Peripheral blood BDNF and soluble CAM proteins as possible markers of prolonged disorders of consciousness: a pilot study.

Although clinical examination still represents the gold standard for the differential diagnosis of prolonged disorders of consciousness (pDoC), the introduction of innovative markers is essential for diagnosis and prognosis, due to the problem of covert cognition. We evaluated the brain-derived neurotrophic factor protein (BDNF) and the soluble cell adhesion molecules proteins (CAMs) in a cohort of prolonged disorders of consciousness patients to identify a possible application in the clinical context. Furthermore, peripheral blood determinations were correlated with imaging parameters such as white matter hyperintensities (WMH), cranial standardized uptake value (cSUV), electroencephalography (EEG) data and clinical setting. Our results, although preliminary, identify BDNF as a possible blood marker for the diagnosis of pDoC (p value 0.001), the soluble CAMs proteins CD44, Vcam-1, E-selectin (p value < 0.01) and Icam-3 (p value < 0.05) showed a higher peripheral blood value in pDoC compared with control. Finally, soluble Ncam protein could find useful applications in the clinical evolution of the pDoC, showing high levels in the MCS and EMCS subgroups (p value < 0. 001) compared to VS/UWS.

Management of systemic prostate cancer: current algorithm from castration sensitive to castration resistant setting.

In recent years, the advanced knowledge of clinical, biological and molecular features of prostate cancer have led to the introduction of new drugs and have allowed the relocation of old drugs in different settings. In this way, the new concepts of systemic disease arise: high risk or high volume vs. low risk and low volume disease castration sensitive prostate cancer (CSPC), diversifying the use of previously approved drugs (CRPC) and opening new scenarios for sequence therapy. The aim of this review is to integrate new developments into the medical management of systemic prostate cancer.

PET/MRI for staging patients with Hodgkin lymphoma: equivalent results with PET/CT in a prospective trial.

To compare FDG-PET/unenhanced MRI and FDG-PET/diagnostic CT in detecting infiltration in patients with newly diagnosed Hodgkin lymphoma (HL). The endpoint was equivalence between PET/MRI and PET/CT in correctly defining the revised Ann Arbor staging system. Seventy consecutive patients with classical-HL were prospectively investigated for nodal and extra-nodal involvement during pretreatment staging with same-day PET/CT and PET/MRI. Findings indicative of malignancy with the imaging procedures were regarded as lymphoma infiltration; in case of discrepancy, positive-biopsy and/or response to treatment were evidenced as lymphoma. Sixty of the 70 (86%) patients were evaluable having completed the staging program. Disease staging based on either PET/MRI or PET/CT was correct for 54 of the 60 patients (90% vs. 90%), with difference between proportions of 0.0 (95% CI, -9 to 9%; P=0.034 for the equivalence test). As compared with reference standard, invasion of lymph nodes was identified with PET/MRI in 100% and with PET/CT in 100%, of the spleen with PET/MRI in 66% and PET/CT in 55%, of the lung with PET/MRI in 60% and PET/CT in 100%, of the liver with PET/MRI in 67% and PET/CT in 100%, and of the bone with PET/MRI in 100% and PET/CT in 50%. The only statistically significant difference between PET/MRI and PET/CT was observed in bony infiltration detection rates. For PET/CT, iodinate contrast medium infusions' average was 86 mL, and exposure to ionizing radiation was estimated to be 4-fold higher than PET/MRI. PET/MRI is a promising safe new alternative in the care of patients with HL.

Early diagnosis of multiple sclerosis by OCT analysis using Cohen's d method and a neural network as classifier.

BACKGROUND: The consequences of inflammation, demyelination, axonal degeneration and neuronal loss in the central nervous system, typical of the development of multiple sclerosis (MS), are manifested in thinning of the retina and optic nerve. The purpose of this work is to diagnose early-stage MS patients based on analysis of retinal layer thickness obtained by swept-source optical coherence tomography (SS-OCT). METHOD: OCT (Triton® SS-OCT device -Topcon, Tokyo, Japan-) recordings were obtained from 48 control subjects and 48 recently diagnosed MS patients. The following thicknesses were measured on a 45 × 60 grid: retinal nerve fibre layer (RNFL), ganglion cell layer (GCL+), GCL++, retinal thickness and choroid. Using Cohen's d effect size, it was determined the regions and layers with greatest capacity to discriminate between control subjects and patients. Points exceeding the threshold set were used as inputs for an automatic classifier: support vector machine and feed-forward neural network. RESULTS: In MS at clinical onset the layer with greatest discriminant capacity is GCL++ [AUC = 0.83] which exhibits a horseshoe-like macular topographic distribution. It is followed by retina, GCL+ and RNFL; choroidal thicknesses do not provide discriminatory capacity. Using a neural network as a classifier between controls and MS patients, obtains sensitivity of 0.98 and specificity of 0.98. CONCLUSIONS: This work suggest that OCT may serve as an important complementary role to other clinical tests, particularly regarding neurodegeneration. It is possible to characterise structural alterations in retina and diagnose early-stage MS with high degree of accuracy using OCT and artificial neural networks.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Penile cancer: prognostic and predictive factors in clinical decision-making.

Penile cancer (PC) is a typical tumor of non-industrialized countries. The incidence is 20-30 times higher in Africa and South America, considering the elevated prevalence of sexually transmitted diseases. Histologically, PC includes squamous cell carcinoma (SCPC), the most frequent, and nonsquamous carcinoma (NSCPC). Early diagnosis is the goal, whereas later diagnosis relates to poor functional outcomes and worse prognosis. The 5-year survival rate is 85% for patients with histologically regional negative lymph nodes, compared to 29%-40% for those with histologically regional positive lymph nodes. To date no new drugs are approved, and there are few new data about molecular mechanisms underlying tumorigenesis. The SCPC remains a rare tumor and the current therapeutic algorithm is based principally on retrospective analysis and less on prospective trials. In this review article, biomarkers of prognosis and efficacy of current treatments are summarized with a focus on those that have the potential to affect treatment decision-making in SCPC.

Advanced/metastatic bladder cancer: current status and future directions.

In 2015 bladder cancer was the fourth most frequent malignancy and the eighth cause of death for cancer. At diagnosis, about 30% of bladder cancer (BC) patients present a muscle-invasive bladder cancer (MIBC) and 5% a metastatic bladder carcinoma (MBC). For fit MBC patients, combination chemotherapy (CC) is the standard of care for first-line treatment. CC includes both the treatment with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) either the classical or the dose-dense MVAC regimen, and the doublet therapy with cisplatin and gemcitabine (CG). Median progression free survival (PFS) was 7 months and median overall survival (OS) was 15 months. The present review provides an update on the management of MBC, with focus on target therapies, immune checkpoint inhibition, looking for prognostic and predictive factors.

Electroencephalographic and Neuroimaging Asymmetry Correlation in Patients with Attention-Deficit Hyperactivity Disorder.

The present study explores the correlation between electroencephalographic and neuroimaging asymmetry index from EEG-MRI functional connectome and EEG power analysis in inattention, motion, and mixed profile subgroups of ADHD. Sixty-two subjects from Healthy Brain Network Biobank of the Child Mind Institute dataset were selected basing on the quotient score. From both MRI and EEG asymmetry index, Pearson's correlation, ANOVA, and partial least square analysis were performed matching left and right brain parcels and channels. The asymmetry index significantly correlated across subjects between fMRI and power-EEG in the inattention group in frontal and temporal areas for theta and alpha bands, an anticorrelation in the same areas for delta band was found. Significant patterns of hemispheric asymmetry index have been reported, involving EEG bands that underlie cognitive impairments in ADHD. Alpha and theta bands were altered in the inattention group of patients, reflecting widespread deficiency of basic attentional processing.

The role of allergoids in allergen immunotherapy: from injective to sublingual route.

Summary: Summary Allergen immunotherapy (AIT) is aimed at inducing tolerance to allergens, such as pollens, dust mites or moulds, by administering increasing amounts of the causative allergen through subcutaneous or sublingual route. The evidence of efficacy of AIT is high, but the issue of safety, especially for the subcutaneous route, must be taken into account. The search for safer AIT products aimed at reducing the allergenicity, and thus adverse reactions, while maintaining the immunogenicity, that is essential for effectiveness, gave rise to the introduction of allergoids, which were conceived to fulfill these requirements. In the first allergoids glutaraldehyde or formaldehyde were used as cross-linking agent to polymerize allergens, this resulting in high molecular weight molecules (200,000 to 20,000,000 daltons) which were significantly less allergenic due to a decreased capacity to bridge IgE on its specific receptor, while maintaining the immunogenicity and thus the therapeutic efficacy. In recent years further agents, acting as adjuvants, such as L-tyrosine, monophosphoryl lipid A, aluminium hydroxide, were added to polymerized extracts. Moreover, a carbamylated monomeric allergoid was developed and, once adsorbed on calcium phosphate matrix, used by subcutaneous route. At the same time, in virtue of its peculiarities, such allergoid revealed particularly suitable for sublingual administration. A lot of clinical evidences show that it is well tolerated, largely safer and effective. Importantly, the higher safety of allergoids allows faster treatment schedules that favor patient compliance and, according to pharmaco-economic studies, they might be more cost-effective than other AIT options.

Identification of clusters in multifocal electrophysiology recordings to maximize discriminant capacity (patients vs. control subjects).

PURPOSE: To propose a new method of identifying clusters in multifocal electrophysiology (multifocal electroretinogram: mfERG; multifocal visual-evoked potential: mfVEP) that conserve the maximum capacity to discriminate between patients and control subjects. METHODS: The theoretical framework proposed creates arbitrary N-size clusters of sectors. The capacity to discriminate between patients and control subjects is assessed by analysing the area under the receiver operator characteristic curve (AUC). As proof of concept, the method is validated using mfERG recordings taken from both eyes of control subjects (n = 6) and from patients with multiple sclerosis (n = 15). RESULTS: Considering the amplitude of wave P1 as the analysis parameter, the maximum value of AUC = 0.7042 is obtained with N = 9 sectors. Taking into account the AUC of the amplitudes and latencies of waves N1 and P1, the maximum value of the AUC = 0.6917 with N = 8 clustered sectors. The greatest discriminant capacity is obtained by analysing the latency of wave P1: AUC = 0.8854 with a cluster of N = 12 sectors. CONCLUSION: This paper demonstrates the effectiveness of a method able to determine the arbitrary clustering of multifocal responses that possesses the greatest capacity to discriminate between control subjects and patients when applied to the visual field of mfERG or mfVEP recordings. The method may prove helpful in diagnosing any disease that is identifiable in patients' mfERG or mfVEP recordings and is extensible to other clinical tests, such as optical coherence tomography.

Non-Gaussian models of diffusion weighted imaging for detection and characterization of prostate cancer: a systematic review and meta-analysis.

The importance of Diffusion Weighted Imaging (DWI) in prostate cancer (PCa) diagnosis have been widely handled in literature. In the last decade, due to the mono-exponential model limitations, several studies investigated non-Gaussian DWI models and their utility in PCa diagnosis. Since their results were often inconsistent and conflicting, we performed a systematic review of studies from 2012 examining the most commonly used Non-Gaussian DWI models for PCa detection and characterization. A meta-analysis was conducted to assess the ability of each Non-Gaussian model to detect PCa lesions and distinguish between low and intermediate/high grade lesions. Weighted mean differences and 95% confidence intervals were calculated and the heterogeneity was estimated using the I2 statistic. 29 studies were selected for the systematic review, whose results showed inconsistence and an unclear idea about the actual usefulness and the added value of the Non-Gaussian model parameters. 12 studies were considered in the meta-analyses, which showed statistical significance for several non-Gaussian parameters for PCa detection, and to a lesser extent for PCa characterization. Our findings showed that Non-Gaussian model parameters may potentially play a role in the detection and characterization of PCa but further studies are required to identify a standardized DWI acquisition protocol for PCa diagnosis.

MR Imaging-Histology Correlation by Tailored 3D-Printed Slicer in Oncological Assessment.

3D printing and reverse engineering are innovative technologies that are revolutionizing scientific research in the health sciences and related clinical practice. Such technologies are able to improve the development of various custom-made medical devices while also lowering design and production costs. Recent advances allow the printing of particularly complex prototypes whose geometry is drawn from precise computer models designed on in vivo imaging data. This review summarizes a new method for histological sample processing (applicable to e.g., the brain, prostate, liver, and renal mass) which employs a personalized mold developed from diagnostic images through computer-aided design software and 3D printing. Through positioning the custom mold in a coherent manner with respect to the organ of interest (as delineated by in vivo imaging data), the cutting instrument can be precisely guided in order to obtain blocks of tissue which correspond with high accuracy to the slices imaged. This approach appeared crucial for validation of new quantitative imaging tools, for an accurate imaging-histopathological correlation and for the assessment of radiogenomic features extracted from oncological lesions. The aim of this review is to define and describe 3D printing technologies which are applicable to oncological assessment and slicer design, highlighting the radiological and pathological perspective as well as recent applications of this approach for the histological validation of and correlation with MR images.

Prognostic and predictive factors in testicular cancer.

OBJECTIVE: Testicular cancer is a relatively rare neoplasia, with an incidence of about 1,5% among male malignancies, usually in the third and fourth decade of life. Although several histological variants are known, with some histotypes affecting older patients (e.g., spermatocytic seminoma), there is a clear predominance (90-95%) of germ cell tumors among young adults patients1. Testicular Germ Cell Tumor (TGCT), undoubtedly the seminoma histological variant more than non-seminoma one, is definitely a highly curable disease, with a distinctive sensitivity to cisplatin-based therapy (and for seminomas to radiotherapy) and an outstanding cure rate of nearly 80% even for patients with advanced disease. So far, clinical and pathohistological features supported our efforts to choose the best treatment option for patients suffering from this malignancy, but we don't clearly enough know molecular and pathological features underlying different clinical behaviors, mostly in early-stage disease: by improving this knowledge, we should better "shape" therapeutic or surveillance programs for each patient, also in order to avoid unnecessary, if not harmful, treatments.

Clinical and immunological effects of a treatment with desentizating low-dose multicomponents in IgE mediated and non IgE mediated food allergies: observational retrospective pilot study.

BACKGROUND: Alimentary allergy has high impact on the quality of life (Qol) of patients and their families: it represents an economic burden for individuals and National Health System. The disease, particularly frequent in pediatric age, recognizes different pathogenetic mechanisms and expresses itself through the production of IgE (IgE mediated form) antibodies or through cell-mediated immunune responses (non IgE mediated forms). The aim of this clinical observational retrospective study is to evaluate the effect of a long-term treatment with Low Dose Medicine (LDM) drugs in pediatric patients affected by IgE and non IgE mediated food allergy. OBJECTIVE: The purpose of the study is to determine the efficacy of the treatment with Allergy Plex (Guna Laboratory, Milan, Italy) to induce clinical and/or immunological tolerance both to IgE mediated and non IgE mediated food allergy; the secondary endpoint is to investigate the treatment tolerability, the reduction of positivity to Skin Prick test and Patch test to food allergens and the decrease on the peripheral blood of the specific IgE to food allergens. The treatment efficacy was measured through a clinical score. METHODS: In this study the immunomodulant activity of Allergy Plex 13, Allergy Plex 7 and Allergy Plex 10 (Guna S.p.A., Milano, Italy) was evaluated. In every patient the state of allergical clinical responses and the immuno-allergological state were evaluated by means of specific parameters letting know the regulatory response to the allergical Th fenotype. RESULTS: Data about Clinical tolerance to food, Symptomatological clinical score, ECP, ACTH, Cortisol; IL-4, IL-10 was collected. There was evidence of improvement of clinical score, reduction of the diameter of cutaneous pomphus obtained through the Prick test and a decrease of IgE specifics values. CONCLUSIONS: The data issued from this study seem to confirm the efficacy of treatment with Allergy Plex in allowing the restoration of immune tolerance and the definite reduction of the clinical score.

Use of balloon catheter dilation and steroid-eluting stent in light and severe rhinosinusitis of frontal sinus: a multicenter retrospective randomized study.

OBJECTIVE: Frontal sinus surgery has an increased rate of re-stenosis, if compared to other sinuses. It depends mainly on recurrent inflammation and abnormal scarring at the frontal recess and its reduction represents one of the keys to therapeutic success. Balloon catheter dilation (BCD) and implantable sinus stents/spacers represent strategies to improve sinus ventilation respecting the integrity of mucosa and reducing abnormal post-surgical scarring. The purpose of this study was to evaluate the effectiveness, safety and correct indication about the use of BCD and a non-absorbable stent (Relieva Stratus™ MicroFlow spacer) in the management of chronic rhinosinusitis (CRS) of the frontal sinus. PATIENTS AND METHODS: In this multicentric retrospective study we included a population of 76 frontal sinuses with non-polypoid CRS. 41 frontal sinuses were treated with BCD alone and 35 frontal sinuses with BCD + Spacer. We analyzed both radiological (Lund-McKay CT scoring modified by Zinreich) and symptomatological results (SNOT-20 questionnaire) before surgery and after 12 months, dividing our population in two main groups: group "L" (light/mild frontal CRS) and group "S" (moderate/severe frontal CRS). RESULTS: Our results confirm a good safety and effectiveness of BCD in the management of frontal CRS and show a good safety but a not significative effectiveness of Relieva Stratus™ MicroFlow spacer when added to BCD in the management of light and severe frontal chronic rhinosinusitis. CONCLUSIONS: BCD is an acclared option in the management of frontal CRS and in the near future, utilization of stents/spacers could become a new and effective weapon in the management of rhinosinusitis, both like an adjunct to standard therapies, and in patient populations where the use of systemic drugs is contraindicated.

Should omalizumab be used in severe asthma/COPD overlap?

A large number of patients suffering from asthma or chronic obstructive pulmonary disease (COPD) can show overlapping features of both diseases. Several subjects affected by asthma-COPD overlap (ACO) may be at a severe stage, poorly responsive to triple therapy including inhaled corticosteroids, long-acting ß2 agonists and muscarinic antagonists. This review tries to explore whether omalizumab can be used in poorly controlled severe ACO patients. According to the few studies available, omalizumab may improve asthma outcomes in ACO, although the magnitude of improvements may be lower in comparison to those obtained in subjects affected only by severe asthma. Omalizumab, by acting on IgE, might improve the eosinophilic pattern which is characteristic of the ACO asthma inflammation component. It can be hypothesized that a prevalence of Th1/Th17 airway inflammation pathways can modulate a lower response to anti-IgE while a Th2 pattern can lead to a higher effectiveness to omalizumab in ACO. High levels of IgE, FeNO and blood eosinophil count may be markers of a better response to omalizumab. In conclusion, on the basis of the few studies available, omalizumab could be effective in poorly-controlled severe ACO, although to a reduced extent in comparison to patients affected only by asthma.