Guideline on the requirements of external quality assessment programs in molecular pathology

Molecular pathology is an integral part of daily diagnostic pathology and used for classification of tumors, for prediction of prognosis and response to therapy, and to support treatment decisions. For these reasons, analyses in molecular pathology must be highly reliable and hence external quality assessment (EQA) programs are called for. Several EQA programs exist to which laboratories can subscribe, but they vary in scope, number of subscribers, and execution. The guideline presented in this paper has been developed with the purpose to harmonize EQA in molecular pathology. It presents recommendations on how an EQA program should be organized, provides criteria for a reference laboratory, proposes requirements for EQA test samples, and defines the number of samples needed for an EQA program. Furthermore, a system for scoring of the results is proposed as well as measures to be taken for poorly performing laboratories. Proposals are made regarding the content requirements of an EQA report and how its results should be communicated. Finally, the need for an EQA database and a participant manual are elaborated. It is the intention of this guideline to improve EQA for molecular pathology in order to provide more reliable molecular analyses as well as optimal information regarding patient selection for treatment.     

Uncovering novel actors in astrocyte–neuron crosstalk in Parkinson's disease: the Wnt/β‐catenin signaling cascade as the common final pathway for neuroprotection and self‐repair

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopaminergic (DAergic) neuronal cell bodies in the substantia nigra pars compacta and gliosis. The cause and mechanisms underlying the demise of nigrostriatal DAergic neurons are ill‐defined, but interactions between genes and environmental factors are recognized to play a critical role in modulating the vulnerability to PD. Current evidence points to reactive glia as a pivotal factor in PD pathophysiology, playing both protective and destructive roles. Here, the contribution of reactive astrocytes and their ability to modulate DAergic neurodegeneration, neuroprotection and neurorepair in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) rodent model of PD will be discussed in the light of novel emerging evidence implicating wingless‐type mouse mammary tumor virus integration site (Wnt)/β‐catenin signaling as a strong candidate in MPTP‐induced nigrostriatal DAergic plasticity. In this work, we highlight an intrinsic Wnt1/frizzled‐1/β‐catenin tone that critically contributes to the survival and protection of adult midbrain DAergic neurons, with potential implications for drug design or drug action in PD. The dynamic interplay between astrocyte‐derived factors and neurogenic signals in MPTP‐induced nigrostriatal DAergic neurotoxicity and repair will be summarized, together with recent findings showing a critical role of glia–neural stem/progenitor cell (NPC) interactions aimed at overcoming neurodegeneration and inducing neurorestoration. Understanding the intrinsic plasticity of nigrostriatal DAergic neurons and deciphering the signals facilitating the crosstalk between astrocytes, microglia, DAergic neurons and NPCs may have major implications for the role of stem cell technology in PD, and for identifying potential therapeutic targets to induce endogenous neurorepair.     

Volume reduction of cystic lesions after surgical decompression: a computerised three-dimensional computed tomographic evaluation

Objectives

This study was performed to evaluate the three-dimensional radiographic variation in mandibular odontogenic cystic lesions after decompression.

Materials and methods

Pre- and post-decompression computed tomography (CT) evaluations in 20 patients affected by keratocysts (n?=?10), dentigerous cysts (n?=?9) and ameloblastoma (n?=?1) were analysed using software designed for three-dimensional measurement of volumes; the results were correlated with treatment duration, age, sex and histological type.

Results

The mean (range) decompression time was 5.70 (3–12)?months. The mean (SD) pre- and post-decompression volumes were 9.50 (7.74) and 4.65 (4.34)?cm³, respectively (P?<?0.001), with a mean (SD) reduction of 49.86 % (19.34 %). The volume reduction was positively correlated with the duration of decompression (P?<?0.001), whereas no correlations with other variables were found (P?=?0.2357). The median monthly reduction in cyst volume was 11.34 % (mean, 13.52 %; range, 4.45–30.43 %) (P?<?0.001).

Conclusions

This three-dimensional CT investigation demonstrated the effectiveness of decompression in the treatment of mandibular odontogenic cystic lesions and showed a positive correlation between the duration of treatment and volume reduction.

Clinical relevance

Decompression treatment, which is simple to perform and generally well-accepted by patients, is a reliable method to considerably reduce the volume of mandibular odontogenic cystic lesions before surgical removal. Extended decompression time seems to improve results of the reduction process.     

ADP-induced platelet aggregation and thrombin generation are increased in Essential Thrombocythemia and Polycythemia Vera

Introduction

Essential Thrombocythemia (ET) and Polycythemia Vera (PV) patients are characterized by an increased rate of thrombotic complications and by several abnormalities of platelets, more pronounced in JAK2V617F positive patients. The aim of this study was to characterize the platelet aggregation as well as the platelet procoagulant potential induced by several different agonists in ET and PV patients.

Materials and Methods

Venous blood samples were obtained from 65 ET and 51 PV patients. Whole blood impedance aggregometry was utilized to characterize platelet aggregation induced by collagen, ADP, thrombin receptor activating peptide and arachidonic acid, while the Calibrated Automated Thrombogram (CAT) assay was used to determine the thrombin generation (TG) potential induced by ADP in platelet-rich plasma. CAT assay was also performed in the presence of annexin V to evaluate the contribution of platelet phospholipids to TG.

Results and Conclusions

ADP-induced platelet aggregation and TG were significantly increased in ET and PV patients compared to controls. The highest values were observed in JAK2V617F positive patients and in patients on aspirin. In these subjects, annexin V was less effective in inhibiting both basal and ADP-induced TG.This study demonstrates for first time that platelets from ET and PV patients are more responsive to the ADP stimulus, in terms of both increased platelet aggregation, and enhanced TG, particularly in the JAK2V617F positive patients. Our data support the hypothesis that the use of ADP receptor inhibitors, in addition to aspirin, might be considered in the prevention of thrombosis in these conditions, by allowing a more complete inhibition of platelet functions.     

An uncommon clinical feature of IAN injury after third molar removal: a delayed paresthesia case series and literature review

After an inferior alveolar nerve (IAN) injury, the onset of altered sensation usually begins immediately after surgery. However, it sometimes begins after several days, which is referred to as delayed paresthesia. The authors considered three different etiologies that likely produce inflammation along the nerve trunk and cause delayed paresthesia: compression of the clot, fibrous reorganization of the clot, and nerve trauma caused by bone fragments during clot organization. The aim of this article was to evaluate the etiology of IAN delayed paresthesia, analyze the literature, present a case series related to three different causes of this pathology, and compare delayed paresthesia with the classic immediate symptomatic paresthesia.     

In-office bacteria test for a microbial monitoring during the conventional and self-ligating orthodontic treatment

This study investigated the microbial level of Streptococcus mutans and Lactobacillus spp. during an orthodontic treatment, and compare the data with untreated control subjects. Sixty young adult subjects were selected (average 20.5, DS 1.62), among which 40 underwent an orthodontic treatment (20 were treated with self-ligating brackets and 20 with conventional brackets) and 20 were controls. Plaque Index, salivary flow and buffering capacity of saliva were assessed before the beginning of the orthodontic treatment. Then the microbial counts were obtained by using an in-office bacteria test. The plaque index (PI) increased over time in each group as well as salivary flow, mostly in subjects treated with self-ligating brackets, suggesting a difference between conventional and self-ligating brackets. S.mutans showed a different trend of colonization in the two treated groups, as for subjects treated with conventional brackets it showed the greater value at the early stage of treatment (T1), followed by a decrease at T2. Lactobacillus spp. showed significant increase over time in the two treated groups, respect to the control group. Linear regression analysis showed no significant predictor for the microbial count at T2. The assortment of the various species of bacteria change over time during the orthodontic treatment, and seems to show different trends, depending on the type of orthodontic device. Consequently a periodical microbial monitoring using in-office bacteria tests, seems indicated.