucosa. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignant suspected mucosa requires strict evaluation criteria.This study aims to validate an eight-point score for the correct assessment of malignancy.We performed confocal laser endomicroscopy between March and October 2020 in 13 patients. 197 sequences (11.820 images) originated from the marginal area of pharyngeal and laryngeal carcinomas. Specimens were taken at corresponding locations and analyzed in HE staining as a standard of reference. A total of six examiners evaluated the sequences based on a scoring system; they were blinded to the histopathological examination. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are interrater reliability and receiver operator characteristics.Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. Confocal laser endomicroscopy of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 83.2%, 81.3%, 85.5%, 86.7%, and 79.7%, respectively, with a κ-value of 0.64, and an area under the curve of 0.86.The results confirm that this scoring system is applicable in the laryngeal and pharyngeal mucosa to classify benign and malignant tissue. A scoring system based on defined and reproducible characteristics can help translate this experimental method to broad clinical practice in head and neck diagnosis.

Introduction: In the last years, the use of opioid analgesics has increased, as well as their morbidity and mortality, especially in the United States. Most patients after sinonasal surgery receive opioid analgesics, although up to 90% have leftover opioid pills. Around 70% of these patients keep the opioid analgesics, which could possibly lead to improper use. The objective of the following study was the investigation of the need for, use of, timing and side effects of opioid and non-opioid analgesics after sinonasal surgery. Methods: This was a retrospective study of (n = 280) patients who underwent sinonasal surgery in the Otolaryngology Department of the University Erlangen-Nürnberg between January and December 2018. The postoperative pain (3-5 days after surgery) using the numeric rating scale and the postoperative need for on-demand opioids and non-opioid analgesics in relation to demographic and surgical parameters were evaluated. Results: Of total, 59.64% of all patients received opioid analgesics postoperatively on the day of surgery. On the first postoperative day (POD1), the mean pain score yielded the highest values; however, only 0.71% of the patients needed opioid analgesics, and pain was sufficiently controlled with non-opioids or no pain medication at all. There was a significant reduction of the pain score from POD2 to 5 ( P = .01; P < .01, respectively). Only 1.8% of the patients needed an opioid analgesic from POD1-5. Of total, 2.1% of the patients presented with a postoperative bleeding complication, and only 1 (0.4%) patient needed endoscopic coagulation. Conclusion: Our results indicate that the majority of patients need opioid analgesics almost exclusively on the day of surgery. There were no major complications in patients taking either opioid or non-opioids. Our results indicate that the postoperative pain regimen from POD1 should initially be started using non-opioid analgesics and be further escalated to opioid analgesics in individual cases.

European archives of oto-rhino-laryngology and head & neck 278(11), 4433-4439 (2021). doi:10.1007/s00405-021-06659-y, Published by Springer, Berlin ; Heidelberg