Next-level precision medicine: why the theragnostic approach is the future.

Theragnostics represents one of the most innovative fields of precision medicine with a huge potential in the field of oncology in the next years. The use of a pair of selective radiopharmaceuticals for cellular receptors, used for diagnostic and therapeutic purposes (PRRT), finds applications in the Neuroendocrine tumors and metastatic Castration-Resistant prostate cancer (mCRPC) thanks, respectively, to somatostatin receptor agonists and PSMA-based peptides. Further evolutions of theragnostics will be possible to the radioimmunoconjugates used both in the diagnostic (Immuno-PET) and in the therapeutic fields (radioimmunotherapy). It is evident that in the "omics-era," theragnostics could become a necessary method, not only in order to improve our knowledge of tumor biology, but also, to find more and more targeted therapies in a multidisciplinary context and in a tailor-based approach.

Role of astrocytes in major neurological disorders: the evidence and implications.

Given the huge amount and great complexity of astrocyte functions in the maintenance of brain homeostasis, it is easily understood how alterations in their physiology may be involved in the pathogenesis of many, if not all, neurological disorders. This assumption is strongly supported by accumulated evidence produced in humans and in experimental models of pathology. Based on these considerations, it is reasonable to encourage studies aimed at improving the knowledge about the implicated mechanisms, and astroglial cells can be considered as the innovative target for new, and possibly more effective, drug therapies.

Association between the volume of carotid artery plaque and its subcomponents and the volume of white matter lesions in patients selected for endarterectomy.

OBJECTIVE: The amount of cerebral white matter lesions (WMLs) and the severity of carotid artery disease are correlated in this study. The association between the severity of WMLs and the volume of the different components of carotid artery plaque is also evaluated. MATERIALS AND METHODS: Fifty consecutive patients (39 men, 11 women; mean [SD] age, 71 ± 9 years) with carotid artery stenosis who underwent carotid endarterectomy were included in this study. On admission, patients underwent head and neck CT angiography (CTA) and brain MRI. The CTA-based plaque volume and the percentages of the three main plaque components (fatty, mixed, and calcified) were calculated according to the attenuation values. Leukoaraiosis lesion volume on FLAIR images was determined using a semiautomated segmentation technique. Pearson correlation was conducted between the leukoaraiosis lesion volume on FLAIR images and the volumes of the different plaque components. RESULTS: Pearson correlation analysis was performed to determine WML volume versus total carotid plaque volume (ρ = 0.2531; p = 0.0262), fatty plaque volume (ρ = 0.387; p = 0.0005), mixed plaque volume (ρ = 0.1709; p = 0.15), and calcified plaque volume (ρ = 0.0146; p = 0.899). The WML volume was also compared against fatty plaque percentage (ρ = 0.343; p = 0.0018), mixed plaque percentage (ρ = 0.181; p = 0.124), and calcified plaque percentage (ρ = -0.209; p = 0.068). CONCLUSION: The cerebral WML volume and the total volume of the plaque are correlated. The amount of fat within the plaque is an additional risk factor, whereas the calcified component seems to be protective.

Breast Imaging Physics in Mammography (Part I).

Breast cancer is the most frequently diagnosed neoplasm in women in Italy. There are several risk factors, but thanks to screening and increased awareness, most breast cancers are diagnosed at an early stage when surgical treatment can most often be conservative and the adopted therapy is more effective. Regular screening is essential but advanced technology is needed to achieve quality diagnoses. Mammography is the gold standard for early detection of breast cancer. It is a specialized technique for detecting breast cancer and, thus, distinguishing normal tissue from cancerous breast tissue. Mammography techniques are based on physical principles: through the proper use of X-rays, the structures of different tissues can be observed. This first part of the paper attempts to explain the physical principles used in mammography. In particular, we will see how a mammogram is composed and what physical principles are used to obtain diagnostic images.

Breast Imaging Physics in Mammography (Part II).

One of the most frequently detected neoplasms in women in Italy is breast cancer, for which high-sensitivity diagnostic techniques are essential for early diagnosis in order to minimize mortality rates. As addressed in Part I of this work, we have seen how conditions such as high glandular density or limitations related to mammographic sensitivity have driven the optimization of technology and the use of increasingly advanced and specific diagnostic methodologies. While the first part focused on analyzing the use of a mammography machine from a physical and dosimetric perspective, in this paper, we will examine other techniques commonly used in breast imaging: contrast-enhanced mammography, digital breast tomosynthesis, radio imaging, and include some notes on image processing. We will also explore the differences between these various techniques to provide a comprehensive overview of breast lesion detection techniques. We will examine the strengths and weaknesses of different diagnostic modalities and observe how, with the implementation of improvements over time, increasingly effective diagnoses can be achieved.

Targeting neuroinflammation in Alzheimer's disease.

Almost 47 million people suffer from dementia worldwide, with an estimated new case diagnosed every 3.2 seconds. Alzheimer's disease (AD) accounts for approximately 60%-80% of all dementia cases. Given this evidence, it is clear dementia represents one of the greatest global public health challenges. Currently used drugs alleviate the symptoms of AD but do not treat the underlying causes of dementia. Hence, a worldwide quest is under way to find new treatments to stop, slow, or even prevent AD. Besides the classic targets of the oldest therapies, represented by cholinergic and glutamatergic systems, ß-amyloid (Aß) plaques, and tau tangles, new therapeutic approaches have other targets. One of the newest and most promising strategies is the control of reactive gliosis, a multicellular response to brain injury. This phenomenon occurs as a consequence of a persistent glial activation, which leads to cellular dysfunctions and neuroinflammation. Reactive gliosis is now considered a key abnormality in the AD brain. It has been demonstrated that reactive astrocytes surround both Aß plaques and tau tangles. In this condition, glial cells lose some of their homeostatic functions and acquire a proinflammatory phenotype amplifying neuronal damage. So, molecules that are able to restore their physiological functions and control the neuroinflammatory process offer new therapeutic opportunities for this devastating disease. In this review, we describe the role of neuroinflammation in the AD pathogenesis and progression and then provide an overview of the recent research with the aim of developing new therapies to treat this disorder.

MR Imaging in Diagnosis of Pelvic Floor Descent: Supine versus Sitting Position.

Introduction. Functional disorders of the pelvic floor represent have a significant impact on the quality of life. The advent of open-configuration systems allowed for the evaluation of defecation with MR imaging in sitting position. The purpose of the present study is to compare the results of static and dynamic pelvic MR performed in supine position versus sitting position, using a new MR prototype machine, in the diagnosis of pelvic floor descent. Materials and Methods. Thirty-one patients with pelvic floor disorders were enrolled, and underwent MR Defecography in supine position with 1.5 T closed magnet (MAGNETOM Symphony, Siemens, Germany) and in sitting position with a 0.25-Tesla open magnet system (G-Scan ESAOTE, Italy). Results. In rest and squeezing phases, positions of bladder, vagina, and ARJ were significantly different when the patient was imaged in supine versus sitting position. In the defecation phase, a significant difference for the bladder and vagina position was detected between the two exams whereas a significant difference for the ARJ was not found. A statistically significant difference exists when the pelvic floor descent is evaluated in sitting versus supine position. Conclusion. Our results show that MR Defecography in sitting position may represent a useful tool to correctly diagnose and grade the pelvic organ descent.

3D-EAUS and MRI in the Activity of Anal Fistulas in Crohn's Disease.

Aim. This study aspires to assess the role of 3D-Endoanal Ultrasound (3D-EAUS) and Magnetic Resonance Imaging (MRI) in preoperative evaluation of the primary tract and internal opening of perianal fistulas, of secondary extensions and abscess. Methods. During 2014, 51 Crohn's disease patients suspected for perianal fistula were enrolled. All patients underwent physical examination with both the methods and subsequent surgery. Results. In the evaluation of CD perianal fistulas, there are no significant differences between 3D-EAUS and MRI in the identification of abscess and secondary extension. Considering the location, 3D-EAUS was more accurate than MRI in the detection of intersphincteric fistulas (p value = 10(-6)); conversely, MRI was more accurate than 3D-EAUS in the detection of suprasphincteric fistulas (p value = 0.0327) and extrasphincteric fistulas (p value = 4 ⊕ 10(-6)); there was no significant difference between MRI and 3D-EAUS in the detection of transsphincteric fistulas. Conclusions. Both 3D-EAUS and MRI have a crucial role in the evaluation and detection of CD perianal fistulas. 3D-EAUS was preferable to MRI in the detection of intersphincteric fistulas; conversely, in the evaluation of suprasphincteric and extrasphincteric fistulas the MRI was preferable to 3D-EAUS.

Does neuroinflammation turn on the flame in Alzheimer's disease? Focus on astrocytes.

Data from animal models and Alzheimer's disease (AD) subjects provide clear evidence for an activation of inflammatory pathways during the pathogenetic course of such illness. Biochemical and neuropathological studies highlighted an important cause/effect relationship between inflammation and AD progression, revealing a wide range of genetic, cellular, and molecular changes associated with the pathology. In this context, glial cells have been proved to exert a crucial role. These cells, in fact, undergo important morphological and functional changes and are now considered to be involved in the onset and progression of AD. In particular, astrocytes respond quickly to pathology with changes that have been increasingly recognized as a continuum, with potentially beneficial and/or negative consequences. Although it is now clear that activated astrocytes trigger the neuroinflammatory process, however, the precise mechanisms have not been completely elucidated. Neuroinflammation is certainly a multi-faceted and complex phenomenon and, especially in the early stages, exerts a reparative intent. However, for reasons not yet all well known, this process goes beyond the physiologic control and contributes to the exacerbation of the damage. Here we scrutinize some evidence supporting the role of astrocytes in the neuroinflammatory process and the possibility that these cells could be considered a promising target for future AD therapies.