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BACKGROUND: Daratumumab as a monoclonal antibody has shown promising results in the treatment of relapsed/refractory multiple myeloma (RRMM). However, the efficacy and safety of daratumumab-based regimens compared to control regimens have not been fully established. METHODS: The search was conducted using electronic databases (PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases) up to December 2022. We conducted a meta-analysis of randomized controlled trials that evaluated the efficacy and safety of daratumumab in the treatment of RRMM. Data were extracted from eligible studies and were presented as hazard ratio or risk ratio (RR) with 95% confidence interval (CI). RESULTS: A total of 5 randomized controlled trials comprising 2003 patients were included in this meta-analysis. The results showed that daratumumab-based regimens significantly improved progression-free survival compared to control regimens (hazard ratio = 0.44, 95% CI 0.32-0.60, P < .00001). Additionally, daratumumab-based regimens significantly improved overall response rate compared to control regimens (RR = 1.25, 95% CI 1.16-1.36, P < .00001). the rate of minimal residual disease was also significantly higher in the daratumumab-based regimens (RR = 6.10, 95% CI 4.09-9.11, P < .00001). However, there was an increased risk of pneumonia, upper respiratory tract infections, and diarrhea in the daratumumab-based regimens. CONCLUSION: Our results suggest that daratumumab-based regimens are effective in the treatment of RRMM, improving progression-free survival, minimal residual disease, and overall response rate. However, there is an increased risk of pneumonia, upper respiratory tract infections, and diarrhea. Further studies are needed to determine the long-term safety and efficacy of daratumumab in the treatment of multiple myeloma.
Asunto(s)
Mieloma Múltiple , Enfermedades Nasales , Infecciones del Sistema Respiratorio , Humanos , Mieloma Múltiple/tratamiento farmacológico , Neoplasia Residual , Ensayos Clínicos Controlados Aleatorios como Asunto , Anticuerpos Monoclonales/efectos adversos , DiarreaRESUMEN
Objective: To evaluate the clinical correlation of epithelial-mesenchymal transition (EMT) with PRL-3 and MMP9 expression in the circulating tumor cells (CTCs) of patients with colorectal cancer (CRC). Materials and Methods: Between January 2016 and December 2018, the EMT phenotype-based subsets of CTCs and the expression levels of PRL-3 and MMP9 in CTCs were identified, and their clinical values in 172 patients were evaluated. The CTCs were isolated, classified, and counted using the CanPatrol™ CTC filtration system. The CTC subsets (epithelial cells, mesenchymal cells and biphenotypic cells), as well as PRL-3 and MMP9 expression, were detected by RNA in situ hybridization. Results: CTCs were detected in 93.0% (160/172) of the included patients with CRC. Positive PRL-3 and MMP9 expression in CTC and M-CTC was found in 75.0% (102/136) and 80.8% (97/120) of the patients, respectively. The proportion of patients with positive PRL-3 and MMP9 expression in M-CTC was significantly associated with distant metastasis (p<0.05). The patients with ≥6 CTCs tended to show poorer progression-free survival (PFS) and overall survival (OS) rates (p=0.016, 0.02, respectively), and the patients with ≥3 M-CTC also showed poor PFS (p=0.0013). Additionally, the patients with positive PRL-3 and MMP9 expression in CTCs had significantly poorer PFS (p=0.0024) and OS (p=0.095) than the patients with negative PRL-3 and MMP9 expression. Multivariate Cox analysis uncovered that positive PRL-3 and MMP9 expression in CTCs may be an independent prognostic factor for worse PFS. Conclusion: EMT phenotypes and CTC numbers can be used as prognostic indicators for metastasis and survival in patients with CRC, and the combination of PRL-3 and MMP9 expression in CTCs is a promising clinical marker for patients with CRC.
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Introduction: In order to reveal the composition of the subsurface hydrothermal bacterial community in the zones of magmatic tectonics and their response to heat storage environments. Methods: In this study, we performed hydrochemical analysis and regional sequencing of the 16S rRNA microbial V4-V5 region in 7 Pleistocene and Lower Neogene hot water samples from the Gonghe basin. Results: Two geothermal hot spring reservoirs in the study area were found to be alkaline reducing environments with a mean temperature of 24.83°C and 69.28°C, respectively, and the major type of hydrochemistry was SO4-Cl·Na. The composition and structure of microorganisms in both types of geologic thermal storage were primarily controlled by temperature, reducing environment intensity, and hydrogeochemical processes. Only 195 ASVs were shared across different temperature environments, and the dominant bacterial genera in recent samples from temperate hot springs were Thermus and Hydrogenobacter, with both genera being typical of thermophiles. The correlation analysis showed that the overall level of relative abundance of the subsurface hot spring relied on a high temperature and a slightly alkaline reducing environment. Nearly all of the top 4 species in the abundance level (53.99% of total abundance) were positively correlated with temperature and pH, whereas they were negatively correlated with ORP (oxidation-reduction potential), nitrate, and bromine ions. Discussion: In general, the composition of bacteria in the groundwater in the study area was sensitive to the response of the thermal storage environment and also showed a relationship with geochemical processes, such as gypsum dissolution, mineral oxidation, etc.
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OBJECTIVE: To investigate A1 pulley thickness of flexor tendon in healthy volunteers and to analyze its influence factors. METHODS: The study included 90 healthy volunteers and the A1 pulley thickness at bilateral fingers was measured using high frequency ultrasound. The following parameters were recorded for each participant: age, gender, weight, height, body mass index (BMI). RESULTS: High-frequency ultrasound can clearly show A1 pulley. There was no significant difference in A1 pulley thickness between the bilateral fingers ( P>0.05). A1 pulley thickness was significantly different in different fingers ( P<0.05). Further comparison showed that A1 pulley thickness could be divided into two subsets: thumb and little finger ((0.196±0.051) mm), index, middle and ring fingers ((0.230±0.055) mm). A1 pulley thickness was positively correlated with age ( r=0.468, P<0.001). The normal reference ranges for thumb and little finger were 0.09-0.23 mm, 0.12-0.30 mm and 0.12-0.32 mm, respectively. The normal reference ranges for index, middle and ring fingers were 0.11-0.27 mm, 0.15-0.35 mm and 0.17-0.35 mm in volunteers aged 3-19 yr., 20-49 yr., and ≥50 yr., respectively. Gender and BMI had negligible impact on A1 pulley thickness ( P>0.05). CONCLUSION: High-frequency ultrasound can clearly show and measure A1 pulley. Site and age should be taken into account when determining the reference range of normal A1 pulley thickness. High-frequency ultrasound can be a quantitative evaluation method for A1 pulley lesions.