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1.
Proc Natl Acad Sci U S A ; 121(36): e2405543121, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39190349

RESUMO

Higher levels of aneuploidy, characterized by imbalanced chromosome numbers, are associated with lethal progression in prostate cancer. However, how aneuploidy contributes to prostate cancer aggressiveness remains poorly understood. In this study, we assessed in patients which genes on chromosome 8q, one of the most frequently gained chromosome arms in prostate tumors, were most strongly associated with long-term risk of cancer progression to metastases and death from prostate cancer (lethal disease) in 403 patients and found the strongest candidate was cohesin subunit gene, RAD21, with an odds ratio of 3.7 (95% CI 1.8, 7.6) comparing the highest vs. lowest tertiles of mRNA expression and adjusting for overall aneuploidy burden and Gleason score, both strong prognostic factors in primary prostate cancer. Studying prostate cancer driven by the TMPRSS2-ERG oncogenic fusion, found in about half of all prostate tumors, we found that increased RAD21 alleviated toxic oncogenic stress and DNA damage caused by oncogene expression. Data from both organoids and patients indicate that increased RAD21 thereby enables aggressive tumors to sustain tumor proliferation, and more broadly suggests one path through which tumors benefit from aneuploidy.


Assuntos
Aneuploidia , Carcinogênese , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Progressão da Doença , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Carcinogênese/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Cromossomos Humanos Par 8/genética , Regulação Neoplásica da Expressão Gênica , Dano ao DNA
2.
Am J Hum Genet ; 110(11): 1950-1958, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37883979

RESUMO

As large-scale genomic screening becomes increasingly prevalent, understanding the influence of actionable results on healthcare utilization is key to estimating the potential long-term clinical impact. The eMERGE network sequenced individuals for actionable genes in multiple genetic conditions and returned results to individuals, providers, and the electronic health record. Differences in recommended health services (laboratory, imaging, and procedural testing) delivered within 12 months of return were compared among individuals with pathogenic or likely pathogenic (P/LP) findings to matched individuals with negative findings before and after return of results. Of 16,218 adults, 477 unselected individuals were found to have a monogenic risk for arrhythmia (n = 95), breast cancer (n = 96), cardiomyopathy (n = 95), colorectal cancer (n = 105), or familial hypercholesterolemia (n = 86). Individuals with P/LP results more frequently received services after return (43.8%) compared to before return (25.6%) of results and compared to individuals with negative findings (24.9%; p < 0.0001). The annual cost of qualifying healthcare services increased from an average of $162 before return to $343 after return of results among the P/LP group (p < 0.0001); differences in the negative group were non-significant. The mean difference-in-differences was $149 (p < 0.0001), which describes the increased cost within the P/LP group corrected for cost changes in the negative group. When stratified by individual conditions, significant cost differences were observed for arrhythmia, breast cancer, and cardiomyopathy. In conclusion, less than half of individuals received billed health services after monogenic return, which modestly increased healthcare costs for payors in the year following return.


Assuntos
Neoplasias da Mama , Cardiomiopatias , Adulto , Humanos , Feminino , Estudos Prospectivos , Aceitação pelo Paciente de Cuidados de Saúde , Arritmias Cardíacas , Neoplasias da Mama/genética , Cardiomiopatias/genética
3.
Brief Bioinform ; 24(1)2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36549921

RESUMO

Cancer initiation and progression are likely caused by the dysregulation of biological pathways. Gene set analysis (GSA) could improve the signal-to-noise ratio and identify potential biological insights on the gene set level. However, platforms exploring cancer multi-omics data using GSA methods are lacking. In this study, we upgraded our GSCALite to GSCA (gene set cancer analysis, http://bioinfo.life.hust.edu.cn/GSCA) for cancer GSA at genomic, pharmacogenomic and immunogenomic levels. In this improved GSCA, we integrated expression, mutation, drug sensitivity and clinical data from four public data sources for 33 cancer types. We introduced useful features to GSCA, including associations between immune infiltration with gene expression and genomic variations, and associations between gene set expression/mutation and clinical outcomes. GSCA has four main functional modules for cancer GSA to explore, analyze and visualize expression, genomic variations, tumor immune infiltration, drug sensitivity and their associations with clinical outcomes. We used case studies of three gene sets: (i) seven cell cycle genes, (ii) tumor suppressor genes of PI3K pathway and (iii) oncogenes of PI3K pathway to prove the advantage of GSCA over single gene analysis. We found novel associations of gene set expression and mutation with clinical outcomes in different cancer types on gene set level, while on single gene analysis level, they are not significant associations. In conclusion, GSCA is a user-friendly web server and a useful resource for conducting hypothesis tests by using GSA methods at genomic, pharmacogenomic and immunogenomic levels.


Assuntos
Neoplasias , Farmacogenética , Humanos , Fosfatidilinositol 3-Quinases/genética , Genômica/métodos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Oncogenes
4.
Artigo em Inglês | MEDLINE | ID: mdl-38820122

RESUMO

RATIONALE: Quantitative interstitial abnormalities (QIA) are a computed tomography (CT) measure of early parenchymal lung disease associated with worse clinical outcomes including exercise capacity and symptoms. The presence of pulmonary vasculopathy in QIA and its role in the QIA-outcome relationship is unknown. OBJECTIVES: To quantify radiographic pulmonary vasculopathy in quantitative interstitial abnormalities (QIA) and determine if this vasculopathy mediates the QIA-outcome relationship. METHODS: Ever-smokers with QIA, outcome, and pulmonary vascular mediator data were identified from the COPDGene cohort. CT-based vascular mediators were: right ventricle-to-left ventricle ratio (RV/LV), pulmonary artery-to-aorta ratio (PA/Ao), and pre-acinar intraparenchymal arterial dilation (PA volume 5-20mm2 in cross-sectional area, normalized to total arterial volume). Outcomes were: six-minute walk distance (6MWD) and modified Medical Council Research Council (mMRC) Dyspnea score ≥2. Adjusted causal mediation analyses were used to determine if the pulmonary vasculature mediated the QIA effect on outcomes. Associations of pre-acinar arterial dilation with select plasma biomarkers of pulmonary vascular dysfunction were examined. MAIN RESULTS: Among 8,200 participants, QIA burden correlated positively with vascular damage measures including pre-acinar arterial dilation. Pre-acinar arterial dilation mediated 79.6% of the detrimental impact of QIA on 6MWD (56.2-100%, p<0.001). PA/Ao was a weak mediator and RV/LV was a suppressor. Similar results were observed in the QIA-mMRC relationship. Pre-acinar arterial dilation correlated with increased pulmonary vascular dysfunction biomarker levels including angiopoietin-2 and NT-proBNP. CONCLUSIONS: Parenchymal quantitative interstitial abnormalities (QIA) deleteriously impact outcomes primarily through pulmonary vasculopathy. Pre-acinar arterial dilation may be a novel marker of pulmonary vasculopathy in QIA.

5.
Eur Heart J ; 45(17): 1505-1511, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38551446

RESUMO

The sex disparity in outcomes of patients with cardiovascular disease is well-described and has persisted across recent decades. While there have been several proposed mechanisms to explain this disparity, there are limited data on female patient-physician sex concordance and its association with outcomes. The authors review the existing literature on the relationship between patient-physician sex concordance and clinical outcomes in patients with cardiovascular disease, the evidence of a benefit in clinical outcomes with female patient-physician sex concordance, and the possible drivers of such a benefit and highlight directions for future study.


Assuntos
Doenças Cardiovasculares , Relações Médico-Paciente , Humanos , Feminino , Masculino , Fatores Sexuais , Resultado do Tratamento
6.
J Infect Dis ; 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39436737

RESUMO

We assessed neutralizing antibody responses in a well-characterized cohort of 60 women with different Chlamydia trachomatis infection outcomes noted at a treatment visit and 3-month follow-up. We found varying rates of neutralization (inhibition of C. trachomatis) in sera at different dilution levels and varying neutralizing antibody titers across outcomes. Median neutralization rates were significantly higher in sera at high dilutions (1:320-1:1280) from women with spontaneous resolution versus persisting infection before treatment (all P< .05). These findings suggest that neutralizing antibody responses may contribute to protective immunity against chlamydia.

7.
J Infect Dis ; 230(1): 141-151, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39052725

RESUMO

BACKGROUND: The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. METHODS: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022 to March 2023 among adults (aged ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test positive by molecular assay) and controls (influenza test negative), applying inverse-propensity-to-be-vaccinated weights. RESULTS: The analysis included 85 389 ED/UC ARI encounters (17.0% influenza A positive; 37.8% vaccinated overall) and 19 751 hospitalizations (9.5% influenza A positive; 52.8% vaccinated overall). VE against influenza A-associated ED/UC encounters was 44% (95% confidence interval [CI], 40%-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza A-associated hospitalizations was 35% (95% CI, 27%-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively. CONCLUSIONS: VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.


Assuntos
Serviço Hospitalar de Emergência , Hospitalização , Vacinas contra Influenza , Influenza Humana , Eficácia de Vacinas , Humanos , Influenza Humana/prevenção & controle , Influenza Humana/epidemiologia , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Adulto , Masculino , Feminino , Estados Unidos/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Idoso , Adulto Jovem , Adolescente , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Assistência Ambulatorial/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Estações do Ano
8.
Semin Cancer Biol ; 95: 75-87, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37499847

RESUMO

Radiomics is the extraction of predefined mathematic features from medical images for predicting variables of clinical interest. Recent research has demonstrated that radiomics can be processed by artificial intelligence algorithms to reveal complex patterns and trends for diagnosis, and prediction of prognosis and response to treatment modalities in various types of cancer. Artificial intelligence tools can utilize radiological images to solve next-generation issues in clinical decision making. Bone tumors can be classified as primary and secondary (metastatic) tumors. Osteosarcoma, Ewing sarcoma, and chondrosarcoma are the dominating primary tumors of bone. The development of bone tumor model systems and relevant research, and the assessment of novel treatment methods are ongoing to improve clinical outcomes, notably for patients with metastases. Artificial intelligence and radiomics have been utilized in almost full spectrum of clinical care of bone tumors. Radiomics models have achieved excellent performance in the diagnosis and grading of bone tumors. Furthermore, the models enable to predict overall survival, metastases, and recurrence. Radiomics features have exhibited promise in assisting therapeutic planning and evaluation, especially neoadjuvant chemotherapy. This review provides an overview of the evolution and opportunities for artificial intelligence in imaging, with a focus on hand-crafted features and deep learning-based radiomics approaches. We summarize the current application of artificial intelligence-based radiomics both in primary and metastatic bone tumors, and discuss the limitations and future opportunities of artificial intelligence-based radiomics in this field. In the era of personalized medicine, our in-depth understanding of emerging artificial intelligence-based radiomics approaches will bring innovative solutions to bone tumors and achieve clinical application.


Assuntos
Inteligência Artificial , Neoplasias Ósseas , Humanos , Diagnóstico por Imagem , Prognóstico , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/terapia
9.
Clin Infect Dis ; 79(3): 604-611, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-38767234

RESUMO

BACKGROUND: We aimed to test the hypothesis that development of metastatic infection represents a distinct clinical endpoint from death due to Staphylococcus aureus bacteremia (SAB). METHODS: We conducted a retrospective observational study of adults with SAB between 20 December 2019 and 23 August st2022 (n = 464). Simple logistic regression, odds ratios, and z-scores were used to compare host, clinical, and microbiologic features. RESULTS: Co-occurrence of attributable mortality and metastatic infection was infrequent. Charlson Comorbidity Index and age were strongly associated with attributable mortality, but not metastatic infection. We compared patients with fatal SAB (without clinically-apparent metastatic complications, 14.4% of cohort), metastatic SAB (without attributable mortality, 22.2%), neither complication (56.7%), and overlapping fatal/metastatic SAB (6.7%). Compared to SAB without complications, fatal SAB was specifically associated with older age and multi-morbidity. Metastatic SAB was specifically associated with community acquisition, persistent fever, persistent bacteremia, and recurrence. Endocarditis was over-represented in the fatal/metastatic SAB overlap group, which shared patient characteristics with fatal SAB. In contrast to other (predominantly musculoskeletal) metastatic complications, endocarditis was associated with increased mortality, with death occurring in older multi-morbid patients later after SAB onset. CONCLUSIONS: Patients with SAB experience distinct clinical endpoints: (i) early death, associated with multi-morbidity and age; (ii) metastatic (predominantly musculoskeletal) SAB; (iii) endocarditis, associated with late death occurring in older people with multi-morbidity, and (iv) bacteraemia without complications. These distinctions could be important for selecting appropriate outcomes in clinical trials: different interventions might be required to reduce mortality versus improve clinical response in patients with metastatic SAB.


Assuntos
Bacteriemia , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/microbiologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Staphylococcus aureus/isolamento & purificação , Adulto , Idoso de 80 Anos ou mais
10.
Clin Gastroenterol Hepatol ; 22(3): 488-498.e14, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37775028

RESUMO

BACKGROUND & AIMS: The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted. METHODS: To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated. RESULTS: One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD. CONCLUSIONS: The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.


Assuntos
Diabetes Mellitus , Fígado Gorduroso , Síndrome Metabólica , Humanos , Fígado Gorduroso/complicações , Fígado Gorduroso/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Cardio-Oncologia
11.
Breast Cancer Res Treat ; 206(1): 67-76, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38568368

RESUMO

PURPOSE: We compared 21-gene recurrence score (RS) distribution and expression of the single-gene/gene groups within this assay between BC patients with pathogenic variants (PV) in BRCA1/2 vs the general 21-gene-tested BC population. METHODS: This retrospective study included consecutive 21-gene-tested female ER + HER2-negative BC patients with germline PVs in BRCA1/2. RS/gene expression data were compared to a previously described commercial use database (CDB, N = 799,986). Chi-square and 1-sample t test were used to compare RS distribution and single-gene/gene group scores between the study group and the CDB. RESULTS: Study group patients (N = 81) were younger and their RS results were higher compared to the CDB (age: median [IQR], 56 [47-61.5] vs 60 [51-67] years; p < 0.001; proportion of patients with RS ≥ 26: 49.4% vs 16.4%, p < 0.001). Expression of 12/16 cancer genes in the assay and the ER, proliferation, and invasion gene group scores differed significantly between the study group and the CDB, all in a direction contributing to higher RS. The differences between the study group and the CDB were mostly retained, upon stratifying the patients by menopausal status. CONCLUSION: BC patients with PVs in BRCA1/2 have higher RS results that stem from distinct gene expression profiles in the majority of genes in the 21-gene assay.


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Proteína BRCA2/genética , Proteína BRCA1/genética , Idoso , Estudos Retrospectivos , Biomarcadores Tumorais/genética , Mutação em Linhagem Germinativa , Mutação , Heterozigoto , Adulto , Predisposição Genética para Doença
12.
Breast Cancer Res Treat ; 208(1): 203-214, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38904892

RESUMO

PURPOSE: Patients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and limited treatment options. Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is approved for patients with mTNBC who have received ≥ 2 systemic therapies (≥ 1 in the metastatic setting) based on the ASCENT study (NCT02574455). The current study describes real-world SG use and outcomes in patients with mTNBC in the United States. METHODS: This retrospective, observational study included adult patients with mTNBC from the ConcertAI Patient360™ database who received SG in the second line (2L) and later from April 2020 to May 2022. SG use patterns, effectiveness, and tolerability are described. RESULTS: This analysis included 230 patients (median age 60 years, 26% Black, 17% with ECOG performance status ≥ 2, 66% in community settings; median of 2 prior lines of treatment in the metastatic setting); median follow-up was 7.2 months. Median (95% CI) real-world overall survival was 10.0 (8.3-11.1) months for all patients and 13.9 (9.8-not estimable) months in the 2L subgroup (n = 77). Granulocyte-colony stimulating factor (G-CSF) was administered concomitantly with SG in 134 (58%) patients; 35 (15%) received G-CSF for the first time. Median (IQR) time from SG start to G-CSF use was 8.5 (8.0-29.0) days. Seventeen (7%) patients discontinued SG due to toxicity. CONCLUSIONS: Using a real-world, ethnically diverse population of patients with mTNBC presenting with poor prognosis, these data reinforced the findings from ASCENT. In routine clinical practice, SG is an effective treatment in the 2L setting, consistent with treatment guidelines.


Assuntos
Anticorpos Monoclonais Humanizados , Camptotecina , Imunoconjugados , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/mortalidade , Pessoa de Meia-Idade , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Estudos Retrospectivos , Idoso , Estados Unidos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Camptotecina/efeitos adversos , Camptotecina/administração & dosagem , Imunoconjugados/uso terapêutico , Imunoconjugados/efeitos adversos , Imunoconjugados/administração & dosagem , Adulto , Metástase Neoplásica , Resultado do Tratamento , Idoso de 80 Anos ou mais
13.
BMC Med ; 22(1): 77, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378606

RESUMO

BACKGROUND: The coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) represents an uncommon serological pattern observed in patients with hepatitis B virus (HBV) infection, and its underlying mechanism and clinical significance have not been well established. The aim of this study was to investigate the association between this serological profile and clinical treatment outcomes in children with chronic hepatitis B (CHB). METHODS: This retrospective cohort study included 372 treatment-naïve CHB children from the Hunan Children's Hospital. The participants were categorized into HBsAb-positive group and HBsAb-negative group. The associations between HBsAb positive status to clinical outcomes were assessed using Cox proportional hazard regression. Receiver operating characteristic curve was conducted to evaluate the prediction ability in HBsAg loss. RESULTS: The coexistence of HBsAg and HBsAb accounted for 23.39% (87/372) of the participants. The crude incidence rates of HBsAg loss, hepatitis B e antigen (HBeAg) clearance, and HBV-DNA undetectability were higher in the HBsAb-positive group compared with the HBsAb-negative group (37.46 vs. 17.37, 49.51 vs. 28.66, 92.11 vs. 66.54 per 100 person-years, respectively, all P < 0.05). The Cox regression analysis revealed a significant association between this serological profile and an increased likelihood of HBsAg loss (HR = 1.78, P = 0.001), and HBeAg clearance (HR = 1.78, P = 0.001). In addition, a combination of HBsAb ≥ 0.84 log10 IU/L and age ≤ 5 years can help identify patients likely to achieve HBsAg loss after antiviral therapy, with an AUC of 0.71. CONCLUSIONS: Children who are positive for both HBsAg and HBsAb demonstrate a higher probability of favorable outcomes after antiviral treatment. Thus, children with HBsAb-positive CHB should be actively treated to achieve functional cure.


Assuntos
Antígenos de Superfície da Hepatite B , Hepatite B Crônica , Criança , Humanos , Pré-Escolar , Antígenos de Superfície da Hepatite B/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Antígenos E da Hepatite B/uso terapêutico , Estudos Retrospectivos , Vírus da Hepatite B , Resultado do Tratamento , Anticorpos Anti-Hepatite B/uso terapêutico , Antivirais/uso terapêutico
14.
J Urol ; : 101097JU0000000000004297, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39423101

RESUMO

PURPOSE: As the prevalence of Benign Prostatic Hyperplasia (BPH) increases, the demand for surgical interventions that optimize patient outcomes while minimizing complications grows. This systematic review compares the efficacy, efficiency, and safety of Holmium Laser Enucleation of the Prostate (HoLEP) with Robotic-Assisted Simple Prostatectomy (RASP), providing insights for evidence-based surgical decision-making in BPH treatment. MATERIALS AND METHODS: Adhering to PRISMA guidelines, the study protocol was registered with Prospero [CRD42024509627]. Searches were conducted in Medline, Embase, Web of Science, Scopus, and CINAHL up to February 1, 2024, to include studies that compare HoLEP and RASP in BPH patients. Risk of Bias was evaluated using the Newcastle Ottawa Scale. RESULTS: HoLEP and RASP demonstrated equivalent effectiveness in treating BPH, as shown by similar functional outcomes like maximum urinary flow rate and post-void residual volume. However, HoLEP outperformed RASP in several operational efficiency metrics, reducing operative time by 49.48 minutes, hospitalization duration by 1.5 days, and catheterization period by 3.8 days. HoLEP also significantly reduced the risk of blood transfusions by 75%. Patients undergoing RASP were 1.87 times more at risk for grade 2 complications and 3.41 times more at risk for developing grade 3 or above complications. CONCLUSIONS: HoLEP and RASP are effective for managing BPH. HoLEP shows advantages in recovery metrics and lower blood transfusion rates, while RASP benefits from ease of implementation in robotic-equipped facilities. Optimizing surgical outcomes will depend on reducing disparities in technique adoption, improving surgical training, and aligning with evidence-based guidelines.

15.
HIV Med ; 25(8): 897-909, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38443319

RESUMO

INTRODUCTION: Co-infection with HIV and mpox is a significant issue for public health because of the potential combined impact on clinical outcomes. However, the existing literature lacks a comprehensive synthesis of the available evidence. The purpose of this meta-analysis is to provide insight into the impact of HIV and mpox co-infection on clinical outcomes. METHODS: We systematically searched major electronic databases (PubMed, Embase, Cochrane Central, and Web of Science) for pertinent studies published up to June 2023. Included were studies that described the clinical outcomes of people who had both mpox and HIV. We performed the analysis using OpenMeta and STATA 17 software. RESULTS: With an overall number of participants of 35 207, 21 studies that met the inclusion criteria were considered. The greatest number of the studies (n = 10) were cohort designs, with three being cross-sectional and eight being case series studies. The meta-analysis found that people who had both HIV and mpox had a higher hospitalization rate than those who only had mpox (odds ratio [OR] 1.848; 95% confidence interval [CI] 0.918-3.719, p = 0.085, I2 = 60.19%, p = 0.020). Furthermore, co-infected patients had higher mortality rates than those who did not have HIV co-infection (OR 3.887; 95% CI 2.272-6.650, p < 0.001). Meta-regression analysis showed that CD4 levels can significantly predict the risk of hospitalization (p = 0.016) and death (p = 0.031). DISCUSSION: HIV causes immunosuppression, making it difficult for the body to mount an effective immune response against pathogens such as mpox. Individuals who are co-infected are at a higher risk of severe disease and death, according to our findings. Although hospitalization rates did not differ significantly between the two groups, it is critical to prioritize interventions and improve management strategies tailored specifically for people living with HIV. CONCLUSION: This meta-analysis provides substantial evidence that HIV and mpox co-infection has a negative impact on clinical outcomes. Co-infected individuals had higher hospitalization and significantly higher mortality rates. These findings highlight the significance of early diagnosis, prompt treatment initiation, and effective management strategies for people living with HIV and mpox.


Assuntos
Coinfecção , Infecções por HIV , Hospitalização , Humanos , Infecções por HIV/complicações , Hospitalização/estatística & dados numéricos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade
16.
Rheumatology (Oxford) ; 63(SI): SI72-SI85, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320586

RESUMO

aPLs are a major determinant of the increased cardiovascular risk in patients with SLE. They adversely affect clinical manifestations, damage accrual and prognosis. Apart from the antibodies included in the 2006 revised classification criteria for APS, other non-classical aPLs might help in identifying SLE patients at increased risk of thrombotic events. The best studied are IgA anti-ß2-glycoprotein I, anti-domain I ß2-glycoprotein I and aPS-PT. Major organ involvement includes kidney and neuropsychiatric systems. aPL/APS severely impacts pregnancy outcomes. Due to increased thrombotic risk, these patients require aggressive cardiovascular risk factor control. Primary prophylaxis is based on low-dose aspirin in high-risk patients. Warfarin is the gold-standard drug for secondary prophylaxis.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Trombose , Gravidez , Feminino , Humanos , Síndrome Antifosfolipídica/complicações , Anticorpos Antifosfolipídeos , Lúpus Eritematoso Sistêmico/complicações , beta 2-Glicoproteína I
17.
Ann Surg Oncol ; 31(5): 3249-3260, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38294612

RESUMO

BACKGROUND: Despite existing society guidelines, management of pancreatic (PanNEN) and small bowel (SBNEN) neuroendocrine neoplasms remains inconsistent. The purpose of this study was to identify patient- and/or disease-specific characteristics associated with increased odds of being offered surgery for PanNEN and SBNEN. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program database and the National Cancer Database (NCDB) were queried for patients with PanNEN/SBNEN. Demographic and pathologic data were compared between patients who were offered surgery and those who were not. Multivariate logistic regression was performed to identify factors independently associated with being offered surgery. RESULTS: In SEER, there were 3641 patients with PanNEN (54.7% were offered surgery) and 5720 with SBNEN (86.0% were offered surgery). On multivariate analysis of SEER, non-white race was associated with decreased odds of surgery offer for SBNEN [odds ratio (OR) 0.58, p < 0.001], but not PanNEN (p = 0.187). In NCDB, there were 28,483 patients with PanNEN (57.5% were offered surgery) and 42,675 with SBNEN (86.9% were offered surgery). On multivariate analysis of NCDB, non-white race was also associated with decreased odds of surgery offer for SBNEN (OR 0.61, p < 0.001) but not PanNEN (p = 0.414). CONCLUSIONS: This study's findings suggest that, in addition to previously reported disparities in surgical resection and surgery refusal rates, racial/ethnic disparities also exist earlier in the course of treatment, with non-white patients being less likely to be offered surgery for SBNEN but not for PanNEN; this is potentially due to discrepancies in rates of referral to academic centers for pancreas and small bowel malignancies.


Assuntos
Neoplasias Duodenais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/cirurgia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Programa de SEER , População Branca , Estados Unidos , Brancos
18.
Ann Surg Oncol ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277546

RESUMO

BACKGROUND: US News and World Report (USNWR) hospital rankings influence patient choice of hospital, but their association with surgical outcomes remains ill-defined. We sought to characterize clinical outcomes and costs of surgery for colon cancer among USNWR top ranked and unranked hospitals. METHODS: Using Medicare Standard Analytic Files, patients aged ≥65 years undergoing surgery for colon cancer were identified. Hospitals were categorized as 'ranked' or 'unranked' based on USNWR cancer hospital rankings. One-to-one matching was performed between patients treated at ranked and unranked hospitals, and clinical outcomes and costs of surgery were compared. RESULTS: Among 50 ranked and 2522 unranked hospitals, 13,650 patient pairs were compared. Overall, 30-day mortality was 2.13% in ranked hospitals versus 3.68% in unranked hospitals (p < 0.0001), and the overall paired cost difference was $8159 (p < 0.0001). As patient risk increased, 30-day mortality differences became larger, with the ranked hospitals having 30-day mortality of 7.59% versus 11.84% for unranked hospitals among the highest-risk patients (p < 0.0001). Overall paired cost differences also increased with increasing patient risk, with cost of care being $72,229 for ranked hospitals versus $56,512 for unranked hospitals among the highest-risk patients (difference = $14,394; p = 0.02). The difference in cost per 1% reduction in 30-day mortality was $9009 (95% confidence interval [CI] $6422-$11,597) for lowest-risk patients, which dropped to $3387 (95% CI $2656-$4119) for highest-risk patients (p < 0.0001). CONCLUSION: Treatment at USNWR-ranked hospitals, particularly for higher-risk patients, was associated with better outcomes but higher-cost care. The benefit of being treated at highly ranked USNWR hospitals was most pronounced among high-risk patients.

19.
Ann Surg Oncol ; 31(7): 4281-4297, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38480565

RESUMO

BACKGROUND: Radical esophagectomy for resectable esophageal cancer is a major surgical intervention, associated with considerable postoperative morbidity. The introduction of robotic surgical platforms in esophagectomy may enhance advantages of minimally invasive surgery enabled by laparoscopy and thoracoscopy, including reduced postoperative pain and pulmonary complications. This systematic review aims to assess the clinical and oncological benefits of robot-assisted esophagectomy. METHODS: A systematic literature search of the MEDLINE (PubMed), Embase and Cochrane databases was performed for studies published up to 1 August 2023. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols and was registered in the PROSPERO database (CRD42022370983). Clinical and oncological outcomes data were extracted following full-text review of eligible studies. RESULTS: A total of 113 studies (n = 14,701 patients, n = 2455 female) were included. The majority of the studies were retrospective in nature (n = 89, 79%), and cohort studies were the most common type of study design (n = 88, 79%). The median number of patients per study was 54. Sixty-three studies reported using a robotic surgical platform for both the abdominal and thoracic phases of the procedure. The weighted mean incidence of postoperative pneumonia was 11%, anastomotic leak 10%, total length of hospitalisation 15.2 days, and a resection margin clear of the tumour was achieved in 95% of cases. CONCLUSIONS: There are numerous reported advantages of robot-assisted surgery for resectable esophageal cancer. A correlation between procedural volume and improvements in outcomes with robotic esophagectomy has also been identified. Multicentre comparative clinical studies are essential to identify the true objective benefit on outcomes compared with conventional surgical approaches before robotic surgery is accepted as standard of practice.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Procedimentos Cirúrgicos Robóticos/métodos , Esofagectomia/métodos , Complicações Pós-Operatórias/etiologia , Prognóstico , Laparoscopia/métodos
20.
Ann Surg Oncol ; 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39414703

RESUMO

BACKGROUND: In the United States, hepatitis C virus-associated hepatocellular carcinoma incidence and mortality are highest among minorities. Socioeconomic constraints play a major role in inequitable treatment. We evaluated the association between race/ethnicity and outcomes in a population that overcame treatment barriers. METHODS: We report a retrospective cohort study of 666 patients across 20 institutions in the United States Hepatocellular Carcinoma Liver Transplantation Consortium from 2015 to 2019 with hepatitis C virus-associated hepatocellular carcinoma who completed direct-acting antiviral therapy and underwent liver transplantation. Patients were excluded if they had a prior liver transplantation, hepatocellular carcinoma recurrence, no prior liver-directed therapy, or if race/ethnicity data were unavailable. Patients were stratified by race/ethnicity. Primary outcomes were recurrence-free survival and overall survival, and secondary outcome was major postoperative complication. RESULTS: Race/ethnicity was not associated with differences in 5-year recurrence-free survival (White 90%, Black 88%, Hispanic 92%, Other 87%; p = 0.85), overall survival (White 85%, Black 84%, Hispanic 84%, Other 93%; p = 0.70), or major postoperative complication. CONCLUSIONS: Race/ethnicity was not associated with worse oncologic or postoperative outcomes among those who completed direct-acting antiviral therapy and underwent liver transplantation, suggesting that overcoming socioeconomic constraints equalizes outcomes across racial/ethnic groups. Eliminating barriers that prohibit care access among minorities must be a priority.

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