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Purpose: Epiretinal membranes (ERM) pose a common challenge in vitreoretinal pathology, often causing vision impairment in older adults. The Preceyes Surgical System (PSS) supports the surgical removal of ERM through robot-assisted membrane peeling (RA-MP). This study compares surgical times and iatrogenic hemorrhages between manual membrane peeling (MMP) and RA-MP using PSS. Methods: Nine patients underwent RA-MP with PSS, whereas 16 patients (18 eyes) underwent MMP for comparative analysis. Surgical durations were categorized into RA-MP, manual forceps utilization in PSS surgeries (mRA-MP), and traditional MMP. Cumulative manual manipulation duration (cMMP), instrument grasps, and intraoperative hemorrhages were statistically analyzed using the Mann-Whitney U test. Results: RA-MP showed significantly longer peeling times compared to MMP (P < 0.001). Flap initiation grasps were similar between methods (P = 0.86), RA-MP demonstrated a significant reduction in peeling grasps (P = 0.01) and mean grasps per minute (P < 0.001). Although RA-MP resulted in fewer hemorrhages, the difference did not reach statistical significance relative to MMP (P = 0.08). Discussion: Although RA-MP tended to extend surgical time, it offered advantages in reducing tissue trauma and intraoperative hemorrhages. Further research is needed to explore the learning curve for novice surgeons and evaluate the safety profile of RA-MP. Translational Relevance: RA-MP may offer potential advantages over manual surgery, particularly in terms of reduced tissue trauma and intraoperative hemorrhages. Despite its longer duration compared with manual techniques, RA-MP may lead to fewer grasping maneuvers and lower rates of hemorrhages, thereby enhancing the safety and precision of vitreoretinal surgeries.
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Membrana Epirretiniana , Duração da Cirurgia , Procedimentos Cirúrgicos Robóticos , Humanos , Membrana Epirretiniana/cirurgia , Idoso , Masculino , Feminino , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Idoso de 80 Anos ou mais , Vitrectomia/métodos , Vitrectomia/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Acuidade VisualRESUMO
Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes. These molecular responses to dexamethasone were detected in circulating and pulmonary monocytes, and they were directly linked to survival. Monocyte single-cell RNA sequencing (scRNA-seq)-derived signatures were enriched in whole blood transcriptomes of patients with fatal outcome in two independent cohorts, highlighting the potential for identifying non-responders refractory to dexamethasone. Our findings link the effects of dexamethasone to specific immunomodulation and reversal of monocyte dysregulation, and they highlight the potential of single-cell omics for monitoring in vivo target engagement of immunomodulatory drugs and for patient stratification for precision medicine approaches.
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Tratamento Farmacológico da COVID-19 , COVID-19 , Dexametasona , Monócitos , SARS-CoV-2 , Análise de Célula Única , Humanos , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Masculino , Feminino , Transcriptoma , Pessoa de Meia-Idade , Idoso , Glucocorticoides/uso terapêutico , Glucocorticoides/farmacologia , Pulmão/patologia , AdultoRESUMO
The SARS-CoV-2 genome has been shown to be m6A methylated at several positions inâ vivo. Strikingly, a DRACH motif, the recognition motif for adenosine methylation, resides in the core of the transcriptional regulatory leader sequence (TRS-L) at position A74, which is highly conserved and essential for viral discontinuous transcription. Methylation at position A74 correlates with viral pathogenicity. Discontinuous transcription produces a set of subgenomic mRNAs that function as templates for translation of all structural and accessory proteins. A74 is base-paired in the short stem-loop structure 5'SL3 that opens during discontinuous transcription to form long-range RNA-RNA interactions with nascent (-)-strand transcripts at complementary TRS-body sequences. A74 can be methylated by the human METTL3/METTL14 complex inâ vitro. Here, we investigate its impact on the structural stability of 5'SL3 and the long-range TRS-leader:TRS-body duplex formation necessary for synthesis of subgenomic mRNAs of all four viral structural proteins. Methylation uniformly destabilizes 5'SL3 and long-range duplexes and alters their relative equilibrium populations, suggesting that the m6A74 modification acts as a regulator for the abundance of viral structural proteins due to this destabilization.
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Adenosina , Metiltransferases , RNA Mensageiro , RNA Viral , SARS-CoV-2 , Transcrição Gênica , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , SARS-CoV-2/química , RNA Viral/química , RNA Viral/metabolismo , RNA Viral/genética , Metiltransferases/química , Metiltransferases/metabolismo , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Humanos , Metilação , Adenosina/química , Adenosina/análogos & derivados , Conformação de Ácido Nucleico , Genoma ViralRESUMO
OBJECTIVE: Although aging has a strong impact on visual acuity (VA) and falls, their interaction is understudied in generally healthy older adults. This study aimed to examine if and to what extent baseline VA is associated with an increased risk of all and injurious falls over 3 years in generally healthy community-dwelling older adults. DESIGN: Observational analysis of DO-HEALTH, a double-blind, randomized controlled trial. SETTING AND PARTICIPANTS: Multicenter trial with 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without any major health events in the 5 years prior to enrollment, sufficient mobility, and good cognitive status. METHODS: The numbers of all and injurious falls were recorded prospectively by diary and in-person assessment every 3 months. Decreased VA at baseline was defined as better-eye VA lower than 1.0. We applied negative binomial regression models for all and injurious falls, adjusted for age, sex, prior falls, treatment allocation, study site, baseline body mass index, and use of walking aids. RESULTS: Among the 2131 participants included in this analysis (mean age: 74.9 years, 61.7% were women, 82.6% at least moderately physically active), 1464 (68.7%) had decreased VA. Overall, 3290 falls including 2116 injurious falls were recorded over 3 years. Decreased VA at baseline was associated with a 22% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) = 1.22, 95% CI 1.07, 1.38, P = .003] and 20% increased incidence rate of injurious falls (aIRR = 1.20, 95% CI 1.05, 1.37, P = .007). CONCLUSIONS AND IMPLICATIONS: Our findings suggest that decreased VA is an independent predictor of an about 20% increased risk of all and injurious falls, highlighting the importance of regular eye examinations and VA measurements for fall prevention, even in generally healthy and active older adults.
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Acidentes por Quedas , Acuidade Visual , Humanos , Acidentes por Quedas/estatística & dados numéricos , Idoso , Masculino , Feminino , Acuidade Visual/fisiologia , Estudos Prospectivos , Idoso de 80 Anos ou mais , Método Duplo-Cego , Europa (Continente)/epidemiologia , Vida Independente , Medição de RiscoRESUMO
Electroretinography (ERG) provides crucial insights into retinal function and the integrity of the visual pathways. However, ERG assessments classically require a complicated technical background with costly equipment. In addition, the placement of corneal or conjunctival electrodes is not always tolerated by the patients, which restricts the measurement for pediatric evaluations. In this short review, we give an overview of the use of the RETeval portable ERG device (LKC Technologies, Inc., Gaithersburg, MD, USA), a modern portable ERG device that can facilitate screening for diseases involving the retina and the optic nerve. We also review its potential to provide ocular biomarkers in systemic pathologies, such as Alzheimer's disease and central nervous system alterations, within the framework of oculomics.
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Eletrorretinografia , Desenho de Equipamento , Doenças Retinianas , Humanos , Eletrorretinografia/instrumentação , Eletrorretinografia/economia , Doenças Retinianas/diagnóstico , Análise de Falha de Equipamento , Miniaturização , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Programas de Rastreamento/instrumentação , Programas de Rastreamento/economia , Seleção Visual/instrumentação , Seleção Visual/economia , Custos de Cuidados de SaúdeRESUMO
Autoencoders are frequently used to embed molecules for training of downstream deep learning models. However, evaluation of the chemical information quality in the latent spaces is lacking and the model architectures are often arbitrarily chosen. Unoptimized architectures may not only negatively affect latent space quality but also increase energy consumption during training, making the models unsustainable. We conducted systematic experiments to better understand how the autoencoder architecture affects the reconstruction and latent space quality and how it can be optimized towards the encoding task as well as energy consumption. We can show that optimizing the architecture allows us to maintain the quality of a generic architecture but using 97% less data and reducing energy consumption by around 36%. We additionally observed that representing the molecules as SELFIES reduced the reconstruction performance compared to SMILES and that training with enumerated SMILES drastically improved latent space quality. Scientific Contribution: This work provides the first comprehensive systematic analysis of how choosing the autoencoder architecture affects the reconstruction performance of small molecules, the chemical information content of the latent space as well as the energy required for training. Demonstrated on the MOSES benchmarking dataset it provides first valuable insights into how autoencoders for the embedding of small molecules can be designed to optimize their utility and simultaneously become more sustainable, both in terms of energy consumption as well as the required amount of training data. All code, data and model checkpoints are made available on Zenodo (Oestreich et al. Small molecule autoencoders: architecture engineering to optimize latent space utility and sustainability. Zenodo, 2024). Furthermore, the top models can be found on GitHub with scripts to encode custom molecules: https://github.com/MarieOestreich/small-molecule-autoencoders .
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As the number and complexity of transcriptomic datasets increase, there is a rising demand for accessible and user-friendly analysis tools. Here, we present hCoCena (horizontal construction of co-expression networks and analysis), a toolbox facilitating the analysis of a single dataset, as well as the joint analysis of multiple datasets. We describe steps for workspace setup, formatting tables, data processing, and network integration. We then detail procedures for gene clustering, gene set enrichment analysis, and transcription factor enrichment analysis. For complete details on the use and execution of this protocol, please refer to Oestreich et al.1.
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Perfilação da Expressão Gênica , Transcriptoma , Transcriptoma/genética , Análise por Conglomerados , Fatores de TranscriçãoRESUMO
T follicular helper (TFH) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse TFH cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor-ß (TGF-ß) induces robust expression of TFH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4+ T cells in vitro. TGF-ß-induced mouse CXCR5+ TFH cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated TFH cells and provide critical help to B cells. The study further reveals that TGF-ß-induced CXCR5 expression is independent of Bcl6 but requires the transcription factor c-Maf. Classical TGF-ß-containing T helper 17 (TH17)-inducing conditions also yield separate CXCR5+ and IL-17A-producing cells, highlighting shared and distinct cell fate trajectories of TFH and TH17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-ß-induced TFH cell program, that TFH and TH17 cells share a common developmental stage, and that c-Maf acts as a switch factor for TFH versus TH17 cell fates in TGF-ß-rich environments in vitro and in vivo.
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Linfócitos T Auxiliares-Indutores , Fator de Crescimento Transformador beta , Animais , Camundongos , Fator de Crescimento Transformador beta/metabolismo , Linfócitos B , Linfócitos T CD4-Positivos , Diferenciação Celular , Proteínas Proto-Oncogênicas c-maf/metabolismoRESUMO
Background: The prevalence of COVID-19 breakthrough infections in healthcare workers (HCWs) remains an issue of concern. This study examines the different characteristics associated with breakthrough infections in HCWs. Methods: From the total participants in the TüSeRe:exact study (n = 1046), we specifically included study participants who had received three vaccinations and were not infected prior to the third vaccination. Participants were invited to complete an online questionnaire, which included inquiries about any breakthrough infections they might have experienced. Univariate Cox regression analysis was used to investigate the association between participant characteristics and breakthrough infections. Results: Among 629 HCWs (497 female and 132 male), 241 (38%) experienced breakthrough infections during the follow-up period. The frequency of breakthrough infections was 39.2% (195/497) among female participants and 34.8% (46/132) among male participants (p = 0.357). The Cox regression model adjusted for age and sex showed that participants with cardiovascular disease (hazard ratio (95%CI) = 0.621 (0.392-0.985); p = 0.043) and those taking antihypertensives (hazard ratio (95%CI) = 0.551 (0.331-0.915); p = 0.021) had a significantly lower hazard ratio for breakthrough infections. The use of analgesics after the first vaccine (hazard ratio (95%CI) = 1.343 (1.025-1.759); p = 0.032) was associated with an increased risk of breakthrough infections. Conclusions: These findings can inform targeted preventive measures and risk management strategies to protect frontline workers and maintain a resilient healthcare system during the ongoing pandemic.
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Introduction: Today, modern technology is used to diagnose and treat cardiovascular disease. These medical devices provide exact measures and raw data such as imaging data or biosignals. So far, the Broad Integration of These Health Data into Hospital Information Technology Structures-Especially in Germany-is Lacking, and if data integration takes place, only non-Evaluable Findings are Usually Integrated into the Hospital Information Technology Structures. A Comprehensive Integration of raw Data and Structured Medical Information has not yet Been Established. The aim of this project was to design and implement an interoperable database (cardio-vascular-information-system, CVIS) for the automated integration of al medical device data (parameters and raw data) in cardio-vascular medicine. Methods: The CVIS serves as a data integration and preparation system at the interface between the various devices and the hospital IT infrastructure. In our project, we were able to establish a database with integration of proprietary device interfaces, which could be integrated into the electronic health record (EHR) with various HL7 and web interfaces. Results: In the period between 1.7.2020 and 30.6.2022, the data integrated into this database were evaluated. During this time, 114,858 patients were automatically included in the database and medical data of 50,295 of them were entered. For technical examinations, more than 4.5 million readings (an average of 28.5 per examination) and 684,696 image data and raw signals (28,935 ECG files, 655,761 structured reports, 91,113 x-ray objects, 559,648 ultrasound objects in 54 different examination types, 5,000 endoscopy objects) were integrated into the database. Over 10.2 million bidirectional HL7 messages (approximately 14,000/day) were successfully processed. 98,458 documents were transferred to the central document management system, 55,154 materials (average 7.77 per order) were recorded and stored in the database, 21,196 diagnoses and 50,353 services/OPS were recorded and transferred. On average, 3.3 examinations per patient were recorded; in addition, there are an average of 13 laboratory examinations. Discussion: Fully automated data integration from medical devices including the raw data is feasible and already creates a comprehensive database for multimodal modern analysis approaches in a short time. This is the basis for national and international projects by extracting research data using FHIR.
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Visceral adipose tissue (VAT) is an energy store and endocrine organ critical for metabolic homeostasis. Regulatory T (Treg) cells restrain inflammation to preserve VAT homeostasis and glucose tolerance. Here, we show that the VAT harbors two distinct Treg cell populations: prototypical serum stimulation 2-positive (ST2+) Treg cells that are enriched in males and a previously uncharacterized population of C-X-C motif chemokine receptor 3-positive (CXCR3+) Treg cells that are enriched in females. We show that the transcription factors GATA-binding protein 3 and peroxisome proliferator-activated receptor-γ, together with the cytokine interleukin-33, promote the differentiation of ST2+ VAT Treg cells but repress CXCR3+ Treg cells. Conversely, the differentiation of CXCR3+ Treg cells is mediated by the cytokine interferon-γ and the transcription factor T-bet, which also antagonize ST2+ Treg cells. Finally, we demonstrate that ST2+ Treg cells preserve glucose homeostasis, whereas CXCR3+ Treg cells restrain inflammation in lean VAT and prevent glucose intolerance under high-fat diet conditions. Overall, this study defines two molecularly and developmentally distinct VAT Treg cell types with unique context- and sex-specific functions.
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Proteína 1 Semelhante a Receptor de Interleucina-1 , Linfócitos T Reguladores , Feminino , Masculino , Humanos , Gordura Intra-Abdominal , Citocinas , Inflamação , GlucoseRESUMO
Introduction: People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared multiple omics data layers. Methods: Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis by ATAC-seq as well as ex vivo drug stimulation were performed in a small number of blood samples derived from PLHIV and healthy controls from the 200-HIV cohort study. Results: Single-cell RNA-seq analysis revealed that most immune cells in peripheral blood of PLHIV are altered in their transcriptomes and that a specific functional monocyte state previously described in acute HIV infection is still existing in PLHIV while other monocyte cell states are only occurring acute infection. Further, a reverse transcriptome approach on a rather small number of PLHIV was sufficient to identify drug candidates for reversing the transcriptional phenotype of monocytes in PLHIV. Discussion: These scientific findings and technological advancements for clinical application of single-cell transcriptomics form the basis for the larger 2000-HIV multicenter cohort study on PLHIV, for which a combination of bulk and single-cell transcriptomics will be included as the leading technology to determine disease endotypes in PLHIV and to predict disease trajectories and outcomes.
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Fármacos Anti-HIV , Infecções por HIV , Humanos , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Monócitos , Estudos Multicêntricos como AssuntoRESUMO
Cardiovascular diseases are the leading cause of death worldwide. The diagnoses of cardiovascular diseases are usually carried out by cardiologists utilizing Electrocardiograms (ECGs). To assist these physicians in making an accurate diagnosis, there is a growing need for reliable and automatic ECG classifiers.In this study, a new method is proposed to classify 12-lead ECG recordings. The proposed model is composed of four components: the CNN(Convolutional Neural Network) module, the transformer module, the global hybrid pooling layer, and a classification layer. To improve the classification performance, the model takes the discrete wavelet transform of ECG signals as the model inputs and utilizes a hybrid pooling layer to condense the most important features over each period.The proposed model is evaluated using the test set of the China Physiological Signal Challenge 2018 dataset with 12-lead ECGs. It performs with an average accuracy of 0.86 and an average F1-scores of 0.83. The scores are particularly good for the block conditions (LBBB, RBBB, I-AVB). The main advantage of the proposed model is that, it obtains good results with a significantly smaller number of parameters compared to other individual and ensemble models.Clinical relevance- This work establishes a new ECG classifier model with high performance and low model size. It can make automatic ECG analysis more accessible, efficient, and accurate, especially in remote or underserved areas.
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Doenças Cardiovasculares , Análise de Ondaletas , Humanos , Processamento de Sinais Assistido por Computador , Redes Neurais de Computação , Eletrocardiografia/métodosRESUMO
BACKGROUND: Direct cardiac reprogramming is currently being investigated for the generation of cells with a true cardiomyocyte (CM) phenotype. Based on the original approach of cardiac transcription factor-induced reprogramming of fibroblasts into CM-like cells, various modifications of that strategy have been developed. However, they uniformly suffer from poor reprogramming efficacy and a lack of translational tools for target cell expansion and purification. Therefore, our group has developed a unique approach to generate proliferative cells with a pre-CM phenotype that can be expanded in vitro to yield substantial cell doses. METHODS: Cardiac fibroblasts were reprogrammed toward CM fate using lentiviral transduction of cardiac transcriptions factors (GATA4, MEF2C, TBX5, and MYOCD). The resulting cellular phenotype was analyzed by RNA sequencing and immunocytology. Live target cells were purified based on intracellular CM marker expression using molecular beacon technology and fluorescence-activated cell sorting. CM commitment was assessed using 5-azacytidine-based differentiation assays and the therapeutic effect was evaluated in a mouse model of acute myocardial infarction using echocardiography and histology. The cellular secretome was analyzed using mass spectrometry. RESULTS: We found that proliferative CM precursor-like cells were part of the phenotype spectrum arising during direct reprogramming of fibroblasts toward CMs. These induced CM precursors (iCMPs) expressed CPC- and CM-specific proteins and were selectable via hairpin-shaped oligonucleotide hybridization probes targeting Myh6/7-mRNA-expressing cells. After purification, iCMPs were capable of extensive expansion, with preserved phenotype when under ascorbic acid supplementation, and gave rise to CM-like cells with organized sarcomeres in differentiation assays. When transplanted into infarcted mouse hearts, iCMPs prevented CM loss, attenuated fibrotic scarring, and preserved ventricular function, which can in part be attributed to their substantial secretion of factors with documented beneficial effect on cardiac repair. CONCLUSIONS: Fibroblast reprogramming combined with molecular beacon-based cell selection yields an iCMP-like cell population with cardioprotective potential. Further studies are needed to elucidate mechanism-of-action and translational potential.
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Infarto do Miocárdio , Miócitos Cardíacos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Remodelação Ventricular , Proteínas com Domínio T/genética , Fatores de Transcrição MEF2/genética , Infarto do Miocárdio/terapia , Infarto do Miocárdio/tratamento farmacológico , Fibroblastos , Reprogramação Celular/genéticaRESUMO
To monitor the progression of infectious diseases, it is useful to assess immunoreactivity against various antigenic determinants, and measure different antibody isotypes because they appear at different stages of the host immune response. With Lyme borreliosis, the pathogenic agent can be one of the multiple members of the Borrelia species. Therefore, correct sample classification requires evaluating the immunoreactivity against different antigens of different Borrelia species. Additionally, anti-pathogen IgG and IgM responses can have different elicitation time courses during disease progression. Here we demonstrate the development of a two-reporter multiplex immunoassay that has utility in identifying Borrelia-specific immune response in human serum samples by simultaneously evaluating both IgG and IgM immunoreactivity against different bacterial antigens in the same reaction well. This dual-reporter approach retains the analytical performance of single-reporter methods while conserving time and resources and reducing sample size requirements. This assay allows essentially double the serological information to be generated from a blood sample in half the time.
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Borrelia burgdorferi , Doença de Lyme , Humanos , Imunoglobulina G , Sensibilidade e Especificidade , Anticorpos Antibacterianos , Doença de Lyme/diagnóstico , Antígenos de Bactérias , Imunoglobulina M , Testes Sorológicos/métodosRESUMO
COVID-19 convalescent plasma (CCP) with high neutralizing antibodies has been suggested in preventing disease progression in COVID-19. In this study, we investigated the relationship between clinical donor characteristics and neutralizing anti-SARS-CoV-2 antibodies in CCP donors. COVID-19 convalescent plasma donors were included into the study. Clinical parameters were recorded and anti-SARS-CoV-2 antibody levels (Spike Trimer, Receptor Binding Domain (RBD), S1, S2 and nucleocapsid protein) as well as ACE2 binding inhibition were measured. An ACE2 binding inhibition < 20% was defined as an inadequate neutralization capacity. Univariate and multivariable logistic regression analysis was used to detect the predictors of inadequate neutralization capacity. Ninety-one CCP donors (56 female; 61%) were analyzed. A robust correlation between all SARS-CoV-2 IgG antibodies and ACE2 binding inhibition, as well as a positive correlation between donor age, body mass index, and a negative correlation between time since symptom onset and antibody levels were found. We identified time since symptom onset, normal body mass index (BMI), and the absence of high fever as independent predictors of inadequate neutralization capacity. Gender, duration of symptoms, and number of symptoms were not associated with SARS-CoV-2 IgG antibody levels or neutralization. Neutralizing capacity was correlated with SARS-CoV-2 IgG antibodies and associated with time since symptom onset, BMI, and fever. These clinical parameters can be easily incorporated into the preselection of CCP donors.
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COVID-19 , Humanos , Feminino , COVID-19/terapia , Enzima de Conversão de Angiotensina 2 , Glicoproteína da Espícula de Coronavírus , Soroterapia para COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Anticorpos Neutralizantes , Doadores de Sangue , Imunoglobulina G , Imunização PassivaRESUMO
Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.
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Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Animais , Camundongos , Neutrófilos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pulmão , InflamaçãoRESUMO
PURPOSE: To analyze the indications, complications, and early course of recovery of intraocular lens (IOL) exchange surgery. MATERIAL AND METHODS: Records of patients who underwent IOL exchange during a 6-year period at a tertiary referral center were reviewed and the indications and complications after surgical intervention were analyzed. Their effects on postoperative corrected distance visual acuity (CDVA), intraocular pressure (IOP), use of IOP-lowering medications, and refractive cylindrical power were assessed. RESULTS: One hundred and seventy-one eyes (165 patients) were investigated. The most frequent indication for IOL exchange was lens dislocation in 163 eyes (95.32%). The main causes of IOL dislocation were pseudoexfoliation syndrome (PEX) in 98 eyes (57.31%) and complications during cataract surgery in 40 eyes (23.39%). During IOL exchange, an anterior iris-claw fixation was performed in 159 eyes (92.98%). After significant initial deterioration to 1.59 ± 1.08 logMAR on postoperative day 1 (p ≤ 0.001), the CDVA recovered to preoperative levels within 28 days. A significant decrease in IOP was observed on postoperative day 1 (p = 0.04). The most common postoperative complications were corneal edema in 114 eyes (66.67%) and vitreous hemorrhage in 67 eyes (39.18%). CONCLUSION: The high early postoperative prevalence of corneal edema and intraocular hemorrhage was found to affect visual recovery after IOL exchange, causing a significant initial deterioration of CDVA and a delay of full visual recovery. These findings suggest that surgical approaches minimizing the risk of this type of complications should be favored.
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Edema da Córnea , Lentes Intraoculares , Humanos , Estudos Retrospectivos , Implante de Lente Intraocular/efeitos adversos , Lentes Intraoculares/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Esclera/cirurgiaRESUMO
PURPOSE: The Preceyes Surgical System (PSS) is a robotic assistive device that may enhance surgical precision. This study assessed pre- and intra-operative times and surgeons' perceptions of robot-assisted epiretinal membrane peeling (RA-MP). METHODS: We analyzed the time requirement of three main tasks: the preparation of the PSS (I), patient preparation (II), and surgery (III). Following surgery, the surgeons were asked questions about their experience. RESULTS: RA-MP was performed in nine eyes of nine patients. Task I required an average time of 12.3 min, initially taking 15 min but decreasing to 6 min in the last surgery. Task II showed a mean time of 47.2 (range of 36-65) min. Task III had a mean time of 72.4 (range of 57-100) min. A mean time of 27.9 (range of 9-46) min was necessary for RA-MP. The responses to the questionnaire revealed a trend towards increasing ease and reduced stress as familiarity with the PSS increased. CONCLUSIONS: A substantial reduction in pre- and intra-operative times, decreasing to a total of 115 min, was demonstrated. RA-MP was positively anticipated by the surgeons and led to no hand or arm strain while being more complex than manual MP.