RESUMEN
Tree-type hydraulic fracturing (TTHF) is a new technology that can enhance the permeability of coal seams in a balanced manner and increase the coalbed methane production rate. However, the heterogeneity of coal seams is a major challenge in achieving balanced permeability enhancement by TTHF. Traditional methods based on digital image processing are difficult to apply in practice. To address these challenges, we proposed a 2D numerical model of coal seams based on the combined finite-discrete element method (FDEM). The elastic modulus of the coal seams obeys a Weibull distribution, and the coal heterogeneity was quantified by an index m. The effects on the fracture initiation pressure, the fracturing influence range, and displacements of TTHF were analyzed from four aspects, including the homogeneity index of coal, the arrangement angle of branch boreholes, the horizontal stress difference, and the injection rate of the fracturing fluid. The results show that TTHF has a significant effect on the balanced permeability enhancement in coal reservoirs, particularly with strong heterogeneity, and the best permeability enhancement for TTHF is achieved when the branch boreholes are arranged at 45°. The branch boreholes are prefabricated in advance to create a pressure relief area around the injection point, and the hydraulic fracture propagation is affected by the horizontal stress difference only when the fracturing influence range exceeds this area. When the horizontal stress difference increases from 0 to 4 MPa, its fracture initiation pressure increases from 8.93 to 10.86 MPa, with an increase of 21.61%. In addition, the initial stage of fluid injection was found to be crucial for achieving balanced permeability enhancement in TTHF, and a higher injection rate can expand the fracturing influence range. The numerical model has profound implications for the field application of TTHF technology.
RESUMEN
BACKGROUND AIMS: The Revised Electronic Causality Assessment Method (RECAM), a computerized update of the Roussel Uclaf Causality Assessment Methodology (RUCAM), was recently proposed. In this study, we validated and compared the utility of the RECAM and RUCAM in Chinese patients with a single conventional or herbal agent-induced liver injury. METHODS: In this retrospective multicenter cohort of well-established DILI and non-DILI patients from 5 centers in China, the diagnostic performance of the RUCAM and RECAM was compared by AUC analysis. The consistency was evaluated by weighted kappa. The major causes of discrepancy were explored. RESULTS: A total of 481 DILI and 100 non-DILI patients were included. In total, 62.6% of the DILI cases were induced by conventional agents, and 37.4% were induced by herbs. The RECAM had relatively higher AUC than RUCAM for overall [0.947 (0.926-0.964) vs. 0.867 (0.836-0.893), p=0.0016], conventional agents [0.923 (0.890-0.949) vs. 0.819 (0.775-0.858), p=0.0185], and herbs [0.972 (0.941-0.989) vs.0.911 (0.866-0.944), p=0.0199]. Latency, scores associated with hepatitis B, and hepatotoxicity information of the insulting drugs were the 3 main causes for the inconsistency between RECAM and RUCAM scores. CONCLUSIONS: The RECAM had relatively better diagnostic performance than RUCAM, with a higher AUC for Chinese DILI patients. Timely updates of the LiverTox category and refinement of serum markers to exclude hepatitis B activity would further improve the applicability of RECAM in areas where the use of herbs and resolution of past HBV infections are common.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatitis B , Humanos , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , China , ElectrónicaRESUMEN
BACKGROUND AND AIMS: Liver biopsy can provide critical information in patients with drug-induced liver injury (DILI). Our study aimed to compare the histopathological features of DILI at different time points from the onset to liver biopsy. METHODS: We conducted a single-centre retrospective observational study. The clinical and follow-up data were extracted, and the pathological slides were reviewed. RESULTS: 129 patients were included. The median age was 52 and 75% were women. They were divided into <1 month, 1-3 months, and >3 months groups according to the durations from onset of the disorder to liver biopsy. The aminotransferase, alkaline phosphatase, and bilirubin levels showed no significant differences at onset but significantly decreased with time among the three groups (all p<0.05) at the time of liver biopsy. Histological injury patterns were significantly different among the three groups (p<0.01). Hepatocellular, canalicular, and cholestasis of Kupffer cells were significantly less frequent in the >3 months group (p<0.01). For patients taking herbs, bridging necrosis and cholestatic injury were significantly more frequent in the <1 month group (p<0.01). Furthermore, ductopenia, cholate stasis, and foam-like cells were equally distributed in the three groups but were significantly associated with poor prognosis. CONCLUSIONS: Biopsy time significantly affects liver pathology: the earlier, the more acute cholestatic-hepatitic pattern, the later, the more chronic injury patterns. The prognostic features (ductopenia, cholate stasis, and foam-like cells) occurred equally in all three groups. Our study provides valuable information for liver pathologists aiding in their better interpretation of the liver biopsy from patients with DILI.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Colestasis , Humanos , Femenino , Persona de Mediana Edad , Masculino , Hígado/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Colestasis/patología , Biopsia , Colatos/efectos adversosRESUMEN
BACKGROUND: To clarify the associations between BMI and the incidences of all-cause death or liver-related death (LRD)/liver transplantation (LT) in drug-induced liver injury (DILI). METHODS: DILI patients from three hospitals were retrospectively retrieved and follow-up from 2009 to 2021. They were categorized into underweight (BMIâ <â 18.5â kg/m 2 ), normal weight (BMI of 18.5-23.9â kg/m 2 ), overweight (BMI of 24-27.9â kg/m 2 ) and obese (BMIâ ≥â 28â kg/m 2 ) groups. Cox regression models were conducted to reveal the effect of BMI on all-cause death or LRD/LT. RESULTS: A total of 1469 eligible DILI patients were included: underweight 73 (4.97%), normal weight 811 (55.21%), overweight 473 (32.20%) and obese 112 (7.62%). Eighty-nine patients (6.06%) had all-cause death, of which 66 patients (4.49%) had LRD/LT. The median age was 52 years old, and females were 1039 (70.73%). The associations between BMI and all-cause mortality ( nonlinear test Pâ <â 0.01) or liver-related mortality/LT ( nonlinear test P â =â 0.01) were J-shaped. Multivariate Cox regression analysis showed that underweight (HR: 3.02, 95% CI: 1.51-6.02) was significantly associated with all-cause mortality after adjusting for age and sex. Furthermore, obese males were significantly associated with liver-related mortality/LT (HR: 3.49, 95% CI: 1.13-10.72) after additional adjustment for serological indices and comorbidities. CONCLUSION: Association between BMI and mortality is a J-shape. The overall mortality was significantly higher in underweight and obese group. Male obesity is independently associated with LRD/LT. These findings indicate that DILI patients with extreme BMI would have a high risk of dismal outcomes, which warrants extra medical care.
Asunto(s)
Sobrepeso , Delgadez , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Estudios Retrospectivos , Índice de Masa Corporal , Delgadez/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Factores de RiesgoRESUMEN
The induction of type-I interferons (IFN-Is) is important for the efficacy of chemotherapy. By investigating the role of amino acids in regulation of IFN-I production under chemo-drug treatment in bladder cancer (BC) cells, we find an inherent AhR-dependent negative feedback to restrain STING signaling and IFN-I production. Mechanistically, in a ligand dependent manner, AhR bridges STING and CUL4B/RBX1 E3 ligase complex, facilitating STING degradation through ubiquitin-proteasome pathway. Inhibition of AhR increases STING levels and reduces tumor growth under cisplatin or STING agonist treatment. Endogenous AhR ligands are mainly consisted of tryptophan (Trp) metabolites; dietary Trp restriction, blocking the key Trp metabolism rate-limiting enzyme IDO1 or inhibition of cellular Trp importation also show similar effect as AhR inhibition. Clinically, BC patients with higher intratumoral expression of AhR or stronger intratumoral Trp metabolism (higher IDO1 or Kyn levels) that lead to higher AhR activation show worse response rate to neoadjuvant chemotherapy (NAC).
Asunto(s)
Interferón Tipo I , Neoplasias de la Vejiga Urinaria , Humanos , Cisplatino , Vejiga Urinaria , Aminoácidos , Proteínas CullinRESUMEN
Dysregulation of transcription is a hallmark of cancer, including bladder cancer (BLCA). CRISPR-Cas9 screening using a lentivirus library with single guide RNAs (sgRNAs) targeting human transcription factors and chromatin modifiers is used to reveal genes critical for the proliferation and survival of BLCA cells. As a result, the nuclear transcription factor Y subunit gamma (NFYC)-37, but not NFYC-50, is observed to promote cell proliferation and tumor growth in BLCA. Mechanistically, NFYC-37 interacts with CBP and SREBP2 to activate mevalonate pathway transcription, promoting cholesterol biosynthesis. However, NFYC-50 recruits more of the arginine methyltransferase CARM1 than NFYC-37 to methylate CBP, which prevents the CBP-SREBP2 interaction and subsequently inhibits the mevalonate pathway. Importantly, statins targeting the mevalonate pathway can suppress NFYC-37-induced cell proliferation and tumor growth, indicating the need for conducting a clinical trial with statins for treating patients with BLCA and high NFYC-37 levels, as most patients with BLCA have high NFYC-37 levels.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Neoplasias de la Vejiga Urinaria , Humanos , Ácido Mevalónico/metabolismo , ARN Guía de Sistemas CRISPR-Cas , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Several models have been proposed to predict acute liver failure/death in patients with drug-induced liver injury (DILI), but the predictive performances of them have not been systematically compared. We aim to compare the current models for their predictive potency of mortality at DILI onset. METHODS: DILI patients hospitalized at both Beijing Friendship Hospital and the Fifth Medical Center of PLA General Hospital were categorized into death/liver transplantation (LT) or survival without LT group. Predictive potency of 28-day, 90-day, 6-month and 12-month death/LT outcomes of Hy's Law, nHy's Law, Robles-Diaz Model, drug-induced liver toxicity (DrILTox ALF) Score, Model for End-stage Liver Disease (MELD) Score, and Ghabril Model was compared by Delong method. RESULTS: A total of 6.3% (83/1314) patients died or received LT within 12 months after DILI onset. The area under receiver operating characteristic of Hy's Law, nHy's Law, and Robles-Diaz Model was all lower than 0.750 for the prediction of within 12 months' mortality. DrILTox ALF Score, MELD Score and Ghabril Model showed better predictive potency of 28-day [0.896 (0.878-0.912), 0.934 (0.919-0.947), 0.935 (0.921-0.948), respectively], 90-day [0.883 (0.864-0.899), 0.951 (0.938-0.962), 0.952 (0.939-0.963), respectively], 6-month [0.820 (0.799-0.841), 0.905 (0.888-0.921) and 0.908 (0.891-0.923), respectively] and 12-month [0.801 (0.779-0.823), 0.882 (0.863-0.899) and 0.885 (0.866-0.902), respectively] mortality. CONCLUSION: Despite the difference of clinical characteristics and implicated-drug categories between China and industrialized countries, we demonstrate that MELD Score and Ghabril Model have the best predictive performance in the prediction of mortality within 12 months after DILI onset.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Enfermedad Hepática en Estado Terminal , Fallo Hepático Agudo , Humanos , Pronóstico , Índice de Severidad de la Enfermedad , Fallo Hepático Agudo/inducido químicamenteRESUMEN
Cancer-associated fibroblasts (CAFs) play a role in response to cancer treatment and patient prognosis. CAFs show phenotypic and functional heterogeneity and differ widely in tumors of different tissue origin. Here, we use single-cell RNA sequencing of bladder cancer (BC) patient samples and report a CAF subpopulation characterized by overexpression of the urea transporter SLC14A1. This population is induced by interferon signaling and confers stemness to BC cells via the WNT5A paracrine pathway. Activation of cGAS-STING signaling in tumor cells drives interferon production, thereby revealing a link between cGAS-STING signaling and SLC14A1+ CAF differentiation. Furthermore, the inhibition of SLC14A1+ CAF formation via targeting of STAT1 or STING sensitizes tumor cells to chemotherapy. More important, BC patients with high proportions of intratumoral SLC14A1+ CAFs show cancer stage-independent poor outcome and a worse response rate to neoadjuvant chemotherapy or immunotherapy.
Asunto(s)
Fibroblastos Asociados al Cáncer , Células Madre Neoplásicas , Neoplasias de la Vejiga Urinaria , Proteína Wnt-5a , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos , Interferones , Nucleotidiltransferasas/metabolismo , Pronóstico , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/patología , Proteína Wnt-5a/genética , Proteína Wnt-5a/metabolismoRESUMEN
INTRODUCTION: Bladder cancer (BC) is one of the most common malignant cancers, with poor prognosis and high incidence. Cisplatin is the standard chemotherapy for muscle invasive bladder cancer; however, chemotherapy resistance remains a major challenge. Moreover, oncogenic signalling and the specific mechanisms underlying cisplatin resistance in BC remain largely unclear METHODS: In this study, RT-PCR, Western blot, immunofluorescence, and immunohistochemistry were used to measure gene and protein expression. Colony formation assay and flow cytometry were performed to evaluate the proliferation of BC cells. Gene set enrichment analysis was performed to identify the function in which ZBTB11 was involved. Luciferase and chromatin immunoprecipitation experiments were performed to determine the transcriptional regulation mechanism of ZBTB11. The effects of ZBTB11 on the malignant phenotypes of BC cells were examined in vitro and in vivo RESULTS: The results showed that ZBTB11 was remarkably upregulated in BC tissues, which was associated with poor prognosis in patients with BC. Furthermore, we found that knockdown of ZBTB11 remarkably inhibited the proliferation and tumorigenesis of BC cells by inducing apoptosis. Mechanistically, the knockdown of ZBTB11 transcriptionally inhibited DDX1 to suppress R-loop clearance, resulting in DNA damage in BC cells. Importantly, the ZBTB11/DDX1 axis is required for the chemotherapy resistance of BC cells to cisplatin CONCLUSION: Our findings not only reveal an underlying mechanism by which the ZBTB11/DDX1 axis promotes the tumorigenesis of BC but also provide a potential target for a combination strategy of cisplatin-based chemotherapy for BC.
Asunto(s)
MicroARNs , Neoplasias de la Vejiga Urinaria , Humanos , Cisplatino/farmacología , Cisplatino/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Estructuras R-Loop , Línea Celular Tumoral , Carcinogénesis/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Proliferación Celular/genética , ARN Helicasas DEAD-box/metabolismoRESUMEN
Aims: To develop, optimize, and validate a novel model using alanine aminotransferase (ALT) and total bilirubin (TB) dynamic evolution patterns in predicting acute liver failure (ALF) in drug-induced liver injury (DILI) patients. Methods: The demographics, clinical data, liver biopsy, and outcomes of DILI patients were collected from two hospitals. According to the dynamic evolution of ALT and TB after DILI onset, the enrolled patients were divided into ALT-mono-peak, TB-mono-peak, double-overlap-peak, and double-separate-peak (DSP) patterns and compared. Logistic regression was used to develop this predictive model in both discovery and validation cohorts. Results: The proportion of ALF was significantly higher in patients with the DSP pattern than in the ALT-mono-peak pattern and DOP pattern (10.0 vs. 0.0% vs. 1.8%,p < 0.05). The area under receiver operating characteristic curve (AUROC) of the DSP pattern model was 0.720 (95% CI: 0.682-0.756) in the discovery cohort and 0.828 (95% CI: 0.788-0.864) in the validation cohort in predicting ALF, being further improved by combining with international normalized ratio (INR) and alkaline phosphatase (ALP) (AUROC in the discovery cohort: 0.899; validation cohort: 0.958). Histopathologically, patients with the DSP pattern exhibited a predominantly cholestatic hepatitis pattern (75.0%, p < 0.05) with a higher degree of necrosis (29.2%, p = 0.084). Conclusion: DILI patients with the DSP pattern are more likely to progress to ALF. The predictive potency of the model for ALF can be improved by incorporating INR and ALP. This novel model allows for better identification of high-risk DILI patients, enabling timely measures to be instituted for better outcome.
RESUMEN
This study aimed to understand the suicidal ideation and suicidal attempts among cancer patients during the COVID-19 pandemic. The data were collected from patients diagnosed with cancer while attending the largest cancer center in the south of China. A structured questionnaire was used to investigate patients' demographic data, suicidal behavior, and factors related to COVID-19. Mental health conditions were measured by the Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, and the Brief Symptom Inventory. Comorbidities and medical conditions of cancer patients were extracted from the electronic healthcare records. Among the 5670 cancer patients, 755 (13.3%) reported suicidal ideation, and 266 (4.7%) reported suicidal attempts during the COVID-19 pandemic. The age group with the highest risk of suicidal ideation was 20-24 years (23.9%). Lifetime history of suffering from mental disorders, longer time since cancer diagnosis, regional and distant tumor stage, depression, anxiety, hostility, having a higher frequency of worrying about cancer management due to COVID-19, higher frequency feeling of overwhelming psychological pressure due to COVID-19, having a higher level of barriers to manage cancer due to COVID-19, and higher barriers to continue treatment of cancer due to inconveniences caused by COVID-19, were all significantly associated with increased risk of suicidal ideation. We also identified the risk factors of suicide attempts. This is the first study investigating the prevalence and risk factors associated with suicidal ideation and suicidal attempts in Chinese cancer patients during the COVID-19 pandemic. Our findings suggest that it is essential to monitor the mental health conditions of this vulnerable population, especially for cancer patients who have comorbidity with a history of mental disorders. Also, government policymakers should take action to protect cancer patients to avoid any interruption of their continued treatment. Further efforts are urgently required to develop specific psychological interventions to reduce the risk factors among cancer patients during the COVID-19 pandemic.
Asunto(s)
COVID-19 , Neoplasias , Adulto , COVID-19/epidemiología , Humanos , Neoplasias/complicaciones , Neoplasias/epidemiología , Pandemias , Factores de Riesgo , Ideación Suicida , Intento de Suicidio/psicología , Adulto JovenRESUMEN
BACKGROUND: This study verified and assessed 26 biochemical indicators tested by a dry chemistry analyzer using the hemolytic index test function to determine the degree of interference and the trends among the hemolysis samples on the test results. This study also sought to ensure that reasonable test reports could be issued taking into account practical clinical needs. METHODS: The samples were manually divided into the control group and the test group. The hemolytic index and biochemical indicators of the samples were tested using the Ortho Vitros 5600 to compare the deviation of the test results between the 2 groups. The judgment standard was set as 1/3 of the total error allowable as required by the quality assessment criterion of the National Center for Clinical Laboratories. The interference degree of hemolysis on the dry chemistry-based biochemical indicators was assessed, and the hemolytic thresholds of 26 biochemical indicators provided by the manufacturer were verified in terms of their validity and rationality. RESULTS: The hemolytic thresholds of 26 dry chemistry-based biochemical indicators were verified to analyze the degree of interference. The results revealed that hemolysis interfered with 17 indicators. Hemolysis positively interfered with the test results of phosphorus, creatine kinase, gamma glutamyl transpeptidase (γ-GGT), magnesium, iron, total protein, potassium, total bilirubin, lactate dehydrogenase, albumin, and aspartate aminotransferase, but negatively interfered with cholinesterase, direct high-density lipoprotein cholesterol, glucose, elevated carbon dioxide alkaline phosphatase, and alanine aminotransferase. A negative deviation of γ-GGT by hemoglobin was described in the manufacturer's statement, but our test data showed a positive deviation by hemolysis. The hemolytic threshold verification results of the other biochemical indicators were consistent with the manufacturer's statement. CONCLUSIONS: The hemolytic index test function was used to determine which samples were interfered with by hemolysis to make an analytical judgment according to the hemolytic interference thresholds of the different test items, verify the validity of the hemolytic thresholds of the test items, perform reasonable tests on the hemolytic samples, and issue valid reports to reduce the rejection rate of the hemolytic samples, shorten the turnaround time (TAT) of laboratories.
Asunto(s)
Hemoglobinas , Hemólisis , Aspartato Aminotransferasas , Bilirrubina , Humanos , L-Lactato DeshidrogenasaRESUMEN
Background: Despite rapid advances in the treatment of prostate cancer (PCa), the optimal treatment for elderly patients with PCa remains unclear due to a lack of high-quality evidence. This study aimed to evaluate whether surgical procedures are beneficial for PCa patients aged 75 years and older and compare the effects of focal ablation and prostatectomy. Methods: Male patients aged 75 years and older who were diagnosed with Tis-T2/N0/M0 PCa between 2000 and 2017 were retrospectively identified from the Surveillance, Epidemiology, and End Results program database. Cox regression models were used to test for statistical differences between the overall survival (OS) and disease-specific survival (DSS). Results: A total of 114,506 patients aged 75 years and older with PCa were included in this study, among which 60,131 died during the study period. The most prevalent surgical procedure for these patients was focal ablation. The local excision rate increased with advancing age, while the prostatectomy rate decreased sharply with age. The proportion of the elderly patients who underwent a focal ablation also increased with the age at diagnosis. The survival rate of patients aged 75 years and older who underwent a focal ablation was significantly worse than that for those who did not undergo any surgical procedures (OS: HR, 1.32, P<0.001; DSS: HR, 1.58, P<0.001). Although only a few of the patients underwent prostatectomy, the procedure was still related to improved OS and DSS (OS: HR, 0.60, P< 0.001; DSS: HR, 0.37, P<0.001) rates. Conclusions: Focal ablation has gradually replaced prostatectomy as the most common surgical procedure for elderly patients with PCa in the United States. However, our results revealed that the procedure might not provide benefits for elderly patients with PCa; instead, we found that focal ablation resulted in increased negative effects on patient prognoses. Elderly patients should have the same opportunity to be treated with standard surgical interventions as younger patients.
RESUMEN
The current study aimed to explore mental health problems in patients diagnosed with cancer during the COVID-19 pandemic. A cluster sampling, cross-sectional survey with 6213 cancer patients was conducted in one of the largest cancer centers in China. The socio-demographic and clinical characteristics, psychosomatic conditions, interpersonal relationships and social support, COVID-19 infection-related psychological stress, and mental health status were measured. Medical conditions were extracted from patients' electronic healthcare records. Among the 6213 cancer patients, 23.4% had depression, 17.7% had anxiety, 9.3% had PTSD, and 13.5% had hostility. Hierarchical liner regression models showed that having a history of mental disorder, excessive alcohol consumption, having a higher frequency of worrying about cancer management due to COVID-19, having a higher frequency feeling of overwhelming psychological pressure from COVID-19, and having a higher level of fatigue and pain were the predominant risk factors for mental health problems in cancer patients. However, there were only 1.6% of them were seeking psychological counseling during COVID-19. We also revealed the protective factors associated with lower risk of mental health problems among cancer patients. The present study revealed a high prevalence of mental health problems and gaps in mental health services for cancer patients, which also indicated high distress from COVID-19-elevated risks. We call for systematic screening of mental health status for all cancer patients, and developing specific psychological interventions for this vulnerable population.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/psicología , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Neoplasias/epidemiología , Neoplasias/psicología , Neumonía Viral/psicología , COVID-19 , China/epidemiología , Análisis por Conglomerados , Comorbilidad , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Prevalencia , Factores de Riesgo , SARS-CoV-2 , Apoyo Social , Estrés Psicológico/epidemiología , Estrés Psicológico/psicologíaRESUMEN
PURPOSE: To indirectly compare the efficacy and safety of systemic therapies used for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). METHODS: The relevant randomized controlled trials were retrieved from PubMed and the Cochrane Library. Network meta-analyses were used to compare multiple drugs simultaneously for the outcomes of nmCRPC. Direct evidence in trials and indirect evidence across trials were combined by the network meta-analyses to estimate the treatment efficiency. OUTCOME: Eight studies were included in our research. For prostate-specific antigen progression-free survival, the rate of progression was significantly decreased following apalutamide, enzalutamide, bicalutamide+dutasteride, and bicalutamide treatment compared with placebo. Compared with placebo treatment, metastases-free survival was significantly increased in patients who received apalutamide (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.23-0.35), enzalutamide (HR: 0.29, 95% CI: 0.24-0.35), and darolutamide (HR: 0.42, 95% CI: 0.35-0.50). Direct comparison showed significant survival benefits in patients who received second-generation anti-androgen therapy (apalutamide, enzalutamide, and darolutamide: HR: 0.74, 95% CI: 0.61-0.91) compared with patients who received placebo. With respect to metastases-free survival, based on SUCRA analysis, there was 80% and 78% probability that apalutamide and enzalutamide were preferred treatment, while darolutamide was likely to be second-best choice. Compared with placebo, all agents were not associated with significantly higher likelihood of serious adverse events and grade 3 to 4 adverse events. CONCLUSION: Our outcomes support equivalent efficacy and similar risk of adverse effects between apalutamide, enzalutamide, and darolutamide, supporting the use of these antiandrogen agents in high-risk of progression nmCRPC.
Asunto(s)
Metaanálisis en Red , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
To investigate the relationship between cervical and thoracic sagittal alignment parameters measured by magnetic resonance imaging (MRI) and x-ray in patients with cervical spondylosisData from 120 symptomatic patients who presented with cervical spondylosis between April 2015 and January 2016 were retrospectively analyzed. Patients received both a cervical MRI and a cervical radiograph during a single visit. The thoracic inlet angle (TIA), T1 slope (T1S), neck tilt (NT), C2-C7 angle (C2-C7), and C2-C7 sagittal vertical axis (C2-7 SVA) were assessed. Pearson correlation coefficient, paired t test, and linear regression models were used to analyze parameters obtained by cervical MRI and radiography.The difference in mean thoracic inlet angle x-ray (TIAX) and thoracic inlet angle MRI (TIAM) (TIAM-TIAX) (0.72 ± 5.82°) was not significant (Pâ>â.05). There were significant differences in mean T1 slope x-ray (T1SX) and T1 slope MRI (T1SM) (T1SM-T1SX) (-2.55â±â6.14°), mean neck tilt x-ray (NTX) and neck tilt MRI (NTM) (NTM-NTX) (3.26â±â6.01°), mean C2-C7 angle x-ray (C2-7X) and C2-C7 angle MRI (C2-7âM) (C2-7M-C2-7X) (-3.57â±â10.00°), and mean C2-C7 sagittal vertical axis X ray (C2-7 SVAX) and C2-C7 sagittal vertical axis MRI (C2-7 SVAM) (C2-7 SVAM-C2-7 SVAX) (-4.50â±â1.26âmm) (all Pâ≤â.001). There were positive correlations between TIAM and TIAX (râ=â0.807), T1SM and T1SX (râ=â0.581), NTM and NTX (râ=â0.759), cervical loidosis MRI and cervical loidosis x-ray (râ=â0.666), and SVAM and SVAX (râ=â0.226).MRI may be useful to evaluate thoracic inlet and sagittal alignment parameters in patients with cervical spondylosis. Patients with cervical spondylosis may have a relatively low capacity for compensation in the cervical region.
Asunto(s)
Vértebras Cervicales/patología , Espondilosis/patología , Vértebras Torácicas/patología , Vértebras Cervicales/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Espondilosis/diagnóstico por imagen , Vértebras Torácicas/diagnóstico por imagenRESUMEN
The study aims to investigate the effects of aging on the cervical spine.Outpatients in the study were grouped by age. The cervical spine image in the sagittal plane from participants in the supine position was acquired with MRI. Thoracic inlet angle (TIA), T1 slope (T1S), neck tilt (NT), and cervical angle (CC2-7) were measured.NT and TIA measured 41.84â±â9.26 and 64.15â±â10.72 in participants younger than 40, and 53.02â±â9.52 and 72.09â±â10.49 in participants older than 40 (Pâ<â.01). CC2-7 measured 6.11â±â9.88 in participants younger than 40, significantly lower compared with participants older than 40, which measured 10.89â±â11.02 (Pâ=â.003). TIS did not differ significantly between the 2 groups (Pâ=â.087). No significant difference was found in all measurements between the female and male participants. Age was moderately correlated with NT (râ=â0.466, Pâ<â.01) and TIA (râ=â0.512, P < .01), but weakly correlated with CC2-7 (râ=â0.315, P < .01) and TIS (râ=â0.210, Pâ=â.005). TIA showed a strong correlation with NT (râ=â0.748, P < .01) and a moderate correlation with T1S (râ=â0.458, P < .01). Lastly, T1S was strongly correlated with CC2-7 (râ=â0.701, P < .01).The result showed that NT, CC2-7, and TIA, but not T1S, increased with age.
Asunto(s)
Envejecimiento/fisiología , Pesos y Medidas Corporales/estadística & datos numéricos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/fisiología , Imagen por Resonancia Magnética/estadística & datos numéricos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The aim of this study is to investigate the relationship between the Modic changes (MCs) and sagittal parameters of the cervical spine.We conducted a retrospective review of 100 outpatients with magnetic resonance imaging (MRI) scans of the cervical spine (50 male and 50 female). MRI parameters were measured, including neck tilt, T1 slope (T1â), thoracic inlet angle (TIA), and cervical lordosis (CL: Cobb C2-7). Patients were divided into 4 groups according to the presence or absence of MC and T1s, respectively: MC(+) and MC(-) groups, as well as H-T1s (T1s ≥25°) and L-T1s subgroups (T1s <25°). Relationships between the MC and sagittal alignment in the cervical spine and other parameters were evaluated via Spearman correlation coefficient. Radiologic parameters were compared between the MC(+) group and MC(-) group, and the prevalences of MC were compared between the H-T1s and L-T1s groups.T1s was significantly correlated with TIA and CL, with correlation coefficients of 0.562 and 0.725, respectively. T1 slope was significantly higher in patients with MC than those without MC (Pâ=â.041), and the prevalence of MC was higher in the H-T1s group than the L-T1s group (37.5% and 17.1%, respectively). However, the relationship between the parameters of sagittal balance and MC was not significant.The present study demonstrated that high T1 slope is a potential risk factor for the development of MC due to impaired sagittal balance, especially in the C5-6 cervical segment.
Asunto(s)
Vértebras Cervicales/anatomía & histología , Enfermedades de la Columna Vertebral/patología , Adulto , Anciano , Fenómenos Biomecánicos , Femenino , Humanos , Lordosis/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: To assess the correlation between lumbar disc degeneration (LDD), multifidus muscle atrophy (LMA), and facet joints degeneration in patients with L4-L5 lumbar disc herniation (LDH). METHODS: Sixty patients with L4-L5 LDH diagnosed by a 1.5 T MRI scanner were enrolled in the study group and another 60 patients with non-specific back pain were enrolled in the control group. LDD, LMA, and facet joints degeneration were examined and analyzed independently by two independent orthopedic surgeons using T2-weighted images. Wilcoxon test was used for analyzing the difference of LDD and facet joints degeneration between L3-L4 and L5-S1 and difference of LMA between the herniated and control groups. Correlation analysis of the three degeneration grades at the same level was determined by Spearman rank correlation test. RESULTS: In the herniated group, most LMA at L3-L4 level was grade 1 (42, 70.0%); grade 2 (33, 55.0%) at L4-L5 level; and grade 3 (27, 45.0%) at L5-S1 level. LMA and LDD grading were significantly different between L3-L4 and L5-S1 levels (P < 0.05). In the herniation group, the Spearman value for LDD and LMA grading were 0.352 (P < 0.01) at L3-L4 and 0.036 (P > 0.05) at the L5-S1 level. The differences in LMA between the herniated and control groups at the three levels were significant (P < 0.05). CONCLUSIONS: Disc degeneration and multifidus muscles atrophy were positively correlated at the L3-L4 disc level. A lumbar extension muscle strengthening program could be helpful in preventing muscle atrophy and lumbar spinal degeneration.
Asunto(s)
Degeneración del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Músculos Paraespinales/diagnóstico por imagen , Articulación Cigapofisaria/diagnóstico por imagen , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: The objective of this study was to analyze the interobserver reliability and intraobserver reproducibility of the new AOSpine thoracolumbar spine injury classification system in young Chinese orthopedic surgeons with different levels of experience in spinal trauma. Previous reports suggest that the new AOSpine thoracolumbar spine injury classification system demonstrates acceptable interobserver reliability and intraobserver reproducibility. However, there are few studies in Asia, especially in China. METHODS: The AOSpine thoracolumbar spine injury classification system was applied to 109 patients with acute, traumatic thoracolumbar spinal injuries by two groups of spinal surgeons with different levels of clinical experience. The Kappa coefficient was used to determine interobserver reliability and intraobserver reproducibility. RESULTS: The overall Kappa coefficient for all cases was 0.362, which represents fair reliability. The Kappa statistic was 0.385 for A-type injuries and 0.292 for B-type injuries, which represents fair reliability, and 0.552 for C-type injuries, which represents moderate reliability. The Kappa coefficient for intraobserver reproducibility was 0.442 for A-type injuries, 0.485 for B-type injuries, and 0.412 for C-type injuries. These values represent moderate reproducibility for all injury types. The raters in Group A provided significantly better interobserver reliability than Group B (P < 0.05). There were no between-group differences in intraobserver reproducibility. CONCLUSIONS: This study suggests that the new AO spine injury classification system may be applied in day-to-day clinical practice in China following extensive training of healthcare providers. Further prospective studies in different healthcare providers and clinical settings are essential for validation of this classification system and to assess its utility.