Predicting early recurrence after resection of initially unresectable colorectal liver metastases: the role of baseline and pre-surgery clinical, radiological and molecular factors in a real-life multicentre experience.

BACKGROUND: Advances in surgical techniques and systemic treatments have increased the likelihood of achieving radical surgery and long-term survival in metastatic colorectal cancer (mCRC) patients with initially unresectable colorectal liver metastases (CRLMs). Nonetheless, roughly half of the patients resected after an upfront systemic therapy experience disease relapse within 6 months from surgery, thus leading to the question whether surgery is actually beneficial for these patients. MATERIALS AND METHODS: A real-world dataset of mCRC patients with initially unresectable liver-limited disease treated with conversion chemotherapy followed by radical resection of CRLMs at three high-volume Italian institutions was retrospectively assessed with the aim of investigating the association of baseline and pre-surgical clinical, radiological and molecular factors with the risk of relapse within 6 or 12 months from surgery. RESULTS: Overall, 268 patients were included in the analysis and 207 (77%) experienced recurrence. Ninety-six (46%) of them had disease relapse within 6 months after CRLM resection and in spite of several variables associated with early recurrence at univariate analyses, only primary tumour resection at diagnosis [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.89, P = 0.02] remained significant in the multivariable model. Among patients with resected primary tumours, pN+ stage was associated with higher risk of disease relapse within 6 months (OR 3.02, 95% CI 1.23-7.41, P = 0.02). One hundred and forty-nine patients (72%) had disease relapse within 12 months after CRLMs resection but none of the analysed variables was independently associated with outcome. CONCLUSIONS: Clinical, radiological and molecular factors assessed before and after conversion chemotherapy do not reliably predict early recurrence after secondary resection of initially unresectable CRLMs. While novel markers are needed to optimize the cost/efficacy balance of surgical procedures, CRLM resection should be offered as soon as metastases become resectable during first-line chemotherapy to all patients eligible for surgery.

Red blood cell derived extracellular vesicles during the process of autologous blood doping.

The purpose of this pilot study was to investigate the effects of the transfusion of one erythrocyte concentrate on the number of circulating red blood cell extracellular vesicles (RBC-EVs) and their clearance time. Six, healthy volunteers donated their blood and were transfused with their RBC concentrate after 35-36 days of storage. One K2 EDTA and one serum sample were collected before donation, at four timepoints after donation and at another six timepoints after transfusion. RBC-EVs were analyzed on a Cytek Aurora flow cytometer. A highly significant increase (p < 0.001) of RBC-EVs from an average of 60.1 ± 19.8 (103 /µL) at baseline to 179.3 ± 84.7 (103 /µL) in the first 1-3 h after transfusion could be observed. Individual differences in the response to transfusion became apparent with one volunteer showing no increase and another an increased concentration at one timepoint after donation due to an influenza infection. We concluded that in an individualized passport approach, increased RBC-EVs might be considered as additional evidence when interpreting suspicious Athletes Biological Passport (ABPs) but for this additional research related to sample collection and transport processes as well as method development and harmonization would be necessary.

Coral reef fishes reveal strong divergence in the prevalence of traits along the global diversity gradient.

Coral reefs are experiencing declines due to climate change and local human impacts. While at a local scale these impacts induce biodiversity loss and shifts in community structure, previous biogeographical analyses recorded consistent taxonomic structure of fish communities across global coral reefs. This suggests that regional communities represent a random subset of the global species and traits pool, whatever their species richness. Using distributional data on 3586 fish species and latest advances in species distribution models, we show marked gradients in the prevalence of size classes and diet categories across the biodiversity gradient. This divergence in trait structure is best explained by reef isolation during past unfavourable climatic conditions, with large and piscivore fishes better represented in isolated areas. These results suggest the risk of a global community re-organization if the ongoing climate-induced reef fragmentation is not halted.

Engineering atomic-scale magnetic fields by dysprosium single atom magnets.

Atomic scale engineering of magnetic fields is a key ingredient for miniaturizing quantum devices and precision control of quantum systems. This requires a unique combination of magnetic stability and spin-manipulation capabilities. Surface-supported single atom magnets offer such possibilities, where long temporal and thermal stability of the magnetic states can be achieved by maximizing the magnet/ic anisotropy energy (MAE) and by minimizing quantum tunnelling of the magnetization. Here, we show that dysprosium (Dy) atoms on magnesium oxide (MgO) have a giant MAE of 250 meV, currently the highest among all surface spins. Using a variety of scanning tunnelling microscopy (STM) techniques including single atom electron spin resonance (ESR), we confirm no spontaneous spin-switching in Dy over days at ≈ 1 K under low and even vanishing magnetic field. We utilize these robust Dy single atom magnets to engineer magnetic nanostructures, demonstrating unique control of magnetic fields with atomic scale tunability.

Unconventional Spin Relaxation Involving Localized Vibrational Modes in Ho Single-Atom Magnets.

We investigate the spin relaxation of Ho single atom magnets on MgO/Ag(100) as a function of temperature and magnetic field. We find that the spin relaxation is thermally activated at low field, while it remains larger than 1000 s up to 30 K and 8 T. This behavior contrasts with that of single molecule magnets and bulk paramagnetic impurities, which relax faster at high field. Combining our results with density functional theory, we rationalize this unconventional behavior by showing that local vibrations activate a two-phonon Raman process with a relaxation rate that peaks near zero field and is suppressed at high field. Our work shows the importance of these excitations in the relaxation of axially coordinated magnetic atoms.

Spin Excitations in a 4f-3d Heterodimer on MgO.

We report on the magnetic properties of HoCo dimers as a model system for the smallest intermetallic compound of a lanthanide and a transition metal atom. The dimers are adsorbed on ultrathin MgO(100) films grown on Ag(100). New for 4f elements, we detect inelastic excitations with scanning tunneling spectroscopy and prove their magnetic origin by applying an external magnetic field. In combination with density functional theory and spin Hamiltonian analysis, we determine the magnetic level distribution, as well as sign and magnitude of the exchange interaction between the two atoms. In contrast to typical 4f-3d bulk compounds, we find ferromagnetic coupling in the dimer.

Treatment options of simple bone cysts: the role of bone substitutes, growth factors and literature review.

The solitary bone cyst is a typical tumor-like lesion of the immature skeleton, whose etio-pathogenesis is still unclear. The purpose of this work is to perform a review of the literature about the different surgical approaches focusing on the role of bone substitutes and growth factors. Literature analysis shows injection techniques of substances such as methylprednisolone, autologous bone marrow, demineralized bone matrix, calcium sulphate and surgical techniques that involve the resection and curettage associated with bone graft and/or intramedullary nailing. Although there are good results currently associated to these techniques and the different ways of treatment, the only evidence-based treatment is given by injections of steroids. However, given the high rate of failure, autologous bone marrow and platelet gel represent a viable therapeutic option.

Silver-Coated Hip Megaprosthesis in Oncological Limb Savage Surgery.

Silver coating has demonstrated good antimicrobial activity and low toxicity. Silver-coated megaprostheses have been introduced in oncological musculoskeletal surgery considering the high rate of infection. We conducted a retrospective analysis on 68 cases of primary or metastatic bone tumors, affecting the proximal femur, treated between 2005 and 2016 with wide margins resection and tumor implants reconstruction. All patients were treated by the same surgeon, with antibiotic prophylaxis according to a standard protocol. In 55.9% of patients silver-coated hip hemiarthroplasty was implanted; in the remaining 44.1% uncoated megaprostheses were implanted. Patients were reevaluated recording the complications and focusing the analysis on infective complications. The average follow-up was 46.5 months. No patient has shown any sign of local or general silver toxicity. A SEM analysis was conducted on the 3-silver-coated hip hemiarthroplasty explanted confirming a severe degradation with a small amount of residual silver on the coating surface. Silver-coated hip prostheses have a lower rate of early infection than traditional implants but showed a reduction of antimicrobial activity for silver coating wear. We recommend using silver-coated prosthesis as primary implants for limb salvage surgery, in primary or metastatic bone tumors affecting the proximal femur, considering the absence of signs of toxicity and the lower rate of early infection.

Magnetic remanence in single atoms.

A permanent magnet retains a substantial fraction of its saturation magnetization in the absence of an external magnetic field. Realizing magnetic remanence in a single atom allows for storing and processing information in the smallest unit of matter. We show that individual holmium (Ho) atoms adsorbed on ultrathin MgO(100) layers on Ag(100) exhibit magnetic remanence up to a temperature of 30 kelvin and a relaxation time of 1500 seconds at 10 kelvin. This extraordinary stability is achieved by the realization of a symmetry-protected magnetic ground state and by decoupling the Ho spin from the underlying metal by a tunnel barrier.

Fibular nerve palsy after hip replacement: Not only surgeon responsibility. Hereditary neuropathy with liability to pressure palsies (HNPP) a rare cause of nerve liability.

Mononeuropathy after surgery may occur and hereditary neuropathy with liability to pressure palsies is a possible pathological condition related to paresis after hip surgery. We present a case of 66-year-old man presenting severe weakness at inferior limb muscles after hip prosthesis revision. Clinic and electrophysiology showed severe right fibular nerve damage and ultrasound found a marked enlargement of the same nerve, associated with focal enlargements in other nerves. A diagnosis of hereditary neuropathy with liability to pressure palsies was suspected and confirmed by genetic test. The patient gradually recovered returning to a normal daily active life. Ultrasound was crucial for diagnosis. The suspicion and diagnosis of latent neuropathy, which can occur after surgical intervention, may lead to a better understand of the risks of the surgery, specific for the patient, and avoid the wrong attribution to surgical malpractice.

SILVER COATED PROSTHESIS IN ONCOLOGICAL LIMB SALVAGE SURGERY REDUCE THE INFECTION RATE.

Silver coatings, used in many surgical devices, have demonstrated good antimicrobial activity and low toxicity. Oncological musculoskeletal surgery have a high risk of infection, so in the last decades, silver-coated mega-prostheses have been introduced and are becoming increasingly widespread. In this study, a retrospective analysis of 158 cases of bone tumors, primary or metastatic, treated between 2005- 2015 with wide margins resection and tumor implants reconstruction, was performed. The average age was 59 years (range 11-78 years), the same surgeon with antibiotic prophylaxis according to a standard protocol treated all patients. Silver-coated prostheses were implanted in 58.5% of patients and uncoated tumor prostheses in the remaining 41.5%. Patients were re-evaluated annually and complications were recorded, focusing analysis on infective complications. The average follow-up was 39.7 months: 23.4% of patients died at a median time of 35.3 months after surgery; 18.4% developed complications that required new surgery, of which 12.6% of these were due to infection. Patients treated with silver-coated implants developed early infection in 2.2% of cases against the 10.7% of the patients treated with standard tumor prosthesis. This difference between the two groups was statistically significant. The percentage of late infections occurring from 6 months after surgery was similar in both groups. Silver blood level taken in a sample of patients at different times after surgery, always showed values well below the threshold of toxicity and no patient showed any sign of local or general toxicity secondary to silver. Our study demonstrates that tumor silver-coated implants have a rate of early infection significantly lower than traditional implants, while there were no differences in the rate of late infections as described also in the literature. We recommend the use of silver–coated prosthesis as primary implants for limb salvage surgery in primary or metastatic bone tumors, considering the absence of toxicity and the lower rate of early infection.

Origin of Perpendicular Magnetic Anisotropy and Large Orbital Moment in Fe Atoms on MgO.

We report on the magnetic properties of individual Fe atoms deposited on MgO(100) thin films probed by x-ray magnetic circular dichroism and scanning tunneling spectroscopy. We show that the Fe atoms have strong perpendicular magnetic anisotropy with a zero-field splitting of 14.0±0.3 meV/atom. This is a factor of 10 larger than the interface anisotropy of epitaxial Fe layers on MgO and the largest value reported for Fe atoms adsorbed on surfaces. The interplay between the ligand field at the O adsorption sites and spin-orbit coupling is analyzed by density functional theory and multiplet calculations, providing a comprehensive model of the magnetic properties of Fe atoms in a low-symmetry bonding environment.

Human hepatoma cell lines on gas foaming templated alginate scaffolds for in vitro drug-drug interaction and metabolism studies.

Liver in vitro systems that allow reliable prediction of major human in vivo metabolic pathways have a significant impact in drug screening and drug metabolism research. In the present study, a novel porous scaffold composed of alginate was prepared by employing a gas-in-liquid foaming approach. Galactose residues were introduced on scaffold surfaces to promote cell adhesion and to enhance liver specific functions of the entrapped HepG2/C3A cells. Hepatoma cells in the gal-alginate scaffold showed higher levels of liver specific products (albumin and urea) and were more responsive to specific inducers (e.g. dexamethasone) and inhibitors (e.g. ketoconazole) of the CYP3A4 system than in conventional monolayer culture. HepG2/C3A cells were also more efficient in terms of rapid elimination of testosterone, used as a model substance, at rates comparable to those of in vivo excretion. In addition, an improvement in metabolism of testosterone, in terms of phase II metabolite formation, was also observed when the more differentiated HepaRG cells were used. Together the data suggest that hepatocyte/gas templated alginate-systems provide an innovative high throughput platform for in vitro drug metabolism and drug-drug interaction studies, with broad fields of application, and might provide a valid tool for minimizing animal use in preclinical testing of human relevance.

Controlling the spin of co atoms on pt(111) by hydrogen adsorption.

We investigate the effect of H adsorption on the magnetic properties of individual Co atoms on Pt(111) with scanning tunneling microscopy. For pristine Co atoms, we detect no inelastic features in the tunnel spectra. Conversely, CoH and CoH2 show a number of low-energy vibrational features in their differential conductance identified by isotope substitution. Only the fcc-adsorbed species present conductance steps of magnetic origin, with a field splitting identifying their effective spin as Seff=2 for CoH and 3/2 for CoH2. The exposure to H2 and desorption through tunnel electrons allow the reversible control of the spin in half-integer steps. Because of the presence of the surface, the hydrogen-induced spin increase is opposite to the spin sequence of CoHn molecules in the gas phase.

Magnetism of Ho and Er atoms on close-packed metal surfaces.

We investigated the magnetic properties of individual Ho atoms adsorbed on the (111) surface of Pt, which have been recently claimed to display single ion magnetic behavior. By combining x-ray absorption spectroscopy and magnetic dichroism measurements with ligand field multiplet calculations, we reveal a ground state which is incompatible with long spin relaxation times, in disagreement with former findings. A comparative study of the ground state and magnetic anisotropy of Ho and Er on Pt(111) and Cu(111) emphasizes the different interaction of the 4f orbitals with localized and delocalized substrate states. In particular, we find a striking rotation of the magnetization easy axis for Er, which changes from out of plane on Pt(111) to in plane on Cu(111).

Tailoring the magnetism of Co atoms on graphene through substrate hybridization.

We determine the magnetic properties of individual Co atoms adsorbed on graphene (G) with x-ray absorption spectroscopy and magnetic circular dichroism. The magnetic ground state of Co adatoms strongly depends on the choice of the metal substrate on which graphene is grown. Cobalt atoms on G/Ru(0001) feature exceptionally large orbital and spin moments, as well as an out-of-plane easy axis with large magnetic anisotropy. Conversely, the magnetic moments are strongly reduced for Co/G/Ir(111), and the magnetization is of the easy-plane type. We demonstrate how the Co magnetic properties, which ultimately depend on the degree of hybridization between the Co 3d orbitals and graphene π bands, can be tailored through the strength of the graphene-substrate coupling.

Magnetic moment and anisotropy of individual Co atoms on graphene.

We report on the magnetic properties of single Co atoms on graphene on Pt(111). By means of scanning tunneling microscopy spin-excitation spectroscopy, we infer a magnetic anisotropy of K=-8.1 meV with out-of-plane hard axis and a magnetic moment of 2.2µ(B). Co adsorbs on the sixfold graphene hollow site. Upon hydrogen adsorption, three differently hydrogenated species are identified. Their magnetic properties are very different from those of clean Co. Ab initio calculations support our results and reveal that the large magnetic anisotropy stems from strong ligand field effects due to the interaction between Co and graphene orbitals.