Paget's disease of bone in The Netherlands: a population-based radiological and biochemical survey--the Rotterdam Study.

Serum ALP may be a good indicator of Paget's disease in epidemiologic studies. Subjects with raised and normal ALP from a population cohort were matched (1 in 6, total 548), and radiographs were taken. ALP was an excellent marker of the disease (RR, 10.9), but the majority of those affected had normal ALP. INTRODUCTION: Evidence from radiographic surveys of limited skeletal sites has shown that Paget's disease of bone (PDB) is common in the elderly and has a distinct geographic variation. There is no information, however, about the relation of serum alkaline phosphatase (ALP) activity, a marker of the disease, and its prevalence in the population. MATERIALS AND METHODS: We analyzed data from a well-defined Dutch population cohort (the Rotterdam study) with the following specific aims: (1) to assess the relationship between serum ALP activity and prevalence of radiographically diagnosed PDB, (2) to estimate the overall prevalence of the disease in the Netherlands, and (3) to assess the appearance of the disease with time. Using a nested case-control design, subjects with an increased serum ALP and normal serum liver enzymes were matched for gender and age (1 to 6) with subjects with normal serum ALP activity. Radiographs of the thoracic and lumbar spine, pelvis, proximal femurs, knees, wrists, and hands were taken. RESULTS AND CONCLUSIONS: PDB was diagnosed in 20.5% of subjects with elevated serum ALP activity and in 2.3% in those with normal serum ALP activity, increasing with age in both groups. The relative risk (RR) for PDB in the presence of raised serum ALP activity was 10.9 (95% CI, 4.8, 24.9). The estimated prevalence of PDB in the population was 3.6%, and the large majority (about 86%) had normal serum ALP activity, contrasting findings in bone clinics where the opposite is the case. Finally, in subjects with normal and raised serum ALP activity but no PDB at baseline, radiographs taken 6-9 years later showed no evidence of the disease. This study demonstrated that serum ALP activity is a sensitive marker of PDB in men and women >55 years of age, but the majority of those affected have normal serum ALP activity.     

Large left atrial myxoma presented as fever of unknown origin: a challenging diagnosis and a review of the literature

Myxoma is the most common type of primary tumors of the heart in adults. The majority of patients with myxomas may experience symptoms due to central or peripheral embolism or intracardiac obstruction, while in some cases, they may be completely asymptomatic. Rarely, patients develop unusual symptoms that complicate the diagnostic evaluation. Herein, we describe the case of a 70-year-old patient with a long-lasting low-grade fever due to a large left atrial myxoma revealed during a transthoracic echocardiography.     

SOST expression is restricted to the great arteries during embryonic and neonatal cardiovascular development.

Spatial-temporal regulation of bone morphogenetic protein (BMP) and Wnt activity is essential for normal cardiovascular development, and altered activity of these growth factors causes maldevelopment of the cardiac outflow tract and great arteries. In the present study, we show that SOST, a Dan family member reported to antagonize BMP and Wnt activity, is expressed within the medial vessel wall of the great arteries containing smooth muscle cells. The ascending aorta, aortic arch, brachiocephalic artery, common carotids, and pulmonary trunk were all associated with SOST expressing smooth muscle cells, while the heart itself, including the valves, and more distal arteries, that is, pulmonary arteries, subclavian arteries, and descending aorta, were negative. SOST was expressed from embryonic day 15.5 up to the neonatal period. SOST expression, however, did not correspond with inhibition of Smad-dependent BMP activity or beta-catenin-dependent Wnt activity in the great arteries. Activity of both signaling pathways was already down-regulated before induction of SOST expression.     

Inhibition of Amiodarone‐Induced Lung Fibrosis but not Alveolitis by Angiotensin System Antagonists

Abstract: Earlier work in this laboratory showed that amiodarone induces apoptosis in alveolar epithelial cells by a mechanism inhibitable by angiotensin system antagonists. A variety of recent studies suggests a critical role for alveolar epithelial cell apoptosis in the pathogenesis of lung fibrosis. On this basis we hypothesized that amiodarone‐induced alveolar epithelial cell apoptosis and lung fibrosis in vivo might be inhibitable by the angiotensin converting enzyme inhibitor captopril or the angiotensin receptor antagonist losartan. Amiodarone‐induced lung fibrosis was induced in male Wistar rats by oral adminstration over six months. Replicate groups of rats received captopril or losartan in addition to amiodarone. Apoptosis was detected by increased total lung activity of caspase 3 and in situ end labeling (ISEL) of fragmented DNA. Collagen was localized and quantitated by the picrosirius red technique. Alveolar epithelial cell apoptosis was detected in amiodarone‐treated animals as early as three weeks after the start of amiodarone administration; by six months exposure, the incidence of alveolar epithelial cell apoptosis was significantly reduced by coadministration of captopril or losartan. Alveolar wall collagen accumulation also was significantly attenuated by captopril (100%) or losartan (74%), but neither agent blunted the accumulation of alveolar macrophages evoked by amiodarone (5.3‐fold at 6 months). Lung neutrophil content was unchanged by amiodarone treatment for three weeks or six months. These results indicate that amiodarone induces alveolar epithelial cell apoptosis in vivo that is inhibitable by angiotensin antagonists. They also support the hypothesis that blockade of angiotensin formation or function attenuates amiodarone‐induced lung fibrosis irrespective of the severity of alveolitis.     

“Heart failure in COVID-19 patients: Critical care experience”: A letter to the editor

Coronavirus disease 2019 (COVID-19) is associated with poor cardiovascular outcomes in patients with heart failure (HF) of all categories of ejection fraction (EF), but mainly in patients with HF with reduced EF. Moreover, cardiac transplant patients exhibit worse cardiovascular prognosis, high mortality, and more admissions to the intensive care unit. In general, COVID-19 seems to de-teriorate the clinical status of HF and favors the development of acute respiratory distress syndrome and multiorgan failure, especially in the presence of cardiovascular comorbidities such as diabetes mellitus, kidney dysfunction, and older age. COVID-19 may induce new-onset HF with complex mechanisms that involve myocardial injury. Indeed, myocardial injury comprises a large category of detrimental effects for the myocardium, such as myocardial infarction type 1 or type 2, Takotsubo cardiomyopathy, microvascular dysfunction and myocarditis, which are not easily distinguished by HF. The pathophysiologic mechanisms mainly involve direct myocardial damage by severe acute respiratory syndrome coronavirus 2, cytokine storm, hypercoagulation, inflammation, and endothelial dysfunction. The proper management of patients with COVID-19 involves careful patient evaluation and ongoing monitoring for complications such as HF.     

Immune-checkpoint inhibitor-associated grade 3 hepatotoxicity managed with enteric-coated budesonide monotherapy: A case report

Rationale:The introduction of immune-checkpoint inhibitors (ICPI) in recent years has changed the natural course of many neoplasms. However, patients receiving these medications may present immune-mediated adverse events; management includes temporary or permanent cessation of treatment and corticosteroids, occasionally combined with other immunomodulators. Such immunosuppression, however, also has numerous adverse events and even if it is effective in controlling toxicity, it delays immunotherapy reinitiation, as current evidence requires dose tapering to ≤10 mg prednisolone equivalent before rechallenge. Enteric-coated budesonide is a corticosteroid formulation acting primarily to the intestine and liver, as a result of its extensive first-pass hepatic metabolism.Patient concerns:A 76-year-old woman treated with ipilimumab for metastatic melanoma presented with abdominal pain, vomiting, and diarrhea for at least the previous 4 days. Laboratory tests, among others, revealed elevated aminotransferases and C-reactive protein. During hospitalization, the patient also developed fever.Diagnosis:The patient, after excluding alternative causes of aminotransferase elevation, was diagnosed with grade 3 ipilimumab-associated hepatotoxicity.Interventions:Budesonide monotherapy was administered; initial daily dose was 12 mg.Outcomes:Fever subsided after the first dose of budesonide. Aminotransferases returned to normal-near normal approximately 1 month after the first dose of budesonide. After this point, daily dose was reduced by 3 mg every 2 weeks, with no clinical or biochemical relapse.Conclusions:This case of ICPI hepatitis is, to our knowledge, the first in the literature managed with budesonide monotherapy. Therefore, budesonide may be a potentially attractive option for the management of ICPI-associated liver injury in cases where corticosteroid treatment is necessary due to its safety profile and the potential advantage of faster immunotherapy rechallenge in selected patients without requiring dose tapering, in contrast to systemically acting corticosteroids. Clinical trials should be conducted in the future in order to validate or refute these findings.     

Predicting confrontation naming item difficulty

Background: Item response theory (IRT; Lord & Novick, 1968) is a psychometric framework that can be used to model the likelihood that an individual will respond correctly to an item. Using archival data (Mirman et al., 2010), Fergadiotis, Kellough, and Hula (2015) estimated difficulty parameters for the Philadelphia Naming Test (PNT; Roach, Schwartz, Martin, Grewal, & Brecher, 1996) using the 1-parameter logistic IRT model. Although the use of IRT in test development is advantageous, its reliance on sample sizes exceeding 200 participants make it difficult to implement in aphasiology. Therefore, alternate means of estimating the item difficulty of confrontation naming test items warrant investigation. In a preliminary study aimed at automatic item calibration, Swiderski, Fergadiotis, and Hula (2016) regressed the difficulty parameters from the PNT on word length, age of acquisition (Kuperman, Stadthagen-Gonzalez, & Brysbaert, 2012), lexical frequency as quantified by the Log10CD index (Brysbaert & New, 2009), and naming latency (Székely et al., 2003). Although the model's predictive utility was high, a substantial proportion (20%) of the response time data were missing. Further, only 39% of the picture stimuli from Székely and colleagues (2003) were identical to those on the PNT. Given that the IRT sample size requirements limit traditional calibration approaches in aphasiology and that the initial attempts in predicting IRT difficulty parameters in our pilot study were based on incomplete response time data this study has two specific aims.

Aims: To estimate naming latencies for the 175 items on the PNT, and assess the utility of psycholinguistic variables and naming latencies for predicting item difficulty.

Methods and Procedures: Using a speeded picture naming task we estimated mean naming latencies for the 175 items of the PNT in 44 cognitively healthy adults. We then re-estimated the model reported by Swiderski et al (2016) with the new naming latency data.

Outcomes and Results: The predictor variables described above accounted for a substantial proportion of the variance in the item difficulty parameters (Adj. R² = .692).

Conclusions: In this study we demonstrated that word length, age of acquisition, lexical frequency, and naming latency from neurotypical young adults usefully predict picture naming item difficulty in people with aphasia. These variables are readily available or easily obtained and the regression model reported may be useful for estimating confrontation naming item difficulty without the need for collection of response data from large samples of people with aphasia.     

Promotion and Prevention in Child,Adolescent and Young People Mental Health: The Greek Experience of Participation in the Mental Health Network Programme of the European Commission

In 1997 the European Commission established the Mental Health Promotion Network to seek out, disseminate and promote best practice in mental health promotion and the prevention of mental disorders. The Network has commissioned a number of projects including two projects addressing the promotion of mental health and prevention of mental disorders in children and adolescents. Anticipated results included the establishment of criteria to identify good practice, development of a European database of good practice and widespread dissemination of good practice that could be implemented throughout the Community. The paper discusses the involvement and experiences of the staff employed in one organisation, from Greece, who have participated in the work Network, and highlights some of the difficulties faced and lessons learnt from participation in a multi-national project.