Co-carriage of Plasmid NDM and Chromosomal KPC in Klebsiella pneumoniae ST255 Human Wound Isolate in Brazil.

Multidrug-resistant K. pneumoniae is one of the main causes of hospital-acquired infections worldwide and frequently carries antimicrobial resistance genes in moving elements. In this study, we described a K. pneumoniae clinical isolate carrying simultaneous chromosomal blaKPC, and plasmid-mediated blaNDM and blaOXA-9. The isolate is multidrug-resistant and belongs to ST 225. While blaKPC were identified in the chromosome, the blaNDM was mediated by IncFII(K) plasmid and the blaOXA-9, in a IncFIB(K) plasmid. The blaKPC context was composed by Tn4401 transposon and two insertion sequences ISKpn6 and ISKpn7. The co-production of diverse ß-lactamases brings an alert about a new adaptive profile of K. pneumoniae strains and their dissemination in the hospital-acquired infectious.

Preparation of stable and long-lived source samples for the stand-alone beam program at the Facility for Rare Isotope Beams.

At the Facility for Rare Isotope Beams (FRIB), an oven-ion source combination was used to create rare isotope beams in support of the stand-alone user beam program of the ReAccelerator (ReA) facility. This ion source, called Batch-Mode Ion Source (BMIS), was loaded with enriched stable nuclides (30Si, 50Cr, and 58Fe) and long-lived radionuclides (26Al, 32Si). The introduced samples, herein designated as source samples, were thermally volatilized in the BMIS oven, and then ionization was used to generate the required beams. Owing to the different chemical behavior of the used samples, it was important to tailor the sample loading process for each desired beam species. An important parameter here is the volatility of the introduced species, which influences the adequate release of the isotope of interest. Additionally, any co-present, volatile components will affect the ion yields of the desired isotope, while isobaric contaminants will decrease the beam purity. To manufacture isotope source samples that meet these characteristics, various chemical methodologies were developed. All prepared samples were successfully used in BMIS to deliver beams for various user beam experiments. The here-established sample preparation techniques will greatly aid future efforts in developing offline rare-isotope beams.

Evaluation of XGEN Multi Sepsis Flow Chip Molecular Assay for Early Diagnosis of Bloodstream Infection.

Among healthcare-associated infections that can affect a critically ill patient, bloodstream infections are one of the most frequent causes of mortality, especially in hospitalized patients. The objective of this work is to evaluate the performance of the XGEN Multi Sepsis Flow Chip for the rapid diagnosis of bloodstream infections compared with conventional tests. In total, 101 positive blood culture samples were included, and the results obtained by the phenotypic conventional method (culture with susceptibility profile) were compared with results obtained by the XGEN Multi Sepsis Flow Chip. This molecular assay allows the simultaneous detection of the main bloodstream infection pathogens, and their most common antibiotic resistance markers in a short period of time. It was possible to observe substantial agreement between the methods for identifying the genus of pathogens. Considering species, the agreement was excellent. In relation to susceptibility, excellent agreement was noted between the detected resistance genes and susceptibility profile obtained through conventional antibiograms. The evaluated assay presented very early and satisfactory results for identification and detection of resistance genes of the main pathogens involved in bloodstream infections.

Unravelling complex transposable elements surrounding blaGES-16 in a Pseudomonas aeruginosa ExoU strain.

OBJECTIVES: We characterised the complex surrounding regions of blaGES-16 in a Pseudomonas aeruginosa exoU+ strain (P-10.226) in Brazil. METHODS: Species identification was performed by MALDI-TOF MS, and the antimicrobial susceptibility profile was determined by broth microdilution based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. The whole genome sequencing (WGS) of P-10.226 strain was performed using both short-read paired-end sequencing on the Illumina MiSeq platform as well as the long-read Oxford Nanopore MinION. RESULTS: WGS analysis showed that P-10.226 carried blaGES-16, which was found as a gene cassette inserted into a novel class I integron, In1992 (aadB-blaOXA-56-blaGES-16-aadB-aadA6c), whose 3'-CS was truncated by a nested transposable element, IS5564::ISPa157. The structure was even more complex since IS6100-ΔIS6100 structure and a TnAs2-like harbouring the operon merRTPADE was found downstream In1992. Fragments of TnAs3 harbouring 25-bp imperfect inverted repeats were identified bordering the intl1 of In1992 and also flanking IS6100-ΔIS6100, which might be genetic marks of its previous presence in the genome. Interestingly, In1992 also shows a distinct cassette array from In581 (blaGES-16-dfrA22-aacA27-aadA1), which was previously reported in Serratia marcescens strains recovered in Brazil. Finally, exoU gene, which encodes a potent cytotoxin of type III secretion systems (T3SS) effector proteins from P. aeruginosa and is associated to severe infections, was also detected. CONCLUSION: We described the novel In1992 carrying blaGES-16 surrounded by complex transposition events in a XDR P. aeruginosa strain. The identification of many sets of direct repeats adjacent to TnAs3 fragments indicates a major past of transposition events that shaped the current genetic environment of In1992.

Genomic analyses of ciprofloxacin-resistant Neisseria gonorrhoeae isolates recovered from the largest South American metropolitan area.

We sequenced 13 Neisseria gonorrhoeae isolates exhibiting distinct susceptibility profiles and which were recovered over 12 years in the metropolitan region of São Paulo, Brazil. Whole Genome Sequencing (WGS) was performed on an Illumina MiSeq™ 2 × 300 bp paired-end reads. Bioinformatics analyses were carried out using CGE, PATRIC, and BLAST databases for manual curation of obtained genomes. Multilocus sequence typing (MLST) analysis identified seven STs, namely ST1580, ST1590, ST1901, ST1902, ST8161, ST9363, and ST15640. Moreover, a diversity of mutations was observed in MtrR/G45D-A39T, PIB/G120K-A121S, and PBP1/L421P. Mutations associated with sulfonamides (DHPS/R228S) and rifampicin (RNAP/H552N) were also detected, as well as tetracycline resistance determinants, namely rpsJ/V57M and tet(M). The results presented herein can contribute to the knowledge of N. gonorrhoeae strains circulating in Sao Paulo, Brazil.

Broad-spectrum antimicrobial consumption trends and correlation with bacterial infections and antimicrobial resistance over 5 years.

OBJECTIVES: Consumption trends of four broad-spectrum antimicrobials and their correlation with antimicrobial resistance in Gram-negative bacilli (GNB) from 2013-2017 within intensive care units (ICUs) were explored. METHODS: Consumption of meropenem (MEM), polymyxin B (PMB), piperacillin/tazobactam (TZP) and cefepime (FEP) in defined daily doses per 1000 patient-days (DDD/1000PD) was measured. Infection-related GNB isolates were grouped according to specific resistance profiles. Time series of antimicrobial consumption and their parametric correlation with each grouped resistant GNB were explored. RESULTS: A total of 1423 GNB were evaluated. A significant linear decline in consumption was observed for MEM [slope -3.88, 95% confidence interval (CI) -4.96 to -2.81; P < 0.0001] and PMB (slope -3.51, 95% CI -5.528 to -1.495; P = 0.0009). A significant decline in MEM-non-susceptible Acinetobacter spp. (R2 = 0.476; P = 0.006) and an increase in FEP-non-susceptible Escherichia coli (R2 = 0.124; P = 0.006) was observed. A significant correlation between MEM consumption and MEM-non-susceptible Acinetobacter spp. (r = 0.43; P = 0.001) was observed. MEM consumption and MEM-non-susceptible Acinetobacter spp. showed a positive correlation. CONCLUSION: Reduction in the consumption of broad-spectrum antimicrobials may alter the frequency of infection-related isolates and their antimicrobial resistance profiles.

New species records of Gasteruptiidae (Hymenoptera, Evanioidea) from Eastern Uruguay.

In this study, the Gasteruptiidae (Hymenoptera, Evanioidea) collected in three environments at the Department of Rocha, in Eastern Uruguay, were documented based on a survey carried out with Malaise traps between December 2014 and December 2016. During the samplings, four species of Gasteruption Latreille, 1796 were captured, being 14 females and three males of Gasteruption brachychaetun Schrottky, 1906; eight females and five males of Gasteruption brasiliense (Blanchard, 1840); one female of Gasteruption helenae Macedo, 2011 and one female of Gasteruption brandaoi Macedo, 2011. Gasteruption brachychaetun, G. helenae and G. brandaoi are recorded by the first time from Uruguay.

Role of the left coronary artery geometry configuration in atherosusceptibility: CFD simulations considering sPTT model for blood.

The achievement of clinically viable methodologies to simulate the hemodynamics in patient-specific coronary arteries is still a major challenge. Therefore, the novelty of this work is attained by the introduction of the viscoelastic property of blood in the numerical simulations, to study the role of the left coronary artery (LCA) geometry configuration in the atherosusceptibility. Apparently healthy patients were used and four different methodologies were tested. The methodology giving the most accurate results at the same time of having the lowest computational time is the one considering the viscoelastic property of blood and computational fluid dynamics. A Pearson correlation analysis was used to highlight relationships between geometric configuration and hemodynamic descriptors based on the simulated wall shear stress (WSS). The left main stem (LMS) has the greatest atherosusceptibility followed by the left anterior descending artery (LAD) since the relative residence time (RRT) average values are 3.81 and 3.70 Pa-1, respectively. The geometric parameters with relevant contribution to directional flow change are the cross-sectional areas, especially the one of LMS segment (ALMS), and the curvature of LMS segment. For LMS and LAD segments, when ALMS increases, blood flow disturbance (r = 0.81 in LMS and r = 0.74 in LAD) and atherosusceptibility (r = 0.84 in LMS and r = 0.85 in LAD) increases. When the LMS curvature decreases, the WSS magnitude (r = 0.80 in LMS and r = 0.83 in LAD) decreases, and disturbance (r=-0.80 in LMS and r=-0.91 in LAD) and atherosusceptibility (r=-0.74 in LMS and r=-0.74 in LAD) increases.

In vitro synergy of ticarcillin/clavulanate in combination with aztreonam and ceftolozane/tazobactam against SPM-1-producing Pseudomonas aeruginosa strains.

Minimal inhibitory concentrations (MICs) of ticarcillin/clavulanic acid (TLc), ceftolozane/tazobactam (C/T), and aztreonam (AT) were determined for 6 SPM-1-producing Pseudomonas aeruginosa (PSA) using Etest® strips and the synergistic effect of such antimicrobials against was evaluated by gradient diffusion strip crossing (GDSC) test. The fraction inhibitory concentration indexes (FICI) were calculated and showed a synergistic (n = 3) and additive (n = 2) effects of TLc + AT against SPM-1 producers, while TLc + C/T combination caused no effect. Average MIC reduction of TLc and AT by GDSC was 3-fold and 2-fold dilutions, respectively. Thus, TLc + AT might be a candidate as a combination therapy to treat SPM-1-producing PSA infections.

Dynamic of High-Risk Acinetobacter baumannii Major Clones in a Brazilian Tertiary Hospital During a Short Time Period.

We characterized by whole-genome sequencing (WGS) six carbapenem-resistant Acinetobacter baumannii strains isolated from a Brazilian tertiary hospital during a 14-day period. The ISAba1-blaOXA-23 structure was found in the chromosome of five isolates, whereas blaOXA-72 was inserted in a 16.6-kb plasmid in two isolates. The presence of ISAba1-blaADC-like justified the high broad-spectrum cephalosporins minimal inhibitory concentrations (MICs) (MIC50, > 512 mg/L) verified in all isolates. Only minocycline (MIC50, ≤ 0.5 µg/mL), polymyxin B (MIC50, 0.5 µg/mL), and tigecycline (MIC50, 0.5 µg/mL) were in vitro active against such isolates. A diversity of other antimicrobial resistance determinants (aph(3')-VIa, aadA1, aac(3')-IIa, strA, strB, sul2, drfA1, mph(E), msr(E), tetB, and floR) was also observed, which may confer resistance to at last six distinct antimicrobial classes. Four distinct pulsed-field gel electrophoresis (PFGE) profiles were observed during the study period, which belonged to ST79/ST258 (n = 2; IC5), ST25/ST229 (n = 2; IC7), ST1 (n = 1; IC1), and ST162/ST235 (n = 1; IC4). Although the ST1 isolate that carried blaOXA-23 and blaOXA-72 was introduced in this hospital setting by a transferred patient, two clonally related ST79/ST258 isolates carrying either one of these carbapenemase encoding genes were recovered from two patients who were hospitalized within the same period of time in the same hospital unit. Finally, a good correlation between PFGE/MLST, blaOXA-51 variant, and single nucleotide polymorphisms was also observed. Here we demonstrated that distinct extensively drug-resistant A. baumannii clones can circulate in the same hospital setting during a short time period, illustrating a very complex epidemiological scenario for this priority pathogen.

Gasteruptiidae (Hymenoptera, Evanioidea) of three savannah phytophysiognomies of the Estação Ecológica do Jataí, in southeastern Brazil, under three sampling methods and a new record for Gasteruption helenae Macedo, 2011.

In this study, the Gasteruptiidae species found at the Estação Ecológica de Jataí (EEJ), in Luiz Antonio, São Paulo, Brazil, were documented, based on a survey carried out with Malaise, Moericke and light traps that lasted for three years, between January 2007 and December 2009. During the samplings at EEJ, 13 female specimens of Gasteruption Latreille, 1796 were captured: six of G. bispinosum Kieffer, 1904, six of G. brasiliense (Blanchard, 1840) and a single specimen of G. helenae Macedo, 2011 that is the first record for São Paulo state.

COMPARATIVE ANALYSIS OF COVID-19 MORTALITY IN BRAZIL, RIO DE JANEIRO, CAMPOS DOS GOYTACAZES, MACAE, CABO FRIO AND RIO DAS OSTRAS

Objective: To analyze quantitatively and comparatively the deaths by COVID-19 of the four largest municipalities in the North of Rio de Janeiro and Baixada Litoranea of Rio de Janeiro, within the national context. Methods: We used data from the Civil Registry and demographic information to elaborate a general picture of the pandemic up to the 31st epidemiological week in several aspects: evolution, scope, age, sex, race and impact on other causes of death. Results: We characterized the evolution of the pandemic. We found an exponential dependence on the mortality rate by age and a higher lethality in the male population. We determined that COVID-19 represents an important fraction of the causes of death in 2020, being associated with a significant excess of deaths in relation to 2019 and also with the change in mortality patterns due to other causes. Conclusion: Mortality is an effective and powerful indicator for understanding the infection and its pandemic, and it must be taken into account during the construction of public policies to deal with it.

In vitro synergy of ceftolozane/tazobactam in combination with fosfomycin or aztreonam against MDR Pseudomonas aeruginosa.

OBJECTIVES: Carbapenem-resistant Pseudomonas aeruginosa (CR-PSA) imposes great limitations on empirical therapeutic choices, which are further complicated by metallo-ß-lactamase production. This study evaluated in vitro antimicrobial synergy of ceftolozane/tazobactam in combination with aztreonam and fosfomycin against MDR PSA. METHODS: MICs were determined by broth microdilution and gradient strips. The effect of ceftolozane/tazobactam+aztreonam and ceftolozane/tazobactam+fosfomycin combinations were tested against 27 MDR PSA isolates carrying blaSPM-1 (n = 13), blaIMP (n = 4), blaVIM (n = 3), blaGES-1 (n = 2) and blaCTX-M-like (n = 2), and 3 isolates with no acquired ß-lactamase production detected by gradient diffusion strip crossing (GDSC). Six genetically unrelated SPM-1-producing isolates were also evaluated by time-kill analysis (TKA). RESULTS: All CR-PSA isolates harbouring blaSPM-1, blaGES-1 and blaIMP-1 were categorized as resistant to ceftolozane/tazobactam, meropenem and fosfomycin, with 70% being susceptible to aztreonam. Synergism for ceftolozane/tazobactam+fosfomycin and ceftolozane/tazobactam+aztreonam combinations was observed for 88.9% (24/27) and 18.5% (5/27) of the isolates by GDSC, respectively. A 3- to 9-fold reduction in ceftolozane/tazobactam MICs was observed, depending on the combination. Ceftolozane/tazobactam+fosfomycin was synergistic by TKA against one of six SPM-1-producing isolates, with additional non-synergistic bacterial density reduction for another isolate. Aztreonam peak concentrations alone demonstrated a ≥3 log10 cfu/mL reduction against all six isolates, but all strains were within the susceptible range for the drug. No antagonism was observed. CONCLUSIONS: In the context of increasing CR-PSA and the genetic diversity of resistance mechanisms, new combinations and stewardship strategies may need to be explored in the face of increasingly difficult to treat pathogens.

Phe-Phe Di-Peptide Nanostructure Self-Assembling Modulated by Luminescent Additives.

In this work, supramolecular l-l-diphenylalanine (Phe-Phe) nanostructures were self-assembled in solvents of distinct polarity and in the presence of luminescent additives of distinct conjugation length that physically adhere to the nanostructures to provide growth environments of distinct properties. When the additive is poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene], an electron donor polymer, and solvent is tetrahydrofuran (THF), Phe-Phe vesicle-like structures are obtained, whereas in water and in the presence of a similar additive in structure, poly[5-methoxy-2-(3-sulfopropoxy)-1,4-phenylenevinylene], nanotubes are formed. In contrast, when 9-vinyl-carbazole, an electron acceptor additive is used, nanotubes are formed even when THF is the solvent. The same structures are obtained when the additive is the macromolecule poly(vinyl carbazole). The morphologies of these self-assembled structures were observed by scanning electron microscopy, and their photophysical behavior was determined by steady-state fluorescence spectroscopy and time-resolved fluorescence spectroscopy. These data analyzed altogether inform about the formation mechanisms of such structures and about the influence that distinct interactions exert on self-assembling and charge-transfer processes through formation of complexes between the luminescent additives and the Phe-Phe nano- and microstructures.

The Impact of the Right Coronary Artery Geometric Parameters on Hemodynamic Performance.

PURPOSE: Coronary artery geometry can have a significant impact in the hemodynamic behavior of coronary blood flow, influencing atherosclerotic plaque formation. The present work focuses on, through a statistical study, the connection between several geometric parameters of the right coronary artery-ostium cross-sectional area, angles between the common trunk and the side-branches, tortuosity, curvature and cross-sectional area in each side-branch-and their influence on hemodynamic descriptors. Parameters such as low wall shear stress and local disturbed flow, which are associated with atherosclerosis formation, were analysed. METHODS: Computed tomography images of ten healthy individuals were selected to reconstruct in vivo three-dimensional models of right coronary arteries. Blood flow was simulated through a compliant model with realistic boundary conditions. Calculated hemodynamic descriptors values were correlated with the geometric parameters using the Pearson correlation coefficient (r) and the p value. RESULTS: The strongest correlations were found in the middle and distal segments of the right coronary artery. A decrease in the ostium area promotes a decrease in the WSS magnitude from the proximal to the distal segment (r = 0.82). Very strong correlations (r > 0.90) were achieved between geometric parameters (cross-sectional area, angle, tortuosity) of the right-ventricular branch and the wall shear stress magnitude in the middle and distal segments. CONCLUSIONS: Low values of tortuosity, smaller cross-sectional area and higher angle of the right-ventricular branch leads to a hemodynamic behavior more propitious to atherosclerosis formation, within the study cases. The right-ventricular branch seems to have the highest influence in the hemodynamic behavior of the right coronary artery.

Correlation between geometric parameters of the left coronary artery and hemodynamic descriptors of atherosclerosis: FSI and statistical study.

The hemodynamics conditioned by coronary geometry may play an important role in the creation of a pro-atherogenic environment in specific locations of the coronary tree. The aim of this study is to identify how several geometric parameters of the left coronary artery - cross-section areas, proximal left anterior descending artery length, angles between the branches and the septum, curvature and tortuosity - can be related with hemodynamic descriptors, using a computational fluid-structure interaction method. It is widely accepted that the hemodynamic indicators play an important role in identifying possible pro-atherogenic locations. A statistical study, using Pearson correlation coefficient and P value, was performed for a population study of 8 normal human left coronary arteries presenting right-dominant circulation. Within the study cases, arteries with high caliber (r = 0.88), high angles LMS-LAD (r = 0.49), LAD-LCx (r = 0.57) and LAD-Septum (r = 0.52), and high tortuosity LMS-LCx (r = 0.63) were correlated with a hemodynamic behavior propitious to plaque formation in the left anterior descending artery. In contrast, high proximal left anterior descending artery length (r = -0.41), high angle LMS-LCx (r = -0.59), high tortuosity LMS-LAD (r = -0.56) and LAD-LCx (r = -0.55) and high curvature of LMS (r = -0.60) and LCx (r = -0.56) can lead to non-favorable hemodynamic conditions for atheroma formation. Graphical abstract.

Radiographic assessment of the proximal tibial angles in dogs and cats with and without cranial cruciate ligament rupture / Avaliação radiográfica dos ângulos da tibia proximal em cães e gatos com e sem ruptura do ligamento cruzado cranial

The influence of the proximal tibial angles in the cranial cruciate ligament (CCL) rupture in dogs is still controversial, and little is known regarding this topic in cats. The aim of this study was to evaluate and compare the angles of the proximal portion of the tibia in dogs and cats with and without CCL rupture. Retrospective and prospective radiographs of the stifle joints were obtained and divided into four groups. Group 1 was composed of 70 stifle joint images of dogs without orthopedic disorders (healthy dogs), group 2 had 70 stifle joint images of dogs with CCL rupture, group 3 had 50 stifle joint images of cats without orthopedic disorders (healthy cats) and group 4 had 25 stifle joint images of cats with CCL rupture. Radiographs were taken with the stifle joint in the mediolateral projection, positioned at the angle of hind limb support. Between the two groups of dogs evaluated, the dogs with CCL rupture had statistically greater tibial plateau angle (TPA) compared with healthy dogs. No difference was shown in relation to the TPA between healthy cats and cats with CCL rupture. In relation to the patellar ligament angle by tibial plateau method the values for the healthy dogs were significantly higher than those for the CCL ruptured dogs. Similarly, healthy cats had significantly higher mean values than cats with CCL rupture. In the patellar ligament angle by common tangent method there was no significantly difference between the two groups of dogs. Between the two groups of cats, animals with CCL rupture had statistically higher mean values than healthy cats. In general, the groups of dogs showed higher mean values than the groups of cats. For the patellar ligament insertion angle (PLIA) healthy dogs showed a significantly higher mean than dogs with CCL rupture. There was no significant difference between the groups of cats. In conclusion, the TPA and the PLIA possibly influence the etiology of CCL rupture in dogs but not in cats. The low patellar ligament angle measured by common tangent method may favorably influence the reduced incidence of CCL rupture in cats.(AU)

A influência dos ângulos da parte proximal da tíbia sobre a ruptura do ligamento cruzado cranial (LCC) em cães é ainda controversa, e pouco é descrito sobre este tópico em gatos. O objetivo deste estudo foi avaliar e comparar os ângulos da tíbia proximal em cães e gatos, ambas as espécies com e sem ruptura do LCC. Foram obtidos exames radiográficos retrospectivos e prospectivos das articulações do joelho e divididos em quatro grupos: no grupo 1 foram incluídas 70 imagens radiográficas da articulação do joelho de cães sem distúrbios ortopédicos (cães saudáveis), no grupo 2 foram 70 imagens radiográficas articulação do joelho de cães com ruptura do LCC, no grupo 3 foram 50 imagens radiográficas da articulação do joelho de gatos sem distúrbios ortopédicos (gatos saudáveis), e no grupo 4 foram 25 imagens radiográficas articulação do joelho de gatos com ruptura do LCC. As imagens radiográficas da articulação do joelho foram obtidas na projeção mediolateral, mantendo-se a articulação posicionada na angulação de apoio do membro pélvico. Em relação ao ângulo do platô tibial (APT), os cães com ruptura do LCC tiveram estatisticamente maiores valores médios do APT quando comparados aos cães saudáveis. Não foi observada diferença significativa em relação ao APT entre os gatos saudáveis e os gatos com ruptura do LCC. Em relação ao ângulo do ligamento patelar mensurado pelo método do platô tibial, os valores médios observados para os cães saudáveis foram significativamente mais elevados do que os valores encontrados para os cães com ruptura do LCC. De forma semelhante, os gatos saudáveis também apresentaram valores médios mais elevados do que os gatos com ruptura do LCC. Para o ângulo do ligamento patelar mensurado pelo método da tangente comum, não foram observadas diferenças significativas entre os dois grupos de cães. No entanto, entre os dois grupos de gatos, os animais com ruptura do LCC apresentaram valores médios significativamente mais elevados do que os gatos saudáveis. Em geral, os grupos de cães demonstraram valores médios mais elevados quando comparados aos grupos de gatos. Em relação ao ângulo de inserção do ligamento patelar (AILP), os cães saudáveis apresentaram valores médios significativamente mais elevados do que os cães com ruptura do LCC. No entanto, não foi observada diferença significativa entre os dois grupos de gatos. Em conclusão, o APT e o AILP possivelmente exercem influência na etiologia da ruptura do LCC em cães, mas não influenciam nos gatos. Em gatos, os reduzidos ângulos do ligamento patelar observados pelo método da tangente comum podem influenciar favoravelmente na baixa incidência da ruptura do LCC nessa espécie.(AU)

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment)

ABSTRACT: The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy.