Difficulties on the access to innovative targeted therapies for lung cancer in Spain.

PURPOSE: Spanish Lung Cancer Group (SLCG) conducted a review to analyze the barriers to access to innovative targeted therapies for non-small cell lung cancer (NSCLC) in clinical practice in Spain. METHODS: Review all relevant content published on websites of European Commission, European Medicines Agency, and Spanish Agency of Medicines and Medical Products regarding the authorization and access to oncology treatments. RESULTS: More than 20 targeted therapies are available to treat different molecular alterations in patients with NSCLC. European Commission has approved treatments for genomic alterations involving the following genes: ALK, RET, ROS1, EGFR, BRAF, NTRK, KRAS, MET. However, the availability of these therapies in Spain is not complete, as innovative treatments are not reimbursed or funded late, with only five of these alterations currently covered by National Health System. CONCLUSION: SLCG considers imperative to improve the access in Spain to innovative treatments for NSCLC to reduce inequity across European countries.

Semiempirical Two-Dimensional Model of the Bipolar Resistive Switching Process in Si-NCs/SiO2 Multilayers.

In this work, the SET and RESET processes of bipolar resistive switching memories with silicon nanocrystals (Si-NCs) embedded in an oxide matrix is simulated by a stochastic model. This model is based on the estimation of two-dimensional oxygen vacancy configurations and their relationship with the resistive state. The simulation data are compared with the experimental current-voltage data of Si-NCs/SiO2 multilayer-based memristor devices. Devices with 1 and 3 Si-NCs/SiO2 bilayers were analyzed. The Si-NCs are assumed as agglomerates of fixed oxygen vacancies, which promote the formation of conductive filaments (CFs) through the multilayer according to the simulations. In fact, an intermediate resistive state was observed in the forming process (experimental and simulated) of the 3-BL device, which is explained by the preferential generation of oxygen vacancies in the sites that form the complete CFs, through Si-NCs.

Lysophosphatidylinositol Promotes Chemotaxis and Cytokine Synthesis in Mast Cells with Differential Participation of GPR55 and CB2 Receptors.

Mast cells (MCs) are the main participants in the control of immune reactions associated with inflammation, allergies, defense against pathogens, and tumor growth. Bioactive lipids are lipophilic compounds able to modulate MC activation. Here, we explored some of the effects of the bioactive lipid lysophosphatidylinositol (LPI) on MCs. Utilizing murine bone marrow-derived mast cells (BMMCs), we found that LPI did not cause degranulation, but slightly increased FcεRI-dependent ß-hexosaminidase release. However, LPI induced strong chemotaxis together with changes in LIM kinase (LIMK) and cofilin phosphorylation. LPI also promoted modifications to actin cytoskeleton dynamics that were detected by an increase in cell size and interruptions in the continuity of the cortical actin ring. The chemotaxis and cortical actin ring changes were dependent on GPR55 receptor activation, since the specific agonist O1602 mimicked the effects of LPI and the selective antagonist ML193 prevented them. The LPI and O1602-dependent stimulation of BMMC also led to VEGF, TNF, IL-1α, and IL-1ß mRNA accumulation, but, in contrast with chemotaxis-related processes, the effects on cytokine transcription were dependent on GPR55 and cannabinoid (CB) 2 receptors, since they were sensitive to ML193 and to the specific CB2 receptor antagonist AM630. Remarkably, GPR55-dependent BMMC chemotaxis was observed towards conditioned media from distinct mouse and human cancer cells. Our data suggest that LPI induces the chemotaxis of MCs and leads to cytokine production in MC in vitro with the differential participation of GPR55 and CB2 receptors. These effects could play a significant role in the recruitment of MCs to tumors and the production of MC-derived pro-angiogenic factors in the tumor microenvironment.

Digital and Analog Resistive Switching Behavior in Si-NCs Embedded in a Si/SiO2 Multilayer Structure for Neuromorphic Systems.

In this work, we report the digital and analog resistive-switching (RS) characteristics in a memristor based on silicon nanocrystals (Si-NCs) integrated into a complementary metal-oxide-semiconductor (MOS) structure. Si-NCs with a diameter of 5.48 ± 1.24 nm embedded in a SiO2/Si-NCs/SiO2 multilayer structure acts as an RS layer. These devices exhibit bipolar RS with an intermediate resistance step during SET and RESET processes, which is believed to lie in the Si-NCs layer acting as charge-trapping nodes. The endurance studies of about 70 DC cycles indicate an ON/OFF ratio of ~106 and a retention time larger than 104 s. Long-term potentiation (LTP, -2 V) and long-term depression (LTD, +4 V) are obtained by applying consecutive identical pulse voltages of 150 ms duration. The current value gradually increases/decreases (LTP/LTD) as the pulse number increases. Three consecutive identical pulses of -2 V/150 ms (LTP) separated by 5 and 15 min show that the last current value obtained at the end of each pulse train is kept, confirming an analog RS behavior. These characteristics provide a possible way to mimic biological synapse functions for applications in neuromorphic computing in Si-NCs-based CMOS structures.

Synthesis of (µ2,η3-allyl-η5-oxapentadienyl)diiron pentacarbonyl complexes, an unusual reaction product from η4-(vinylketene)Fe(CO)3 complexes: structure and electron density distribution analysis.

The synthesis of a series of ferrocenylvinylketenes as stable η4-[Fe(CO)3] complexes (3a-f) was successfully accomplished through the reaction of η2-[Fe(CO)4] complexes under mild carbonylation conditions. The reactivity of 3a-f under thermal conditions afforded the unexpected formation of a novel family of (µ2,η3-allyl-η5-oxapentadienyl)diiron pentacarbonyl complexes 5a-f proposed to be formed by a sequence metathesis-haptotropic rearrangement between the starting η4-vinylketene iron(0) complex 3 and a η4-vinylcarbene iron(0) complex trapped in situ after a reversible carbonylation process favored by the thermal conditions. An electron density distribution analysis (EDD) of 5e using high-resolution X-ray diffraction data in combination with the DFT framework was performed to understand the electronic communication between the two iron fragments.

Development of Heterojunction c-Si/a-Si1-xCx:H PIN Light-Emitting Diodes.

In this work, we explored the feasibility of the fabrication of PIN light-emitting diodes (LEDs) consisting of heterojunctions of amorphous silicon-carbide (a-Si1-xCx:H) thin films and crystalline silicon wafers (c-Si). The objective is the future development of electro-photonic systems in the same c-Si wafer, containing transistors, sensors, LEDs and waveguides. Two different heterojunction LEDs were fabricated consisting of PIN and PIN+N structures, where a-Si1-xCx:H thin films were used as P-type and I-type layers, while an N-type c-Si substrate was used as an active part of the device. The amorphous layers were deposited by the plasma-enhanced chemical vapor deposition (PECVD) technique at a substrate temperature of 200 °C. The PIN device presented electroluminescence (EL) only in the forward bias, while the PIN+N device presented in both the forward and reverse biases. The EL in reverse bias was possible due to the addition of an N+-type a-Si:H layer between the c-Si substrate and the I-type a-Si1-xCx:H active layer. Likewise, the EL intensity of the PIN+N structure was higher than that of the PIN device in forward bias, indicating that the addition of the N-type a-Si:H layer makes electrons flow more efficiently to the I layer. In addition, both devices presented red EL in the full area, which is observed with the naked eye.

Valproic acid restricts mast cell activation by Listeria monocytogenes.

Mast cells (MC) play a central role in the early containment of bacterial infections, such as that caused by Listeria monocytogenes (L.m). The mechanisms of MC activation induced by L.m infection are well known, so it is possible to evaluate whether they are susceptible to targeting and modulation by different drugs. Recent evidence indicates that valproic acid (VPA) inhibits the immune response which favors L.m pathogenesis in vivo. Herein, we examined the immunomodulatory effect of VPA on L.m-mediated MC activation. To this end, bone marrow-derived mast cells (BMMC) were pre-incubated with VPA and then stimulated with L.m. We found that VPA reduced MC degranulation and cytokine release induced by L.m. MC activation during L.m infection relies on Toll-Like Receptor 2 (TLR2) engagement, however VPA treatment did not affect MC TLR2 cell surface expression. Moreover, VPA was able to decrease MC activation by the classic TLR2 ligands, peptidoglycan and lipopeptide Pam3CSK4. VPA also reduced cytokine production in response to Listeriolysin O (LLO), which activates MC by a TLR2-independent mechanism. In addition, VPA decreased the activation of critical events on MC signaling cascades, such as the increase on intracellular Ca2+ and phosphorylation of p38, ERK1/2 and -p65 subunit of NF-κB. Altogether, our data demonstrate that VPA affects key cell signaling events that regulate MC activation following L.m infection. These results indicate that VPA can modulate the functional activity of different immune cells that participate in the control of L.m infection.

Study of the Effect of Nitric Acid in Electrochemically Synthesized Silicon Nanocrystals: Tunability of Bright and Uniform Photoluminescence.

In this work, we show a correlation between the composition and the microstructural and optical properties of bright and uniform luminescent porous silicon (PSi) films. PSi films were synthesized by electrochemical etching using nitric acid in an electrolyte solution. PSi samples synthesized with nitric acid emit stronger (up to six-fold greater) photoluminescence (PL) as compared to those obtained without it. The PL peak is shifted from 630 to 570 nm by changing the concentration ratio of the HF:HNO3:(EtOH-H2O) electrolyte solution, but also shifts with the excitation energy, indicating quantum confinement effects in the silicon nanocrystals (Si-NCs). X-ray photoelectron spectroscopy analysis shows a uniform silicon content in the PSi samples that emit the strongest PL. High-resolution transmission electron microscopy reveals that the Si-NCs in these PSi samples are about ~2.9 ± 0.76 nm in size and are embedded in a dense and stoichiometric SiO2 matrix, as indicated by the Fourier transform infrared analysis. On the other hand, the PSi films that show PL of low intensity present an abrupt change in the silicon content depth and the formation of non-bridging oxygen hole center defects.

Iodine-promoted insertion of the oxygen atom from water in η4-vinylketene[Fe(CO)3] complexes.

Iodine promotes the in situ formation of iron(II) species from η4-vinylketene[Fe(CO)3] (3a-h) as a key intermediate for the synthesis of 2(5H)-furanones (4a-h) by a sequential water-insertion/carbon-oxygen coupling under mild reaction conditions. Compounds 4a-h were obtained in good to excellent yields. A possible reaction pathway was also proposed by DFT calculations. This methodology can be extended to the synthesis of (5H)-pyrrol-2-ones using anilines, with moderate yields and a few limitations.

Mast Cell-Tumor Interactions: Molecular Mechanisms of Recruitment, Intratumoral Communication and Potential Therapeutic Targets for Tumor Growth.

Mast cells (MCs) are tissue-resident immune cells that are important players in diseases associated with chronic inflammation such as cancer. Since MCs can infiltrate solid tumors and promote or limit tumor growth, a possible polarization of MCs to pro-tumoral or anti-tumoral phenotypes has been proposed and remains as a challenging research field. Here, we review the recent evidence regarding the complex relationship between MCs and tumor cells. In particular, we consider: (1) the multifaceted role of MCs on tumor growth suggested by histological analysis of tumor biopsies and studies performed in MC-deficient animal models; (2) the signaling pathways triggered by tumor-derived chemotactic mediators and bioactive lipids that promote MC migration and modulate their function inside tumors; (3) the possible phenotypic changes on MCs triggered by prevalent conditions in the tumor microenvironment (TME) such as hypoxia; (4) the signaling pathways that specifically lead to the production of angiogenic factors, mainly VEGF; and (5) the possible role of MCs on tumor fibrosis and metastasis. Finally, we discuss the novel literature on the molecular mechanisms potentially related to phenotypic changes that MCs undergo into the TME and some therapeutic strategies targeting MC activation to limit tumor growth.

Effect of the Graded Silicon Content in SRN/SRO Multilayer Structures on the Si Nanocrystals and Si Nanopyramids Formation and Their Photoluminescence Response.

Two multilayer (ML) structures, composed of five layers of silicon-rich oxide (SRO) with different Si contents and a sixth layer of silicon-rich nitride (SRN), were deposited by low pressure chemical vapor deposition. These SRN/SRO MLs were thermally annealed at 1100 °C for 180 min in ambient N2 to induce the formation of Si nanostructures. For the first ML structure (MLA), the excess Si in each SRO layer was about 10.7 ± 0.6, 9.1 ± 0.4, 8.0 ± 0.2, 9.1 ± 0.3 and 9.7 ± 0.4 at.%, respectively. For the second ML structure (MLB), the excess Si was about 8.3 ± 0.2, 10.8 ± 0.4, 13.6 ± 1.2, 9.8 ± 0.4 and 8.7 ± 0.1 at.%, respectively. Si nanopyramids (Si-NPs) were formed in the SRO/Si substrate interface when the SRO layer with the highest excess silicon (10.7 at.%) was deposited next to the MLA substrate. The height, base and density of the Si-NPs was about 2-8 nm, 8-26 nm and ~6 × 1011 cm-2, respectively. In addition, Si nanocrystals (Si-ncs) with a mean size of between 3.95 ± 0.20 nm and 2.86 ± 0.81 nm were observed for the subsequent SRO layers. Meanwhile, Si-NPs were not observed when the excess Si in the SRO film next to the Si-substrate decreased to 8.3 ± 0.2 at.% (MLB), indicating that there existed a specific amount of excess Si for their formation. Si-ncs with mean size of 2.87 ± 0.73 nm and 3.72 ± 1.03 nm were observed for MLB, depending on the amount of excess Si in the SRO film. An enhanced photoluminescence (PL) emission (eight-fold more) was observed in MLA as compared to MLB due to the presence of the Si-NPs. Therefore, the influence of graded silicon content in SRN/SRO multilayer structures on the formation of Si-NPs and Si-ncs, and their relation to the PL emission, was analyzed.

Institutional arthroplasty registry: what is the minimum acceptable dataset to be included in your hospital? Recommendations from a single-country national consensus using the Delphi method.

PURPOSE: Institutional arthroplasty registries are very popular nowadays; however, very few efforts have been made in order to standardize the information to be collected, thus limiting the possibility of inter-institutional data interpretation. This manuscript reports the results of a single-country consensus designed to define the minimum standardized dataset to be recorded within an institutional arthroplasty registry. METHODS: A national consensus was carried out among all members of the Colombian Society of Hip and Knee Surgeons using the Delphi method. Eleven questions and answers comprising every potential domain of an institutional registry of hip and knee arthroplasty were defined. According to the methodology, anonymous voting and multiple discussion rounds were performed. Three levels of agreement were defined: Strong consensus: equal to or greater than 80%, weak consensus between 70 and 79.9%, and no consensus below 70%. RESULTS: All of the questions reached consensus level. The minimum dataset was defined to include demographic and clinical information, intraoperative and implant details, follow-up and early complications, implant survival, and functional outcome scores, as well as the validation model to assess information quality within the database. Currently, this dataset is being implemented voluntarily by the members of our national society. DISCUSSION: A national consensus is a feasible method to build homogeneous arthroplasty registries. We recommend such an exercise since it establishes the basis to compare and add data between institutions and the joint analysis of said information in a national registry.

Mutant Huntingtin affects toll-like receptor 4 intracellular trafficking and cytokine production in mast cells.

BACKGROUND: Huntington's disease (HD) is caused by the expression of a mutated variant of Huntingtin (mHtt), which results in the complex pathology characterized by a defective function of the nervous system and altered inflammatory responses. While the neuronal effects of mHtt expression have been extensively studied, its effects on the physiology of immune cells have not been fully described. Mast cells (MCs) are unique tissue-resident immune cells whose activation has been linked to protective responses against parasites and bacteria, but also to deleterious inflammatory allergic reactions and, recently, to neurodegenerative diseases. METHODS: Bone marrow-derived mast cells (BMMCs) were obtained from wild-type (WT-) and mHtt-expressing (R6/1) mice to evaluate the main activation parameters triggered by the high-affinity IgE receptor (FcεRI) and the Toll-like receptor (TLR) 4. Degranulation was assessed by measuring the secretion of ß-hexosaminidase, MAP kinase activation was detected by Western blot, and cytokine production was determined by RT-PCR and ELISA. TLR-4 receptor and Htt vesicular trafficking was analyzed by confocal microscopy. In vivo, MC-deficient mice (c-KitWsh/Wsh) were intraperitonally reconstituted with WT or R6/1 BMMCs and the TLR4-induced production of the tumor necrosis factor (TNF) was determined by ELISA. A survival curve of mice treated with a sub-lethal dose of bacterial lipopolysaccharide (LPS) was constructed. RESULTS: R6/1 BMMCs showed normal ß-hexosaminidase release levels in response to FcεRI, but lower cytokine production upon LPS stimulus. Impaired TLR4-induced TNF production was associated to the lack of intracellular dynamin-dependent TLR-4 receptor trafficking to perinuclear regions in BMMCs, a diminished ERK1/2 and ELK-1 phosphorylation, and a decrease in c-fos and TNF mRNA accumulation. R6/1 BMMCs also failed to produce TLR4-induced anti-inflammatory cytokines (like IL-10 and TGF-ß). The detected defects were also observed in vivo, in a MCs-dependent model of endotoxemia. R6/1 and c-KitWsh/Wsh mice reconstituted with R6/1 BMMCs showed a decreased TLR4-induced TNF production and lower survival rates to LPS challenge than WT mice. CONCLUSIONS: Our data show that mHtt expression causes an impaired production of pro- and anti-inflammatory mediators triggered by TLR-4 receptor in MCs in vitro and in vivo, which could contribute to the aberrant immunophenotype observed in HD.

Mast Cells Localize in Hypoxic Zones of Tumors and Secrete CCL-2 under Hypoxia through Activation of L-Type Calcium Channels.

Hypoxia is a condition that together with low pH, high amounts of reactive oxygen species (ROS), and increased adenosine levels characterize tumor microenvironment. Mast cells (MCs) are part of tumor microenvironment, but the effect of hypoxia on the production of MC-derived cytokines has not been fully described. Using the hypoxia marker pimonidazole in vivo, we found that MCs were largely located in the low-oxygen areas within B16-F1 mice melanoma tumors. In vitro, hypoxia promoted ROS production, a ROS-dependent increase of intracellular calcium, and the production of MCP 1 (CCL-2) in murine bone marrow-derived MCs. Hypoxia-induced CCL-2 production was sensitive to the antioxidant trolox and to nifedipine, a blocker of L-type voltage-dependent Ca2+ channels (LVDCCs). Simultaneously with CCL-2 production, hypoxia caused the ROS-dependent glutathionylation and membrane translocation of the α1c subunit of Cav1.2 LVDCCs. Relationship between ROS production, calcium rise, and CCL-2 synthesis was also observed when cells were treated with H2O2 In vivo, high CCL-2 production was detected on hypoxic zones of melanoma tumors (where tryptase-positive MCs were also found). Pimonidazole and CCL-2 positive staining diminished when B16-F1 cell-inoculated animals were treated with trolox, nifedipine, or the adenosine receptor 2A antagonist KW6002. Our results show that MCs are located preferentially in hypoxic zones of melanoma tumors, hypoxia-induced CCL-2 production in MCs requires calcium rise mediated by glutathionylation and membrane translocation of LVDCCs, and this mechanism of CCL-2 synthesis seems to operate in other cells inside melanoma tumors, with the participation of the adenosine receptor 2A.

Prevalence and molecular epidemiology of bovine leukemia virus in Colombian cattle.

Bovine leukemia virus (BLV) is one of the five agents considered most significant for cattle. It is important to determine the prevalence and molecular epidemiology of BLV throughout the country in order to gain a more thorough understanding of the current situation of BLV and to reveal the possibility of masked genotypes that the primers used by OIE are unable to identify. Blood samples were collected at random from 289 cows distributed in 75 farms across the country. PCR amplification of env, gag and tax gene segments was performed. The obtained amplicons were sequenced and then subjected to phylogenetic analyses. A total of 62% of the cows present at 92% of the farms were BLV-positive for gag fragment. Genotype 1 was exclusively detected by env gene segment when analyzed using previously reported primers. However, tax gene analysis revealed circulation of genotype 6 variants, which were also detected based on env gene analysis with newly designed primers. These results indicate that current genotyping approaches based on partial env sequencing may bias BLV genetic variability approaches and underestimate the diversity of the detected BLV genotypes. This report is one of the first molecular and epidemiological studies of BLV conducted in Colombia, which contributes to the global epidemiology of the virus; it also highlights the substantial impact of BLV on the country's livestock and thus is a useful resource for farmers and government entities.

Seroprevalence and risk factor associated with respiratory viral pathogens in dual-purpose cattle of Aguachica, Rio de Oro, and La Gloria municipalities in Cesar department, Colombia.

AIM: The research was conducted to determine the seroprevalence and risk factor associated with respiratory viral pathogens in dual-purpose cattle of Aguachica, Rio de Oro and La Gloria municipalities in Cesar department, Colombia. MATERIALS AND METHODS: The seroprevalence study was done from the random sampling (n=1000) of blood collected from 29 dual-purpose herds, located in three municipalities (Aguachica, Rio de Oro, and La Gloria) of Cesar department. The presence of antibodies against bovine herpesvirus type 1 (BHV-1), bovine respiratory syncytial virus (BRSV), bovine viral diarrhea virus (BVDV), and bovine parainfluenza-3 virus (BPI-3V) in the samples was detected by indirect enzyme-linked immunosorbent assay. Epidemiological data were obtained using a questionnaire administered to the owner or manager of each herd. RESULTS: The overall highest seroprevalence was observed for BHV-1 (94.7%), followed by BRSV (98.6%), BVDV (35.2%), and BPI-3V (47.1%). Regarding the seroprevalence by municipalities, there was a statistical association (p<0.05) for BVDV; however, for BRSV, BHV-1, and BPI-3V, no statistical association was found (p>0.05) between seropositive values and the municipalities, indicating that animal was seropositive in similar proportions in the three municipalities. Female sex and older animals (>24 months) were a significant risk factor for BHV-1 and BPI-3V infection. Regarding the clinical signs, there was a statistical association (p<0.05) between the seropositive values of BVDV and most of clinical signs observed, except for abortion. CONCLUSION: This research confirms the high seroprevalence of the respiratory viral pathogens in nonvaccinated cattle within the study areas. Therefore, appropriate sanitary management practices and routine vaccination programs should be adopted to reduce the seroprevalence of these infectious agents.

TLR4 Receptor Induces 2-AG-Dependent Tolerance to Lipopolysaccharide and Trafficking of CB2 Receptor in Mast Cells.

Mast cells (MCs) contribute to the control of local inflammatory reactions and become hyporesponsive after prolonged TLR4 activation by bacterial LPS. The molecular mechanisms involved in endotoxin tolerance (ET) induction in MCs are not fully understood. In this study, we demonstrate that the endocannabinoid 2-arachidonoylglycerol (2-AG) and its receptor, cannabinoid receptor 2 (CB2), play a role in the establishment of ET in bone marrow-derived MCs from C57BL/6J mice. We found that CB2 antagonism prevented the development of ET and that bone marrow-derived MCs produce 2-AG in a TLR4-dependent fashion. Exogenous 2-AG induced ET similarly to LPS, blocking the phosphorylation of IKK and the p65 subunit of NF-κB and inducing the synthesis of molecular markers of ET. LPS caused CB2 receptor trafficking in Rab11-, Rab7-, and Lamp2-positive vesicles, indicating recycling and degradation of the receptor. 2-AG also prevented LPS-induced TNF secretion in vivo, in a MC-dependent model of endotoxemia, demonstrating that TLR4 engagement leads to 2-AG secretion, which contributes to the negative control of MCs activation. Our study uncovers a functional role for the endocannabinoid system in the inhibition of MC-dependent innate immune responses in vivo.

High prevalence of persistently infected animals from bovine viral diarrhea in Colombian cattle.

BACKGROUND: Bovine Viral Diarrhea Virus (BVDV) is associated with gastrointestinal, respiratory and reproductive diseases of livestock across the world that causes continuous economic losses in the cattle industry. This virus can establish a persistent infection (PI) in calves after the fetal infection, making BVDV positive catle carriers and primary reservoirs which will constantly transmit the virus to healthy and new-born animals. For this reason, the detection of the PI animals in herds is the first line of prevention of the viral infection. RESULTS: In this study, PI animals were detected in five different regions of Colombia through RT-PCR techniques and confirmed by sequencing. BVDV genotypes were determined using one fragment of the 5'UTR. It was found a 7% BVDV prevalence in animals and 22% in farms; and genotype 1 was identified as a single genotype for all of the samples. All samples were BVDV 1a. CONCLUSION: This is the first report in Colombia with higher prevalence rates compared with other places in the world, turned out to be of great importance for the ranchers, the vaccine producers and animal health control parties.

Adherencia a las guías internacionales de tromboprofilaxis en pacientes sometidos a cirugía ortopédica mayor en Colombia: Resultados del Registro DEIMOS / Adherence to the international thromboprophylaxis guidelines in patients undergoing major orthopaedic surgery in Colombia: Results of the DEIMOS registry

Introducción A pesar de que la implementación de guías de práctica clínica se relaciona con la disminución en la incidencia de eventos tromboembólicos pacientes sometidos a cirugía ortopédica mayor (COM), la adherencia a la tromboprofilaxis sigue siendo baja. El objetivo de este trabajo es describir la adherencia a la 8ª edición de las guías de American College of Chest Physicians (ACCP) en Colombia. Materiales y métodos Se presentan los resultados del registro DEIMOS para Colombia. Este estudio longitudinal, multicéntrico, multinacional evaluó la adherencia a las recomendaciones de tromboprofilaxis intrahospitalaria y extendida de la 8ª edición de las guías ACCP después de COM, mediante un seguimiento realizado entre 4 y 6 semanas postoperatorias. Resultados De los 244 pacientes incluidos en el registro DEIMOS para Colombia, 240 completaron el seguimiento: 108 pacientes de reemplazo total de rodilla (RTR), 77 de reemplazo total de cadera (RTC) y 59 de cirugía por fractura de cadera (FC). La adherencia intrahospitalaria fue de 80.5% (IC 95%: 71.7-89.4) para RTC, 82.4% (IC 95%: 75-2-89-6) para RTR y 94.9% (IC 95%: 89.3-100.0) para FC. La adherencia extendida fue de 75.3% (IC 95%: 65.7-85-0) para RTC, 73.1% (IC 95%: 64.8-81.5) para RTR y 93.2% (IC 95%: 86.8-99.6) para FC. Discusión El registro DEIMOS para Colombia evidencia una adecuada adherencia a la tromboprofilaxis después de cirugía por FC. Sin embargo, la adherencia al régimen extendido después de RTC y RTR es baja. Es necesario implementar esfuerzos adicionales para mejorar la protección de estos pacientes después del alta hospitalaria.

Background Patients who undergo major orthopaedic surgery have an elevated risk of venous thromboembolism (VTE). International guidelines recommendations for VTE prevention have shown to be effective in reducing the frequency of thromboembolic events, but compliance to these recommendations is still low. The purpose of the present study is to report the adherence to the American College of Chest Physicians (ACCP) guidelines 2008 in Colombia. Material and methods A report is presented on the Colombian results for the DEIMOS registry. This is a multinational, multicentre, observational, longitudinal study. Twenty orthopaedic wards were asked to include consecutive patients who were admitted for major orthopaedic surgery. Patient demographics, surgical information, type of anaesthesia and VTE prophylaxis were prospectively recorded, and the use of VTE prevention methods was assessed during the following visits. Adherence to the 2008 ACCP guidelines was then determined. Results A total of 244 patients were included in Colombia, and 240 of them had a complete follow-up. The analysis included 108 total knee arthroplasties, 77 hip replacements and 59 hip fracture surgeries. Adherence to 2008 ACCP guidelines for in-hospital prophylaxis was 80.5% (95% CI; 71.7-89.4) for hip arthroplasty, 82.4% (95% CI; 75.2-89.6) for knee arthroplasty, and 94.9% CI; 89.3-100.0) for hip fracture surgeries. Adherence for extended prophylaxis was 75.3% (95% CI; 65.7-85.0) for hip arthroplasties, 73.1% (95% CI; 64.8-81.5) for knee arthroplasties, and 93.2% (95% CI; 86.8-99.6) for hip fracture surgery. Discussion The DEIMOS registry reports good compliance to VTE prophylaxis guidelines after hip fracture surgery in Colombia. However, adherence to extended prophylaxis guidelines is still low after total hip and knee arthroplasties. Efforts should be made to improve the protection of these patients after hospital discharge.

PREVALENCIA DE Babesia caballi, Theileria equi Y TRIPANOSOMIASIS Y ANÁLISIS DE FACTORES DE RIESGO EN EQUINOS DE ANTIOQUIA, COLOMBIA / PREVALENCE OF Babesia caballi, Theileria equi AND TRYPANOSOMIASIS AND ANALYSIS OF RISK FACTORS IN HORSES OF ANTIOQUIA, COLOMBIA

RESUMEN Esta investigación, se llevó a cabo, debido a la poca información nacional existente en hemoparásitos equinos y su objetivo fue determinar la prevalencia de babesiosis y tripanosomiasis, en el Valle de Aburrá y Rionegro, municipios de Antioquia (Colombia), así como algunos factores de riesgo asociados a la presentación de seropositividad, a estas enfermedades. En 223 predios, con una población de 1.008 equinos, se tomó muestra de sangre venosa, para realizar el diagnóstico serológico y molecular. La información epidemiológica fue obtenida, a través de la aplicación de una encuesta dirigida a las personas a cargo de los animales. Para el análisis estadístico, se aplicó Chi cuadrado de independencia y la Prueba Exacta de Fisher, cuando fue necesario. Para las asociaciones bivariadas, se calcularon estimaciones del riesgo (OR) por variable explicativa, con sus respectivos intervalos de confianza, del 95% (I.C. 95%). Se encontró una prevalencia del 11,9%, para babesiosis y de 1,9%, para tripanosomiasis; como factor de protección, se encontró el hecho de salir a una feria. Para la piroplasmosis, el lugar geográfico, el sexo, estar castrado, ser positivos a Anemia Infecciosa Equina (AIE), estrongílidos u oxiurus fueron factores de riesgo. Para tripanosomiasis, el factor de riesgo fue estar infestado con Dermacentor nitens o ser mular. Se deben reforzar métodos de vigilancia epidemiológica activa, sobre todo, en casos de movilización continua de equinos o desarrollo de eventos, que involucren presencia masiva de ejemplares.

ABSTRACT This research was carried out due to the little existing national information on equine hemoparasites; the objective was to determine babesiosis and trypanosomiasis prevalence in the Aburrá Valley and Rionegro Antioquia (Colombia) as well as some risk factors associated with the seropositivitie of these diseases. In 223 lots with a population of 1.008 equine venous blood sample was taken for serological diagnosis and molecular. Epidemiological information was obtained through the application of a survey addressed to persons in charge of the animals. For the statistical analysis, Chi square of independence or Fisher's Exact Test was applied when necessary. For the bivariate associations, risk estimates (OR) were calculated by explanatory variable, with their respective 95% confidence intervals (95% CI).It was found a prevalence of 11.9% for babesiosis and 1.9% for trypanosomiasis and as protection factor found the fact of going to trade fairs. Geographic location, sex and being neutered, be positive for Equine Infectious Anemia (AIE), strongyles or oxiurus was a risk factor for piroplasmosis. For Trypanosomiasis the risk factor was to be infested with ticks Dermacentor nitens or be mule. Methods of active epidemiological surveillance should be reinforced, especially in cases of continuous mobilization of equines or development of events that involve massive presence of horses.