The study aimed to explore the relationships of skeletal muscle mass with disease severity in metabolic-associated fatty liver disease (MAFLD) patients with different methods. Consecutive subjects undergoing bioelectrical impedance analysis were included. The steatosis grade and liver fibrosis were evaluated by MRI-derived proton density fat fraction and two-dimensional shear wave elastography. The appendicular skeletal muscle mass (ASM) was adjusted by height2 (ASM/H2), weight (ASM/W) and BMI (ASM/BMI). Overall, 2223 subjects (50·5 %, MAFLD; 46·9 %, male) were included, with the mean age 37·4 ± 10·6 years. In multivariate logistic regression analysis, the subjects with the lowest quartile (Q1) of ASM/W or ASM/BMI had higher risk ratios for MAFLD (OR (95 % CI) in male: 2·57 (1·35, 4·89), 2·11(1·22, 3·64); in female: 4·85 (2·33, 10·01), 4·81 (2·52, 9·16), all P < 0·05, all for Q1 v. Q4). The MAFLD patients with lower quartiles of ASM/W had the higher risk OR for insulin resistance (IR), both in male and female (2·14 (1·16, 3·97), 4·26 (1·29, 14·02) for Q4 v. Q1, both P < 0·05). While the significant OR were not observed when ASM/H2 and ASM/BMI were used. There were significant dose-dependent associations between decreased ASM/W as well as ASM/BMI and moderate-severe steatosis (2·85(1·54, 5·29), 1·90(1·09, 3·31), both P < 0·05) in male MAFLD patients. In conclusion, ASM/W is superior to ASM/H2 and ASM/BMI in predicting the degree of MAFLD. A lower ASM/W is associated with IR and moderate-severe steatosis in non-elderly male MAFLD.
A novel dual-band substrate integrated waveguide (SIW) bandpass filter, which is suitable for 5G millimeter wave wireless communication system, is presented in this paper. The filter is based on the TE101 and TE102 modes in a SIW isosceles triangular cavity with small size and compact structure. A row of metal vias are arranged on each side of the isosceles triangle SIW cavity. In order to be equivalent to the electric wall to prevent energy leakage. Metal vias are used to perturb the resonant modes simultaneously. The designed filter is fabricated and the measurement results verify the effectiveness of this design method. The test results show that the filter has the advantages of high selectivity, large bandwidth and low loss. The two passbands centered at 26GHz and 36.5GHz with BW1 = 7.1% and BW2 = 8.2%, the minimum in-band insertion losses are 1.4 and 1.0 dB, respectively. It's stopband suppression can be lower than -70dB.
Patients with small-cell lung cancer (SCLC) patients demonstrate varied survival outcomes. Previous studies have reported that lipoproteins are associated with prognosis in various cancers; however, the role of low-density lipoprotein (LDL) and low-density lipoprotein- cholesterol (LDLR) in patients with SCLC has not been studied. In this study, the impact of LDL and LDLR on the prognosis of SCLC patients was evaluated. A total of 601 patients with SCLC were retrospectively evaluated, in which 198 patients had adequate tissues for immunohistochemistry, and serum LDL and LDLR expression levels at baseline were tested. X-tile tool, and univariate and multivariate Cox analysis were used to assess the association between LDL, LDLR and overall survival (OS). Univariate analysis demonstrated that a lower LDL level was significantly associated with superior OS (P = 0.037). Similarly, LDLR also significantly predicted OS (P = 0.003). Multivariate Cox analyses confirmed that lower LDL and LDLR expression was independent prognostic factors associated with longer OS (P = 0.019 and P = 0.027, respectively). This study showed that both LDL and LDLR are prognostic indexes for survival in patients with SCLC. Patients with high LDL or LDLR expression level may benefit from treatment that modulates lipoprotein combined with platinum-based chemotherapy.
Background: Erlotinib-based combination therapy leads to increased efficacy but also toxicity for EGFR-mutated NSCLC. Reducing the dose of erlotinib could improve treatment tolerability, but few evidences are available regarding its efficacy at reduced dose. This randomized phase-2 study intends to compare the efficacy and tolerability between lower dose erlotinib (100 mg/d) and standard dose gefitinib (250 mg/d) in EGFR-mutated NSCLC. Methods: Patients with EGFR-mutated advanced NSCLC were randomized at 1:1 ratio to receive erlotinib 100 mg/d or gefitinib 250 mg/d until disease progression or unacceptable toxicity. The primary endpoint was disease control rate (DCR). Results: Between April 2013 and September 2018, 171 patients were randomized to receive erlotinib (n = 85) and gefitinib (n = 86); 74 in the erlotinib group and 83 in the gefitinib group were include in analysis. DCR with erlotinib and gefitinib were 91% [95% CI 81.7-95.3] and 93% [85.1-96.6], respectively (P = 0.613). Response rate was 62% [50.8-72.4] in the erlotinib group and 53% [42.4-63.4] in the gefitinib group (P = 0.247). No significant difference was observed between erlotinib and gefitinib in median progression-free survival [10.1 vs. 11.3 months, HR = 1.295 [0.893-1.879], P = 0.171] and median overall survival [26.6 vs. 28.7 months, HR = 0.999 [0.637-1.569], P = 0.998]. Subgroup analyses by line of treatment, EGFR subtypes and status of central nervous system (CNS) metastasis found similar results. More toxicity [any-grade, 80 [96%] vs. 66 [89]; grade 3-4, 11 [13%] vs. 4 [5%]] and toxicity-related discontinuation [10 [12%] vs. 3 [4%]] occurred with gefitinib compared with erlotinib. But no significant difference was observed. Conclusion: Lower dose erlotinib (100 mg/d) achieved comparable efficacy compared with standard dose gefitinib (250 mg/d) in EGFR-mutated NSCLC. Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT01955421.
Immunotherapy has brought about a paradigm shift in the treatment of cancer. However, the majority of patients exhibit resistance or become refractory to immunotherapy, and the underlying mechanisms remain to be explored.
Abstract Background Pruritus is one of the most common and challenging side effects of epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) and has impaired patients' quality of life and treatment compliance. Our study evaluated the efficacy and safety of aprepitant in managing EGFR‐TKIs–related pruritus. Methods This randomized, double‐blind, placebo‐controlled study was conducted between December 2016 and August 2020 in China. Patients were eligible if they were 18 years or older and had histologically confirmed locally advanced or metastatic non–small cell lung cancer (NSCLC) with first onset of moderate to severe pruritus during EGFR‐TKI treatment. Results A total of 130 eligible patients were randomly assigned to aprepitant ( n = 65) or desloratadine ( n = 65) groups. The median (interquartile range [Q1, Q3]) age was 63 (54, 70) years, and 79 (60.8%) were women. Mean visual analog scale scores at baseline were 6.35 (95% confidence interval [CI], 5.89–6.82) in the aprepitant group and 5.94 (95% CI, 5.56–6.32) in the desloratadine group. After 1 week of treatment, 33 (53.2%) patients responded to aprepitant, which was significantly higher than that of 14 (23.7%) patients responded to desloratadine ( p = .001). Moreover, patients in the aprepitant group had a significantly shorter response time than patients in the desloratadine group (mean [days], 13.39 [95% CI, 11.08–15.70] vs. 16.67 [95% CI, 14.19–19.13], p = .04). The most frequent drug‐related adverse events in aprepitant group and desloratadine were constipation and dry mouth, and all adverse events were grade 1–2. Conclusions To the authors’ knowledge, this is the first study to prospectively present that aprepitant elicited a better and faster response and mild toxicity for managing EGFR‐TKI induced pruritus than desloratadine. Trial registration ClinicalTrials.gov Identifier: NCT02646020 .
Surufatinib (S, a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) has exhibited encouraging efficacy in NSCLC patients (pts) as 3rd line or futher therapy in a phase II trial (NCT04922658). The purpose of this study is to evaluate the efficacy and safety of S + Toripalimab (T, an anti-PD-1 antibody) + chemotherapy (AP) in nsq-NSCLC pts. Here, we report the preliminary results. This single-arm, phase Ⅱ study (NCT05003037) has two cohorts. Naive advanced nsq-NSCLC pts without driver gene mutation were enrolled in cohort 1and pts with mutated driver genes failing with tyrosine kinase inhibitors (TKIs) entered cohort 2. Both cohorts received S (250mg, qd, po, adjusted by DLTs in 1st cycle) plus T (240mg, iv, d1, q3w, fixed dose) and AP (q3w). After 4 cycles followed by maintenance therapy with S plus T and A, q3w. Primary endpoint is PFS. Secondary endpoints include ORR, DCR, OS, and safety. Until Sep 5, 2023, 40 pts were enrolled in cohort 1 (median age 60 years, male 89.7%, TNM stage IV 100%, brain metastases (BMs) 48.7%). 25 pts were assigned to cohort 2 (median age 58 years, male 48%, TNM stage IV 96%). The most common mutated genes were EGFR (64%), HER2 (16%), and MET (8%). Most commonly used TKIs included osimertinib (36%), gefitinib (24%), and almonertinib (24%). RP2D of S was 250mg, po, qd, q3w in both cohorts (1/0 DLT occurred in 6 pts in cohort 1/2). Among pts with at least one post-baseline tumor assessment (n=38 in cohort 1, 24 in cohort 2), ORRs were 57.9% and 54.2%, DCRs were 94.7% and 95.8%. Median PFS was 10.2 months (95%CI 6.8, 13.4; BMs: 7.2m; non-BMs: not reached) in cohort 1, was not reached in cohort 2. The most common treatment-emergent adverse events (Total; Grade ≥3) in cohort 1 were diarrhea (67.5%; 2.5%), proteinuria (57.5%; 5.0%), and anemia (50.0%; 2.5%); in cohort 2 were decreased platelet count (56.0%; 32.0%), fatigue (48.0%; 0) and diarrhea (40.0%; 0). Surufatinib plus toripalimab and AP showed promising anti-tumor activity and acceptable toxicity for the treatment of advanced nsq-NSCLC, whether the driver gene is mutated or not. The combination of the 4 agents might be a novel therapeutic option for advanced nsq-NSCLC.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)