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

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

[Serum markers of liver fibrogenesis and fibrosis].

Abstract Serum levels of some extracellular matrix components increased in different liver diseases are studied. Hyaluronic acid (HA) and amino-terminal propeptide of type III procollagen (PNIIIP) have been the most extensively studied serum components. In particular, serum levels of PNIIIP seem to be mainly correlated with histological activity in chronic hepatitis. Considering the close pathophysiological relationship between histological activity and fibrogenesis, it is possible to consider PNIIIP as a marker of fibrogenesis. Thus, serum PNIIIP could be a useful tool for monitoring the therapeutic response in patients with chronic hepatitis in treatment with antifibrogenetic and antifibrotic agents. Like PNIIIP, serum HA concentrations increase in patients with liver fibrosis. There is evidence that serum levels of HA are more strongly correlated with histological grades of liver fibrosis than serum PNIIIP. This suggests that serum HA may be preferable for discriminating patients with cirrhosis from those without cirrhosis. There are other extracellular matrix components and a combination of several serum markers could increase their diagnostic value, but further studies are needed to confirm this

[Drugs inhibiting the hepatic fibrogenesis].

Abstract The treatment of chronic liver disease represents still now an open problem in medicine. The first objective of therapy has to be the causal agent removal; however, there are many cases (viral infections, autoimmunity, genetic disease) in which it is not possible to reach this issue; in these situations the secondary objective of the therapy is to inhibit the hepatic fibrogenesis, in attempt of easing or blocking the transformation of chronic liver disease in cirrhosis. The aim of this work is to review the various compounds which showed an antifibrotic activity, using a simple classification model, allowing a fast setting of different compounds. These last, on the basis of their main action, can be divided into two main groups: drugs with direct action, which interfere with collagen metabolism (for instance interferons, glucocorticoids, prolyl 4-hydroxylase inhibitors, cyclosporin A, colchicine, D-penicillamine, phosphatidylcholine and so on) and drugs with indirect action, that decrease the inflammatory stimuli, capable of stirring up the fibrogenetic hepatic process (S-adenosylmethionine, malotilate, ursodeoxycholic acid, ribavirin and so on). There are drugs that have both mechanisms of action, without the prevalence of one or other mechanism (prostaglandins)

[The physiopathological mechanism of hepatic fibrosis].

Abstract Liver fibrosis is the end result of an imbalance between synthesis and degradation of extracellular matrix proteins of the liver. The extracellular matrix of the liver is complex. It comprises multiple components of three major types of macromolecules: proteins, glycoproteins and proteoglycans. The normal liver contains limited amounts of extracellular matrix composed of elastin, fibronectin, collagen, proteoglycans and other macromolecules. These molecules have specific structure-function properties. In the liver they provide a structural framework and modulate tissue repair. The fibrogenesis is a reaction to liver injury, it leads to marked impairment of hepatic sinusoidal blood flow and ultimately to cirrhosis associated with portal hypertension and hepatocyte dysfunction. The process of fibrosis is the result from complex interactions between extracellular matrix macromolecules, hepatic cells, cytokines and growth factors, that activate the stellate cells of the liver to induce the synthesis of extracellular matrix components that deposit into the local extracellular matrix and to produce the inhibitor of metalloproteinase. The end result of these activities is an imbalance in the synthesis/degradation homeostasis of the liver, that is, liver fibrosis

Hemipelvectomy and reconstruction in a patient with advanced Marjolin's ulcer: a case report.

Patients with squamous cell carcinoma of the lower limb may exhibit locally advanced or metastatic disease. Surgical resection to control the primary tumor is often extensive.The case of a 51-year-old man with squamous cell carcinoma on Marjolin?€™s ulcer affected, rapidly growing, and involving soft and bone tissues is described. Treatment required performing a hemipelvectomy. Immediate reconstruction was chosen as surgical procedure planning the harvest of 4 superficial muscles and 1 deep muscle of the abdomen to protect the pelvic content and to eliminate the dead spaces.The chosen technique minimized postoperative complications, and at 7 years follow-up, the patient is disease free

Antibiotic therapy of transaxillary augmentation mammoplasty.

Background: Capsular contracture is the most common complication and the main cause of dissatisfaction after augmentation mammoplasty, for both the patient and the plastic surgeon. The formation of fibrous tissue around the prosthesis alters the form or the consistency of the implant, thus modifying the breast shape, its contour and its softness. The initial satisfaction with the achieved aesthetical result is then transformed into great dissatisfaction, due to the presence of a shapeless and undesired mass. Patients and Methods: The following study considered data collected between 1998 and 2007. Sixty-seven female patients (aged between 35 and 53 years) who suffered from mammary hypotrophy and had undergone submuscular augmentation mammoplasty were enrolled. All the implanted prostheses were round and texturized, with a volume of 250 cm3 to 450 cm3. The patients underwent pre-, intra- and postoperative antibiotic therapy in order to prevent clinical and subclinical infection of the implants. Results: The follow-up ranged from a period of two to nine years. All patients were examined during the first antibiotic administration and again subsequently, after 1, 3, 6 and 12 months, to evaluate the results in terms of capsular contracture. Of all patients, 90% presented a degree I Baker’s classification, the remaining 10% a degree II. Not one of the patients treated showed grade III or IV capsular contracture nor was there any need to remove the prosthesis during the examination period. Conclusion: It is clear that a main role in capsular contracture is played by the infectious process, with the activation of specific inflammatory cells. Interfering with the infectious process can prevent fibrotic reaction evolving into capsular contracture. Although the process causing capsular contracture is multifactorial, our study showed a favourable response can be achieved when using antibiotic therapy associated with the transaxillary approach