RESUMEN
INTRODUCTION: Mortality in emergency departments (EDs) is not well known. This study aimed to assess the impact of the first-wave pandemic on deaths accounted in the ED of older patients with COVID and non-COVID diseases. METHODS: We used data from the Emergency Department and Elderly Needs (EDEN) cohort (pre-COVID period) and from the EDEN-COVID cohort (COVID period) that included all patients ≥65 years seen in 52 Spanish EDs from April 1 to 7, 2019, and March 30 to April 5, 2020, respectively. We recorded patient characteristics and final destination at ED. We compared older patients in the pre-COVID period, with older patients with non-COVID and with COVID-19. ED-mortality (before discharge or hospitalization) is the prior outcome and is expressed as an adjusted odds ratio (aOR) with 95% interval confidence. RESULTS: We included 23,338 older patients from the pre-COVID period (aged 78.3 [8.1] years), 6,715 patients with non-COVID conditions (aged 78.9 [8.2] years) and 3,055 with COVID (aged 78.3 [8.3] years) from the COVID period. Compared to the older patients, pre-COVID period, patients with non-COVID and with COVID-19 were more often male, referred by a doctor and by ambulance, with more comorbidity and disability, dementia, nursing home, and more risk according to qSOFA, respectively (p < 0.001). Compared to the pre-COVID period, patients with non-COVID and with COVID-19 were more often to be hospitalized from ED (24.8% vs. 44.3% vs. 79.1%) and were more often to die in ED (0.6% vs. 1.2% vs. 2.2%), respectively (p < 0.001). Compared to the pre-COVID period, aOR for age, sex, comorbidity and disability, ED mortality in elderly patients cared in ED during the COVID period was 2.31 (95% confidence interval [CI]: 1.76-3.06), and 3.75 (95% CI: 2.77-5.07) for patients with COVID. By adding the variable qSOFA to the model, such OR were 1.59 (95% CI: 1.11-2.30) and 2.16 (95% CI: 1.47-3.17), respectively. CONCLUSIONS: During the early first pandemic wave of COVID-19, more complex and life-threatening older with COVID and non-COVID diseases were seen compared to the pre-COVID period. In addition, the need for hospitalization and the ED mortality doubled in non-COVID and tripled in COVID diagnosis. This increase in ED mortality is not only explained by the complexity or severity of the elderly patients but also because of the system's overload.
Asunto(s)
COVID-19 , Pandemias , Anciano , Humanos , Masculino , COVID-19/epidemiología , Estudios Retrospectivos , Hospitalización , Servicio de Urgencia en HospitalRESUMEN
Hepatoblastoma stands as the most prevalent liver cancer in the pediatric population. Characterized by a low mutational burden, chromosomal and epigenetic alterations are key drivers of its tumorigenesis. Transcriptome analysis is a powerful tool for unraveling the molecular intricacies of hepatoblastoma, shedding light on the effects of genetic and epigenetic changes on gene expression. In this study conducted in Brazilian patients, an in-depth whole transcriptome analysis was performed on 14 primary hepatoblastomas, compared to control liver tissues. The analysis unveiled 1,492 differentially expressed genes (1,031 upregulated and 461 downregulated), including 920 protein-coding genes (62%). Upregulated biological processes were linked to cell differentiation, signaling, morphogenesis, and development, involving known hepatoblastoma-associated genes (DLK1, MEG3, HDAC2, TET1, HMGA2, DKK1, DKK4), alongside with novel findings (GYNG4, CDH3, and TNFRSF19). Downregulated processes predominantly centered around oxidation and metabolism, affecting amines, nicotinamides, and lipids, featuring novel discoveries like the repression of SYT7, TTC36, THRSP, CCND1, GCK and CAMK2B. Two genes, which displayed a concordant pattern of DNA methylation alteration in their promoter regions and dysregulation in the transcriptome, were further validated by RT-qPCR: the upregulated TNFRSF19, a key gene in the embryonic development, and the repressed THRSP, connected to lipid metabolism. Furthermore, based on protein-protein interaction analysis, we identified genes holding central positions in the network, such as HDAC2, CCND1, GCK, and CAMK2B, among others, that emerged as prime candidates warranting functional validation in future studies. Notably, a significant dysregulation of non-coding RNAs (ncRNAs), predominantly upregulated transcripts, was observed, with 42% of the top 50 highly expressed genes being ncRNAs. An integrative miRNA-mRNA analysis revealed crucial biological processes associated with metabolism, oxidation reactions of lipids and carbohydrates, and methylation-dependent chromatin silencing. In particular, four upregulated miRNAs (miR-186, miR-214, miR-377, and miR-494) played a pivotal role in the network, potentially targeting multiple protein-coding transcripts, including CCND1 and CAMK2B. In summary, our transcriptome analysis highlighted disrupted embryonic development as well as metabolic pathways, particularly those involving lipids, emphasizing the emerging role of ncRNAs as epigenetic regulators in hepatoblastomas. These findings provide insights into the complexity of the hepatoblastoma transcriptome and identify potential targets for future therapeutic interventions.
RESUMEN
We report the case of a patient with severe chronic diarrhea. He was admitted on multiple occasions for this reason, with the cause remaining undetected. After obtaining a detailed medical history and performing several studies, the patient was diagnosed with microscopic colitis and enteropathy due to Olmesartan. In the literature, both diseases appear concurrently only in a few cases. Here we highlight the importance of conducting a comprehensive medical history and maintaining high clinical suspicion to avoid delays in the diagnosis of these uncommon pathologies, as well as unnecessary tests and empirical treatments.
RESUMEN
Primary follicular lymphoma of the duodenum (FLD) is a rare variant of follicular lymphoma (FL), which represents only 1-4% of gastrointestinal non-hodgkin lymphomas (NHL). It usually appears in the second portion of the duodenum as micronodular lesions and the diagnosis is often incidental. Unlike other NHLs, the prognosis is excellent and the treatment ranges from "watch and wait" to rituximab-based immunochemotherapy regimens, depending on the symptoms and the presence of systemic involvement.
RESUMEN
Introduction: Allergic rhinoconjunctivitis (AR) is an IgE-mediated inflammation of nasal and ocular mucosa after environmental allergen exposure, mainly by house dust mites (HDM). AR affects more than one third of the population worldwide and it is associated with loss of quality of life (QoL). Aim: To analyse the improvement in the QoL in 50 patients with moderate-persistent AR due to house HDM before and after receiving 1 year of subcutaneous specific aeroallergen immunotherapy treatment (SAIT). Material and methods: A prospective observational study was performed based on clinical practice in 50 patients with moderate-severe persistent AR due to HDM and candidates to SAIT. Forty-one patients completed the study. Patients were evaluated with the ESPRINT short-version QoL questionnaire, a score of medication use and visual analogue scale (VAS) symptom score, prior to and 12 months after SAIT. Results: Forty-one patients (25 women, mean age 26.9 years). Mean ESPRINT values prior to the start SAIT was 3.06 (moderate-severe) and 1 year after starting subcutaneous SAIT the mean value dropped in all patients to 0.88 (mild). The VAS score symptom dropped from 8.26 to 3.68. 97.56% of patients used 3 or more drugs (oral antihistamine, ophthalmic/intranasal antihistamine, intranasal corticosteroid and/or oral antileukotrienes) prior to starting SAIT, and 1 year after it, 58.53% used one on-demand medication to control symptoms, oral antihistamine or nasal spray, and not daily use. Conclusions: Subcutaneous SAIT seems to be a valid treatment in our patients with moderate-persistent AR due to HDM, since it reduces the ESPRINT score, VAS score and the use of medication. An improvement in the quality of life and satisfaction was observed by the patients themselves.
RESUMEN
Intensified pediatric chemotherapy regimens to treat adolescents and young adults (AYA) patients with Philadelphia negative acute lymphoblastic leukemia (ALL) have been associated with better outcomes. The local BFM 2009-based scheme complements the risk stratification assessing the measurable residual disease (MRD) along the induction phase with increasing levels of sensitivity. The present retrospective multicenter analysis included 171 AYA (15-40 years) patients treated accordingly between 2013 and 2019. Ninety-one percent obtained morphological complete remission, 67% a negative (<0.1%) MRD at day 33 (TP1), and 78% a negative (<0.01%) MRD at day 78 (TP2). The overall survival (OS) and the event-free survival (EFS) at 2 years were 62%±4.1 and 55%±4.1, respectively. The OS and EFS were significant better for prednisone responders, who achieved <10% BM blast at day 15, a negative MRD at TP1 or at TP2, and for low-risk patients. Age ≤30 years and WBC <30×109/L, particularly among B-phenotype, were also associated with longer OS. In the multivariable analyses, TP1 MRD positive (OS HR 2.8, 95% CI 1.4-5.7, p=0.004; EFS HR 3.0, 95% CI 1.6-5.7, p=0.001) and at TP2 (OS HR 2.6, 95% CI 1.3-5.3, p=0.012; EFS HR 2.6, 95% CI 1.3-5.1, p=0.006) were independently associated with earlier events. Age >30 years was also associated with a shorter survival (HR 3.1, 95% CI 1.3-7.5, p=0.014). Therefore, those 68 patients ≤30 years with TP1/TP2 negative MRD depicted a longer OS (2 years 85%±4.8). Based on our real-world data, the pediatric-based scheme is feasible in Argentina associated with better outcomes for younger AYA patients who achieved negative MRD at day 33 and 78.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Prednisona/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inducción de Remisión , Riesgo , Estudios Retrospectivos , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/genética , Pronóstico , Supervivencia sin Enfermedad , Estudios Multicéntricos como AsuntoRESUMEN
Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.
Asunto(s)
Neoplasias , Nitrosaminas , Tabaco sin Humo , Humanos , Carcinógenos/toxicidad , Mutágenos , Neoplasias/inducido químicamente , Nitratos , Nitritos , Nitrosaminas/toxicidad , Nitrosaminas/química , Nitrosaminas/metabolismo , Tabaco sin Humo/toxicidadRESUMEN
Mechanochemical synthesis routes offer a sustainable, simple method for preparing materials. In this work, NiAl2O4 was synthesised by a mechanically activated method using a high-energy planetary mill and a calcination step. This study aims to identify the effect of different milling energies on the phases, chemical environments and surface composition of the material. In addition, it explores the thermal impact on the decomposition and structure of the materials. The materials were characterised by X-ray phosphorescence (XPS), solid-state UV-VIS (SS-UV-VIS), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), high-resolution transmission electron microscopy (HR-TEM) and thermal gravimetry differential scanning calorimetry (TGA-DSC). A co-precipitated material is used as a reference along with the ground reagents which were used as a baseline. From this in-depth analysis of the material, a good understanding of the disordered partially inverse spinel structure is provided. This study has found that with calcination temperatures of 750 °C and 900 °C a mixed NiAl2O4 : NiO phase is produced with a Ni enriched surface. The surface is found to be relatively stable with the increase from 750 °C to 900 °C.
RESUMEN
INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) is increasingly utilized in trauma care, yet its elective use during high-risk surgeries remains unreported. CASE REPORT: We report a successful instance of prophylactic ECMO support via a Veno-Venoarterial (V-VA) configuration during high-risk surgery in a patient with extensive trauma, including severe thoracic damage and a highly unstable thoracic spine fracture. V-VA ECMO prevented complications such as hemodynamic and respiratory collapse associated with chest compression during the surgical procedure, as the patient should be in a prone position. DISCUSSION: The potential of ECMO as prophylactic support in high-risk surgery amongst trauma patients underscores a novel application of this technology. Complex configurations must be evaluated to avoid associated ECMO complications. CONCLUSION: Our case highlights the potential of prophylactic ECMO hybrid modes, indicating their safe application during high-risk procedures in select trauma patients.
RESUMEN
Objective: We aimed to evaluate the efficacy of the combination of atorvastatin and N-acetyl cysteine in increasing platelet counts in patients with immune thrombocytopenia who were resistant to steroid therapy or had a relapse after treatment. Material and Methods: The patients included in this study received oral treatment of atorvastatin at a dose of 40 mg daily and N-acetyl cysteine at a dose of 400 mg every 8 h. The desired treatment duration was 12 months, but we included patients who completed at least 1 month of treatment in the analysis. The platelet counts were measured prior to the administration of the study treatment and in the first, third, sixth, and twelfth months of treatment (if available). A p value < 0.05 was considered statistically significant. Results: We included 15 patients who met our inclusion criteria. For the total treatment duration, the global response was 60% (nine patients); eight patients (53.3%) had a complete response and one patient (6.7%) had a partial response. Six patients (40%) were considered as having undergone treatment failure. Of the responder group, five patients maintained a complete response after treatment (55.5%), three patients maintained a partial response (33.3%), and one patient (11.1%) lost their response to the treatment. All of the patients in the responder group had significant increases in their platelet counts after treatment (p < 0.05). Conclusion: This study provides evidence of a possible treatment option for patients with primary immune thrombocytopenia. However, further studies are needed.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Atorvastatina/farmacología , Atorvastatina/uso terapéutico , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Background and Objectives: Central aortic pressure (CAP) can be measured through noninvasive methods, and CAP wave analysis can provide information about arterial stiffness. The objective of this study was to compare CAP in women with preeclampsia and normotensive postpartum women from an urban region in western Mexico. Materials and Methods: We recruited 78 women in immediate puerperium, including 39 with preeclampsia and 39 with normotension, who received delivery care in our hospital between September 2017 and January 2018. Pulse wave analysis was used to assess central hemodynamics as well as arterial stiffness with an oscillometric device. For this purpose, the measurement of the wave of the left radial artery was obtained with a wrist applanation tonometer and the ascending aortic pressure wave was generated using the accompanying software (V 1.1, Omron, Japan). Additionally, the systolic CAP, diastolic pressure, pulse pressure, heart rate, and rise rate adjusted for a heart rate of 75 bpm were determined. The radial pulse wave was calibrated using the diastolic and mean arterial pressures obtained from the left brachial artery. For all the statistical analyses, we considered p < 0.05 to be significant. Results: The results were as follows: a systolic CAP of 125.40 (SD 15.46) vs. 112.10 (SD 10.12) with p < 0.0001 for women with and without preeclampsia, respectively. Systolic CAP was significantly elevated in women with preeclampsia and could indicate an elevated risk of cardiovascular disease. Conclusion: CAP is an important parameter that can be measured in this group of patients and is significantly elevated in women with postpartum preeclampsia, even when the brachial blood pressure is normal.
Asunto(s)
Preeclampsia , Rigidez Vascular , Embarazo , Humanos , Femenino , Presión Sanguínea , Presión Arterial , México/epidemiología , Periodo Posparto , Rigidez Vascular/fisiología , Análisis de la Onda del PulsoRESUMEN
This study aimed to analyze the crystalline structure of dental enamel in pediatric patients with chronic kidney disease (CKD) by X-ray diffraction (XRD). The six tested samples had a mineral composition similar to hydroxyapatite, according to sheet JCPDS(Joint Committee on Powder Diffraction Standards) card #09-0432, which is normally found in dentine, and presented a lower amount of whitlockites (Ca, Mg)3(PO4)2. Pattern phases showed an increase in organic matter and a decrease in inorganic matter. At an interval of approximately 2θ = 15.7° to 27.2°, amorphous organic matter corresponding to hydrated glucose was found. The hydroxyapatite patterns in this study differed from that of dental enamel found on permanent teeth.
Asunto(s)
Esmalte Dental , Insuficiencia Renal Crónica , Humanos , Niño , Difracción de Rayos X , Durapatita/análisis , Durapatita/química , Dentición Permanente , Insuficiencia Renal Crónica/complicacionesRESUMEN
BACKGROUND: Fragile X syndrome, the major cause of inherited intellectual disability among men, is due to deficiency of the synaptic functional regulator FMR1 protein (FMRP), encoded by the FMRP translational regulator 1 (FMR1) gene. FMR1 alternative splicing produces distinct transcripts that may consequently impact FMRP functional roles. In transcripts without exon 14 the translational reading frame is shifted. For deepening current knowledge of the differential expression of Fmr1 exon 14 along the rat nervous system development, we conducted a descriptive study employing quantitative RT-PCR and BLAST of RNA-Seq datasets. RESULTS: We observed in the rat forebrain progressive decline of total Fmr1 mRNA from E11 to P112 albeit an elevation on P3; and exon-14 skipping in E17-E20 with downregulation of the resulting mRNA. We tested if the reduced detection of messages without exon 14 could be explained by nonsense-mediated mRNA decay (NMD) vulnerability, but knocking down UPF1, a major component of this pathway, did not increase their quantities. Conversely, it significantly decreased FMR1 mRNA having exon 13 joined with either exon 14 or exon 15 site A. CONCLUSIONS: The forebrain in the third embryonic week of the rat development is a period with significant skipping of Fmr1 exon 14. This alternative splicing event chronologically precedes a reduction of total Fmr1 mRNA, suggesting that it may be part of combinatorial mechanisms downregulating the gene's expression in the late embryonic period. The decay of FMR1 mRNA without exon 14 should be mediated by a pathway different from NMD. Finally, we provide evidence of FMR1 mRNA stabilization by UPF1, likely depending on FMRP.
Asunto(s)
Empalme Alternativo , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Prosencéfalo , Empalme Alternativo/genética , Animales , Desarrollo Embrionario , Exones/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Prosencéfalo/embriología , ARN Helicasas/genética , ARN Helicasas/metabolismo , ARN Mensajero/metabolismo , Ratas , Transactivadores/genética , Transactivadores/metabolismoRESUMEN
BACKGROUND AND AIMS: Hepatoblastoma (HBL) is a devastating pediatric liver cancer with multiple treatment options, but it ultimately requires surgery for a cure. The most malicious form of HBL is a chemo-resistant aggressive tumor that is characterized by rapid growth, metastases, and poor response to treatment. Very little is known of the mechanisms of aggressive HBL, and recent focuses have been on developing alternative treatment strategies. In this study, we examined the role of human chromosomal regions, called aggressive liver cancer domains (ALCDs), in liver cancer and evaluated the mechanisms that activate ALCDs in aggressive HBL. RESULTS: We found that ALCDs are critical regions of the human genome that are located on all human chromosomes, preferentially in intronic regions of the oncogenes and other cancer-associated genes. In aggressive HBL and in patients with Hepatocellular (HCC), JNK1/2 phosphorylates p53 at Ser6, which leads to the ph-S6-p53 interacting with and delivering the poly(adenosine diphosphate ribose) polymerase 1 (PARP1)/Ku70 complexes on the oncogenes containing ALCDs. The ph-S6-p53-PARP1 complexes open chromatin around ALCDs and activate multiple oncogenic pathways. We found that the inhibition of PARP1 in patient-derived xenografts (PDXs) from aggressive HBL by the Food and Drug Administration (FDA)-approved inhibitor olaparib (Ola) significantly inhibits tumor growth. Additionally, this is associated with the reduction of the ph-S6-p53/PARP1 complexes and subsequent inhibition of ALCD-dependent oncogenes. Studies in cultured cancer cells confirmed that the Ola-mediated inhibition of the ph-S6-p53-PARP1-ALCD axis inhibits proliferation of cancer cells. CONCLUSIONS: In this study, we showed that aggressive HBL is moderated by ALCDs, which are activated by the ph-S6-p53/PARP1 pathway. By using the PARP1 inhibitor Ola, we suppressed tumor growth in HBL-PDX models, which demonstrated its utility in future clinical models.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Hepatoblastoma , Neoplasias Hepáticas , Ftalazinas/farmacología , Piperazinas/farmacología , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Animales , Células Cultivadas , Hepatoblastoma/tratamiento farmacológico , Hepatoblastoma/metabolismo , Humanos , Autoantígeno Ku/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Ratones , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Proteínas Quinasas S6 Ribosómicas/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The development of new anticancer compounds is one of the challenges of bioinorganic and medicinal chemistry. Naringenin and its metal complexes have been recognized as promising inhibitors of cell proliferation, having enormous potential to act as an antioxidant and antitumorigenic agent. Lung cancer is the second most commonly diagnosed type of cancer. Therefore, this study is devoted to investigate the effects of Cu(II), naringenin (Nar), binary Cu(II)-naringenin complex (CuNar), and the Cu(II)-naringenin containing bathophenanthroline as an auxiliary ligand (CuNarBatho) on adenocarcinoma human alveolar basal epithelial cells (A549 cells) that are used as models for the study of drug therapies against lung cancer. The ternary complex shows selectivity being high cytotoxic against malignant cells. The cell death generated by CuNarBatho involves ROS production, loss of mitochondrial membrane potential, and depletion of GSH level and GSH/GSSG ratio. The structure-relationship activity was assessed by comparison with the reported Cu(II)-naringenin-phenanthroline complex. The CuNarBatho complex was synthesized and characterized by elemental analysis, molar conductivity, mass spectrometry, thermogravimetric measurements and UV-VIS, FT-IR, EPR, Raman and 1H-NMR spectroscopies. In addition, the binding to bovine serum albumin (BSA) was studied at the physiological conditions (pH = 7.4) by fluorescence spectroscopy.
Asunto(s)
Antineoplásicos , Complejos de Coordinación , Neoplasias Pulmonares , Antineoplásicos/química , Antioxidantes/farmacología , Cationes , Complejos de Coordinación/química , Cobre/química , Flavanonas , Disulfuro de Glutatión , Humanos , Ligandos , Neoplasias Pulmonares/tratamiento farmacológico , Fenantrolinas/farmacología , Especies Reactivas de Oxígeno , Albúmina Sérica Bovina/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
OBJECTIVE: To assess the efficacy and safety of abatacept (ABA) in monotherapy (ABAMONO) vs combined ABA [ABA plus MTX (ABAMTX) or ABA plus non-MTX conventional synthetic DMARDs (csDMARDs) (ABANON-MTX)] in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was a restrospective multicentre study of RA-ILD Caucasian patients treated with ABA. We analysed in the three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcome variables: (i) dyspnoea; (ii) forced vital capacity (FVC) and diffusion capacity of the lung for the carbon monoxide (DLCO); (iii) chest high-resolution CT (HRCT); (iv) DAS28-ESR; (v) CS-sparing effect; and (vi) ABA retention and side-effects. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used to assess the differences between the three groups. RESULTS: We studied 263 RA-ILD patients (mean ± s.d. age 64.6 ± 10 years) [ABAMONO (n = 111), ABAMTX (n = 46) and ABANON-MTX (n = 106)]. At baseline, ABAMONO patients were older (67 ± 10 years) and took higher prednisone dose [10 (interquartile range 5-15) mg/day]. At that time, there were no statistically significant differences in sex, seropositivity, ILD patterns, FVC and DLCO, or disease duration. Following treatment, in all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnoea and chest HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in CS-sparing effect in the group on combined ABA (ABAMTX or ABANON-MTX). However, in the multivariable analysis, there were no differences in any outcome variables between the three groups. CONCLUSION: In Caucasian individuals with RA-ILD, ABA in monotherapy or combined with MTX or with other conventional-DMARDs seems to be equally effective and safe. However, a CS-sparing effect is only observed with combined ABA.
Asunto(s)
Abatacept/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Metotrexato/uso terapéutico , Anciano , Antirreumáticos/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The Mexican Caribbean is a vital nesting destination for loggerhead (Caretta caretta) and green (Chelonia mydas) sea turtles. Since 2015, massive periodical landings of pelagic Sargassum species (sargasso) have affected coastal ecosystems. Dense accumulations of sargasso on the shoreline may preclude access to sea turtles' preferred nesting areas and compromise hatching. In this study, we assess whether the number of nests and hatches of loggerhead and green sea turtles has been affected by the massive influx of sargasso. We compare data from before (2010-2014) and after (2015-2019) the first sargasso event, obtained from the same 17 marine turtle camps, which collectively account for 72.3 km of sampling distance over a 210 km section of shoreline. No differences in preferences on nesting beaches were recorded between periods for the two species. The mean number of nests per kilometer of coastline remained without statistically significant changes between periods in 16 camps and increased significantly in one camp for each species. Overall, the mean annual number of nests per kilometer of beach was 37% higher in the period after massive landings of sargasso began. The mean number of hatchlings increased significantly in one camp for C. mydas and in three for C. caretta. Periodical massive landings of sargasso from 2015 to 2019 do not appear to have compromised nesting and hatching of loggerhead and green sea turtles along the Mexican Caribbean coast.
Asunto(s)
Sargassum , Tortugas , Animales , Región del Caribe , Ecosistema , Comportamiento de NidificaciónRESUMEN
The National Quality Control Program in Mycology (PNCCM) of Argentina was established in 1996 to improve the quality of the mycological diagnosis, to help establish and to set up standardized procedures and continuous training of laboratory staff. The aim of this study was to assess the effectiveness of the PNCCM in the 1996-2018 period. Data from the National Mycology Laboratory Network (NMLN) and PNCCM database was used to estimate the increase in the number of controlled laboratories and jurisdictions, the percentage of participation, the improvement in the quality of results and the adherence to the program. Satisfaction surveys were performed to assess user satisfaction. The number of controlled laboratories increased from 29 to 146; participation increased from 49% to 93% and general adherence was 72% in the evaluated period (1996-2018). Improvement in the quality of the results was 15% for low complexity samples; 7% for intermediate complexity samples and 14% for the identification of high complexity strains. Up to 84% of the users consider the PNCCM to be "very good" and 16% "satisfactory". These results show the importance of the PNCCM, which is widely accepted by mycological diagnostic laboratories from Argentina.
Asunto(s)
Laboratorios , Micología , Argentina , Pruebas Diagnósticas de Rutina , Humanos , Control de CalidadRESUMEN
Single-walled carbon nanotubes (SWCNTs) can be doped with potassium, similar to graphite, leading to intercalation compounds. These binary systems exhibit a clear metallic character. However, the entire picture of how electron doping (e-doping) modifies the SWCNTs' vibrational spectra as a function of their diameter, chirality, and metallicity is still elusive. Herein, we present a detailed study of the intercalation and solid state reduction of metallic and semiconducting enriched HiPco SWCNTs. We performed a combined experimental and theoretical study of the evolution of their Raman response with potassium exposure, focusing specifically on their radial breathing mode (RBM). We found the charge donated from the potassium atoms occupies antibonding π orbitals of the SWCNTs, weakening their C-C bonds, and reducing the RBM frequency. This RBM downshift with increasing doping level is quasi-linear with a steplike behavior when the Fermi level crosses a van Hove singularity for semiconducting species. Moreover, this weakening of the C-C bonds is greater with decreasing curvature, or increasing diameter. Overall, this suggests the RBM downshift with e-doping is proportional to both the SWCNT's integrated density of states (DOS) ϱ(ε) and diameter d. We have provided a precise and complete description of the complex electron doping mechanism in SWCNTs up to a charge density of -18 me/C, far beyond that achievable by standard gate voltage studies, not being the highest doping possible, but high enough to track the effects of doping in SWCNTs based on their excitation energy, diameter, band gap energy, chiral angle, and metallicity. This work is highly relevant to tuning the electronic properties of SWCNTs for applications in nanoelectronics, plasmonics, and thermoelectricity.
RESUMEN
There have been several efforts to predict mortality after autologous stem cell transplantation (ASCT), such as the hematopoietic cell transplant-comorbidity index (HCT-CI), described for allogeneic stem cell transplantation and validated for ASCT, but there is no composite score in the setting of ASCT combining comorbidities with other clinical characteristics. Our aim is to describe a comprehensive score combining comorbidities with other clinical factors and to analyze the impact of this score on nonrelapse mortality (NRM), overall survival (OS), and early morbidity endpoints (mechanical ventilation, shock or dialysis) after ASCT. For the training cohort, we retrospectively reviewed data of 2068 adult patients who received an ASCT in Argentina (October 2002 to June 2017) for multiple myeloma or lymphoma. For the validation cohort, we analyzed 2168 ASCTs performed in the Medical College of Wisconsin and Spanish stem cell transplant group (Grupo Español de Trasplante Hematopoyético (GETH)) (January 2012 to December 2018). We first performed a multivariate analysis for NRM in order to select and assign weight to the risk factors included in the score (male patients, aged 55 to 64 and ≥65 years, HCT-CI ≥3, Hodgkin lymphoma and non-Hodgkin lymphoma). The hazard ratio for NRM increased proportionally with the score. Patients were grouped as low risk (LR) with a score of 0 to 1 (686, 33%), intermediate risk (IR) with a score of 2 to 3 (1109, 53%), high risk (HR) with a score of 4 (198, 10%), and very high risk (VHR) with a score of ≥5 (75, 4%). The score was associated with a progressive increase in all the early morbidity endpoints. Moreover, the score was significantly associated with early NRM (day 100: 1.5% versus 2.4% versus 7.6% versus 17.6%) as well as long term (1 to 3 years; 1.8% to 2.3% versus 3.8% to 4.9% versus 11.7% to 14.5% versus 25.0% to 27.4%, respectively; P< .0001) and OS (1 to 5 years; 94% to 73% versus 89% to 75% versus 76% to 47% versus 65% to 52% respectively; P < .0001). The score was validated in an independent cohort (N = 2168) and was significantly associated with early and late events. In conclusion, we developed and validated a novel score predicting NRM and OS in 2 large cohorts of more than 2000 autologous transplant patients. This tool can be useful for tailoring conditioning regimens or defining risk for transplant program decision making.