The role of immune PSA complex (iXip) in the prediction of prostate cancer

Purpose: To analyse the performance of iXip in the prediction of prostate cancer (PCa) and high-grade PCa. Methods: A consecutive series of men undergoing MRI/FUSION prostate biopsies were enrolled in one centre. Indications for prostate biopsy included abnormal prostate-specific antigen (PSA) levels (PSA>4 ng/ml) and/or abnormal digital rectal examination (DRE) and/or abnormal MRI. All patients underwent the evaluation of serum PSA-IgM concentration and the iXip ratio was calculated. Accuracy iXip for the prediction of PCa was evaluated using multivariable binary regression analysis and receiver operator characteristics (ROC) curves. Results: Overall 160 patients with a median age of 65 (62/73) years were enrolled. Overall, 42% patients were diagnosed with PCa and 75% of them had high-grade cancer (Epstein ≥ 3). Patients with PCa were older and presented higher PSA levels, higher PIRADS scores and lower prostate volumes (PVs). On ROC analysis iXip presented an area under the curve (AUC) of 0.57 in the prediction of PCa and of 0.54 for the prediction of high-grade PCa. Conclusions: In our experience, immune PSA complexes are not predictors of PCa. iXip analysis should not be included in the diagnostic pathway of patients at increased risk of PCa

A systematic review of the biological processes involved in deep-brain stimulation for parkinson’s disease: A focus on the potential disease-modifying effects

Deep-Brain Stimulation (DBS) is an important treatment option for the management of Parkinson’s disease (PD) and is a common symptomatic treatment. However, an increasing number of studies have examined the biological processes to assess if DBS can also modify the natural history of PD by acting on its pathophysiological mechanisms. Relevant literature published up to November 2020 was systematically searched on databases such as PubMed, ISI Web of Knowledge, Academic Search Index, and Science Citation Index. The following predefined inclusion criteria were applied to the full-text versions of the selected articles: I) recruiting and monitoring of PD subjects that were previously treated with DBS and ii) investigating the electrophysiological, biochemical, epigenetic, or neuroimaging effects of DBS. Studies focusing exclusively on motor and clinical changes were excluded. Reviews, case reports, studies on animal models, and computational studies were also not considered. Out of 2,960 records screened, 43 studies met the inclusion criteria. Only three studies described a potential disease-modifying effect of DBS. However, a wide heterogeneity was observed in the investigated biomarkers, and the design and methodological issues of several studies limited their ability to find potential disease-modifying features. Specifically, 60.4% of the trials followed-up subjects for no more than 1 year from the surgical intervention, and 67.4% observed patients with PD only once after DBS. Moreover, 64.2% of the studies enrolled late-stage PD patients. Most of the studies (88.4%) reported that DBS only had a symptomatic effect, with several of them showing some limitations in the study design and recruitment of patients. Further studies using shared biomarkers are encouraged to assess if and how DBS might affect the progression of PD. Based on the existing preclinical literature, prospective clinical trials examining the course of PD in early-stage patients are needed

Safety and Efficacy of Monoclonal Antibodies for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Published and Unpublished Clinical Trials

Background: Monoclonal antibodies (mAbs) are currently among the most investigated targets for potential disease-modifying therapies in Alzheimer's disease (AD). Objective: Our objectives were to identify all registered trials investigating mAbs in MCI due to AD or AD at any stage, retrieve available published and unpublished data from all registered trials, and analyze data on safety and efficacy outcomes. Methods: A systematic search of all registered trials on ClinicalTrials.gov and EUCT was performed. Available results were searched on both platforms and on PubMed, ISI Web of Knowledge, and The Cochrane Library. Results: Overall, 101 studies were identified on 27 mAbs. Results were available for 50 trials investigating 12 mAbs. For 18 trials, data were available from both published and unpublished sources, for 21 trials only from published sources, and for 11 trials only from unpublished sources. Meta-analyses of amyloid-related imaging abnormalities (ARIA) events showed overall risk ratios of 10.65 for ARIA-E and of 1.75 for ARIA-H. The meta-analysis of PET-SUVR showed an overall significant effect of mAbs in reducing amyloid (SMD -0.88), but when considering clinical efficacy, data on CDR-SB showed that treated patients had a statistically significant but clinically non-relevant lower worsening (MD -0.15). Conclusion: Our results suggest that the risk-benefit profile of mAbs remains unclear. Research should focus on clarifying the effect of amyloid on cognitive decline, providing data on treatment response rate, and accounting for minimal clinically important difference. Research on mAbs should also investigate the possible long-term impact of ARIA events, including potential factors predicting their onset

Cholangiocarcinoma: Challenges and future needs

Cholangiocarcinoma (CCA) is a malignant neoplasm that arises from the biliary tract epithelia. CCA is the second most common primary liver tumour after hepatocellular carcinoma, representing 10-25% of primary hepatic malignancies (1). CCA is rare in many parts of the world, such as Europe and the United States (US), accounting for <3% of all malignant tumours. However, there is a dramatic geographic variation in its incidence, which reflects regional differences in risk factors and epidemiology (2,3)

Side-to-side caval anastomosis in a patient receiving a liver graft from a marginal donor with situs inversus totalis

The donor situs inversus totalis status was considered an absolute contraindication to liver transplantation due to the technical difficulties involved. Only in recent years has a very young deceased donor with situs inversus totalis been considered as a potential donor

Relationship between GH/IGF-1 Axis, graft recovery, and early survival in patients undergoing liver transplantation

High levels of IGF-1 have been reported in patients with initial poor function of the graft after liver transplantation (LT). Correlation with other clinical variables or early survival has not been extensively investigated

Everolimus and Advagraf Ab Initio in Combined Liver and Kidney Transplant With Donor-Specific Antibodies: A Case Report

Although donor-specific antibodies are regarded as a contraindication for kidney transplantation, the data available for combined liver and kidney transplantation (cLKTx) are scarce, and there is no established therapeutic approach for this category of transplant recipients. De novo use of everolimus and a reduced dose of calcineurin inhibitor reportedly provides excellent kidney function compared with a standard regimen containing a calcineurin inhibitor. This strategy, however, has been applied in only some recipient categories. Here we report a case of A highly sensitized male patient who underwent a cLKTx and received everolimus with low-dose tacrolimus (once-daily prolonged-release formulation) as ab initio immunosuppressive treatment. The pretransplant panel-reactive antibody estimate was 97%, and multiple anti-HLA antibodies were detected at the time of transplantation. Thus far, patient and allograft survival have reached 2 years, with the recipient remaining on a regimen of immunosuppression with everolimus and low-dose tacrolimus, with no episodes of rejection