The natural history of multiple osteochondromas in a large Italian cohort of pediatric patients.

Abstract Importance Multiple osteochondromas is a rare hereditary skeletal disorder, characterized by bony protrusions arising from growth plates on long bones during skeletal development. The disorder frequently leads to diminished stature, deformities and functional limitations. Understanding of the natural history of multiple osteochondromas and its evolution in children and adolescents is limited. Objective To provide valuable information on the natural history of multiple osteochondromas, to inform recommendations for treatment and prevent impairments caused by osteochondromas. Design This retrospective cohort study in children with multiple osteochondromas includes longitudinal data collected from first to last follow-up visit for patient demographics, and over 36 months for disease evolution. Setting Data were collected from the Registry of Multiple Osteochondromas, which includes data from circa 1200 patients with multiple osteochondromas treated from 2003 to 2017 at IRCCS Istituto Ortopedico Rizzoli in Bologna. Participants Patients ≤18 years with multiple osteochondromas, who provided written informed consent and had data for ≥1 12-month follow-up visit. Main outcome(s) and measurement(s) Demographics, clinical features, incidence of surgeries, and disease evolution (progression or regression) were assessed. Results were summarized using descriptive statistics, annual rates of new clinical features and surgeries, and Kaplan-Meier estimates. Patient height was evaluated following Italian growth charts. Results 158 patients were included in these analyses. Throughout follow-up, 80.4% of patients developed new osteochondromas, 57.6% developed new deformities, 23.4% developed new functional limitation(s). New osteochondroma(s) were developed by 28.5% patients by Month 12, 39.9% at Month 24, 50% at Month 36. Most new osteochondromas were detected in the younger population; patients aged 0–4 years underwent a significantly higher number of lesions within 12, 24 and 36 months of follow-up. The overall incidence of patients with ≥1 new deformity within 12 months was 17.7%, with incidences decreasing with increasing age (p = .023). In addition, the analyses on height highlight that 13 years is a cut off age for slow growth of the stature (p  Conclusions and relevance This natural history study reports the main set of clinically relevant data for patients with multiple osteochondromas during skeletal development, providing insight for patient management and development of therapeutic interventions

Immunohistochemical evaluation of bone metastases

  Introduction. Metastases are the most common type of malignancy involving the bone, while bone is the third most frequent site for metastases, after the lung and liver. In some patients, medical history, physical and laboratory exami­nation are not conclusive to identify the primary tumor site. In such cases a bone biopsy and immunohistochemical analysis may contribute to the diagnosis, determination of appropriate treatment and evaluation of prognosis. In this study, we tried to evaluate the imunochistochemical expression in bone metastases. Material and methods. We reviewed 125 patients, with a mean age of 63 years, treated for bone metastases in our institution. All patients received palliative orthopaedic surgery for bone metastatic carcinoma. Fifty-eight patients had already an established diagnosis of the primary tumor, while 67 patients presented metastases with an unknown primary tumor origin. Immunohistochemical analysis was performed to intra-operative bone biopsy specimens. The expression of cytokeratine 7, cytokeratin 20 and the expression of a panel of other organ-specific markers were re­corded. In patients with a known primary tumor, we examined the relationship between the origin of metastases, as suggested by the cytokeratin phenotype, compared with the one indicated by the initial histological diagnosis. We also recorded the efficacy of organ-specific markers to identify the primary tumor origin in epithelial bone metastases and we evaluated the prognosis between patients with a immunohistologically determined primary tumor origin, with those with an undetermined one. Results. Associations of cytokeratine 7 and cytokeratine 20 expression confirmed diagnosis in 51 out of the 58 patients (88%) with a known primary tumor (Cohen’s K test 0.79 SE 0.80, P < 0.0005). Immunohistochemical analysis also contributed to establish the diagnosis of patients with an unknown primary tumor, yielding diagnosis in 35 out of the 67 cases (52%). Patients with an immunochistologically undetermined primary tumor site presented a statisti­cally significant poorer prognosis. Conclusions. Cytokeratine 7 and cytokeratine20 are useful immunochistochemical markers in determining a pre­liminary evaluation of bone metastases. Organ-specific immunohistochemical markers have a reliable role in either suggesting or confirming the possible origin of metastases. An indeterminate immunohistochemical phenotype seems to relate to a less differentiated lesion, with a worse prognosis

Ultrathin random copolymer-grafted layers for block copolymer self-assembly

Hydroxyl-terminated P(S-r-MMA) random copolymers (RCPs) with molecular weights (Mn) from 1700 to 69000 and a styrene unit fraction of approximately 61% were grafted onto a silicon oxide surface and subsequently used to study the orientation of nanodomains with respect to the substrate, in cylinder-forming PS-b-PMMA block copolymer (BCP) thin films. When the thickness (H) of the grafted layer is greater than 5-6 nm, a perpendicular orientation is always observed because of the efficient decoupling of the BCP film from the polar SiO2 surface. Conversely, if H is less than 5 nm, the critical thickness of the grafted layer, which allows the neutralization of the substrate and promotion of the perpendicular orientation of the nanodomains in the BCP film, is found to depend on the Mn of the RCP. In particular, when Mn = 1700, a 2.0 nm thick grafted layer is sufficient to promote the perpendicular orientation of the PMMA cylinders in the PS-b-PMMA BCP film. A proximity shielding mechanism of the BCP molecules from the polar substrate surface, driven by chain stretching of the grafted RCP molecules, is proposed

Immunohistochemical evaluation of bone metastases

  Introduction. Metastases are the most common type of malignancy involving the bone, while bone is the third most frequent site for metastases, after the lung and liver. In some patients, previous medical history, physical and laboratory examination are not conclusive to identify the primary tumor site. In such cases a bone biopsy and im­munohistochemical analysis may contribute to the diagnosis, determination of appropriate treatment and evaluation of prognosis. In this study, we tried to evaluate the imunochistochemical expression in bone metastases. Material and methods. We reviewed 125 patients, with a mean age of 63 years, treated for bone metastases in our institution. All patients received palliative orthopaedic surgery for bone metastatic carcinoma. Fifty-eight patients had already an established diagnosis of the primary tumor, while 67 patients presented metastases with an unknown primary tumor origin. Immunohistochemical analysis was performed to intra-operative bone biopsy specimens. The expression of cytokeratine 7, cytokeratin 20 and the expression of a panel of other organ-specific markers were re­corded. In patients with a known primary tumor, we examined the relationship between the origin of metastases, as suggested by the cytokeratin phenotype, compared with the one indicated by the initial histological diagnosis. We also recorded the efficacy of organ-specific markers to identify the primary tumor origin in epithelial bone metastases and we evaluated the prognosis between patients with a immunohistologically determined primary tumor origin, with those with an undetermined one. Results. Associations of cytokeratine 7 and cytokeratine 20 expression confirmed diagnosis in 51 out of the 58 patients (88%) with a known primary tumor (Cohen’s K test 0.79 SE 0.80, P < 0.0005). Immunohistochemical analysis also contributed to establish the diagnosis of patients with an unknown primary tumor, yielding diagnosis in 35 out of the 67 cases (52%). Patients with an immunochistologically undetermined primary tumor site presented a statisti­cally significant poorer prognosis. Conclusions. Cytokeratine 7 and cytokeratine20 are useful immunochistochemical markers in determining a pre­liminary evaluation of bone metastases. Organ-specific immunohistochemical markers have a reliable role in either suggesting or confirming the possible origin of metastases. An indeterminate immunohistochemical phenotype seems to relate to a less differentiated lesion, with a worse prognosis. Introduction. Metastases are the most common type of malignancy involving the bone, while bone is the third most frequent site for metastases, after the lung and liver. In some patients, previous medical history, physical and laboratory examination are not conclusive to identify the primary tumor site. In such cases a bone biopsy and im­munohistochemical analysis may contribute to the diagnosis, determination of appropriate treatment and evaluation of prognosis. In this study, we tried to evaluate the imunochistochemical expression in bone metastases. Material and methods. We reviewed 125 patients, with a mean age of 63 years, treated for bone metastases in our institution. All patients received palliative orthopaedic surgery for bone metastatic carcinoma. Fifty-eight patients had already an established diagnosis of the primary tumor, while 67 patients presented metastases with an unknown primary tumor origin. Immunohistochemical analysis was performed to intra-operative bone biopsy specimens. The expression of cytokeratine 7, cytokeratin 20 and the expression of a panel of other organ-specific markers were re­corded. In patients with a known primary tumor, we examined the relationship between the origin of metastases, as suggested by the cytokeratin phenotype, compared with the one indicated by the initial histological diagnosis. We also recorded the efficacy of organ-specific markers to identify the primary tumor origin in epithelial bone metastases and we evaluated the prognosis between patients with a immunohistologically determined primary tumor origin, with those with an undetermined one. Results. Associations of cytokeratine 7 and cytokeratine 20 expression confirmed diagnosis in 51 out of the 58 patients (88%) with a known primary tumor (Cohen’s K test 0.79 SE 0.80, P < 0.0005). Immunohistochemical analysis also contributed to establish the diagnosis of patients with an unknown primary tumor, yielding diagnosis in 35 out of the 67 cases (52%). Patients with an immunochistologically undetermined primary tumor site presented a statisti­cally significant poorer prognosis. Conclusions. Cytokeratine 7 and cytokeratine20 are useful immunochistochemical markers in determining a pre­liminary evaluation of bone metastases. Organ-specific immunohistochemical markers have a reliable role in either suggesting or confirming the possible origin of metastases. An indeterminate immunohistochemical phenotype seems to relate to a less differentiated lesion, with a worse prognosis

Virtual Surgical Planning, 3D-Printing and Customized Bone Allograft for Acute Correction of Severe Genu Varum in Children

Complex deformities of lower limbs are frequent in children with genetic or metabolic skeletal disorders. Early correction is frequently required, but it is technically difficult and burdened by complications and recurrence. Herein, we described the case of a 7-year-old girl affected by severe bilateral genu varum due to spondyloepiphyseal dysplasia. The patient was treated by patient-specific osteotomies and customized structural wedge allograft using Virtual Surgical Planning (VSP) and 3D-printed patient-specific instrumentation (PSI). The entire process was performed through an in-hospital 3D-printing Point-of-Care (POC). VSP and 3D-printing applied to pediatric orthopedic surgery may allow personalization of corrective osteotomies and customization of structural allografts by using low-cost in-hospital POC. However, optimal and definitive alignment is rarely achieved in such severe deformities in growing skeleton through a single operation

Hospital discharge in patients at risk of surgical site infection: antimicrobial stewardship at Ferrara University Hospital, Italy.

Introduction. The appropriate use of antibiotics is a global priority in order to avoid antibiotic resistance. Up to 50% of antibiotics usage in hospital is inappropriate (e.g. prolonged surgical prophylaxis, “defensive medicine” approach).In 2015, at the Ferrara University Hospital, an antimicrobial stewardship intervention to reduce antimicrobial prescription at the time of hospital discharge in patients at risk of surgical site infection was implemented. This programme included: update meetings for health professionals, focused meetings for critical wards, reviews of some surgical prophylaxis protocols, recommendations to reduce broad-spectrum antimicrobials use, and planning of an audit. The purpose of this study has been to evaluate the effect of this antimicrobial stewardship programme.Methods. To evaluate the effect of this intervention, a study has been carried out including inpatients in surveillance for surgical site infection who had surgery during the last quarter of 2014 (pre-intervention group; 461 patients) and of 2015 (post-intervention group; 532 patients).Results. The proportion of patients with prescription of at least one antimicrobial at discharge decreased from 33% to 24.4% (p=0.002). The most prescribed categories of antimicrobials in both groups were the combination of penicillins with beta-lactamase inhibitors (with prescription rate reduced from 21.9% to 18%; p=0.13) and fluoroquinolones (from 8.2% to 3.2%; p<0.001). Conclusions. This statistically significant reduction in antimicrobial prescription after the intervention was registered without a change in surgical site infections rate (from 3.5% to 3.2%; p=0.08). Therefore, this intervention was effective in reducing the antimicrobial prescription at discharge, without affecting patients' safety

Films made from poly(vinyl alcohol-co-ethylene) and soluble biopolymers isolated from postharvest tomato plant

Blended films were obtained from polyvinyl alcohol‐co‐ethylene (EVOH) with 52 kDa weight average molecular weight (Mw) and three water soluble biopolymers isolated from exhausted tomato plants hydrolysates. Two biopolymers contained mainly polysaccharides and had 27 and 79 kDa Mw, respectively. The third contained mainly lignin‐like C moieties and had 392 kDa MW. The films were fabricated with a biopolymer/EVOH w/w ratio ranging from 0.1 to 0.9. All blends had molecular weight and solubility which were substantially different from the starting materials. They were characterized for the chemical nature, and the thermal, rheological, and mechanical properties. Evidence of a chemical reaction between the biopolymers and EVOH was found. Generally, the films exhibited higher mechanical strength but lower strain at break then the neat EVOH. The best performing blended film was fabricated from the 27 kDa Mw polysaccharide. This contained less than 10% biopolymer. It exhibited 1043 MPa Young's modulus and 70% strain at break against 351 MPa modulus and 86% strain for neat EVOH. The results offer scope for investigating biopolymers sourced from other biowastes to understand more the reasons of the observed effects and exploit their full potential to modify or to replace synthetic polymers

gSeaGen: The KM3NeT GENIE-based code for neutrino telescopes

Program summary Program Title: gSeaGen CPC Library link to program files: http://dx.doi.org/10.17632/ymgxvy2br4.1 Licensing provisions: GPLv3 Programming language: C++ External routines/libraries: GENIE [1] and its external dependencies. Linkable to MUSIC [2] and PROPOSAL [3]. Nature of problem: Development of a code to generate detectable events in neutrino telescopes, using modern and maintained neutrino interaction simulation libraries which include the state-of-the-art physics models. The default application is the simulation of neutrino interactions within KM3NeT [4]. Solution method: Neutrino interactions are simulated using GENIE, a modern framework for Monte Carlo event generators. The GENIE framework, used by nearly all modern neutrino experiments, is considered as a reference code within the neutrino community. Additional comments including restrictions and unusual features: The code was tested with GENIE version 2.12.10 and it is linkable with release series 3. Presently valid up to 5 TeV. This limitation is not intrinsic to the code but due to the present GENIE valid energy range. References: [1] C. Andreopoulos at al., Nucl. Instrum. Meth. A614 (2010) 87. [2] P. Antonioli et al., Astropart. Phys. 7 (1997) 357. [3] J. H. Koehne et al., Comput. Phys. Commun. 184 (2013) 2070. [4] S. Adrián-Martínez et al., J. Phys. G: Nucl. Part. Phys. 43 (2016) 084001.The gSeaGen code is a GENIE-based application developed to efficiently generate high statistics samples of events, induced by neutrino interactions, detectable in a neutrino telescope. The gSeaGen code is able to generate events induced by all neutrino flavours, considering topological differences between tracktype and shower-like events. Neutrino interactions are simulated taking into account the density and the composition of the media surrounding the detector. The main features of gSeaGen are presented together with some examples of its application within the KM3NeT project.French National Research Agency (ANR) ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS)European Union (EU)Institut Universitaire de France (IUF), FranceIdEx program, FranceUnivEarthS Labex program at Sorbonne Paris Cite ANR-10-LABX-0023 ANR-11-IDEX-000502Paris Ile-de-France Region, FranceShota Rustaveli National Science Foundation of Georgia (SRNSFG), Georgia FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Universities and Research (MIUR)PRIN 2017 program Italy NAT-NET 2017W4HA7SMinistry of Higher Education, Scientific Research and Professional Training, MoroccoNetherlands Organization for Scientific Research (NWO) Netherlands GovernmentNational Science Centre, Poland 2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento, Spain (MCIU/FEDER) PGC2018-096663-B-C41 PGC2018-096663-A-C42 PGC2018-096663-BC43 PGC2018-096663-B-C44Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia, Spain SOMM17/6104/UGRGeneralitat Valenciana: Grisolia, Spain GRISOLIA/2018/119GenT, Spain CIDEGENT/2018/034La Caixa Foundation LCF/BQ/IN17/11620019EU: MSC program, Spain 71367