Time Course of Mechanical Ventilation Driving Pressure Levels in Pediatric Acute Respiratory Distress Syndrome: Outcomes in a Prospective, Multicenter Cohort Study From Colombia, 2018-2022.

OBJECTIVES: High driving pressure (DP, ratio of tidal volume (V t ) over respiratory system compliance) is a risk for poor outcomes in patients with pediatric acute respiratory distress syndrome (PARDS). We therefore assessed the time course in level of DP (i.e., 24, 48, and 72 hr) after starting mechanical ventilation (MV), and its association with 28-day mortality. DESIGN: Multicenter, prospective study conducted between February 2018 and December 2022. SETTING: Twelve tertiary care PICUs in Colombia. PATIENTS: One hundred eighty-four intubated children with moderate to severe PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median (interquartile range [IQR]) age of the PARDS cohort was 11 (IQR 3-24) months. A total of 129 of 184 patients (70.2%) had a pulmonary etiology leading to PARDS, and 31 of 184 patients (16.8%) died. In the first 24 hours after admission, the plateau pressure in the nonsurvivor group, compared with the survivor group, differed (28.24 [IQR 24.14-32.11] vs. 23.18 [IQR 20.72-27.13] cm H 2 O, p < 0.01). Of note, children with a V t less than 8 mL/kg of ideal body weight had lower adjusted odds ratio (aOR [95% CI]) of 28-day mortality (aOR 0.69, [95% CI, 0.55-0.87]; p = 0.02). However, we failed to identify an association between DP level and the oxygenation index (aOR 0.58; 95% CI, 0.21-1.58) at each of time point. In a diagnostic exploratory analysis, we found that DP greater than 15 cm H 2 O at 72 hours was an explanatory variable for mortality, with area under the receiver operating characteristic curve of 0.83 (95% CI, 0.74-0.89); there was also increased hazard for death with hazard ratio 2.5 (95% CI, 1.07-5.92). DP greater than 15 cm H 2 O at 72 hours was also associated with longer duration of MV (10 [IQR 7-14] vs. 7 [IQR 5-10] d; p = 0.02). CONCLUSIONS: In children with moderate to severe PARDS, a DP greater than 15 cm H 2 O at 72 hours after the initiation of MV is associated with greater odds of 28-day mortality and a longer duration of MV. DP should be considered a variable worth monitoring during protective ventilation for PARDS.

Etiology and the challenge of diagnostic testing of community-acquired pneumonia in children and adolescents.

BACKGROUND: Pneumonia is the leading cause of mortality in pediatric population. The etiology of pneumonia in this population is variable and changes according to age and disease severity and where the study is conducted. Our aim was to determine the etiology of community-acquired pneumonia (CAP) in children aged 1 month to 17 years admitted to 13 Colombian hospitals. METHODS: Prospective cohort study. Hospitalized children with radiologically confirmed CAP and ≤ 15 days of symptoms were included and followed together with a control group. Induced sputum (IS) was submitted for stains and cultures for pyogenic bacteria and Mycobacterium tuberculosis, and multiplex PCR (mPCR) for bacteria and viruses; urinary antigens for pneumococcus and Legionella pneumophila; nasopharyngeal swabs for viruses, and paired serology for atypical bacteria and viruses. Additional cultures were taken at the discretion of primary care pediatricians. RESULTS: Among 525 children with CAP, 71.6% had non-severe pneumonia; 24.8% severe and 3.6% very severe pneumonia, and no fatal cases. At least one microorganism was identified in 84% of children and 61% were of mixed etiology; 72% had at least one respiratory virus, 28% pyogenic bacteria and 21% atypical bacteria. Respiratory syncytial virus, Parainfluenza, Rhinovirus, Influenza, Mycoplasma pneumoniae, Adenovirus and Streptococcus pneumoniae were the most common etiologies of CAP. Respiratory syncytial virus was more frequent in children under 2 years and in severe pneumonia. Tuberculosis was diagnosed in 2.3% of children. IS was the most useful specimen to identify the etiology (33.6%), and blood cultures were positive in 3.6%. The concordance between all available diagnostic tests was low. A high percentage of healthy children were colonized by S. pneumoniae and Haemophilus influenzae, or were infected by Parainfluenza, Rhinovirus, Influenza and Adenovirus. CONCLUSIONS: Respiratory viruses are the most frequent etiology of CAP in children and adolescents, in particular in those under 5 years. This study shows the challenges in making an etiologic diagnosis of CAP in pediatric population because of the poor concordance between tests and the high percentage of multiple microorganisms in healthy children. IS is useful for CAP diagnosis in pediatric population.

Tocilizumab in giant cell arteritis: differences between the GiACTA trial and a multicentre series of patients from the clinical practice.

OBJECTIVES: A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice. METHODS: Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week). RESULTS: Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice. CONCLUSIONS: Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.

A novel pathogenic variant in PRF1 associated with hemophagocytic lymphohistiocytosis.

Familial Hemophagocytic Lymphohistiocytosis type 2 (FHL2) results from mutations in PRF1. We described two unrelated individuals who presented with FHL, in whom severely impaired NK cytotoxicity and decrease perforin expression was observed. DNA sequencing of PRF1 demonstrated that both were not only heterozygous for the p.54R > C/91A > V haplotype but also presented with the novel variant p.47G > V at the perforin protein. Perforin mRNA was found to be increased in a individual with that genotype. A carrier of the novel variant also demonstrated altered perforin mRNA and protein expression. Phylogenetic analysis and multiple alignments with perforin orthologous demonstrated a high level of conservation at Gly47. PolyPhen-2 and PROVEAN predicted p.47G > V to be "probably damaging" and "deleterious", respectively. A thermodynamic analysis showed that this variant was highly stabilizing, decreasing the protein internal energy. The ab initio perforin molecular modeling indicated that Gly47 is buried inside the hydrophobic core of the MACPF domain, which is crucial for the lytic pore formation and protein oligomerization. After the in silico induction of the p.47G > V mutation, Val47 increased the interactions with the surrounding amino acids due to its size and physical properties, avoiding a proper conformational change of the domain. To our knowledge, this is the first description supporting that p.47G > V is a pathogenic variant that in conjunction with p.54R > C/91A > V might result in the clinical phenotype of FHL2.

Association between the lactate-albumin ratio and microcirculation changes in Pediatric Septic patients.

A lactate/albumin ratio (LAR) greater than 0.5 measured early in the course of pediatric critical illness is associated with greater mortality. Whether the elevated LAR can be explained by microcirculation disorders in children with sepsis is not known. In this longitudinal retrospective study (January 2021-January 2024), serum albumin and lactate were measured on admission to the pediatric intensive care unit (PICU), with sublingual video microscopy performed simultaneously to measure microcirculation. A total of 178 children were included, 37% of whom had septic shock measured with the Phoenix Sepsis Score. Patients with remote sepsis had greater odds of an elevated LAR (aOR 6.87: 95% CI 1.98-23.73; p < 0.01). Children with an elevated LAR had more microvascular blood flow abnormalities (aOR 1.31 95% CI 1.08-1.58; p < 0.01), lower 4-6-micron capillary density (aOR 1.03 95% CI 1.01-1.05; p < 0.01) and greater odds of dying (aOR 3.55 95% CI 1.21-10.38; p = 0.02) compared to those with a low LAR. We found no association between LAR and endothelial glycocalyx degradation. A normal LAR is associated with less risk of microcirculatory injury (aOR 0.77 95% CI 0.65-0.93; p < 0.01). In children with sepsis, an elevated LAR is associated with microcirculation abnormalities (microvascular density and flow). The lactate/albumin ratio is a potentially useful biomarker for microcirculatory injury in sepsis.

Association Between Tidal Volume in Invasive Mechanical Ventilation and Mortality in Children With Extracorporeal Membrane Oxygenation.

Mechanical ventilation (MV) strategies in children on extracorporeal membrane oxygenation (ECMO) have not been studied much and the ventilatory parameters to avoid greater lung damage are still unclear. Our objective was to determine the relationship between conventional tidal volume (4-8 ml/kg, CTV) versus low tidal volume (<4 ml/kg, LTV) and mortality in children with MV at the beginning of ECMO. This was a retrospective cohort study that included 101 (10.9 months interquartile range [IQR]: 6.0-24.0) children. Children with LTV had greater odds of hospital mortality (adjusted odds ratio [aOR]: 2.45; 95% confidence interval [CI]: 1.05-5.71; p = 0.03) regardless of age, reason for ECMO, and disease severity, as well as a longer duration of MV after ECMO. We found no differences between the groups in other MV settings. The CTV group required fewer fibrobronchoscopies than patients with LTV (aOR: 0.38; 95% CI: 0.15-0.99; p = 0.04). We found that a tidal volume (VT) lower than 4 ml/kg at the onset of ECMO support in children with MV was associated with higher odds of mortality, longer post-decannulation ventilation, and a greater need for fibrobronchoscopies. Lung-protective bundles in patients with ECMO and MV should consider the VT to maintain plateau and driving pressure that avoid major lung injury caused by MV.

Acute Intrathoracic Tuberculosis in Children and Adolescents with Community-Acquired Pneumonia in an Area with an Intermediate Disease Burden.

Tuberculosis (TB) in the pediatric population is a major challenge. Our objective was to describe the clinical and microbiological characteristics, radiological patterns, and treatment outcomes of children and adolescents (from 1 month to 17 years) with community-acquired pneumonia (CAP) caused by TB. We performed a prospective cohort study of a pediatric population between 1 month and 17 years of age and hospitalized in Medellín, Colombia, with the diagnosis of radiologically confirmed CAP that had ≤ 15 days of symptoms. The mycobacterial culture of induced sputum was used for the bacteriological confirmation; the history of TB contact, a tuberculin skin test, and clinical improvement with treatment were used to identify microbiologically negative TB cases. Among 499 children with CAP, TB was diagnosed in 12 (2.4%), of which 10 had less than 8 days of a cough, 10 had alveolar opacities, 9 were younger than 5 years old, and 2 had close contact with a TB patient. Among the TB cases, 50% (6) had microbiological confirmation, 8 had viral and/or bacterial confirmation, one patient had multidrug-resistant TB, and 10/12 had non-severe pneumonia. In countries with an intermediate TB burden, Mycobacterium tuberculosis should be included in the etiological differential diagnosis (as a cause or coinfection) of both pneumonia and severe CAP in the pediatric population.

Induced sputum as an adequate clinical specimen for the etiological diagnosis of community-acquired pneumonia (CAP) in children and adolescents.

OBJECTIVES: This study aimed to evaluate the utility of induced sputum (IS) for the diagnosis of community-acquired pneumonia (CAP) in pediatric population. METHODS: This cross-sectional study included pediatric population aged between 1 month and 17 years who were hospitalized with a diagnosis of CAP in 13 hospitals in Colombia, in whom an IS sample was obtained. Gram staining, aerobic bacterial and mycobacterial culture tests, and polymerase chain reaction (PCR) for 6 atypical bacteria and 15 respiratory viruses were performed. We evaluated the quality of IS samples. RESULTS: IS samples were collected in 516 of 525 children included in this study. The median age was 32 months, 38.6% were younger than 2 years, and 40.9% were between 2 and 5 years. Two patients had transient hypoxemia during the procedure. The quality of the IS obtained was good in 48.4% and intermediate in 24.5%. Identification of a respiratory pathogen was achieved with an IS sample (with Gram staining, culture test, and PCR) in 372 of 516 children with CAP. CONCLUSION: Our study shows that IS is an adequate sample for the diagnosis of CAP in pediatric population that required hospitalization. The procedure was safe, well tolerated, and with better diagnostic yields compared with the rest of the samples obtained.

Potential distributions of pre-Columbian people in Tropical Andean landscapes.

Much has yet to be learned of the spatial patterning of pre-Columbian people across the Tropical Andes. Using compiled archaeological data and a suite of environmental variables, we generate an ensemble species distribution model (SDM) that incorporates general additive models, random forest models and Maxent models to reconstruct spatial patterns of pre-Columbian people that inhabited the Tropical Andes east of the continental divide, within the modern countries of Bolivia, Peru and Ecuador. Within this region, here referred to as the eastern Andean flank, elevation, mean annual cloud frequency, distance to rivers and precipitation of the driest quarter are the environmental variables most closely related to human occupancy. Our model indicates that 11.04% of our study area (65 368 km2) was likely occupied by pre-Columbian people. Our model shows that 30 of 351 forest inventory plots, which are used to generate ecological understanding of Andean ecosystems, were likely occupied in the pre-Columbian period. In previously occupied sites, successional trajectories may still be shaping forest dynamics, and those forests may still be recovering from the ecological legacy of pre-Columbian impacts. Our ensemble SDM links palaeo- and neo-ecology and can also be used to guide both future archaeological and ecological studies. This article is part of the theme issue 'Tropical forests in the deep human past'.

Oncological Follow-up with 2-[18F]-FDG PET/CT in Li-Fraumeni Syndrome

Li-Fraumeni syndrome is a rare disorder caused by abnormalities of the tumor-suppressor protein P53 gene. We present the case of a 26-years-old female diagnosed with bilateral ductal carcinoma. The genetic panel for breast cancer gene 1 (BRCA1) and BRCA2 mutations was negative and positive heterozygous germline tumor protein P53 gene mutations, considering Li-Fraumeni syndrome. A 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) was used for postsurgical staging to show the right lung hypermetabolic nodule. A lobectomy was accomplished, and histopathology reported pulmonary adenocarcinoma. A year later, oncological follow-up was conducted with 2-[18F]-FDG PET/CT without evidence of abnormalities.

River connectivity and climate behind the long-term evolution of tropical American floodplain lakes.

This study presents the long-term evolution of two floodplains lakes (San Juana and Barbacoas) of the Magdalena River in Colombia with varying degree of connectivity to the River and with different responses to climate events (i.e., extreme floods and droughts). Historical limnological changes were identified through a multiproxy-based reconstruction including diatoms, sedimentation, and sediment geochemistry, while historical climatic changes were derived from the application of the Standardised Precipitation-Evapotranspiration Index. The main gradients in climatic and limnological change were assessed via multivariate analysis and generalized additive models. The reconstruction of the more isolated San Juana Lake spanned the last c. 500 years. Between c. 1,620 and 1,750 CE, riverine-flooded conditions prevailed as indicated by high detrital input, reductive conditions, and dominance of planktonic diatoms. Since the early 1800s, the riverine meander became disconnected, conveying into a marsh-like environment rich in aerophil diatoms and organic matter. The current lake was then formed around the mid-1960s with a diverse lake diatom flora including benthic and planktonic diatoms, and more oxygenated waters under a gradual increase in sedimentation and nutrients. The reconstruction for Barbacoas Lake, a waterbody directly connected to the Magdalena River, spanned the last 60 years and showed alternating riverine-wetland-lake conditions in response to varying ENSO conditions. Wet periods were dominated by planktonic and benthic diatoms, while aerophil diatom species prevailed during dry periods; during the two intense ENSO periods of 1987 and 1992, the lake almost desiccated and sedimentation rates spiked. A gradual increase in sedimentation rates post-2000 suggests that other factors rather than climate are also influencing sediment deposition in the lake. We propose that hydrological connectivity to the Magdalena River is a main factor controlling lake long-term responses to human pressures, where highly connected lakes respond more acutely to ENSO events while isolated lakes are more sensitive to local land-use changes.

Cost-Effectiveness of Therapeutic Drug Monitoring-Guided Adalimumab Therapy in Rheumatic Diseases: A Prospective, Pragmatic Trial.

INTRODUCTION: To assess the clinical and cost-effectiveness of therapeutic drug monitoring (TDM) based on serum adalimumab levels compared to standard of care in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. METHODS: This was a non-inferiority, multicentric, non-randomized, pragmatic trial including adult patients diagnosed with moderate-to-severe, clinically stable rheumatic diseases treated with adalimumab. Consecutive patients were assigned 1:2 to the control (CG) or the intervention group (IG), based on the site of inclusion, and followed up for 18 months. Adalimumab serum levels were measured at each study visit and released to the IG only to modify dosing strategy. Data on disease activity, healthcare resource utilization and health-related quality of life (HRQoL) measured through the EQ-5D-5L were collected. Number of persistent and overall flares, time to first flare, days experiencing high disease activity, total direct costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: Of the 169 recruited patients, 150 were included in the analysis (52 and 98 patients in the CG and IG, respectively). The primary endpoint was not met as persistent flares were not significantly lower in the IG, although mean (SD) number of flares was numerically lower in the IG (0.67 [0.70] versus 0.90 [0.82], P = 0.073), respectively. Based on EQ-5D-5L utilities, HRQoL was significantly higher in the IG at 3 (P = 0.001) and 6 months (P = 0.035), which overall translated into 0.075 QALYs gained per patient for the IG at month 18. Overall, direct costs were significantly lower for the IG patients (€15,311.59 [4,870.04] versus €17,378.46 [6,556.51], P = 0.030), resulting in the intervention being dominant, leading to increased QALY at a lower overall cost CONCLUSION: Adalimumab dose tapering based on TDM for rheumatic patients led to an increased quality of life and QALY gain and entailed lower costs, being a more cost-effective alternative than clinically guided management.

Tocilizumab in refractory giant cell arteritis. Monotherapy versus combined therapy with conventional immunosuppressive drugs. Observational multicenter study of 134 patients.

OBJECTIVE: To compare the efficacy and safety of TCZ in monotherapy (TCZMONO) vs. combined with conventional immunosuppressive drugs (TCZCOMBO) in Giant Cell Arteritis (GCA) in a clinical practice scenario. METHODS: Multicenter study of 134 patients with refractory GCA. Patients on TCZMONO (n = 82) were compared with those on TCZCOMBO (n = 52). Drugs were methotrexate (MTX) (n = 48), azathioprine (n = 3), and leflunomide (n = 1). The main outcomes were: prolonged remission (normalization of clinical and laboratory parameters for at least 6 months) and the number of relapses. RESULTS: Patients on TCZCOMBO were younger (68.8 ± 8.0 vs 71.2 ± 9.0 years; p = 0.04), with a trend to a longer GCA duration (median [IQR],18.5 [6.25-34.0] vs. 13.0 [7.75-33.5] months; p = 0.333), higher C-reactive protein (CRP) levels (2.1[1-4.7] vs 1.2 [0.2-2.4] mg/dL; p = 0.003), and more prevalence of extra-cranial large-vessel vasculitis (LVV) (57% vs. 34.1%; p = 0.007). In both groups, rapid and sustained improvement was observed. Despite the longer GCA duration, and the higher CRP levels and prevalence of LVV in the TCZCOMBO, the improvement was similar in both groups at 12 months. Moreover, in the TCZCOMBO group, prolonged remission was significantly higher at 12-month. Relapses and serious adverse events were similar in both groups. CONCLUSION: In clinical practice, TCZ in monotherapy or combined with conventional immunosuppressive agents is effective and safe in patients with GCA. Nevertheless, the addition of immunosuppressive drugs, usually MTX, seems to allow a higher rate of prolonged remission, even in patients with a longer GCA duration, more extra-cranial LVV involvement, and higher acute-phase reactants.

Association of quantum dot nanoparticles with Pseudomonas aeruginosa biofilm.

Quantum dots (QDs) of two different surface chemistries (carboxyl [COOH] and polyethylene glycol [PEG] modified) were utilized to determine the impact of surface functionality on QD mobility and distribution in Pseudomonas aeruginosa PAO1 biofilms. Confocal laser scanning microscopy was utilized to evaluate QD association with biofilm components (proteins, cells, and polysaccharides). Quantum dots did not preferentially associate with cell surfaces compared but did colocalize with extracellular proteins in the biofilm matrix. Neither PEG nor COOH QDs were found to be internalized by individual bacterial cells. Neither QD functionality nor flow rate of QD application (0.3 mL min(-1) or 3.0 mL min(-1)) resulted in a marked difference in QD association with P. aeruginosa biofilms. However, center of density determinations indicated COOH QDs could more easily penetrate the biofilm matrix by diffusion than PEG QDs. Biofilms with PEG QDs associated had rougher polysaccharide layers and rougher cell distribution than biofilms with COOH QDs. This work suggests natural biofilms may serve as deposition locations in natural and engineered environmental systems, and biofilm structural parameters may change based on exposure to nanomaterials of varied physical characteristics.

A century of limnological evolution and interactive threats in the Panama Canal: Long-term assessments from a shallow basin.

Large tropical river dam projects are expected to accelerate over the forthcoming decades to satisfy growing demand for energy, irrigation and flood control. When tropical rivers are dammed the immediate impacts are relatively well studied, but the long-term (decades-centuries) consequences of impoundment remain poorly known. We combined historical records of water quality, river flow and climate with a multi-proxy (macrofossils, diatoms, biomarkers and trace elements) palaeoecological approach to reconstruct the limnological evolution of a shallow basin in Gatun Lake (Panama Canal, Panama) and assess the effects of multiple linked factors (river damming, forest flooding, deforestation, invasive species, pollution and hydro-climate) on the study area. Results show that a century after dam construction, species invasion, deforestation and salt intrusions have forced a gradual change in the study basin from a swamp-type environment towards a more saline lake-governed system of benthic-littoral production likely associated with the expansion of macrophyte stands. Hydrology still remains the most important long-term (decades) structural factor stimulating salinity intrusions, primary productivity, deposition of minerals, and reduction of water transparency during wet periods. During dry periods, physical-chemical conditions are in turn linked to clear water and aerobic conditions while nutrients shift to available forms for the aquatic biota in the detrital-rich reductive sediments. Our study suggests that to preserve the natural riverine system functioning of this area of the Panama Canal, management activities must address long-term ecosystem structural drivers such as river flow, runoff patterns and physical-chemical conditions.

Prevalence of soil transmitted helminths in school-aged children, Colombia, 2012-2013.

BACKGROUND: This study aims to establish the prevalence of soil-transmitted helminth (STH) intestinal infections, nutritional status, and anemia in school children aged 7 to 10 years old in the biogeographic provinces of Colombia in 2012-2013. STH prevalence in the country has not been described within the last 30 years and it is needed in order to establish policies its control in the country. METHODOLOGY: National Survey of STH in school-aged children with a multistage stratified probability sampling was conducted. The overall prevalence and intensity of STH infection, as well as for each parasite, (A. lumbricoides, T. trichiura and hookworms) were calculated for the country and for each of the nine biogeographic provinces. PRINCIPAL FINDINGS: Stool samples were collected from 6045 children in eight out of nine biogeographic provinces. The combined prevalence of STH in the country was 29.6%. T. trichiura was the most prevalent helminth (18.4%), followed by A. lumbricoides (11.3%), and hookworms (6.4%). For A. lumbricoides and hookworms, the highest prevalence values were found in the Amazonía province (58.0% and 35.7%, respectively). Regarding STH intensity, most cases showed moderate intensity (41.3%) for A. lumbricoides, and light intensity, for T. trichiura and hookworms. The national prevalence of anemia in school-aged children was 14.2%, lowest in the Nor-Andina province (3.5%), and highest in the Territorios Insulares oceánicos del Caribe province (45.1%). SIGNIFICANCE: Colombia has a moderate risk of STH infection in school-aged populations, with considerable variation in the prevalence values among the biogeographic provinces. Like any public health issue, this problem should be handled with a comprehensive approach that involves deworming programs and strategies for STH control according to the specific epidemiological and socioeconomic conditions and sanitation service coverage in each biogeographic province. The program should be further supported by intersectoral action to improve living conditions, particularly the excreta disposal, promoted at municipality levels.

Wood anatomy of two species of the genus Chrysochlamys (Clusiaceae: Clusioideae: Clusieae) from the northern Andes of Colombia.

Chrysochlamys is a genus of neotropical angiosperms distributed in wet and riparian forests from Bolivia to Mexico in altitudes from near sea-level to close to 3000 m. The wood anatomy of two species of the genus was investigated. Branches of mature stems were collected in a secondary wet forest in Colombian Northern Andes. Slides were obtained and visualized using light microscopy. Gelatinous fiber bands were found and described in C. colombiana and C. dependens. There was a higher amount of septate fibers in the latter. Average ray height and pigment deposit content in ray cells was greater in C. colombiana relative to C. dependens, but rays were commonly wider in the second one. The diversity of vessel-ray pit shapes in C. dependens is greater than in C. colombiana. In both cases rays are considered to be paedomorphic type I. Scanty to absent axial and apotracheal parenchyma was found for both species. We discuss the similarities and differences of the two species in order to establish diagnostic wood features. Also we include brief notes in comparative anatomy with other members of the Clusieaceae family, emphasizing in the incongruences found with previous reports for the genus. This is the first descriptive work in wood anatomy of C. colombiana and C. dependens.

Identification of a 3'-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association Study.

OBJECTIVE: To investigate the genetic background influencing the development of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA). METHODS: We performed a genome-wide association study (GWAS) in which, after quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analyzed in 2,989 RA patients of European origin. Data on subclinical atherosclerosis, obtained through assessment of carotid intima-media thickness (CIMT) and presence/absence of carotid plaques by carotid ultrasonography, were available for 1,355 individuals. RESULTS: A genetic variant of the RARB gene (rs116199914) was associated with CIMT values at the genome-wide level of significance (minor allele [G] ß coefficient 0.142, P = 1.86 × 10-8 ). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biologic pathway enrichment and predictive protein-protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (Gene Ontology no. 0032964; false discovery rate-adjusted P = 4.01 × 10-3 ). Furthermore, our data suggest potential influences of the previously described candidate CV risk loci NFKB1, MSRA, and ZC3HC1 (P = 8.12 × 10-4 , P = 5.94 × 10-4 , and P = 2.46 × 10-4 , respectively). CONCLUSION: The present findings strongly suggest that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA.

Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice.

OBJECTIVE: Tocilizumab (TCZ) has shown efficacy in clinical trials on giant cell arteritis (GCA). Real-world data are scarce. Our objective was to assess efficacy and safety of TCZ in unselected patients with GCA in clinical practice Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: (a) TCZ route (SC vs. IV); (b) GCA duration (≤6 vs. >6 months); (c) serious infections (with or without); (d) ≤15 vs. >15 mg/day at TCZ onset. RESULTS: 134 patients; mean age, 73.0 ± 8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0-33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4-3.2] to 0.11 [0.05-0.5] mg/dL (p < 0.0001), ESR from 33 [14.5-61] to 6 [2-12] mm/1st hour (p < 0.0001) and decrease in patients with anemia from 16.4% to 3.8% (p < 0.0001) were observed. Regardless of administration route or disease duration, clinical improvement leading to remission at 6, 12, 18, 24 months was observed in 55.5%, 70.4%, 69.2% and 90% of patients. Most relevant adverse side-effect was serious infections (10.6/100 patients-year), associated with higher doses of prednisone during the first three months of therapy. CONCLUSION: In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials.

Mercury contamination in breast milk of nursing mothers in gold mining municipalities of Antioquia, Colombia

Introduction: Breast milk is essential for human development, but it may contain toxics derived from environmental pollution, especially in mining areas. Objective: To assess the prevalence of mercury contamination in breast milk and factors associated with its transfer to nursing mothers living in municipalities with gold mining. Materials and methods: We conducted a cross-sectional study with 150 nursing mothers in four municipalities of Antioquia (El Bagre, Segovia, Remedios and Zaragoza) with a mining tradition. We surveyed these mothers to obtain information on their sociodemographic, occupational and environmental factors related to mercury, and we took breast milk, urine and hair samples. We calculated mercury level averages and the contamination prevalence per municipality. Results: Mercury average in breast milk was 2.5 (± standard deviation: 9.2) mg/L. The prevalence of mercury contamination in samples with a high level of mercury was 11.7%. Conclusion: This study shows that there is a serious problem of mercury contamination in gold mining regions of Antioquia, with significant involvement of the most vulnerable population.