Progression of partial to complete ruptures of the Achilles tendon during rehabilitation: A study using a finite element model.

Substantial research on complete Achilles tendon ruptures is available, but guidance on partial ruptures is comparatively sparse. Conservative management is considered acceptable in partial tendon ruptures affecting less than 50% of the tendon's width, but supporting experimental evidence is currently lacking. Using a previously validated finite element model of the Achilles tendon, this study aimed to assess whether loading conditions simulating an early functional rehabilitation protocol could elicit progression to a complete rupture in partial ruptures of varying severity. In silico tendon rupture simulations were performed to locate the most likely rupture site for least, moderate, and extreme subtendon twist configurations. These three models were split at the corresponding rupture site and two sets of partial ruptures were created for each, starting from the medial and lateral sides, and ranging from 10% to 50% loss of continuity. Simulations were conducted with material parameters from healthy and tendinopathic tendons. Partial ruptures were considered to progress if the volume of elements showing a maximum principal strain above 10% exceeded 3 mm3 . To assess whether the tendinopathic tendons typical geometric characteristics could compensate for the inferior material properties found in tendinopathy, an additional model with increased cross-sectional area in the free tendon region was developed. Progression to complete ruptures occurred even with less than a 50% loss of continuity, regardless of subtendon twisting, and material parameters. The tendinopathic tendon model with increased cross-sectional area showed similar results. These findings suggest the current criteria for surgical treatment of partial ruptures should be reconsidered. Statement of clinical significance: The clinical significance and most appropriate treatment of partial ruptures of the Achilles tendon is unclear. Despite the widespread use of the "50% rule" in treatment decisions of partial tendon ruptures, experimental evidence supporting it is missing. The present study provides new data, from a validated aponeurotic and free Achilles tendon finite element model, showing that partial ruptures may progress to complete ruptures under loading conditions elicited from functional rehabilitation protocols, even for partial ruptures affecting less than 50% of the tendon's width. Under these novel findings, the current criteria for surgical treatment of partial ruptures should be reconsidered.

Evidence-Based Checklist to Delay Cardiac Arrest in Brain-Dead Potential Organ Donors: The DONORS Cluster Randomized Clinical Trial.

Importance: The effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear. Objective: To evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU). Design, Setting, and Participants: The Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020. Interventions: Hospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care. Main Outcomes and Measures: The primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group. Results: Among the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006). Conclusions and Relevance: This cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist. Trial Registration: ClinicalTrials.gov Identifier: NCT03179020.

Assessing the impact of center volume on the cost-effectiveness of centralizing ERCP.

BACKGROUND AND AIMS: ERCP is a complex endoscopic procedure in which the center's procedure volume influences outcomes. With the increasing healthcare expenses and limited resources, promoting cost-effective care becomes essential for healthcare provision. This study performed a cost-effectiveness analysis to evaluate the hypothesis that high-volume (HV) centers perform ERCP with higher quality at lower costs than low-volume (LV) centers. METHODS: A baseline case compared the current distribution of ERCPs among HV and LV centers with a hypothetical scenario in which all ERCPs are performed at HV centers. A cost-effectiveness analysis was constructed, followed by one-way and two-way sensitivity analyses and probabilistic sensitivity analysis (PSA) using Monte Carlo simulations. RESULTS: In the baseline case, the ICER was -141,017€/year, due to the hypothetical scenario's lower costs and slightly higher QALYs. The model was most sensitive to changes in the transportation costs (109.34%), probability of significant adverse events (AEs) after successful ERCP at LV centers (42.12%), utility after ERCP with significant AEs (30.10%), and probability of significant AEs after successful ERCP at HV centers (23.53%) but only transportation cost above 3,407€ changed the study outcome. The current ERCP distribution would only be cost-effective if LV centers achieved higher success (≥ 92.4% vs. 89.3%) with much lower significant AEs (≤ 0.5% vs 6.7%). The study's main findings remained unchanged while combining all model parameters in the PSA. CONCLUSIONS: Our findings show that HV centers have high-performance rates at lower costs, raising the need to consider the principle of centralization of ERCPs into HV centers to improve the quality of care.

Return-to-performance in elite soccer players after Achilles tendon ruptures: a study using a weighted plus/minus metric and matched-control analysis.

PURPOSE: Studies have shown decreased match participation and shortened careers in athletes suffering Achilles tendon ruptures (ATRs), but assessment using a true performance metric is lacking. Plus/minus (PM) metrics provide a practical and objective approach to player performance assessment and are commonly used in other sports. This study aimed to quantify and compare individual player performance variations in elite football league players who sustained ATRs and returned to play within 1 year compared to those without ATRs, using a PM metric. METHODS: Player and team data were sourced from Transfermarkt.com. Male players sustaining ATRs between 2007 and 2018 were identified through injury reports. A control group (CTRL) was matched by position, age, height, and league, with a 6:1 ratio of controls to ATR subjects. The day of injury was considered "time zero". Year -1 corresponds to the 360 days preceding injury, and Year 1 to the interval between 360 and 720 days after. Performance in the player's main team was evaluated using a previously validated weighted PM metric. Only data from Year -1 and Year 1 were used for ATR versus CTRL group comparisons. Statistical significance was set at p < 0.05. RESULTS: The ATR group included 125 athletes. Data from more than 76,000 matches were analyzed. No statistically significant differences in net weighted PM metric between Year -1 and Year 1 were found. CONCLUSION: No differences were found between athletes suffering from ATRs and controls regarding the weighted PM metric. LEVEL OF EVIDENCE: III.

Horneros consider their neighbors as precious foes regardless of territory size and human disturbance.

Research on neighbor-stranger discrimination theory has revealed the significance of social context and biological traits affecting the mechanisms that drive social discrimination, such as the dear enemy or nasty neighbor effects (strangers or neighbors more threatening, respectively). Nevertheless, the effects of territory size and human activity on neighbor-stranger experiments have yet to be explored. By examining behavioral responses to spontaneous duets of neighbors and playbacks of strangers' duets, we tested whether rufous horneros (Furnarius rufus) in smaller territories show heightened aggression, responding more strongly to strangers and less to neighbors than those in larger territories. This could be expected because birds in larger territories might struggle to differentiate competitors due to limited interactions, hindering familiarity with neighbors. Meanwhile, birds in smaller territories are likely to treat neighbors as dear enemies due to the need to minimize territorial costs caused by presumed frequent intrusions or to protect limited resources. Contrary to predictions, rufous horneros responded more strongly to strangers than neighbors, regardless of owner territory sizes. This suggests that the presumed higher intruder frequency in smaller territories does not necessarily lead to adjusted dear enemy relationships. Yet, small territory holders exhibited heightened vocal responses to duets of unfamiliar intruders, indicating a stronger 'dear enemy' effect compared to birds with larger territories. We also tested whether dear enemy relationships would be heightened during weekends. This is linked to the difficulty urban birds might face in distinguishing neighbors from strangers during high human activity days (i.e., on weekdays), due to factors like noise masking intruder acoustic cues and heightened vigilance. Territorial owners exhibited consistent dear enemy behavior towards neighbors, regardless of our proxy for human activity. This underscores their ability in identifying competitor identities within urban settings.

Integrating modeled environmental variability into neural network training for underwater source localization.

Supervised machine learning (ML) is a powerful tool that has been applied to many fields of underwater acoustics, including acoustic inversion. ML algorithms depend on the existence of extensive labeled datasets, which are difficult to obtain for the task of underwater source localization. A feed-forward neural network (FNN) trained on imbalanced or biased data may end up suffering from a problem analogous to model mismatch in matched field processing (MFP), that is, producing incorrect results due to a difference between the environment sampled by the training data and the actual environment. To overcome this issue, physical and numerical propagation models can act as data augmentation tools to compensate for the lack of comprehensive acoustic data. This paper examines how modeled data can be effectively used for training FNNs. Mismatch tests compare the output from a FNN and MFP and show that the network becomes more robust to various kinds of mismatches when trained on diverse environments. A systematic analysis of how the training dataset's variability impacts a FNN's localization performance on experimental data is carried out. Results show that networks trained with synthetic data achieve better and more robust performance than regular MFP when environment variability is taken into account.

Comparison of molecular methods for Bartonella henselae detection in blood donors.

The Bartonella genus consists of neglected pathogens associated with potentially transfusional-transmitted and fatal human diseases. We aimed to evaluate Bartonella sp. prevalence in 500 blood donors and compare the results with the data already published about these samples. We used molecular diagnostic methods to detect Bartonella sp.-DNA from blood and liquid culture samples: (A) conventional PCR for two gene regions, the ITS targeting the genus Bartonella and the specific gltA Bartonella henselae; (B) nested PCR for the ftsZ gene and (C) qualitative real-time PCR for the gltA gene, both B. henselae specific. We obtained 30/500 (6%) DNA detections from the blood samples; 77/500 (15.4%) DNA detections from liquid culture samples and five (1%) samples had DNA detection from both. In total, we detected B. henselae DNA from 102/500 (20.4%) donors. The samples used in this study had already been submitted for Bartonella sp.-DNA detection using only a conventional PCR in liquid culture. Sixteen samples (3.2%) were positive previously, and from these 16 samples, 13 were negative in the new investigation. We concluded that the use of liquid culture combined with different molecular tests increases the possibility of detecting Bartonella sp.-DNA, but the tests do not avoid false-negative results. More than a fifth of blood donors had at least one PCR that detected Bartonella sp.-DNA among the eight molecular reactions performed now (four reactions in whole blood and four in liquid culture). Seven percent had B. henselae-DNA detection for two or more distinct regions. Considering the results obtained previously, the DNA of Bartonella spp. was detected or the agent isolated in 23% of analyzed blood donors. The results establish that the low bacteremia and the fastidious characteristics of the bacterium are challenges to laboratory diagnosis and can make it difficult to confirm the infection in patients with bartonelloses.

Disruption of the skin, gill, and gut mucosae microbiome of gilthead seabream fingerlings after bacterial infection and antibiotic treatment.

The activity of the microbiome of fish mucosae provides functions related to immune response, digestion, or metabolism. Several biotic and abiotic factors help maintaining microbial homeostasis, with disruptions leading to dysbiosis. Diseases and antibiotic administration are known to cause dysbiosis in farmed fish. Pathogen infections greatly affect the production of gilthead seabream, and antibiotic treatment is still frequently required. Here, we employed a 16S rRNA high-throughput metataxonomics approach to characterize changes in the gut, skin, and gill microbiomes occurring due to infection with Photobacterium damselae subsp. piscicida and subsequent antibiotic treatment with oxytetracycline (OTC), as well as during recovery. Although microbiota response differed between studied tissues, overall changes in composition, diversity, structure, and predicted function were observed in all mucosae. The skin and gill microbiomes of diseased fish became largely dominated by taxa that have been frequently linked to secondary infections, whereas in the gut the genus Vibrio, known to include pathogenic bacteria, increased with OTC treatment. The study highlights the negative impacts of disease and antibiotic treatment on the microbiome of farmed fish. Our results also suggest that fish transportation operations may have profound effects on the fish microbiome, but further studies are needed to accurately evaluate their impact.

Design and validation of a finite element model of the aponeurotic and free Achilles tendon.

The Achilles tendon (AT) is a common injury site. Ruptures are usually located in the free tendon but may cross the myotendinous junction into the aponeurotic region. Considering the possibility of aponeurotic region involvement in AT ruptures, a novel three dimensional (3D) finite element (FE) model that includes both the aponeurotic and free AT regions and features subtendon twisting and sliding was developed. It was hypothesized that the model would be able to predict in vivo data collected from the literature, thus being considered valid, and that model outputs would be most sensitive to subtendon twist configurations. The 3D model was constructed using magnetic resonance images. The model was divided into soleus and gastrocnemius subtendons. In addition to a frictionless contact condition, the interaction between subtendons was modeled using two contact formulations: sliding with anisotropic friction and no sliding. Loads were applied on the tendon's most proximal cross-section and anterior surface, with magnitudes estimated from in vivo studies. Model outputs were compared with experimental data regarding 3D deformation, transverse plane rotation, and nodal displacements in the free tendon. The FE model adequately simulated the free tendon behavior regarding longitudinal strain, cross-section area variation, transverse plane rotation, and sagittal nodal displacements, provided that subtendon sliding was allowed. The frictionless model exhibited noticeable medial transverse sliding of the soleus subtendon, which was present to a much lesser degree in the anisotropic friction model. Model outputs were most sensitive to variations in subtendon twist and dispersion of the collagen fiber orientations. Clinical Significance: This Achilles tendon finite element model, validated using in vivo experimental data, may be used to study its mechanical behavior, injury mechanisms, and rupture risk factors.

Modified triple Kessler with least risk of elongation among Achilles tendon repair techniques: a systematic review and network meta-analysis of human cadaveric studies.

PURPOSE: Current treatment recommendations emphasize early loading, with preservation of tendon length and physiologic tension. The objective of this systematic review and network meta-analysis was to compare failure load and elongation after cyclic loading of Achilles tendon repair techniques at time-zero. METHODS: The databases PubMed, CENTRAL and Web of Science were searched for all published in-vitro studies comparing Achilles tendon repair techniques, or augmentation with autografts/biomaterials, and reports of failure load or elongation after cyclic loading. Only studies using human cadaveric Achilles tendons and matched pairs, or randomized specimen allocation, were selected for quantitative synthesis. A network meta-analysis per primary outcome was performed. Results were summarized as P score rankings and their validity was assessed using statistical methods. RESULTS: Sixteen studies, comprising 367 tendon repairs, were included. The following repair techniques were used (n = number of studies): Krackow (n = 8), Achillon (n = 4), double Krackow (n = 3), Bunnell (n = 3), Percutaneous Achilles Repair System (n = 3), Percutaneous Achilles Repair System Midsubstance (n = 2), Kessler (n = 3), double Kessler (n = 1), modified triple Kessler (n = 1), triple bundle (n = 1), a multifilament stainless steel cable-crimp technique (n = 1) and a double loop knot stitch (n = 1). Five studies assessed augmentation with autografts/biomaterials. Regarding the failure load, biomaterial augmented Krackow repairs occupied the first four positions in the ranking, followed by the multifilament stainless steel cable-crimp and Percutaneous Achilles Repair System Midsubstance techniques. Concerning elongation after cyclic loading, the triple Kessler was ranked first, followed by the Achillon and Percutaneous Achilles Repair System Midsubstance techniques. A negligible correlation between ranks was found (rs = 0.11; p = 0.75n.s.), meaning that a higher repair tensile strength is not necessarily related to improved performance in regard to avoidance of elongation. CONCLUSION: In the failure load network meta-analysis, biomaterial augmented Krackow repairs ranked highest, but noticeable statistical heterogeneity was found. Regarding elongation with cyclic loading, the modified triple Kessler stitch showed the highest probability of ranking first. LEVEL OF EVIDENCE: Level IV.

Early analysis shows that endoscopic flexor hallucis longus transfer has a promising cost-effectiveness profile in the treatment of acute Achilles tendon ruptures.

PURPOSE: Current options for treating an Achilles tendon rupture (ATR) include conservative and surgical approaches. Endoscopic flexor hallucis longus (FHL) transfer has been recently proposed to treat acute ruptures, but its cost-effectiveness potential remains to be evaluated. Therefore, the objective of this study was to perform an early cost-effectiveness analysis of endoscopic FHL transfer for acute ATRs, comparing the costs and benefits of current treatments from a societal perspective. METHODS: A conceptual model was created, with a decision tree, to outline the main health events during the treatment of an acute ATR. The model was parameterized using secondary data. A systematic review of the literature was conducted to gather information on the outcomes of current treatments. Data related to outcomes of endoscopic FHL transfers in acute Achilles ruptures was obtained from a single prospective study. Analysis was limited to the two first years. The incremental cost-effectiveness ratio was the main outcome used to determine the preferred strategy. A willingness-to-pay threshold of $100,000 per quality-adjusted life-year was used. Sensitivity analyses were performed to determine whether changes in input parameters would cause significant deviation from the reference case results. Specifically, a probability sensitivity analysis was conducted using Monte Carlo simulations, and a one-way sensitivity analysis was conducted by sequentially varying each model parameter within a given range. RESULTS: For the reference case, incremental cost-effectiveness ratios exceeded the willingness-to-pay threshold for all the surgical approaches. Overall, primary treatment was the main cost driver. Conservative treatment showed the highest direct costs related to the treatment of complications. In the probabilistic sensitivity analysis, at a willingness-to-pay threshold of $100,000, open surgery was cost-effective in 50.9%, minimally invasive surgery in 55.8%, and endoscopic FHL transfer in 72% of the iterations. The model was most sensitive to parameters related to treatment utilities, followed by the costs of primary treatments. CONCLUSION: Surgical treatments have a moderate likelihood of being cost-effective at a willingness-to-pay threshold of $100,000, with endoscopic FHL transfer showing the highest likelihood. Following injury, interventions to improve health-related quality of life may be better suited for improved cost-effectiveness. LEVEL OF EVIDENCE: Level III.

Current Concept Review: State of Acute Lateral Ankle Injury Classification Systems.

Acute lateral ankle sprain (ALAS) is one of the most frequent musculoskeletal injuries, with a great impact on health and socioeconomic factors. There are few consensuses on this subject and multiple therapeutic options that are difficult to compare due to the lack of a universally adopted classification system. The objective of this study is to is to report the actual knowledge on how ALAS are classified and reported and not to make any therapeutic recommendation. A comprehensive literature review of the literature was carried out through a search in the MEDLINE, Cochrane Library and Google Scholar databases, with identification of articles that describe ways to classify lateral ankle sprains or with relevant content for their classification. Twenty-five different classification systems were identified. The majority of articles referring to ALAS use an unspecific classification. Most classification systems divide sprains into 3 degrees. The most used parameters are the anatomy of the injury, clinical parameters, functional loss and the presence of instability. No articles were found to verify the validity of the systems used, namely regarding their association with therapeutic proposals or prognostic predictions. Based on the available evidence, recommendations cannot be made regarding the most appropriate classification system. The considerable heterogeneity of the existing literature makes it difficult to compare studies and to optimize the treatment and follow-up of these injuries. Future research in this area is necessary to define a practical and rigorous system that can be used universally.

Ehrlichiosis and Anaplasmosis: An Update.

Canine ehrlichiosis and anaplasmosis are zoonotic tick-borne diseases with broad distribution. Advances in diagnostics have enhanced our understanding of the species of rickettsial organisms involved, their expanding geographic distribution, and their impact on the health of dogs, cats, and people. While clinical remission can be achieved with appropriate antimicrobial therapy, optimal treatment modalities for the elimination of infection remain somewhat uncertain. Protection through vaccines for ehrlichiosis or anaplasmosis remains elusive. This review provides practicing veterinarians with the most current information about the transmission, diagnosis, and management of ehrlichiosis and anaplasmosis in dogs and cats.

Pre-injury performance is most important for predicting the level of match participation after Achilles tendon ruptures in elite soccer players: a study using a machine learning classifier.

PURPOSE: Achilles tendon ruptures (ATR) are career-threatening injuries in elite soccer players due to the decreased sports performance they commonly inflict. This study presents an exploratory data analysis of match participation before and after ATRs and an evaluation of the performance of a machine learning (ML) model based on pre-injury features to predict whether a player will return to a previous level of match participation. METHODS: The website transfermarkt.com was mined, between January and March of 2021, for relevant entries regarding soccer players who suffered an ATR while playing in first or second leagues. The difference between average minutes played per match (MPM) 1 year before injury and between 1 and 2 years after the injury was used to identify patterns in match participation after injury. Clustering analysis was performed using k-means clustering. Predictions of post-injury match participation were made using the XGBoost classification algorithm. The performance of this model was evaluated using the area under the receiver operating characteristic curve (AUROC) and Brier score loss (BSL). RESULTS: Two hundred and nine players were included in the study. Data from 32,853 matches was analysed. Exploratory data analysis revealed that forwards, midfielders and defenders increased match participation during the first year after injury, with goalkeepers still improving at 2 years. Players were grouped into four clusters regarding the difference between MPMs 1 year before injury and between 1 and 2 years after the injury. These groups ranged between a severe decrease (n = 34; - 59 ± 13 MPM), moderate decrease (n = 75; - 25 ± 8 MPM), maintenance (n = 70; 0 ± 8 MPM), or increase (n = 30; 32 ± 13 MPM). Regarding the predictive model, the average AUROC after cross-validation was 0.81 ± 0.10, and the BSL was 0.12, with the most important features relating to pre-injury match participation. CONCLUSION: Most players take 1 year to reach peak match participation after an ATR. Good performance was attained using a ML classifier to predict the level of match participation following an ATR, with features related to pre-injury match participation displaying the highest importance. LEVEL OF EVIDENCE: I.

Is arginine supplementation effective in preventing preeclampsia in pregnant women / A suplementação de arginina é efetiva em prevenir pré-eclâmpsia em gestantes?

Objectives: The objective of this study was to review data from randomized controlled trials to assess whether or not the supplementation of L-Arginine (L-Arg) is effective in reducing the incidence of preeclampsia (PE) in pregnancies at risk of developing the disorder. Methods: We aimed to systematic review randomized controlled trials, including those which compared L-Arg supplementation with placebo in pregnant women at high risk of PE development, analyzing PE incidence as the main outcome. Data were collected from MEDLINE/ Pubmed, EMBASE/ Elsevier, LILACS/ BVS and Cochrane. Results: A total of 46 papers were identified in the primary search. After analysis of eligibility, inclusion and exclusion criteria, two articles (which respected in detail all the stages of evaluation) were included in the present review. A risk of bias assessment was performed. Data analysis revealed that the incidence of PE was significantly lower in both studies, and no major adverse effects were reported. The limitations of this study were the lack of standardization between the trials analyzed and the relative low number of studies included. Conclusions: The supplementation with L-Arg appears to reduce the incidence of PE in pregnant women with high risk for its developmen (AU)

Objetivo: O objetivo deste estudo foi revisar dados de ensaios clínicos randomizados para avaliar se a suplementação de L-Arginina é efetiva para reduzir a incidência de pré-eclâmpsia em gestantes com alto risco de desenvolver a doença. Métodos: Realizamos uma revisão sistemática de ensaios clínicos randomizados, incluindo aqueles que compararam a suplementação de L-Arginina com placebo em gestantes de alto risco de desenvolvimento de pré-eclâmpsia, analisando a incidência de pré-eclâmpsia como desfecho principal. Os estudos foram selecionados do MEDLINE/ Pubmed, EMBASE/ Elsevier, LILACS/ BVS e Cochrane. Resultados: Um total de 46 estudos foram identificados na busca primária. Após análise da elegibilidade, dos critérios de inclusão e de exclusão, dois artigos (que respeitaram em detalhes todas etapas de avaliação) foram incluídos na presente revisão. Foi realizada uma avaliação de risco de viés. A análise dos dados revelou que a incidência de pré-eclâmpsia foi significativamente menor em ambos os estudos, e nenhum efeito adverso importante foi relatado. As limitações deste estudo foram a falta de padronização entre os ensaios clínicos analisados e o número relativamente baixo de estudos incluídos. Conclusão: A suplementação com L-Arginina parece reduzir a incidência de pré-eclâmpsia em gestantes de alto risco para seu desenvolvimento (AU)

Is arginine supplementation effective in preventing preeclampsia in pregnant women? / A suplementação de arginina é efetiva em prevenir pré-eclâmpsia em gestantes?

ABSTRACT: Objectives: The objective of this study was to review data from randomized controlled trials to assess whether or not the supplementation of L-Arginine (L-Arg) is effective in reducing the incidence of preeclampsia (PE) in pregnancies at risk of developing the disorder. Methods: We aimed to systematic review randomized controlled trials, including those which compared L-Arg supplementation with placebo in pregnant women at high risk of PE development, analyzing PE incidence as the main outcome. Data were collected from MEDLINE/ Pubmed, EMBASE/ Elsevier, LILACS/ BVS and Cochrane. Results: A total of 46 papers were identified in the primary search. After analysis of eligibility, inclusion and exclusion criteria, two articles (which respected in detail all the stages of evaluation) were included in the present review. A risk of bias assessment was performed. Data analysis revealed that the incidence of PE was significantly lower in both studies, and no major adverse effects were reported. The limitations of this study were the lack of standardization between the trials analyzed and the relative low number of studies included. Conclusions: The supplementation with L-Arg appears to reduce the incidence of PE in pregnant women with high risk for its development. (AU)

RESUMO: Objetivo: O objetivo deste estudo foi revisar dados de ensaios clínicos randomizados para avaliar se a suplementação de L-Arginina é efetiva para reduzir a incidência de pré-eclâmpsia em gestantes com alto risco de desenvolver a doença. Métodos: Realizamos uma revisão sistemática de ensaios clínicos randomizados, incluindo aqueles que compararam a suplementação de L-Arginina com placebo em gestantes de alto risco de desenvolvimento de pré-eclâmpsia, analisando a incidência de pré-eclâmpsia como desfecho principal. Os estudos foram selecionados do MEDLINE/ Pubmed, EMBASE/ Elsevier, LILACS/ BVS e Cochrane. Resultados: Um total de 46 estudos foram identificados na busca primária. Após análise da elegibilidade, dos critérios de inclusão e de exclusão, dois artigos (que respeitaram em detalhes todas etapas de avaliação) foram incluídos na presente revisão. Foi realizada uma avaliação de risco de viés. A análise dos dados revelou que a incidência de pré-eclâmpsia foi significativamente menor em ambos os estudos, e nenhum efeito adverso importante foi relatado. As limitações deste estudo foram a falta de padronização entre os ensaios clínicos analisados e o número relativamente baixo de estudos incluídos. Conclusão: A suplementação com L-Arginina parece reduzir a incidência de pré-eclâmpsia em gestantes de alto risco para seu desenvolvimento. (AU)

A review of Covid-19 and acute kidney injury: from pathophysiology to clinical results / Uma revisão da Covid-19 e lesão renal aguda: da fisiopatologia aos resultados clínicos

Abstract Acute kidney injury (AKI) in hospitalized patients with COVID-19 is associated with higher mortality and a worse prognosis. Nevertheless, most patients with COVID-19 have mild symptoms, and about 5% can develop more severe symptoms and involve hypovolemia and multiple organ dysfunction syndrome. In a pathophysiological perspective, severe SARS-CoV-2 infection is characterized by numerous dependent pathways triggered by hypercytokinemia, especially IL-6 and TNF-alpha, leading to systemic inflammation, hypercoagulability, and multiple organ dysfunction. Systemic endotheliitis and direct viral tropism to proximal renal tubular cells and podocytes are important pathophysiological mechanisms leading to kidney injury in patients with more critical infection, with a clinical presentation ranging from proteinuria and/or glomerular hematuria to fulminant AKI requiring renal replacement therapies. Glomerulonephritis, rhabdomyolysis, and nephrotoxic drugs are also associated with kidney damage in patients with COVID-19. Thus, AKI and proteinuria are independent risk factors for mortality in patients with SARS-CoV-2 infection. We provide a comprehensive review of the literature emphasizing the impact of acute kidney involvement in the evolutive prognosis and mortality of patients with COVID-19.

Resumo A lesão renal aguda (LRA) em pacientes hospitalizados com COVID-19 está associada a maior mortalidade e um pior prognóstico. No entanto, a maioria dos pacientes com COVID-19 tem sintomas leves e cerca de 5% podem desenvolver sintomas mais graves e envolver hipovolemia e síndrome de disfunção de múltiplos órgãos. Em uma perspectiva fisiopatológica, a infecção grave por SARS-CoV-2 é caracterizada por numerosas vias dependentes desencadeadas por hipercitocinemia, especialmente IL-6 e TNF-alfa, levando à inflamação sistêmica, hipercoagulabilidade e disfunção de múltiplos órgãos. A endotelite sistêmica e o tropismo viral direto às células tubulares proximais renais e podócitos são mecanismos fisiopatológicos importantes que levam à lesão renal em pacientes com infecção mais crítica, com uma apresentação clínica que varia de proteinúria e/ou hematúria glomerular a LRA fulminante, exigindo terapias renais substitutivas. Glomerulonefrite, rabdomiólise e drogas nefrotóxicas também estão associadas a danos renais em pacientes com COVID-19. Assim, a LRA e a proteinúria são fatores de risco independentes para mortalidade em pacientes com infecção por SARS-CoV-2. Fornecemos uma revisão abrangente da literatura, enfatizando o impacto do envolvimento renal agudo no prognóstico evolutivo e na mortalidade de pacientes com COVID-19.

COVID-19 and chronic kidney disease: a comprehensive review / COVID-19 e doença renal crônica: uma revisão abrangente

Abstract Kidney impairment in hospitalized patients with SARS-CoV-2 infection is associated with increased in-hospital mortality and worse clinical evolution, raising concerns towards patients with chronic kidney disease (CKD). From a pathophysiological perspective, COVID-19 is characterized by an overproduction of inflammatory cytokines (IL-6, TNF-alpha), causing systemic inflammation and hypercoagulability, and multiple organ dysfunction syndrome. Emerging data postulate that CKD under conservative treatment or renal replacement therapy (RRT) is an important risk factor for disease severity and higher in-hospital mortality amongst patients with COVID-19. Regarding RAAS blockers therapy during the pandemic, the initial assumption of a potential increase and deleterious impact in infectivity, disease severity, and mortality was not evidenced in medical literature. Moreover, the challenge of implementing social distancing in patients requiring dialysis during the pandemic prompted national and international societies to publish recommendations regarding the adoption of safety measures to reduce transmission risk and optimize dialysis treatment during the COVID-19 pandemic. Current data convey that kidney transplant recipients are more vulnerable to more severe infection. Thus, we provide a comprehensive review of the clinical outcomes and prognosis of patients with CKD under conservative treatment and dialysis, and kidney transplant recipients and COVID-19 infection.

Resumo O comprometimento renal em pacientes hospitalizados com infecção por SARS-CoV-2 está associado ao aumento da mortalidade hospitalar e pior evolução clínica, levantando preocupações em relação a pacientes com doença renal crônica (DRC). De uma perspectiva fisiopatológica, a COVID-19 é caracterizada por uma superprodução de citocinas inflamatórias (IL-6, TNF-alfa), causando inflamação sistêmica e hipercoagulabilidade, e síndrome de disfunção de múltiplos órgãos. Dados emergentes postulam que a DRC sob tratamento conservador ou terapia renal substitutiva (TRS) é um fator de risco importante para a gravidade da doença e maior mortalidade hospitalar entre pacientes com COVID-19. Em relação à terapia com bloqueadores RAAS durante a pandemia, havia uma suposição inicial de que a classe pudesse causar um aumento potencial na infectividade, e impacto deletério na gravidade da doença e mortalidade, mas que não foi confirmada na literatura médica. Além disso, o desafio de implementar o distanciamento social em pacientes que necessitam de diálise durante a pandemia incentivou sociedades nacionais e internacionais a publicar recomendações sobre a adoção de medidas de segurança para reduzir o risco de transmissão e otimizar o tratamento de diálise durante a pandemia COVID-19. Os dados atuais mostram que os receptores de transplante renal são mais vulneráveis a infecções mais graves. Assim, fizemos uma revisão abrangente dos desfechos clínicos e prognóstico de pacientes com DRC sob tratamento conservador e diálise, e receptores de transplante renal e infecção por COVID-19.

Data analysis workflow for the detection of canine vector-borne pathogens using 16 S rRNA Next-Generation Sequencing.

BACKGROUND: Vector-borne diseases (VBDs) impact both human and veterinary medicine and pose special public health challenges. The main bacterial vector-borne pathogens (VBPs) of importance in veterinary medicine include Anaplasma spp., Bartonella spp., Ehrlichia spp., and Spotted Fever Group Rickettsia. Taxon-targeted PCR assays are the current gold standard for VBP diagnostics but limitations on the detection of genetically diverse organisms support a novel approach for broader detection of VBPs. We present a methodology for genetic characterization of VBPs using Next-Generation Sequencing (NGS) and computational approaches. A major advantage of NGS is the ability to detect multiple organisms present in the same clinical sample in an unsupervised (i.e. non-targeted) and semi-quantitative way. The Standard Operating Procedure (SOP) presented here combines industry-standard microbiome analysis tools with our ad-hoc bioinformatic scripts to form a complete analysis pipeline accessible to veterinary scientists and freely available for download and use at https://github.com/eltonjrv/microbiome.westernu/tree/SOP . RESULTS: We tested and validated our SOP by mimicking single, double, and triple infections in genomic canine DNA using serial dilutions of plasmids containing the entire 16 S rRNA gene sequence of (A) phagocytophilum, (B) v. berkhoffii, and E. canis. NGS with broad-range 16 S rRNA primers followed by our bioinformatics SOP was capable of detecting these pathogens in biological replicates of different dilutions. These results illustrate the ability of NGS to detect and genetically characterize multi-infections with different amounts of pathogens in a single sample. CONCLUSIONS: Bloodborne microbiomics & metagenomics approaches may help expand the molecular diagnostic toolbox in veterinary and human medicine. In this paper, we present both in vitro and in silico detailed protocols that can be combined into a single workflow that may provide a significant improvement in VBP diagnostics and also facilitate future applications of microbiome research in veterinary medicine.