Multidisciplinary working group: key role for percutaneous endovascular AV fistula program. Point of view.

Chronic kidney disease is a progressive condition that affects more than 10% of the general population worldwide. Hemodialysis is the most common therapeutic option for kidney failure, which develops in around one out of 1000 individuals in the general population. Hemodialysis needs a vascular access to connect to the extracorporeal machine. In the last few years percutaneous endovascular arterio-venous fistula technique has been increasingly employed with very promising results. Several advantages have been demonstrated in comparison to the standard surgical creation of an arteriovenous fistula. The percutaneous endovascular arterio-venous fistula technique requires multidisciplinary team work. In our practice, we have organized a multidisciplinary team that includes nephrologists, play a key role, interventional radiologists, vascular surgeons, anesthesiologists, and dialysis nurses. Procedural outcomes and feedback received from patients and family members are evaluated periodically in order to improve results. Nephrologists are involved in each step of the management of the percutaneous endovascular arterio-venous fistula: selection, mapping, creation, and follow up. Patient empowerment, education and involvement is required at each step. A dedicated training program, involving patients and the caregiver team is therefore needed. Additional research is required to confirm the benefit of the multidisciplinary team management in end-stage kidney disease patients.

A closer look to the new frontier of artificial intelligence in the percutaneous treatment of primary lesions of the liver.

The purpose of thermal ablation is induction of tumor death by means of localized hyperthermia resulting in irreversible cellular damage. Ablative therapies are well-recognized treatment modalities for HCC lesions and are considered standard of care for HCC nodules < 3 cm in diameter in patients not suitable for surgery. Effective lesion treatment rely on complete target volume ablation. Technical limitations are represented by large (> 3 cm) or multicentric nodules as well as complex nodule location and poor lesion conspicuity. Artificial Intelligence (AI) is a general term referred to computational algorithms that can analyze data and perform complex tasks otherwise prerogative of Human Intelligence. AI has a variety of application in percutaneous ablation procedures such as Navigational software, Fusion Imaging, and robot-assisted ablation tools. Those instruments represent relative innovations in the field of Interventional Oncology and promising strategies to overcome actual limitations of ablative therapy in order to increase feasibility and technical results. This work aims to review the principal application of Artificial Intelligence in the percutaneous ablation of primary lesions of the liver with special focus on how AI can impact in the treatment of HCC especially on potential advantages on the drawbacks of the conventional technique.

A systematic review and Meta-analysis on the association between Hand-Foot Syndrome (HFS) and Cancer Chemotherapy Efficacy.

Hand-foot syndrome (HFS) is a common skin toxicity of traditional chemotherapies. Some studies showed that HFS has an association with progression-free survival (PFS) and the overall survival (OS). So far, there is not available any systematic literature reviews or meta-analysis aimed to assess the associations between HFS, PFS and OS. For this reason, this study aims to quantitatively summarize, critically review, and interpret the recent literature related to the associations between HFS and efficacy of chemotherapy in terms of PFS and OS. Queries shaped by PICOM framework, a systematic search of three electronic databases (PubMed, Scopus, and Science Direct) was carried out for the period between January 2010 and December 2017. Quantitative data pooling was based on the calculation of Hazard Ratio (HR) with 95% Confidence Interval (95% CI) for the OS and PFS associated to the presence of HFS, through the data of original publications. Five papers were included in this systematic review for the quantitative data pooling. Patients with HFS showed improved PFS (HR = 0.532 [0.431-0.656]; p = 0.000) and improved OS (HR = 0.522 [0.427-0.638]; p = 0.000). HFS causes a reduction of compliance with oncology treatments. Healthcare providers should use this result as a trigger to foster patients' coping and the one of their family caregivers, enhancing their adherence to cancer treatments.

MicroRNA-222 regulates muscle alternative splicing through Rbm24 during differentiation of skeletal muscle cells.

A number of microRNAs have been shown to regulate skeletal muscle development and differentiation. MicroRNA-222 is downregulated during myogenic differentiation and its overexpression leads to alteration of muscle differentiation process and specialized structures. By using RNA-induced silencing complex (RISC) pulldown followed by RNA sequencing, combined with in silico microRNA target prediction, we have identified two new targets of microRNA-222 involved in the regulation of myogenic differentiation, Ahnak and Rbm24. Specifically, the RNA-binding protein Rbm24 is a major regulator of muscle-specific alternative splicing and its downregulation by microRNA-222 results in defective exon inclusion impairing the production of muscle-specific isoforms of Coro6, Fxr1 and NACA transcripts. Reconstitution of normal levels of Rbm24 in cells overexpressing microRNA-222 rescues muscle-specific splicing. In conclusion, we have identified a new function of microRNA-222 leading to alteration of myogenic differentiation at the level of alternative splicing, and we provide evidence that this effect is mediated by Rbm24 protein.

Epidemiology of multiple sclerosis: results from a large observational study in the UK.

Multiple sclerosis (MS) progression to mortality may not be solely determined by the underlying autoimmune process. We conducted a study in a large cohort of MS patients with the aim of describing characteristics of MS patients and identification of predictors for all-cause mortality in this patient group. We performed a retrospective analysis of primary care data from the UK Clinical Practice Research Datalink. Incident MS cases diagnosed between 1993 and 2006 were identified and validated using electronic and original medical records. Patients were followed to identify deaths; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional regression with age as time-scale. In total, 1713 incident MS cases were identified. Following MS diagnosis, frequent comorbidities were infections (80%), and depression (46%). Adjusted HRs (95% CIs) for all-cause mortality were: 2.0 (1.2-3.4) for current smoking; 7.6 (3.2-17.7) for alcohol abuse; 2.7 (1.6-4.5) for pneumonia and influenza; 4.1 (2.7-6.3) for urinary tract infections; 2.2 (1.2-4.2) for heart disease and 4.9 (2.9-8.0) for cancer. Our results suggest that MS survival is influenced not only by the underlying autoimmune process, but also by patient comorbidities and lifestyle factors.

Mortality of patients with multiple sclerosis: a cohort study in UK primary care.

We aimed to estimate rates, causes and risk factors of all-cause mortality in a large population-based cohort of multiple sclerosis (MS) patients compared with patients without MS. Using data from the UK General Practice Research Database, we identified MS cases diagnosed during 2001-2006 and validated using patients' original records where possible. We also included MS cases during 1993-2000 identified and validated in an earlier study. Cases were matched to up to ten referents without MS by age, sex, index date (date of first MS diagnosis for cases and equivalent reference date for controls), general practice and length of medical history before first MS diagnosis. Patients were followed up to identify deaths; hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox-proportional regression. MS patients (N = 1,822) had a significantly increased risk of all-cause mortality compared with referents (N = 18,211); adjusted HR 1.7 (95 % CI 1.4-2.1). Compared with referents, female MS patients had a higher but not significantly different HR for death than males; adjusted HR 1.86 (95 % CI 1.46-2.38) vs. HR 1.31 (95 % CI 0.93-1.84), respectively. The most commonly recorded cause of death in MS patients was 'MS' (41 %), with a higher proportion recorded among younger patients. A significantly higher proportion of referents than MS patients had cancer recorded as cause of death (40 vs. 19 %). Patients with MS have a significant 1.7-fold increased risk of all-cause mortality compared with the general population. MS is the most commonly recorded cause of death among MS patients.

Irreversible work and inner friction in quantum thermodynamic processes.

We discuss the thermodynamics of closed quantum systems driven out of equilibrium by a change in a control parameter and undergoing a unitary process. We compare the work actually done on the system with the one that would be performed along ideal adiabatic and isothermal transformations. The comparison with the latter leads to the introduction of irreversible work, while that with the former leads to the introduction of inner friction. We show that these two quantities can be treated on an equal footing, as both can be linked with the heat exchanged in thermalization processes and both can be expressed as relative entropies. Furthermore, we show that a specific fluctuation relation for the entropy production associated with the inner friction exists, which allows the inner friction to be written in terms of its cumulants.

Core-hole effects in fullerene molecules and small-diameter conducting nanotubes: a density functional theory study.

Core-hole induced electron excitations in fullerene molecules, and small-diameter conducting carbon nanotubes, are studied using density functional theory with minimal, split-valence, and triply-split-valence basis sets plus the generalized gradient approximation by Perdew-Burke-Ernzerhof for exchange and correlation. Finite-size computations are performed on the carbon atoms of a C(60) Bucky ball and a piece of (3, 3) armchair cylindrical network, terminated by hydrogen atoms, while periodically boundary conditions are imposed on a (3, 3) nanotube unit cell. Sudden creation of the core state is simulated by replacing a 1s electron pair, localized at a central site of the structures, with the effective pseudo-potentials of both neutral and ionized atomic carbon. Excited states are obtained from the ground-state (occupied and empty) electronic structure of the ionized systems, and their overlaps with the ground state of the neutral systems are computed. These overlaps enter Fermi's golden rule, which is corrected with lifetime and finite-temperature effects to simulate the many-electron response of the nanoobjects. A model based on the linked cluster expansion of the vacuum persistence amplitude of the neutral systems, in a parametric core-hole perturbation, is developed and found to be reasonably consistent with the density functional theory method. The simulated spectrum of the fullerene molecule is found to be in good agreement with x-ray photoemission experiments on thick C(60) films, reproducing the low energy satellites at excitation energies below 4 eV within a peak position error of ca. 0.3 eV. The nanotube spectra show some common features within the same experiments and describe well the measured x-ray photoelectron lineshape from nanotube bundles with an average diameter of 1.2 nm.

Angiogenesis in hand chondroma: an immunohistochemical study.

Hand chondroma is a particular cartilagineous tumour, being clinically benign, but morphologically malignant. This study investigates the expression of VEGF together with other growth factors and proliferation markers such as TGFß2, Ki-67, TNF, FGF1, P53 in 8 cases of hand chondroma treated with courettage, in order to define the ethiopathogenesis of this tumour and the clinical significance of the resulting immunohistochemical profile, with particular respect to angiogenesis. VEGF was expressed in all cases; 5 cases were positive for TFGß2 and 3 for PDGF. None of the other factors was expressed. On the basis of histologic results a specific model of tumour progression based on the indicators of angiogenesis could be related to hand tumours, in which VEGF expression should be the first stadium of the tumour aggressiveness, and the following PDGF, TGF 2 expression should be accompanied with a morphological outline worsening. Nevertheless the non constant expression of these indicators and the absent expression of proliferated indicators can explain the scant tendency to the relapse in presence of accurate curettage. It is important to remember that the cellular polymorphism typical of the cartilaginous tumours does not allow the application of an only oncogenesis model.

Role of many body shake-up in core-valence-valence electron emission from single wall carbon nanotubes.

Auger core-valence-valence transitions from single wall Carbon nanotubes are studied using a tight-binding calculational scheme with nearest neighbor overlap, hopping interactions, and a double-zeta basis set. The resulting Hamiltonian approximates the unperturbed pi and sigma bands of the nanomaterials coupled with the free electron states outside the solid and the core-hole. As a first step, the Fermi's golden rule is applied to determine the so called one-electron spectrum of emitted electrons from different tubes, in which either the neutralizing or the ejected electrons, in the initial state, lie within nearest neighboring atomic sites to the core-hole. Many-body corrections are effectively modeled using a broadening function, which accounts for dynamic screening effects involving the initial and final states. Particular attention is paid to the asymmetric component of the broadening function, responsible for the shake-up of pi electrons. Finally, the Cini-Sawatzky distortion function is used to describe the final state effect of the hole-hole interaction. A quantitative estimation of the interplay of shake-up processes is proposed by adjusting the asymmetric parameters of the broadening function to reproduce measurements of Auger electrons ejected from bundles of single wall Carbon nanotubes.

Charge transfer in single and multiple scattering events at metal surfaces: a wavepacket study of the Na(+)/Cu(100) system.

Resonant neutralization of hyperthermal energy Na(+) ions impinging on Cu(100) surfaces is studied, focusing on two specific collision events: one in which the projectile is reflected off the surface, the other in which the incident atom penetrates the outer surface layers initiating a series of scattering processes, within the target, and coming out together with a single surface atom. A semi-empirical model potential is adopted that embeds: (i) the electronic structure of the sample, (ii) the central field of the projectile, and (iii) the contribution of the Cu atom ejected in multiple scattering events. The evolution of the ionization orbital of the scattered atom is simulated, backwards in time, using a wavepacket propagation algorithm. The output of the approach is the neutralization probability, obtained by projecting the time-reversed valence wavefunction of the projectile onto the initially filled conduction band states. The results are in agreement with available data from the literature (Keller et al 1995 Phys. Rev. Lett. 75 1654) indicating that the motion of surface atoms, exiting the targets with kinetic energies of the order of a few electronvolts, plays a significant role in the final charge state of projectiles.

Vitamin K and D association stimulates in vitro osteoblast differentiation of fracture site derived human mesenchymal stem cells.

There is growing interest in osteoinductive agents for fracture healing especially in patients with non-union or delayed-union fractures. The aim of the present study is the assessment of the association of Vitamins D3 and K1 on proliferation and differentiation of human mesenchymal stem cells (hMSCs) derived from fracture sites in view of a possible clinical use. The synergic effect of Vitamin D3 and Vitamin K2 in preventing osteoporosis has been documented in clinical practice; however no reports investigating this association for fracture healing are present. Our data show a different outcome on cell proliferation linked to the different timing of drug administration as well as a synergic effect of the two vitamins on cell differentiation. The high level of osteocalcin and carboxylated osteocalcin detected in hMSCs treated with the association of the two vitamins in comparison with controls and with single vitamin administration underline the differentiation of these cells into osteoblastic phenotype. Our results indicate for the first time that vitamin D3 and K1 association is able to modulate in vitro the differentiation towards osteoblastic phenotype of hMSCs derived from fracture sites, thus offering clinicians a promising and low-cost strategy for reparative osteogenesis.

Delineating v-Src downstream effector pathways in transformed myoblasts.

In this study, we delineate the intracellular signalling pathways modulated by a conditional v-Src tyrosine kinase that lead to unrestrained proliferation and block of differentiation of primary avian myoblasts. By inhibiting Ras-MAPK kinase and phosphatidylinositol 3-kinase with different means, we find that both pathways play crucial roles in controlling v-Src-sustained growth factor and anchorage independence for proliferation. The Ras-MAPK kinase pathway also contributes to block of differentiation independently of cell proliferation since inhibition of this pathway both in proliferating and growth-arrested v-Src-transformed myoblasts induces expression of muscle-specific genes, fusion into multinucleated myotubes and assembly of specialized contractile structures. Importantly, we find that the p38 MAPK pathway is inhibited by v-Src in myoblasts and its forced activation results in growth inhibition and expression of differentiation, indicating p38 MAPK as a critical target of v-Src in growth transformation and myogenic differentiation. Furthermore, we show that downregulation of p38 MAPK activation may occur via Ras-MAPK kinase, thus highlighting a cross-regulation between the two pathways. Finally, we report that the simultaneous inhibition of MAPK kinase and calpain, combined to activation of p38 MAPK, are sufficient to reconstitute largely the differentiation potential of v-Src-transformed myoblasts.

A very rare localization of metastatic lung carcinoma to the interosseous membrane.

INTRODUCTION: Soft tissue is a rare localization of carcinoma metastasis. Skeletal muscle is considered the most frequent site. The aim of this paper is to report a very rare localization of soft-tissue metastasis of lung adenocarcinoma in the lower leg interosseous membrane, surgically treated at our department. MATERIALS AND METHODS: A 66-year-old man with a history of lung adenocarcinoma was admitted to our department because he complained of a pain resistant to drugs that had persisted for 1 month. Imaging showed that the lesion was unique, localized in the interosseous membrane, with a distal margin more than 2 cm above the ankle platform. A distal fibula resection, including the tumour and a reconstruction according to Capanna type A2 was performed. RESULTS: At the 6 months follow-up, the patient was walking without external support. CONCLUSION: Surgery is not the treatment of choice for soft-tissue metastases, but it may be recommended when the lesion is unique and inducing a pain resistant to anti-inflammatory drugs.

Acrylic cement added with antiblastics in the treatment of bone metastases. Ultrastructural and in vitro analysis.

An increased long-term survival of patients with alignant tumours also increases the possibility of the development of skeletal metastases and pathological fractures. The management of bone metastases includes the removal of gross disease and the administration of local adjuvants. We have investigated the possibility of adding antiblastic drugs to acrylic cement. Cylinders of acrylic cement were manufactured containing three different antiblastic drugs, methotrexate, cisplatin and doxorubicin. We performed in vitro analysis on MCF-7 human breast cancer cells in order to evaluate the biological effect of the mixtures and surface analysis of the acrylic cement-cisplatin cylinders using energy-dispersive x-ray analysis (EDAX). All drugs were released in an active form from the cement. Each drug had a different effect on cell viability. Doxorubicin had the greatest effect on breast cancer cells. Surface analysis showed that antiblastic drugs were present in the form of granules. These results confirm the potential of antiblastic-loaded cement as a possible adjuvant in the local treatment of bone metastases. Further studies should be undertaken to determine whether the release of antiblastic drugs from cement is elution or if they are only released from the surface.

Osseointegration in hip prostheses: experimental study in sheep.

Sixteen 2- to 3-year-old sheep were submitted to a hemiarthroplasty of the hip joint with a specially designed femoral component. The proximal two thirds of the stem had a circumferential, plasma-sprayed, porous coating with hydroxyapatite. The animals where killed a 15, 30, 60, 90, 120, 180, 200, 270, 360, and 540 days after surgery. Femurs were submitted to plain radiographs, computerised tomography (CT) scan, and dual energy X-ray absorptiometry (DEXA). Cross-sections were obtained at four different levels and studied using scanning electron microscopy. In the coated portion of the stem, apposition of woven immature bone was evident at 15-30 days and mature lamellar bone by 30 days. With time, the gap between the endosteum and the coated surface was filled by bridges of lamellar bone with a marked trabecular orientation. In the distal uncoated portion of the stem, the implant was initially surrounded by fibrous tissue that, with time, transformed into lamellar bone.

Percutaneous elastic fixation of proximal humeral fractures: operative indications, techniques, results and complications.

We present a technique of osteosynthesis of proximal humeral fractures using Kirschner wires, assembled in an elastic manner. We report 29 patients (mean age, 68 years) with types II, III and V fractures, according to Neer's classification, treated with closed or open (seldom) reduction and percutaneous pinning. The pin placement was antegrade: the wires started on the epiphysis and aimed at the diaphysis, with the proximal ends fixed with an external clamp and the distal ends crossed and laying on the endosteal surface. Patients were evaluated with the Constant-Murley scale at the end of treatment. Radiological and clinical outcome was satisfactory in all but one patient, in whom the closed reduction was insufficient. Percutaneous elastic pinning is an effective treatment of proximal humeral fractures. If necessary, it should be associated with open reduction.

N-Acyl-N-phenyl ureas of piperidine and substituted piperidines endowed with anti-inflammatory and anti-proliferative activities.

Six series of N-acyl-N-phenyl ureas 1-6 of piperidine (1), and 2-ethyl- (2), 3-methyl- (3), 4-methyl- (4), 4-phenyl- (5), cis-2,6-dimethyl- (6) piperidine were synthesised and evaluated for their anti-inflammatory, anaesthetic, anti-pyretic properties. Some derivatives of series 1 and 5 were also assayed for anti-proliferative activity. Several compounds showed an anti-inflammatory activity comparable or slighty inferior to that of indomethacin in rats (1c,d, 2a,b,g,h, 3b, 4h, 5d,e). Moreover, an appreciable anti-inflammatory activity was also found in 2c,e, 3e,f,g, 4g, 5a,b,c,f,h, and 6a,b,d. All the compounds were devoid of anti-pyretic activity and only a few of them exhibited a low level of infiltration anaesthesia in mice. Compound 5a showed a broad spectrum anti-cancer activity (at low micromolar concentrations), particulary significant against leukemia subpanel.

Synthesis of new N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-thieno[2,3-h]-1-benzopyran-2-ones.

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-thieno[2,3-h]-1-benzopyran-2-ones (4a-f), by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo[b]thiophen-4(5)-ones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. A moderate local anaesthetic activity was observed in the title compounds, particularly in 4e.