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1.
J Craniofac Surg ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563559

RESUMO

BACKGROUND: The sagittal fracture of the mandibular condyle can be fixed with absorbable long screws. Absorbable long screws are generally inserted from the lateral crest of the condyle and are as close as possible to the medial pole of the condyle to obtain sufficient retention force. However, in clinical practice, patients with locally comminuted condylar fractures and partial defects in the lateral crest are often encountered. We validated the use of absorbable plates and long screws to fix mandibular condylar fractures with lateral crest defects, and postoperative follow-up showed good results. METHODS: The preoperative design indicated that if conventional long screws were used, more soft tissue need to be pulled downward to achieve the appropriate drilling angle. If an absorbable plate was used, the degree of downward pulling of soft tissue was smaller, which can better protect the parotid gland tissue and facial nerve. The surgery was performed according to the preoperative design, using an absorbable plate scheme. RESULTS AND DISCUSSION: Postoperative CT confirmed a stable anatomical reduction of condyle. Four-month follow-up showed that the patient's facial shape, occlusion, and mouth opening were all good. Follow-up CT showed good fracture healing. It is feasible to use absorbable plates and long absorbable screws to fix mandibular condylar sagittal fracture accompanied by lateral condylar crest defect.

2.
J Craniofac Surg ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568848

RESUMO

The use of absorbable plates can be challenging for mandibular fractures involving bilateral dentition. Chewing and mouth opening movements may cause loosening or breakage of absorbable materials, leading to displacement of bone segments and resulting in malocclusion. The use of absorbable materials for bilateral mandibular fracture surgery itself raises concerns for surgeons. Timely intermaxillary elastic traction is essential for these patients after surgery to maintain correct occlusion. The surgical approaches were performed with intraoral mandibular sulcus incisions. During the surgery, intermaxillary fixation screws were implanted and steel wires were used for intermaxillary ligation and fixation to restore the occlusal. After the fractured segments were sequentially reduced, they were fixed with inion 2.0 absorbable plates. The patient underwent intermaxillary elastic traction for 1 week. Elastic mask was used to assist in stabilizing the position of the jawbone and maintaining occlusion. After discharge, the patient continued traction at home for 3 weeks before removing the intermaxillary fixation screws. The patient recovered well after surgery without any complications. The postoperative occlusal relationship is good. Postoperative CT showed good reduction of the fractured segments. For the case reported in this article, elastic traction was promptly implemented after surgery. We emphasize that restoring occlusion is always the treatment goal for jawbone fractures. We believe that keeping the intermaxillary fixation screws for a month is a wise choice to be prepared for unexpected needs.

3.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38557678

RESUMO

Disease ontologies facilitate the semantic organization and representation of domain-specific knowledge. In the case of prostate cancer (PCa), large volumes of research results and clinical data have been accumulated and needed to be standardized for sharing and translational researches. A formal representation of PCa-associated knowledge will be essential to the diverse data standardization, data sharing and the future knowledge graph extraction, deep phenotyping and explainable artificial intelligence developing. In this study, we constructed an updated PCa ontology (PCAO2) based on the ontology development life cycle. An online information retrieval system was designed to ensure the usability of the ontology. The PCAO2 with a subclass-based taxonomic hierarchy covers the major biomedical concepts for PCa-associated genotypic, phenotypic and lifestyle data. The current version of the PCAO2 contains 633 concepts organized under three biomedical viewpoints, namely, epidemiology, diagnosis and treatment. These concepts are enriched by the addition of definition, synonym, relationship and reference. For the precision diagnosis and treatment, the PCa-associated genes and lifestyles are integrated in the viewpoint of epidemiological aspects of PCa. PCAO2 provides a standardized and systematized semantic framework for studying large amounts of heterogeneous PCa data and knowledge, which can be further, edited and enriched by the scientific community. The PCAO2 is freely available at https://bioportal.bioontology.org/ontologies/PCAO, http://pcaontology.net/ and http://pcaontology.net/mobile/.


Assuntos
Ontologias Biológicas , Neoplasias da Próstata , Humanos , Masculino , Inteligência Artificial , Semântica , Neoplasias da Próstata/genética
4.
Comput Struct Biotechnol J ; 23: 1339-1347, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38585647

RESUMO

Over the past decade, information for precision disease medicine has accumulated in the form of textual data. To effectively utilize this expanding medical text, we proposed a multi-task learning-based framework based on hard parameter sharing for knowledge graph construction (MKG), and then used it to automatically extract gastric cancer (GC)-related biomedical knowledge from the literature and identify GC drug candidates. In MKG, we designed three separate modules, MT-BGIPN, MT-SGTF and MT-ScBERT, for entity recognition, entity normalization, and relation classification, respectively. To address the challenges posed by the long and irregular naming of medical entities, the MT-BGIPN utilized bidirectional gated recurrent unit and interactive pointer network techniques, significantly improving entity recognition accuracy to an average F1 value of 84.5% across datasets. In MT-SGTF, we employed the term frequency-inverse document frequency and the gated attention unit. These combine both semantic and characteristic features of entities, resulting in an average Hits@ 1 score of 94.5% across five datasets. The MT-ScBERT integrated cross-text, entity, and context features, yielding an average F1 value of 86.9% across 11 relation classification datasets. Based on the MKG, we then developed a specific knowledge graph for GC (MKG-GC), which encompasses a total of 9129 entities and 88,482 triplets. Lastly, the MKG-GC was used to predict potential GC drugs using a pre-trained language model called BioKGE-BERT and a drug-disease discriminant model based on CNN-BiLSTM. Remarkably, nine out of the top ten predicted drugs have been previously reported as effective for gastric cancer treatment. Finally, an online platform was created for exploration and visualization of MKG-GC at https://www.yanglab-mi.org.cn/MKG-GC/.

5.
Technol Cancer Res Treat ; 23: 15330338241246636, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38629205

RESUMO

OBJECTIVE: This study intends to examine the anticipatory power of clinical and radiological parameters in detecting clinically significant prostate cancer in patients demonstrating Prostate Imaging Reporting and Data System 3 lesions. METHODS: This was a retrospective study. The study included participation from 453 patients at the First Affiliated Hospital of Soochow University, sampled between September 2017 through August 2022. Each patient underwent a routine 12-core prostate biopsy followed by a 2 to 5 core fusion-targeted biopsy. We utilized both univariate and multivariate logistic regression analyses to identify the parameters that have a correlation with clinically significant prostate cancer. The predictive ability of these parameters was assessed using the receiver operating characteristic curve, leading to the creation of a nomogram. RESULTS: Clinically significant prostate cancer was detected in 68 out of 453 patients with Prostate Imaging Reporting and Data System 3 lesions (15.01%). Among Prostate Imaging Reporting and Data System 3a and 3b patients, 4.78% (3.09% of the total) and 33.75% (11.92% of the total), respectively, had clinically significant prostate cancer. Systematic biopsy improved prostate cancer and clinically significant prostate cancer detection rates by 7.72% and 3.09%, respectively, compared to targeted biopsy. Without systematic biopsy, there would be an undetected rate of 15% for prostate cancer and 8.13% for clinically significant prostate cancer in Prostate Imaging Reporting and Data System 3b patients. Several clinical parameters, including age, prostate-specific antigen density, lesion volume, apparent diffusion coefficient, and digital rectal examination, were statistically significant in the logistic regression analysis for clinically significant prostate cancer. The individual diagnostic accuracies of these parameters for clinically significant prostate cancer were 0.648, 0.645, 0.75, 0.763, and 0.7, respectively, but their combined accuracy improved to 0.866. A well-fit nomogram based on the identified risk factors was constructed (χ2 = 10.254, P = .248). CONCLUSION: The combination of age, prostate-specific antigen density, lesion volume, apparent diffusion coefficient, and digital rectal examination presented a higher diagnostic value for clinically significant prostate cancer than any single parameter in patients with Prostate Imaging Reporting and Data System 3 lesions. Systematic biopsy proved crucial for biopsy-naive patients with Prostate Imaging Reporting and Data System 3 lesions and should not be omitted.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodos
6.
bioRxiv ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38559049

RESUMO

The viral infection process covers a large range of spatiotemporal scales. Tracking the viral infection process with fluorescent labels over long durations while maintaining a fast sampling rate requires bright and highly photostable labels. StayGold is a recently identified green fluorescent protein that has a greater photostability and higher signal intensity under identical illumination conditions as compared to existing fluorescence protein variants. Here, StayGold protein fusions were used to generate virus-like particles (StayGold-VLPs) to achieve hour-long 3D single-virus tracking (SVT) with one thousand localizations per second (kHz sampling rate) in live cells. The expanded photon budget from StayGold protein fusions prolonged the tracking duration, facilitating a comprehensive study of viral trafficking dynamics with high temporal resolution over long timescales. The development of StayGold-VLPs presents a simple and general VLP labeling strategy for better performance in SVT, enabling exponentially more information to be collected from single trajectories and allowing for the future possibility of observing the whole life cycle of a single virus.

7.
Urol Oncol ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38600002

RESUMO

OBJECTIVE: Renal cell carcinoma (RCC) is a common malignant tumor with a high incidence in males and the elderly, and clear cell RCC (ccRCC) is the most common RCC subtype. ccRCC is highly metastatic with a poor prognosis. Therefore, it is crucial to obtain a detailed understanding of the molecular mechanism of ccRCC and to identify suitable biomarkers to realize early diagnosis and improve prognosis. METHODS: We analyzed data from the Cancer Genome Atlas, investigated the overall differential expression of CD276 in ccRCC, and evaluated the influence of CD276 on patient survival and prognosis. We also performed gene set enrichment analysis (GSEA) and pathway enrichment analysis and investigated cell infiltration and drug responsiveness to further assess the regulatory effect of CD276 on ccRCC. Furthermore, we verified CD276 expression in RCC cell lines and control cell lines. RESULTS: The CD276 expression level in ccRCC samples was higher than that in corresponding samples adjacent to the tumors. Moreover, high CD276 expression levels were positively correlated with poor prognosis in patients with RCC. GSEA revealed that CD276 was significantly involved in immune-related pathways, and the level of CD276 expression was confirmed as associated with immune cell infiltration to some extent. Notably, some drugs were predicted to act on CD276, and this was confirmed by molecular docking. Furthermore, high levels of CD276 expression in RCC cell lines were verified. CONCLUSION: CD276 expression was significantly increased in ccRCC tissues and cells and positively correlated with patient prognosis. CD276 is a potential prognostic biomarker of ccRCC. Overall, this study provides a potential therapeutic strategy for ccRCC.

8.
Int J Mol Sci ; 25(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38542235

RESUMO

Currently, several types of inhalable liposomes have been developed. Among them, liposomal pressurized metered-dose inhalers (pMDIs) have gained much attention due to their cost-effectiveness, patient compliance, and accurate dosages. However, the clinical application of liposomal pMDIs has been hindered by the low stability, i.e., the tendency of the aggregation of the liposome lipid bilayer in hydrophobic propellant medium and brittleness under high mechanical forces. Biomineralization is an evolutionary mechanism that organisms use to resist harsh external environments in nature, providing mechanical support and protection effects. Inspired by such a concept, this paper proposes a shell stabilization strategy (SSS) to solve the problem of the low stability of liposomal pMDIs. Depending on the shell material used, the SSS can be classified into biomineralization (biomineralized using calcium, silicon, manganese, titanium, gadolinium, etc.) biomineralization-like (composite with protein), and layer-by-layer (LbL) assembly (multiple shells structured with diverse materials). This work evaluated the potential of this strategy by reviewing studies on the formation of shells deposited on liposomes or similar structures. It also covered useful synthesis strategies and active molecules/functional groups for modification. We aimed to put forward new insights to promote the stability of liposomal pMDIs and shed some light on the clinical translation of relevant products.


Assuntos
Biomineralização , Lipossomos , Humanos , Inaladores Dosimetrados , Administração por Inalação
9.
Clin Transl Oncol ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38472559

RESUMO

OBJECTIVE: To clarify the composition of lesions in different magnetic resonance imaging (MRI) partitions of positive surgical margins (PSM) after laparoscopic radical prostatectomy, explore the influence of lesion location on PSM, and construct a clinical prediction model to predict the risk of PSM. MATERIALS AND METHODS: This retrospective cohort study included 309 patients who underwent laparoscopic radical prostatectomy from 2018 to 2021 in our center was performed. 129 patients who met the same criteria from January to September 2022 were external validation cohorts. RESULTS: The incidence of PSM in transition zone (TZ) lesions was higher than that in peripheral zone (PZ) lesions. The incidence of PSM in the middle PZ was lower than that in other regions. Prostate specific antigen (PSA), clinical T-stage, the number of positive cores, international society of urological pathology (ISUP) grade (biopsy), MRI lesion location, extracapsular extension, seminal vesicle invasion (SVI), pseudo-capsule invasion (PCI), long diameter of lesions, lesion volume, lesion volume ratio, PSA density were related to PSM. MRI lesion location and PCI were independent risk factors for PSM. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a clinical prediction model for PSM, including five variables: the number of positive cores, SVI, MRI lesion location, long diameter of lesions, and PSA. CONCLUSION: The positive rate of surgical margin in middle PZ was significantly lower than that in other regions, and MRI lesion location was an independent risk factor for PSM.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38527975

RESUMO

BACKGROUND: To examine the association of use of different antivirals with hospital acquired acute kidney injury (AKI) among Chinese adults with herpes zoster. METHODS: The study selected 3273 adult patients who received antiviral therapy for herpes zoster during hospitalization from the China Renal Data System (CRDS). We identified and staged AKI using patient-level serum creatinine data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We compared the relative risks of hospital acquired AKI among patients treated with different antivirals using Cox proportional hazards models. RESULTS: Among 3273 patients, 1480 (45%), 681 (21%), 489 (15%) and 623 (19%) were treated with acyclovir/valacyclovir, ganciclovir, penciclovir/famciclovir, and foscarnet, respectively. During the follow-up period, a total of 111 cases of hospital acquired AKI occurred, predominantly classified as AKI stage 1. The cumulative incidences of hospital acquired AKI were 5%, 3%, 3% and 1%, in the patients receiving acyclovir/valacyclovir, ganciclovir, penciclovir/famciclovir, and foscarnet, respectively. Compared with acyclovir/valacyclovir, penciclovir/famciclovir/ganciclovir and foscarnet were associated with a lower risk of hospital acquired AKI, with an adjusted hazard ratio [aHR] of 0.59 (95% CI, 0.37-0.94) and 0.27 (95% CI, 0.11-0.63), respectively. Compared with intravenous acyclovir, intravenous penciclovir/ganciclovir and foscarnet were associated with a lower risk of hospital acquired AKI with an aHR of 0.53 (95% CI, 0.29-0.98) and 0.31 (95% CI, 0.12-0.76), respectively. The associations were consistent across various subgroups and sensitivity analyses. CONCLUSIONS: Among antiviral therapies for herpes zoster, we found different risks of hospital acquired AKI among the patients receiving different antivirals, in particular, those administered intravenously. Among intravenous antivirals, acyclovir was associated with highest risk of hospital acquired AKI, followed by penciclovir/ganciclovir and foscarnet. Confirmation studies with large samples from other populations are warranted.

11.
J Transl Med ; 22(1): 253, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459561

RESUMO

Tobacco pollutants are prevalent in the environment, leading to inadvertent exposure of pregnant females. Studies of these pollutants' toxic effects on embryonic development have not fully elucidated the potential underlying mechanisms. Therefore, in this study, we aimed to investigate the developmental toxicity induced by cigarette smoke extract (CSE) at concentrations of 0.25, 1, and 2.5% using a zebrafish embryo toxicity test and integrated transcriptomic analysis of microRNA (miRNA) and messenger RNA (mRNA). The findings revealed that CSE caused developmental toxicity, including increased mortality and decreased incubation rate, in a dose-dependent manner. Moreover, CSE induced malformations and apoptosis, specifically in the head and heart of zebrafish larvae. We used mRNA and miRNA sequencing analyses to compare changes in the expression of genes and miRNAs in zebrafish larvae. The bioinformatics analysis indicates that the mechanism underlying CSE-induced developmental toxicity was associated with compromised genetic material damage repair, deregulated apoptosis, and disturbed lipid metabolism. The enrichment analysis and RT-qPCR show that the ctsba gene plays a crucial function in embryo developmental apoptosis, and the fads2 gene mainly regulates lipid metabolic toxicity. The results of this study improve the understanding of CSE-induced developmental toxicity in zebrafish embryos and contribute insights into the formulation of novel preventive strategies against tobacco pollutants during early embryonic development.


Assuntos
Poluentes Ambientais , MicroRNAs , Animais , Feminino , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Embrião não Mamífero/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Poluentes Ambientais/metabolismo , Poluentes Ambientais/farmacologia
12.
Front Endocrinol (Lausanne) ; 15: 1329247, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405137

RESUMO

Background: Organophosphate esters (OPEs) may interfere with thyroid function, but the relationship between OPEs and thyroid disease remains unclear. This study aims to elucidate the relationship between OPEs exposure and thyroid disease risk in the general population in the United States. Method: Data were obtained from the 2011-2014 National Health and Nutrition Examination Survey cycle. All participants were tested for seven OPE metabolites in their urine and answered questions about whether they had thyroid disease through questionnaires. Logistic regression was employed to analyze the association between exposure to individual OPE metabolites and thyroid disease. Weighted Quantile Sum (WQS) regression modeling was utilized to assess exposure to mixed OPE metabolites and risk of thyroid disease. Bayesian kernel machine regression(BKMR) models to analyze the overall mixed effect of OPE metabolites. Result: A total of 2,449 participants were included in the study, 228 of whom had a history of thyroid disease. Bis(1,3-dichloro-2-propyl) phos (BDCPP), Diphenyl phosphate (DPHP) and Bis(2-chloroethyl) phosphate (BCEP) were the top three metabolites with the highest detection rates of 91.75%, 90.77% and 86.57%, respectively. In multivariate logistic regression models, after adjustment for confounding variables, individuals with the highest tertile level of BCEP were significantly and positively associated with increased risk of thyroid disease (OR=1.57, 95% CI=1.04-2.36), using the lowest tertile level as reference. In the positive WQS regression model, after correcting for confounding variables, mixed exposure to OPE metabolites was significantly positively associated with increased risk of thyroid disease (OR=1.03, 95% CI=1.01-1.06), with BCEP and DPHP having high weights. In the BKMR model, the overall effect of mixed exposure to OPE metabolites was not statistically significant, but univariate exposure response trends showed that the risk of thyroid disease decreased and then increased as BCEP exposure levels increased. Conclusion: The study revealed a significant association between exposure to OPE metabolites and an increased risk of thyroid disease, with BCEP emerging as the primary contributor. The risk of thyroid disease exhibits a J-shaped pattern, whereby the risk initially decreases and subsequently increases with rising levels of BCEP exposure. Additional studies are required to validate the association between OPEs and thyroid diseases.


Assuntos
Retardadores de Chama , Doenças da Glândula Tireoide , Adulto , Humanos , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Teorema de Bayes , Organofosfatos/efeitos adversos , Organofosfatos/urina , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/epidemiologia , Fosfatos , Ésteres
14.
Environ Pollut ; 346: 123356, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38266696

RESUMO

Bisphenol F (BPF), one of the major alternatives of Bisphenol A (BPA), is becoming extensively used in industrial production with great harm to human beings and environment. Recent studies have revealed that environmental exposure is crucial to the initiation and development of depression. Thereby, the aim the present study is to ascertain the correlationship between the BPF exposure and depression occurrence. In the current study, BPF strikingly triggered depression-like changes in mice through the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST), accompanied by the perturbation of the kynurenine (KYN) metabolic pathway along the "liver-brain" axis. Mechanistically, the neurotransmitters from the tryptophan metabolic pathway were converted to the toxic KYN pathway after BPF treatment. With the ELISA assay, it revealed that the toxic KYN metabolites, including KYN and 3-hydroxykynurenine (3-HK), were strikingly increased in the mouse brains which was ascribed to the enhanced expression of the rate-limiting enzymes Indoleamine 2,3-dioxygenase (IDO1) and Kynurenine 3-monooxygenase (KMO) respectively. Interestingly, the increased brain KYN induced by BPF was also validated partially from the periphery, since the ELISA and western blotting results indicated the significantly increased KYN in the serum and L-type amino acid transporter 1 (LAT1) in the brain, the key transporter responsible for KYN and 3-HK crossing the blood-brain barrier. Intriguingly, the liver-derived KYN metabolic pathway was the important source of the peripheral KYN and 3-HK, as BPF substantially enhanced hepatic IDO1, Tryptophan, 2, 3-dioxygenase (TDO2), and KMO levels indicated by western blotting. This study is the first to delineate previously unrecognized BPF-induced depression by regulating the KYN metabolic pathway along the "liver-brain" axis; therefore, targeting LAT1 or hepatic KYN signaling may provide a potentially unique therapeutic intervention in BPF-induced depression.


Assuntos
Compostos Benzidrílicos , Cinurenina , Fenóis , Triptofano , Humanos , Camundongos , Animais , Cinurenina/metabolismo , Triptofano/metabolismo , Depressão/induzido quimicamente , Encéfalo/metabolismo , Fígado/metabolismo , Redes e Vias Metabólicas
15.
J Transl Med ; 22(1): 62, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38229160

RESUMO

Metastasis is the leading cause of high mortality in colorectal cancer (CRC), which is not only driven by changes occurring within the tumor cells, but is also influenced by the dynamic interaction between cancer cells and components in the tumor microenvironment (TME). Currently, the exploration of TME remodeling and its impact on CRC metastasis has attracted increasing attention owing to its potential to uncover novel therapeutic avenues. Noteworthy, emerging studies suggested that tumor-associated macrophages (TAMs) within the TME played important roles in CRC metastasis by secreting a variety of cytokines, chemokines, growth factors and proteases. Moreover, TAMs are often associated with poor prognosis and drug resistance, making them promising targets for CRC therapy. Given the prognostic and clinical value of TAMs, this review provides an updated overview on the origin, polarization and function of TAMs, and discusses the mechanisms by which TAMs promote the metastatic cascade of CRC. Potential TAM-targeting techniques for personalized theranostics of metastatic CRC are emphasized. Finally, future perspectives and challenges for translational applications of TAMs in CRC development and metastasis are proposed to help develop novel TAM-based strategies for CRC precision medicine and holistic healthcare.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Macrófagos/metabolismo , Neoplasias do Colo/patologia , Citocinas/metabolismo , Prognóstico , Microambiente Tumoral , Neoplasias Colorretais/patologia
16.
Eur J Prev Cardiol ; 31(3): 337-345, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966728

RESUMO

AIMS: This study aimed to evaluate the safety of the currently recommended target of LDL cholesterol (LDL-C) control on mortality in patients with atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: Using deidentified electronic health record data, we conducted a multicentre retrospective cohort study involving individuals with documented ASCVD who had received statin treatment for at least 3 months across China. The primary outcomes assessed encompassed all-cause mortality, CV mortality, and non-CV mortality. Relationships between post-treatment LDL-C concentrations and outcomes were evaluated using restricted cubic spline curves based on Cox proportional hazards regression analyses. Additionally, competitive risk models were employed to explore associations between LDL-C levels and cause-specific mortality. Among 33 968 participants, we identified nearly linear associations of post-treatment LDL-C level with all-cause mortality and CV mortality during a median follow-up of 47 months. Notably, patients who achieved the recommended target of LDL-C (<1.4 mmol/L) were at significantly lower risks of all-cause mortality [hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.69-0.86] and CV mortality (subdistribution HR, 0.68; 95% CI, 0.58-0.79), compared with those with LDL-C ≥ 3.4 mmol/L. This survival benefit was consistent in patients with different intensities of LDL-C reduction and other subgroup analyses. And no correlation was found between post-treatment LDL-C concentration and non-CV mortality. CONCLUSION: Our findings supported the safety of currently recommended target of LDL-C control and the 'lower is better' principle in patients with ASCVD.


Intensive control of LDL cholesterol (LDL-C) has been widely recommended for cardiovascular (CV) protection in patients with atherosclerotic CV disease. Nevertheless, a U-shaped association between LDL-C levels and all-cause mortality has been noted in several general population studies, prompting concerns regarding the safety of intensive lipid control. In this multicentre cohort comprising 33 968 patients at the highest CV risk, we found that patients with lower post-treatment LDL-C level were at lower risk of both all-cause and CV mortality, and this survival benefit was unaffected by intensity of LDL-C reduction, types of lipid-lowering agents, and other clinical characteristics.


Assuntos
Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , LDL-Colesterol , Doenças Cardiovasculares/diagnóstico , Fatores de Risco , Estudos Retrospectivos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
17.
Am J Nephrol ; 55(1): 25-36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37963441

RESUMO

INTRODUCTION: Rituximab has been proven effective and safe in pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). We aimed to analyze the efficacy and safety of rituximab in adult FR/SDNS patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). METHODS: A retrospective cohort study at three nephrology centers in China included adult FR/SDNS patients with biopsy-proven MCD or FSGS. Primary outcomes were relapse frequency and first relapse-free survival time. Adverse events were well recorded, and logistic regression analyses were used to investigate the risk factors of relapse. RESULTS: Eighty-one patients (age, 25.0 years; interquartile range, 20.0-40.5; 67% males; 82.7% MCD) received an average rituximab dose of 1,393.8 ± 618.7 mg/2 years during the 2-year follow-up period. The relapse frequency, calculated as the ratio of relapse times to follow-up years, significantly decreased after rituximab treatment (0.04 [0.00, 0.08] vs. 1.71 [1.00, 2.45], p < 0.001). The first relapse-free survival time was 16.7 ± 8.0 months. Fifty-seven patients (70.4%) achieved cessation of corticosteroids and immunosuppressants within 3 months after the first rituximab infusion. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Low serum albumin level before rituximab and high CD56+CD16+ natural killer cell count after rituximab were independent risk factors of relapse within 2 years after rituximab treatment. CONCLUSION: Rituximab was proven an effective and safe treatment option for adult FR/SDNS patients with MCD or FSGS in maintaining disease remission and minimizing corticosteroid exposure.


Assuntos
Glomerulosclerose Segmentar e Focal , Nefrose Lipoide , Síndrome Nefrótica , Masculino , Adulto , Humanos , Criança , Feminino , Rituximab/efeitos adversos , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Estudos Retrospectivos , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/induzido quimicamente , Nefrose Lipoide/tratamento farmacológico , Nefrose Lipoide/induzido quimicamente , Imunossupressores/efeitos adversos , Recidiva , Doença Crônica , Resultado do Tratamento
19.
Kidney Dis (Basel) ; 9(6): 517-528, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38089444

RESUMO

Introduction: Comprehensive data on the risk of hospital-acquired (HA) acute kidney injury (AKI) among adult users of opioid analgesics are lacking. This study aimed to systematically compare the risk of HA-AKI among the users of various opioid analgesics. Methods: This multicenter, retrospective real-world study analyzed 255,265 adult hospitalized patients who received at least one prescription of opioid analgesic during the first 30 days of hospitalization. The primary outcome was the time from the first opioid analgesic prescription to HA-AKI occurrence. 12 subtypes of opioid analgesics were analyzed, including 9 for treating moderate-to-severe pain and 3 for mild-to-moderate pain. We examined the association between the exposure to each subtype of opioid analgesic and the risk of HA-AKI using Cox proportional hazards models, using the most commonly used opioid analgesic as the reference group. Results: As compared to dezocine, the most commonly used opioid analgesic for treating moderate-to-severe pain, exposure to morphine, but not the other 7 types of opioid analgesics, was associated with a significantly increased risk of HA-AKI (adjusted hazard ratio: 1.56, 95% confidence interval: 1.40-1.78). The association was consistent in stratified analyses and in a propensity-matched cohort. There were no significant differences in the risk of HA-AKI among the opioid analgesic users with mild-to-moderate pain after adjusting for confounders. Conclusion: The use of morphine was associated with an increased risk of HA-AKI in adult patients with moderate-to-severe pain. Opioid analgesics other than morphine should be chosen preferentially in adult patients with high risk of HA-AKI when treating moderate-to-severe pain.

20.
Front Oncol ; 13: 1280208, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090483

RESUMO

Camrelizumab, a monoclonal antibody, blocks programmed cell death protein-1 from binding to T cells and programmed cell death ligand 1 on tumor cells, thereby ensuring sustained T cell activation and blocking immune escape of various types of cancer, including nasopharyngeal carcinoma. Reactive cutaneous capillary endothelial hyperplasia (RCCEP) is the most common immune-related adverse event in patients treated with camrelizumab. We report a case nasopharyngeal carcinoma in a patient with camrelizumab-induced RCCEP. A 68-year-old man diagnosed with nasopharyngeal carcinoma developed RCCEP at multiple locations after 3 months of camrelizumab treatment. RCCEP of the right lower eyelid affected closure of the right eye. In this report, we also reviewed previous literature on camrelizumab-induced RCCEP. In summary, the mechanism underlying camrelizumab-induced RCCEP remains unclear. RCCEP typically gradually subsides after discontinuing camrelizumab treatment. Larger nodules can be treated with lasers, ligation, or surgery. Although surgical excision is effective, RCCEP may recur in patients undergoing camrelizumab treatment. RCCEP management may not be required in the absence of adverse effects on the patient's daily life.

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