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Background: Hypofractionated radiotherapy in the treatment of prostate cancer has been widely studied. However, in the postoperative setting it has been less explored. The objective of this prospective study is to evaluate the safety and efficacy of hypofractionated radiotherapy in postoperative prostate cancer. Materials and methods: A prospective study was designed to include patients with prostate cancer with an indication of postoperative radiotherapy as adjuvant or salvage. A hypofractionated radiotherapy scheme of 51 Gy in 17 fractions was performed with the possibility of treating the pelvis at a dose of 36 Gy in 12 fractions sequentially. Safety was evaluated based on acute and late toxicity [according to the Radiation Therapy Oncology Group (RTOG) scale and Common Terminology Criteria Adverse Events (CTCAE) v4.03], International Prognostic Scoring System (IPSS) over time, and quality of life. Results: From August 2020 to June 2022, 31 patients completed treatment and were included in this report. 35.5% of patients received elective treatment of the pelvic nodal areas. Most patients reported minimal or low acute toxicity, with an acute gastrointestinal (GI) and genitourinary (GU) grade 3 or greater toxicity of 3.2% and 0%, respectively. The evolution in time of the IPSS remained without significant differences (p = 0.42). With the exception of a significant improvement in the domains of hormonal and sexual symptoms of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire, the rest of the domains [EPIC, European Organization for Research and Treatment of Cancer (EORTC) Core quality of life questionnaire (C-30) and Prostate Cancer module (PR-25)] were maintained without significant differences over time. With a follow-up of 15.4 months, late GI and GU grade 2 toxicity was reported greater than 0% and 9.6%, respectively. Conclusions: Hypofractionated radiotherapy in postoperative prostate cancer appears to be safe with low reports of relevant acute or late toxicity. Further follow-up is required to confirm these results. Trial registration: The protocol was approved by the accredited Medical Ethical Committee of Pontificia Universidad Católica de Chile. All participants accepted and wrote informed consent.
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Since the COVID-19 pandemic started, there has been much speculation about how COVID-19 and antimicrobial resistance may be interconnected. In this study, untreated wastewater was sampled from Hospital A designated to treat COVID-19 patients during the first wave of the COVID-19 pandemic alongside Hospital B that did not receive any COVID-19 patients. Metagenomics was used to determine the relative abundance and mobile potential of antibiotic resistant genes (ARGs), prior to determining the correlation of ARGs with time/incidence of COVID-19. Our findings showed that ARGs resistant to macrolides, sulfonamides, and tetracyclines were positively correlated with time in Hospital A but not in Hospital B. Likewise, minor extended spectrum beta-lactamases (ESBLs) and carbapenemases of classes B and D were positively correlated with time, suggesting the selection of rare and/or carbapenem-resistant genes in Hospital A. Non-carbapenemase blaVEB also positively correlated with both time and intI1 and was copresent with other ARGs including carbapenem-resistant genes in 6 metagenome-assembled genomes (MAGs). This study highlighted concerns related to the dissemination of antimicrobial resistance (AMR) during the COVID-19 pandemic that may arise from antibiotic use and untreated hospital wastewater.
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Antibacterianos , COVID-19 , Humanos , Antibacterianos/farmacología , Aguas Residuales , Pandemias , Genes Bacterianos , Farmacorresistencia Bacteriana/genética , HospitalesRESUMEN
There is evidence of learning loss due to the COVID-19 pandemic, but there is no related information for Mexico. The objective of the study is to estimate learning loss in reading and numeracy in Mexico. We compared the results of two household surveys conducted in 2019 and 2021. We interviewed 3161 children between 10 and 15 years. We estimated a learning loss according with SES in a range from 0.34-0.45 SD in reading and 0.62-0.82 SD in mathematics by COVID-19 pandemic, and an increase in learning poverty in a range of 25.7%-15.4% in reading and 29.8%-28.8% in numeracy. Gaps in fundamental learning by gender and SES increased. There is an urgent need develop a clear strategy to perform personalized diagnoses and implement remedial courses to address learning loss.
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There is increasing interest in wastewater-based epidemiology (WBE) of SARS-CoV-2 RNA to serve as an early warning system for a community. Despite successful detection of SARS-CoV-2 RNA in wastewaters sampled from multiple locations, there is still no clear idea on the minimal number of cases in a community that are associated with a positive detection of the virus in wastewater. To address this knowledge gap, we sampled wastewaters from a septic tank (n = 57) and biological activated sludge tank (n = 52) located on-site of a hospital. The hospital is providing treatment for SARS-CoV-2 infected patients, with the number of hospitalized patients per day known. It was observed that depending on which nucleocapsid gene is targeted by means of RT-qPCR, a range of 253-409 positive cases out of 10,000 persons are required prior to detecting RNA SARS-CoV-2 in wastewater. There was a weak correlation between N1 and N2 gene abundances in wastewater with the number of hospitalized cases. This correlation was however not observed for N3 gene. The frequency of detecting N1 and N2 gene in wastewater was also higher than that for N3 gene. Furthermore, nucleocapsid genes of SARS-CoV-2 were detected at lower frequency in the partially treated wastewater than in the septic tank. In particular, N1 gene abundance was associated with water quality parameters such as total organic carbon and pH. In instances of positive detection, the average abundance of N1 and N3 genes in the activated sludge tank were reduced by 50 and 70% of the levels detected in septic tank, suggesting degradation of the SARS-CoV-2 gene fragments already occurring in the early stages of the wastewater treatment process.
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COVID-19 , SARS-CoV-2 , Brotes de Enfermedades , Humanos , ARN Viral/genética , Aguas ResidualesRESUMEN
Many biological contaminants are disseminated through water, and their occurrence has potential detrimental impacts on public and environmental health. Conventional monitoring tools rely on cultivation and are not robust in addressing modern water quality concerns. This review proposes metagenomics as a means to provide a rapid, nontargeted assessment of biological contaminants in water. When further coupled with appropriate methods (e.g., quantitative PCR and flow cytometry) and bioinformatic tools, metagenomics can provide information concerning both the abundance and diversity of biological contaminants in reclaimed waters. Further correlation between the metagenomic-derived data of selected contaminants and the measurable parameters of water quality can also aid in devising strategies to alleviate undesirable water quality. Here, we review metagenomic approaches (i.e., both sequencing platforms and bioinformatic tools) and studies that demonstrated their use for reclaimed-water quality monitoring. We also provide recommendations on areas of improvement that will allow metagenomics to significantly impact how the water industry performs reclaimed-water quality monitoring in the future.
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Monitoreo del Ambiente/métodos , Metagenoma , Metagenómica/métodos , Eliminación de Residuos Líquidos , Calidad del AguaRESUMEN
Extracellular DNA (eDNA) cannot be effectively removed by most of the existing wastewater treatment technologies and can contribute to the gain of new functional traits when transformed into competent bacteria present in downstream environments. This study evaluates the contributions of solar and UV-C254nm irradiation to the transformation of eDNA in Acinetobacter baylyi ADP1. Solar irradiation was evaluated because it is a natural environmental stressor to which eDNA would be exposed during wastewater reuse. UV-C254nm was evaluated as an alternative to a chlorine-based disinfection strategy. Our findings showed that solar disinfection increased the natural transformation frequency by up to 2.0-fold after irradiance at 153 mJ/cm2. This was largely mediated by reactive oxygen species generation, which was correlated with an upregulation of both DNA repair (recA and ddrR) and competence (comA and pilX) genes. In contrast, even though UV-C254nm exposure was accompanied by the upregulation of DNA repair (recA, ddrR, and uvrB) genes and, hence, possibly higher integration rates of eDNA, we observed a concentration-dependent decrease in transformation rates. This decrease in transformation was likely due to the UV dimerization of eDNA, which resulted in the integration of damaged genes that cannot be transcribed into any functional gene products. These results imply that even though sunlight stimulates eDNA uptake and integration in the natural environment, UV disinfection implemented at a treatment plant can potentially minimize subsequent detrimental effects by damaging the extracellular genetic material and ensuring that there is no substantial expression of these transformed genes.
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Acinetobacter , ADN , Daño del ADN , Desinfección , Luz Solar , Rayos UltravioletaRESUMEN
The process of natural transformation allows for the stable uptake, integration, and functional expression of extracellular DNA. This mechanism of horizontal gene transfer has been widely linked to the acquisition of antibiotic resistance and virulence factors. Here, we demonstrate that bromoacetic acid (BAA)-a regulated drinking water disinfection byproduct (DBP)-can stimulate natural transformation rates in the model organism Acinetobacter baylyi ADP1. We demonstrate that transformation stimulation in response to BAA is concentration-dependent and is linked to the ability of this compound to generate DNA damage via oxidative stress. In presence of BAA, transcription of recA was upregulated 20-40% compared to the nontreated controls, indicating that this component of the DNA damage response could be associated with the increase in transformation. Other genes associated with DNA translocation across the cytoplasmic membrane (i.e., pilX, comA) did not exhibit increased transcription in the presence of BAA, indicating that the enhancement of transformation is not associated with increased translocation rates of environmental DNA. Overall, these results lead us to speculate that elevated recA transcription levels could lead to increased integration rates of foreign DNA within the recipient cell during DNA repair. Lastly, we show that an artificial DBP cocktail simulating the environmental concentrations of five water DBP classes stimulates natural transformation by almost 2-fold. The results of this study suggest that mutagens like DBPs may play an important role in enhancing the fixation rates of extracellular DNA in the environmental metagenome.
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Acinetobacter , ADN , Daño del ADN , Desinfección , AguaRESUMEN
Bacteriophages active against a New Delhi metallo beta lactamase (NDM)-positive E. coli PI-7 were isolated from municipal wastewater and tested for their lytic effect against the bacterial host. Bacteriophages were highly specific to E. coli PI-7 when tested for host-range. After determining host-specificity, bacteriophages were tested for their ability to sensitize E. coli PI-7 to solar irradiation. Solar irradiation coupled with bacteriophages successfully reduced the length of the lag-phase for E. coli PI-7 from 4 h to 2 h in buffer solution. The reduction of lag-phase length was also observed in filtered wastewater effluent and chlorinated effluent. Previously, we found through gene expression analysis that cell wall, oxidative stress, and DNA repair functions played a large role in protecting E. coli PI-7 against solar damage. Here, gene expression analysis of bacteriophage-supplemented solar-irradiated E. coli PI-7 revealed downregulation of cell wall functions. Downregulation of functions implicated in scavenging and detoxifying reactive oxygen species, as well as DNA repair genes, was also observed in bacteriophage-supplemented solar-irradiated E. coli PI-7. Moreover, solar irradiation activates recA, which can induce lytic activity of bacteriophages. Overall, the combined treatment led to gene responses that appeared to make E. coli PI-7 more susceptible to solar disinfection and bacteriophage infection. Our findings suggest that bacteriophages show good potential to be used as a biocontrol tool to complement solar irradiation in mitigating the persistence of antibiotic-resistant bacteria in reuse waters.
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Bacteriófagos , Infecciones por Escherichia coli , Desinfección , Escherichia coli , Humanos , beta-LactamasasRESUMEN
The presence of emerging biological pollutants in treated wastewater effluents has gained attention due to increased interest in water reuse. To evaluate the effectiveness of the removal of such contaminants by the conventional wastewater treatment process, the fate and decay kinetics of NDM-1-positive Escherichia coli strain PI7 and its plasmid-encoded antibiotic resistance genes (ARGs) were assessed in microcosms of anaerobic and aerobic sludge. Results showed that E. coli PI7 decayed at a significantly lower rate under anaerobic conditions. Approximate half-lives were 32.4 ± 1.4 h and 5.9 ± 0.9 h in the anaerobic and aerobic microcosms, respectively. In the aerobic microcosms, after 72 h of operation, E. coli PI7 remained detectable, but no further decay was observed. Instead, 1 in every 10,000 E. coli cells was identified to be recalcitrant to decay and persist indefinitely in the sludge. ARGs associated with the E. coli PI7 strain were detected to have transferred to other native microorganisms in the sludge or were released to the liquid fraction upon host decay. Extracellular DNA quickly degraded in the liquid fraction of the aerobic sludge. In contrast, no DNA decay was detected in the anaerobic sludge water matrix throughout the 24-h sampling period. This study suggests an increased likelihood of environmental dispersion of ARGs associated with anaerobically treated wastewater effluents and highlights the potential importance of persister cells in the dissemination of E. coli in the environment during reuse events of treated wastewater.IMPORTANCE This study examines the decay kinetics of a pathogenic and antibiotic resistant strain of Escherichia coli in microcosms simulating biological treatment units of aerobic and anaerobic sludge. The results of this study point at a significantly prolonged persistence of the E. coli and the associated antibiotic resistance gene in the anaerobic sludge. However, horizontal transfer of the plasmid encoding the antibiotic resistance gene was detected in the aerobic sludge by a cultivation method. A subpopulation of persister E. coli cells was also detected in the aerobic sludge. The findings of this study suggest potential areas of concern arising from pathogenic and antibiotic-resistant E. coli during both anaerobic and aerobic sludge treatment processes.
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Proteínas de Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Aguas del Alcantarillado/microbiología , beta-Lactamasas/metabolismo , Aerobiosis , Anaerobiosis , Escherichia coli/clasificación , Escherichia coli/enzimología , Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Plásmidos/genética , Plásmidos/metabolismo , Aguas del Alcantarillado/química , Aguas Residuales/microbiología , beta-Lactamasas/genéticaRESUMEN
This study examined the decay kinetics and molecular responses of two Escherichia coli strains upon solar irradiation. The first is E. coli PI-7, a virulent and antibiotic-resistant strain that was isolated from wastewater and carries the emerging NDM-1 antibiotic resistance gene. The other strain, E. coli DSM1103, displayed lower virulence and antibiotic resistance than E. coli PI-7. In a buffer solution, E. coli PI-7 displayed a longer lag phase prior to decay and a longer half-life compared with E. coli DSM1103 (6.64 ± 0.63 h and 2.85 ± 0.46 min vs 1.33 ± 0.52 h and 2.04 ± 0.36 min). In wastewater, both E. coli strains decayed slower than they did in buffer. Although solar irradiation remained effective in reducing the numbers of both strains by more than 5-log10 in <24 h, comparative genomics and transcriptomics revealed differences in the genomes and overall regulation of genes between the two E. coli strains. A wider arsenal of genes related to oxidative stress, cellular repair and protective mechanisms were upregulated in E. coli PI-7. Subpopulations of E. coli PI-7 expressed genes related to dormancy and persister cell formation during the late decay phase, which may have accounted for its prolonged persistence. Upon prolonged solar irradiation, both E. coli strains displayed upregulation of genes related to horizontal gene transfer and antibiotic resistance. Virulence functions unique to E. coli PI-7 were also upregulated. Our findings collectively indicated that, whereas solar irradiation is able to reduce total cell numbers, viable E. coli remained and expressed genes that enable survival despite solar treatment. There remains a need for heightened levels of concern regarding risks arising from the dissemination of E. coli that may remain viable in wastewater after solar irradiation.
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Escherichia coli/aislamiento & purificación , Aguas Residuales , Infecciones por Escherichia coli , Semivida , Energía SolarRESUMEN
The emergence of resistance to last-resort antibiotics is a public health concern of global scale. Besides direct person-to-person propagation, environmental pathways might contribute to the dissemination of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Here, we describe the incidence of blaNDM-1, a gene conferring resistance to carbapenems, in the wastewater of the city of Jeddah, Saudi Arabia, over a 1-year period. blaNDM-1 was detected at concentrations ranging from 10(4) to 10(5) copies/m(3) of untreated wastewater during the entire monitoring period. These results indicate the ubiquity and high incidence of blaNDM-1 in the local wastewater. To track the bacteria carrying blaNDM-1, we isolated Escherichia coli PI7, a strain of sequence type 101 (ST101), from wastewater around the Hajj event in October 2013. Genome sequencing of this strain revealed an extensive repertoire of ARGs as well as virulence and invasive traits. These traits were further confirmed by antibiotic resistance profiling and in vitro cell internalization in HeLa cell cultures. Given that this strain remains viable even after a certain duration in the sewerage, and that Jeddah lacks a robust sanitary infrastructure to fully capture all generated sewage, the presence of this bacterium in the untreated wastewater represents a potential hazard to the local public health. To the best of our knowledge, this is the first report of a blaNDM-1-positive E. coli strain isolated from a nonnosocomial environment in Saudi Arabia and may set a priority concern for the need to establish improved surveillance for carbapenem-resistant E. coli in the country and nearby regions.
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Escherichia coli/aislamiento & purificación , Genoma Bacteriano , Plásmidos/química , Resistencia betalactámica/genética , beta-Lactamasas/genética , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Escherichia coli/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Plásmidos/metabolismo , Arabia Saudita , Aguas Residuales/microbiología , beta-Lactamasas/aislamiento & purificaciónRESUMEN
Long-term (>2.5 years) surveillance of SARS-CoV-2 RNA concentrations in wastewater was conducted within an enclosed university compound. This study aims to demonstrate how coupling wastewater-based epidemiology (WBE) with meta-data can identify which factors contribute toward the dissemination of SARS-CoV-2 within a local community. Throughout the pandemic, the temporal dynamics of SARS-CoV-2 RNA concentrations were tracked by quantitative polymerase chain reaction and analyzed in the context of the number of positive swab cases, the extent of human movement, and intervention measures. Our findings suggest that during the early phase of the pandemic, when strict lockdown was imposed, the viral titer load in the wastewater remained below detection limits, with <4 positive swab cases reported over a 14-day period in the compound. After the lockdown was lifted and global travel gradually resumed, SARS-CoV-2 RNA was first detected in the wastewater on 12 August 2020 and increased in frequency thereafter, despite high vaccination rates and mandatory face-covering requirements in the community. Accompanied by a combination of the Omicron surge and significant global travel by community members, SARS-CoV-2 RNA was detected in most of the weekly wastewater samples collected in late December 2021 and January 2022. With the cease of mandatory face covering, SARS-CoV-2 was detected in at least two of the four weekly wastewater samples collected from May through August 2022. Retrospective Nanopore sequencing revealed the presence of the Omicron variant in the wastewater with a multitude of amino acid mutations, from which we could infer the likely geographical origins through bioinformatic analysis. This study demonstrated that long-term tracking of the temporal dynamics and sequencing of variants in wastewater would aid in identifying which factors contribute the most to SARS-CoV-2 dissemination within the local community, facilitating an appropriate public health response to control future outbreaks as we now live with endemic SARS-CoV-2.
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COVID-19 , Humanos , COVID-19/epidemiología , Control de Enfermedades Transmisibles , ARN Viral , Estudios Retrospectivos , SARS-CoV-2 , Aguas Residuales , Monitoreo Epidemiológico Basado en Aguas ResidualesRESUMEN
Silver carp (Hypophthalmichthys molitrixi) was processed by sous-vide method at different temperatures (60, 65, 70, and 75°C). Then, the microbiological quality of the processed samples was monitored during cold storage (4°C) for 21 days. The target microorganisms were Enterobacteriaceae, Lactic Acid bacteria (LAB), Pseudomonas, Psychrotrophs, and total viable count (TVC). In samples processed at 75°C, the presence of Enterobacteriaceae, Pseudomonas and Psychrotrophs were not detectable up to 15 days of storage and lactic acid bacteria were not detectable even at the end of the storage period. A radial basis function neural network (RBFNN) model was established to predict the changes in the microbial content of silver carp. In this step, the relationship between processing temperature and storage duration on microbial growth was modeled by ANNs (artificial neural networks). The optimal ANN topology for modeling Enterobacteriaceae, Pseudomonas, and Psychrotroph contained 9 neurons in the hidden layer, but it contained 15 and 14 neurons for TVC and LAB, respectively. By experimenting with the temperature of -80°C, it was revealed that the obtained ANN model has a high potential for prediction.
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Carpas , Animales , Temperatura , Enterobacteriaceae , FríoRESUMEN
BACKGROUND: The aneurysmal bone cyst is a benign neoplasm that tends to form the appearance of a mass with a bony septum that forms cavities with blood inside. It is estimated to represent 1% of bone tumours and has an incidence of 0.14 per 100,000 people worldwide. Current publications have not shown a multidisciplinary approach that can benefit patients, mainly in the functionality and quality of the management approach. OBJECTIVE: Describe the multidisciplinary approach and the benefits of quality of life and functionality in this diagnosis. CASE: A paediatric patient was diagnosed with an aneurysmal bone cyst located in the cervical spine, which initially manifested with muscle pain, enlargement of the posterior cervical region, and difficulty in performing arcs of movement. He was treated with multidisciplinary management with surgery, embolisation, radiation, and bisphosphonate support. CONCLUSION: The purpose of approaching multidisciplinary management helped to improve the accompanying symptoms that prevented our patient from having an active and quality life. However, more successful cases have not been reported to establish the best therapeutic protocol.
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BACKGROUND: Radiomics refers to the acquisition of traces of quantitative features that are usually non-perceptible to human vision and are obtained from different imaging techniques and subsequently transformed into high-dimensional data. Diffuse midline gliomas (DMG) represent approximately 20% of pediatric CNS tumors, with a median survival of less than one year after diagnosis. We aimed to identify which radiomics can discriminate DMG tumor regions (viable tumor and peritumoral edema) from equivalent midline normal tissue (EMNT) in patients with the positive H3.F3K27M mutation, which is associated with a worse prognosis. PATIENTS AND METHODS: This was a retrospective study. From a database of 126 DMG patients (children, adolescents, and young adults), only 12 had H3.3K27M mutation and available brain magnetic resonance DICOM file. The MRI T1 post-gadolinium and T2 sequences were uploaded to LIFEx software to post-process and extract radiomic features. Statistical analysis included normal distribution tests and the Mann-Whitney U test performed using IBM SPSS® (Version 27.0.0.1, International Business Machines Corp., Armonk, NY, USA), considering a significant statistical p-value ≤ 0.05. RESULTS: EMNT vs. Tumor: From the T1 sequence 10 radiomics were identified, and 14 radiomics from the T2 sequence, but only one radiomic identified viable tumors in both sequences (p < 0.05) (DISCRETIZED_Q1). Peritumoral edema vs. EMNT: From the T1 sequence, five radiomics were identified, and four radiomics from the T2 sequence. However, four radiomics could discriminate peritumoral edema in both sequences (p < 0.05) (CONVENTIONAL_Kurtosis, CONVENTIONAL_ExcessKurtosis, DISCRETIZED_Kurtosis, and DISCRETIZED_ExcessKurtosis). There were no radiomics useful for distinguishing tumor tissue from peritumoral edema in both sequences. CONCLUSIONS: Less than 5% of the radiomic characteristics identified tumor regions of medical-clinical interest in T1 and T2 sequences of conventional magnetic resonance imaging. The first-order and second-order radiomic features suggest support to investigators and clinicians for careful evaluation for diagnosis, patient classification, and multimodality cancer treatment planning.
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This is a paired prospective comparative cohort study with 58 patients, in order to analyze the clinical LD-WLI in patients with moderate or severe COVID19 pneumonia. The results of this study show that the Radiotherapy could be an option to improve the clinical response for patients with COVID-19.
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COVID-19 , COVID-19/radioterapia , Estudios de Cohortes , Humanos , Pulmón/efectos de la radiación , Estudios Prospectivos , SARS-CoV-2 , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the effect of ixekizumab on self-reported functioning and health in patients with active nonradiographic axial spondyloarthritis (SpA). METHODS: COAST-X was a randomized, controlled trial conducted in patients with nonradiographic axial SpA over 52 weeks. Participants were randomized at a ratio of 1:1:1 to receive 80 mg of ixekizumab subcutaneously every 4 weeks or 2 weeks or placebo for 52 weeks. Self-reported functioning and health end points included the Medical Outcomes Study Short Form 36 (SF-36) health survey, Assessment of Spondyloarthritis International Society (ASAS) health index, and European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) health-utility descriptive system. RESULTS: Compared to placebo, ixekizumab treatment resulted in improvement of SF-36 physical component summary scores from baseline, with a score of 4.7 improving to 8.9 with ixekizumab therapy every 4 weeks (P < 0.05) and a score of 9.3 with ixekizumab therapy every 2 weeks (P < 0.01); the greatest improvements were observed in the domains of physical functioning, role-physical, and bodily pain at weeks 16 and 52. A higher proportion of patients receiving ixekizumab therapy every 2 weeks reported ≥3 improvements based on the ASAS health index from baseline to weeks 16 and 52 (P < 0.05). Significantly more patients receiving ixekizumab every 4 weeks reported improvements in "good health status" on the ASAS health index (ASAS score of ≤5) at weeks 16 and 52 (P < 0.05). Patients receiving ixekizumab reported improvements on the EQ-5D-5L compared to those who received placebo at week 16 (0.11 versus 0.17 for patients receiving treatment every 4 weeks and 0.19 for patients receiving treatment every 2 weeks; P < 0.05), which remained consistent at week 52. There were no clinical meaningful differences in responses based on the ixekizumab dosing regimen for patients who received ixekizumab therapy every 2 weeks or every 4 weeks. CONCLUSION: In patients with nonradiographic axial SpA, therapy with ixekizumab was superior to placebo in the improvement of self-reported functioning and health at weeks 16 and 52.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Antirreumáticos/administración & dosificación , Espondiloartritis Axial no Radiográfica/tratamiento farmacológico , Adulto , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del TratamientoRESUMEN
The aim of our study was to investigate the changes produced by low-dose radiotherapy (LDRT) in the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1) and inflammatory markers in patients with COVID-19 pneumonia treated with LDRT and their interactions with clinical and radiological changes. Data were collected from the IPACOVID prospective clinical trial (NCT04380818). The study included 30 patients treated with a whole-lung dose of 0.5 Gy. Clinical follow-up, as well as PON1-related variables, cytokines, and radiological parameters were analyzed before LDRT, at 24 h, and 1 week after treatment. Twenty-five patients (83.3%) survived 1 week after LDRT. Respiratory function and radiological images improved in survivors. Twenty-four hours after LDRT, PON1 concentration significantly decreased, while transforming growth factor beta 1 (TGF-ß1) increased with respect to baseline. One week after LDRT, patients had increased PON1 activities and lower PON1 and TGF-ß1 concentrations compared with 24 h after LDRT, PON1 specific activity increased, lactate dehydrogenase (LDH), and C-reactive protein (CRP) decreased, and CD4+ and CD8+ cells increased after one week. Our results highlight the benefit of LDRT in patients with COVID-19 pneumonia and it might be mediated, at least in part, by an increase in serum PON1 activity at one week and an increase in TGF-ß1 concentrations at 24 h.
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Current treatments for giardiasis include drugs with undesirable side effects, which increase the levels of therapeutic desertion and promote drug resistance in the parasites. Herein, we describe the antigiardiasic evaluation on Giardia lamblia trophozoites of a structurally diverse collection of 74 molecules. Among these scaffolds, we discovered a benzopyrrolizidine derivative with higher antigiardiasic activity (IC50 = 11 µM) and lower cytotoxicity in human cell cultures (IC50 = 130 µM) than those displayed by the current gold-standard drugs (metronidazole and tinidazole). Furthermore, this compound produced morphologic modifications of trophozoites, with occasional loss of one of the nuclei, among other changes not observed with standard giardicidal drugs, suggesting that it might act through a novel mechanism of action.