Systemic therapy timing and use in patients with advanced melanoma at the end of life: A retrospective cohort study.

Novel systemic therapies for advanced melanoma improve survival, but carry potential serious side effects and high costs. This study aimed to assess the timing and use of systemic therapies in the months before death. Patients diagnosed with advanced melanoma (July 2017-June 2020) who died before July 2020 were selected from the Netherlands Cancer Registry. We evaluated the timing of systemic therapies within 30 days and 3 months before death, and studied patient and tumor characteristics associated with systemic therapy use between diagnosis and death. Out of 1097 patients 68% received systemic therapy. Almost 25% and 10% started a new therapy within 90 days and within 30 days before death, respectively. Female sex, elevated LDH, BRAF mutation, poor ECOG performance status (≥3), and high comorbidity index reduced the odds of receiving immune therapy. Poor performance status and high comorbidity decreased the odds for both therapies. A considerable number of patients started systemic therapy shortly before death, emphasizing the importance of considering potential benefits and drawbacks through shared decision-making.

The p48 flow diverter: First clinical results in 25 aneurysms in three centers.

BACKGROUND: The novel low-profile p48 flow diverter has been designed to treat aneurysms on small vessels of 1.75-3mm. We report our first clinical experiences. METHODS: Between March 2018-January 2020, 22 patients with 25 aneurysms were treated with the p48 in 3 centers. One patient had 3 aneurysms covered by one p48 and one patient had 2 aneurysms. There were 5 men, 17 women, with a mean age of 55 years (median 59, range 29-73 years). RESULTS: In 25 aneurysms, 24 p48 flow diverters were placed. In 1 patient additional coils were placed in the aneurysm. Procedural vessel rupture by the micro guidewire occurred in 2 patients and vessel rupture during p48 balloon dilatation occurred in 1 patient. Overall, the permanent morbidity rate was 13.6% (3 of 22, 95%CI 3.9-34.2%) and mortality was 4.5% (1 of 22, 95%CI <0.01-23.5%). Most complications were procedure-related and not device-specific. Of 22 patients with 25 aneurysms treated with p48, 18 patients with 20 aneurysms had angiographic follow-up after 5-18 months. Of 19 aneurysms, 10 were occluded and 7 showed a remnant. Two aneurysms were open after 6 months. Three aneurysms were still not occluded after 12, 14, and 18 months and these 3 were retreated. Retreatment rate was 16% (3 of 19) and the adequate occlusion rate was 90% (17 of 19). CONCLUSIONS: Treatment of aneurysms in small-caliber vessels with the p48 is feasible and effective but is not without complications. More data is needed to establish indications, safety, and efficacy more accurately.

Endovascular treatment of brain arteriovenous malformations using a liquid embolic agent: results of a prospective, multicentre study (BRAVO).

OBJECTIVES: To evaluate the safety and efficacy of a new liquid embolic agent in brain arteriovenous malformation (bAVMs) embolisation. METHODS: A prospective, multicentre series was conducted at 11 interventional centres in Europe to evaluate embolisation of bAVMs with the new liquid embolic agent. Technical conditions, complications, clinical outcome and anatomical results were independently analysed. RESULTS: From December 2005 to December 2008, 117 patients (72 male; 45 female, aged 18-75 years) were included. Clinical presentation was mostly haemorrhage (34.2 %) and seizures (28.2 %). Most AVMs were located in the brain hemispheres (85.5 %). AVMs were <3 cm in 52.1 % of patients and ≥ 3 cm in 47.9 %. Morbidity was observed in 6/117 patients (5.1 %), related to haemorrhagic events in 2 cases and non-haemorrhagic complications in 4 cases. Five patients (4.3 %) died in relation to the treatment (bleeding in 4 patients and extensive venous thrombosis in 1). Complete occlusion of the AVM by embolisation alone was obtained in 23.5 % of patients. Complementary treatment was performed in 82.3 % of patients with partial AVM occlusion, mostly radiosurgery. CONCLUSIONS: In this prospective, multicentre, European, observational series, the new liquid embolic agent proved to be suitable for BAVM embolisation, with acceptable morbidity and mortality and good efficacy. KEY POINTS: • Numerous interventional techniques have been used to embolise brain arteriovenous malformations (AVMs). • This prospective multicentre study demonstrates the suitability of a liquid embolic agent. • The safety of treatment using Onyx is acceptable. • Such embolisation leads to complete AVM occlusion in 23.5 % of patients.

Percutaneous vertebroplasty is not a risk factor for new osteoporotic compression fractures: results from VERTOS II.

BACKGROUND AND PURPOSE: PV is increasingly used as treatment for osteoporotic VCFs. However, controversy exists as to whether PV increases the risk for new VCFs during follow-up. The purpose of our research was to assess the incidence of new VCFs in patients with acute VCFs randomized to PV and conservative therapy. MATERIALS AND METHODS: VERTOS II is a prospective multicenter randomized controlled trial comparing PV with conservative therapy in 202 patients. Incidence, distribution, and timing of new VCFs during follow-up were assessed from spine radiographs. In addition, further height loss during follow-up of treated VCFs was measured. RESULTS: After a mean follow-up of 11.4 months (median, 12.0; range, 1-24 months), 18 new VCFs occurred in 15 of 91 patients after PV and 30 new VCFs in 21 of 85 patients after conservative therapy. This difference was not significant (P = .44). There was no higher fracture risk for adjacent-versus-distant vertebrae. Mean time to new VCF was 16.2 months after PV and 17.8 months after conservative treatment (logrank, P = .45). The baseline number of VCFs was the only risk factor for occurrence (OR, 1.43; 95% CI, 1.05-1.95) and number (P = .01) of new VCFs. After conservative therapy, further height loss of treated vertebrae occurred more frequently (35 of 85 versus 11 of 91 patients, P < .001) and was more severe (P < .001) than after PV. CONCLUSIONS: Incidence of new VCFs was not different after PV compared with conservative therapy after a mean of 11.4 months' follow-up. The only risk factor for new VCFs was the number of VCFs at baseline. PV contributed to preservation of stature by decreasing both the incidence and severity of further height loss in treated vertebrae.

Variation in intakes of calcium, phosphorus, magnesium, iron and potassium in 10 countries in the European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND/OBJECTIVES: Adequate mineral intake is important for the maintenance of bone health, cellular function and general metabolism, and possibly in the aetiology of cancer and other chronic diseases. This study aimed at investigating variation in intakes of selected minerals across 10 European countries participating in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. METHODS: Nutrient intakes for 36 034 subjects, aged between 35 and 74 years, in 27 centres were obtained using standardized 24-h dietary recall software (EPIC-SOFT). Mean intakes of calcium, phosphorus, magnesium, iron and potassium were calculated by centre and weighted by season and day of the week and were also stratified by age group. The contribution of food groups to total nutrient intake was calculated. RESULTS: There was clear geographical variability in intakes, with differences ranging from 35% for magnesium to 90% for iron in men and 36% for potassium to 75% for calcium in women, and a twofold difference in sources of haem iron (meat and fish). There was a geographical gradient in iron intake, with higher intakes in Southern than in Northern Europe and also around a twofold north-south gradient in the contribution of fruits and vegetables to potassium intake. Compared with reference intakes, the majority of age groups and centres had intakes above the recommended levels. Dairy foods and products contributed the most to calcium and phosphorus intake in almost all centres. Cereals and cereal products contributed the most to magnesium and iron intakes, except in Greece and Germany. CONCLUSIONS: Intakes of minerals vary substantially throughout Europe, with some geographical variability in their food sources.

Percutaneous vertebroplasty as treatment for Kummell's disease.

We report a case with classic clinical findings and imaging features of Kummell's disease. Kummell's disease is a post-traumatic vertebral body collapse. Initially after the trauma patients are usually asymptomatic but after months they develop a symptomatic and progressive kyphosis of the lower thoracic or lumbar spine. On a conventional radiograph a collapsed vertebral body with a fracture cleft is typical and on MRIT2 weighted images the double line sign is characteristic for Kummell's disease; an increased linear area of hyper-intensity surrounded by an area of low signal. Percutaneous vertebroplasty is an adequate treatment for stabilization of the fracture and pain reduction in patients with Kummell's disease.

Endovascular treatment of vein of Galen aneurysmal malformation.

A vein of Galen aneurysmal malformation represents an arteriovenous fistula draining in a dilated precursor of the vein of Galen. We report a case of an incidentally detected large aneurysmal malformation of the vein of Galen in a 25-year-old man.The malformation was visualized with CT, MRI and digital subtraction angiography.This uncommon vascular malformation is rarely detected in adults as symptoms usually arise during childhood. This patient had no neurological complaints but the angiography showed, however, a steal phenomenon from the anterior circulation. The lesion was treated with good results by means of endovascular embolization with coils.

VERTOS II: percutaneous vertebroplasty versus conservative therapy in patients with painful osteoporotic vertebral compression fractures; rationale, objectives and design of a multicenter randomized controlled trial.

BACKGROUND: The standard care in patients with a painful osteoporotic vertebral compression fracture (VCF) is conservative therapy. Percutaneous vertebroplasty (PV), a minimally invasive technique, is gaining popularity as a new treatment option. Many prospective and retrospective studies have reported on the effectiveness and safety of PV, but no large randomized controlled trial (RCT) has been published. OBJECTIVE: To estimate cost-effectiveness of PV compared to conservative therapy in terms of: pain reduction, quality of life, complications, secondary fractures and mortality. MATERIALS AND METHODS: The VERTOS II study is designed as a prospective, multicenter RCT. Patients with a painful VCF with bone edema on MR imaging, local back pain for 6 weeks or less, osteopenia and aged 50 years or older, after obtaining informed consent are included and randomized for PV or conservative therapy. In total 200 patients will be enrolled. Follow-up is at regular intervals during a 1-year period with standard questionnaires, addressing: clinical symptoms, pain medication, Visual Analogue Scale (VAS) score, quality of life and cost-effectiveness. Secondary fractures, necessary additional therapies and complications are recorded. CONCLUSION: The VERTOS II study is the first methodologically sound RCT designed to assess the cost-effectiveness of PV compared to conservative therapy in patients with an acute osteoporotic VCF. TRIAL REGISTRATION: http://www.clinicaltrials.gov, NCT00232466.

A dural craniocervical fistula in a patient with progressive cervical myelopathy.

A 47-year-old male patient with a dural craniocervical fistula is presented. One year after a car accident the man was admitted to the emergency department with severe nausea and progressive paralysis of the lower legs. MRI examination of the brain and cervical spine discovered cervical myelopathy and tortuous blood vessels anterior to the pons and cervical medulla. Angiography was performed to provide the final diagnosis of craniocervical fistula. An embolization of the fistula was performed, and all of the patient's complaints disappeared within three days.

[In-house apartments: an attempt to handle complex chronic psychiatric disorders]. / Inleunappartementen: een poging om complexe chronische psychiatrische problematiek hanteerbaar te maken.

SUMMARY: A ward of the ggnet, a mental health centre in Apeldoorn, has developed a unique way of coping with often complex and severe problems of patients with chronic psychiatric disorders. It has created a one-person facility, called an in-house apartment. The in-house apartments have been evaluated and appear to be an effective way of dealing with some patients with complex chronic psychiatric disorders - specific types of psychiatric disorders and personality problems.

Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study.

PURPOSE: To prospectively assess the short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures (VCF) treated with percutaneous vertebroplasty (PV) compared with optimal pain medication (OPM). METHODS: Randomization of patients in 2 groups: treatment by PV or OPM. After 2 weeks, patients from the OPM arm could change therapy to PV. Patients were evaluated 1 day and 2 weeks after treatment. Visual analog score (VAS) for pain and analgesic use were assessed before, and 1 day and 2 weeks after start of treatment. Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) and Roland-Morris Disability (RMD) questionnaire scores were assessed before and 2 weeks after start of treatment. Follow-up scores in patients requesting PV treatment after 2 weeks OPM treatment were compared with scores during their OPM period. RESULTS: Eighteen patients treated with PV compared with 16 patients treated with OPM had significantly better VAS and used less analgesics 1 day after treatment. Two weeks after treatment, the mean VAS was less but not significantly different in patients treated with OPM, whereas these patients used significantly less analgesics and had better QUALEFFO and RMD scores. Scores in the PV arm were influenced by occurrence of new VCF in 2 patients. After 2 weeks OPM, 14 patients requested PV treatment. All scores, 1 day and 2 weeks after PV, were significantly better compared with scores during conservative treatment. CONCLUSION: Pain relief and improvement of mobility, function, and stature after PV is immediate and significantly better in the short term compared with OPM treatment.

[Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures: first short term results]. / Percutane vertebroplastiek bij osteoporotische wervelinzakkingsfracturen: eerste kortetermijnresultaten.

OBJECTIVE: To describe the technique of percutaneous vertebroplasty and the short-term results in patients with symptomatic, osteoporotic vertebral compression fractures. DESIGN: Prospective follow-up study. METHOD: In a pilot-study to evaluate the short-term safety and effectiveness of percutaneous vertebroplasty, 18 consecutive patients with a total of 33 osteoporotic thoracic or lumbar vertebral compression fractures were treated from October 2001 to June 2002 with a follow-up of 3-6 months. The indication for treatment was a symptomatic, therapy-resistant osteoporotic vertebral compression fracture. Percutaneous vertebroplasty was performed under radiographic control, after previous intraossal venography, using bone cement mixed with barium sulphate. Post-procedural follow-up consisted of radiological evaluation with conventional thoracolumbar X-rays and MRI scans, and interviews of the patients. RESULTS: Percutaneous vertebroplasty was technically successful in 31 of 33 vertebral fractures (94%), and in 16 of 18 patients (89%). One patient with extreme venous contrast leakage could not be treated. Sixteen patients had less or no pain after treatment. One patient retained thoracolumbar back pain after inadequate cementations and refused further treatment. None of the patients reported aggravation of symptoms following the procedure. Contrast leakage was absent in 18 vertebrae. In 8 vertebrae there was contrast leakage to paravertebral veins. In three of these cases the leakage was so severe that embolisation was performed, with success in one case. In 13 vertebrae, cement leakage to intervertebral and paravertebral spaces and pedicular cement spurs were seen, without clinical consequences. Immediately after the procedure and during follow-up there were no clinically relevant complications. CONCLUSION: Percutaneous vertebroplasty was a technically feasible treatment in these patients with symptomatic, therapy-resistant, osteoporotic vertebral fractures. The first short-term results were comparable with results in the literature. A prospective randomised intervention study will be needed to compare percutaneous vertebroplasty with optimal conservative treatment.

Online sentence processing in adults who stutter and adults who do not stutter.

This study had two specific aims. The first aim was to investigate whether, during a silent reading task, persons who stutter encode phonological and semantic information move slowly then persons who do not stutter. The second aim was to investigate how the syntactic context of stimulus sentences influences the speed of coding. Fourteen adult persons who stutter and 14 adult persons who do not stutter participated in a self-paced word-by-word reading experiment. While reading a prose text silently, participants monitored target words that were specified before the presentation of the text. The target words to be monitored for were phonologically similar, categorically related, or identical to a cue word. The influence of syntactic information on the word-monitoring reaction time was studied by presenting the text either as normal prose, in a syntactically correct but semantically anomalous version, or in random word order. The results suggest that the two groups are not different with respect to the speed of word identification but that persons who stutter retrieve semantic information more slowly than persons who do not stutter.

Chondrosarcoma in a patient with relapsing polychondritis.

A case of a chondrosarcoma in a patient with relapsing polychondritis was presented. The association of these two unusual disorders of cartilaginous tissue has never been described before. The clinical presentation and radiologic and histologic features were discussed.

[Noninvasive diagnosis of splenic artery aneurysm]. / Nicht-invasive Diagnostik von Milzarterienaneurysmata.

The findings and problems of differential diagnosis of splenic artery aneurysms are illustrated by three patients. By a combination of Doppler sonography and conventional duplex sonography, it was possible to achieve a correct and non-invasive diagnosis.

Hyperparathyroidism-an unusual case.

A case of primary hyperparathyroidism is described that presented unusual features. The patient had been treated previously for squamous cell carcinoma of the lung and therefore it was necessary to exclude ectopic hyperparathyroidism. The results of the tests generally used to distinguish primary from ectopic hyperparathyroidism-the serum chloride level, the serum calcium response to cortisone suppression and the absence of residual or recurrent tumour-suggested that the patient did have the primary form of the disorder. Exploration of the neck revealed no parathyroid tumour or hyperplasia, and the mediastinal parathyroid adenoma was localized only by determination of parathyroid hormone in the venous drainage from the neck and mediastinum.