A Population-Based Registry Analysis on Hospitalized COVID-19 Patients with Previous Cardiovascular Disease: Clinical Profile, Treatment, and Predictors of Death.

A high percentage of patients with COVID-19 (coronavirus disease 2019) have previous cardiovascular disease (CVD). The findings presented here came from an epidemiological population-based registry study (real-world data) that enrolled all in-hospital COVID-19 patients with previous CVD from 1 March to 31 May 2020. Death, other comorbidities, hospital stay variables, ventilation type, and main clinical outcomes were evaluated. In Castile and Leon, 35.83% of the 7307 in-hospital COVID-19 patients who participated in this study had previous CVD, particularly arrhythmias (48.97%), cerebrovascular disease (25.02%), ischemic heart disease (22.8%), and chronic heart failure (20.82%). Of the patients, 21.36% were men and more than 90% were over 65 years of age, and the mortality rate achieved 32.93%. The most used medicines were antibiotics (91.41%), antimalarials (73.3%), steroids (46.64%), and antivirals (43.16%). The main predictors of death were age over 65 years (OR: 5), ventilation needs (OR: 2.81), treatment with anti-SIRS (systemic inflammatory response syndrome) medicines (OR: 1.97), antivirals (OR: 1.74) or steroids (OR: 1.68), SIRS (OR: 5.75), SARS (severe acute respiratory syndrome) (OR: 2.44), or AKI (acute kidney injury) (OR: 1.63) occurrence. Chronic heart failure and cerebrovascular disease were associated with a worse clinical course of COVID-19, especially in men older than 65 years with diabetes who developed SIRS, SARS, or AKI.

Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., ß-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.

Clinical Profile, Pharmacological Treatment, and Predictors of Death Among Hospitalized COVID-19 Patients With Acute Kidney Injury: A Population-Based Registry Analysis.

Introduction: One of the worst clinical outcomes of the coronavirus disease 2019 (COVID-19) pandemic was acute kidney injury (AKI). Methods: This manuscript presents results from a population-based registry study assessing treatment, comorbidities, and predictors of hospital death among COVID-19 patients with AKI from March 1st to May 31th, 2020. Death, oxygen delivery and ventilation, acute dialysis need, use of medications, and various clinical outcomes, in addition to the length of stay in the hospital and intensive care unit (ICU), were evaluated. Results: In Castile and Leon, the largest region of Spain, 10.87% of the patients admitted for COVID-19 (n = 7,307) developed AKI. These patients were known by having hypertension (57.93%), cardiovascular disease (48.99%), diabetes (26.7%) and chronic kidney disease (14.36%), and they used antibiotics (90.43%), antimalarials (60.45%), steroids (48.61%), antivirals (33.38%), anti-systemic inflammatory response syndrome (SIRS) drugs (9.45%), and tocilizumab (8.31%). Mortality among patients with AKI doubled that observed in patients without AKI (46.1 vs. 21.79%). Predictors of hospital death in COVID-19 patients with AKI were ventilation needs (OR = 5.9), treatment with steroids (OR = 1.7) or anti-SIRS (OR = 2.4), severe acute respiratory syndrome (SARS) occurrence (OR = 2.8), and SIRS occurrence (OR = 2.5). Conclusions: Acute kidney injury is a frequent and serious complication among COVID-19 patients, with a very high mortality, that requires more attention by treating physicians, when prescribing medications, by looking for manifestations particular to the disease, such as SARS or SIRS.

A study on the morphoquantitative and cytological characteristics of the bulbar conjunctiva of the maned wolf (Chrysocyon brachyurus; Illiger, 1815).

The maned wolf, Chrysocyon brachyurus, is a near-threatened carnivore inhabiting the Brazilian Cerrado. Few studies have been conducted on this species, and even fewer have explored its ophthalmological characteristics. Vision is critical to wild canids; thus, this study aimed to provide a morphoquantitative description of the bulbar conjunctiva of the maned wolf using cytological and histological analyses. Ten healthy maned wolves from a conservational centre, including 4 females and 6 males aged 1-12 years (6.5 ± 2.8), were included in the study. The samples for cytological analysis were collected from the inferior conjunctival sac using a cytobrush, and conjunctival tissue was collected for histological analysis from the temporal canthus zone. The cytological samples were stained using the Papanicolaou method, and the histological sections were stained using haematoxylin and eosin, Periodic acid-Schiff, picrosirius red and Masson's trichrome stains. The cytological samples were studied for stain quality, and the different cell types were counted. Histological examination was used to determine tissue types in the conjunctiva and their proportions. Analyses revealed a stratified squamous epithelium with some goblet cells and eventual pigmentation in the basal layer. Loose connective tissue with the presence of some mononuclear and polymorphonuclear cells was also observed. The epithelium of the maned wolf's bulbar conjunctiva resembles that of dogs and other carnivore species; furthermore, its physiological and pathological responses were similar to those of other carnivore species.

Microbiological assessment at slaughter of chicken carcasses from commercial, backyard and semi-backyard production systems.

INTRODUCTION: Smaller scale, alternative, chicken production systems are gaining popularity globally. However, this brings public health and market confidence concerns, especially where there are no established standards of production. The aim of this study was to carry out a microbiological analysis of chicken carcasses from the commercial, backyard and semi-backyard production systems, slaughtered in the same slaughterhouse. METHODOLOGY: Samples of 102 chicken carcasses were taken in two steps of the slaughter (A: after bleeding; and B: after chiller tank) and were subjected to aerobic mesophilic, coliforms at 35 °C and coliforms at 45 °C counts, and Salmonella spp. detection. Salmonella spp. isolates were subjected to antimicrobial resistance analysis. RESULTS: At slaughter step A, carcasses from the backyard system had less contamination than carcasses from the commercial system, with a difference of 0.7 log10 CFU/mL. Salmonella was identified in carcasses of all production systems and in both slaughter steps. Nine chicken carcasses were positive for Salmonella and no significant difference was observed in the occurrence of Salmonella amongst the carcasses from different production systems. Two Salmonella isolates, that presented the highest resistance profiles (one isolate was resistant to eight and the other to six out of ten tested antibiotics), were identified on carcasses from the semi-backyard system. CONCLUSIONS: Carcasses from the backyard system had a lower microbial count at the initial step of the slaughter process than the commercial production system. In addition, greater resistance to antimicrobials was observed in Salmonella isolates from semi-backyard system.

Clinical Profile, Treatment and Predictors during the First COVID-19 Wave: A Population-Based Registry Analysis from Castile and Leon Hospitals.

The first wave of the COVID-19 pandemic collapsed the hospitals in Castile and Leon (Spain). An analysis of the clinical characteristics, drug therapies and principal outcome predictors in the COVID-19 hospitalized patients from 1 March to 31 May 2020 is presented through a population-based registry study. Hospital stay variables, ventilation mode data and clinical outcomes were observed. In Castile and Leon hospitals, 7307 COVID-19 patients were admitted, with 57.05% being male and a median of 76 years. The mortality rate was 24.43%, with a high incidence of severe acute respiratory syndrome (SARS) (14.03%) and acute kidney injury (AKI) (10.87%). The most used medicines were antibiotics (90.83%), antimalarials (42.63%), steroids (44.37%) and antivirals, such as lopinavir/ritonavir (42.63%). The use of tocilizumab (9.37%) and anti-SIRS (systemic inflammatory response syndrome) medicines (7.34%) were remarkable. Fundamentally, death occurred more likely over 65 years of age (OR: 9.05). In addition, the need for ventilation was associated with a higher probability of death (OR: 3.59), SARS (OR: 5.14) and AKI (OR: 2.31). The drug-use pattern had been modified throughout the COVID-19 first wave. Multiple factors, such as age, gender and the need for mechanical ventilation, were related to the worst evolution prognosis of the disease.

The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies.

This manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common "off-label" (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs.

Anatomic study of the arterial vascularization of the brain base of paca (Cuniculus paca) / Estudo anatômico da vascularização arterial da base do encéfalo da paca (Cuniculus paca)

Paca (Cuniculus paca Linnaeus, 1766), rodent belong to the Cuniculidae family, has encouraged numerous scientific researches and for this reason could be an experimental model in both human and veterinary areas. And recently, the economic exploitation of the meat cuts, has being direct implication in its zootechnical importance. However, no anatomical descriptions regarding the vascularization of the base of the brain in this rodent has being found. Thus, the aim of the present study was to describe the arteries and the pattern of the vasculature and to compare it with the other species already established in the literature. For this, five pacas, donated by the Unesp Jaboticabal Wildlife Sector, were euthanized followed by the vascular arterial system was injected with red-stained-centrifuged latex by the common carotid artery. After craniectomy, the brains were removed and the arteries were identified and, in addition, compared with those described in other animal species. The presence of the right and left vertebral arteries, close to the medulla oblongata, was detected, originating the basilar artery, which divided into the terminal branches of the right and left basilar artery. Ventral to the optic tract there was the right internal carotid artery and the left, dividing the middle cerebral artery and left rostral and right; dorsal to the optic chiasm, the medial branch of the rostral cerebral arteries was identified. Based on the results, it is concluded that the vascularization of the paca brain base is supplied by the carotid and vertebrobasilar system.(AU)

A paca (Cuniculus paca Linnaeus 1766), roedor da família Cuniculidae, tem encorajado inúmeras pesquisas científicas, tornando-a modelo experimental tanto na área humana quanto na veterinária, além da recente exploração econômica de seus cortes cárneos, que favoreceu diretamente sua importância zootécnica. No entanto, não há até o momento, descrições anatômicas referentes à padronização da vascularização da base do encéfalo neste roedor. Assim, o objetivo do presente trabalho foi realizar tal delineamento arterial nessa região do sistema nervoso central e compará-lo com as demais espécies já estabelecidas na literatura. Para isso, foram eutanasiadas cinco pacas doadas pelo setor de Animais Silvestres da Unesp Jaboticabal, as quais foram submetidas posteriormente à injeção de látex centrifugado e corante líquido xadrez vermelho, pela artéria carótida comum. Após craniectomia e segregação do encéfalo de todos os cadáveres, realizou-se a identificação das artérias presentes na base deste órgão e, ademais, comparação destas com as descritas cientificamente em outras espécies animais. Detectou-se a presença das artérias vertebral direita e esquerda, próximas à medula oblonga, originando a artéria basilar, que se dividiu nos ramos terminais da artéria basilar direito e esquerdo. Ventral ao trato óptico verificou-se a artéria carótida interna direita e esquerda dividindo-se na artéria cerebral média e rostral direita e esquerda; ainda, dorsal ao quiasma óptico, identificou-se o ramo medial das artérias cerebrais rostrais. Com base nos resultados obtidos, conclui-se que a vascularização da base do encéfalo da paca é suprida pelo sistema carotídeo e vertebro-basilar.(AU)

The Impact of Iron Supplementation for Treating Anemia in Patients with Chronic Kidney Disease: Results from Pairwise and Network Meta-Analyses of Randomized Controlled Trials.

After relative erythropoietin deficiency, iron deficiency is the second most important contributing factor for anemia in chronic kidney disease (CKD) patients. Iron supplementation is a crucial part of the treatment of anemia in CKD patients, and intravenous (IV) iron supplementation is considered to be superior to per os (PO) iron supplementation. The differences between the available formulations are poorly characterized. This report presents results from pairwise and network meta-analyses carried out after a comprehensive search in sources of published and unpublished studies, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations (International prospective register of systematic reviews PROSPERO reference ID: CRD42020148155). Meta-analytic calculations were performed for the outcome of non-response to iron supplementation (i.e., hemoglobin (Hgb) increase of <0.5-1.0 g/dL, or initiation/intensification of erythropoiesis-stimulating agent (ESA) therapy, or increase/change of iron supplement, or requirements of blood transfusion). A total of 34 randomized controlled trials (RCT) were identified, providing numerical data for analyses covering 93.7% (n = 10.097) of the total study population. At the network level, iron supplementation seems to have a more protective effect against the outcome of non-response before the start of dialysis than once dialysis is initiated, and some preparations seem to be more potent (e.g., ferumoxytol, ferric carboxymaltose), compared to the rest of iron supplements assessed (surface under the cumulative ranking area (SUCRA) > 0.8). This study provides parameters for adequately following-up patients requiring iron supplementation, by presenting the most performing preparations, and, indirectly, by making it possible to identify good responders among all patients treated with these medicines.

Effects of pneumoperitoneum and trendelenburg position on intraocular pressure (IOP) in isofluorane anesthetised cats / Efeitos do pneumoperitônio e da posição de trendelenburg sobre a pressão intraocular em gatos anestesiados com isoflurano

The aim of this study was to determine whether a pneumoperitoneum of 10 mmHg combined or not with the Trendelenburg position could lead to significant changes in intraocular pressure (IOP), ocular pressure perfusion (OPP), and cardiorespiratory variables; as well as determine whether a correlation exists between IOP and mean arterial blood pressure (MAP), and/or partial pressure of carbon dioxide in arterial blood (PaCO2) in cats. Animals were allocated in two groups (n=7/group): GC (without inclination) and GTREN (Trendelenburg position). The variables were recorded before (baseline) and during 30 minutes (T5-T30) after insufflation. In GTREN, a reduction in heart rate was observed at T5 and in respiratory rate at T5 and T15. There was an increase in IOP at T5-T30 in comparison to baseline. There was a reduction in potential of hydrogen in arterial blood in both groups at all times in comparison to baseline. Partial pressure of carbon dioxide in arterial blood was increased at T15-T30 in GC and at T5-T30 in GTREN. In conclusion, the pneumoperitoneum of 10mmHg CO2 did not significantly affect IOP or OPP in cats anaesthetised with isofluorane and kept under spontaneous ventilation. However, induced pneumoperitoneum combined with Trendelenburg position resulted in an increase in IOP in cats subjected to the same anaesthetic conditions, but did not affect OPP.

O objetivo deste estudo foi determinar se o pneumoperitônio de 10 mmHg associado, ou não, à posição de Trendelenburg poderia levar a alterações significativas na Pressão Intraocular (PIO), Pressão de Perfusão Ocular (PPO) e variáveis cardiorrespiratórias, bem como determinar se havia correlação entre a PIO e a Pressão Arterial Média (PAM) e/ou Pressão Parcial de Dióxido de Carbono no Sangue Arterial (PaCO2) em gatos. Os animais foram alocados em dois grupos (n = 7/grupo): GC (sem inclinação) e GTREN (posição de Trendelenburg). As variáveis foram registradas antes (linha de base) e durante 30 minutos (T5-T30) após a insuflação. No GTREN, foi observada redução na frequência cardíaca em T5 e, na frequência respiratória, em T5 e T15. Houve aumento da PIO no T5-T30 comparativamente ao valor basal. Houve redução no Potencial de Hidrogênio no sangue arterial em ambos os grupos em todos os momentos comparativamente à linha de base. A Pressão Parcial de Dióxido de Carbono no sangue arterial aumentou em T15-T30 no GC e em T5-T30 no GTREN. Concluiu-se que o pneumoperitônio de 10mmHg CO2 não afetou significativamente a PIO ou a PPO em gatos anestesiados com isofluorano e mantidos sob ventilação espontânea. No entanto, o pneumoperitônio induzido combinado à posição de Trendelenburg resultou em aumento da PIO em gatos submetidos às mesmas condições anestésicas, mas não afetou a PPO.

Genetic factors contributing to autism spectrum disorder in Williams-Beuren syndrome.

BACKGROUND: The hallmark of the neurobehavioural phenotype of Williams-Beuren syndrome (WBS) is increased sociability and relatively preserved language skills, often described as opposite to autism spectrum disorders (ASD). However, the prevalence of ASD in WBS is 6-10 times higher than in the general population. We have investigated the genetic factors that could contribute to the ASD phenotype in individuals with WBS. METHODS: We studied four males and four females with WBS and a confirmed diagnosis of ASD by the Autism Diagnostic Interview-Revised. We performed a detailed molecular characterisation of the deletion and searched for genomic variants using exome sequencing. RESULTS: A de novo deletion of 1.55 Mb (6 cases) or 1.83 Mb (2 cases) at 7q11.23 was detected, being in 7/8 patients of paternal origin. No common breakpoint, deletion mechanism or size was found. Two cases were hemizygous for the rare T allele at rs12539160 in MLXIPL, previously associated with ASD. Inherited rare variants in ASD-related or functionally constrained genes and a de novo nonsense mutation in the UBR5 gene were identified in six cases, with higher burden in females compared with males (p=0.016). CONCLUSIONS: The increased susceptibility to ASD in patients with WBS might be due to additive effects of the common WBS deletion, inherited and de novo rare sequence variants in ASD-related genes elsewhere in the genome, with higher burden of deleterious mutations required for females, and possible hypomorphic variants in the hemizygous allele or cis-acting mechanisms on imprinting.

Cholesterol-Lowering Treatment in Chronic Kidney Disease: Multistage Pairwise and Network Meta-Analyses.

Pairwise and network meta-analyses on the relationship between the efficacy of the use of statins with or without ezetimibe and reductions in low-density lipoprotein cholesterol (LDLc) and C-reactive protein (CRP) in patients with chronic kidney disease (CKD) are presented. In the pairwise meta-analysis, statins with or without ezetimibe were shown to be efficacious in reducing major adverse cardiovascular events (MACE) in patients with CKD and an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2, in the context of both primary prevention [odds ratio (OR)/95% confidence interval (95% CI)/I2/number of studies (n): 0.50/0.40-0.64/0%/6] and primary/secondary prevention (0.66/0.57-0.76/57%/18). However, in the Bayesian network meta-analysis, compared to the placebo, only atorvastatin 80 mg daily and atorvastatin and rosuvastatin at doses equivalent to simvastatin 20 mg daily reduced the odds of MACEs in this patient population. The network meta-analysis for LDLc and CRP treatment objectives also showed that, regardless of eGFR and excluding dialysis patients, the number of MACEs decreased in patients with CKD, with reductions in both LDLc and CRP of less than 50% (surface under the cumulative ranking (SUCRA)/heterogeneity (vague)/n: 0.77/0.14/3). The evaluation of the benefits of drugs may lead to individualized therapy for CKD patients: Cholesterol-lowering treatment for CKD patients with high levels of both LDLc and CRP is suggested.

Effects of dexmedetomidine combined with commonly administered opioids on clinical variables in dogs.

OBJECTIVE To evaluate cardiopulmonary, sedative, and antinociceptive effects of dexmedetomidine combined with commonly administered opioids in dogs. ANIMALS 8 healthy Beagles. PROCEDURES Dogs were sedated by IM administration of each of 7 treatments. Treatments comprised dexmedetomidine (0.01 mg/kg; Dex) and the same dose of dexmedetomidine plus butorphanol (0.15 mg/kg; Dex-But), meperidine (5 mg/kg; Dex-Mep), methadone (0.5 mg/kg; Dex-Meth), morphine (0.5 mg/kg; Dex-Mor), nalbuphine (0.5 mg/kg; Dex-Nal), or tramadol (5 mg/kg; Dex-Tram). Cardiorespiratory and arterial blood gas variables and sedative and antinociceptive scores were measured before drug injection (time 0; baseline) and at 15-minute intervals for 120 minutes. RESULTS Heart rate was reduced at all time points after injection of Dex-But, Dex-Mep, Dex-Meth, and Dex-Mor treatments. There was a significant reduction of mean arterial blood pressure for Dex-But, Dex-Mep, and Dex-Mor treatments at all time points, compared with baseline. There was a significant decrease in respiratory rate, compared with the baseline value, for Dex, Dex-But, Dex-Meth, and Dex-Tram treatments from 15 to 120 minutes. A significant decrease in arterial blood pH was detected from baseline to 120 minutes for all treatments, with differences among Dex, Dex-Mep, and Dex-Mor. Reduction in Pao2 was greater for the Dex-Mep treatment than for the other treatments. The highest sedation scores were detected for Dex-Mep and Dex-Meth treatments. Antinociceptive effects were superior for Dex-But, Dex-Meth, Dex-Mor, and Dex-Nal treatments. CONCLUSIONS AND CLINICAL RELEVANCE Drug combinations caused similar cardiorespiratory changes, with greater sedative effects for Dex-Mep and Dex-Meth and superior antinociceptive effects for Dex-But, Dex-Meth, Dex-Mor, and Dex-Nal.

Recuentos de células T reguladoras en sangre periférica como biomarcador predictivo del resultado del trasplante renal: revisión sistemática / Peripheral blood regulatory T cell counts as a predictive biomarker for the outcome of kidney transplant: A systematic review

Fundamento y objetivo: Las células T reguladoras circulantes podrían convertirse en un adecuado biomarcador para los trasplantados renales. El objetivo de este estudio es evaluar el efecto de los inhibidores de la mammalian target of rapamycin (I-mTOR, «diana de rapamicina en células de mamífero») en las células reguladoras, y el interés clínico de este efecto. Material y métodos: Revisión sistemática de trabajos publicados y no publicados. Bases de datos y repositorios del mundo entero. Se buscaron ensayos controlados aleatorizados y estudios de cohortes que compararon recuentos de células reguladoras y episodios de rechazo entre trasplantados tratados con y sin I-mTOR. Los trabajos podían medir la correlación células reguladoras-filtrado glomerular. Se evaluó la codependencia células reguladoras-eficacia de los I-mTOR. Resultados: Se incluyeron 5 ensayos y 9 estudios. Las diferencias clínicas no permitieron una estimación cuantitativa del efecto de la inmunosupresión en el número de células reguladoras. Sin embargo, observamos que hay más células reguladoras con sirolimus o everolimus. El número de episodios de rechazo fue similar con anticalcineurínicos que con I-mTOR, a pesar de las diferencias en el número de células reguladoras. La correlación combinada células reguladoras-filtrado glomerular fue prospectivamente de 0,114, con un intervalo de confianza al 95% (IC 95%) de 0,062-0,406, y retrospectivamente, de 0,13 (IC 95% 0,0-0,361). Existen pruebas directas, aunque de bajo nivel (aleatorización estratificada por el biomarcador), respecto a la codependencia células reguladoras-eficacia de los I-mTOR. Conclusión: El número de células reguladoras puede asociarse a buenos resultados o desenlaces en los tratados con I-mTOR (eficacia antirrechazo), considerando la relación entre estas células y la función del injerto. Registro: PROSPERO (CRD42016046285) (AU)

Background and objective: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. Material and methods: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated. Results: Five trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy. Conclusions: Regulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function Registration: PROSPERO (CRD42016046285) (AU)

Peripheral blood regulatory T cell counts as a predictive biomarker for the outcome of kidney transplant: A systematic review. / Recuentos de células T reguladoras en sangre periférica como biomarcador predictivo del resultado del trasplante renal: revisión sistemática.

BACKGROUND AND OBJECTIVE: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. MATERIAL AND METHODS: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated. RESULTS: Five trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy. CONCLUSIONS: Regulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function. REGISTRATION: PROSPERO (CRD42016046285).

Behavioral Profiles of Children With Williams Syndrome From Spain and the United States: Cross-Cultural Similarities and Differences.

To identify similarities and differences in the behavioral profile of children with Williams syndrome from Spain (n = 53) and the United States (n = 145), we asked parents of 6- to 14-year-olds with Williams syndrome to complete the Child Behavior Checklist 6-18. The distribution of raw scores was significantly higher for the Spanish sample than the American sample for all of the higher-order factors and half of both the empirically based and Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented scales. In contrast, analyses based on country-specific T-scores indicated that the distribution for the Spanish sample was significantly higher than for the American sample only on the Social Problems scale. No gender differences were found. Genetic and cultural influences on children's behavior and cultural influences on parental ratings of behavior are discussed.

Mechanical flexural ex vivo study of osteotomized swine femurs stabilized with two types of polyamide 12 rods / Estudo mecânico de flexão, ex-vivo, de fêmures suínos osteotomizados, estabilizados com dois tipos de haste de poliamida 12

ABSTRACT: Long bone fractures are commonly in surgery routine and several bone imobilization techniques are currently available. Technological progress has enabled to use low cost materials in surgical procedures. Thus, the aim of this study was to evaluate the applicability of polyamide 12 rods, solid and hollow in swine femurs, comparing them through flexion strength. This study had as second aim to fix the locking errors, commom place in interlocking nails, once polyamide 12 allows perforation in any direction by orthopaedic screw. Six groups were used: G1 - eight whole swine femurs; G2 - eight whole swine femurs with drilled medullary canal; G3 - two solid polyamide 12 rods; G4 - two hollow polyamide 12 rods; G5 - eight osteotomized drilled swine femurs with a solid polyamide 12 rod implanted in the medullary canal and locked by four 316L stainless steel screws; and G6 - similar to G5 but using hollow rods instead of solid ones. No significant differences were observed for the modulus of rupture between solid and hollow rods, demonstrating that both rods had similar performances. These results led to the speculation that the addition of other polymers to the hollow rods could increase their strength and thus the bone-implant system. Furthermore, the comparison between G1, G5 and G6 could be analyzed using the finite element method in future. New polymeric materials may be developed based on the data from this study, strengthening the bone-implant system and making possible screws to be placed in any direction, nullifying the detrimental forces on the fracture site.

RESUMO: Fraturas em ossos longos são comumente encontradas na rotina cirúrgica e várias técnicas de imobilização óssea estão disponíveis. Com o avanço tecnológico, tornou-se viável utilizar materiais de baixo custo nos procedimentos, portanto esse estudo objetivou avaliar a aplicabilidade de hastes de poliamida 12, sólidas e vazadas, implantadas em fêmures suínos, comparando-as segundo as forças de flexão e aos erros de bloqueio, corriqueiros nesse implante, uma vez que a poliamida 12 permite sua perfuração em qualquer direção por meio de parafusos ortopédicos. Seis grupos foram usados: G1 - oito fêmures suínos íntegros; G2 - oito fêmures suínos, fresados intramedularmente; G3 - duas hastes maciças de poliamida 12; G4 - duas hastes vazadas de poliamida 12; G5 - oito fêmures suínos osteotomizados e fresados, com haste de poliamida 12 maciça implantada no canal medular e bloqueada com quatro parafusos de aço inoxidável 316L e G6 - diferente de G5 apenas por utilizar hastes vazadas. Não foram observadas diferenças significativas no módulo de ruptura entre hastes sólidas e vazadas, demonstrando que ambas apresentaram o mesmo desempenho. Estes resultados levaram à especulação de que adicionar outros polímeros às hastes vazadas aumentaria sua força e, portanto, do sistema osso-implante. Além disso, a comparação entre G1, G5 e G6 poderia no futuro ser analisada utilizando o método dos elementos finitos. Novos polímeros podem ser desenvolvidos baseando-se nos dados deste estudo, reforçando o sistema osso-implante e também possibilitando o uso de perfurações para o bloqueio no transoperatório em qualquer direção, anulando as forças deletérias atuantes no sítio de fratura.

Facial emotion processing in patients with social anxiety disorder and Williams-Beuren syndrome: an fMRI study.

BACKGROUND: Social anxiety disorder (SAD) and Williams-Beuren syndrome (WBS) are 2 conditions with major differences in terms of genetics, development and cognitive profiles. Both conditions are associated with compromised abilities in overlapping areas, including social approach, processing of social emotional cues and gaze behaviour, and to some extent they are associated with opposite behaviours in these domains. We examined common and distinct patterns of brain activation during a facial emotion processing paradigm in patients with SAD and WBS. METHODS: We examined patients with SAD and WBS and healthy controls matched by age and laterality using functional MRI during the processing of happy, fearful and angry faces. RESULTS: We included 20 patients with SAD and 20 with WBS as well as 20 matched controls in our study. Patients with SAD and WBS did not differ in the pattern of limbic activation. We observed differences in early visual areas of the face processing network in patients with WBS and differences in the cortical prefrontal regions involved in the top-down regulation of anxiety and in the fusiform gyrus for patients with SAD. Compared with those in the SAD and control groups, participants in the WBS group did not activate the right lateral inferior occipital cortex. In addition, compared with controls, patients with WBS hypoactivated the posterior primary visual cortex and showed significantly less deactivation in the right temporal operculum. Participants in the SAD group showed decreased prefrontal activation compared with those in the WBS and control groups. In addition, compared with controls, participants with SAD showed decreased fusiform activation. Participants with SAD and WBS also differed in the pattern of activation in the superior temporal gyrus, a region that has been linked to gaze processing. LIMITATIONS: The results observed in the WBS group are limited by the IQ of the WBS sample; however, the specificity of findings suggests that the pattern of brain activation observed for WBS is more likely to reflect a neurobiological substrate rather than intellectual impairment per se. CONCLUSION: Patients with SAD and WBS showed common and specific patterns of brain activation. Our results highlight the role of cortical regions during facial emotion processing in individuals with SAD and WBS.

Associação dexametasona oral e apinefrina inalatória é mais efetiva do que as intervenções isoladas de epinefrina ou dexametasona para o tratamento de bronquiolite / Association apinefrina inhaled and oral dexamethasone is more effective than isolated interventions of epinephrine or dexamethasone for the treatment of bronchiolitis

A combinação da nebulização de epinefria e a dexametasona oral em modestos benefícios para crianças com bronquiolites e mantém 1 em 11 fora do hospital.As revisões da Cochrane não sugerem o uso dessas medicações isoladamente.Também sugerem a necessidade de mais estudos aleatórios duplo-cegos para se chegar em um tratamento ideal.Este POEM nos mostra que o uso combinado de medicações é uma ação terapêutica positiva ainda que não definitiva.

Eritropoetina não diminui mortalidade em pacientes com câncer / Erythropoietin does not reduce mortality in patients with cancer

Pacientes com câncer tratados com estimuladores de eritropoiese apresentam risco de morte similiar aos que utilizaram a Eitropoetina.