Evaluation of [18F]2FP3 in pigs and non‐human primates

So far, no suitable 5‐HT₇R radioligand exists for clinical positron emission tomography (PET) imaging. [¹⁸F]2FP3 was first tested in vivo in cats, and the results were promising for further evaluations. Here, we evaluate the radioligand in pigs and non‐human primates (NHPs). Furthermore, we investigate species differences in 5‐HT₇R binding with [³H]SB‐269970 autoradiography in post‐mortem pig, NHP, and human brain tissue. Specific binding of [¹⁸F]2FP3 was investigated by intravenous administration of the 5‐HT₇R specific antagonist SB‐269970. [³H]SB‐269970 autoradiography was performed as previously described. [¹⁸F]2FP3 was synthesized in an overall yield of 35% to 45%. High brain uptake of the tracer was found in both pigs and NHPs; however, pretreatment with SB‐269970 only resulted in decreased binding of 20% in the thalamus, a 5‐HT₇R–rich region. Autoradiography on post‐mortem pig, NHP, and human tissues revealed that specific binding of [³H]SB‐269970 was comparable in the thalamus of pig and NHP. Despite the high uptake of [¹⁸F]2FP3 in both species, the binding could only be blocked to a limited degree with the 5‐HT₇R antagonists. We speculate that the affinity of the radioligand is too low for imaging the 5‐HT₇Rs in vivo and that part of the PET signal arises from targets other than the 5‐HT₇R.     

Integration of PET-imaging into radiotherapy treatment planning for low-grade meningiomas improves outcome

European Journal of Nuclear Medicine and Molecular Imaging - Meningiomas have an excellent survival prognosis, and radiotherapy (RT) is a central component of interdisciplinary treatment. During...     

Association of cardiovascular risk factors with the different presentations of acute coronary syndrome

OBJECTIVE:

to identify the relationship between different presentations of acute coronary syndrome and cardiovascular risk factors among hospitalized individuals.

METHOD:

cross-sectional study performed in a teaching hospital in São Paulo, in the State of São Paulo (SP). Socio-demographic, clinical and anthropometric data of 150 individuals hospitalized due to acute coronary syndrome were collected through interviews and review of clinical charts. Association between these data and the presentation of the syndrome were investigated.

RESULTS:

there was a predominance of ST segment elevation acute myocardial infarction. There was significant association of systemic hypertension with unstable angina and high values of low density lipoprotein with infarction, without influence from socio-demographic characteristics.

CONCLUSION:

arterial hypertension and high levels of low-density lipoprotein were associated with different presentations of coronary syndrome. The results can provide support for health professionals for secondary prevention programs aimed at behavioural changing.     

Predicting effective connectivity from resting‐state networks in healthy elderly and patients with prodromal Alzheimer's disease

Using functional neuroimaging techniques two aspects of functional integration in the human brain have been investigated, functional connectivity and effective connectivity. In this study we examined both connectivity types in parallel within an executive attention network during rest and while performing an attention task. We analyzed the predictive value of resting‐state functional connectivity on task‐induced effective connectivity in patients with prodromal Alzheimer's disease (AD) and healthy elderly. We found that in healthy elderly, functional connectivity was a significant predictor for effective connectivity, however, it was frequency‐specific. Effective top‐down connectivity emerging from prefrontal areas was related with higher frequencies of functional connectivity (e.g., 0.08–0.15 Hz), in contrast to effective bottom‐up connectivity going to prefrontal areas, which was related to lower frequencies of functional connectivity (e.g., 0.001–0.03 Hz). In patients, the prediction of effective connectivity by functional connectivity was disturbed. We conclude that functional connectivity and effective connectivity are interrelated in healthy brains but this relationship is aberrant in very early AD. Hum Brain Mapp 35:954–963, 2014. © 2013 Wiley Periodicals, Inc.     

LEAP: Using machine learning to support variant classification in a clinical setting

Advances in genome sequencing have led to a tremendous increase in the discovery of novel missense variants, but evidence for determining clinical significance can be limited or conflicting. Here, we present Learning from Evidence to Assess Pathogenicity (LEAP), a machine learning model that utilizes a variety of feature categories to classify variants, and achieves high performance in multiple genes and different health conditions. Feature categories include functional predictions, splice predictions, population frequencies, conservation scores, protein domain data, and clinical observation data such as personal and family history and covariant information. L2‐regularized logistic regression and random forest classification models were trained on missense variants detected and classified during the course of routine clinical testing at Color Genomics (14,226 variants from 24 cancer‐related genes and 5,398 variants from 30 cardiovascular‐related genes). Using 10‐fold cross‐validated predictions, the logistic regression model achieved an area under the receiver operating characteristic curve (AUROC) of 97.8% (cancer) and 98.8% (cardiovascular), while the random forest model achieved 98.3% (cancer) and 98.6% (cardiovascular). We demonstrate generalizability to different genes by validating predictions on genes withheld from training (96.8% AUROC). High accuracy and broad applicability make LEAP effective in the clinical setting as a high‐throughput quality control layer.     

Side effect management during immune checkpoint blockade using CTLA‐4 and PD‐1 antibodies for metastatic melanoma – an update

CTLA‐4 and PD‐1 play a key role in tumor‐induced downregulation of lymphocytic immune responses. Immune checkpoint inhibitors have been shown to alter the immune response to various cancer types. Anti‐CTLA‐4 and anti‐PD‐1 antibodies affect the interaction between tumor, antigen‐presenting cells and T lymphocytes. Clinical studies of the anti‐CTLA‐4 antibody ipilimumab and the anti‐PD‐1 antibodies nivolumab and pembrolizumab have provided evidence of their positive effects on overall survival in melanoma patients. Combined treatment using ipilimumab and nivolumab has been shown to achieve five‐year survival rates of 52 %. Such enhancement of the immune response is inevitably associated with adverse events. Knowledge of the spectrum of side effects is essential, both in terms of prevention and management. Adverse events include colitis, dermatitis, hypophysitis, thyroiditis, hepatitis and other, less common autoimmune phenomena. In recent years, considerable progress has been made in the detection and treatment of the aforementioned immune‐related adverse events. However, early diagnosis of rare neurological or cardiac side effects, which may be associated with increased mortality, frequently pose a challenge. The present update highlights our current understanding as well as new insights into the spectrum of side effects associated with checkpoint inhibitors and their management.     

Standards der ernährungsmedizinischen Versorgung in der ambulanten und stationären Pädiatrie durch spezialisierte Einrichtungen der Kinder- und Jugendmedizin

Monatsschrift Kinderheilkunde - Eine adäquate Energie- und Nährstoffversorgung ist Grundlage für ein gesundes Wachstum und Voraussetzung für die Erhaltung von Gesundheit und...     

Eating disorders in old age

There are 5 women over the age of 55 with an eating disorder described. In view of a possible increase in the eating disorders among the elderly, the correct diagnosis and treatment of these disorders were emphasized.