Use of Radium-223 Dichloride in Patients With Osteonecrosis of the Jaw Induced by Zoledronic Acid: Report of 2 Cases.

Bisphosphonates, a group of inorganic pyrophosphate analogues that prevent the loss of bone density, are commonly used in patients with bone metastases; the calcium-mimetic a-emitter radium-223 dichloride (Ra223) is a bone-targeting therapy used in patients with metastatic castration-resistant prostate cancer (mCRPC)-related bone metastases. Both treatments reduce pain and disability; Ra223 is associated with significantly improved overall survival in mCRPC. Patients who receive bisphosphonate therapy are at risk of developing osteonecrosis of the jaw, especially in those who do not undergo an accurate oral evaluation and sanitation before the beginning of therapy, and in patients who present with conditions that facilitate the development of this problem, such as inadequate oral and dental care, lack of prophylactic antimicrobial mouth rinsing, patient comorbidity, or suboptimal suturing after tooth extraction. Although there is possible synergism between bisphosphonates and Ra223 therapy, there is no consensus about the use of Ra223 in patients with previous/current osteonecrosis of the jaw induced by zoledronic acid. However, our experience suggests that Ra223 therapy might not be contraindicated in patients with osteonecrosis of the jaw induced by zoledronic acid if an appropriate multidisciplinary approach is followed, and we report 2 cases of patients with current or previous osteonecrosis of the jaw induced by zoledronic acid, who were treated with Ra223 for mCRPCrelated bone metastases. Multidisciplinary management, including accurate clinical and radiological evaluation before beginning therapy with Ra223, together with oral sanitation and periodic controls during treatment, allowed successful administration of Ra223 while reducing side effects, with absent or minimal worsening of osteonecrosis

Alginate Lyases and Fucanases from Uncultured Microorganisms of Coastal Sediments of Southern Patagonia

Fucoidans and alginates, major polysaccharides of the brown algae cell matrix, have various biological properties. Their high molecular weight hinder some biomedical applications, but this limitation can be overcome through enzymatic degradation to obtain bioactive oligosaccharides. The goal of this work was to identify and characterize fucanases and alginate lyases from uncultured marine bacteria, related to poorly characterized CAZy families (GH107, GH168 and PL38). Using a series of HMMs specific for these families, homologous sequences were identified in a metagenomic dataset from intertidal sediments of Ushuaia Bay (Tierra del Fuego Island, Argentina), a Subantarctic environment with high brown algae biomass. Seven sequences related to the GH107 family (9-40 % protein identity with members of the family) and 21 sequences related to the GH168 family (9 a 80 % identity) were identified in the dataset. In addition, 16 sequences were related to members of the PL38 family. Most members of this family contain a PF05426 (Alginate Lyase) domain, but the only biochemically characterized enzyme is a glucuronan lyase with negligible alginate lyase activity. Putative PL38 sequences showed 30-71 % identity with members of the family. Based on in silico analyses, we selected four sequences related to the GH107 family and two related to the PL38 family for heterologous expression. Fucanase activity was evaluated by carbohydrate polyacrylamide gel electrophoresis (C-PAGE), with four substrates from different species of brown algae. One of the expressed proteins, #113643 (probably from a Planctomycetes), showed the highest level of expression, and the addition of the purified enzyme resulted in the degradation of fucoidans faster than previously characterized members of the GH107 family, in the substrate purified from Macrocystis pyrifera. The enzyme was active at low temperatures (5 - 45 °C), and in a wide range of salinity concentrations (9.5 - 861 mM NaCl) and pH values (4.5 - 9). Alginate lyase activity was measured by following the increase in Abs235nm. Proteins #216008 (Gammaproteobacteria) and #149193 (Bacteroidetes) also showed high expression levels and both enzymes displayed alginate lyase activity, adding a new activity to the PL38 family. This study increases the current knowledge on fucoidan and alginate degradation potential in microbial communities from Subantarctic sediments, and describes novel enzymes from bacteria of an extreme environment for brown algae biomass utilization. JG and CM contributed equally to the work.Fil: Gonzalez, Jessica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Molina, Celeste Amancay Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Musumeci, Matias Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Entre Ríos. Universidad Nacional de Entre Ríos. Centro de Investigaciones y Transferencia de Entre Ríos; ArgentinaFil: Lozada, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; ArgentinaFil: Ponce, Nora Marta Andrea. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Subsede del Centro de Investigaciones en Hidratos de Carbono | Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono. Subsede del Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Stortz, Carlos Arturo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Subsede del Centro de Investigaciones en Hidratos de Carbono | Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono. Subsede del Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Dionisi, Hebe Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaWorld Microbe ForumWashingtonEstados UnidosAmerican Society for MicrobiologyFederation of European Microbiological Societie

Diagnosis, treatment, and follow-up of a case of Wolman disease with hemophagocytic lymphohistiocytosis

: Wolman Disease (WD) is a severe multi-system metabolic disease due to lysosomal acid lipase (LAL) deficiency. We report on a WD infant who developed an unusual hemophagocytic lymphohistiocytosis (HLH) phenotype related to WD treated with sebelipase alfa. A male baby came to our attention at six months of life for respiratory insufficiency and sepsis, abdominal distension, severe hepatosplenomegaly, diarrhea, and severe growth retardation. HLH was diagnosed and treated with intravenous immunoglobulin, steroids, cyclosporine, broad-spectrum antimicrobial therapy, and finally with the anti-IL-6 drug tocilizumab. WD was suspected for the presence of adrenal calcifications and it was confirmed by LAL enzyme activity and by molecular analysis of LIPA. Plasma oxysterols cholestan-3β,5α,6β-triol (C-triol), and 7-ketocholesterol (7-KC) were markedly increased. Sebelipase alfa was started with progressive amelioration of biochemical and clinical features. The child died from sepsis, 2 months after sebelipase discontinuation requested by parents. Our case shows the importance of an early diagnosis of WD and confirms the difficulty to reach a diagnosis in the HLH phenotype. Sebelipase alpha is an effective treatment for LAL deficiency, also in children affected by WD. Further data are necessary to confirm the utility of measuring plasma c-triol as a biochemical marker of the disease

Children with special health care needs attending emergency department in Italy: analysis of 3479 cases

Background: Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient's demographic data, clinical history, and health services requirements. Methods: Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals. Results: Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as 'urgent', with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs. Conclusions: Access of CSHCN to an ED is not infrequent. For this reason, it is fundamental for pediatricians working in any kind of ED to increase their general knowledge about CHSCN and to gain expertise in the management of such patients and their related medical complexity

Validation of the 3-variable prognostic score (3-PS) in mCRPC patients treated with 223 Radium-dichloride: a national multicenter study

Objective: Radium-223 (223Ra) has been approved for treatment in patients with metastatic castration-resistant prostatic cancer (mCRPC) and bone metastasis. This α-emitting radionuclide has a beneficial effect on pain and is also capable to increase overall survival (OS). Several studies evaluated the prognostic value of different biomarkers at baseline, such as serum values, imaging parameters or pain. To date, however, clinicians lack a validated and simple system to assess which patients will most likely benefit from 223Ra treatment. The 3-variable prognostic score (3-PS), proposed in a single-center study in 2017 classifies patients in five prognostic groups with a specific OS. This study aims to validate the 3-PS in a larger multicenter population. Methods: Four hundred and thirty mCRPC patients treated with 223Ra from six different centers were analyzed. The 3-PS score consists of the collection of baseline hemoglobin, prostatic specific antigen and Eastern cooperative oncology group performance status and was initially applied to the whole population (total group). The score was then validated on the 338 patient's subgroup (clean group) obtained by subtracting the 92 patients enrolled for the original study of the 3-PS score. This purified group served as further validation evidence. Results: Statistical analysis showed that the 3-PS score was valid on the total group as well as in the clean group as the AUC estimated (0.74) falls within the CI of the AUC calculated on the validation sample (95% CI 0.66-0.82). Conclusion: This study confirms the validity of the 3-PS score for mCRPC patients. This score is simple, noninvasive and affordable and can be easily used to select patients that will most probably complete 223Ra treatment. In addition, this tool provides an exact estimate of life expectancy in terms of OS

Non-Occlusive Mesenteric Ischemia in Children With Diabetic Ketoacidosis: Case Report and Review of Literature

IntroductionDespite the use of technology, recurrent diabetic ketoacidosis (DKA) prevention remains an unmet need in children and adolescents with T1D and may be accompanied by life-threatening acute complications. We present a rare case of non-occlusive mesenteric ischemia (NOMI) with overt manifestation after DKA resolution and a discussion of recent literature addressing DKA-associated NOMI epidemiology and pathogenesis in children and adolescents.Case PresentationA 13-year-old female with previously diagnosed T1D, was admitted at our emergency department with hypovolemic shock, DKA, hyperosmolar state and acute kidney injury (AKI). Mildly progressive abdominal pain persisted after DKA correction and after repeated ultrasound evaluations ultimately suspect for intestinal perforation, an intraoperative diagnosis of NOMI was made.ConclusionThe diagnosis of DKA-associated NOMI must be suspected in pediatric patients with DKA, persistent abdominal pain, and severe dehydration even after DKA resolution

Il progetto dell’ICoH Repository e il contributo della Medicina del Lavoro italiana allo sviluppo della tutela della salute dei lavoratori

Il presente studio intende promuovere l'Icoh Heritage Repository, un archivio digitale realizzato per la raccolta e sistematizzazione dei contributi scientifici in Medicina del Lavoro presentati in occasione dei 32 Congressi internazionali ICOH dal 1906 al 2018. Tali atti congressuali sono stati organizzati e digitalizzati in maniera sistematizzata, aggiornata e di facile accessibilità all'interno di un Repository accessibile in open access dal sito dell'ICOH.. Nella fase di sperimentazione dell’efficacia ed efficienza del Repository, si è scelto di presentare lo studio di tre medici del lavoro che con i loro contributi scientifici, rispettivamente in tema di lotta all’anchilostomiasi (Volante, 1906), solfocarbonismo (Quarelli, 1928) e cancerogenicità del cloruro di vinile monomero (Viola, 1969) hanno dato un apporto fondamentale allo sviluppo della Medicina del Lavoro e all’evoluzione della normativa in tema di salute e sicurezza sul lavoro

Pharmacokinetic evaluation of Eltrombopag in ITP pediatric patients

Background: Eltrombopag (EPAG) is an oral thrombopoietin receptor agonist, approved for refractory primary immune thrombocytopenia (ITP) in pediatric patients. In two pediatric RCTs, EPAG led to an improvement of platelet counts and a reduction in bleeding severity. However, a significant number of pediatric patients did not achieve the primary endpoints. We performed a pharmacokinetic evaluation of EPAG in pediatric patients with refractory ITP. Methods: Outpatients aged from 1 to 17 y, affected by refractory ITP to first-line treatment, were enrolled for a pharmacokinetic assessment. The analysis of drug plasma concentration was performed by the LC-MS/MS platform. Non-compartmental and statistical subgroup analyses were carried out using the R package ncappc. Results: Among 36 patients eligible for PK analysis, the median dose of EPAG given once daily was 50 mg. The EPAG peak occurs between 2 and 4 h with a population Cmax and AUC 0–24 geo-mean of 23, 38 μg/ml, and 275, 4 µg*h/mL, respectively. The pharmacokinetic profile of EPAG did not show a dose proportionality. Female patients showed a statistically significant increase of dose-normalized exposure parameters, increasing by 110 and 123% for Cmax and AUC 0–24, respectively, when compared to male patients. Patients aged 1–5 y showed values increased by more than 100% considering both exposure parameters, compared to older children. Furthermore, patients presenting complete response (83%), showed augmented EPAG exposure parameters compared to subjects with partial or no response. Conclusion: These data highlight the need to further explore the variability of EPAG exposure and its pharmacokinetic/pharmacodynamic profile in pediatric patients also in a real-life setting

Contribution of ICOH to Address the Different OSH Needs among Countries: Results of a Survey

The aim of this study is to map the coverage of occupational safety and health (OSH) rules and provisions and their enforcement at a country level worldwide. Members’ participation in the International Commission on Occupational Health (ICOH) activities was also investigated. We used a questionnaire-based survey to collect data. An online questionnaire was administered from February 14 to March 18, 2018 to all ICOH members for the triennium 2015 to 2017 (n = 1929). We received 384 completed questionnaires from 79 countries, with a 20% response rate. To synthesize information about the coverage of OSH rules and provisions and their level of enforcement, a synthetic coverage index was calculated and combined with country, gross domestic product (GDP) per capita and the human development index (HDI). We used multiple correspondence analysis (MCA) to analyze the members’ participation in ICOH activities. More than 90.0% of the sample declared that in their own country there is a set of rules and provisions regulating OSH in the workplace, and training procedures and tools to improve workers’ awareness. However, these rules and training procedures are mainly “partially” enforced and utilized (39.0% and 45.4%). There was no statistically significant association between country and GDP per capita and the synthetic coverage index, whilst controlling for HDI. The level of engagement in ICOH activities is higher in senior members (aged 65 years or older), coming from high-income countries, having held a position within ICOH, with a higher level of education and a researcher position. An integrated and multidisciplinary approach, which includes research, education and training, is needed to address OSH issues and their impact both at global and country level

Monitoring of physicochemical parameters of soils after applying pig slurry. Analysis of its application in short and long periods in the province of Córdoba, Argentina

Soil amendment with manures from intensive livestock breeding is, currently, a usual practice which could produce positive and/or negative effect on several soil properties. In this work, the effect of consecutive additions of pig slurry (PS), during 1 and 15 years, in two different farms in the Province of Córdoba (Argentina), was analyzed. Also, a control soil (without amendment), and an untilled soil were studied for comparison for each farm. This is the first research to be conducted in this part of the country. In this research we study the effect of PS applications in large commercial pig farms. For all soils and PS samples collected the following parameters: pH, electrical conductivity (EC), total N (TN), available phosphorus (P), Na, K, Ca and Mg, were analyzed. PS presents an alkaline pH, high EC, high phosphorus and nitrogen content. The statistical analysis, shown that PS application for 15 years could significantly modify the soil physicochemical properties, but one PS application before harvest, is similar to soil control. The soil amended with PS through 15 years shown: higher pH (7.57), and EC (3.09 dSm−1) values, and high P content (264 ppm), probably due to the low P mobility. Values of TN (2.15 g L−1) increased with the PS application, making this. The PS application, as a soil amendment, an advantage treatment for TN conservation and to avoid the commercial fertilizer use. PS application has to be planned in order to increase the soil nutrient recovery. The PS doses (m3 ha−1) must be carefully calculated to prevent soil nutrient unbalance and possible soil and/or groundwater contamination. These results could be an important contribution on the proper PS application, as soil amendment, in the province of Córdoba and in other Argentinian regions.Fil: Dionisi, Carla Patricia. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; ArgentinaFil: Mignone, Ricardo Andres. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santiago del Estero. Universidad Nacional de Santiago del Estero. Centro de Investigaciones y Transferencia de Santiago del Estero; ArgentinaFil: Rubenacker, Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; ArgentinaFil: Pfaffen, Maria Valeria del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Bachmeier, Omar Antonio. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; ArgentinaFil: Campitelli, Paola Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; ArgentinaFil: Yudi, Lidia Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Juárez, Ana Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin