Hepatitis C virus point-of-care microelimination approach in a vulnerable population in the South of Spain.

Background: Since the introduction of direct-acting antivirals, thousands of chronic hepatitis C patients have been successfully treated. However, vulnerable populations have a higher prevalence of hepatitis C virus (HCV) infection and face barriers that impede their access to antivirals. We carried out an HCV microelimination program focused on vulnerable population groups in Malaga. Methods: People in drug addiction treatment centers and homeless shelters in Malaga who participated in the program between October 2020 and October 2021 were included. After providing participants with educational information on HCV, a dry drop test (DDT) was used to collect blood for subsequent screening for HCV infection. The participants who were diagnosed with HCV infection were scheduled for comprehensive healthcare assessments, including blood tests, ultrasonography, elastography, and the prescription of antivirals, all conducted in a single hospital visit. Sustained viral response (SVR) was analysed 12 weeks after end of treatment. Results: Of the 417 persons invited to participate, 271 (65%) agreed to participate in the program. These participants were screened for HCV infection and 28 of them were diagnosed with HCV infection (10%). These hepatitis C-infected patients had a mean age of 53 ± 9 years; 86% were males and 93% were or had been drug users. Among 23 patients with HCV infection, HCV genotype 1a predominated (74%). Medical exams showed that 19% (4/21) had advanced fibrosis (F3-4), and 5% (1/21) had portal hypertension. Finally, 23 infected patients received treatment with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir and SVR was confirmed in 22 patients (96%). Conclusions: Drug users and homeless people have a higher prevalence of HCV infection than the general population. The microelimination program with educational activity and screening tools achieved a high participation rate, easy healthcare access, and a high rate of SVR despite the SARS-CoV-2 pandemic.

Plasma levels of YKL-40 as a prognostic factor in childhood acute lymphoblastic leukemia.

YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is an inflammatory glycoprotein secreted by different types of cells, such as inflammatory cells. The levels of this protein are elevated in the serum or plasma of patients with different types of cancer, and high concentrations are associated with poor prognosis and short survival in patients with liver, breast, lung, bladder and endometrial cancers. In Mexico, acute lymphoblastic leukemia (ALL) is the most common type of cancer affecting the pediatric population. The prognosis of patients with ALL is difficult to establish. Hence, the objective of the present study was to analyze the plasma levels of YKL-40 in Mexican children with ALL and investigate its role as a prognostic factor. A case-control study was performed in a population of 90 children aged 1-18 years, among whom 45 had ALL and 45 were hematologically healthy. The levels of YKL-40 in plasma samples were measured using ELISA and were found to be significantly higher in children with ALL compared with those in controls (P<0.0001). Children with ALL who had high plasma levels of YKL-40 (≥36.34 ng/ml) had shorter survival compared with those with low levels (<36.34 ng/ml; P<0.05). The findings of the present study revealed that the YKL-40 plasma level, age/initial leukocyte count and central nervous system invasion were associated with the prognosis of children with ALL [odds ratio (OR)=6.06, 95% confidence interval (CI): 1.1-31.6, P=0.03; OR=8.53, 95% CI: 1.2-58.2, P=0.03; and OR=6.45, 95% CI: 1.01-41.2, P=0.04, respectively]. Therefore, YKL-40 plasma levels may serve as a prognostic biomarker in pediatric patients with ALL.

Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) up to 15 Months Post-Infection.

The recent COVID-19 pandemic is a treatment challenge in the acute infection stage but the recognition of chronic COVID-19 symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC) may affect up to 30% of all infected individuals. The underlying mechanism and source of this distinct immunologic condition three months or more after initial infection remains elusive. Here, we investigated the presence of SARS-CoV-2 S1 protein in 46 individuals. We analyzed T-cell, B-cell, and monocytic subsets in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly elevated in PASC patients up to 15 months post-acute infection compared to healthy controls (P=0.002 and P=0.01, respectively). A statistically significant number of non-classical monocytes contained SARS-CoV-2 S1 protein in both severe (P=0.004) and PASC patients (P=0.02) out to 15 months post-infection. Non-classical monocytes were sorted from PASC patients using flow cytometric sorting and the SARS-CoV-2 S1 protein was confirmed by mass spectrometry. Cells from 4 out of 11 severe COVID-19 patients and 1 out of 26 PASC patients contained ddPCR+ peripheral blood mononuclear cells, however, only fragmented SARS-CoV-2 RNA was found in PASC patients. No full length sequences were identified, and no sequences that could account for the observed S1 protein were identified in any patient. That non-classical monocytes may be a source of inflammation in PASC warrants further study.

CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14.

OBJECTIVE: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global pandemic. Emerging results indicate a dysregulated immune response. Given the role of CCR5 in immune cell migration and inflammation, we investigated the impact of CCR5 blockade via the CCR5-specific antibody leronlimab on clinical, immunological, and virological parameters in severe COVID-19 patients. METHODS: In March 2020, 10 terminally ill, critical COVID-19 patients received two doses of leronlimab via individual emergency use indication. We analyzed changes in clinical presentation, immune cell populations, inflammation, as well as SARS-CoV-2 plasma viremia before and 14 days after treatment. RESULTS: Over the 14-day study period, six patients survived, two were extubated, and one discharged. We observed complete CCR5 receptor occupancy in all donors by day 7. Compared with the baseline, we observed a concomitant statistically significant reduction in plasma IL-6, restoration of the CD4/CD8 ratio, and resolution of SARS-CoV2 plasma viremia (pVL). Furthermore, the increase in the CD8 percentage was inversely correlated with the reduction in pVL (r = -0.77, p = 0.0013). CONCLUSIONS: Our study design precludes clinical efficacy inferences but the results implicate CCR5 as a therapeutic target for COVID-19 and they form the basis for ongoing randomized clinical trials.

Repeated Coronavirus Disease 2019 Molecular Testing: Correlation of Severe Acute Respiratory Syndrome Coronavirus 2 Culture With Molecular Assays and Cycle Thresholds.

BACKGROUND: Repeated coronavirus disease 2019 (COVID-19) molecular testing can lead to positive test results after negative results and to multiple positive results over time. The association between positive test results and infectious virus is important to quantify. METHODS: A 2-month cohort of retrospective data and consecutively collected specimens from patients with COVID-19 or patients under investigation were used to understand the correlation between prolonged viral RNA positive test results, cycle threshold (Ct) values and growth of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cell culture. Whole-genome sequencing was used to confirm virus genotype in patients with prolonged viral RNA detection. Droplet digital polymerase chain reaction was used to assess the rate of false-negative COVID-19 diagnostic test results. RESULTS: In 2 months, 29 686 specimens were tested and 2194 patients underwent repeated testing. Virus recovery in cell culture was noted in specimens with a mean Ct value of 18.8 (3.4) for SARS-CoV-2 target genes. Prolonged viral RNA shedding was associated with positive virus growth in culture in specimens collected up to 21 days after the first positive result but mostly in individuals symptomatic at the time of sample collection. Whole-genome sequencing provided evidence the same virus was carried over time. Positive test results following negative results had Ct values >29.5 and were not associated with virus culture. Droplet digital polymerase chain reaction results were positive in 5.6% of negative specimens collected from patients with confirmed or clinically suspected COVID-19. CONCLUSIONS: Low Ct values in SARS-CoV-2 diagnostic tests were associated with virus growth in cell culture. Symptomatic patients with prolonged viral RNA shedding can also be infectious.

Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is now pandemic with nearly three million cases reported to date. Although the majority of COVID-19 patients experience only mild or moderate symptoms, a subset will progress to severe disease with pneumonia and acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. Emerging results indicate a dysregulated immune response characterized by runaway inflammation, including cytokine release syndrome (CRS), as the major driver of pathology in severe COVID-19. With no treatments currently approved for COVID-19, therapeutics to prevent or treat the excessive inflammation in severe disease caused by SARS-CoV-2 infection are urgently needed. Here, in 10 terminally-ill, critical COVID-19 patients we report profound elevation of plasma IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma viremia. Following compassionate care treatment with the CCR5 blocking antibody leronlimab, we observed complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma viremia. Consistent with reduction of plasma IL-6, single-cell RNA-sequencing revealed declines in transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation, restoring immunologic deficiencies, and reducing SARS-CoV-2 plasma viral load via disruption of the CCL5-CCR5 axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 for COVID-19.

Association Between the 5,10-MTHFR 677C>T and RFC1 80G>A Polymorphisms and Acute Lymphoblastic Leukemia.

BACKGROUND: Polymorphisms in folate-related genes are closely related to the development of cancer. The 5,10-MTHFR 677C>T and RFC1 80G>A polymorphisms are associated with an increased risk of susceptibility to pediatric ALL. OBJECTIVE: The aim of this study was to illustrate the association between 5,10-MTHFR 677C>T and RFC1 80G>A polymorphisms and ALL in a Mexican population. MATERIALS AND METHODS: This study was conducted in 60 pediatric ALL patients and 60 healthy individuals. The 5,10-MTHFR 677C>T and RFC1 80G>A polymorphisms were detected by the PCR-RFLP method. RESULTS: Our investigation revealed that the 5,10-MTHFR 677 C/T and 5,10-MTHFR 677T/T genotypes are associated with susceptibility to pediatric ALL (OR = 1.9, 95% IC = 1.36-12.09, p = 0.012 and OR = 2.8, 95% CI = 1.49-22.82, p = 0.011, respectively). Likewise, the G/A genotype from the RFC1 80G>A polymorphism showed an increased ALL risk compared to RFC1 G80G genotype (OR = 3. 3, 95% CI = 1.75-8.87, p = 0.002). CONCLUSION: Therefore, our results suggest that the 5,10-MTHFR 677C>T and RFC1 80G>A polymorphisms are factors involved in the susceptibility to ALL in Mexican population.

Deregulation of folate pathway gene expression correlates with poor prognosis in acute leukemia.

The present study analyzed the mRNA expression levels of genes involved in the transport and metabolism of methotrexate (MTX) (RFC1, ABCC1, ABCB1, GGH, FPGS, ATIC, TS, MTHFR, MTRR, MS and MTHFD1) in patients with acute leukemia (AL). The expression levels of the examined genes were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in patients with AL (ALL:50/AML:19) and 66 healthy individuals. The mRNA expression levels of RFC1, MS, MTRR, MTHFR and ABCB1 were decreased (P<0.05), while those of GGH, FPGS, TS and MTHFD1 (P<0.05) were overexpressed in patients with AL. Patients with high mRNA levels of GGH (OR=4.28, 95% CI=1.29-14.14), TS (OR=7.14, 95% CI 1.84-27.81), MTHFR (OR=4.81, 95% CI=1.31-17.64), ABCB1 (OR=4.61, 95% CI=1.33-15.97) and ABCC1 (OR=5.50, 95% CI=1.12-27.06) had a higher chance of relapse. Interestingly, high mRNA levels of RFC1 are a protective factor in the risk of AL relapse (OR=0.22, 95% 0.06-0.80). The results of the present study indicated that deregulation of folate pathway gene expression is associated with poor prognosis in AL and that the expression levels of these markers could serve as novel molecular targets for the treatment of patients with AL.

Traumatismo dentoalveolares, características clínicas e imagenológicas: Una revisión de la literatura / Dentoalveolar traumatism, clinical and imagenological characteristics: a literature review

El traumatismo dentoalveolar resulta del impacto de una fuerza externa, con variación de intensidad, que afecta la calidad de vida del individuo debido a la alteración en la estética por alteración de la apariencia, problemas funcionales al alterar el habla, lo que genera un impacto psicológico y social. Las causas van desde una simple caída hasta prácticas deportivas, accidentes automovilísticos, violencia, manejo de herramientas de trabajo. Los niños y adolescentes son los más susceptibles, y las piezas anteriores superiores las que frecuentemente son más afectadas. El manejo multidisciplinario de la lesión y el estudio con exámenes complementarios, como la radiografía, son indispensables para el diagnóstico de los traumatismos. Asimismo, avances tecnológicos como la tomografía de haz cónico han mejorado la observación al proporcionar cortes transversales. (AU)

Dentoalveolar trauma results from the impact of an external force, of varying intensity, affecting the quality of life of the individual due to aesthetic alteration caused by an altered appearance, and functional problems caused by alteration of speech, producing a psychological and social impact. Causes may range from a simple fall, to sporting activities, car acci-dents, violence, or the use of tools in the workplace. Children and adolescents are the most susceptible groups and the anterior superior areas are those most often affected. Multidisciplinary manage-ment of the injury and studies involving complementary tests such as radio-graphy are essential for the diagnosis of trauma. Technological advances such as the use of cone beam tomography have improved diagnosis by providing cross section scans.m (AU)

Overexpression of dihydrofolate reductase is a factor of poor survival in acute lymphoblastic leukemia.

Dihydrofolate reductase (DHFR) has an important function in DNA synthesis and is a target of methotrexate, which is a crucial treatment option for acute lymphoblastic leukemia (ALL). However, the number of studies conducted to date on DHFR expression in childhood ALL is limited. The aim of the present study was to determine whether the expression of DHFR is associated with survival in childhood ALL. The expression of DHFR in 96 children with ALL and 100 control individuals was determined using reverse transcription-quantitative polymerase chain reaction. The results of the present study demonstrated that the expression of DHFR mRNA in children with ALL was significantly increased (P<0.001), compared with that in the control group. In addition, increased levels of DHFR mRNA were observed in patients with B-cell lineage, compared with patients with T-cell lineage ALL (P<0.05). The Kaplan-Meier estimator analysis revealed that children with ALL who exhibited increased levels of DHFR mRNA had a decreased overall survival time (P<0.05). It was observed that certain patient prognostic features (including age, sex, white blood cell count and high DHFR expression), are associated with poor survival (log-rank test, P<0.05). Therefore, the results of the present study indicated that DHFR upregulation is a factor for poor survival in ALL.

[Synthesis of antibiotic loaded polylactic acid nanoparticles and their antibacterial activity against Escherichia coli O157:H7 and methicillin-resistant Staphylococcus aureus].

INTRODUCTION: Polymeric nanoparticles are promising nanotechnology tools to fight pathogenic bacteria resistant to conventional antibiotics. OBJECTIVE: To synthesize polylactic acid nanoparticles loaded with ofloxacin and vancomycin, and to determine their antibacterial activity against Escherichia coli O157:H7 and methicillin-resistant Staphylococcus aureus (MRSA). MATERIALS AND METHODS: We synthesized ofloxacin or vancomycin loaded polylactic acid nanoparticles by the emulsification-solvent evaporation method, and characterized them by dynamic light scattering, laser Doppler electrophoresis and scanning electron microscopy. We evaluated in vitro antibacterial activity of ofloxacin- and vancomycin-loaded polylactic acid nanoparticles against E. coli O157:H7 and MRSA using the broth microdilution method. RESULTS: Ofloxacin- and vancomycin-loaded polylactic acid nanoparticles registered a positive surface charge density of 21 mV and an average size lower than 379 nm. In vitro minimum inhibitory concentration (MIC50) of ofloxacin-polylactic acid nanoparticles was 0,001 µg/ml against E. coli O157:H7, i.e., 40 times lower than the free ofloxacin (MIC50: 0.04 µg/ml), indicating enhanced antibacterial activity while the in vitro MIC50 of vancomycin-polylactic acid nanoparticles was 0,005 µg/ml against MRSA, i.e., 100 times lower than that of free vancomycin (MIC50: 0.5 µg/ml). CONCLUSION: Polylactic acid nanoparticles loaded with ofloxacin and vancomycin showed a higher antibacterial activity. Polymeric nanoparticles are a possible alternative for drug design against pathogenic bacterial strains of public health interest.

Síntesis de nanopartículas de ácido poliláctico cargadas con antibióticos y su actividad antibacteriana contra Escherichia coli O157:H7 y Staphylococcus aureus resistente a meticilina / Synthesis of antibiotic loaded polylactic acid nanoparticles and their antibacterial activity against Escherichia coli O157:H7 and methicillin-resistant Staphylococcus aureus

Resumen Introducción: Las nanopartículas poliméricas constituyen una herramienta nanotecnológica que podría ayudar a combatir los microorganismos patógenos que han desarrollado resistencia a los antibióticos convencionales. Objetivo: Sintetizar nanopartículas de ácido poliláctico cargadas con ofloxacina y vancomicina, y determinar su actividad antibacteriana frente a Escherichia coli O157:H7 y Staphylococcus aureus resistente a la meticilina (SARM). Materiales y métodos: Las nanopartículas de ácido poliláctico cargadas con ofloxacina y vancomicina se sintetizaron utilizando el método de emulsión y evaporación de solvente. Se caracterizaron mediante dispersión de luz en modo dinámico, electroforesis Doppler con láser y microscopía electrónica de barrido (S-TEM). Se evaluó la actividad antibacteriana in vitro de las nanopartículas de ácido poliláctico con ofloxacina contra E. coli O157:H7 y nanopartículas de ácido poliláctico con vancomicina contra SARM, mediante el método de microdilución en caldo. Resultados: Se obtuvieron nanopartículas poliméricas con tamaños inferiores a 379 nm y carga superficial positiva de hasta 21 mV. Las nanopartículas cargadas con ofloxacina presentaron una concentración inhibitoria mínima (CIM50) de 0,001 μg/ml frente a E. coli O157:H7, valor 40 veces menor que la concentración de antibiótico libre necesaria para lograr el mismo efecto (CIM50=0,04 μg/ml). Para SARM, las nanopartículas mejoraron la potencia farmacológica in vitro de la vancomicina al exhibir una MIC50 de 0,005 μg/ml, comparada con la de 0,5 μg/ml del antibiótico libre. Conclusiones: Se mejoró el efecto antibacteriano de la ofloxacina y la vancomicina incorporadas en la matriz polimérica de ácido poliláctico. Las nanopartículas poliméricas constituirían una alternativa para el control de cepas bacterianas de interés en salud pública.

Abstract Introduction: Polymeric nanoparticles are promising nanotechnology tools to fight pathogenic bacteria resistant to conventional antibiotics. Objective: To synthesize polylactic acid nanoparticles loaded with ofloxacin and vancomycin, and to determine their antibacterial activity against Escherichia coli O157:H7 and methicillin-resistant Staphylococcus aureus (MRSA). Materials and methods: We synthesized ofloxacin or vancomycin loaded polylactic acid nanoparticles by the emulsification-solvent evaporation method, and characterized them by dynamic light scattering, laser Doppler electrophoresis and scanning electron microscopy. We evaluated in vitro antibacterial activity of ofloxacin- and vancomycin-loaded polylactic acid nanoparticles against E. coli O157:H7 and MRSA using the broth microdilution method. Results: Ofloxacin- and vancomycin-loaded polylactic acid nanoparticles registered a positive surface charge density of 21 mV and an average size lower than 379 nm. In vitro minimum inhibitory concentration (MIC50) of ofloxacin-polylactic acid nanoparticles was 0,001 μg/ml against E. coli O157:H7, i.e., 40 times lower than the free ofloxacin (MIC50: 0.04 μg/ml), indicating enhanced antibacterial activity while the in vitro MIC50 of vancomycin-polylactic acid nanoparticles was 0,005 μg/ml against MRSA, i.e., 100 times lower than that of free vancomycin (MIC50: 0.5 μg/ml). Conclusion: Polylactic acid nanoparticles loaded with ofloxacin and vancomycin showed a higher antibacterial activity. Polymeric nanoparticles are a possible alternative for drug design against pathogenic bacterial strains of public health interest.

On-line coupling of physiologically relevant bioaccessibility testing to inductively coupled plasma spectrometry: Proof of concept for fast assessment of gastrointestinal bioaccessibility of micronutrients from soybeans.

In-vitro physiologically relevant gastrointestinal extraction based on the validated Unified BARGE Method (UBM) is in this work hyphenated to inductively coupled plasma optical emission spectrometry in a batch-flow configuration for real-time monitoring of oral bioaccessibility assays with high temporal resolution. A fully automated flow analyzer is designed to foster in-line filtration of gastrointestinal extracts at predefined times (≤15 min) followed by on-line multi-elemental analysis of bioaccessible micro-nutrients, viz., Cu, Fe and Mn, in well-defined volumes of extracts (300 µL) of transgenic and non-transgenic soybean seeds taken as model samples. The hyphenated flow setup allows for recording of temporal extraction profiles to gain full knowledge of the kinetics of the gastrointestinal digestion processes, including element leaching and concomitant precipitation and complexation reactions hindering bioavailability. Simplification of the overall standard procedure is also feasible by identification of steady-state extraction conditions. Our findings indicate that reliable measurement of oral bioaccessible pools of Cu, Fe and Mn in soybean might be obtained in less than 180 min rather than 240 min as endorsed by UBM. Using a matrix-matched external calibration, limits of detection according to the 3s criteria were 0.5 µg/g for Mn, 0.6 µg/g for Cu and 2.3 µg/g for Fe. Trueness of the automatic bioaccessibility method was confirmed by mass balance validation with recoveries ranging from 87 to 116% regardless of the target element and sample. Cu was the micronutrient with the highest oral bioaccessibility ranging from 73% to 83% (7.5-7.9 µg/g) for non-transgenic and transgenic soybeans, respectively, followed by Mn and Fe within the ranges of 29-31% (10.8-11.4 µg/g) and 11-15% (8-14 µg/g), respectively, regardless of transgenesis. The proposed kinetic method is proven suitable for fast and expedient estimation of the nutritional value of soybeans and elucidation of the potential effect of transgenesis onto bioaccessible fractions of elements.

Comparison of Nonculture Blood-Based Tests for Diagnosing Invasive Aspergillosis in an Animal Model.

The EuropeanAspergillusPCR Initiative (EAPCRI) has provided recommendations for the PCR testing of whole blood (WB) and serum/plasma. It is important to test these recommended protocols on nonsimulated "in vivo" specimens before full clinical evaluation. The testing of an animal model of invasive aspergillosis (IA) overcomes the low incidence of disease and provides experimental design and control that is not possible in the clinical setting. Inadequate performance of the recommended protocols at this stage would require reassessment of methods before clinical trials are performed and utility assessed. The manuscript describes the performance of EAPCRI protocols in an animal model of invasive aspergillosis. Blood samples taken from a guinea pig model of IA were used for WB and serum PCR. Galactomannan and ß-d-glucan detection were evaluated, with particular focus on the timing of positivity and on the interpretation of combination testing. The overall sensitivities for WB PCR, serum PCR, galactomannan, and ß-d-glucan were 73%, 65%, 68%, and 46%, respectively. The corresponding specificities were 92%, 79%, 80%, and 100%, respectively. PCR provided the earliest indicator of IA, and increasing galactomannan and ß-d-glucan values were indicators of disease progression. The combination of WB PCR with galactomannan and ß-d-glucan proved optimal (area under the curve [AUC], 0.95), and IA was confidently diagnosed or excluded. The EAPRCI-recommended PCR protocols provide performance comparable to commercial antigen tests, and clinical trials are warranted. By combining multiple tests, IA can be excluded or confirmed, highlighting the need for a combined diagnostic strategy. However, this approach must be balanced against the practicality and cost of using multiple tests.

Bacterial contamination of propofol vials used in operating rooms of a third-level hospital.

We found a 6.1% bacterial contamination rate among 198 propofol vials collected after clinical use in 12 operating rooms of a high-complexity hospital in Cali, Colombia. Some propofol vials were used for extended periods (up to 72 hours), and only 26.1% of vials were punctured once. Median time of use, although not statistically significant, was higher in positive samples (7.2 vs 3.5 hours, P = .08). Education on the topic should stress that vials are single-patient use and must be immediately discarded after use.

α-Lipoic Acid Protects Against Ischemia-Reperfusion Injury in Simultaneous Kidney-Pancreas Transplantation.

BACKGROUND: Multiple factors have been implicated in the process of ischemia-reperfusion injury (IRI) in organ transplantation. Among these factors, oxidative damage seems to initiate the injury. α-lipoic acid (ALA) is a potent antioxidant that is used in patients with diabetic polyneuropathy. The aim of the present study was to determine the effect of ALA in patients undergoing simultaneous kidney-pancreas transplant by evaluating the functional recovery of the graft and biochemical markers of IRI. METHODS: Twenty-six patients were included in the following groups: (i) untreated control; (ii) donor and recipient (DR) ALA-treated, in which ALA was administered both to the deceased donor and to the recipients; and (iii) recipient ALA-treated group. The expression of inflammatory genes, as observed in biopsies taken at the end of surgery, as well as the serum cytokines, secretory leukocyte protease inhibitor, regenerating islet-derived protein 3ß/pancreatitis-associated protein, amylase, lipase, glucose, and creatinine levels were quantified as markers of organ function. RESULTS: The DR group showed high levels of TGFß and low levels of C3 and TNFα in the kidneys, whereas high levels of C3 and heme oxygenase were identified in pancreas biopsies. Decreases in serum IL-8, IL-6, secretory leukocyte protease inhibitor, and regenerating islet-derived protein 3 ß/pancreatitis-associated protein were observed after surgery in the DR group. Serum lipase and amylase were lower in the DR group than in the control and recipient groups. Early kidney dysfunction and clinical pancreatitis were higher in the control group than in either treatment group. CONCLUSIONS: These results show that ALA preconditioning is capable of reducing inflammatory markers while decreasing early kidney dysfunction and clinical posttransplant pancreatitis.

Efficacy of the investigational echinocandin ASP9726 in a guinea pig model of invasive pulmonary aspergillosis.

ASP9726 is an investigational echinocandin with in vitro activity against Aspergillus species. We evaluated the pharmacokinetics and efficacy of this agent in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.5, 5, and 10 mg/kg of body weight/day by subcutaneous injection. Immunosuppressed guinea pigs were inoculated with A. fumigatus AF293, and ASP9726 (2.5, 5, and 10 mg/kg/day), voriconazole (10 mg/kg by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal injection) was administered for 8 days. Changes in fungal burden were measured by enumerating CFU and by quantitative PCR of specimens from within the lungs, as well as by analysis of serum (1 → 3)-ß-D-glucan and galactomannan. Lung histopathology was also evaluated. ASP9726 plasma concentrations increased in a dose-proportional manner, and the drug was well tolerated at each dose. Each dose of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal burden as measured by quantitative PCR and by determining (1 → 3)-ß-D-glucan and galactomannan levels, but only voriconazole significantly reduced numbers of CFU. ASP9726 at 5 mg/kg also significantly improved survival. Histopathology demonstrated morphological changes in hyphae in animals exposed to ASP9726 and caspofungin, consistent with the activities of the echinocandins. These results suggest that ASP9726 may be efficacious for the treatment of invasive pulmonary aspergillosis.

High miR-24 expression is associated with risk of relapse and poor survival in acute leukemia.

MicroRNAs (miRNAs) play an essential role in the development and progression of acute leukemia (AL). miR-24 promotes the survival of hematopoietic cells. However, little is known concerning the function of miR-24 in human AL. The aim of the present study was to investigate the clinical significance of miR-24 expression in AL. miR-24 expression in 147 patients with AL and 100 healthy individuals was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). The results showed that compared with the healthy individuals, the expression of miR-24 in AL patients was significantly higher (p<0.001). In addition, miR-24 was expressed at significantly higher levels in acute myeloid leukemia (AML) patients and at significantly lower levels in acute lymphoblastic leukemia (ALL) (p<0.001). More importantly, Kaplan-Meier analysis showed that AL patients with high miR-24 expression tended to have shorter overall survival (p<0.05). In the multivariate analysis stratified for known prognostic variables, miR-24 was identified as an independent prognostic marker. Our data indicated that miR-24 upregulation was associated with poor prognosis in AL. miR-24 was identified for the first time as an independent marker for predicting the clinical outcome of AL patients.

Fisiopatología de la septicemia neonatal equina / Pathophysiology of Equine Neonatal Septicemia / Fisiopatologia da septicemia neonatal equina

La septicemia neonatal es la mayor causa de mortalidad y morbilidad en equinos en sus primeros siete días de vida y dentro de su fisiopatología. Es importante tener en cuenta los factores predisponentes extrínsecos e intrínsecos al potro que los hace susceptibles a la entrada de agentes que principalmente son de etiología bacteriana. No obstante, se deben considerar otros tipos de etiología infecciosa (virus y hongos), así como las etiologías de índole no infecciosa. Se menciona una amplia variedad de mecanismos que producen distintas lesiones que deben atenderse con medidas de cuidado crítico neonatal, por lo que es imprescindible para el clínico de equinos conocer los mecanismos de patogenicidad de la enfermedad, la presentación clínica y las lesiones anatomopatológicas. Así, los conceptos del síndrome de respuesta inflamatoria sistémica (SIRS), síndrome de disfunción multiorgánica (MODS) y el colapso circulatorio periférico o shock son algunos de los elementos que se definen como los pilares de la fisiopatología de la septicemia neonatal, y se han estudiado ampliamente en medicina de equinos. Este trabajo muestra una revisión corta de los mecanismos de desencadenamiento de la septicemia neonatal, y resalta la importancia de investigaciones epidemiológicas en Colombia; muestra la necesidad de hacer trabajos retrospectivos y prospectivos y de dar a conocer algunas de las medidas de prevención de la enfermedad en equinos.

Neonatal septicemia is a major cause of mortality and morbidity in horses in their first seven days of life and within their pathophysiology. It is important to consider the extrinsic and intrinsic predisposing factors which make foals susceptible to agents of primarily bacterial etiology. However, other types of infectious etiology (viruses and fungi) should be considered too, as well as noninfectious etiologies. The paper mentions a wide variety of mechanisms that produce different injuries that must be addressed with measures of critical neonatal care, so it is imperative for the veterinarian to know the pathogenic mechanisms of the disease, its clinical presentation and anatomo-pathological lesions. Thus, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and peripheral circulatory collapse or shock are some of the elements defined as the pillars of the pathophysiology of neonatal septicemia, extensively studied in equine medicine. This paper presents a short review of the triggering mechanisms of neonatal septicemia highlighting the importance of epidemiological investigations in Colombia. It shows the need for retrospective and prospective studies and for divulgation of some of the preventive measures of the disease in horses.

A septicemia neonatal é a maior causa de mortalidade e morbidade em equinos em seus primeiros sete dias de vida e dentro de sua fisiopatologia. É importante ter em conta os fatores predisponentes extrínsecos e intrínsecos ao potro que os faz suscetíveis na entrada de agentes que principalmente são de etiologia bacteriana. Não obstante, se devem considerar outros tipos de etiologia infecciosa (vírus e fungos), Assim como as etiologias de índole não infecciosa. Menciona-se uma ampla variedade de mecanismos que produzem diferentes lesões que devem atender-se com medidas de cuidado crítico neonatal, por isso é imprescindível para que o clínico de equinos possa conhecer os mecanismos de patogenicidade da doença, a apresentação clínica e as lesões anatomopatológicas. Assim, os conceitos da síndrome de resposta inflamatória sistêmica (SIRS), síndrome de disfunção multiorgânica (MODS) e o colapso circulatório periférico ou shock são alguns dos elementos que se definem como os pilares da fisiopatologia da septicemia neonatal, e estudaram-se amplamente em medicina de equinos. Este trabalho amostra uma revisão curta dos mecanismos de desencadeamento da septicemia neonatal, e destaca a importância de pesquisas epidemiológicas na Colômbia; mostra a necessidade de fazer trabalhos retrospectivos e prospectivos e de dar a conhecer algumas das medidas de prevenção da doença em equinos.