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.

The multidisciplinary approach to eosinophilia.

Eosinophilic granulocytes are normally present in low numbers in the bloodstream. Patients with an increased number of eosinophilic granulocytes in the differential count (eosinophilia) are common and can pose a clinical challenge because conditions with eosinophilia occur in all medical specialties. The diagnostic approach must be guided by a thorough medical history, supported by specific tests to guide individualized treatment. Neoplastic (primary) eosinophilia is identified by one of several unique acquired genetic causes. In contrast, reactive (secondary) eosinophilia is associated with a cytokine stimulus in a specific disease, while idiopathic eosinophilia is a diagnosis by exclusion. Rational treatment is disease-directed in secondary cases and has paved the way for targeted treatment against the driver in primary eosinophilia, whereas idiopathic cases are treated as needed by principles in eosinophilia originating from clonal drivers. The vast majority of patients are diagnosed with secondary eosinophilia and are managed by the relevant specialty-e.g., rheumatology, allergy, dermatology, gastroenterology, pulmonary medicine, hematology, or infectious disease. The overlap in symptoms and the risk of irreversible organ involvement in eosinophilia, irrespective of the cause, warrants that patients without a diagnostic clarification or who do not respond to adequate treatment should be referred to a multidisciplinary function anchored in a hematology department for evaluation. This review presents the pathophysiology, manifestations, differential diagnosis, diagnostic workup, and management of (adult) patients with eosinophilia. The purpose is to place eosinophilia in a clinical context, and therefore justify and inspire the establishment of a multidisciplinary team of experts from diagnostic and clinical specialties at the regional level to support the second opinion. The target patient population requires highly specialized laboratory analysis and therapy and occasionally has severe eosinophil-induced organ dysfunction. An added value of a centralized, clinical function is to serve as a platform for education and research to further improve the management of patients with eosinophilia. Primary and idiopathic eosinophilia are key topics in the review, which also address current research and discusses outstanding issues in the field.

[Cutaneous capillary malformations with cerebral implementation].

Capillary malformations - arteriovenous malformation, hereditary hemorrhagic telangiectasia and Sturge-Weber syndrome - are rare diseases in which cutaneous capillary malformations (CM) may be associated with cerebral vascular malformations. The clinical presentation of each disease is described with focus on how to distinguish them in the clinic and differential diagnoses are listed. This review finds that upon thorough and careful examination of patients, cutaneous CM might be a diagnostic hallmark for underlying disease and therefore a significant clinical observation.

A retrospective cohort study of patients with eosinophilia referred to a tertiary centre.

INTRODUCTION: Patients with eosinophilia (an increased number of eosinophilic granulocytes > 0.5 × 108/l in the blood) are encountered in all medical specialties and frequently need thorough workup to identify the eliciting causes and decide whether treatment is indicated. In Denmark, highly specialised centres for eosinophilic diseases or conditions have been established to provide a foundation for the management of complicated cases. Here, we present experiences from such a multidisciplinary centre. METHODS: This was a retrospective study of all patients seen in our tertiary centre for eosinophilia in the 2016-2019 period. RESULTS: Referrals mainly derived from specialised secondary care and to a lesser degree from primary care physicians. Patients were either asymptomatic or exhibited symptoms from up to three organ systems and presented a median eosinophil count of 1.7 × 108/l. Up to eight new clonality analyses or imaging studies per patient were performed after referral. One of these, T-cell receptor analysis, was performed frequently but provided limited information, whereas, e.g., flow cytometry proved more clinically applicable owing to its broader diagnostic range. In total, 51 patients were evaluated and classified as secondary (59%), myeloid neoplasm with PDGFRA rearrangement (2%), idiopathic hypereosinophilic syndrome (31%) and idiopathic hypereosinophilia (8%). CONCLUSION: The value of a multidisciplinary and versatile approach in a highly specialised centre has a positive impact on diagnostic processes as well as on the evaluation of treatment need. FUNDING: none. TRIAL REGISTRATION: not relevant.

Successful treatment of massive haemoptysis in a young woman with anastomosis of right internal mammary artery to right superior pulmonary vein fistula.

A 21-year-old, otherwise healthy, female patient was admitted with haemoptysis. Chest X-ray and CT found a consolidated right middle pulmonary lobe. Catheter angiography of ascending aorta visualised two hypertrophic and tortuous branches of the right internal mammary artery with a fistula to the right superior pulmonary vein. The inflow was embolised with coils. Catheter angiography of descending aorta found hypertrophic right bronchial arteries and right phrenic artery supplying a web-like network of vessels, which drained to the right superior pulmonary vein with discrete filling of an accessory right middle pulmonary vein. CT angiography with a catheter for contrast administration in the ascending aorta was performed for characterisation. After two additional episodes of haemoptysis, right middle lobe lobectomy was performed. Perioperatively pulmonary artery blood supply to the right middle pulmonary lobe was absent and an atretic accessory middle pulmonary vein was seen. The patient was discharged 7 days afterwards without sequelae.

[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.

Granulomatous inflammation in lymph nodes of the head and neck-a retrospective analysis of causes in a population with very low incidence of tuberculosis.

The purpose of this study was to investigate the risk of the patient having: (1) TB, (2) sarcoidosis, (3) atypical mycobacteria, or (4) malignant disease, if FNAC or histology from a cervical lymph node shows granulomatous inflammation (GI). And to elucidate clinical characteristics associated with these causes of GI, patients with a pathological diagnosis of GI in head and neck lymph nodes were identified though a search of the Danish national pathology database. Charts were reviewed to identify the final clinical diagnosis and specific clinical characteristics. For the most common clinical diagnoses, association to clinical characteristics was analyzed using logistic regression (Odense University Hospital January 2006 to December 2015). We included 121 patients. Clinical diagnoses fell into the following categories: sarcoidosis (26%), tuberculosis (TB) (22%), cat scratch disease (6%), atypical mycobacteriosis (7%), malignancy (2%), and other (4%). In 33% of cases, the diagnosis was unknown. In the pediatric group, atypical mycobacteriosis was the most frequent clinical diagnosis (50%). TB and sarcoidosis were dependent variables in regression analysis. Characteristics significantly related to TB were histology showing necrotizing GI, gland localization in level 3-6, and origin other than Danish and TB being the tentative diagnosis. Characteristics significantly related to sarcoidosis were histology showing non-necrotizing GI, gland localization in level 3-6, the patient being of Danish origin, and unknown duration of symptoms. TB and sarcoidosis were the most common clinical diagnoses, and they were associated with specific clinical characteristics. In a third of cases, a specific clinical diagnosis was never given.

Patient-recorded benefit from nasal closure in a Danish cohort of patients with hereditary haemorrhagic telangiectasia.

BACKGROUND: Nasal closure, also known as the modified Young's procedure was introduced in Denmark in 2008, as a surgical solution to severe epistaxis in patients with hereditary haemorrhagic telangiectasia (HHT). The objective of this study was to report the overall satisfaction of the procedure from a patient's point of view as well as the occurrence of complications. METHODS: All the HHT patients who underwent nasal closure from 2008 to 2018 were included in the study. The patients were evaluated for postoperative complications and subjective outcome using Glasgow Benefit Inventory (GBI). RESULTS: Ten patients were included in the study and were observed for a mean of 64 months. None of the patients was completely free of complications, and reversal was requested in a single case. Haemoglobin levels rose with an average of 2.8 g/dl. The average GBI score after surgery was 38.05. Nine of ten patients would recommend nasal closure to fellow HHT patients. CONCLUSION: Nasal closure is highly recommended among patients, but due to the rate of postoperative complications, the procedure should be reserved for a carefully selected group of HHT patients.

[Glomuvenous malformations].

In this review, the importance of correct diagnosis of glomuvenous malformations (GVM) is emphasised, and different treatment modalities are discussed. GVM are simple venous malformations located in the skin and subcutis, and GVM has a characteristic blue to reddish cobblestone-like appearance with not fully compressible elements, which can be associated with pain on palpation. Clinically, GVM differ from blue rubber bleb naevus syndrome and common/familial cutaneo-mucosal venous malforma-tions in appearance, compressibility and in having a normal D-dimer concentration.

Evaluation of day-care tonsil surgery in young children.

INTRODUCTION: The National Clinical Guideline for Ton-sillectomy (Danish Health Authority, 2016) suggests inpatient admission after elective tonsil surgery in patients aged < 4 years at the time of surgery. We aimed to evaluate the safety of tonsil surgery as day surgery in children ≤ 4 years of age. METHODS: The charts of 414 patients aged 2-15 years who underwent elective tonsillectomy, adenotonsillectomy or tonsillotomy at Svendborg Hospital, Denmark, from February 2010 to April 2015 were reviewed in a retrospective cohort. We investigated post-operative complications, defined as post-operative haemorrhage and unplanned contacts or revisits to the hospital. RESULTS: A total of 389 patients were divided into two groups by age (≤ 4/> 4 years). In all, 108 patients contacted or revisited the hospital after discharge. Patients aged ≤ 4 years accounted for the majority of contacts unrelated to bleeding and associated with complaints of pain and pain medication. Haemorrhage occurred in 22 (5.7%) patients, 19 of whom were > 4 years. The rates of haemorrhage, readmission and secondary surgery were significantly higher in patients aged > 4 years than in the remaining patients. CONCLUSIONS: Patients ≤ 4 years experienced significantly less haemorrhage but had more unplanned contacts than patients > 4 years. For reassurance of caretakers, easy access to telephone contact with hospital staff in the post-operative period is important. FUNDING: none. TRIAL REGISTRATION: not relevant.

Sinogenic intracranial complications: is adalimumab a culprit?

We present two 11-year-old girls with chronic recurrent multifocal osteomyelitis, treated with adalimumab. Both developed severe intracranial complications to sinusitis. Patient 1 had been treated with adalimumab for 15 months when she developed acute sinusitis complicated by an orbital abscess, forehead swelling, a subdural empyema and osteomyelitis of the frontal bone. She was treated with a rhinosurgical and neurosurgical approach with intravenous antibiotics.Patient 2 had been in adalimumab treatment for 10 weeks. Adalimumab was discontinued 8 weeks prior to developing subdural empyema and subcortical abscesses in combination with sinusitis. She was treated with endoscopic sinus surgery and intravenous antibiotics. Both patients had developed psoriasis and episodes of infection during treatment. They were non-septic and had low fever on presentation. None of the patients suffered any long-term neurological sequelae. The immunosuppressive treatment with adalimumab is considered to be the cause of the sinogenic intracranial complications in our cases.

Quality-of-Life Differences among Diagnostic Subgroups of Children Receiving Ventilating Tubes for Otitis Media.

OBJECTIVE: The pathological picture may differ considerably between diagnostic subgroups of children with otitis media receiving ventilating tubes. The aims of this study are to investigate differences in quality of life among diagnostic subgroups of children treated with ventilating tubes and to investigate possible predictors for clinical success. STUDY DESIGN: Longitudinal observational study. SETTING: Secondary care units. METHODS: Four hundred ninety-one families were enrolled in the study. The Otitis Media-6 questionnaire was applied in the assessment of child quality of life. Caregivers completed questionnaires at 7 time points from before treatment to 18-month follow-up. Logistic regression analysis was used to investigate possible predictors for clinical success. RESULTS: Response rates ranged from 96% to 81%; diagnostic distribution: 15% recurrent acute otitis media (rAOM), 47% otitis media with effusion (OME), and 38% mixed diagnosis of rAOM and OME (rAOM/OME). There were no significant differences between children diagnosed with rAOM and children diagnosed with rAOM/OME. However, these children had a significantly poorer quality of life at baseline compared with children diagnosed with only OME. Factors associated with clinical success included a diagnosis of rAOM, number of interrupted nights, physician visits, and canceled social activities due to OM. CONCLUSIONS: Results highlight the importance of distinguishing between diagnostic subgroups of children having ventilating tube treatment. A diagnosis of rAOM was found to predict baseline quality of life. Children with rAOM with or without OME were found to suffer significantly more than children with only OME before treatment. Factors associated with disease severity were found to predict clinical success.

[Hereditary haemorrhagic telangiectasia diagnosed in connection with a traffic accident]. / Morbus Osler diagnosticeret hos 16-årig i forbindelse med en trafikulykke.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular dysplasia and haemorrhage. It is manifested by mucocutaneous telangiec-tases and arteriovenous malformations in organs such as lungs, liver and brain. We present a case of HHT. A 16-year-old patient with a history of recurrent epistaxis was admitted to the local hospital with chest pain and desaturation. A CT scan revealed pulmonary arteriovenous malformations.

Otitis Media and Caregiver Quality of Life: Psychometric Properties of the Modified Danish Version of the Caregiver Impact Questionnaire.

OBJECTIVE: Otitis media in children may have a considerable impact on caregiver quality of life. The disease-specific Caregiver Impact Questionnaire is designed to assess caregiver quality of life in relation to child otitis media. Assessment of the psychometric properties of this instrument is limited. This study assesses the psychometric properties of this instrument including validity, reproducibility, responsiveness, and interpretability. STUDY DESIGN: Longitudinal validation study. SETTING: Secondary care units. METHODS: Analyses were based on data from 435 families. Validity was assessed using confirmatory factor analysis, internal consistency, and hypothesis testing. Test-retest reliability and measures of smallest detectable change were investigated in the assessment of reproducibility. Responsiveness was investigated by means of hypothesis testing and receiver operating characteristic analysis. An anchor-based distribution method was applied for determining minimal important change as perceived by the respondent. RESULTS: Factor analysis confirmed the hypothesized 1-factor structure with an acceptable fit. Cronbach's alpha was .90. In the analysis of construct validity, 88.9% of the hypothesized correlations were correctly predicted. Intraclass correlation coefficient was 0.87 and smallest detectable change corresponded to approximately one-fourth of the scale. Responsiveness was found to be good and a change score of 13.8 represented minimal important change. CONCLUSION: The modified Danish version of the Caregiver Impact Questionnaire is a valid and reproducible measurement tool that is also sensitive to measuring change in the current setting. A change score representing minimal important change as perceived by the respondent is proposed. Results of this study support the use of this instrument.

Caregiver Quality of Life and Daily Functioning in Relation to Ventilating Tube Treatment.

OBJECTIVE: Caregiver quality of life and daily functioning may improve after ventilating tube treatment in children with otitis media. The aims of this study are to assess possible changes in caregiver quality of life and daily functioning in relation to ventilating tube treatment and to investigate possible predictors for clinical success. STUDY DESIGN: Longitudinal observational study. SETTING: Secondary care units. METHODS: Four hundred ninety-one families were enrolled in the study. The Caregiver Impact Questionnaire was applied in the assessment of caregiver quality of life. Caregivers completed questionnaires at baseline and at 1, 3, 6, 12, and 18 months' follow-up. Variables on caregiver daily functioning comprised 4 weeks' history of number of interrupted nights, absenteeism, cancelled social activities, and doctor visits as a result of otitis media in the child. RESULTS: Response rates ranged from 96% to 79%. Significant improvements in disease-specific quality of life were seen after treatment. The poorest baseline quality of life was found in caregivers of children with recurrent acute otitis media. Significant improvements were found on all variables on daily functioning. Predictors for caregiver-perceived clinical success included child sex, number of interrupted nights, doctor visits, absenteeism, and cancelled social activities. CONCLUSION: Results of this study support the notion that caregivers of children with otitis media with defined surgical indications improve their quality of life and daily functioning after ventilating tube treatment. Factors related to caregiver functioning and disease severity were found to be associated with caregivers experiencing important improvements after treatment.

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.

[A case of possibly life-threatening abscess formation in cervical lymph node tuberculosis]. / Livstruende abscedering af halsglandel tuberculose.

Abscess formation in the cervical lymph nodes is a well-known clinical manifestation. Special care should be taken in atypical cases. In this article we describe the case of a young foreign male with tuberculosis-induced cervical abscess formation where surgery revealed a large connecting mediastinal abscess.

[Treatment of inverted papilloma with endonasal endoscopic sinus surgery]. / Behandling af invert papillom med endonasal endoskopisk sinuskirurgi.

INTRODUCTION: Inverted papilloma is a benign sinonasal tumour and has a marked tendency to recur after surgical excision. The tumour may be associated with malignancy and during growth it may destroy surrounding tissue. The treatment is either lateral rhinotomy or endoscopic sinus surgery. The aim of the study was to describe the course of all patients treated with endoscopic sinus surgery at the ENT Department at Vejle County Hospital during the period 1 January to 31 December 1999. MATERIAL AND METHODS: Twenty-eight journals of patients diagnosed with inverted nasal papillomas were reviewed retrospectively. RESULTS: All patients underwent endoscopic sinus surgery with at least antrostomy. Caldwell-Luc's operation was additionally performed in 16 patients. There was a male predominance of 6:1. Seven suffered recurrences after the primary surgical procedure, none of the recurrences were associated with carcinoma. We did not see any serious side effects to the treatment. DISCUSSION: Endoscopic sinus surgery in combination with Caldwell-Luc can be recommended as an alternative treatment to lateral rhinotomy in patients with inverted papillomas. Preoperative staging with CT or MR-scanning, experienced surgeons, and a close follow-up period of five years must be recommended.