Analysis of Healthcare-associated Infections before and during the COVID-19 pandemic in a Colombian hospital

Introduction: Healthcare-associated infections pose a significant challenge, contributing to hospital morbidity and mortality. Objective: To describe the behavior of Healthcare Associated Infections before and during the pandemic reported to a high-complexity health institution in Colombia. Material and Methods: In our retrospective observational study on Healthcare-Associated Infections (HAIs), we analyzed data from all in-patients diagnosed with HAIs between 2018 and 2020. This included clinical, demographic, microbiological, and microbial susceptibility information collected from the Committee on Nosocomial Infections' prospective database. Data from 391 isolates were obtained using Whonet software for antimicrobial resistance surveillance. Results: We found 504 cases of HAIs (2018-2020) with an overall in-hospital infection rate of 2.55/1000 patient-days. The median age for pediatric patients was 5 years, and for adults, 56 years, with 57% male. The leading admission diagnoses were oncologic disease complications (31%). Bacteremia had a 30-day mortality rate of 13%, predominantly catheter-associated (37%). Gram-negative bacilli, notably Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa, represented 58% cases of HAI. Discussion: The critical need for specific interventions and antimicrobial management to control HAIs, especially given the challenges posed by the COVID-19 pandemic, is highlighted. Conclusions: This is the first report on HAIs incidence at a tertiary hospital in Bucaramanga, Santander (Colombia). Bacteremia was predominant; 75% of HAIs patients had comorbidities. Gram-negative bacilli prevailed; a notable rise in ICU respiratory infections occurred during the 2020 COVID-19 pandemic. Resistance to cephalosporins and carbapenems was prevalent.

A finite element study comparing Advansync® and Twin Block in mandibular anterior repositioning.

OBJECTIVE: This study aims to utilize the finite element method (FEM) to compare the dentoalveolar and mandibular effects associated with anterior mandibular repositioning using AdvanSync® (ADV) and Twin Block (TB). METHODS: A patient with Class II skeletal malocclusion and mandibular retrognathism was selected. A TB appliance was subsequently applied. Computed Tomography (CT) scans were acquired at the beginning of treatment (T1) and 8 months later (T2). Concurrently, a numerical TB model was validated through FEM simulations, which were compared with the T2 results. The ADV appliance was virtually simulated to evaluate stress and deformation on the condyle, symphysis, first lower molar and lower central incisors. RESULTS: Both simulations demonstrated significant mandibular advancement. However, ADV led to less incisor proclination and more molar intrusion compared to TB. ADV exhibited increased stress in the lower molar area, while TB had higher stress in the lower incisor region. Stress and deformations in the condyle and mandibular symphysis were similar in both simulations, with the highest stress observed at the condylar neck and the lowest at the upper pole of the condylar head. CONCLUSIONS: Both appliances achieved similar levels of mandibular advancement, with greater proclination of the lower central incisors and more widespread distribution of stress and molar intrusion when using ADV compared to TB.

In vitro assessment of ruminal biohydrogenation of polyunsaturated fatty acids in diets with different types and levels of protected fat and diverse sources of fibre.

The objective was to assess the in vitro rumen fermentation characteristics, methane production, and biohydrogenation of unsaturated fatty acids of diets with two protected fat (PF) sources from soybean or linseed oil, two levels of PF (0 and 6%) and two forage sources (canola silage (CS) or alfalfa hay (AH)) in a factorial 2x2x2 completely randomised design. Only fatty acids content at final incubation was affected (P<0.05) by triple interaction, where C18:2 was highest with AH plus 6% soybean PF (4.41mg/g DM), while C18:3 was with CS plus 6% linseed oil protected (1.98mg/g DM). C18:2 cis-9 trans-11 had high concentration (308 mg/g DM; P<0.05) with AH plus 6% PF regardless PF type, and C18:1 trans-11 was higher with 6% PF than without PF (13.41 vs 7.89 mg/g DM). Cumulative methane production was not affected by treatments (0.9973 ± 0.1549 mmol/g DM; P>0.05). Gas production and in vitro NDF digestibility were lower with 6% PF of linseed than soybean (160.88 vs 150.97 ml; and 69.28vs 62.89 %, respectively P<0.05). With linseed PF the NH3-N concentration was highest in CS than AH (41.27 vs 27.95 mg/dL; P<0.05) but IVDMD had the opposite result (78.54 vs 85.04). In conclusion, although methane production was not affected and in vitro digestibility and gas production were reduced with linseed PF, the concentration of C18:3 and C18:1 trans-11 was increased, which could improve the lipid profile of milk. The negative effects on digestibility were less with AH than of CS regardless of PF type and level.

Association between neutrophil-to-lymphocyte ratio in the first seven days of sepsis and mortality.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of sepsis has been found to be higher in non-survivors than in survivors, and that is associated with mortality. A higher NLR in non-survivors than in survivors has been reported in two studies during patient follow-up; however, NLR was not controlled for sepsis severity. Thus, the objective of this study was to determine whether there is an association between NLR in the first seven days and mortality controlling for sepsis severity. METHODS: This observational study, which included septic patients, was conducted in the Intensive Care Units of 3 Spanish hospitals. NLR was recorded on the first, fourth, and eighth day of sepsis. Multiple logistic regression analyses were carried out to determine the association between NLR during the first 7 days of sepsis diagnosis and mortality controlling for sepsis severity. RESULTS: Thirty-day non-surviving patients (n=68) compared to surviving patients (n=135) showed higher NLR on the first (p<0.001), fourth (p<0.001), and eighth (p<0.001) day of sepsis diagnosis. Multiple logistic regression analysis found an association between NLR at days first (p<0.001), fourth (p=0.004), and eighth (p=0.01) of sepsis diagnosis and mortality controlling for SOFA and lactic acid in those days. CONCLUSIONS: The new finding of our study was the association between NLR in the first seven days of sepsis and mortality controlling for sepsis severity.

Association between neutrophil-to-lymphocyte ratio in the first seven days of sepsis and mortality / Asociación entre la relación neutrófilos/linfocitos durante los primeros siete días de sepsis y mortalidad

IntroductionThe neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of sepsis has been found to be higher in non-survivors than in survivors, and that is associated with mortality. A higher NLR in non-survivors than in survivors has been reported in two studies during patient follow-up; however, NLR was not controlled for sepsis severity. Thus, the objective of this study was to determine whether there is an association between NLR in the first seven days and mortality controlling for sepsis severity.MethodsThis observational study, which included septic patients, was conducted in the Intensive Care Units of 3 Spanish hospitals. NLR was recorded on the first, fourth, and eighth day of sepsis. Multiple logistic regression analyses were carried out to determine the association between NLR during the first 7 days of sepsis diagnosis and mortality controlling for sepsis severity.ResultsThirty-day non-surviving patients (n=68) compared to surviving patients (n=135) showed higher NLR on the first (p<0.001), fourth (p<0.001), and eighth (p<0.001) day of sepsis diagnosis. Multiple logistic regression analysis found an association between NLR at days first (p<0.001), fourth (p=0.004), and eighth (p=0.01) of sepsis diagnosis and mortality controlling for SOFA and lactic acid in those days.ConclusionsThe new finding of our study was the association between NLR in the first seven days of sepsis and mortality controlling for sepsis severity.

IntroducciónSe ha objetivado que la relación neutrófilos/linfocitos (NLR) en el momento del diagnóstico de la sepsis es mayor en fallecidos que en supervivientes y que está asociada con la mortalidad. En dos estudios, se ha reportado mayor NLR en fallecidos durante la evolución; sin embargo, NLR no se controló por la gravedad de la sepsis. Por lo tanto, el objetivo de este estudio consistió en determinar si existe una asociación entre NLR durante los primeros siete días y mortalidad, controlando por gravedad de la sepsis.MétodosEste estudio observacional, incluyendo pacientes sépticos, fue realizado en las Unidades de Cuidados Intensivos de tres hospitales españoles. Se registró NLR en los días 1, 4 y 8 del diagnóstico de la sepsis. Se realizó regresión logística múltiple para determinar la asociación entre NLR durante los primeros siete días y mortalidad (a los 30 días), controlando por gravedad de la sepsis.ResultadosLos pacientes fallecidos en los primeros 30 días (n = 68), comparados con los supervivientes (n = 135), tuvieron mayor NLR en los días 1 (p < 0,001), 4 (p < 0,001) y 8 (p < 0,001) del diagnóstico de la sepsis. La regresión logística múltiple mostró la asociación entre NLR en los días 1 (p < 0,001), 4 (p = 0,004) y 8 (p = 0,01) del diagnóstico de la sepsis y mortalidad, controlando por SOFA y lactatemia en esos días.ConclusionesEl nuevo hallazgo de nuestro estudio fue la asociación entre NLR durante los primeros siete días de la sepsis y la mortalidad, controlando por gravedad de la sepsis.

Mortality prediction of patients with spontaneous intracerebral hemorrhage by serum soluble Fas ligand concentrations.

BACKGROUND: A study of patients with spontaneous intracerebral hemorrhage (SIH) found a higher content of Fas ligand in the perihematomic brain area compared to healthy brain areas. The objective of this study was to analyze whether blood soluble Fas ligand (sFasL) concentrations could be used to estimate the prognosis of SIH patients. METHODS: Observational and prospective study performed in five Spanish Intensive Care Units. Patients with severe supratentorial SIH, defined as Glasgow Coma Scale (GCS) <9, were included. Serum sFasL levels were determined at the time of diagnosis of severe SIH. Mortality at 30 days was the end-point study. RESULTS: Surviving SIH patients (n = 41) compared to nonsurvivors (n = 38) showed lower serum sFasL levels (p < 0.001). The area under curve of mortality prediction for serum sFasL levels was 0.79 (95% CI = 0.70-0.89; p < 0.001). Multiple logistic regression analysis found an association of serum sFasL concentrations with 30-day mortality (ORo = 1,034; 95% CI = 1,010-1,058; p = 0,006) after controlling for midline shift, early hematoma evacuation, and intracerebral hemorrhage score. CONCLUSIONS: The capability of serum sFasL to predict SIH patient mortality is the main novel finding of our study. ABBREVIATIONS: APACHE II: Acute Physiology and Chronic Health Evaluation; aPTT: activated partial thromboplastin time; FIO2: fraction of inspired oxygen; GCS: Glasgow Coma Scale; ICU: Intensive Care Unit; INR: international normalized ratio; PaO2: pressure of arterial oxygen.

Synthesis of Copper Nanoparticles Stabilized with Organic Ligands and Their Antimicrobial Properties.

In this work, we report the synthesis of copper nanoparticles (Cu NPs), employing the chemical reduction method in an aqueous medium. We used copper sulfate pentahydrate (CuSO4·5H2O) as a metallic precursor; polyethylenimine (PEI), allylamine (AAM), and 4-aminobutyric acid (AABT) as stabilizing agents; and hydrated hydrazine as a reducing agent. The characterization of the obtained nanoparticles consisted of X-ray, TEM, FTIR, and TGA analyses. Through these techniques, it was possible to detect the presence of the used stabilizing agents on the surface of the NPs. Finally, a zeta potential analysis was performed to differentiate the stability of the nanoparticles with a different type of stabilizing agent, from which it was determined that the most stable nanoparticles were the Cu NPs synthesized in the presence of the PEI/AAM mixture. The antimicrobial activity of Cu/PEI/AABT toward P. aeruginosa and S. aureus bacteria was high, inhibiting both bacteria with low contact times and copper concentrations of 50-200 ppm. The synthesis method allowed us to obtain Cu NPs free of oxides, stable to oxidation, and with high yields. The newly functionalized Cu NPs are potential candidates for antimicrobial applications.

The venom of the scorpion Centruroides limpidus, which causes the highest number of stings in Mexico, is neutralized by two recombinant antibody fragments.

Phage display and directed evolution have made it possible to generate recombinant antibodies in the format of single chain variable fragments (scFvs) capable of neutralizing different toxins and venoms of Mexican scorpions. Despite having managed to neutralize a significant number of venoms, some others have not yet been completely neutralized, due to the diversity of the toxic components present in them. An example is the venom of the scorpion Centruroides limpidus, which contains three toxins of medical importance, called Cll1, Cll2 and Cl13. The first two are neutralized by scFv 10FG2, while Cl13, due to its sequence divergence, was not even recognized. For this reason, the aim of the present work was the generation of a new scFv capable of neutralizing Cl13 toxin and thereby helping to neutralize the whole venom of this scorpion. By hybridoma technology, a monoclonal antibody (mAb B7) was generated, which was able to recognize and partially neutralize Cl13 toxin. From mAb B7, its scFv format was obtained, named scFv B7 and subjected to three cycles of directed evolution. At the end of these processes, scFv 11F which neutralized Cl13 toxin was obtained. This scFv, administered in conjunction with scFv 10FG2, allowed to fully neutralize the whole venom of Centruroides limpidus scorpion.

Antimicrobial Property of Polypropylene Composites and Functionalized Copper Nanoparticles.

Copper nanoparticles (CuNPs) functionalized with polyethyleneimine (PEI) and 4-aminobutyric acid (GABA) were used to obtain composites with isotactic polypropylene (iPP). The iPP/CuNPs composites were prepared at copper concentrations of 0.25-5.0 wt % by melt mixing, no evidence of oxidation of the CuNP was observed. Furthermore, the release of copper ions from iPP/CuNPs composites in an aqueous medium was studied. The release of cupric ions was higher in the composites with 2.5 and 5.0 wt %. These composites showed excellent antibacterial activity (AA) toward Pseudomona aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). The incorporation of CuNP into the iPP polymeric matrix slightly decreased the thermal stability of the composite material but improved the crystallinity and the storage modulus. This evidence suggests that CuNPs could work as nucleating agents in the iPP crystallization process. The iPP/CuNPs composites presented better AA properties compared to similar composites reported previously. This behavior indicates that the new materials have great potential to be used in various applications that can be explored in the future.

Imaging Enterobacterales infections in patients using pathogen-specific positron emission tomography.

Enterobacterales represent the largest group of bacterial pathogens in humans and are responsible for severe, deep-seated infections, often resulting in sepsis or death. They are also a prominent cause of multidrug-resistant (MDR) infections, and some species are recognized as biothreat pathogens. Tools for noninvasive, whole-body analysis that can localize a pathogen with specificity are needed, but no such technology currently exists. We previously demonstrated that positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-sorbitol (18F-FDS) can selectively detect Enterobacterales infections in murine models. Here, we demonstrate that uptake of 18F-FDS by bacteria occurs via a metabolically conserved sorbitol-specific pathway with rapid in vitro 18F-FDS uptake noted in clinical strains, including MDR isolates. Whole-body 18F-FDS PET/computerized tomography (CT) in 26 prospectively enrolled patients with either microbiologically confirmed Enterobacterales infection or other pathologies demonstrated that 18F-FDS PET/CT was safe, could rapidly detect and localize Enterobacterales infections due to drug-susceptible or MDR strains, and differentiated them from sterile inflammation or cancerous lesions. Repeat imaging in the same patients monitored antibiotic efficacy with decreases in PET signal correlating with clinical improvement. To facilitate the use of 18F-FDS, we developed a self-contained, solid-phase cartridge to rapidly (<10 min) formulate ready-to-use 18F-FDS from commercially available 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) at room temperature. In a hamster model, 18F-FDS PET/CT also differentiated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from secondary Klebsiella pneumoniae pneumonia-a leading cause of complications in hospitalized patients with COVID-19. These data support 18F-FDS as an innovative and readily available, pathogen-specific PET technology with clinical applications.

Evaluation of mandibular buccal shelf characteristics in the Colombian population: A cone-beam computed tomography study.

OBJECTIVE: To evaluate the mandibular buccal shelf (MBS) in terms of the angulation and bone depth and thickness according to sex, age, and sagittal and vertical skeletal patterns in a Colombian population using cone-beam computed tomography (CBCT). Accordingly, the optimal site for miniscrew insertion in this area was determined. METHODS: This descriptive, retrospective study included 64 hemi-arches of 34 patients. On CBCT images, the angulation, buccal bone depth (4 and 6 mm from the cementoenamel junction [CEJ] of MBS), and buccal bone thickness (6 and 11 mm from the CEJ of MBS) were measured at the mesial and distal roots of the mandibular first and second molars. RESULTS: There were no statistically significant differences in the angulation, depth, and thickness of MBS between male and female patients. The values for the bone around the distal root of the mandibular second molar were significantly greater than the other values. The osseous characteristics were significantly better in participants aged 16-24 years. Class III patients exhibited the best osseous characteristics, with the bone depth at 6 mm being significantly different from that in Class I and Class II patients. Although values tended to be greater in patients with low angles, the difference was not statistically significant. CONCLUSIONS: MBS provides an optimal bone surface for miniscrew insertion, with better osseous characteristics at the distal root of the mandibular second molar, 4 mm from CEJ. Adolescent patients, Class III patients, and patients with a low angle exhibit the most favorable osseous characteristics in the MBS area.

Association between serum sFasL concentrations and sepsis mortality.

BACKGROUND: There are scarce data on soluble Fas Ligand (sFasL), one of the main ligands that activate the apoptosis extrinsic pathway, in septic patients. In a small study of septic children were found higher plasma sFasL levels in non-survivors compared with survivors; however, an association between blood sFasL levels and mortality controlling for sepsis severity was not stablished due to the small sample size of the study. Therefore, the main objective of this study was to determine whether there is an association between blood sFasL concentrations and mortality in septic patients controlling for sepsis severity. Methods: Septic patients were included in this observational and prospective study conducted in three Spanish Intensive Care Units. Serum samples at diagnosis of sepsis were obtained for serum sFasL levels determination. RESULTS: Thirty-day non-surviving patients (n = 85) with respect to surviving patients (n = 151) showed higher serum sFasL levels (p<.001). Multiple logistic regression analysis found an association between serum sFasL levels and mortality (odds ratio [OR] = 1.007; 95% confidence interval [CI] = 1.003-1.010; p<.001) after controlling for age, septic shock, SOFA, INR and aPTT. The area under the curve (AUC) for mortality prediction by serum sFasL levels was of 62% (95% CI = 56-69%; p=.003). In Kaplan-Meier analysis was found that patients with serum sFasL levels >109 pg/mL had a higher mortality rate (hazard ratio = 3.6; 95% CI = 1.93-6.78; p<.001). CONCLUSIONS: The main new finding from our study was that serum sFasL concentrations were associated with mortality in septic patients controlling for sepsis severity. Highlights Blood sFasL concentrations were higher in non-survivor than in survivor patients. There is an association between blood sFasL concentrations and mortality in septic patients. Blood sFasL concentrations could predict mortality of septic patients.

Association between neutrophil-to-lymphocyte ratio in the first seven days of sepsis and mortality.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of sepsis has been found to be higher in non-survivors than in survivors, and that is associated with mortality. A higher NLR in non-survivors than in survivors has been reported in two studies during patient follow-up; however, NLR was not controlled for sepsis severity. Thus, the objective of this study was to determine whether there is an association between NLR in the first seven days and mortality controlling for sepsis severity. METHODS: This observational study, which included septic patients, was conducted in the Intensive Care Units of 3 Spanish hospitals. NLR was recorded on the first, fourth, and eighth day of sepsis. Multiple logistic regression analyses were carried out to determine the association between NLR during the first 7 days of sepsis diagnosis and mortality controlling for sepsis severity. RESULTS: Thirty-day non-surviving patients (n=68) compared to surviving patients (n=135) showed higher NLR on the first (p<0.001), fourth (p<0.001), and eighth (p<0.001) day of sepsis diagnosis. Multiple logistic regression analysis found an association between NLR at days first (p<0.001), fourth (p=0.004), and eighth (p=0.01) of sepsis diagnosis and mortality controlling for SOFA and lactic acid in those days. CONCLUSIONS: The new finding of our study was the association between NLR in the first seven days of sepsis and mortality controlling for sepsis severity.

Approach to ocular toxoplasmosis including pregnant women.

PURPOSE OF REVIEW: To discuss available information on the effectiveness of anti-toxoplasma therapy for ocular toxoplasmosis and to provide clinicians with a practical approach to the disease. RECENT FINDINGS: Only eleven randomized studies were identified. In the three studies for acute retinitis, there was a clear trend in favor of treatment. In the two studies for the prevention of recurrences, trimethoprim-sulfamethoxazole prophylaxis was superior to placebo. In the six studies comparing different regimens, there was no statistically significant difference between the regimens. In the setting of acute posterior uveitis suspected to be caused by toxoplasma, serological testing should always be obtained, and anti-toxoplasma drug treatment, and corticosteroids should be instituted for at least 6 weeks. Toxoplasmic chorioretinitis during pregnancy represents a particular challenge. SUMMARY: Treatment with at least two drugs and corticosteroids should be offered to patients with active toxoplasmic chorioretinitis. Pregnant women with confirmed acute infection and concomitant acute retinitis should be treated for the ocular lesion(s) and to prevent vertical transmission. Pregnant women with chronic Toxoplasma infection acquired prior to gestation and concomitant retinitis by reactivation should be treated for the retinitis and monitored for vertical transmission.

Presentación del síndrome de Wernicke-Korsakoff secundario a encefalitis por citomegalovirus, a propósito de un caso / Wernicke-Korsakoff syndrome secondary to cytomegalovirus encephalitis: A case report

Resumen El citomegalovirus (CMV) es uno de los microorganismos oportunistas con mayor prevalencia en pacientes inmunocomprometidos, aunque su reactivación ha descendido después de la introducción de la terapia antirretroviral altamente activa (Highly Active Antiretroviral Therapy, HAART). En las coinfecciones, la encefalitis se ha reportado como una de las condiciones más frecuentes. Se presenta el caso de un paciente adulto joven con infección por virus de la inmunodeficiencia humana (HIV) que tuvo un rápido deterioro neurológico evidenciado en síntomas y signos clínicos clásicos del síndrome de Wernicke-Korsakoff y que no presentaba factores de riesgo para deficiencia de tiamina. En las imágenes de la resonancia magnética cerebral, se detectaron hallazgos típicos del síndrome, y se identificó citomegalovirus (CMV) en el líquido cefalorraquídeo. Con el tratamiento específico para el CMV, se logró el control de los síntomas, aunque hubo secuelas neurológicas que mejoraron. Este es uno de los pocos casos reportados a nivel mundial de síndrome de Wernicke secundario a encefalitis por citomegalovirus.

Abstract Cytomegalovirus (CMV) is one of the opportunistic microorganisms with the highest prevalence in immunocompromised patients. Reactivation has decreased after the introduction of highly active antiretroviral therapy (HAART). Encephalitis has been reported in the coinfection as one of the most frequent presentations. We present the case of a young adult patient with HIV infection and rapid neurological deterioration due to classic clinical symptoms and signs of the Wernicke-Korsakoff syndrome, with no risk factors for thiamine deficiency, with images by nuclear magnetic resonance typical of the syndrome, and identification of cytomegalovirus in cerebrospinal fluid. The specific treatment for CMV managed to control the symptoms with neurological sequelae in progression towards improvement. This is one of the few cases reported in the literature of Wernicke syndrome secondary to cytomegalovirus encephalitis.

A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia.

BACKGROUND: Treatment of sickle cell anemia is a challenging task and despite the well understood genetic and biochemical pathway of sickle hemoglobin, current therapy continues to be limited to the symptomatic treatment of pain, supplemental oxygen, antibiotics, red blood cell transfusions and hydroxyurea. SANGUINATE is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities. METHODS: An open-label randomized Phase Ib study was performed in adult sickle cell anemia patients. Two dose levels of SANGUINATE were compared to hydroxyurea in 24 homozygotes for Hb SS. Twelve subjects received either a low dose (160mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. Another 12 subjects received either a high dose (320mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. The primary endpoint was the safety of SANGUINATE versus hydroxyurea in sickle cell anemia patients. Secondary endpoints included determination of the plasma pharmacokinetics and assessment of hematologic measurements. RESULTS: Musculoskeletal related adverse events were the most common. Transient troponin I levels increased in three patients, one of whom had an increase in tricuspid regurgitant velocity; however, no clinical signs were noted. Following an assessment of vital signs, tricuspid regurgitant velocity, electrocardiogram, serum biochemistry, hematology, urinalysis, and analysis of reported adverse events, SANGUINATE was found to be safe in stable sickle cell anemia patients. CONCLUSIONS: The clinical trial met its primary objective of demonstrating an acceptable safety profile for SANGUINATE in patients with sickle cell anemia. This trial established the safety of SANGUINATE at both dose levels and permitted its advance to Phase II trials.

A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia

Abstract Background: Treatment of sickle cell anemia is a challenging task and despite the well understood genetic and biochemical pathway of sickle hemoglobin, current therapy continues to be limited to the symptomatic treatment of pain, supplemental oxygen, antibiotics, red blood cell transfusions and hydroxyurea. SANGUINATE is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities. Methods: An open-label randomized Phase Ib study was performed in adult sickle cell anemia patients. Two dose levels of SANGUINATE were compared to hydroxyurea in 24 homozygotes for Hb SS. Twelve subjects received either a low dose (160 mg/kg) of SANGUINATE or 15 mg/kg hydroxyurea. Another 12 subjects received either a high dose (320 mg/kg) of SANGUINATE or 15 mg/kg hydroxyurea. The primary endpoint was the safety of SANGUINATE versus hydroxyurea in sickle cell anemia patients. Secondary endpoints included determination of the plasma pharmacokinetics and assessment of hematologic measurements. Results: Musculoskeletal related adverse events were the most common. Transient troponin I levels increased in three patients, one of whom had an increase in tricuspid regurgitant velocity; however, no clinical signs were noted. Following an assessment of vital signs, tricuspid regurgitant velocity, electrocardiogram, serum biochemistry, hematology, urinalysis, and analysis of reported adverse events, SANGUINATE was found to be safe in stable sickle cell anemia patients. Conclusions: The clinical trial met its primary objective of demonstrating an acceptable safety profile for SANGUINATE in patients with sickle cell anemia. This trial established the safety of SANGUINATE at both dose levels and permitted its advance to Phase II trials.

[Wernicke-Korsakoff syndrome secondary to cytomegalovirus encephalitis: A case report].

Cytomegalovirus (CMV) is one of the opportunistic microorganisms with the highest prevalence in immunocompromised patients. Reactivation has decreased after the introduction of highly active antiretroviral therapy (HAART). Encephalitis has been reported in the coinfection as one of the most frequent presentations.We present the case of a young adult patient with HIV infection and rapid neurological deterioration due to classic clinical symptoms and signs of the Wernicke-Korsakoff syndrome, with no risk factors for thiamine deficiency, with images by nuclear magnetic resonance typical of the syndrome, and identification of cytomegalovirus in cerebrospinal fluid. The specific treatment for CMV managed to control the symptoms with neurological sequelae in progression towards improvement.This is one of the few cases reported in the literature of Wernicke syndrome secondary to cytomegalovirus encephalitis.

Consenso Colombiano para la estratificación, diagnostico, Tratamiento y Prevención de la Infección por citomegalovirus en Pacientes Adultos con trasplante renal / Colombian consensus for stratification, diagnosis, treatment and prevention of cytomegalovirus infection in adults patients with renal transplant

El citomegalovirus es una de las principales causas de infección y enfermedad en receptores de trasplante renal, con un notorio impacto en términos de morbilidad, mortalidad y costos. Sin embargo, no existe en Colombia una práctica clínica estandarizada entre los centros de trasplante, por lo cual, es de suma importancia disponer de guías con el fin de orientar la estratificación, el diagnóstico de laboratorio, el tratamiento y la prevención de la infección y enfermedad por citomegalovirus en pacientes adultos con trasplante renal. A través de la metodología ADAPTE para la evaluación de calidad y transculturización de guías de práctica clínica a nuestro medio, un grupo multidisciplinario realizó una revisión sistemática de la literatura: se seleccionaron las guías internacionales, las cuales fueron evaluadas con el instrumento AGREE II en términos de calidad. Con la guía base seleccionada se buscó la evidencia existente para contestar a las preguntas, de acuerdo con el método de desarrollo de recomendaciones GRADE. Se realizaron recomendaciones para la estratificación, el diagnóstico, el tratamiento y la prevención de la infección y enfermedad por citomegalovirus en pacientes adultos con trasplante renal en Colombia.

Cytomegalovirus is a primary cause of infection and illness in patients who have had renal transplantation, with a significant impact on morbidity, mortality and economic costs. However, there is no standardized clinical practice in transplant centers in Colombia, and it is important to have guidelines to stratify, diagnose, treat and prevent cytomegalovirus infection and disease. Through ADAPTE's methodology for the quality evaluation and adaptation of clinical practice guidelines in our setting, a multidisciplinary group carried out a systematic review of the medical literature, selecting international guidelines that were evaluated with the AGREE-II instrument in terms of quality. With each selected guideline, an evidence table was constructed and the GRADE strategy was performed to develop recommendations. Recommendations related to stratification, laboratory diagnosis, treatment and prevention of infections and disease caused by cytomegalovirus in adult transplant patients were developed.

[Fusarium species associated with basal rot of garlic in North Central Mexico and its pathogenicity]. / Patogenicidad de especies de Fusarium asociadas a la pudrición basal del ajo en el centro norte de México.

Garlic in Mexico is one of the most profitable vegetable crops, grown in almost 5,451ha; out of which more than 83% are located in Zacatecas, Guanajuato, Sonora, Puebla, Baja California and Aguascalientes. Blossom-end rot caused by Fusarium spp is widely distributed worldwide and has been a limiting factor in onion and garlic production regions, not only in Mexico but also in other countries. The presence of Fusarium oxysporum has been reported in Guanajuato and Aguascalientes. Fusarium culmorum has been reported in onion cultivars of Morelos; and Fusarium proliferatum, Fusarium verticillioides, Fusarium solani and Fusarium acuminatum have been previously reported in Aguascalientes. The goal of this work was identifying the Fusarium species found in Zacatecas, Guanajuato and Aguascalientes, to assess their pathogenicity. Plants with disease symptoms were collected from hereinabove mentioned States. The samples resulted in the identification of: F. oxysporum, F. proliferatum, F. verticillioides, F. solani and F. acuminatum species; out of which Aguascalientes AGS1A (F. oxysporum), AGS1B (F. oxysporum) and AGSY-10 (F. acuminatum) strains showed higher severity under greenhouse conditions.