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Resumen La arteriopatia autosomica dominante cerebral con infartos subcorticales y leucoencefalopatia es una enfermedad autosomica dominante de pequenos vasos causada por mutaciones del gen NOTCH3. Tipicamente se presenta con migrana, eventos isquemicos cerebrales recurrentes y trastornos cognitivos. Las crisis epilepticas son inusuales como manifestacion inicial, pero aun mas infrecuente es su presentacion como status epilepticus no convulsivo 1 . Se presenta una serie familiar de 3 casos con esta arteriopatia, entre los cuales 2 de ellos tuvieron status epilepticus como manifestacion de la enfermedad.

Biological dressings such as collagen and hyaluronic acid represent the main advanced tools that plastic surgeons, dermatologists and vulnologists use today to treat chronic wounds or ulcers that do not tend to heal. These types of dressings are important because they create a moist and physiological interface at the wound level, are of natural origin, easy to use, hypo-allergenic, economical and do not create discomfort for the patient during dressing changes. We treated 128 patients (divided into four groups based on type of dressing) with non-complex superficial chronic wounds in comparison with a traditional dressing (fitostimoline gauze or polyurethane foam). We analyzed wound characteristics, healing time, and operator and patient satisfaction. A significantly higher recovery rate was observed in the “Collagen-coated plates” treatment group compared to Standard Treatment. Additionally, a significantly higher probability of recovery was observed compared to the alternative two experimental devices (Collagen-coated plates + HA and Collagen-based spray). However, the main limitation of the randomization of this study is the presence in the “Collagen-based spray” group of localized wounds, mainly in the fingers and hand. No side effects were reported in relation to the procedures or the experimental products. Collagen may be considered as a valuable therapeutic tool in non-complex chronic wounds by virtue of its low immunogenicity, flexibility and applicability in biocompatible scaffolds, and represents driving force toward enhanced wound care.

Acute kidney injury (AKI) is a common finding in Neotatal Intensive Care Units (NICU). Sepsis is one the main causes of AKI in preterm newborns. AKI has been associated with significant death rates. Early detection of the condition is the first step to improving prevention, treatment, and outcomes, while decreasing length of hospitalization, care costs, and morbimortality. AKI may progress to chronic kidney disease (CKD), a condition linked with dialysis and greater risk of cardiovascular disease. This review article aims to discuss cases of AKI in preterm newborns with sepsis, the use of biomarkers in lab workup, and the use of non-conventional biomarkers for the early identification of AKI.

Data on the etiological factors underlying the co-occurrence of common adolescent pain with anxiety and depression symptoms are very limited. Opioid prescriptions for adolescent pain problems are on the rise in North America and constitute a risk factor for diversion, misuse, and substance use. In this study, we aimed to investigate the phenotypic and etiological association among pain, depression, and anxiety and to test their link to substance use in adolescents. By taking advantage of the Italian National Twin Registry and of the relatively low incidence of opioid prescriptions in Italy, we applied multivariate modelling analyses to 748 Italian adolescent twins (374 pairs, mean age 16 ± 1.24 years). Twins' responses to the Achenbach Youth Self-Report questionnaire were used to build a composite adolescent pain index and to measure anxiety, depression, and substance use. All monozygotic within-pair correlations were higher than the dizygotic correlations, indicating genetic influences for adolescent pain, anxiety, and depressive problems. A common latent liability factor influenced by genetic and environmental elements shared among pain, depression, and anxiety provided the best fit to explain the co-occurrence of adolescent pain, anxiety, and depression problems. A common phenotypic factor capturing all 3 phenotypes was positively associated (β = 0.19, P < 0.001, confidence interval: 0.10-0.27) with substance use. These findings indicate that several intertwined mechanisms, including genetic factors, can explain a shared liability to common adolescent pain, anxiety, and depression problems. Their association with substance use remains traceable even in societies with relatively low prevalence of opioid prescriptions.

Iris defects and distorted pupils are commonly managed with iris suturing techniques that aim to close the defect and/or reform the physiological pupil. The re-creation of an optimally sized and centered pupil is often challenging because of missing iris, asymmetrical iris damage, or variable tension around the pupil. Current options include removing or cutting iris tissue using microscissors or the vitreous cutter, instrument stretching, or postoperative laser photocoagulation. Iris microendodiathermy is a simple technique that is minimally traumatic, titratable, and controlled, avoids excessive tissue manipulation, and is able to create a round cosmetically pleasing pupil. A bipolar endodiathermy cautery is applied to the iris stroma to induce tissue contraction and to gently pull the pupil in the meridian to which probe is applied. Endothermal pupilloplasty (EDP) may be used to recenter or enlarge a small pupil, thereby avoiding additional trauma inflicted by a vitrector or microscissors that physically cuts the iris.

Petals of edible flowers (EF) are rich in biologically active compounds with many proven benefits for human health. However, studies on the effects of EF in humans after consumption are lacking. This pilot explorative study evaluated the changes in urinary phenolic excretion in healthy volunteers to whom different doses of phenolics from edible roses (Gourmet Roses™) have been added to a meal. Rose petals were picked fresh once a week for three weeks, showing significantly increasing values of total phenolic content, total anthocyanin content, and antioxidant activity (measured as ferric reducing antioxidant power (FRAP) and as DPPH • and ABTS •+ scavenging activities) from the first to the third week. After the meal, direct associations between urinary phenolics and both the EF phenolic content and the antioxidant activity were found in a multiple regression model. These new insights on EF consumption, to be confirmed by larger trials, suggest that the urinary phenolic excretion of healthy volunteers increases with increasing rose phenolic content.

The longitudinal assessment of physical function with high temporal resolution at a scalable and objective level in patients recovering from surgery is highly desirable to understand the biological and clinical factors that drive the clinical outcome. However, physical recovery from surgery itself remains poorly defined and the utility of wearable technologies to study recovery after surgery has not been established.Prolonged postoperative recovery is often associated with long-lasting impairment of physical, mental, and social functions. While phenotypical and clinical patient characteristics account for some variation of individual recovery trajectories, biological differences likely play a major role. Specifically, patient-specific immune states have been linked to prolonged physical impairment after surgery. However, current methods of quantifying physical recovery lack patient specificity and objectivity.Here, a combined high-fidelity accelerometry and state-of-the-art deep immune profiling approach was studied in patients undergoing major joint replacement surgery. The aim was to determine whether objective physical parameters derived from accelerometry data can accurately track patient-specific physical recovery profiles (suggestive of a 'clock of postoperative recovery'), compare the performance of derived parameters with benchmark metrics including step count, and link individual recovery profiles with patients' preoperative immune state.The results of our models indicate that patient-specific temporal patterns of physical function can be derived with a precision superior to benchmark metrics. Notably, six distinct domains of physical function and sleep are identified to represent the objective temporal patterns: "activity capacity" and "moderate and overall activity" (declined immediately after surgery); "sleep disruption and sedentary activity" (increased after surgery); "overall sleep", "sleep onset", and "light activity" (no clear changes were observed after surgery). These patterns can be linked to individual patients' preoperative immune state using cross-validated canonical-correlation analysis. Importantly, the pSTAT3 signal activity in M-MDSCs predicted a slower recovery.Accelerometry-based recovery trajectories are scalable and objective outcomes to study patient-specific factors that drive physical recovery.

Background: In Brazil, the most relevant scorpions for public health are species of the genus Tityus: T. serrulatus, T. bahiensis, T. obscurus and T. stigmurus, the latter occurring mainly in Ceara, showing that severe cases affect more the population at risk, children under 14 years old. Objectives: The survey aims to identify what are the clinical and laboratory changes in children and teenagers affected by scorpion bites, as well as predictive factors in severe cases. Methods: This is an observational, retrospective and quantitative study of poisoning by scorpion accidents attended and notified by the Toxicological Assistance Center of Fortaleza (CIATOX / CE) from January to December 2019. Results: 820 records were diverted, in which 425 (51.83%) women were killed, of which only 3 (0.37%) were pregnant. Regarding the age group, 1-3 years old is more frequent, 183 (22.32%). The species T. stigmurus 534 cases, (65.12%), the feet region 271 cases (33.04%); the origin of the municipality of Fortaleza 773 (94.15%) and the regional II 122 cases (15.78%) had higher occurrences. Of the 820 cases, only 12 underwent laboratory tests, showing changes such as leukocytosis leukocytosis (72.7%), platelets (63.6%), hyperglycemia (83.3%), TGO (100%), LDH (100%), CK - MB (100%) and Amylase (30%). Conclusion: It was found that the epidemiological, clinical and laboratory profile of children and adolescentes is associated with the severity of scorpionism, which indicates an emergency characteristic, especially when it affects children. Keywords: Scorpions, Clinic Epidemiology, Intoxications, Children and youth, Tityus.

Interferons (IFNs) are key cytokines involved in alerting the immune system to viral infection. After IFN stimulation, cellular transcriptional profile critically changes, leading to the expression of several IFN stimulated genes (ISGs) that exert a wide variety of antiviral activities. Despite many ISGs have been already identified, a comprehensive network of coding and non-coding genes with a central role in IFN-response still needs to be elucidated. We performed a global RNA-Seq transcriptome profile of the HCV permissive human hepatoma cell line Huh7.5 and its parental cell line Huh7, upon IFN treatment, to define a network of genes whose coordinated modulation plays a central role in IFN-response. Our study adds molecular actors, coding and non-coding genes, to the complex molecular network underlying IFN-response and shows how systems biology approaches, such as correlation networks, network’s topology and gene ontology analyses can be leveraged to this aim.

Background Complete extension of the thumb and activation of the extensor pollicis longus (EPL) tendon are fundamental to ensure maximum function. Many EPL repair techniques are described in the literature. Methods The authors present an alternative technique using the brachioradialis (BR) tendon. Thirty patients with injuries of the EPL tendon in zone 8 were studied. In all cases, neither direct suture repair nor traditional tendon transfer was possible. Results Thumb extension was restored in all patients with satisfactory extension recovery. All patients achieved excellent extension; good functional results were observed in 2 cases, and in 1 case satisfactory results were achieved using the Geldmacher assessment and the Kapandji assessment. The overall results were rated as excellent, good, fair, or poor according to the Quick Disabilities of the Arm, Shoulder, and Hand Scale. Discussion The BR tendon was suitable to treat all cases, in particular injuries occurring near Lister’s tubercle, due to its appropriate length for tenorrhaphy albeit with a short distal head.

Background Distal Phalanx (DP) fractures are the most common hand injuries. Bone fixation associated with soft tissue reconstruction, is often required to ensure more effective outcomes. The aim of the present study is to compare functional outcomes of DP fractures surgically treated with crossed manual drilled 23 Gauge needles vs crossed Kirschner-wires (k-wire). Methods Clinical data included analysis of patient demographics, range of motion (ROM), and complications. Radiographic assessment considered fracture type, location, fracture displacement, and radiographic union. Functional outcomes analysis was performed.The statistical significance was assessed at the level of probability lower than 5%. Results A total of 60 patients from 2012 to 2015 were retrospectively enrolled and among them 12 patients suffering from diabetes or current smokers. A total of 60 DP fractures were treated, 32 with needles (group A) and 28 with k-wire fixation (group B). Time to union, showed in different time points, was significantly lower in group A (≤ 40 days, p = 0.023*) compared to group B. ROM of the distal interphalangeal joint at six months follow-up was 60° in group A and 40° in group B. A significant improvement was observed (p = 0.001*) in the 23 G needle treated group. Functional outcome analysis showed that VAS was significantly lower in group A compared to group B (p = 0.023*). Conclusion Our study showed that the 23 G needle yielded satisfactory results in terms of time to union and range of motion compared to k-wire fixation especially for tuft and shaft DP fractures. Therefore, should be a valid alternative to k-wire fixation in selected patients.

A healthy pregnancy depends on complex interrelated biological adaptations involving placentation, maternal immune responses, and hormonal homeostasis. Recent advances in high-throughput technologies have provided access to multiomics biological data that, combined with clinical and social data, can provide a deeper understanding of normal and abnormal pregnancies. Integration of these heterogeneous datasets using state-of-the-art machine-learning methods can enable the prediction of short- and long-term health trajectories for a mother and offspring and the development of treatments to prevent or minimize complications. We review advanced machine-learning methods that could: provide deeper biological insights into a pregnancy not yet unveiled by current methodologies; clarify the etiologies and heterogeneity of pathologies that affect a pregnancy; and suggest the best approaches to address disparities in outcomes affecting vulnerable populations.

OBJECTIVES To compare the use of curvilinear-array (microconvex) and phased-array transducers for ultrasonographic examination of the lungs in dogs. ANIMALS 13 client-owned dogs with left-sided congestive heart failure. PROCEDURES In a prospective methods comparison study, 24 ultrasonographic examinations of the lungs (4 sites/hemithorax) were performed with both curvilinear-array and phased-array transducers at 3 clinical time points. Two observers independently assessed the number of B lines (scored per site and in total), number of sites strongly positive for B lines (ie, those with > 3 B lines/site), and image quality (scored on a 5-point scale). Analyses included assessment of interobserver agreement with κ analysis, comparison of quality scores between transducers with mixed-effects modeling, and investigation of agreement and bias for B-line data and quality scores between transducers with Passing-Bablok regression. RESULTS Interobserver agreement for total B-line scores and number of strong-positive sites was excellent (κ > 0.80) for both transducers. There was no evidence of analytic bias for the number of B lines or strong-positive sites between transducers. Interobserver agreement for image quality scores was moderate (κ, 0.498 and 0.517 for the curvilinear-array and phased-array transducers, respectively). Both observers consistently assigned higher-quality scores to curvilinear-array images than to phased-array images. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated both curvilinear-array (microconvex) and phased-array transducers can be used by experienced sonographers to obtain diagnostic ultrasonographic images of the lungs in dogs with acute or resolving left-sided congestive heart failure and suggested the former transducer may be preferred, particularly to aid identification of anatomic landmarks for orientation.

Acute kidney injury (AKI) is a frequent and potentially fatal complication of snakebites. In the setting of snakebites, endothelial biomarkers may be used to predict disease severity and can play a major role in AKI pathophysiology. The aim of this study was to investigate the potential role of endothelial biomarkers in predicting AKI in Bothrops envenoming. Therefore, blood and urine samples were collected from 26 patients admitted to the emergency department after Bothrops envenoming at 3 different post-bite points in time: on admission (up to 8 h post-bite), 12–16 h, and 24–28 h post-bite, to investigate the time course of endothelial biomarkers in AKI following Bothrops snakebites. The diagnostic performance of injury biomarkers in Bothrops envenomation was evaluated. AKI was diagnosed using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. There was an association between endothelial injury and increased risk for AKI in bothropic envenoming. Angiopoietin- 1 (Ang-1) and Vascular cell adhesion protein-1 (VCAM-1) were useful biomarkers to predict mild AKI [AUC-ROC: Ang-1 0.82, VCAM-1 0.76] within the interval of 8–16 h post Bothrops snakebites. The use of endothelial biomarkers VCAM-1 e Ang-1 within 12−16 h post-bite may be useful in the early stage of mild AKI related to Bothrops envenoming and might have an effect on the early intervention for renal protection in less severe Bothrops-related AKI.

Marco Bellone,1 Lorenzo Pradelli,1 Stefano Molica,2 Adele Emanuela De Francesco,3 Daniela Ghislieri,4 Emanuele Guardalben,5 Antonietta Caputo4 1Department of Health Economics and Outcome Research, AdRes Health Economics and Outcomes Research, Turin, Italy; 2Dipartimento Onco-ematologico, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy; 3Hospital Pharmacy, Mater Domini Azienda Ospedaliero Universitaria, Catanzaro, Italy; 4Market Access Department, Roche SpA, Monza, Italy; 5Medical Department, Roche SpA, Monza, ItalyCorrespondence: Marco BelloneAdRes Health Economics and Outcomes Research, 17 Via Vittorio Alfieri, Turin 10121, ItalyTel +39 011 765-1239Email m.bellone@adreshe.comObjective: To assess the cost-effectiveness of obinutuzumab (O-chemo) in comparison to rituximab (R-chemo) in patients with untreated advanced follicular lymphoma (FL) at intermediate or high risk from an Italian National Health Service (NHS) perspective.Methods: A previously developed four-state Markov model was adapted to estimate lifetime clinical outcomes and costs of Italian patients with advanced FL and an FL international predictive index score ≥ 2 in treatment with O-chemo and R-chemo. Life expectancy was derived from the GALLIUM and PRIMA clinical trials. Progression-free survival (PFS), early progressive disease (PD), and treatment duration were extrapolated by fitting parametric distributions to empirical data in GALLIUM and late PD to data in PRIMA. Expected survival was weighed by published utilities. Costs updated to 2020 Euros and health gains occurring after the first year were discounted at an annual 3% rate. Probabilistic sensitivity analysis (PSA) was carried out.Results: O-chemo was associated with an incremental survival increase (0.97 life-years [LYs]), even when weighted for quality (0.88 quality-adjusted LYs [QALYs]), and incremental costs (around € 15,000), driven by longer treatment during PFS state relative to R-chemo. The incremental cost-effectiveness ratio and incremental cost-utility ratio are both widely accepted by the Italian NHS (around € 15,500/LY and € 17,000/QALY gained, respectively). PSA simulations confirmed the robustness of results given sensible variations in assumptions.Conclusion: O-chemo has superior clinical efficacy compared to rituximab, and should be considered a cost-effective option in first-line treatment of patients with advanced FL at intermediate or high risk in Italy. Incremental cost-effectiveness ratios are below the threshold considered affordable by developed countries.Keywords: economic evaluation, oncology, FLIPI score, ICER, PFS, QALY

Aim: To investigate the association between cardiovascular risk and biomarkers in patients with Type 2 diabetes (T2DM). Methods: Cross-sectional study, with evaluation of traditional and new biomarkers (serum FGF-23, Syndecan-1 [Sdc-1] and vascular cell adhesion molecule-1 [VCAM-1] and urinary VEGF and kidney injury molecule-1 [KIM-1]) and risk scores (Framingham-FRS and UK Prospective Diabetes Study [UKPDS]). Results: 128 diabetics were included, with predominance of high risk by FRS and low risk by UKPDS. There was an independent association of VCAM-1 and VEGF with higher risk by FRS-lipids and UKPDS. Conclusion: There was an independent association of VCAM-1 and VEGF with higher cardiovascular risk, showing a subclinical endothelial dysfunction in T2DM. The inclusion of novel biomarkers to risk scores may increase accuracy when assessing cardiovascular risk of diabetic individuals.

Background:It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).Methods:CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART.Results:In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (padj = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (padj = 0.048 and padj = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals.Conclusions:All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size.Funding:This work was supported by ZonMw (09120011910035) and FP7 Health (305522).

La trombosi venosa profonda (TVP) è l’ostruzione completa o parziale di una o più vene del circolo venoso profondo degli arti e/o dell’addome e pelvi. È la terza causa di morte più comune dopo l’infarto miocardico e l’ictus ischemico perché può determinare un’embolia polmonare (EP) con rischio di morte improvvisa, precoce o tardiva. In assenza di un tempestivo trattamento anticoagulante adeguato questa temibile complicanza si può verificare fino al 50% dei casi nei primi 3 mesi. È di fondamentale importanza la terapia e l’avvento dei Nuovi Anticoagulanti Orali (NAO) ha rapidamente cambiato gli attuali paradigmi sul trattamento del tromboembolismo venoso finora basato sull’uso embricato degli anticoagulanti iniettabili (eparina non frazionata, eparine a basso peso molecolare e fondaparinux) e degli antagonisti orali della vitamina K(AVK), trattamento complesso e talora problematico. La TVP è una complicanza frequente anche nei pazienti oncologici ed è causa frequente di morbilità e mortalità. Il trattamento ottimale nei pazienti con neoplasia maligna obbliga il clinico alla valutazione di alcuni parametri tra cui il rischio di sanguinamento, l’interazione con farmaci chemioterapici e la tipologia di cancro di cui il paziente è affetto.

Em dezembro de 2019, um novo coronavirus foi identificado e associado a ocorrencia de pneumonia de causa desconhecida na China. SARS-CoV-2 rapidamente disseminou-se, e, atualmente, a COVID-19 e classificada como pandemia. O objetivo desse estudo consiste em discutir as caracteristicas gerais da COVID-19, incluindo a epidemiologia, transmissao, medidas de controle, virologia, diagnostico, apresentacoes clinicas e achados radiologicos e laboratoriais. Nesse contexto, foram consultados artigos publicados em base de dados com a finalidade de comparacao entre paises mais afetados na Asia, Europa e America ate 31 de marco de 2020. A principal forma de transmissao ocorre entre humanos por secrecoes respiratorias, e estudos indicam um substancial envolvimento de pacientes assintomaticos nesse processo. Pacientes com COVID-19 sao predominantemente homens e podem apresentar inumeros sintomas, especialmente febre e tosse. Hipertensao arterial e diabetes mellitus foram as comorbidades mais comuns. Pior prognostico esta associados a aumento da idade, comorbidades e complicacoes. Anormalidades na tomografia computadorizada de torax sao frequentes, sendo opacidades em vidro fosco e infiltrados bilaterais os padroes pulmonares mais comuns, contudo porcentagem significativa dos pacientes nao apresenta alteracoes na admissao. Exames laboratoriais normalmente apresentam linfocitopenia, aumento de contagem de neutrofilos e plaquetas, velocidade de hemossedimentacao, lactato desidrogenase, proteina C reativa, ferritina, bilirrubina total, aspartato aminotransferase, alanina aminotransferase, creatinina, creatina fosfoquinase, mioglobina, glicose e citocinas. Apesar dos achados radiologicos e laboratoriais apresentarem similaridades na China, Italia e EUA, as taxas de mortalidade podem ser conflitantes, sugerindo, portanto, a necessidade de estudos de acordo com cada regiao.

PURPOSE OF THE REPORT The aim of this study was to evaluate safety and efficacy of copper-64(II)dichloride (64Cu(II)Cl2) as a new PET tracer for urological malignancies (UMs). METHODS Patients with UM were enrolled in a prospective study. All patients were staged with preoperative CT and 64Cu(II)Cl2 PET/CT. Patient characteristics, anatomical and functional imaging, and final histopathology were recorded. Surgical specimens for histopathological examination were collected. To determine time-activity curves for 64Cu(II)Cl2 uptake in UM and normal tissues, SUVs were calculated. The safety of 64Cu(II)Cl2 was assessed. RESULTS Twenty-three patients were included. An administered activity of 174.7 MBq (4.72 mCi) for 64Cu(II)Cl2 was equal to 9.80 mSv of the effective dose. The median SUVmax values were 5.7, 0.9, 1.8, and 9.8 for the prostate, bladder, penis, and kidney, respectively. Median SUVmax values were higher in organs with a malignancy in comparison with healthy tissue (prostate [11.5 vs 5.3, P < 0.001], bladder [6.2 vs 0.9, P = 0.007], and penis [3.9 vs 1.3, P = 0.027]), but not in the kidneys (5.0 vs 10.4, P = 0.998). The highest area under the curve (AUC) was reported for prostate cancer (AUC, 0.978), and the lowest for penile cancer (AUC, 0.775). The detection rates based on the best suggested cutoff according to the SUVmax were 85.7% (6/7) for prostate and bladder and 83.3% (5/6) for penile cancer. Neither drug-related effects nor physiologic responses occurred, nor adverse reactions. CONCLUSIONS 64Cu(II)Cl2 is an effective and well-tolerated tracer in patients with UM. Our results show higher SUVmax in cancer patients than in healthy subjects. Our findings suggest that 64Cu(II)Cl2 PET/CT is useful in patients affected by prostate, bladder, and penis cancer.

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through hepatic CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The FDA and the EMA sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like vitamin K antagonists (VKAs), DOACs can determine gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GI bleeding as compared with apixaban and warfarin. In patients taking oral anticoagulant with GI risk factor, PPI could be recommended, even if usefulness of PPIs in these patients deserves further data. Helicobacter pylori should always be searched, and treated, in patients with history of peptic ulcer disease (with or without complication). Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

COVID-19 is a pandemic associated with systemic clinical manifestations. In this study, we aimed to present a narrative review on kidney involvement in COVID-19. Kidney involvement could be derived from direct cytopathic effects, immunological mechanisms, indirect effects on renal tissue through other mediators, and dysfunction or injury of other organs. The evolution of COVID-19 may be complicated with acute kidney injury (AKI) in a significant percentage of patients, and renal dysfunction seems to be associated with worse prognosis. Patients with chronic kidney disease (CKD) seem to be more susceptible to the severe forms of COVID-19. Patients with renal replacement therapy (RRT) are also a vulnerable population as consequence of their advanced age, underlying comorbidities, impaired immune response, and clustering in hemodialysis centers, with requirements for frequent contact with healthcare services. Kidney transplant patients may be at high-risk due to long-term immunosuppression and comorbidities, hence, managing immunosuppression is imperative. Lastly, renal replacement therapy may be required during COVID-19, and different modalities are discussed based on clinical findings and laboratorial aspects. Therefore, COVID-19 seems to affect kidney by different mechanisms, which contributes for AKI development and increases the severity of the disease. Also, patients with CKD and kidney transplant recipients are at higher risk for COVID-19 and mortality.

As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of a previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryo-EM. We show that mAb J08 has low nanomolar affinity against VoCs, binds high on the receptor binding domain (RBD) ridge and is therefore unaffected by most mutations, and can bind in the RBD-up and -down conformations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy.One Sentence SummaryPotent neutralizing monoclonal antibody J08 binds SARS-CoV-2 spike independent of known escape mutations.

Introduction We aimed to summarize current literature about radiation cystitis treatments, providing physician of a summary of current management options. Evidence acquisition A systematic literature review searching on PubMed (Medline), Scopus, and Web of Science databases was performed in March 2021. PRISMA guidelines were followed. Population consisted of patients with a diagnosis of radiation cystitis after pelvic radiotherapy (P). We focused our attention on different treatments, such as conservative or surgical one (I). Single or multiple arms studies were deemed eligible with no mandatory comparison (C). Main outcomes of interest were symptoms control and adverse events rates (O). Evidence synthesis The search identified 1,194 records. Of all, four studies focused on the use of hyperbaric oxygen therapy showing complete response rates ranging from 52 to 87% approximately. Oral administration of cranberry compounds was investigated in one study showing no superiority to placebo. Intravesical instillation of different compounds were investigated in five studies showing the highest complete response rates after alum (60%) and formalin administration (75%). Endoscopic conservative surgical treatments (fibrin glue or vaporization) also showed 75% complete response rates. In patients who did not respond to conservative treatments robotic cystectomy is feasible with overall complication rates of about 59.3% at 90 days. Conclusions Radiotherapy induced cystitis is an under-reported condition after pelvic radiotherapy. Several treatments have been proposed, but in up to 10% of cases salvage cystectomy is necessary. A stepwise approach, with progressive treatment aggressiveness is recommended.

In 2019 the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) created a joint panel of experts with the aim of preparing an official statement on transition in Chronic Intestinal Failure (CIF). The transition from pediatric to adult care has a key role in managing all chronic diseases and in optimizing the compliance to care. Thus SIGENP and SINPE, in light of the growing number of patients with IF who need long-term Parenteral Nutrition (PN) and multidisciplinary rehabilitation programs throughout adulthood, shared a common protocol to provide an accurate and timely process of transition from pediatric to adult centers for CIF. The main objectives of the transition process for CIF can be summarized as the so-called "acronym of the 5 M": 1)Motivate independent choices which are characteristics of the adult world; 2)Move towards adult goals (e.g. self-management of his pathology and sexual issues); 3)Maintain the habitual mode of care; 4) Minimize the difficulties involved in the transition process and 5)Modulate the length of the transition so as to fully share with the adult's team the children's peculiarities.

Background The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. Methods Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. Results The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. Conclusion Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach., We have previously described a novel multivariate method (NMM) with theoretical statistical advantages over existing methods, which we assessed here in 3 cohorts of people living with HIV. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status.

Human Papilloma Virus infection is very frequent in humans and is mainly transmitted sexually. The majority of infections are transient and asymptomatic, however, if the infection persists, it can occur with a variety of injuries to skin and mucous membranes, depending on the type of HPV involved. Some types of HPV are classified as high oncogenic risk as associated with the onset of cancer. The tumors most commonly associated with HPV are cervical and oropharyngeal cancer, epigenetic mechanisms related to HPV infection include methylation changes to host and viral DNA and chromatin modification in host species. This review is focused about epigenethic mechanism, such as MiRNAs expression, related to cervix and oral cancer. Specifically it discuss about molecular markers associated to a more aggressive phenotype. In this way we will analyze genes involved in meiotic sinaptonemal complex, transcriptional factors, of orthokeratins, sinaptogirin, they are all expressed in cancer in a way not more dependent on cell differentiation but HPV-dependent.

Background & Aim: Standard 10-day sequential therapy is advised as first-line therapy for Helicobacter pylori (H. pylori) eradication by current Italian guidelines. Some data suggested that a 14-day regimen may achieve higher eradication rates. This study compared the efficacy of sequential therapy administered for either 10- or 14-days.Methods: This prospective, multicenter, open-label study enrolled patients with H. pylori infection without previous treatment. Patients were receiving a sequential therapy for either 10 or 14 days with esomeprazole 40 mg and amoxicillin 1 g (5 or 7 days) followed by esomeprazole 40 mg, clarithromycin 500 mg and tinidazole 500 mg (5 or 7 days), all given twice daily. Bacterial eradication was checked using 13C-urea breath test. Eradication cure rates were calculated at both Intention-to-treat (ITT) and per-protocol (PP) analyses.Results: A total of 291 patients were enrolled, including 146 patients in 10-day and 145 in the 14-day regimen. The eradication rates were 87% (95% CI = 81.5-92.4) and 90.3% (95% CI = 85.5-95.1) at ITT analysis with the 10- and 14-day regimen, respectively, and 92.7% (95% CI = 88.3-97) and 97% (95% CI = 94.2-99.9) at PP analysis (p =0.37). Among patients, who earlier had interrupted therapy, bacterial eradication was achieved in 8 out of 9 who completed the first therapy phase and performed at least ≥3 days of triple therapy in the second phase.Conclusion: This study found that both 10- and 14-day sequential therapies achieved a high eradication rate for first-line H. pylori therapy in clinical practice.

Objectives: Despite successful antiretroviral (ARV) therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately-chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement.Design: Cross-sectional analysis of 134 PLWH on suppressive ARV therapy, 79 lifestyle-comparable HIV-negative controls aged ≥45 years from the Co-morBidity in Relation to AIDS (COBRA) cohort, and 35 age-matched blood donors (BD).Methods: Biological age was estimated using a validated algorithm based on ten biomarkers. Associations between ‘age advancement’ (biological minus chronological age) and HIV status/parameters, lifestyle, cytomegalovirus (CMV), hepatitis B (HBV) and hepatitis C virus (HCV) infections were investigated using linear regression.Results: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6, 14.9) years] and HIV-negative [5.5 (3.8, 7.2) years] COBRA participants compared to BD [-7.0 (-4.1, -9.9) years, both p's < 0.001)], but also in HIV-positive compared to HIV-negative participants (p < 0.001). Chronic HBV, higher anti-CMV IgG titer and CD8+ T-cell count were each associated with increased age advancement, independently of HIV-status/group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1, 6.8) years among those with nadir CD4+ < 200 cells/μL and by 0.1 (0.06, 0.2) years for each additional month of exposure to saquinavir.Conclusions: Both treated PLWH and lifestyle-comparable HIV-negative individuals show signs of age advancement compared to BD, to which persistent CMV, HBV co-infection and CD8+ T-cell activation may have contributed. Age advancement remained greatest in PLWH and was related to prior immunodeficiency and cumulative saquinavir exposure. published

Purpose: To evaluate the rarity, clinical features and management of Coats disease characterized by fovea-sparing enhancing the importance of pediatric retinal screening and early management to maintain a good visual acuity. Methods: Retrospective analysis of approximately 40 patients affected by Coats disease between 2000 and 2020 at the Retinoblastoma Referral Center and Ophthalmology unit of the University of Siena in Italy. Results: Two patients with fovea sparing Coats disease were included. Both presented an extrafoveal Coats disease (stage 2A by Shields classification) when they were 5 and 6 years old respectively. They had no anterior findings and a presenting visual acuity of 20/20 reflecting the early stage and a milder phenotype of the disease which are indeed more likely to be found in patients older than 3 years at presentation. Both presented telangiectasia and retinal exudation in the affected eye. Standard Argon laser photocoagulation and subsequently Cryotherapy were performed in the telangiectatic retinal periphery of both patients obtaining an excellent control and regression of the disease. Conclusions: Careful pediatric retinal screening and early management are crucial to ensure a good visual prognosis in such an early feature of Coats disease as fovea sparing since this condition unfortunately tends to recall the physician’s attention in more advanced stages. Due to the extremely poor number of articles regarding such a rare feature of Coats disease like fovea sparing, we report our experience.

OBJECTIVE To evaluate the frequency of variants in the pyruvate kinase dehydrogenase 4 (PDK4) and titin (TTN) genes in a group of Doberman Pinschers with dilated cardiomyopathy (DCM) and to determine whether there were unique clinical attributes to each variant. ANIMALS 48 Doberman Pinschers with DCM. PROCEDURES Doberman Pinschers with recently diagnosed DCM were identified, and genomic DNA from each was genotyped with a PCR assay for detection of PDK4 and TTN genetic variants. Dogs were grouped on the basis of whether they had the TTN variant alone, PDK4 variant alone, both variants, or neither variant. Descriptive statistics were compiled for dog age, body weight, and left ventricular dimensions and fractional shortening and for the presence of ventricular and supraventricular arrhythmias and heart failure. Results were compared across groups. RESULTS Of the 48 dogs, 28 had the TTN variant alone, 10 had both variants, 6 had neither variant, and 4 had the PDK4 variant alone. The mean age was younger for dogs with the PDK4 variant alone, compared with other dogs. However, the number of dogs with the PDK4 variant alone was very small, and there was an overlap in age across groups. No other meaningful differences were detected across groups, and independent genotype-phenotype relationships were not identified. CONCLUSIONS AND CLINICAL RELEVANCE Although findings indicated that the TTN variant was most common, 6 dogs had neither variant, and this fact supported the concept of ≥ 1 other genetic contributor to DCM in Doberman Pinschers. Future studies are warranted to evaluate genotype-phenotype relationships in Doberman Pinschers with DCM.

The Icare HOME (TA022, Icare Oy, Vanda, Finland) is rebound tonometer recently approved by the US Food and Drug Administration in March 2017 designed for self-measurement of intraocular pressure (IOP). IOP remains a major modifiable risk factor for glaucoma progression; however, IOP measurements typically occur through single office measurements on Goldmann applanation tonometry (GAT) and do not always reveal the complete picture of patient's IOP patterns and daily fluctuations, which are important for accurate diagnosis and evaluation. Numerous studies have now compared the efficacy of the Icare HOME to that of GAT. The objective of this article is to review the existing literature surrounding the Icare HOME tonometer and its efficacy as a self-tonometer in comparison to GAT. The available literature has shown promising results in its accuracy of measuring IOP but suggests cautious usage in patients with central corneal thicknesses or IOP ranges that are outside of a certain range. This article will also provide details and example cases for when the Icare HOME may be most clinically useful.

Long non-coding RNAs (lncRNAs) play critical roles in various biological functions and disease processes including cancer. The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was initially identified as a lncRNA with elevated expression in primary human non-small cell lung tumors with high propensity to metastasize, and subsequently shown to be highly expressed in numerous other human cancers including breast, ovarian, prostate, cervical, endometrial, gastric, pancreatic, sarcoma, colorectal, bladder, brain, multiple myeloma, and lymphoma. MALAT1 is deeply involved in several physiological processes, including alternative splicing, epigenetic modification of gene expression, cellular senescence, healthy aging, and redox homeostasis. The aim of this work was to investigate the modulation exerted by a single bout of endurance exercise on the level of MALAT1 expression in peripheral blood mononuclear cells (PBMCs) from healthy male donors displaying different training status and redox homeostasis features. Our findings show that MALAT1 is downregulated after acute endurance exercise in subjects whose fitness level guarantee a high expression of SOD1 and SOD2 antioxidant genes and low levels of endogenous oxidative damage. In vitro protocols in Jurkat lymphoblastoid cells exposed to pro-oxidant environment confirmed the link between MALAT1 expression and antioxidant gene modulation, documenting p53 phosphorylation and its recruitment to MALAT1 promoter. Remarkably, analyses of Microarray-Based Gene Expression Profiling revealed high MALAT1 expression in leukemia patients in comparison to healthy control and a significant negative correlation between MALAT1 and SOD1 expression. Collectively our results highlight the beneficial effect of a physically active lifestyle in counteracting aberrant cancer-related gene expression programs by improving the redox buffering capacity.

Issues with traditional implementations of tangent-stiffness-proportional damping model are associated with negative damping forces that develop in the post-yield range when the system stiffness be...

Objective Liver transplant (LT) is a definitive therapeutic option for patients with chronic liver disease. However, acute kidney injury after LT (post-LT AKI) is a frequent complication that may lead to graft dysfunction and decrease life expectancy. Delay in AKI detection by traditional biomarkers boosted research with new biomarkers for post-LT AKI as neutrophil gelatinase-associated lipocalin (NGAL) and syndecan-1. We aim to evaluate associations of intraoperative systemic NGAL and syndecan-1 levels with post-LT AKI. Methods This is a prospective study conducted in 46 patients selected for LT. Patients were evaluated preoperatively and blood samples were collected intraoperatively: T1 (after induction of anesthesia), T2 (anhepatic phase) and T3 (2 h after reperfusion of the graft). Results The mean age was 54 ± 12 years and 60% were male. Post-LT AKI was observed in 24 (52%) patients of which 12% needed dialysis. Serum NGAL and syndecan-1 increased along surgical phases. Mostly, increment values of serum NGAL of T2 to T3 and syndecan-1 at T3 were importantly associated with post-LT AKI. Into a multivariate model with model for end-stage liver disease score, age, gender, warm ischemia, cold ischemia and surgery time, syndecan-1 levels at T3 remains capable to predict post-LT AKI. Serum NGAL had significance only with increment values calculated by the ratio of 'T3/T2'. Finally, serum syndecan-1 at T3 had a better diagnostic performance in receiver operating characteristic curve analysis. Conclusion Serum syndecan-1 levels in 2 h after reperfusion were most useful in early post-LT AKI diagnosis and may be used to construct new risk groups in this context.

Purpose In patients with obesity, micronutrient deficiencies have been reported both before and after bariatric surgery (BS). Obesity is a chronic pro-inflammatory status, and inflammation increases the risk of micronutrient malnutrition. Our objective was to assess in pre-BS patients the prevalence of micronutrient deficiencies and their correlation with blood values of C-reactive protein (CRP). Methods Anthropometric data, instrumental examinations, and blood variables were centrally measured in the first 200 patients undergoing a pre-BS evaluation at the “Città della Salute e della Scienza” Hospital of Torino, starting from January 2018. Results At least one micronutrient deficiency was present in 85.5% of pre-BS patients. Vitamin D deficiency was the most prevalent (74.5%), followed by folate (33.5%), iron (32%), calcium (13%), vitamin B12 (10%), and albumin (5.5%) deficiency. CRP values were high (> 5 mg/L) in 65% of the patients. These individuals showed increased rate of iron, folate, vitamin B12 deficiency, and a higher number of micronutrient deficiencies. In a multiple logistic regression model, increased CRP levels were significantly associated with deficiencies of vitamin B12 (OR = 5.84; 95% CI 1.25–27.2; p = 0.024), folate (OR = 4.02; 1.87–8.66; p p = 0.01). Conclusions Micronutrient deficiencies are common in patients with severe obesity undergoing BS, especially when inflammation is present. In the presence of increased CRP values before surgery, it might be advisable to search for possible multiple micronutrient deficiencies.

Introduction: In this case report we report our experience with rescue intra-arterial chemotherapy in a case of multi-relapsed peripapillary Retinoblastoma (RB) and the importance of high resolution MRI in detecting possible optic disc infiltration. Case report: In 2007, a 14 month-old caucasian girl was referred to our ocular oncology unit for leukocoria. Only left eye was interested, with a single mass of the posterior pole. Patient underwent six cycles of systemic chemotherapy and focal laser consolidation. Several relapses occurred during follow-up. Selective intra-arterial chemotherapy (SIAC) with Melphalan was performed and type IV remission was achieved. A new relapse occurred next to the optic disc. MRI was performed and we decided to try to save the globe with a rescue cycle of SIAC. Conclusion: MRI has demonstrated to be useful in decision making in RB, giving us a last chance to save the globe.

ObjectiveThe evidence base for home parenteral nutrition (HPN) in patients with advanced cancer is lacking. To compare the survival of malnourished patients with cancer undergoing palliative care who received HPN with a homogeneous group of patients, equally eligible for HPN, who did not receive HPN.DesignProspective, cohort study; tertiary university hospital, home care, hospice.MethodsPatients were assessed for HPN eligibility according to the guidelines. In the eligible population, who received both HPN and chemotherapy was excluded, while who received only HPN was included in the HPN+ group and who received neither HPN nor chemotherapy but artificial hydration (AH) was included in the HPN− group.Results301 patients were assessed for HPN eligibility and 86 patients (28.6%) were excluded for having severe organ dysfunction or Karnofsky performance status ConclusionsComparative survival associated with the use of HPN versus AH showed significantly longer survival in malnourished patients with advanced cancer receiving HPN. These data support the guideline recommendation that HPN should be considered when malnutrition represents the overriding threat for the survival of these patients.

Endoscopic submucosal dissection (ESD) for gastric neoplastic lesions removal is largely performed in Asian countries. Unfortunately, ESD diffusion, particularly for gastric lesion removal, is still limited in Western countries. We performed a systematic review of available data coming from Western centers. The en bloc and the R0 resection rates for all neoplastic lesions, including early gastric cancer (EGC) and dysplasia, were calculated, as well as the curative rate for EGC. Complications and the 1-month mortality rates were computed. A total of 22 studies from Europe (N = 15), Latina America (N = 6), and Canada (N = 1) were retrieved, with 1152 patients and 1210 lesions. The en bloc resection was successful in 96% [95% confidence interval (CI) 93-98] with a significant heterogeneity (I2 = 63.5%; P < 0.0001). The R0 was achieved in 84% (95% CI 79-89; I2 = 79.9%; P < 0.001). The resection rate was curative in 72% out of 340 patients with EGC (95% CI 65-79, I2 = 8%; P = 0.36). Overall, complications occurred in 9.5% of patients, including bleeding (5.8%), perforation (3.4%), and stenosis (0.35%). A total of three (0.26%) patients deceased within 1 month, but none was directly related to the procedure. Lesion recurrence was observed in 38 (3.5%; 95% CI 2.3-4.4) cases, including 21 EGC and 17 dysplasia. In Western countries, the en bloc and the R0 resections were successful in the large majority of cases, whilst the resection was curative in 72% of patients with EGC. The complications rate was acceptably low.

We report a patient with reflex tooth-brushing-triggered epilepsy, associated with a post-central lesion within the right somatosensory face area. Contralateral facial sensory and motor phenomena, associated with contralateral upper limb extension, were present at seizure onset after gingival stimulation, but seizures could also be induced by contact with solid food or liquids. Spontaneous seizures also were recorded. Secondary generalization was infrequent. Stereoelectroencephalography implantation was performed, with seizure recording and cortical/subcortical stimulation for mapping, to identify the precise extent of surgical resection. Complete postoperative control of epilepsy was achieved, accompanied by a mild and transient neurological deficit. [Published with video sequence].

Schistosoma mansoni infection is considered a public health problem. Glomerular involvement in schistosomiasis is a well-documented complication, especially in hepatosplenic schistosomiasis (HSS). However, renal tubular function is poorly understood. The aim of this study was to investigate, through urinary exosomes, tubular transporters functionally in HSS patients.Cross-sectional study of 20 HSS patients who had isolated exosomes from urine samples. Protease inhibitor was added in the urine samples who were immediately frozen at -80 °C for further exosomes isolation. After urine had thawed, urinary exosomes were obtained using extensive vortexing, centrifugation and ultracentrifugation steps of urine. Urinary transporters expression from exosomes was evaluated by western blot, including NHE3, AQP2 and NKCC2. Charge amounts for gel electrophoresis were adjusted by urinary creatinine concentration of each patient to avoid urinary concentration bias. All protein expression of HSS patients was relative to healthy controls.The expression of aquaporin-2 (AQP2) was lower in HSS patients than in controls (46.8 ± 40.7 vs. 100 ± 70.2%, P = 0.03) and the expression of the NKCC2 co-transporter was higher (191.7 ± 248.6 vs. 100 ± 43.6%, P = 0.02).The decrease of AQP2 and the increase of NKCC2 expression in HSS patients seem to be involved with the inability of urinary concentration in these patients. These data show renal tubular abnormalities in HSS patients without manifest clinical disease.L'infection à Schistosoma mansoni est considérée comme un problème de santé publique. L'atteinte glomérulaire dans la schistosomiase est une complication bien documentée, en particulier dans la schistosomiase hépatosplénique (SH). Cependant, la fonction tubulaire rénale est mal connue. Le but de cette étude était d'étudier, par le biais d'exosomes urinaires, les transporteurs tubulaires fonctionnellement chez les patients atteints de SH. MÉTHODES: Il s'agit d'une étude transversale sur 20 patients atteints de SH qui avaient des exosomes isolés d'échantillons d'urine. Un inhibiteur de protéase a été ajouté dans les échantillons d'urine qui ont été immédiatement congelés à -80°C pour un isolement supplémentaire des exosomes. Après décongélation de l'urine, des exosomes urinaires ont été obtenus en utilisant des étapes étendues de vortex, de centrifugation et d'ultracentrifugation d'urine. L'expression des transporteurs urinaires d'exosomes a été évaluée par western blot, y compris NHE3, AQP2 et NKCC2. Les quantités de charge pour l'électrophorèse sur gel ont été ajustées par la concentration de créatinine urinaire de chaque patient pour éviter un biais de concentration urinaire. Toute expression protéique des patients atteints de SH était relative à celle de témoins sains. RÉSULTATS: L'expression de l'aquaporine-2 (AQP2) était plus faible chez les patients SH que chez les témoins (46,8 ± 40,7 vs 100 ± 70,2%, P = 0,03) et l'expression du co-transporteur NKCC2 était plus élevée (191,7 ± 248,6 vs 100 ± 43,6%, P = 0,16).La diminution de l'AQP2 et l'augmentation de l'expression de NKCC2 chez les patients SH semblent être impliquées dans l'incapacité de concentration urinaire chez ces patients. Ces données montrent des anomalies tubulaires rénales chez les patients SH sans maladie clinique manifeste.

BACKGROUND Whether peripherally inserted central catheters (PICCs) are appropriate as safe and durable venous access devices (VADs) is still controversial. The aim of this 7-year, prospective cohort study was to compare the incidence rate differences of catheter-related complications (CRCs) among 4 types of central VADs in cancer patients receiving home parenteral nutrition (HPN). METHODS We enrolled all adult cancer outpatients who were candidates for HPN and who had a central VAD inserted during the study period, focusing on the incidence rate of CRCs. RESULTS We evaluated 854 central VADs (401 PICCs, 137 nontunneled centrally inserted central catheters [CICCs], 118 tunneled-cuffed CICCs, and 198 ports) in 761 patients, for a total of 169,116 catheter-days. Overall, the rate of total CRCs was 1.08/1000 catheter-days. The incidence of catheter-related bloodstream infections was low (0.29/1000), particularly for PICCs (0.08/1000; P < .001 vs tunneled-cuffed CICCs) and for ports (0.21/1000; P < .019 vs tunneled-cuffed CICCs). The rates of mechanical complications (0.58/1000) and of catheter-related symptomatic thrombosis (0.09/1000) were low and similar for PICCs, tunneled-cuffed CICCs, and ports. In terms of duration and removal rate due to complications, PICCs were like tunneled-cuffed CICCs and ports. Altogether, PICCs had fewer total complications than tunneled-cuffed CICCs (P < .001), there was no difference in total complications between PICCs and ports. CONCLUSION PICCs had significantly better outcomes than tunneled-cuffed CICCs and were safe and durable as ports. Our extensive, long-term study suggests that PICCs can be successfully used as safe and long-lasting VADs for HPN in cancer patients.

Intravitreal anti-vascular endothelial growth factor (VEGF) drugs aflibercept and ranibizumab are used in neovascular retinal diseases but may be associated with non-ocular haemorrhage. Our objective was to compare the risk of non-ocular haemorrhage with intravitreal aflibercept versus intravitreal ranibizumab and with individual intravitreal anti-VEGFs versus intravitreal dexamethasone. A retrospective cohort study was conducted using four Italian claims databases, covering 18 million inhabitants from 2011 to 2016. Incident aflibercept users were matched 1:4 to incident ranibizumab users. The outcome was incident non-ocular haemorrhage requiring hospitalisation. Incidence per 1000 person-years (PYs) was estimated. Patients were followed for 180 days using an intention-to-treat (ITT) approach. An as-treated (AT) approach was also employed, using grace periods of 60 or 90 days. Analyses were repeated for aflibercept versus dexamethasone and ranibizumab versus dexamethasone. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. We identified incident users of intravitreal ranibizumab (n = 21,766), aflibercept (n = 3150) and dexamethasone (n = 3900). The incidence of haemorrhage was four events per 1000 PYs for each drug. Aflibercept was not associated with increased risk versus ranibizumab at 180 days (HR 0.97 [95% CI 0.37–2.56]). Results were consistent in the AT analysis (HR 1.19 [95% CI 0.52–2.75]). No increased risk was found for aflibercept and ranibizumab at 180 days versus dexamethasone (HR 0.70 [95% CI 0.30–2.60] and HR 0.67 [95% CI 0.33–1.38], respectively). No association was identified between intravitreal aflibercept and non-ocular haemorrhage versus ranibizumab. A comparable risk for these intravitreal anti-VEGFs and intravitreal dexamethasone was observed.

Introduction/Background: Medical imaging education programs across Europe, despite their variability, include clinical practice as a guarantee of quality because learning in a clinical context is more effective and allows for constructive qualification of students. Learning in a clinical simulation context is a strategy to promote simulated clinical experience and assure patient safety. In this work, a learning experience, consisting of simulating a pacemaker implantation, implemented over 3 years with students pursuing the Medical Imaging and Radiotherapy degree at the University of Aveiro was evaluated. Methods: A pacemaker implantation simulation with fluoroscopic support was performed with students (third year) pursuing the Medical Imaging and Radiotherapy degree at the Simulation Centre of our institution over 3 years (2016, 2017–2018), addressing all the simulation phases. An operating theater, video recording system, high-fidelity full-body manikin with remote control and monitoring, anesthesia, and fluoroscopic C-arm imaging equipment were used for the simulation. After the simulation activity, students completed a questionnaire evaluated the importance of this learning experience for their educational process. Results: Overall, the mean score results were consistent, even considering the three independent groups (one for each academic year). Students considered this experience valuable for their education, strongly agreeing that the simulation environment helped their learning process and allowed them to acquire, consolidate, and deepen knowledge. Furthermore, they considered that it impressed on them the necessity to continue to improve their learning, and that they would like to participate in other simulation scenarios. Discussion/Conclusion: This simulation activity was a valuable experience for the learning process of the students because it facilitated the acquisition and consolidation of knowledge. It also allowed the students to be aware of the importance of being engaged in their own education. The results were highly consistent over the 3 years, reinforcing the positive feedback from this experience. Introduction/Contexte: Les programmes d’enseignement de l’imagerie médicale en Europe, malgré leur variabilité, incorporent par consensus la pratique clinique comme garantie de qualité, puisque l’apprentissage en contexte clinique est plus efficace et permet la qualification constructive des étudiants. L’apprentissage en contexte de simulation clinique est une stratégie qui favorise l’expérience clinique simulée tout en assurant la sécurité des patients. Dans cette étude, les auteurs évaluent une expérience d’apprentissage qui consiste en l’implantation simulée d’un stimulateur cardiaque mise en œuvre pendant trois ans auprès des étudiants en Imagerie médicale et Radiothérapie de l’Université d’Aveiro. Méthodologie: Une simulation d’implantation de stimulateur cardiaque avec soutien de fluoroscopie a été effectuée avec des étudiants de 3e année en Imagerie médicale et Radiothérapie au Centre de simulation de notre institution pendant une période de trois ans (2016, 2017 et 2018), en appliquant toutes les phases de la simulation. Une salle d’opération, un système d’enregistrement vidéo, un mannequin de corps complet de haut niveau avec contrôle et surveillance à distance, l’anesthésie et un appareil de fluoroscopie sur arceau ont été utilisés pour la simulation. Après l’exercice, les étudiants répondent à un questionnaire qui permet d’évaluer l’importance de cette expérience d’apprentissage dans leur processus éducationnel. Résultats: Dans l’ensemble, les résultats moyens pour les trois années scolaires ont été très bons et constants, même en tenant compte de la présence de trois groupes différents (un pour chaque année). Les étudiants jugent l’expérience valable pour leur formation, sont fortement d’accord pour dire que l’environnement de simulation a aidé le processus d’apprentissage et leur a permis d’acquérir, de consolider et d’approfondir des connaissances. Ils considèrent en outre que cela a souligné la nécessité d’améliorer leur apprentissage et aimeraient participer à d’autres scénarios de simulation. Discussion/conclusion: Cette activité de simulation est une expérience de grande valeur dans le processus d’apprentissage des étudiants, puisqu’elle facilite l’acquisition et la consolidation des connaissances. Elle permet également aux étudiants de prendre conscience de l’importance de s’engager dans leur propre apprentissage. Les résultats ont présenté un degré élevé de constance pendant les trois années, renforçant la rétroaction positive de l’expérience. published

Cutis verticis gyrata (CVG) is a neurocutaneous syndrome characterized by the formation of folds in the scalp that resembles the cerebral cortex. We present two cases of CVG and intellectual disability with drug‐resistant epilepsy. Recognizing CVG is necessary to provide interdisciplinary support for the treatment of comorbidities associated with this entity.

The aims of the study were to describe the prevalence of obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort, to identify demographic, clinical and HIV-specific factors associated with obesity, and to characterize the association between obesity and sociodemographic, clinical and HIV-specific factors and quality of life (QoL).A cross-sectional analysis was carried out of baseline data from the three groups ["older" people with HIV infection (PWH) aged ≥ 50 years, "younger" PWH aged50 years and HIV-negative controls aged ≥ 50 years] within the POPPY cohort. Obesity was defined as a body mass index (BMI) 30 kg/mA total of 1361 subjects were included in the study, of whom 335 (24.6%) were obese. The prevalence of obesity was higher in controls (22.3%) than in older (16.8%) and younger (14.2%) PWH, with no differences between the two groups of PWH. Factors associated with obesity were older age, female gender, black African ethnicity and alcohol consumption. Recreational drug use and a higher current CD4 T-cell count (in PWH) were associated with lower and higher odds of being obese, respectively. The presence of obesity was associated with worse physical health QoL scores, higher odds of having cardiovascular disease, type 2 diabetes and hypertension, but lower odds of having osteopenia/osteoporosis, irrespective of HIV status.Despite a lower prevalence of obesity in PWH, specific subgroups (women, people of black African origin and older people) were more likely to be obese, and negative health consequences of obesity were evident, regardless of HIV status. Whether targeted preventive strategies can reduce the burden of obesity and its complications in PWH remains to be determined.

Upper limb nerve damage is a common condition, and evidence suggests that functional recovery may be limited following peripheral nerve repair in cases of delayed reconstruction or reconstruction of long nerve defects. A 26-year-old man presented with traumatic injury from a wide, blunt wound of the right forearm caused by broken glass, with soft tissue loss, complete transection of the radial and ulnar arteries, and a large median nerve gap. The patient underwent debridement and subsequent surgery with a microsurgical free radial fasciocutaneous flap to provide a direct blood supply to the hand; the cephalic vein within the flap was employed as a venous vascularized chamber to wrap the sural nerve graft and to repair the wide gap (14 cm) in the median nerve. During the postoperative period, the patient followed an intensive rehabilitation program and was monitored for functional performance over 5 years of follow-up. Our assessment demonstrated skin tropism and sufficient muscle power to act against strong resistance (M5) in the muscles previously affected by paralysis, as well as a good localization of stimuli in the median nerve region and an imperfect recovery of two-point discrimination (S3+). We propose a novel and efficient procedure to repair >10-cm peripheral nerve gap injuries related to upper limb trauma.