Estimating the savings of a national project to prevent healthcare-associated infections in intensive care units.

BACKGROUND: Healthcare-associated infections (HAIs) have a significant impact on patients' morbidity and mortality, and have a detrimental financial impact on the healthcare system. Various strategies exist to prevent HAIs, but economic evaluations are needed to determine which are most appropriate. AIM: To present the financial impact of a nationwide project on HAI prevention in intensive care units (ICUs) using a quality improvement (QI) approach. METHODS: A health economic evaluation assessed the financial results of the QI initiative 'Saúde em Nossas Mãos' (SNM), implemented in Brazil between January 2018 and December 2020. Among 116 participating institutions, 13 (11.2%) fully reported the aggregate cost and stratified patients (with vs without HAIs) in the pre-intervention and post-intervention periods. Average cost (AC) was calculated for each analysed HAI: central-line-associated bloodstream infections (CLABSIs), ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infections (CAUTIs). The absorption model and time-driven activity-based costing were used for cost estimations. The numbers of infections that the project could have prevented during its implementation were estimated to demonstrate the financial impact of the SNM initiative. RESULTS: The aggregated ACs calculated for each HAI from these 13 ICUs - US$8480 for CLABSIs, US$10,039 for VAP, and US$7464 for CAUTIs - were extrapolated to the total number of HAIs prevented by the project (1727 CLABSIs, 3797 VAP and 2150 CAUTIs). The overall savings of the SNM as of December 2020 were estimated at US$68.8 million, with an estimated return on investment (ROI) of 765%. CONCLUSION: Reporting accurate financial data on HAI prevention strategies is still challenging in Brazil. These results suggest that a national QI initiative to prevent HAIs in critical care settings is a feasible and value-based approach, reducing financial waste and yielding a significant ROI for the healthcare system.

One-Year Surveillance of SARS-CoV-2 and Rotavirus in Water Matrices from a Hot Spring Area.

The pandemic of Coronavirus Disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is still impacting not only on human health but also all economic activities, especially in those related to tourism. In this study, in order to characterize the presence of SARS-CoV-2 in a hot spring park in Uruguay, swimming pools water, wastewater, and surface water from this area were analyzed by quantitative PCR. Wastewater from Salto city located next to the hydrothermal spring area was also evaluated as well as the presence of Rotavirus (RV). Overall, SARS-CoV-2 was detected in 13% (13/102) of the analyzed samples. Moreover, this virus was not detected in any of the samples from the swimming pools water and was present in 18% (3/17) of wastewater samples from the hotels area showing the same trend between the titer of SARS-CoV-2 and the number of infected people in Salto city. SARS-CoV-2 was also detected in wastewater samples (32% (11/34)) from Salto city, detecting the first positive sample when 105 persons were positive for SARS-CoV-2. Rotavirus was detected only in 10% (2/24) of the wastewater samples analyzed in months when partial lockdown measures were taken, however, this virus was detected in nearly all wastewater samples analyzed when social distancing measures and partial lockdown were relaxed. Wastewater results confirmed the advantages of using the detection and quantification of viruses in this matrix in order to evaluate the presence of these viruses in the population, highlighting the usefulness of this approach to define and apply social distancing. This study suggests that waters from swimming pools are not a source of infection for SARS-CoV-2, although more studies are needed including infectivity assays in order to confirm this statement.

Detection of Neorickettsia sp. in Oligoryzomys flavescens rodent from a protected urban area in Buenos Aires City (Argentina).

Rodents play an important role in vector-borne pathogens cycle. To detect Anaplasma, Ehrlichia, Neorickettsia, Rickettsia and Borrelia species in rodents from a protected urban area in Buenos Aires City (Argentina) were analyzed 203 organ pools of Mus musculus, Oligoryzomys flavescens, Rattus norvegicus, Deltamys kempi and Scapteromys aquaticus by PCR. Only one O. flavescens (1.2%) was positive by PCR for 16S rRNA fragment for the Anaplasmataceae family and the sequence had 99.7% identity with Neorickettsia risticii. Plus, the sequence obtained for a fragment of the p51 gene for the genus Neorickettsia from positive sample had 95.3-96.1% identity with N. risticii found previously in bats Tadarida brasiliensis from Buenos Aires City. Our study presents the first finding of Neorickettsia in rodents from natural environment, but further studies are necessary about these vector-borne bacteria and the rol of rodents in its epidemiology.

Isoforms of the DHTKD1-Encoded 2-Oxoadipate Dehydrogenase, Identified in Animal Tissues, Are not Observed upon the Human DHTKD1 Expression in Bacterial or Yeast Systems.

Unlike the OGDH-encoded 2-oxoglutarate dehydrogenase (OGDH), which is an essential enzyme present in all animal tissues, expression of the DHTKD1-encoded isoenzyme, 2-oxoadipate dehydrogenase (OADH), depends on a number of factors, and mutant DHTKD1 phenotypes are rarely manifested. Physiological significance of OADH is also obscured by the fact that both isoenzymes transform 2-oxoglutarate and 2-oxoadipate. By analogy with other members of the 2-oxo acid dehydrogenases family, OADH is assumed to be a component of the multienzyme complex that catalyzes oxidative decarboxylation of 2-oxoadipate. This study aims at molecular characterization of OADH from animal tissues. Phylogenetic analysis of 2-oxo acid dehydrogenases reveals OADH only in animals and Dictyostelium discoideum slime mold, within a common branch with bacterial OGDH. Examination of partially purified animal OADH by immunoblotting and mass spectrometry identifies two OADH isoforms with molecular weights of about 130 and 70 kDa. These isoforms are not observed upon the expression of human DHTKD1 protein in either bacterial or yeast system, where the synthesized OADH is of expected molecular weight (about 100 kDa). Thus, the OADH isoforms present in animal tissues, may result from the animal-specific regulation of the DHTKD1 expression and/or posttranslational modifications of the encoded protein. Mapping of the peptides identified in the OADH preparations, onto the protein structure suggests that the 70-kDa isoform is truncated at the N-terminus, but retains the active site. Since the N-terminal domain of OGDH is required for the formation of the multienzyme complex, it is possible that the 70-kDa isoform catalyzes non-oxidative transformation of dicarboxylic 2-oxo acids that does not require the multienzyme structure. In this case, the ratio of the OADH isoforms in animal tissues may correspond to the ratio between the oxidative and non-oxidative decarboxylation of 2-oxoadipate.

Preoperative fasting - "nihil per os" a difficult myth to break down: a randomized controlled study.

INTRODUCTION: For several years the scientific anaesthesia societies declared a preoperative fast of 6 hours for solid foods and 2 hours for clear liquids before elective surgical interventions to be sufficient. The aim of this study is to identify the extent of the gap that exists between the preoperative fasting time required and that actually encountered in operating rooms. PATIENTS AND METHODS: The safety and clinical applicability of a reduction of the preoperative fasting time was investigated through the use of oral solutions enriched with maltodextrin and their effects on the pre- and postoperative well-being that this may have on patients who are candidates for elective abdominal surgery. The study was conducted in two successive phases (I and II) and patients divided into two groups (A and B). DISCUSSION: Clinical practice is slow to change, in fact, in our study the duration of fasting was an average of 19 hours for solids and 13 hours for liquids. The duration of the fasting did not show differences in the various surgical departments, demonstrating that it is a transversal practice and is not only limited to abdominal surgery in which the utility of fasting would theoretically be greater. Among Group patients A, the fasting time for liquids was about 9 hours. This shows that the time is certainly shorter but not much different when compared to the fasting time for liquids in group B which was on average 14 hours. It is important how difficult it is to achieve good compliance from patients when trying to reduce the time of preoperative fasting based on scientific evidence that is now well established. CONCLUSION: The use of carbohydrate-enriched drinks up to 2 hours after induction of anaesthesia appears to be a safe procedure. The use of these solutions reduces the catabolic response to surgery and contributes to maintaining a pre-operative state of well-being by reducing feelings of hunger and thirst and the state of preoperative anxiety.

An extensive field study reveals the circulation of new genetic variants of subtype 1a of bovine viral diarrhea virus in Uruguay.

Bovine viral diarrhea virus (BVDV) is a major pathogen worldwide, causing significant economic losses to the livestock sector. In Uruguay, BVDV seroprevalence at the farm level is >80%. In this work, 2546 serum, blood or tissue samples collected from animals suspected of being affected by BVD between 2015 and 2017 were analyzed by reverse transcription PCR and sequencing. Analysis of the BVDV genomic regions 5'UTR/Npro, Npro and E2 revealed that BVDV-1a, 1i and 2b circulate in the country, with BVDV-1a being the most prevalent subtype. Population dynamics studies revealed that BVDV-1a has been circulating in our herds since ~1990. This subtype began to spread and evolve, accumulating point mutations at a rate of 3.48 × 10-3 substitutions/site/year, acquiring specific genetic characteristics that gave rise to two local genetic lineages of BVDV-1a. These lineages are divergent from those circulating worldwide, as well as the vaccine strain currently used in Uruguay. The most notable differences between field and vaccine strains were found in the E2 glycoprotein, suggesting that the amino acid substitutions could result in failure of cross-protection/neutralization after vaccination. This is the first study that compares Uruguayan BVDV field and vaccine strains with other BVDV strains from throughout the world. The results obtained in this study will be very useful for developing a suitable immunization program for BVDV in Uruguay by identifying local field strains as candidates for vaccine development.

Molecular detection of Bartonella in fleas (Hexapoda, Siphonaptera) collected from wild rodents (Cricetidae, Sigmodontinae) from Argentina.

Bartonella are facultative intracellular Gram-negative bacteria, transmitted mainly by hematophagous arthropods, and the rodents act as a natural reservoir. Different species of Bartonella associated with rodents have been implicated as causing human disease. Studies from Argentina are scarce and no Bartonella from fleas have been reported previously. The present study investigated the presence of Bartonella spp. in fleas associated with sigmodontine rodents in four localities of the Santa Cruz Province, Argentina. In total, 51 fleas (four species) were analysed of which 41.2% were found to be positive for the gltA gene fragment via a nested polymerase chain reaction. All positive fleas were of the species Neotyphloceras crackensis from three different localities. Eight of the 21 amplified samples were sequenced, and the presence of three different genotypes was detected with an identity of 95.5-98.8% amongst themselves. Bartonella genotypes from American rodents and rodent fleas were recovered in a monophyletic group. Similarly, most of the Peruvian and all Argentinean variants constitute a natural group sister of the American remainder. The importance of the Bartonella spp. with respect to public health is unknown, although future studies could provide evidence of the possible involvement of N. crackensis in the Bartonella transmission cycles.

The prevalence of dysphonia and dysphagia in patients affected by immunomediated diseases and the role of psychometric tests.

This cross-sectional investigation examined the prevalence and severity of dysphonia, globus pharyngeus, and dysphagia in patients affected by immunomediated (IM) diseases. Seventy subjects were administered the Voice Handicap Index (VHI) (scale 0-4), Glasgow-Edinburgh Throat Scale (GETS) (scale from 0 to 7) for globus pharyngeus assessment, and modified Swallowing Outcomes After Revised Laryngectomy (SOAL) (scale 0, 1, 2) to test swallowing symptoms. VHI: the mean percentage of answers with a score greater than 1 (corresponding to a frequency of situation's occurrence "sometimes," "almost always," or "always") was 25.7, 26.7, and 44.1% for functional, emotional, and physical groups of sub-items respectively. GETS: the mean percentage of answers with a score ≥ 3 was 60.85%, significantly higher if compared with that of answers with a score < 3 (40.14%). The mean percentages of answers with a score 0-2, 3-4, and 5-7 were 40.1, 16.7, and 43.7% respectively. SOAL: a mean of 57.9% of answers gained a symptomatic score (1 ["a little"] or 2 ["a lot"]) and 41.9%, the score 0. The difference was statistically significant (p < 0.05). The first two most recurrent items with a score 2 ("a lot") were "Do you have a problem swallowing dry food?" (46%) and "Do you have a problem swallowing solid food?" (36%). The study represents the first to describe the globus pharyngeus symptoms in IM population. Moreover, it allows to confirm the recurrence of dysphonia and dysphagia in this type of patients. Particularly, it has been demonstrated that the alteration of swallowing function is related to solid and dry food. The self-assessment questionnaires proved as a useful tool to early detection of dysfunctions in order to avoid further deterioration of quality of life and to prevent serious life-threatening complications.

Two novel Ehrlichia strains detected in Amblyomma tigrinum ticks associated to dogs in peri-urban areas of Argentina.

The aim of this work was to describe two novel strains of Ehrlichia associated to Amblyomma tigrinum from Argentina. Molecular detection of agents belonging to the family Anaplasmataceae was performed targeting three different loci: 16S rRNA gene, dsb gene and a fragment of groESL heat shock operon. The results have shown that two different strains of Ehrlichia sp. associated to A. tigrinum are circulating in peri-urban areas of Argentina. The Ehrlichia strain detected in ticks from San Luis Province, named as Ehrlichia sp. strain San Luis, is closely related to the Ehrlichia chaffeensis. The novel Ehrlichia strain detected in Córdoba Province, named as Ehrlichia sp. strain Córdoba, is phylogenetically related to three Ehrlichia strains from Brazil, two of them isolated from wild carnivorous and the third one isolated from horse. Even though Ehrlichia sp. strain Córdoba was clustered with the three Ehrlichia strains from Brazil, the genetic similarity was too low to consider them as the same taxonomic entity. Blood samples of dogs were positive to Anaplasma platys. The association of these two novel strains with A. tigrinum has epidemiological relevance because adult stages of this tick species are common parasite of dogs in rural and peri-urban areas and they are aggressive to humans. The presence of these two novel Ehrlichia strains implies a potential epidemiological risk in Argentina because the species of the genus Ehrlichia are known to be pathogenic to both domestic mammals and humans.

Wastewater contamination in Antarctic melt-water streams evidenced by virological and organic molecular markers.

Human activities in the Antarctica including tourism and scientific research have been raised substantially in the last century with the concomitant impact on the Antarctic ecosystems through the release of wastewater mainly from different scientific stations activities. The aim of this study was to assess the wastewater contamination of surface waters and sediments of three melt-water streams (11 sites) by leaking septic tanks located in the vicinity of the Uruguayan Scientific Station in the Fildes Peninsula, King George Island, Antarctica, during summer 2015. For this purpose, we combined the analysis of fecal steroids in sediments by using gas chromatography and six enteric viruses in surface waters by quantitative and qualitative PCR. Coprostanol concentrations (from 0.03 to 3.31µgg-1) and fecal steroids diagnostic ratios indicated that stations C7 and C8 located in the kitchen stream presented sewage contamination. Rotavirus was the only enteric virus detected in five sites with concentration ranging from 1.2×105gcL-1 to 5.1×105gcL-1 being three of them located downstream from the leaking AINA and Kitchen septic tanks. This study shows for the first time the presence of both virological and molecular biomarkers of wastewater pollution in surface waters and sediments of three melt-water streams in the vicinity of a scientific station in the Antarctica. These results highlight the importance of the complementation of these biomarkers in two different matrices (surface waters and sediments) to assess wastewater pollution in an Antarctic environment related to anthropogenic activities in the area.

Enzymatic debridement: is HA-collagenase the right synergy? Randomized double-blind controlled clinical trial in venous leg ulcers.

OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of a new ointment containing Hyaluronic Acid and collagenase from non-pathogenic Vibrio alginolyticus. PATIENTS AND METHODS: Double blind, multicenter, controlled clinical trial (no. ISRCTN71239043) conducted to demonstrate the superiority of Hyaluronic Acid-Collagenase applied once a day over placebo in mean reduction of devitalized/fibrinous/slough tissue after 15 days of treatment. 113 patients with venous ulcers were enrolled and randomized to receive active treatment therapy or vehicle preparation. Both arms also received compression therapy. Subjects were assessed at baseline and at 4 different clinical study visits up to a maximum of 30 days. Outcome measures included mean percentage debridement evaluated by digital planimetry, pain during change of dressing measured on a visual analogue scale and adverse event assessment for tolerance. RESULTS: After 15 days the debridement rate in the active group was 67.5% compared to 59% in the placebo group (p = 0.0436). A significantly higher number of patients in the treatment group achieved 100% debridement by day 15 (p = 0.0025) than in the control group, and a higher percentage also demonstrated complete debridement at every other time point. Pain perception was similar in both groups with low levels during medication. No differences in tolerance were observed between groups. CONCLUSIONS: Chronic venous ulcers treated with this novel compound of Hyaluronic Acid and collagenase resulted in a significantly higher debridement rate at Day 15 vs. the control group. Hyaluronic Acid-Collagenase was well tolerated and a low degree of pain was perceived during dressing change. The preparation of 0.2% of Hyaluronic acid-collagenase shows significant benefits in the management of chronic ulcers.

Isolation of Rickettsia massiliae from Rhipicephalus sanguineus Ticks, Buenos Aires (Argentina).

Rickettsia massiliae , a member of the spotted fever group of Rickettsia, was first isolated from a Rhipicephalus turanicus tick in France. In the New World, it has been detected in Rhipicephalus sanguineus ticks from different geographical locations in Argentina and the United States, but it has only been isolated in Arizona. The aim of this study was the isolation and genetic characterization of R. massiliae from R. sanguineus ticks collected from dogs in Buenos Aires city, Argentina. In total, 49 R. sanguineus ticks were collected from 10 dogs and grouped into 10 pools of 4-5 specimens. With a PCR assay, which detects a fragment of the Rickettsia genus-specific 23S-5S intergenic space, 1 pool of 5 ticks was found positive. Generated sequences exhibited 100% identity with R. massiliae . A new isolate, named CABA, was obtained from this pool by inoculating it into monolayers of Vero cells. Genotypic characteristics were determined, and results showed that fragments of the 23S-5S intergenic space, ompA, ompB, gltA, htrA, and sca1 genes had great similarity with R. massiliae strain Bar29 (Spain). Although few human cases have been confirmed for this pathogen, its circulation in urban areas is of great importance to public health. This isolation improves knowledge of the circulating pathogen and could improve future diagnostic processes as it allows the production of more specific antigens for serological testing.

Infection with Ehrlichia canis and Anaplasma platys (Rickettsiales: Anaplasmataceae) in two lineages of Rhipicephalus sanguineus sensu lato (Acari: Ixodidae) from Argentina.

Natural infection with Ehrlichia canis and Anaplasma platys in ticks belonging to the tropical and temperate lineages of Rhipicephalus sanguineus sensu lato from Argentina was evaluated. Samples were tested for Ehrlichia canis infection by PCR assays using 16S rRNA, dsb and p28 gene, while detection of A. platys was performed with 16S rRNA and groESL gene. The assignment of the ticks to each lineage was corroborated with 16S rDNA sequences. All ticks infected with E. canis and A. platys belonged to the tropical lineage. These results constitute the first record of E. canis infection in R. sanguineus s.l ticks from Argentina. No ticks from the temperate lineage were found to be infected with E. canis, coinciding with previous studies performed in Argentina and Uruguay where E. canis infection was not detected in R. sanguineus s.l from the temperate lineage. Because the presence of the tropical lineage of R. sanguineus s.l has been documented in tropical areas of northern Argentina between 22° and 24° of south latitude, the findings of this work indicate that transmission of E. canis and A. platys to dogs by R. sanguineus s.l probably occurs along this region.

Rickettsia infection in Amblyomma tonelliae, a tick species from the Amblyomma cajennense complex.

The present study was performed to evaluate the Rickettsia infection in Amblyomma tonelliae ticks from Argentina. All ticks were subjected to DNA extraction and tested by a battery of PCRs to amplify fragments of four rickettsial genes, 23S-5S, gltA, ompA and htrA. Two ticks were positive. The Rickettsia detected in one tick represents a new lineage which is named Rickettsia sp. strain El Tunal. This new strain belongs to the canadensis group because it is closely related to Rickettsia monteiroi, Rickettsia canadensis and Candidatus "Rickettsia tarasevichiae". They clustered together on a high supported clade with both gltA and htrA genes. The other positive tick was infected with Candidatus "Rickettsia amblyommii". The results presented in this study constitute the first records of Rickettsia infection in A. tonelliae ticks. However, the medical relevance of these findings should be considered cautiously because the pathogenicity of Rickettsia sp. strain El Tunal and Candidatus "R. amblyommii" remains undetermined.

[Molecular detection of Rickettsia massiliae and Anaplasma platys infecting Rhipicephalus sanguineus ticks and dogs, Bahía Blanca (Argentina)]. / Detección molecular de Rickettsia massiliae y Anaplasma platys en garrapatas Rhipicephalus sanguineus y caninos domésticos del municipio de Bahía Blanca (Argentina).

BACKGROUND: Rickettsioses, ehrlichioses and anaplasmoses are caused by Gram negative obligate intracellular bacteria and transmitted mainly by arthropods. AIM: To detect and perform the molecular characterization of these pathogens in ticks and domestic dogs in Bahia Blanca City (Buenos Aires, Argentina). METHODS: Fifty six blood samples from dogs and 82 ticks (75 Rhipicephalus sanguineus and 7 Amblyomma tigrinum) were studied. The samples were analyzed by PCR for Rickettsia (intergenic space 23S-5S rRNA), Ehrlichia/Anaplasma (16S rRNA), and Anaplasma platys (16S rRNA). RESULTS: 12% of R. sanguineus resulted positive for Rickettsia, identified by sequencing as Rickettsia massiliae; and 37.5% of the canine blood samples analyzed were positive for A. platys. Molecular characterization was also performed by amplification of the fragment of the citrate synthase gene (gltA) (Rickettsia genus) and the groESL gene (A. platys). Phylogenetic trees were constructed using the neighbor-joining method. These trees revealed that sequences obtained are similar to those from other geographical regions. CONCLUSION: The results indicate the presence of R. massiliae in R. sanguineus ticks for the second time in an urban area of South America and A. platys infection in dogs, being the southernmost region of Argentina where it has been notified.

Detección molecular de Rickettsia massiliae y Anaplasma platys en garrapatas Rhipicephalus sanguineus y caninos domésticos del municipio de Bahía Blanca (Argentina) / Molecular detection of Rickettsia massiliae and Anaplasma platys infecting Rhipicephalus sanguineus ticks and dogs, Bahía Blanca (Argentina)

Background: Rickettsioses, ehrlichioses and anaplasmoses are caused by Gram negative obligate intracellular bacteria and transmitted mainly by arthropods. Aim: To detect and perform the molecular characterization of these pathogens in ticks and domestic dogs in Bahia Blanca City (Buenos Aires, Argentina). Methods: Fifty six blood samples from dogs and 82 ticks (75 Rhipicephalus sanguineus and 7 Amblyomma tigrinum) were studied. The samples were analyzed by PCR for Rickettsia (intergenic space 23S-5S rRNA), Ehrlichia/Anaplasma (16S rRNA), and Anaplasma platys (16S rRNA). Results: 12% of R. sanguineus resulted positive for Rickettsia, identified by sequencing as Rickettsia massiliae; and 37.5% of the canine blood samples analyzed were positive for A. platys. Molecular characterization was also performed by amplification of the fragment of the citrate synthase gene (gltA) (Rickettsia genus) and the groESL gene (A. platys). Phylogenetic trees were constructed using the neighbor-joining method. These trees revealed that sequences obtained are similar to those from other geographical regions. Conclusion: The results indicate the presence of R. massiliae in R. sanguineus ticks for the second time in an urban area of South America and A. platys infection in dogs, being the southernmost region of Argentina where it has been notified.

Introducción: Las rickettsiosis, ehrlichiosis y anaplasmosis son causadas por bacterias gramnegativas, intracelulares obligadas y transmitidas principalmente por artrópodos. Objetivo: Detectar y caracterizar molecularmente estos patógenos en garrapatas y caninos domésticos del municipio de Bahía Blanca (provincia de Buenos Aires, Argentina). Material y Métodos: Se estudiaron 56 muestras sanguíneas de caninos, 75 garrapatas Rhipicephalus sanguineus y 7 Amblyomma tigrinum. Las muestras fueron analizadas por RPC para Rickettsia (espacio intergénico 23S-5S ARNr), Ehrlichia y Anaplasma (16S ARNr), y Anaplasma platys (16S ARNr). Resultados: Se detectó positividad a Rickettsia en 12% de R. sanguineus, identificándose por secuenciación a Rickettsia massiliae. Las muestras sanguíneas de los caninos resultaron en 37,5% positivas a A. platys. También se caracterizaron molecularmente por la amplificación del fragmento del gen citrato sintasa (gltA) (género Rickettsia) y del gen groESL (A. platys). Se construyeron árboles filogenéticos utilizando el método del vecino más cercano (neighbor-joining) revelando que las secuencias obtenidas son similares a las de otras regiones geográficas. Conclusión: Los resultados indican la presencia de R. massiliae en garrapatas R. sanguineus en una segunda zona urbana de Sudamérica y la infección por A. platys en caninos, siendo la región más austral de Argentina donde ha sido notificada.

Treatment of coronary bifurcation lesions with bioresorbable vascular scaffolds.

AIM: Aim of the study was to report on the feasibility and early safety and efficacy of Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) for coronary artery bifurcations (CABs) treatment at a single high-volume center. METHODS: All patients treated with Absorb implantation at our institution from March 2013 to March 2014 were enrolled in the prospective, single-center, ongoing, all-comers registry, which has the main purpose of evaluating the safety and efficacy of Absorb implantation in unselected patients treated in daily practice. In-hospital and at follow-up clinical outcomes of 46 patients undergoing treatment with Absorb in 46 CAB lesions were reported in the present study. RESULTS: Treated CAB lesions involved the left main in 13.0% of cases, the left anterior descending artery in 65.0%, the left circumflex in 19.6%, and the right coronary artery in 2.2%. Bifurcations were classified as true (47.8%) and non-true (52.2%) according to the Medina classification. The provisional and the two-BVS techniques were used in 78.3% and 21.7%, respectively. Two-BVS techniques included: mini-crush 13.0%; reverse culotte 2.2%; T-stenting 2.2%; and V-stenting 4.3%. No in-hospital adverse events occurred. At 6 months no adverse events occurred. Only one case of target lesion revascularization was observed at day 227. No stent thrombosis occurred during follow-up. CONCLUSION: Our preliminary experience suggested that CABs treatment with Absorb is feasible and associated with promising immediate and short-term clinical outcomes. However, larger studies with long-term follow-up are needed to adequately address the safety and efficacy of BVS use in CABs.

The Polycomb group (PcG) protein EZH2 supports the survival of PAX3-FOXO1 alveolar rhabdomyosarcoma by repressing FBXO32 (Atrogin1/MAFbx).

The Polycomb group (PcG) proteins regulate stem cell differentiation via the repression of gene transcription, and their deregulation has been widely implicated in cancer development. The PcG protein Enhancer of Zeste Homolog 2 (EZH2) works as a catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) by methylating lysine 27 on histone H3 (H3K27me3), a hallmark of PRC2-mediated gene repression. In skeletal muscle progenitors, EZH2 prevents an unscheduled differentiation by repressing muscle-specific gene expression and is downregulated during the course of differentiation. In rhabdomyosarcoma (RMS), a pediatric soft-tissue sarcoma thought to arise from myogenic precursors, EZH2 is abnormally expressed and its downregulation in vitro leads to muscle-like differentiation of RMS cells of the embryonal variant. However, the role of EZH2 in the clinically aggressive subgroup of alveolar RMS, characterized by the expression of PAX3-FOXO1 oncoprotein, remains unknown. We show here that EZH2 depletion in these cells leads to programmed cell death. Transcriptional derepression of F-box protein 32 (FBXO32) (Atrogin1/MAFbx), a gene associated with muscle homeostasis, was evidenced in PAX3-FOXO1 RMS cells silenced for EZH2. This phenomenon was associated with reduced EZH2 occupancy and H3K27me3 levels at the FBXO32 promoter. Simultaneous knockdown of FBXO32 and EZH2 in PAX3-FOXO1 RMS cells impaired the pro-apoptotic response, whereas the overexpression of FBXO32 facilitated programmed cell death in EZH2-depleted cells. Pharmacological inhibition of EZH2 by either 3-Deazaneplanocin A or a catalytic EZH2 inhibitor mirrored the phenotypic and molecular effects of EZH2 knockdown in vitro and prevented tumor growth in vivo. Collectively, these results indicate that EZH2 is a key factor in the proliferation and survival of PAX3-FOXO1 alveolar RMS cells working, at least in part, by repressing FBXO32. They also suggest that the reducing activity of EZH2 could represent a novel adjuvant strategy to eradicate high-risk PAX3-FOXO1 alveolar RMS.

Non-inferiority trial between two dry-powder inhalers containing fluticasone/salmeterol in asthmatic patients.

Asthma is an increasing pathology with poor compliance. Achievement of control is possible but under intensive treatment. In this setting, fluticasone/salmeterol association delivered by dry powder inhalers is a valuable and proved option. A prospective, parallel, open-label, phase IV, multicentre non-inferiority study was conducted to determine therapeutic similarity between 2 different inhalers: Generic DPI and Diskus®, which both deliver a fluticasone/salmeterol association (CAS 80474-14-2/CAS 89365-50-4). A 103 uncontrolled asthmatic patients were randomly assigned in 2 groups, Generic (G) and Diskus® (D), and received the association for 18 weeks through the appropriate device. They were evaluated according to Asthma Quality of Life Questionnaire and GINA/NIH guidelines. To demonstrate non-inferiority, the estimation of the Relative Risk between the Global Score Rate per group with its 95% confidence interval was calculated and compared against a non-inferiority margin obtained from a previous study. The Global Score Rate was 82% for G Group and 83% for D Group. The RR was 1.0124 (95% CI: 0.847-1.210). The margin set at 0.832 was not reached by the lower 95% CI (z=-2.097; p=0.018) pointing out non-inferiority. The results have demonstrated non-inferiority between groups. Thus, the 2 products are therapeutically similar.