Effects of Rheopheresis in dialysis patients with peripheral artery disease and diabetic foot ulcers: A multicentric Italian study.

Background: Peripheral artery disease (PAD) in hemodialysis (HD) patients has a significant social impact due to its prevalence, poor response to standard therapy and dismal prognosis. Rheopheresis is indicated by guidelines for PAD treatment.

Materials And Methods: Twenty-five HD patients affected by PAD stage IV Lerichè-Fontaine and ischemic ulcer 1C or 2C according to the University of Texas Wound Classification System (UTWCS), without amelioration after traditional medical therapy and/or revascularization, were selected and underwent 12 Rheopheresis sessions in 10 weeks.

Adipose tissue macrophage dysfunction is associated with a breach of vascular integrity in NASH.

Background & Aims: In non-alcoholic fatty liver disease (NAFLD), monocytes infiltrate visceral adipose tissue promoting local and hepatic inflammation. However, it remains unclear what drives inflammation and how the immune landscape in adipose tissue differs across the NAFLD severity spectrum. We aimed to assess adipose tissue macrophage (ATM) heterogeneity in a NAFLD cohort.

Biomimetic superabsorbent hydrogel acts as a gut protective dynamic exoskeleton improving metabolic parameters and expanding A. muciniphila.

The rising prevalence of obesity and metabolic disorders worldwide highlights the urgent need to find new long-term and clinically meaningful weight-loss therapies. Here, we evaluate the therapeutic potential and the mechanism of action of a biomimetic cellulose-based oral superabsorbent hydrogel (OSH). Treatment with OSH exerts effects on intestinal tissue and gut microbiota composition, functioning like a protective dynamic exoskeleton.

The gut vascular barrier: a new player in the gut-liver-brain axis.

The intestinal barrier protects our body from external insults through specialized cells organized in a multilayered structure that evolved in symbiosis with the resident microbiota. A breach in the outer mucus and epithelium can be transmitted to the inner gut vascular barrier (GVB), leading to systemic dissemination of microbes or microbe-derived molecules. Several extraintestinal pathologies have been linked to gut microbiota dysbiosis that causes GVB leakage in their early phases.

Gut-Liver Axis in Nonalcoholic Fatty Liver Disease: the Impact of the Metagenome, End Products, and the Epithelial and Vascular Barriers.

Nonalcoholic fatty liver disease (NAFLD) is a systemic, dynamic, heterogeneous, and multiaxis entity, the pathogenesis of which is still uncertain. The gut-liver axis is regulated and stabilized by a complex network encompassing a metabolic, immune, and neuroendocrine cross-talk between the gut, the microbiota, and the liver. Changes in the gut-liver axis affect the metabolism of lipids and carbohydrates in the hepatocytes, and they impact the balance of inflammatory mediators and cause metabolic deregulation, promoting NAFLD and its progression to nonalcoholic steatohepatitis.

Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver.

Metastasis is facilitated by the formation of a "premetastatic niche," which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC.

Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development.

Background & Aims: Fatty liver disease, including non-alcoholic fatty liver (NAFLD) and steatohepatitis (NASH), has been associated with increased intestinal barrier permeability and translocation of bacteria or bacterial products into the blood circulation. In this study, we aimed to unravel the role of both intestinal barrier integrity and microbiota in NAFLD/NASH development.

Methods: C57BL/6J mice were fed with high-fat diet (HFD) or methionine-choline-deficient diet for 1 week or longer to recapitulate aspects of NASH (steatosis, inflammation, insulin resistance).

MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell Lymphomagenesis.

The gene encoding the MEF2B transcription factor is mutated in germinal center (GC)-derived B cell lymphomas, but its role in GC development and lymphomagenesis is unknown. We demonstrate that Mef2b deletion reduces GC formation in mice and identify MEF2B transcriptional targets in GC, with roles in cell proliferation, apoptosis, GC confinement, and differentiation. The most common lymphoma-associated MEF2B mutant (MEF2B) is hypomorphic, yet escapes binding and negative regulation by components of the HUCA complex and class IIa HDACs.

Mutations targeting the coagulation pathway are enriched in brain metastases.

Brain metastases (BMs) are the most common malignancy of the central nervous system. Recently it has been demonstrated that plasminogen activator inhibitor serpins promote brain metastatic colonization, suggesting that mutations in serpins or other members of the coagulation cascade can provide critical advantages during BM formation. We performed whole-exome sequencing on matched samples of breast cancer and BMs and found mutations in the coagulation pathway genes in 5 out of 10 BM samples.

Functional role of CLIC1 ion channel in glioblastoma-derived stem/progenitor cells.

Background: Chloride channels are physiologically involved in cell division and motility. Chloride intracellular channel 1 (CLIC1) is overexpressed in a variety of human solid tumors compared with normal tissues, suggesting a potential involvement of CLIC1 in the regulation of tumorigenesis. This led us to investigate the role of CLIC1 in gliomagenesis.

Marker-independent method for isolating slow-dividing cancer stem cells in human glioblastoma.

Glioblastoma (GBM) is a devastating brain tumor with a poor survival outcome. It is generated and propagated by a small subpopulation of rare and hierarchically organized cells that share stem-like features with normal stem cells but, however, appear dysregulated in terms of self-renewal and proliferation and aberrantly differentiate into cells forming the bulk of the disorganized cancer tissues. The complexity and heterogeneity of human GBMs underlie the lack of standardized and effective treatments.

Outcome and clinico-biological characteristics of advanced breast cancer patients with surgically resected brain metastases: a multidisciplinary approach.

Background: Despite improvements in brain surgery and radiotherapy, patients with brain metastases (BM) from breast cancer still have a poor prognosis. The aim of the present study is to evaluate the outcome of a multimodal therapeutic strategy in an unselected cohort of patients.

Methods: We retrospectively reviewed 24 breast cancer patients who developed BM and were treated with brain surgery, radiotherapy, and/or systemic therapy in the same institutions.

Acute and chronic effects of therapeutic apheresis.

In most patients only a few sessions of apheresis treatment are necessary to see the benefit. This is the case of immunological diseases when the production of a pathologic component is limited in time or in microcirculation disturbances when changes of vascular function may occur. In the first instance the acute effect is likely due to the removal of the corresponding antibody, while in the second case the improvement of the endothelium-dependent vasodilation and the reduction of blood viscosity play a major role.

CD133 is essential for glioblastoma stem cell maintenance.

The role of the cell surface CD133 as a cancer stem cell marker in glioblastoma (GBM) has been widely investigated, since it identifies cells that are able to initiate neurosphere growth and form heterogeneous tumors when transplanted in immune-compromised mice. However, evidences of CD133-negative cells exhibiting similar properties have also been reported. Moreover, the functional role of CD133 in cancer stem/progenitor cells remains poorly understood.

[Production and control of water quality for hemodialysis].

Certain substances present in drinking water can harm hemodialysis patients if they are not removed before the preparation of the dialysate. An optimal water treatment system includes tap water pretreatment and a double reverse osmosis process. Every component, including the delivery of the treated water to the dialysis machines, contributes to preventing chemical and microbiological contamination.

[Chronic kidney disease in the province of Mantua and its developments over the last 40 years].

The incidence and prevalence of end-stage renal disease increased steadily for 35 years in the population of Italy's Mantua province until the end of 2007, when they started to decrease. We describe the results of providing information and raising awareness among residents of the province's capital, Mantua, and of direct teaching and short training courses in hospital wards for general practitioners over a period of 3 years. During this period there was also more consultation activity for all kidney outpatients, from the first to the last stages of chronic kidney disease.

Current strategies for identification of glioma stem cells: adequate or unsatisfactory?

Cancer stem cells (CSCs) were isolated in multiple tumor types, including human glioblastomas, and although the presence of surface markers selectively expressed on CSCs can be used to isolate them, no marker/pattern of markers are sufficiently robust to definitively identify stem cells in tumors. Several markers were evaluated for their prognostic value with promising early results, however none of them was proven to be clinically useful in large-scale studies, leading to outstanding efforts to identify new markers. Given the heterogeneity of human glioblastomas further investigations are necessary to identify both cancer stem cell-specific markers and the molecular mechanisms sustaining the tumorigenic potential of these cells to develop tailored treatments.

Therapeutic apheresis in peripheral and retinal circulatory disorders.

In microcirculation disorders, the therapeutic apheresis seems to have two different effects. The first, achieved after only a few sessions, is acute, consisting of drastic reduction of blood viscosity and obtained with the use of low-density lipoprotein (LDL) apheresis, rheopheresis, or fibrinogen apheresis. The second effect is long term, or chronic, and needs to be evaluated after a long course of treatment.

[Effects of cascade filtration in combination with interferon and ribavirin in the treatment non responder chronic hepatitis C patients].

In 40% of patients with chronic hepatitis C, standard therapy is unable to eradicate the virus. Since the response to pharmacological treatment depends on the initial viral load, there is a rationale for reducing this load by means of apheretic depletion of the C virus. The aim of this work was to administer cascade filtration (CF) to non responder patients affected by hepatitis C (pts) before resuming the pharmacological treatment.

Rai is a new regulator of neural progenitor migration and glioblastoma invasion.

The invasive nature of glioblastoma (GBM) is one important reason for treatment failure. GBM stem/progenitor cells retain the migratory ability of normal neural stem/progenitor cells and infiltrate the brain parenchyma. Here, we identify Rai (ShcC/N-Shc), a member of the family of Shc-like adaptor proteins, as a new regulator of migration of normal and cancer stem/progenitor cells.

Endothelial progenitor cells in sudden sensorineural hearing loss.

Conclusions: Endothelial progenitor cells (EPCs) are a unique subtype of circulating cells with properties similar to those of embryonal angioblasts. They have the potential to proliferate and to differentiate into mature endothelial cells. EPCs are reduced in patients with vascular risk factors due to a decreased mobilization, an increased consumption at the site of damage or a reduced half-life.

[Kidney biopsy in Mantua: 2000-2009 report].

The aim of this study was to report the frequency of kidney diseases related to gender, age, clinical presentation and renal function at the time of kidney biopsy in the population of Mantua province (400,000 residents). We collected the results of 132 real-time ultrasound-guided fine-needle (18 G) kidney biopsies by optical and immunofluorescence microscopy. The clinical presentation at the time of biopsy was nephrotic syndrome in 57%, nephritic syndrome in 22%, and urinary abnormalities in 21% of cases.

Human glioblastoma tumours and neural cancer stem cells express the chemokine CX3CL1 and its receptor CX3CR1.

Human gliomas represent an unmet clinical challenge as nearly two-thirds of them are highly malignant lesions with fast progression, resistance to treatment and poor prognosis. The most severe form, the glioblastoma multiforme, is characterised by a marked and diffuse infiltration through the normal brain parenchyma. Given the multiple effects of chemokines on tumour progression, aim of this study was to analyse the expression of the chemokine CX3CL1 and of its specific receptor CX3CR1 in 36 human surgical glioma samples, with different degrees of histological malignancy and in glioblastoma-derived neurospheres.

Effect of low-density lipoprotein apheresis on circulating endothelial progenitor cells in familial hypercholesterolemia.

Background: Long-term treatment with low-density lipoprotein (LDL) apheresis (LA) has been shown to reduce the incidence of cardiovascular events in patients affected by familial hypercholesterolemia (FH). Data from experimental studies suggest that circulating endothelial progenitor cells (EPCs) can repair the vascular lesions caused by atherosclerosis. Since a reduction of these cells has been demonstrated to predict atherosclerosis progression, the aim of this study was to verify whether LA can increase the percentage of EPCs.