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1.
J Nat Med ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775895

RESUMO

The practice of Chinese herbal medicines for the treatment of COVID-19 in China played an essential role for the control of mortality rate and reduction of recovery time. The iridoids is one of the main constituents of many heat-clearing and detoxifying Chinese medicines that were largely planted and frequently used in clinical practice. Twenty-three representative high content iridoids from several staple Chinese medicines were obtained and tested by a SARS-CoV-2 pseudo-virus entry-inhibition assay on HEK-293 T/ACE2 cells, a live HCoV-OC43 virus infection assay on HRT-18 cells, and a SARS-CoV-2 3CL protease inhibitory FRET assay followed by molecular docking simulation. The anti-pulmonary inflammation activities were further evaluated on a TNF-α induced inflammation model in A549 cells and preliminary SARs were concluded. The results showed that specnuezhenide (7), cornuside (12), neonuezhenide (15), and picroside III (21) exhibited promising antiviral activities, and neonuezhenide (15) could inhibit 3CL protease with an IC50 of 14.3 µM. Docking computation showed that compound 15 could bind to 3CL protease through a variety of hydrogen bonding and hydrophobic interactions. In the anti-pulmonary inflammation test, cornuside (12), aucubin (16), monotropein (17), and shanzhiside methyl ester (18) could strongly decrease the content of IL-1ß and IL-8 at 10 µM. Compound 17 could also upregulate the expression of the anti-inflammatory cytokine IL-10 significantly. The iridoids exhibited both anti-coronavirus and anti-pulmonary inflammation activities for their significance of existence in Chinese herbal medicines, which also provided a theoretical basis for their potential utilization in the pharmaceutical and food industries.

2.
Int J Infect Dis ; : 107084, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38705567

RESUMO

OBJECTIVES: We investigated how booster interval affects the risks of SARS-CoV-2 infection and Covid-19-related hospitalization and death in different age groups. METHODS: We collected data on booster receipts and Covid-19 outcomes between September 22, 2021 and February 9, 2023 for 5,769,205 North Carolina residents ≥12 years of age who had completed their primary vaccination series. We related Covid-19 outcomes to baseline characteristics and booster doses through Cox regression models. RESULTS: For adults ≥65 years of age, boosting every 9 months was associated with proportionate reductions (compared with no boosting) of 18.9% (95% CI, 18.5 to 19.4) in the cumulative frequency of infection, 37.8% (95% CI, 35.3 to 40.3) in the cumulative risk of hospitalization or death, and 40.9% (95% CI, 37.2 to 44.7) in the cumulative risk of death at two years after completion of primary vaccination. The reductions were lower by boosting every 12 months and higher by boosting every 6 months. The reductions were smaller for individuals 12-64 years of age. CONCLUSION: Boosting at a shorter interval was associated with a greater reduction in Covid-19 outcomes, especially hospitalization and death. Frequent boosting conferred greater benefits for individuals aged ≥65 than for individuals aged 12-64.

3.
Front Nutr ; 11: 1335538, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562486

RESUMO

The Chinese name "Lingzhi" refers to Ganoderma genus, which are increasingly used in the food and medical industries. Ganoderma species are often used interchangeably since the differences in their composition are not known. To find compositional metabolite differences among Ganoderma species, we conducted a widely targeted metabolomics analysis of four commonly used edible and medicinal Ganoderma species based on ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Through pairwise comparisons, we identified 575-764 significant differential metabolites among the species, most of which exhibited large fold differences. We screened and analyzed the composition and functionality of the advantageous metabolites in each species. Ganoderma lingzhi advantageous metabolites were mostly related to amino acids and derivatives, as well as terpenes, G. sinense to terpenes, and G. leucocontextum and G. tsugae to nucleotides and derivatives, alkaloids, and lipids. Network pharmacological analysis showed that SRC, GAPDH, TNF, and AKT1 were the key targets of high-degree advantage metabolites among the four Ganoderma species. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes demonstrated that the advantage metabolites in the four Ganoderma species may regulate and participate in signaling pathways associated with diverse cancers, Alzheimer's disease, and diabetes. Our findings contribute to more targeted development of Ganoderma products in the food and medical industries.

4.
Clin Trials ; : 17407745241238443, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618926

RESUMO

BACKGROUND: The current endpoints for therapeutic trials of hospitalized COVID-19 patients capture only part of the clinical course of a patient and have limited statistical power and robustness. METHODS: We specify proportional odds models for repeated measures of clinical status, with a common odds ratio of lower severity over time. We also specify the proportional hazards model for time to each level of improvement or deterioration of clinical status, with a common hazard ratio for overall treatment benefit. We apply these methods to Adaptive COVID-19 Treatment Trials. RESULTS: For remdesivir versus placebo, the common odds ratio was 1.48 (95% confidence interval (CI) = 1.23-1.79; p < 0.001), and the common hazard ratio was 1.27 (95% CI = 1.09-1.47; p = 0.002). For baricitinib plus remdesivir versus remdesivir alone, the common odds ratio was 1.32 (95% CI = 1.10-1.57; p = 0.002), and the common hazard ratio was 1.30 (95% CI = 1.13-1.49; p < 0.001). For interferon beta-1a plus remdesivir versus remdesivir alone, the common odds ratio was 0.95 (95% CI = 0.79-1.14; p = 0.56), and the common hazard ratio was 0.98 (95% CI = 0.85-1.12; p = 0.74). CONCLUSIONS: The proposed methods comprehensively characterize the treatment effects on the entire clinical course of a hospitalized COVID-19 patient.

6.
Biometrics ; 80(1)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38497824

RESUMO

The semiparametric Cox proportional hazards model, together with the partial likelihood principle, has been widely used to study the effects of potentially time-dependent covariates on a possibly censored event time. We propose a computationally efficient method for fitting the Cox model to big data involving millions of study subjects. Specifically, we perform maximum partial likelihood estimation on a small subset of the whole data and improve the initial estimator by incorporating the remaining data through one-step estimation with estimated efficient score functions. We show that the final estimator has the same asymptotic distribution as the conventional maximum partial likelihood estimator using the whole dataset but requires only a small fraction of computation time. We demonstrate the usefulness of the proposed method through extensive simulation studies and an application to the UK Biobank data.


Assuntos
Big Data , Biobanco do Reino Unido , Humanos , Modelos de Riscos Proporcionais , Probabilidade , Simulação por Computador
7.
Biometrics ; 80(1)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38364799

RESUMO

Multivariate panel count data arise when there are multiple types of recurrent events, and the observation for each study subject consists of the number of recurrent events of each type between two successive examinations. We formulate the effects of potentially time-dependent covariates on multiple types of recurrent events through proportional rates models, while leaving the dependence structures of the related recurrent events completely unspecified. We employ nonparametric maximum pseudo-likelihood estimation under the working assumptions that all types of events are independent and each type of event is a nonhomogeneous Poisson process, and we develop a simple and stable EM-type algorithm. We show that the resulting estimators of the regression parameters are consistent and asymptotically normal, with a covariance matrix that can be estimated consistently by a sandwich estimator. In addition, we develop a class of graphical and numerical methods for checking the adequacy of the fitted model. Finally, we evaluate the performance of the proposed methods through simulation studies and analysis of a skin cancer clinical trial.


Assuntos
Neoplasias Cutâneas , Humanos , Simulação por Computador , Modelos Estatísticos , Neoplasias Cutâneas/epidemiologia , Ensaios Clínicos como Assunto
8.
Zool Res ; 45(1): 189-200, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38199973

RESUMO

Monitoring the prevalence of antimicrobial resistance genes (ARGs) is vital for addressing the global crisis of antibiotic-resistant bacterial infections. Despite its importance, the characterization of ARGs and microbiome structures, as well as the identification of indicators for routine ARG monitoring in pig farms, are still lacking, particularly concerning variations in antimicrobial exposure in different countries or regions. Here, metagenomics and random forest machine learning were used to elucidate the ARG profiles, microbiome structures, and ARG contamination indicators in pig manure under different antimicrobial pressures between China and Europe. Results showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs ( P<0.05). ANT(6)-Ib, APH(3')-IIIa, and tet(40) were identified as shared core ARGs between the two pig populations. Furthermore, the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical regions. Lactobacillus and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs, respectively. Forty ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100% and 98.7%, respectively. Indicators for assessing ARG contamination in Chinese and European pigs also achieved high accuracy ( r=0.72-0.88). Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 ARGs. The results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.


Assuntos
Anti-Infecciosos , Microbioma Gastrointestinal , Humanos , Animais , Suínos , Antibacterianos/farmacologia , Esterco , Farmacorresistência Bacteriana/genética
9.
Nat Prod Res ; 38(10): 1719-1726, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37265118

RESUMO

A new lignan, named pouzolignan P (1), together with 14 known ones (2 - 15) were isolated from the roots of Pouzolzia zeylanica (L.) Benn. Their structures were deduced based on the detailed spectroscopic analysis. All the isolates were evaluated for their inhibitory activities toward the ATP citrate lyase (ACLY). Among them, four lignans, isopouzolignan K (3), gnemontanins E (5), gnetuhainin I (6), and styraxlignolide D (15) showed excellent ACLY inhibitory effect with IC50 values of 9.06, 0.59, 2.63, and 7.62 µM, respectively. These compounds were further evaluated for their cholesterol-lowing effects on ox-LDL-induced high-cholesterol HepG2 cells. Compound 15 emerges as the most potent ACLY inhibitor, which significantly decreased the TC level in a dose-dependent manner. In addition, molecular docking simulations elucidated that 15 formed a strong hydrogen-bond interaction with Glu599 of ACLY, which was an important site responsible for the enzyme catalytic activity.


Assuntos
ATP Citrato (pro-S)-Liase , Lignanas , ATP Citrato (pro-S)-Liase/química , Simulação de Acoplamento Molecular , Inibidores Enzimáticos/farmacologia , Colesterol
10.
HGG Adv ; 5(1): 100245, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-37817410

RESUMO

Mendelian randomization has been widely used to assess the causal effect of a heritable exposure variable on an outcome of interest, using genetic variants as instrumental variables. In practice, data on the exposure variable can be incomplete due to high cost of measurement and technical limits of detection. In this paper, we propose a valid and efficient method to handle both unmeasured and undetectable values of the exposure variable in one-sample Mendelian randomization analysis with individual-level data. We estimate the causal effect of the exposure variable on the outcome using maximum likelihood estimation and develop an expectation maximization algorithm for the computation of the estimator. Simulation studies show that the proposed method performs well in making inference on the causal effect. We apply our method to the Hispanic Community Health Study/Study of Latinos, a community-based prospective cohort study, and estimate the causal effect of several metabolites on phenotypes of interest.


Assuntos
Análise da Randomização Mendeliana , Saúde Pública , Humanos , Análise da Randomização Mendeliana/métodos , Estudos Prospectivos , Causalidade , Hispânico ou Latino/genética
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1014538

RESUMO

AIM: To explore the mechanism of osthole on elderly spontaneously hypertensive rats. METHODS: 20-month-old spontaneously hypertensive rats (SHRs) and healthy Wistar-Kyoto (WKY) rats were purchased. SHRs were treated with osthole (i.g.) for 8 weeks. The systolic blood pressure and diastolic blood pressure of rats were monitored. Hematoxylin-eosin staining (H&E), periodic acid-schiff staining (PAS) and Masson staining were used to observe the pathological changes of rat kidney tissues. The activity of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in rat kidney was detected by ELISA kit. PI3K/Akt/mTOR signaling pathway related proteins were detected by western blot. RESULTS: Osthole reduced the systolic and diastolic blood pressure of SHRs, improved the histopathological changes of SHRs kidney, reduced the activity of MDA in SHRs kidney, and increased the activity of SOD and GSH. Osthole reduced the levels of p-PI3K, p-Akt and p-mTOR. CONCLUSION: Osthole reduces the activity of PI3K/Akt/mTOR signaling pathway and exerts a protective effect on renal oxidative stress injury in aged spontaneously hypertensive rats.

12.
Chinese Journal of Pediatrics ; (12): 55-59, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013249

RESUMO

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.


Assuntos
Masculino , Feminino , Humanos , Criança , SARS-CoV-2 , Doença da Artéria Coronariana , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Retrospectivos , COVID-19/complicações , Doenças do Tecido Conjuntivo , Metilprednisolona/uso terapêutico , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico
13.
Phytochemistry ; 217: 113920, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37951561

RESUMO

Ten lignans, including six previously undescribed phenolic ester glycosyl lignans (1-6), were isolated from a well-known traditional Chinese medicine, Qin-Jiao, which is the dry root of Gentiana macrophylla Pall. (Gentianaceae). Their structures were determined by spectroscopic and chemical methods, especially 2D NMR techniques. Quantum chemical calculations of theoretical ECD spectra allowed the determination of their absolute configurations. Refer to its traditional applications for the treatment of rheumatic arthralgia and hepatopathy, these compounds were evaluated on a TNF-α induced MH7A human synoviocyte inflammation model and a D-GalN induced AML12 hepatocyte injury model. Compounds 1, 2, 5, and 6 significantly reduced the release of proinflammatory cytokine IL-1ß in MH7A cells at 15 µM and they also could strongly protect AML12 cells against D-GalN injury at 30 µM. Flow cytometry and Western blot analysis showed that compound 5 ameliorated D-GalN induced AML12 cell apoptosis by upregulating the expression of anti-apoptotic Bcl-2 protein and down-regulating the expression of pro-apoptotic Bax protein.


Assuntos
Medicamentos de Ervas Chinesas , Gentiana , Lignanas , Humanos , Gentiana/química , Lignanas/farmacologia , Glucosídeos/farmacologia , Glucosídeos/química , Medicamentos de Ervas Chinesas/farmacologia , Inflamação
15.
Environ Health Perspect ; 131(12): 127019, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38150316

RESUMO

BACKGROUND: Phthalates have been reported to impair fertility in various studies. However, evidence exploring the associations between phthalate metabolites in follicular fluid (FF) and reproductive outcomes is lacking. OBJECTIVES: To investigate the associations between phthalate metabolite concentrations in FF and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes among women recruited from a fertility clinic. METHODS: We included 641 women undergoing IVF/ICSI treatment from December 2018 to January 2020. The levels of eight phthalate metabolites, including monoethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), were quantified in FF collected on the oocyte retrieval day. Associations between quartiles of individual phthalate metabolite concentrations and nine IVF/ICSI outcomes, including oocyte yield, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth, were estimated with generalized linear models. The effects of phthalate mixtures on IVF/ICSI outcomes were assessed using Bayesian kernel machine regression (BKMR) models. RESULTS: After adjusting for relevant confounders, elevated quartiles of MBzP, MEHHP, and MEHP in FF were inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes (all p for trends <0.10). In comparison with the lowest quartile, the highest quartile of molar sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP) was associated with a reduction of 9.1% [95% confidence interval (CI): -17.1%, -0.37%] and 10.3% (95% CI: -18.8%, -0.94%) in yielded oocyte and mature oocyte numbers, respectively. Furthermore, the BKMR models revealed inverse associations between phthalate mixtures and the numbers of retrieved oocytes and mature oocytes. We generally found null results for implantation, clinical pregnancy, miscarriage, and live birth. DISCUSSION: Certain phthalate metabolites in FF are inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes among women undergoing IVF/ICSI treatment. https://doi.org/10.1289/EHP11998.


Assuntos
Aborto Espontâneo , Poluentes Ambientais , Ácidos Ftálicos , Gravidez , Humanos , Masculino , Feminino , Injeções de Esperma Intracitoplásmicas , Líquido Folicular/metabolismo , Teorema de Bayes , Sêmen/metabolismo , Fertilização in vitro , Ácidos Ftálicos/metabolismo , Exposição Ambiental
16.
Ecotoxicol Environ Saf ; 267: 115616, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37871386

RESUMO

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m2 (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes.


Assuntos
Citocinas , Fator de Necrose Tumoral alfa , Gravidez , Feminino , Humanos , Teorema de Bayes , Estudos Transversais , Líquido Folicular , Interleucina-6 , Fertilização in vitro
17.
ACS Synth Biol ; 12(10): 3008-3019, 2023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37728873

RESUMO

Fructose is an important monosaccharide product widely applied in the food, medicine, and chemical industries. Currently, fructose is mainly manufactured with plant biomass-sourced polysaccharides through multiple steps of digestion, conversion, separation, and purification. The development of cyanobacterial metabolic engineering provides an attractive alternative route for the one-step direct production of fructose utilizing carbon dioxide and solar energy. In this work, we developed a paradigm for engineering cyanobacterial chassis cells into efficient cell factories for the photosynthetic production of fructose. In a representative cyanobacterial strain, Synechococcus elongatus PCC 7942, knockout of fructokinase effectively activated the synthesis and secretion of fructose in hypersaline conditions, independent of any heterologous transporters. The native sucrose synthesis pathway was identified as playing a primary role in fructose synthesis. Through combinatory optimizations on the levels of metabolism, physiology, and cultivation, the fructose yield of the Synechococcus cell factories was stepwise improved to 3.9 g/L. Such a paradigm was also adopted to engineer another Synechococcus strain, the marine species Synechococcus sp. PCC 7002, and facilitated an even higher fructose yield of over 6 g/L. Finally, the fructose synthesized and secreted by the cyanobacterial photosynthetic cell factories was successfully extracted and prepared from the culture broth in the form of products with 86% purity through multistep separation-purification operations. This work demonstrated a paradigm for systematically engineering cyanobacteria for photosynthetic production of desired metabolites, and it also confirmed the feasibility and potential of cyanobacterial photosynthetic biomanufacturing as a simple and efficient route for fructose production.


Assuntos
Frutose , Synechococcus , Frutose/metabolismo , Synechococcus/genética , Synechococcus/metabolismo , Fotossíntese , Engenharia Metabólica , Metabolismo dos Carboidratos , Sacarose/metabolismo , Dióxido de Carbono/metabolismo
18.
JAMA Netw Open ; 6(9): e2335077, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37733342

RESUMO

Importance: Ritonavir-boosted nirmatrelvir and molnupiravir are currently used in the US and in other countries to treat nonhospitalized patients who have mild-to-moderate COVID-19 and who are at high risk for progression to severe disease. The associations of these 2 oral antiviral drugs with hospitalization and death resulting from infection with new SARS-CoV-2 Omicron subvariants, particularly BQ.1.1 and XBB.1.5, are unknown. Objective: To assess the association of nirmatrelvir or molnupiravir use with the risks of hospitalization and death among patients infected with new Omicron subvariants. Design, Setting, and Participants: This was a cohort study of patients who received a diagnosis of COVID-19 at Cleveland Clinic from April 1, 2022, to February 20, 2023 (during which the Omicron variant evolved from BA.2 to BA.4/BA.5, then to BQ.1/BQ.1.1, and finally to XBB/XBB.1.5) and who were at high risk of progressing to severe disease, with follow-up through 90 days after diagnosis. The final date for follow-up data collection was February 27, 2023. Exposures: Treatment with ritonavir-boosted nirmatrelvir or molnupiravir. Main Outcomes and Measures: The primary outcome was time to death. The secondary outcome was time to either hospitalization or death. The association of either nirmatrelvir or molnupiravir use with each outcome was measured by the hazard ratio (HR) adjusted for demographic factors, socioeconomic status, date of COVID-19 diagnosis, coexisting medical conditions, COVID-19 vaccination status, and previous SARS-CoV-2 infection. Results: There were 68 867 patients (29 386 [42.7%] aged ≥65 years; 26 755 [38.9%] male patients; 51 452 [74.7%] non-Hispanic White patients). Thirty of 22 594 patients treated with nirmatrelvir, 27 of 5311 patients treated with molnupiravir, and 588 of 40 962 patients who received no treatment died within 90 days of Omicron infection. The adjusted HRs of death were 0.16 (95% CI, 0.11-0.23) for nirmatrelvir and 0.23 (95% CI, 0.16-0.34) for molnupiravir. The adjusted HRs of hospitalization or death were 0.63 (95% CI, 0.59-0.68) for nirmatrelvir and 0.59 (95% CI, 0.53-0.66) for molnupiravir. The associations of both drugs with both outcomes were observed across subgroups defined by age, race and ethnicity, date of COVID-19 diagnosis, vaccination status, previous infection status, and coexisting conditions. Conclusions and Relevance: These findings suggest that the use of either nirmatrelvir or molnupiravir is associated with reductions in mortality and hospitalization in patients infected with Omicron, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions. Both drugs can, therefore, be used to treat nonhospitalized patients who are at high risk of progressing to severe COVID-19.


Assuntos
COVID-19 , Humanos , Masculino , Feminino , COVID-19/epidemiologia , Teste para COVID-19 , Vacinas contra COVID-19 , Estudos de Coortes , Ritonavir/uso terapêutico , SARS-CoV-2 , Tratamento Farmacológico da COVID-19
20.
World J Clin Cases ; 11(18): 4406-4411, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37449230

RESUMO

BACKGROUND: Primary prostate Burkitt's lymphoma is a rare and aggressive condition with a poor prognosis. Its clinical presentation can be challenging to differentiate from benign prostatic hyperplasia. Given the rarity of primary prostate Burkitt's lymphoma, its diagnosis and treatment remain unclear. CASE SUMMARY: This report presents a case of a 57-year-old male with primary prostate Burkitt's lymphoma, initially misdiagnosed as prostatic hyperplasia. This case's operative process, intraoperative findings and postoperative management are discussed in detail. CONCLUSION: Primary prostate lymphoma is difficult to distinguish from other prostate diseases. Holmium laser enucleation of the prostate (HoLEP), a minimally invasive procedure, is crucial in diagnosing and treating this rare disease. Clinicians should remain vigilant and thoroughly combine physical examination, imaging and test results when encountering patients of younger age with small prostate size but a rapid progression of lower urinary tract symptoms. HoLEP is an essential diagnostic and therapeutic tool in managing primary prostate Burkitt's lymphoma.

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