Detection of somatic and germline pathogenic variants in adult cohort of drug-resistant focal epilepsies.

OBJECTIVE: This study investigates the prevalence of pathogenic variants in the mechanistic target of rapamycin (mTOR) pathway in surgical specimens of malformations of cortical development (MCDs) and cases with negative histology. The study also aims to evaluate the predictive value of genotype-histotype findings on the surgical outcome. METHODS: The study included patients with drug-resistant focal epilepsy who underwent epilepsy surgery. Cases were selected based on histopathological diagnosis, focusing on MCDs and negative findings. We included brain tissues both as formalin-fixed, paraffin-embedded (FFPE) or fresh frozen (FF) samples. Single-molecule molecular inversion probes (smMIPs) analysis was conducted, targeting the MTOR gene in FFPE samples and 10 genes within the mTOR pathway in FF samples. Correlations between genotype-histotype and surgical outcome were examined. RESULTS: We included 78 patients for whom we obtained 28 FFPE samples and 50 FF tissues. Seventeen pathogenic variants (22 %) were identified and validated, with 13 being somatic within the MTOR gene and 4 germlines (2 DEPDC5, 1 TSC1, 1 TSC2). Pathogenic variants in mTOR pathway genes were exclusively found in FCDII and TSC cases, with a significant association between FCD type IIb and MTOR genotype (P = 0.003). Patients carrying mutations had a slightly better surgical outcome than the overall cohort, however it results not significant. The FCDII diagnosed cases more frequently had normal neuropsychological test, a higher incidence of auras, fewer multiple seizure types, lower occurrence of seizures with awareness impairment, less ictal automatisms, fewer Stereo-EEG investigations, and a longer period long-life of seizure freedom before surgery. SIGNIFICANCE: This study confirms that somatic MTOR variants represent the primary genetic alteration detected in brain specimens from FCDII/TSC cases, while germline DEPDC5, TSC1/TSC2 variants are relatively rare. Systematic screening for these mutations in surgically treated patients' brain specimens can aid histopathological diagnoses and serve as a biomarker for positive surgical outcomes. Certain clinical features associated with pathogenic variants in mTOR pathway genes may suggest a genetic etiology in FCDII patients.

Zinc(II) complexes bearing N,N,S ligands: Synthesis, crystal structure, spectroscopic analysis, molecular docking and biological investigations about its antifungal activity.

In the present work, the synthesis, characterization, antifungal activity, molecular docking study and in silico approach of five thiosemicarbazone derivatives and their corresponding zinc(II) complexes are described. The compounds were characterized by elemental analysis, IR, UV-Vis and NMR spectroscopic measurements, molar conductivity measurements, emission spectra, high-resolution mass spectrometry and X ray study. The antifungal activity of the free ligands and synthesized compounds was preliminarily evaluated against Candida albicans (ATCC 90028), Candida tropicalis (ATCC 13803) and Candida glabrata (ATCC 2001), by the minimum inhibitory concentration (MIC) assay. Two complexes, 4 (MIC = 3.18 to 6.37 µM) and 5 (MIC = 25.95 µM for all) showed promising results, being highly active against all strains evaluated. The X-ray analyses shown that the complex 2 crystallizes in the centrosymmetric space group P21/c of the monoclinic system and the coordination sphere around zinc(II) atom is better described as slightly distorted octahedral. The Hirshfeld surface (HS) analysis showed that non-classical H···H and C···H/H···C contacts contribute with 65.9% while the S···H and N···H (21%) and Cl···H and O···H interactions (12%) complete the HS area. The molecular docking results, performed against CYP51 enzyme (sterol 14α-demethylase) of C. albicans and C. glabrata shows that the complexes 4 (ΔG = -10.75 and - 12.90 kcal/ mol) and 5 (ΔG = -11.12 and - 14.53 kcal/ mol) showed the highest binding free energies of all compounds. The ADME-Tox (absorption, distribution, metabolism, excretion and toxicity) in silico parameters evaluated showed promising results for all compounds.

Collaborative Methods Foster Better Data: Insights From a Suicide Data Linkage Project in North Carolina.

The linking of surveillance data sets has increasingly become an essential public health activity. We compared a traditional method in North Carolina (NC) with a newer collaborative approach when linking Hospital Discharge Data (HDD) and NC Violent Death Reporting System (NC-VDRS) data. We found the collaborative approach to be superior, enabling wider ownership combined with subject matter expertise the traditional method lacked. We used Link Plus and Match*Pro software for linkage, which had similar matching results. However, the collaborative process using Match*Pro resulted in fewer matches requiring review and enabled better case adjudication and collaboration between partners. Of the 1361 unique suicides that matched to HDD, 44% (n = 599) had multiple prior hospitalizations. Public health needs to innovate and enable partners to foster solutions when traditional methods are dated and result in less reliable data. The process outlined builds consensus, increases trust, and ultimately saves time.

A new stiffness-sensing test to measure damage evolution in solids.

We propose and assess a procedure to measure the damage evolution in solids as a function of the applied strain, by conducting stiffness-sensing mechanical tests. These tests consist in superimposing to a monotonically increasing applied strain numerous, low-amplitude unloading/reloading cycles, and extracting the current stiffness of the specimens from the slope of the stress-strain curve in each of the unloading/reloading cycles. The technique is applied to a set of polymeric and metallic solids with a wide range of stiffness, including CFRP laminates loaded through the thickness, epoxy resins, injection-moulded and 3D printed PLA and sintered Ti powders. The tests reveal that, for all the materials tested, damage starts developing at the very early stages of deformation, during what is commonly considered an elastic response. We show that the test method is effective and allows enriching the data extracted from conventional mechanical tests, for potential use in data-driven constitutive models. We also show that the measurements are consistent with the results of acoustic and resistive measurements, and that the method can be used to quantify the viscous response of the materials tested.

Medicaid healthcare expenditures for infants with birth defects potentially related to Zika virus infection in North Carolina, 2011-2016.

BACKGROUND: In 2016, Zika virus (ZIKV) was recognized as a human teratogen. North Carolina (NC) had no local transmission of ZIKV but infants with relevant birth defects, including severe brain anomalies, microcephaly, and eye abnormalities, require specialized care and services, the costs of which have not yet been quantified. The objective of this study is to examine NC Medicaid healthcare expenditures for infants with defects potentially related to ZIKV compared to infants with no reported defects. METHODS: Data sources for this retrospective cohort study include NC birth certificates, Birth Defects Monitoring Program data, and Medicaid enrollment and paid claims files. Infants with relevant defects were identified and expenditure ratios were calculated to compare distributions of estimated expenditures during the first year of life for infants with relevant defects and infants with no reported defects. RESULTS: This analysis included 551 infants with relevant defects and 365,318 infants with no reported defects born 2011-2016. Mean total expenditure per infant with defects was $69,244 (median $30,544) for the first year. The ratio of these expenditures relative to infants with no reported defects was 14.5. Expenditures for infants with select brain anomalies were greater than those for infants with select eye abnormalities only. CONCLUSIONS: Infants with defects potentially related to ZIKV had substantially higher Medicaid expenditures than infants with no reported defects. These results may be informative in the event of a future outbreak and are a resource for program planning related to care for infants in NC.

The effects of heterogeneous mechanical properties on the response of a ductile material.

We investigate numerically the small-strain, elastic-plastic response of statistically isotropic materials with non-uniform spatial distributions of mechanical properties. The numerical predictions are compared to simple bounds derived analytically. We explore systematically the effects of heterogeneity on the macroscopic stiffness, strength, asymmetry, stability and size dependence. Monte Carlo analyses of the response of statistical volume elements are conducted at different strain triaxiality using computational homogenisation, and allow exploring the macroscopic yield behaviour of the heterogeneous material. We illustrate quantitatively how the pressure-sensitivity of the yield surface of the solid increases with heterogeneity in the elastic response. We use the simple analytical models developed here to derive an approximate scaling law linking the fatigue endurance threshold of metallic alloys to their stiffness, yield strength and tensile strength.

A computational framework to establish data-driven constitutive models for time- or path-dependent heterogeneous solids.

We propose and implement a computational procedure to establish data-driven surrogate constitutive models for heterogeneous materials. We study the multiaxial response of non-linear n-phase composites via Finite Element (FE) simulations and computational homogenisation. Pseudo-random, multiaxial, non-proportional histories of macroscopic strain are imposed on volume elements of n-phase composites, subject to periodic boundary conditions, and the corresponding histories of macroscopic stresses and plastically dissipated energy are recorded. The recorded data is used to train surrogate, phenomenological constitutive models based on neural networks (NNs), and the accuracy of these models is assessed and discussed. We analyse heterogeneous composites with hyperelastic, viscoelastic or elastic-plastic local constitutive descriptions. In each of these three cases, we propose and assess optimal choices of inputs and outputs for the surrogate models and strategies for their training. We find that the proposed computational procedure can capture accurately and effectively the response of non-linear n-phase composites subject to arbitrary mechanical loading.

fMRI-Based Effective Connectivity in Surgical Remediable Epilepsies: A Pilot Study.

Simultaneous EEG-fMRI can contribute to identify the epileptogenic zone (EZ) in focal epilepsies. However, fMRI maps related to Interictal Epileptiform Discharges (IED) commonly show multiple regions of signal change rather than focal ones. Dynamic causal modeling (DCM) can estimate effective connectivity, i.e. the causal effects exerted by one brain region over another, based on fMRI data. Here, we employed DCM on fMRI data in 10 focal epilepsy patients with multiple IED-related regions of BOLD signal change, to test whether this approach can help the localization process of EZ. For each subject, a family of competing deterministic, plausible DCM models were constructed using IED as autonomous input at each node, one at time. The DCM findings were compared to the presurgical evaluation results and classified as: "Concordant" if the node identified by DCM matches the presumed focus, "Discordant" if the node is distant from the presumed focus, or "Inconclusive" (no statistically significant result). Furthermore, patients who subsequently underwent intracranial EEG recordings or surgery were considered as having an independent validation of DCM results. The effective connectivity focus identified using DCM was Concordant in 7 patients, Discordant in two cases and Inconclusive in one. In four of the 6 patients operated, the DCM findings were validated. Notably, the two Discordant and Invalidated results were found in patients with poor surgical outcome. Our findings provide preliminary evidence to support the applicability of DCM on fMRI data to investigate the epileptic networks in focal epilepsy and, particularly, to identify the EZ in complex cases.

Six-year multicenter study on short-term peripheral venous catheters-related bloodstream infection rates in 246 intensive units of 83 hospitals in 52 cities of 14 countries of Middle East: Bahrain, Egypt, Iran, Jordan, Kingdom of Saudi Arabia, Kuwait, Lebanon, Morocco, Pakistan, Palestine, Sudan, Tunisia, Turkey, and United Arab Emirates-International Nosocomial Infection Control Consortium (INICC) findings.

BACKGROUND: Short-term peripheral venous catheters-related bloodstream infections (PVCR-BSIs) rates have not been systematically studied, and data on their incidence by number of device-days is not available. METHODS: Prospective, surveillance study on PVCR-BSI conducted from September 1st, 2013 to 31st Mays, 2019 in 246 intensive care units (ICUs), members of the International Nosocomial Infection Control Consortium (INICC), from 83 hospitals in 52 cities of 14 countries in the Middle East (Bahrain, Egypt, Iran, Jordan, Kingdom of Saudi Arabia, Kuwait, Lebanon, Morocco, Pakistan, Palestine, Sudan, Tunisia, Turkey, and United Arab Emirates). We applied U.S. RESULTS: We followed 31,083 ICU patients for 189,834 bed-days and 202,375 short term peripheral venous catheter (PVC)-days. We identified 470 PVCR-BSIs, amounting to a rate of 2.32/1000 PVC-days. Mortality in patients with PVC but without PVCR-BSI was 10.38%, and 29.36% in patients with PVC and PVCR-BSI. The mean length of stay in patients with PVC but without PVCR-BSI was 5.94 days, and 16.84 days in patients with PVC and PVCR-BSI. The microorganism profile showed 55.2 % of gram-positive bacteria, with Coagulase-negative Staphylococci (31%) and Staphylococcus aureus (14%) being the predominant ones. Gram-negative bacteria accounted for 39% of cases, and included: Escherichia coli (7%), Klebsiella pneumoniae (8%), Pseudomonas aeruginosa (5%), Enterobacter spp. (3%), and others (29.9%), such as Serratia marcescens. CONCLUSIONS: PVCR-BSI rates found in our ICUs were much higher than rates published from USA, Australia, and Italy. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs.

Six-year multicenter study on short-term peripheral venous catheters-related bloodstream infection rates in 727 intensive care units of 268 hospitals in 141 cities of 42 countries of Africa, the Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific Regions: International Nosocomial Infection Control Consortium (INICC) findings.

BACKGROUND: Short-term peripheral venous catheter-related bloodstream infection (PVCR-BSI) rates have not been systematically studied in resource-limited countries, and data on their incidence by number of device days are not available. METHODS: Prospective, surveillance study on PVCR-BSI conducted from September 1, 2013, to May 31, 2019, in 727 intensive care units (ICUs), by members of the International Nosocomial Infection Control Consortium (INICC), from 268 hospitals in 141 cities of 42 countries of Africa, the Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific regions. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System. RESULTS: We followed 149,609 ICU patients for 731,135 bed days and 743,508 short-term peripheral venous catheter (PVC) days. We identified 1,789 PVCR-BSIs for an overall rate of 2.41 per 1,000 PVC days. Mortality in patients with PVC but without PVCR-BSI was 6.67%, and mortality was 18% in patients with PVC and PVCR-BSI. The length of stay of patients with PVC but without PVCR-BSI was 4.83 days, and the length of stay was 9.85 days in patients with PVC and PVCR-BSI. Among these infections, the microorganism profile showed 58% gram-negative bacteria: Escherichia coli (16%), Klebsiella spp (11%), Pseudomonas aeruginosa (6%), Enterobacter spp (4%), and others (20%) including Serratia marcescens. Staphylococcus aureus were the predominant gram-positive bacteria (12%). CONCLUSIONS: PVCR-BSI rates in INICC ICUs were much higher than rates published from industrialized countries. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs in resource-limited countries.

International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2012-2017: Device-associated module.

BACKGROUND: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2012 to December 2017 in 523 intensive care units (ICUs) in 45 countries from Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. METHODS: During the 6-year study period, prospective data from 532,483 ICU patients hospitalized in 242 hospitals, for an aggregate of 2,197,304 patient days, were collected through the INICC Surveillance Online System (ISOS). The Centers for Disease Control and Prevention-National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI) were applied. RESULTS: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the medical-surgical ICUs, the pooled central line-associated bloodstream infection rate was higher (5.05 vs 0.8 per 1,000 central line-days); the ventilator-associated pneumonia rate was also higher (14.1 vs 0.9 per 1,000 ventilator-days,), as well as the rate of catheter-associated urinary tract infection (5.1 vs 1.7 per 1,000 catheter-days). From blood cultures samples, frequencies of resistance, such as of Pseudomonas aeruginosa to piperacillin-tazobactam (33.0% vs 18.3%), were also higher. CONCLUSIONS: Despite a significant trend toward the reduction in INICC ICUs, DA-HAI rates are still much higher compared with CDC-NHSN's ICUs representing the developed world. It is INICC's main goal to provide basic and cost-effective resources, through the INICC Surveillance Online System to tackle the burden of DA-HAIs effectively.

Systemic activation of Nrf2 pathway in Parkinson's disease.

BACKGROUND: Preclinical studies underlined the relevance of Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor pathway in the pathogenesis of Parkinson's disease (PD). OBJECTIVE: The objective of this study was to explore Nrf2 pathway in vivo in PD, looking for novel disease biomarkers and therapeutic targets. METHODS: The levels of Nrf2, the downstream effectors (NAD(P)H dehydrogenase [quinone] 1 (Nqo1) enzyme, glutathione metabolism enzymes Glutamate-cysteine ligase (GCL) and Glutathione Reductase (GR)), the upstream activators (redox state and mitochondrial dysfunction), and α-synuclein oligomers were assessed in the blood leukocytes of PD patients comparatively to controls. Biochemical data were correlated to clinical parameters. RESULTS: In PD, Nrf2 was highly transcribed and expressed as well as its target effectors. The mitochondrial complex I activity was reduced and the oxidized form of glutathione prevailed, disclosing the presence of pathway's activators. Also, α-synuclein oligomers levels were increased. Nrf2 transcript and oligomers levels correlated with PD duration. CONCLUSIONS: Blood leukocytes mirror pathogenic mechanisms of PD, showing the systemic activation of the Nrf2 pathway and its link with synucleinopathy and clinical events. © 2019 International Parkinson and Movement Disorder Society.

Adolescent providers' knowledge of human papillomavirus vaccination age guidelines in five countries.

Purpose: To examine provider knowledge of HPV vaccination age guidelines in five countries. Methods: A total of 151 providers of adolescent vaccinations in Argentina, Malaysia, South Africa, South Korea, and Spain were interviewed between October 2013 and April 2014. Univariate analyses compared providers' understanding of recommended age groups for HPV vaccination to that of each country's national guidelines. Results: In three of five countries surveyed, most providers (97% South Africa, 95% Argentina, 87% Malaysia) included all nationally recommended ages in their target age group. However, a relatively large proportion of vaccinators in some countries (83% Malaysia, 55% Argentina) believed that HPV vaccination was recommended for women above age 26, far exceeding national guidelines, and beyond the maximum recommended age in the United States. National median minimum and maximum age recommendations cited by the respondents for HPV vaccination were 11 and 29 years in Argentina (national guideline: 11-14), 13 and 48 years in Malaysia (guideline 13-14), 8 and 14 years in South Africa (guideline 9-14), 10 and 20 years in South Korea (guideline 11-14), and 11 and 12 years in Spain (guideline 11-14). In all countries, a higher percentage of vaccinators included all nationally recommended ages for vaccination, as compared to providers who did not administer HPV vaccination. Conclusions: Overall, a substantial proportion of providers incorrectly reported their country's age guidelines for HPV vaccination, particularly the upper age limit. As provider recommendation is among the strongest predictors of successful vaccination uptake among adolescents, improved education and clarification of national guidelines for providers administering HPV vaccination is essential to optimize prevention of infection and associated disease.

The Oxidative Stress-Induced miR-200c Is Upregulated in Psoriasis and Correlates with Disease Severity and Determinants of Cardiovascular Risk.

Psoriasis is a chronic inflammatory skin disease associated with reactive oxygen species (ROS) increase and a higher risk of cardiovascular (CV) events. We previously showed that the miR-200 family (miR-200s) is induced by ROS, miR-200c being the most upregulated member responsible for apoptosis, senescence, ROS increase, and nitric oxide decrease, finally causing endothelial dysfunction. Moreover, circulating miR-200c increases in familial hypercholesterolemic children and in plaques and plasma of atherosclerotic patients, two pathologies associated with increased ROS. Given miR-200s' role in endothelial dysfunction, ROS, and inflammation, we hypothesized that miR-200s were modulated in lesional skin (LS) and plasma of psoriatic patients (Pso) and that their levels correlated with some CV risk determinants at a subclinical level. All Pso had severe psoriasis, i.e., Psoriasis Area and Severity Index (PASI) > 10, and one of the following: at least two systemic psoriasis treatments, age at onset < 40 years, and disease duration > 10 years. RNA was extracted from plasma (Pso, N = 29; Ctrl, N = 29) and from nonlesional skin (NLS) and LS of 6 Pso and 6 healthy subject skin (HS) biopsies. miR-200 levels were assayed by quantitative RT-PCR. We found that all miR-200s were increased in LS vs. NLS and miR-200c was the most expressed and upregulated in LS vs. HS. In addition, circulating miR-200c and miR-200a were upregulated in Pso vs. Ctrl. Further, miR-200c positively correlated with PASI, disease duration, left ventricular (LV) mass, LV relative wall thickness (RWT), and E/e', a marker of diastolic dysfunction. Multiple regression analysis indicates a direct association between miR-200c and both RWT and LV mass. Circulating miR-200a correlated positively only with LV mass and arterial pressure augmentation index, a measure of stiffness, although the correlations were nearly significant (P = 0.06). In conclusion, miR-200c is upregulated in LS and plasma of Pso, suggesting its role in ROS increase and inflammation associated with CV risk in psoriasis.

The role and the interventions of the Hospital Social Service (HSS) for the integration of the health and social activities: a comparative survey between 2008 and 2014 in the Social Service of the "Azienda Ospedaliera Universitaria Policlinico Umberto I" in Rome, Italy.

INTRODUCTION: In the Azienda Ospedaliera Universitaria Policlinico Umberto I in Rome, the Hospital Social Services (HSS) is located within the Directorate of Health, reporting directly to the Chief Medical Officer, providing counselling and supporting clinical services. The HSS is part of a network with its own technical, professional and assessment independence. It often serves as liaison between the hospital and the territory, facilitating the development of services and contributing to public health recovery and maintenance, therefore improving the citizens' standard of living thanks to aid projects and specific interventions. METHODS: The present Report is based on two different studies carried out in 2008 and 2014, both examining the work of the Hospital Social Service in the "Azienda Ospedaliera Universitaria Policlinico Umberto I" in Rome. The purpose is to compare these surveys and work out the results. The data collection is based on a number of social records from the HSS archives (814 records in 2008 and 790 in 2014). The research project followed subsequent stages: planning a draft of the research, where ethnomethodology was used as empirical evaluation technique; collecting data from the HSS's paper and file archives (biographical, clinical and social data); revising, analysing and elaborating the data which showed relevant changes leading to interesting conclusions. RESULTS AND CONCLUSIONS: The comparative analysis of data showed a higher demand of HSS healthcare services, despite a smaller number of beds and hospitalisations available in standard regime. Also, it indicated an increase of patients below 18 years and a decrease of the over-65s age group. As for the geographical origin of patients reported to the HSS, there was a decrease in the percentage of Italian citizens, while the percentage of irregular non-EU and EU patients increased by over 5%. Significant results were found comparing the days between the report to the HSS and patient discharge. Data concerning the 'more than 7 days' group was steady over the years, being more consistent for both the variables considered and increasing in 2014. In the comparative analysis, the interventions with more significant differences were those aimed at promoting homecare and entering sheltered housing. In the former cases, a considerable decrease was observed, if compared to the activation of the integrated health and social homecare services, while there were more requests for homecare assistance; in the latter ones the analysis highlighted a sharp decrease in the percentage of the variable called "assessment to enter Extended Care Units". The causes of these changes are remarkable and have to be found in the political, historical and cultural scenario: - a first factor is the increase in the more recent migratory flow from non-EU countries to Italy, which could explain the rising percentage of foreigners taken over by the HSS; - regional policies, economic cuts imposed on healthcare and higher income limits in order to calculate the patient's economic participation in the costs of institutionalisation have affected the above-mentioned changes; - the innovations in the regulatory field of Latium Region have brought structural changes in long-term care facilities and in the level of care in Extended Care Units (ECU).

A Social Responsibility Guide for Engineering Students and Professionals of all Faith Traditions: An Overview.

The development of the various themes of Catholic Social Teaching (CST) is based on numerous papal documents and ecclesiastical statements. While this paper provides a summary of a number of these documents, this paper focuses on two themes: the common good and care of the environment, and on three documents authored by Pope John Paul II in 1990, by Pope Benedict XVI in 2010, and by Pope Francis in 2015. By analyzing these documents from an engineer's perspective, the author proposes a model for Socially Responsible Engineering. The proposed model is intended to serve as a guide for engineering students and practicing engineers of all faith traditions and to those with no faith tradition at all who wish to incorporate CST in the daily conduct of their personal and professional lives; to provide guidance for the professional the author terms the aspiring Socially Responsible Engineer; and to offer engineers a preferred alternative to the undesirable aspects of the technocratic paradigm. While intended primarily for engineers, this document also serves as a guide for those with expertise in social justice and who, by gaining a better understanding of the thought processes of engineers, can become better mentors for engineering students and practicing engineers seeking to incorporate CST into their daily lives.

Hepatic angiodynamic profile in paediatric patients with hereditary haemorrhagic telangiectasia type 1 and type 2.

BACKGROUND: Liver involvement is a common manifestation of hereditary haemorrhagic telangiectasia (HHT). Although a number of studies have been carried out in adult patients, no study has ever been focused on investigating HHT-related hepatic involvement in paediatric patients. The present study aimed for the first time to systematically estimate the prevalence of HHT-associated liver involvement and to characterize HHT-associated hepatic angiodynamic features in paediatric age. PATIENTS AND METHODS: The study was designed as a cross-sectional survey in an HHT paediatric cohort, subclassified as HHT1 and HHT2 according to the mutated gene. The evaluation of the angiodynamic profile was performed by duplex ultrasound examination. Investigation by multi-slice computed tomography (MSCT) or magnetic resonance angiography (MRA) was performed in patients >12 years. RESULTS: MSCT/MRA examination disclosed silent hepatic involvement in 7/20 (35.0 %) children, and nodular regenerative hyperplasia in two cases. Diameter of common hepatic artery was significantly larger in HHT2 (0.45 ± 0.15 cm) compared to HHT1 (0.33 ± 0.09, p < 0.01) and control children (0.32 ± 0.08, p < 0.05). None of the patients had clinical manifestations of liver involvement. Angiodynamic profiles were different between paediatric and adult HHT patients. CONCLUSIONS: Liver involvement can be detected in paediatric HHT patients, albeit with a lower frequency compared to adults. Paediatric HHT2 children show a higher frequency of liver involvement and a trend to hepatic artery dilation when compared to HHT1 children.

Epileptic networks in patients with bitemporal epilepsy: the role of SEEG for the selection of good surgical candidates.

OBJECTIVE: In this study we investigated the electrical characteristics of seizures recorded by stereo-EEG (SEEG) in a cohort of patients with bitemporal lobe epilepsy (BTLE), in the attempt to verify the presence/absence of different seizure patterns and to identify good surgical candidates. METHODS: We retrospectively reviewed 14 consecutive patients with medically refractory BTLE confirmed by scalp video-EEG (VEEG) recording of bitemporal independent or non-lateralizing seizure onset. All patients had a comprehensive evaluation including history and neurologic examination, MRI, scalp VEEG and SEEG monitoring. Neuropsychological, Wada testing and FDG-PET were performed in most patients. When temporal lobe resection was performed (7 cases), the postoperative follow-up was of at least 1year. RESULTS: Intracranial EEG (SEEG) revealed that only 4/14 (29%) patients were suffering of unilateral TLE. Two groups of patients with distinct SEEG patterns of seizures were identified: a temporo-mesial origin of seizures was the only SEEG pattern observed in 8 patients (Group 1); in 6 patients seizures originated from multiple onset zones in mesial and lateral temporal cortex or from extra-temporal cortex (Group 2). All patients of group 1 (except one who refused surgery) underwent surgery and had a favorable outcome (6 Engel class I; one Engel's class II). The side of surgery was not necessarily the one responsible for the majority of recorded seizures. It was chosen on the basis of MRI findings and consistency of data from presurgical functional investigations, mostly memory assessment and Wada test. SIGNIFICANCE: In patients with suspected BTLE, SEEG proved to be useful in identifying the origin of seizures. Good surgical outcome can be obtained after unilateral resection in patients with bilateral independent seizure onsets or sequential mesial temporal involvement on SEEG if the side of surgery is chosen considering multimodal data.

Italian Intersociety Recommendations on pain management in the emergency setting (SIAARTI, SIMEU, SIS 118, AISD, SIARED, SICUT, IRC).

BACKGRAUND: Pain is the primary reason for admission to the Emergency Department (ED). However, the management of pain in this setting is often inadequate because of opiophagia, fear of excessive sedation, and fear of compromising an adequate clinical assessment. METHODS: An intersociety consensus conference was held in 2010 on the assessment and treatment of pain in the emergency setting. This report is the Italian Intersociety recommendations on pain management in the emergency department setting. RESULTS: The list of level A recommendations includes: 1) use of IV acetaminophen for opioid sparing properties and reduction of opioid related adverse events; 2) ketamine-midazolam combination preferred over fentanyl-midazolam fentanyl-propofol in pediatric patients; 3) boluses of ketamine IV (particularly in the population under the age of 2 years and over the age of 13) can lead to impairment of the upper airways, including the onset of laryngospasm, requiring specific expertise and skills for administration; 4) the use of ketamine increases the potential risk of psychomotor agitation, which can happen in up to 30% of adult patients (this peculiar side effect can be significantly reduced by concomitant systemic use of benzodiazepines); 5) for shoulder dislocations and fractures of the upper limbs, the performance of brachial plexus block reduces the time spent in ED compared to sedation; 6) pain relief and the use of opioids in patients with acute abdominal pain do not increase the risk of error in the diagnostic and therapeutic pathway in adults; 7) in newborns, the administration of sucrose reduces behavioural responses to blood sampling from a heel puncture; 8) in newborns, breastfeeding or formula feeding during the procedure reduces the measures of distress; 9) in pediatric patients, non-pharmacological techniques such as distraction, hypnosis and cognitive-behavioural interventions reduce procedural pain caused by the use of needles; 10) in pediatric patients, preventive application of eutectic mixtures of prilocaine and lidocaine allows arterial and venous samples to be taken in optimum conditions; 11) in pediatric patients, the combination of hypnotics (midazolam) and N2O is effective for procedural pain, but may be accompanied by loss of consciousness. CONCLUSION: The diagnostic-therapeutic pathway of pain management in emergency should be implemented, through further interdisciplinary trials, in order to improve the EBM level of specific guidelines.

Total knee arthroplasty in a patient with thrombocytopenia-absent radius syndrome.

Thrombocytopenia-absent radius (TAR) syndrome is a rare genetic condition with a complex inheritance pattern. This syndrome is classically characterized by hypomegakaryocytic thrombocytopenia as well as bilateral absent radii, shortened ulna, and radially deviated 5-digit hands. During infancy, the predominant manifestations are hemorrhagic complications. Later in life, the bleeding disorder typically improves, but the musculoskeletal abnormalities become of greater concern because of the effects on quality of life. Although the classic musculoskeletal manifestations of TAR syndrome involve the upper extremity, multiple lower-extremity abnormalities have been described, especially dysplasia of the knee. Knee abnormalities include genu varum, varying degrees of laxity or stiffness, patellar abnormalities, concave distal femur, convex medial tibial plateau, and/or absence of the anterior cruciate ligament and posterior cruciate ligament. Several management strategies for lower-extremity abnormalities in TAR syndrome have been described, especially for pediatric patients. Management strategies have not halted the natural progression of knee disease in these patients, and the effect that these knee abnormalities have in adulthood is unclear. Management of knee abnormalities in adults with TAR syndrome is poorly described in the current literature. The authors report a 59-year-old patient with TAR syndrome and knee abnormalities who underwent successful total knee arthroplasty. The patient was followed to the 3-year postoperative visit. At various postoperative time points (7 weeks, 6 months, 1 year, and 3 years), Knee Society Scores and 12-Item Short Form Health Survey scores were recorded. Radiographs obtained at each clinical visit showed well-positioned, well-fixed components. The authors concluded that total knee arthroplasty may be a safe and effective surgical intervention for adults with TAR syndrome and associated knee osteoarthritis.