High risk of ischaemic stroke amongst patients with hereditary haemorrhagic telangiectasia.

BACKGROUND AND PURPOSE: Hereditary haemorrhagic telangiectasia (HHT) is a genetic disease with fragile blood vessels and vascular malformations, potentially causing neurological manifestations, including stroke and cerebral abscesses. The study aimed to investigate neurological manifestations in the Danish HHT database, focusing on pulmonary arteriovenous malformations (PAVMs) as a risk factor for cerebral events. METHODS: Retrospective analysis of the Danish HHT database was conducted, cross-referencing neurological outcomes with the Danish Apoplexy Register for accuracy. Patients were stratified by HHT type. Primary outcomes included ischaemic stroke, transient ischaemic attack and cerebral haemorrhage. Secondary outcomes comprised age, age at HHT diagnosis, age at cerebral ischaemic event, and PAVM and cerebral arteriovenous malformation status. RESULTS: Six hundred and sixty-four HHT patients were included. PAVM was diagnosed in 54% of patients, with higher prevalence in HHT type 1 (70%) compared to HHT type 2 (34%) and juvenile polyposis HHT (66%). Ischaemic stroke or transient ischaemic attack occurred in 12.5%, with a higher risk associated with macroscopic PAVM. Logistic regression showed a nearly 10 times increased risk of ischaemic stroke with macroscopic PAVM. Cerebral abscesses occurred in 3.2% of patients, all with macroscopic PAVM. Incomplete PAVM closure increased cerebral abscess risk. CONCLUSION: This study provides valuable insights into the prevalence of neurological manifestations and vascular events in HHT patients. The presence of PAVM was associated with an increased risk of ischaemic stroke, highlighting the importance of early screening and intervention. The findings emphasize the need for comprehensive management strategies targeting both vascular and neurological complications in HHT patients, especially regarding secondary stroke prevention.

The bleeding diathesis in patients with hereditary haemorrhagic telangiectasia is not due to impaired platelet function.

BACKGROUND: Patients with the rare disease; Hereditary haemorrhagic telangiectasia (HHT) often bleed from telangiectatic lesions in mucosal surfaces. Studies suggest that impaired platelet function may also play a role in their bleeding tendency. The aim of the present study was to investigate whether HHT-patients with epistaxis have impaired platelet function. METHOD: We conducted a case-control study based on a sample size calculation and included 22 HHT-patients (inclusion criteria: epistaxis severity score ≥ 4, no intake of medicine affecting platelet function the last 5 days, HHT-type 1 or 2, age ≥ 18 years) and 20 controls. We assessed the platelet function with standard haemostasis parameters, flow cytometry (platelet function and micro aggregation), rotational thromboelastometry and Platelet Function Analyzer 200. RESULTS: We found no significant difference in mean platelet volume and immature platelet fraction and no difference in platelet activation as measured by exposure of CD62P, CD63P and PAC1 binding. Nor did we find a significant difference in platelet aggregation response in HHT-patients compared with the control group for all agonists (thrombin receptor activating peptide, adenosine diphosphate and collagen-related peptide). The PFA-200 analysis was without difference between the two groups and thromboelastometry showed no impairment of global haemostasis. CONCLUSION: Reduced platelet function is unlikely to contribute to the frequent and long bleeding episodes that HHT-patients suffer from. We propose that further studies should focus on whether patients with HHT have hypercoagulability.

Chronic Rhinosinusitis Outcome Registry (CHRINOSOR): Establishment of an International Outcome Registry Driven by mHealth Technology.

BACKGROUND: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics. OBJECTIVE: To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology. METHODOLOGY: A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion. RESULTS: A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security aspects. Up to 300 patients have already been included. CONCLUSIONS: CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE.

A retrospective cohort study on European Reference Network for Rare Vascular Diseases 5 outcome measures for Hereditary Haemorrhagic Telangiectasia in Denmark.

BACKGROUND: Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by several clinical symptoms including epistaxis, arteriovenous malformations (AVM), and telangiectasia. In 2018, European Reference Network for Rare Vascular Diseases (VASCERN) recommended five outcome measures for HHT-patients to guide health care providers, some with limited experience in treating HHT, and thereby maximizing the number of HHT-patients receiving good care. The outcome measures cover the following aspects: (1) 90% of the patients should receive a pulmonary AVM (PAVM) screening; (2) 90% of the patients should receive written advice on nosebleed; (3) 70% should be assessed for iron deficiency; (4) 100% of the patients should receive written advice on antibiotic (AB) prophylaxis prior to dental and surgical procedures, and (5) 100% of relevant patients should receive written advice on pregnancy. We have introduced the outcome measures as Benchmarks in our HHT-centre and wanted to evaluate the extend of implementation we have achieved. We constantly struggle to secure the best possible treatment of our HHT-patients. METHODS: The study was a non-interventional retrospective study. Data was collected manually from patient records and from the Danish HHT-database. RESULTS: A total of 180 HHT-patients were included, all diagnosed in the period from January 1st, 2016, to December 31st, 2020. All patients were screened for PAVM. We could confirm that 66% of patients who had epistaxis received thoroughly advice. Assessment for iron deficiency was performed in 80% of the adult patients. Thoroughly advice on AB prophylaxis was documented in 75%. Thoroughly advice on pregnancy was documented in 80% of female patients 15-45 years of age. There were no significant differences over time for any of the outcome measures. CONCLUSIONS: The Danish HHT-centre reached the target threshold for outcome measures 1 and 3. It could not be documented that the target thresholds for outcome measures 2, 4, and 5 were achieved. As information and education are a very important part of HHT care, focus on and documentation that all patients receive the relevant advice must be a priority in order to ensure best care.

[Screening for cerebral arteriovenous malformations in patients with hereditary haemorrhagic telangiectasia].

Patients with hereditary haemorrhagic telangiectasia (HHT) are known to suffer from cerebral arteriovenous malformations (CAVMs). In this review, we explore existing literature for bleeding risk, interventional therapy and neuroradiological features in HHT-related CAVMs. Studies estimate the annual intracerebral haemorrhage rate of CAVMs in HHT patients to be 0.667-1.014%. The clinician must balance bleeding risk and the non-negligible procedural risks of interventional therapy. We recommend, in agreement with European guidelines, that screening of asymptomatic HHT patients should only be carried out after careful information.

Dietary patterns and respiratory health in adults from nine European countries-Evidence from the GA2 LEN study.

BACKGROUND: Dietary patterns defined using principal component analysis (PCA) offer an alternative to the analysis of individual foods and nutrients and have been linked with asthma and allergic disease. However, results have not been reproducible in different settings. OBJECTIVE: To identify dietary patterns common to different European countries and examine their associations with asthma and allergic symptoms. METHODS: In sixteen study centers in nine European countries, 3206 individuals aged 15-77 years completed a common, internationally validated, food frequency questionnaire and a respiratory symptoms questionnaire. The outcomes of interest were current asthma, asthma symptoms score (derived based on responses to 5 asthma symptom-related questions), atopy (positive skin prick test). Spirometry was used to estimate forced expiratory volume in 1 second (FEV1 ), forced vital capacity (FVC), the FEV1 /FVC, spirometric restriction (FVC below the lower limit of normal (

[Amyloidosis in larynx].

Localised laryngeal amyloidosis is a rare tumour of the upper respiratory tract, which is characterised by extra-cellular accumulation of proteinaceous material in the submucosa. The aetiology is still unclear. This is a case report of localised multifocal amyloidosis located to larynx and rhinopharynx. A 50-year-old women with a history of progressive dysphonia and dyspnoea underwent ear-nose-throat and haematological investigation with no signs of systemic involvement. The amyloid deposits in larynx were effectively treated with laser resection in general anaesthesia and regular follow-up.

[Acute upper airway obstruction caused by a multinodular goitre after tracheotomy].

This case report illustrates how a multinodular goitre caused acute airway obstruction in a multitrauma 66-year-old male after tracheotomy. The patient had no symptoms of the goitre before the tracheotomy but developed subglottic airway obstruction at the time of decannulation. He underwent a subacute total thyroidectomy which removed the obstructive symptoms. A weakening of the tracheal tube followed by the tracheotomy possibly caused the tracheal stenosis in combination with the goitre.

Prevalence of chronic rhinosinusitis in a population of patients with gastroesophageal reflux disease.

BACKGROUND: An increased coexistence of gastroesophageal reflux disease (GERD) and chronic rhinosinusitis (CRS) has been reported in epidemiologic and register studies, and reflux has been shown more frequently in patients with CRS in studies using esophagus pH manometry compared to participants without CRS. A discussion is ongoing about whether there might be an association between these two diseases and, if so, whether the association is causal. OBJECTIVE: The purpose of this study was to clinically investigate the prevalence and symptom severity scores of CRS among patients with GERD. The results were compared with those of a randomly assigned control group from the general Danish population. METHOD: In this case-control study, 82 patients with GERD were examined for CRS using the European Position Paper on Rhinosinusitis and Nasal Polyps criteria, which combine patient history and anterior/posterior rhinoscopy results. Sinonasal-related quality of life was assessed by using the Sino-Nasal Outcome Test 22 (SNOT-22). These results were compared with those of a population-based control group examined for CRS in the same way. RESULTS: The prevalence of CRS among patients with GERD was 20.7% (95% confidence interval [CI], 12.0%-29.5%), significantly higher than the CRS prevalence of 8.5% (95% CI, 6.8%-10.2%) in the background population. Patients with GERD and CRS had an average SNOT-22 score of 43.8, whereas patients with CRS from the background population scored, on average, 28.1. Having GERD increased the mean SNOT-22 score in patients with CRS by 15.7 (95% CI, 6.5-24.9). CONCLUSION: The results of this study provide additional evidence of an association between GERD and CRS and indicate that GERD may play a role in the development of CRS. The results also show that sinonasal-related quality of life is decreased in patients with CRS who also suffer from GERD.

Do patients with chronic rhinosinusitis benefit from consultation with an ENT-doctor?

CONCLUSION: By consulting an ENT-doctor, patients with chronic rhinosinusitis (CRS), in the general population, receive disease information and adjustment of treatment which can improve disease-specific Quality-of-Life and may improve objective measurements. OBJECTIVES: This study aims to follow persons with clinical diagnosed CRS from the general population, to evaluate their benefit from consultation with an ENT-doctor in terms of severity of symptoms and Quality-of-Life. METHODS: As part of a trans-European study, selected respondents to a survey questionnaire were invited for a clinical visit. Based on the European Position Paper on Rhinosinusitis and Nasal Polyps, persons were diagnosed with CRS and followed for 2 years. Quality-of-Life was measured using the Sino Nasal Outcome Test 22 and European Quality-of-Life - 5 Dimensions. Clinical examination included rhinoscopy, acoustic rhinometry, peak nasal inspiratory flow, smell test, and skin prick test. RESULTS: Out of 91 persons with CRS, only 42% had previously consulted an ENT-doctor, and 51% were in current treatment for CRS. Most patients were advised medical treatment and 20% underwent surgery. Disease-specific Quality-of-Life, peak nasal inspiratory flow, olfactory function, and the nasal volume significantly increased over the 2-year period.

Complement defects in patients with chronic rhinosinusitis.

The complement system is an important part of our immune system, and complement defects lead generally to increased susceptibility to infections and autoimmune diseases. We have studied the role of complement activity in relation with chronic rhinosinusitis (CRS), and more specifically studied whether complement defects collectively predispose individuals for CRS or affect CRS severity. The participants comprised 87 CRS patients randomly selected from the general population, and a control group of 150 healthy blood donors. The CRS patients were diagnosed according to the European Position Paper on Rhinosinusitis and nasal Polyps criteria, and severity was evaluated by the Sino-nasal Outcome Test-22. Serum samples were analysed by ELISA for activity of the respective pathways of complement, and subsequently for serum levels of relevant components. We found that the frequency of complement defects was significantly higher among CRS patients than among healthy control subjects. A majority of Mannan-binding lectin deficient CRS patients was observed. The presence of complement defects had no influence on the severity of subjective symptoms. Our studies show that defects in the complement system collectively may play an immunological role related to the development of CRS. However, an association between severity of symptoms and presence of complement defects could not be demonstrated.

Chronic rhinosinusitis and occupational risk factors among 20- to 75-year-old Danes-A GA(2) LEN-based study.

BACKGROUND: Very little is known about occupational risk factors for chronic rhinosinusitis (CRS). The aim of this study was to evaluate occupational and other potential risk factors for CRS in a Danish population. METHODS: A cross sectional survey study among 4,554 Danes aged 20-75 years evaluated self-reported symptoms of CRS, asthma, and nasal allergy, along with information on smoking habits and occupation. RESULTS: A total of 3,099 returned completed questionnaires (response rate 68.1%). The overall CRS prevalence was 7.8% with no significant differences related to age or gender. Risk ratio estimates revealed an increased risk of CRS among female blue collar workers compared to female white collar workers. Among men the effect of occupation depended on smoking status. Occupational exposure to gasses, fumes, dust, or smoke increased the overall risk of CRS. CRS was reported approximately four times as often in subjects with asthma and in subjects with nasal allergy. Current smoking doubled the CRS prevalence. CONCLUSIONS: CRS prevalence was affected by occupation (blue vs. white collar), but the observed effect depended on gender and smoking status. Exposure to airway irritants (occupational or smoking) increased the CRS prevalence. Studies on larger cohorts are needed to fully assess these tendencies, for example, by more extensive use of Job Exposure Matrix models.

Efficiency of laser treatment in patients with hereditary hemorrhagic telangiectasia.

Earlier studies have shown the effect of laser treatment on epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). At the present time, only very few prospective trials have been performed, and many studies are based on patients' subjective assessment of the severity of epistaxis. This prospective study measures the objective effect of laser treatment in HHT patients with mild to moderate epistaxis. We introduce an objective measure to assess the severity of epistaxis: the bleeding time (BT). Before and after treatment, the quality of life, as measured by the patient, was assessed and compared to normative data. In 30 patients, we measured the BT before laser treatment 1.5 and 6.5 months after treatment. The Short form 36 (SF-36), a validated health questionnaire, was completed before and 6.5 months after treatment. Compared to preoperative value, BT was significantly reduced 1.5 and 6.5 months after laser treatment (p < 0.05) in both cases. No significant difference in quality of life, before and after treatment, was found. The quality of life of the HHT patients was reduced in five out of eight dimensions when compared with the Danish background population. Laser treatment reduces epistaxis in HHT patients with mild to moderate epistaxis for at least 6 months; this group of patients have reduced quality of life compared to the background population.

The Sino-Nasal Outcome Test 22 validated for Danish patients.

INTRODUCTION: Chronic rhinosinusitis (CRS) is a significant health problem whose incidence and prevalence is rising. It calls into attention consensus about diagnosing, assessing symptoms and treatment of patients with CRS. Therefore, a validated Danish measure of health-related quality of life in sinonasal disease is needed. MATERIAL AND METHODS: The Sino-Nasal Outcome Test 22 (SNOT-22) was translated into Danish and its reproducibility was evaluated by test-retesting 40 patients with CRS. The statistical analyses used were Pearson's correlation coefficient, Cronbach's alpha, kappa and Bland-Altman's plot. Reproducibility was also tested for SNOT-22 subscales. RESULTS: The results show good internal correlation with a Cronbach's alpha of 0.83 in the initial test and one of 0.92 in the retest. Pearson's correlation coefficient was 0.70 (p < 0.001), revealing good correlation between the initial scores and the retests scores. Kappa was calculated for each item with a mean value of 0.61 showing substantial agreement. The paired t-test revealed no significant difference between the subscales. CONCLUSION: The Danish version of SNOT-22 is recommended for Danish clinicians and researchers as a patient-reported measure of outcome in sinonasal disorders such as rhinosinusitis and nasal polyposis.