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BACKGROUND: Tumour-infiltrating lymphocytes (TILs) represent a robust biological prognostic biomarker in triple-negative breast cancer (TNBC); however, the contribution of different subsets of immune cells is unclear. We investigated the prognostic value of immune markers, including stromal TILs (sTILs), CD8+T and FOPX3+T cells, PD-1 and PD-L1 in non-metastatic TNBC. METHODS: In total, 259 patients with Stage I-III TNBC were reviewed. The density of sTILs along with the presence of total (t), stromal (s), and intratumoral (i) CD8+T cells and FOPX3+T cells were evaluated by haematoxylin and eosin and immunohistochemical staining. Immunohistochemical staining of PD-1, PD-L1 was also conducted. RESULTS: All immune markers were positively correlated with each other (P < 0.05). In the multivariate analysis, sTILs (P = 0.046), tCD8+T cells (P = 0.024), iCD8+T cells (P = 0.050) and PD-1 (P = 0.039) were identified as independent prognostic factors for disease-free survival (DFS). Further analysis showed that tCD8+T cells (P = 0.026), iCD8+T cells (P = 0.017) and PD-1 (P = 0.037) increased the prognostic value for DFS beyond that of the classic clinicopathological factors and sTILs. CONCLUSIONS: In addition to sTILs, inclusion of tCD8+T, iCD8+T cells, or PD-1 may further refine the prognostic model for non-metastatic TNBC beyond that including classical factors alone.
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Background: Plasma cell mastitis (PCM) is a benign breast disease that is refractory and difficult to cure. We integrated microwave ablation into the treatment of PCM to compare the clinical value of ultrasound-guided microwave ablation and traditional surgery in the treatment of PCM. Methods: A total of 68 patients with PCM who were admitted to 3 centers (Zhejiang Cancer Hospital, Hebei Province Hospital of Traditional Chinese Medicine, and Yantai Affiliated Hospital of Binzhou Medical university) from January 2017 to June 2019 were selected. All patients were diagnosed with PCM after pathological and clinical manifestations. Among these, 38 cases were treated with ultrasound-guided microwave ablation, and 30 cases were treated with traditional surgery. The operation time, hospitalization time, incision healing, intraoperative blood loss, postoperative pain degree, evaluation of breast shape effect, time taken for postoperative lesion disappearance, effective rate, and recurrence were recorded in the follow-up, and the clinical efficacy was compared and observed. Results: The effective rate of the ablation group was 86.8% (33/38), that of the operation group was 46.7% (14/30), and the difference was statistically significant (95% CI: 2.311-24.618; P<0.05). The average time of the lesion completely disappearing was 75.55±43.59 days in the ablation group and 103.87±45.98 days in the operation group, and the difference was statistically significant (P<0.05). The hospital stays, operation time, and intraoperative blood loss of patients in the ablation group were less than those of the operation group, and the difference was statistically significant (95% CI: -10.69 to -6.27, 95% CI: -77.06 to -51.26, and 95% CI: -21.54 to -13.64; P<0.05). The postoperative pain scoring, operative incision healing at 14 days after the operation, and breast appearance evaluation after treatment in the ablation group were better than those of the operation group, and the difference was statistically significant (P<0.05). Conclusions: Compared with traditional surgery, ultrasound-guided microwave ablation is a more effective treatment option for PCM.
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A wide variety of small-molecule pollutants is harmful to human health, and their highly sensitive universal and rapid detection in complex environments remains a challenge. Herein, a multiplexed and ultrasensitive immunochromatographic strip (ICS) was developed for the universal analysis of three kinds of different pollutants based on multilayered fluorescent nanofilm-guided signal amplification. Flexible three-dimensional nanofilms (GO-MQD) with large surface areas, high quantum dot (QD) loading, superior luminescence, and good stability were synthesized through the electrostatic adsorption-mediated layer-by-layer assembly of three layers of small QDs onto two-dimensional graphene oxide (GO) nanosheets, modified with specific antibodies, and utilized as enhanced fluorescent tags in the ICS method for quantitative target detection. By combining the GO-MQD nanofilms and multiplexed ICS, the proposed assay can rapidly and sensitively detect aflatoxin B1, clenbuterol, and kanamycin in actual samples/environmental samples (pork extract, milk, river water, and lake water) with low detection limit (0.87, 2.04, and 0.81â¯pg/mL), fast testing time (15â¯min), good stability and high reproducibility (RSDâ¯<â¯8.71â¯%). The GO-MQD-ICS method developed here exhibits great potential to meet the demands of the on-site and practical detection of small-molecule pollutants.
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Twenty-two labdane-type diterpenoids, including ten pairs of 15-epimers and a pair of 13,15-epimers, were obtained from the aerial parts of a well-known medicinal plant Leonurus japonicus Houtt. While these epimers were separated by chiral HPLC, their structures were established mainly via spectroscopic methods especially NMR, X-ray crystallography and ECD techniques. Among them, seventeen compounds, encompassing three pairs of solvolysis artefacts likely due to the use of ethanol as extracting solvent, were reported for the first time in the current work. Our preliminary anti-inflammatory screening demonstrated that seven diterpenoids displayed noteworthy inhibitory effect on the NO production in LPS-induced RAW264.7â¯cells. In addition, the release of pro-inflammatory factors TNF-α, IL-1ß and IL-6, as well as the expression of iNOS and COX-2 proteins, was also suppressed by the unreported 15,16-epoxy-6ß-hydroxy-15α-methoxy-7,16-dioxolabd-8,13-diene. Further investigation into the preliminary anti-inflammatory mechanism of this compound indicated that it could block the activation of NF-κB signaling pathway.
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BACKGROUND: Few studies have analyzed the consistency between registered acupuncture-moxibustion clinical studies and their published research results as well as their update status of registered information. METHODS: We searched for acupuncture-moxibustion clinical studies that were registered at the World Health Organization International Clinical Trials Registry Platform between 2013 and 2015 and collected data regarding their characteristics and update status. Published results of these registered studies were identified and compared with registered information. RESULTS: A total of 425 registered acupuncture-moxibustion clinical studies were included; 379 (89.2%) of them were interventional studies, and the remaining 46 (10.8%) were observational studies. Forty-six studies (10.8%) were found to have published results, and 51 published articles were identified. Overall, 73.2% (311) of registered studies did not update the research status in time; 46.6% (198) stopped updating before recruiting; 21.6% (92) stopped updating after recruiting; and 4.9% (21) stopped updating after completion. Regarding the 46 studies with published results, 29 (63.0%) were considered to be affected by reporting bias. These reporting biases predominantly involved the omission of some predefined outcomes or endpoints (16 studies), contradictions regarding descriptions of sample sizes (9 studies), discrepancies in treatment measurements or group distribution (7 studies), and inconsistent treatment durations (4 studies). When compared with other studies, significant and various reporting biases could also be commonly found in fields other than acupuncture-moxibustion. CONCLUSIONS: There were many discrepancies between registered information and published reports on acupuncture-moxibustion, which could also be commonly observed in other fields. Moreover, a large proportion of registered studies did not update their research status in time. Efforts should be made to improve the reporting quality and timely updates.
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Four new aconitine-type C19-diterpenoid alkaloids, were isolated from the roots of Aconitum nagarum Stapf which were named as nagarutines A-D (1-4), together with eleven known compounds (5-15). The structures of the compounds were identified by IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were tested for the inhibitory effect on LPS induced NO production in RAW 264.7 macrophages, compound 7 showed moderate anti-inflammatory activity effect and Inhibition rate is about 44.50ï¼ .
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Developing artificial symbionts beyond natural synthesis limitations would bring revolutionary contributions to agriculture, medicine, environment, etc. Here, we initiated a solar-driven multi-organism symbiont, which was assembled by the CO2 fixation module of Synechocystis sp., N2 fixation module of Rhodopseudomonas palustris, biofunctional polypeptides synthesis module of Bacillus licheniformis, and the electron transfer module of conductive cationic poly(fluorene-co-phenylene) derivative. The modular design broke the pathway to synthesize γ-polyglutamic acid (γ-PGA) using CO2 and N2, attributing to the artificially constructed direct interspecific substance and electron transfer. So, the intracellular ATP and NADPH were enhanced by 69 and 30%, respectively, and the produced γ-PGA was enhanced by 104%. The strategy was further extended to produce a commercial antibiotic of bacitracin A. These achievements improve the selectivity and yield of functional polypeptides with one click by CO2 and N2, and also provide an innovative strategy for creating photosynthetic systems on demand.
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Bacillus licheniformis , Dióxido de Carbono , Dióxido de Carbono/metabolismo , Bacillus licheniformis/metabolismoRESUMO
Left-behind children (LBC) have been found to be disadvantaged in academic adaption due to the lack of parental care and supervision they receive. Educational flow, which is known as an optimal learning state for adolescents, would be beneficial for academic adaption among LBC. Self-compassion may provide a growth mindset to improve their abilities and immersion in learning. The present study focuses on educational flow and explores both the level and the protective mechanism of educational flow among LBC using cross-sectional data. Specifically, we examine whether self-compassion contributes to educational flow through future orientation. The study sample comprises participants from a middle school in Henan province. A total of 371 LBC participated in the study, with a mean age of 14.04. We find that family income is positively associated to LBC's educational flow. Furthermore, self-compassion is positively associated with future orientation and educational flow, future orientation is positively associated with educational flow and self-compassion generates higher level of future orientation, which in turn promoting educational flow. Overall, our findings suggest that it is essential to incorporate self-compassion and future orientation when promoting the academic adaption of LBC.
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Background: Nutritionally unhealthy obesity is a newly introduced phenotype characterized by a combined condition of malnutrition and obesity. This study aims to explore the combined influence of obesity and nutritional status on the prevalence and outcome of hypertension. Methods: Participants collected from the National Health and Nutrition Examination Survey (NHANES) database were divided into four subgroups according to their obesity and nutritional conditions, as defined by waist circumference and serum albumin concentration. The lean-well-nourished was set as the reference group. Logistic regression models were applied to evaluate the hypertension risk. Kaplan-Meier analysis and Cox proportional hazard regression models were used to assess the survival curve and outcome risk of participants with hypertension. Results: A total of 28,554 participants with 10,625 hypertension patients were included in the analysis. The lean-malnourished group showed a lower hypertension risk (odds ratio [OR] 0.85, 95% confidence interval [CI]: 0.77-0.94), while the obese-well-nourished condition elevated the risk (OR 1.47, 95% CI: 1.3-1.67). Two malnourished groups had higher mortality risks (HR 1.42, 95% CI: 1.12-1.80 and HR 1.31, 95% CI: 1.03-1.69 for the lean and obese, respectively) than the reference group. The outcome risk of the obese-well-nourished group (HR 1.02, 95% CI: 0.76-1.36) was similar to the lean-well-nourished. Conclusion: Malnutrition was associated with a lower risk of developing hypertension in both lean and obese participants, but it was associated with a worse outcome once the hypertension is present. The lean-malnourished hypertension patients had the highest all-cause mortality risk followed by the obese-malnourished. The obese-well-nourished hypertension patients showed a similar mortality risk to the lean-well-nourished hypertension patients.
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BACKGROUND: Several genioplasty techniques can narrow the width of the chin. Nevertheless, patients with a broad and short chin who received these methods were unsatisfied with the outcomes. The goal of this study was to analyze the clinical outcomes of modified M-shaped genioplasty for broad, flat and short chin deformity. METHODS: Thirty-eight patients with broad, flat and short chins were included in this study from January 2019 to December 2021. The preoperative design was performed individually according to the data of the chin and the patient's desire of final chin shape. Narrowing and vertical elongating genioplasty was performed for all the patients with modified M-shaped genioplasty under general anesthesia according to the preoperative designs. All patients have completed the FACE-Q preoperatively and 3 months postoperatively. The results were evaluated by clinical appearances and FACE-Q scores. RESULTS: The vertical lengthening of the chin was 2-5 mm, with an average of 3.02 mm. The horizontal narrowing width was 3-6 mm, with an average of 5.6 mm. FACE-Q scores in satisfaction with the chin increased significantly from 35.34 ± 9.57 to 72.95 ± 6.81. There were no severe complications took place during the time frame of 3-24 months postoperatively. CONCLUSIONS: The modified M-shaped genioplasty preserved the bone structure in the midsymphyseal area and suprahyoid muscular attachments as far as possible, and the bone segments may be repositioned quickly. This technique produced reliable and esthetically satisfying results in correcting a short, flat and broad chin, with altered vertical length, slope, width and protrusion three-dimensionally. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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With the development of the social economy over the last 30 years, non-alcoholic fatty liver disease (NAFLD) is affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. It is very important to investigate the pathogenesis and treatment of NAFLD for the development of human health. Probucol is an antioxidant with a bis-phenol structure. Although probucol is a clinically used cholesterol-lowering and anti-atherosclerosis drug, its mechanism has not been elucidated in detail. This paper reviews the chemical structure, pharmacokinetics and pharmacological research of probucol. Meanwhile, this paper reviews the mechanism of probucol in NAFLD. We also analyzed and summarized the experimental models and clinical trials of probucol in NAFLD. Although current therapeutic strategies for NAFLD are not effective, we hope that through further research on probucol, we will be able to find suitable treatments to solve this problem in the future.
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Introduction: The efficacy and safety of immunotherapy have been widely recognized in gastrointestinal-related cancers. However, the efficacy of neoadjuvant camrelizumab for locally advanced esophageal squamous cell carcinoma (ESCC) has not been firmly established. This study compared the efficacy of camrelizumab in combination with neoadjuvant DCF (docetaxel, cisplatin and fluorouracil), with DCF alone for ESCC, and exploring biomarkers related to immune infiltration of the ESCC immunotherapy response. Methods: We enrolled and randomly assigned patients with stage II-IVa ESCC to two study treatments: camrelizumab combined with docetaxel, cisplatin and fluorouracil (DCF) regimen and DCF regimen alone. The tissue for multiplex immunofluorescence (mIF) was obtained before and after neoadjuvant therapy. The Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1) and Tumor Regression Grade (TRG) was used to evaluate efficacy. Results: A total of 30 patients were enrolled in the study. Following neoadjuvant camrelizumab, the objective response rate (ORR) and the disease control rate (DCR) were 46.7% (7/15) and 95.7% (14/15), respectively. No patients reported complete remission, while ORR and DCR in the chemotherapy group were 26.7% (4/15) and 86.7% (13/15), respectively. R0 resection after neoadjuvant treatment was achieved in 3 out of 15 patients in the combined group and in all patients (15/15) in the chemotherapy group. In the combined group, M1-type tumor-associated macrophages and CD56dim NK cells were more abundant in responders than in non-responders (p < 0.05). A higher M1/M2 ratio was observed in responders (p < 0.05). With respect to the NGS, among the copy number amplified genes, the 11q13 amplicon (CCND1/FGF19/FGF4/FGF3) showed the highest frequency (47%, 7/15). Conclusions: Neoadjuvant camrelizumab combined with chemotherapy improved ORR in locally advanced ESCC. M1-type tumor-associated macrophages and CD56dim NK cells might be utilized to predict camrelizumab efficacy.
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Introduction: The mechanism of internet game addiction is unclear. Whether anxiety mediates between resourcefulness and internet game addiction and whether gender affect its mediation role have not been studied previously. Methods: A total of 4,889 college students from a college in southwest China were included in this study to complete the investigation, in which three questionnaires were used for evaluation. Results: Pearson's correlation analysis indicated a remarkable negative correlation between resourcefulness with internet game addiction and anxiety, as well as a significant positive correlation between anxiety and this addiction. The structural equation model confirmed the mediation role of anxiety. The multi-group analysis confirmed the moderating role of gender in the mediation model. Discussion: These findings have advanced the results of existing studies, indicating the buffering effect of resourcefulness on internet game addiction and revealing the potential mechanism of this relationship.
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Ansiedade , Comportamento Aditivo , Humanos , Ansiedade/epidemiologia , Transtornos de Ansiedade , Comportamento Aditivo/epidemiologia , Estudantes , InternetRESUMO
BACKGROUND: This study aimed to investigate the effects of multidisciplinary whole-course nutrition management on the nutritional status and complications during the course of treatment in patients with esophageal cancer (EC) undergoing chemoradiotherapy. METHODS: A total of 36 EC patients undergoing chemoradiotherapy were divided into a control group (n = 18) and an intervention group (n = 18). Participants in the control group were given routine nutritional support, whereas those in the intervention group were provided whole-course nutrition management from the nutrition support team. Nutrition-related indicators, that is, serum albumin level (ALB), hemoglobin (Hb), and C reactive protein were assessed before, during, and after treatment in both groups. The incidence of complications (e.g., lymphocytopenia, radiation esophagitis, and myelosuppression), clinical outcomes, length of hospital stay, and hospital costs were also recorded. Differences between the 2 groups were tested using the Mann-Whitney U and chi-square tests. RESULTS: The ALB and Hb levels of the patients in the control group decreased significantly [ALB: -2.6 (-5.6, 0), P = .01; Hb: -12.0 (-27.0, -2.0), P = .04] and C reactive protein increased [8.9 (2.9, 14.9), P = .02] compared to those before treatment, while the indicators of participants in the intervention group did not change (P > .05). The incidence of grade ≥ II lymphocytopenia was higher in the control group than that in the intervention group (33.3% vs 61.1%, P = .03). Moreover, compared with the control group, the average length of hospital stay decreased by 12 days [47 (40, 50) vs 35 (23, 40), P = .001], and in-patient expenses decreased by 20,504 CNY in the intervention group (P = .004). CONCLUSION: Multidisciplinary whole-course nutrition management can maintain the nutritional status of patients with EC undergoing chemoradiotherapy. This may lower the incidence of complications, shorten hospital stays, and reduce in-patient expenses.
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Two Gram-stain-negative, strictly aerobic, chemoheterotrophic, short-rod-shaped and non-motile strains, forming yellow colonies and designated F47161T and F64183T, were isolated from marine sediment of Xiaoshi Island, Wei Hai, PR China. Strain F47161T grew at 15-37 °C (optimally at 30 °C) and pH 6.0-9.0 (optimally at pH 7.5) and in the presence of 1-9â% (w/v) NaCl (optimally at 3â%). Strain F64183T grew at 10-37 °C (optimally at 30 °C) and pH 6.0-8.5 (optimally at pH 7.0) and in the presence of 1-8â% (w/v) NaCl (optimally at 3â%). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that F47161T and F64183T were related to members of the genus Aequorivita. The strains shared 97.4â% 16S rRNA gene sequence similarity to each other. F47161T and F64183T shared highest 16S rRNA gene sequence similarity to Aequorivita sinensis JCM 19789T, and the values were 97.5â% and 98.4 %, respectively. The predominant cellular fatty acids of both F64183T and F47161T were iso-C15â:â0 and iso-C17â:â0 3-OH, but the predominant fatty acids of F47161T also included anteiso-C15â:â0. The sole respiratory quinone of F47161T and F64183T was menaquinone 6 (MK-6), consistent with that observed for all related strains. Between F47161T and F64183T, the average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) values were 75.8â% and 20.5â%, respectively, and between the novel isolates (F47161T and F64183T) and A. sinensis JCM 19789T they were 76.0â% and 94.2â% and 20.6â% and 57.1â%, respectively. The genomic DNA G+C contents of F47161T and F64183T was 37.3â% and 34.5â%, respectively. The polar lipid profiles of F47161T and F64183T contained phosphatidylethanolamine, two aminolipids, one glycolipid, one phosphoglycolipid and two unidentified polar lipids. Differential phenotypic and genotypic characteristics of the two strains indicated that the two strains should be classified as representing two novel species of the genus Aequorivita, for which the names Aequorivita vitellina sp. nov. and Aequorivita xiaoshiensis sp. nov. are proposed. The type strains are F47161T (=MCCC 1H00509T=KCTC 92017T) and F64183T (=MCCC 1H00507T=KCTC 92016T), respectively.
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Central nervous system (CNS) disorders exhibit complex neurophysiological and pathological mechanisms, which seriously affect the quality of life in patients. Acupuncture, widely accepted as complementary and alternative medicine, has been proven to exert significant therapeutic effects on CNS diseases. As a part of the innate immune system, NLRP3 inflammasome contributes to the pathogenesis of CNS diseases via regulating neuroinflammation. To further explore the mechanisms of acupuncture regulating NLRP3 inflammasome in CNS diseases, our study focused on the effects of acupuncture on neuroinflammation and the NLRP3 inflammasome in vascular dementia, Alzheimer's disease, stroke, depression, and spinal cord injury. This study confirmed that the activation of NLRP3 inflammasome promotes the development of CNS diseases, and inhibiting the activation of NLRP3 inflammasome is a potential key target for the treatment of CNS diseases. In addition, it is concluded that acupuncture alleviates neuroinflammation by inhibiting the activation of the NLRP3 inflammasome pathway, thereby improving the progression of CNS diseases, which provides a theoretical basis for acupuncture to attenuate neuroinflammation and improve CNS diseases.
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With the development of the social economy, unhealthy living habits and eating styles are gradually affecting people's health in recent years. As a chronic liver disease, NAFLD is deeply affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. As a protein complex in clinical research, the inflammasomes play a crucial role in the development of NAFLD, atherosclerosis, and other diseases. This paper reviews the types, composition, characteristics of inflammasomes, and molecular mechanism of the inflammasome in NAFLD. Meanwhile, the paper reviews the drugs and non-drugs that target NLRP3 inflammasome in the treatment of NAFLD in the past decades. we also analyzed and summarized the related experimental models, mechanisms, and results of NAFLD. Although current therapeutic strategies for NAFLD are not effective, we expect that we will be able to find an appropriate treatment to address this problem in the future with further research on inflammasome.
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At present, deep learning is widely used in spectral data processing. Deep learning requires a large amount of data for training, while the collection of biological serum spectra is limited by sample numbers and labor costs, so it is impractical to obtain a large amount of serum spectral data for disease detection. In this study, we propose a spectral classification model based on the deep structured semantic model (DSSM) and successfully apply it to Fourier Transform Infrared (FT-IR) spectroscopy for ductal carcinoma in situ (DCIS) detection. Compared with the traditional deep learning model, we match the spectral data into positive and negative pairs according to whether the spectra are from the same category. The DSSM structure is constructed by extracting features according to the spectral similarity of spectra pairs. This new construction model increases the data amount used for model training and reduces the dimension of spectral data. Firstly, the FT-IR spectra are paired. The spectra pairs are labeled as positive pairs if they come from the same category, and the spectra pairs are labeled as negative pairs if they come from different categories. Secondly, two spectra in each spectra pair are put into two deep neural networks of the DSSM structure separately. Then the spectral similarity between the output feature maps of two deep neural networks is calculated. The DSSM structure is trained by maximizing the conditional likelihood of the spectra pairs from the same category. Thirdly, after the training of DSSM is done, the training set and testing set are input into two deep neural networks separately. The output feature maps of the training set are put into the reference library. Lastly, the k-nearest neighbor (KNN) model is used for classification according to Euclidean distances between the output feature map of each unknown sample to the reference library. The category of the unknown sample is judged according to the categories of k nearest samples. We also use principal component analysis (PCA) to reduce dimension for comparison. The accuracies of the KNN model, principal component analysis-k nearest neighbor (PCA-KNN) model, and deep structured semantic model-k nearest neighbor (DSSM-KNN) model are 78.8%, 72.7%, and 97.0%, which proves that our proposed model has higher accuracy.
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Carcinoma Intraductal não Infiltrante , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Semântica , Redes Neurais de Computação , Análise por ConglomeradosRESUMO
Fourteen previously undescribed steroidal alkaloids, including six jervine-type, wabujervine A-E and wabujerside A, seven cevanine-type, wabucevanine A-G, and one secolanidin-type, wabusesolanine A, along with thirteen known steroidal alkaloids, were isolated from the bulbs of Fritillaria unibracteata var. wabuensis. On the basis of comprehensive analysis of IR, HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses, their structures were elucidated. In the zebrafish acute inflammatory models, nine compounds showed anti-inflammatory activity.
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BACKGROUND: Subgroup analyses of the NAPOLI-1 study identified that among patients who were irinotecan naïve prior to entering the clinical trial, a survival benefit was observed between the study arm and control arm. This treatment benefit was not observed among those previously exposed to irinotecan. This study sought to understand the impact of prior exposure to irinotecan on clinical outcomes among patients treated with liposomal irinotecan in the real-world setting. METHODS: This retrospective observational study utilized a nationwide electronic health record (EHR)-derived deidentified database. Data for adult patients with mPDAC treated with liposomal irinotecan-based regimens between January 2016 and October 2020 were analyzed. Patient characteristics, overall survival (OS), and progression-free survival (PFS) were assessed. Cox proportional hazard methods were used to calculate hazard ratios (HRs). HRs were adjusted for demographics and relevant clinical covariates. RESULTS: Six hundred and seventy-five patients with mPDAC treated with a liposomal irinotecan-based regimen were included. The unadjusted OS HR was 1.3 (95% CI: 1.1-1.6, p < 0.001) and unadjusted PFS was HR 1.4 (95% CI: 1.2-1.7, p < 0.001). After adjustment for baseline characteristics, the adjusted OS HR was 1.0 (95% CI: 0.8-1.3, p = 0.8836) and the adjusted PFS HR was 1.1 (95% CI: 0.8-1.4, p = 0.5626). CONCLUSIONS: Prior irinotecan was not found to be a significant predictor of patient outcomes in those later treated with liposomal irinotecan. Thus, the results may inform the rationale for utilizing liposomal irinotecan combination therapy following prior irinotecan exposure in mPDAC, in particular where the prior irinotecan exposure was more distant in time.