Peripheral blood-based biomarkers (PBB) predicting response, survival and immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are still a matter of debate. Thus, we investigated the associations between PBB, the efficacy of ICIs and the incidence of irAEs.Patients with advanced NSCLC, who had been treated at Peking Union Medical College Hospital and received ICIs or chemoimmunotherapy from January 2015 to December 2020, were retrospectively identified. PBBs results were retrieved from medical records. Associations with overall response rate, survival, and incidence of irAEs were assessed using Kruskal-Wallis, Kaplan-Meier analysis, Pearson's chi-squared and Student's t-tests as required. Cox proportional hazards and logistic regression models were used to determine independent risk factors. Analyses were performed on the whole population (n=103), patients receiving ICIs only (n=32), and patients receiving chemoimmunotherapy (n=71). Changes in pretreatment and on-treatment PBB were also analyzed.Among 103 patients, 38 (36.9%) developed irAEs. Pretreatment absolute lymphocyte count (ALC) was related to an increased risk of irAEs in the whole population [odds ratio (OR), 2.165; 95% confidence interval (CI): 1.040 to 4.509, P=0.039] and patients receiving ICIs only (OR, 6.461; 95% CI: 1.067 to 39.112; P=0.042). A low prognostic nutritional index (PNI ≤45) was associated with worse progression-free survival (PFS) and overall survival (OS) in the whole population, in patients receiving ICIs only, and in patients receiving chemoimmunotherapy. High pretreatment interleukin (IL)-6 was associated with both worse PFS and OS in the whole population (IL-6 >13.80 pg/mL), in patients receiving ICIs only (IL-6 >11.30 pg/mL), and in patients receiving chemoimmunotherapy (IL-6 >11.85 pg/mL). Increase of IL-6 during treatment was associated with inferior OS in the whole population (P<0.001).Pretreatment ALC has the potential to predict irAEs in patients with advanced NSCLC treated with ICIs. Additionally, a low level of pretreatment PNI and high level of IL-6 may be associated with shorter survival.
The pathophysiology of vascular lesions after balloon angioplasty remains poorly understood. A major limitation of most experimental studies in this regard is that injury was assessed in healthy arteries. Our aim was to study the effects of hypercholesterolemia in a mouse vascular injury model that mimics human balloon angioplasty.Carotid balloon distension was performed in wild-type (WT) mice on a normal diet (ND), in apolipoprotein E-deficient (ApoE-/-) mice on ND and in ApoE-/- mice fed a high cholesterol diet (CD).Medial cell death (TUNEL) was elevated in all mice at 1 hour and 1 day after angioplasty without differences between the groups. We found enhanced intimal inflammation (%CD45-positive cells) and vascular cell adhesion molecule-1 expression at 7 days (P < 0.05; n > or = 4) as well as increased proliferation rates (BrdU-index) in ApoE-/- CD at 7 and 28 days postinjury (P < 0.05; n > or = 5). Four weeks after injury, these events led to enhanced neointima in ApoE-/- CD compared with WT ND mice (intima/media, P < 0.001; n > or = 8). The amount of lesion formation paralleled the incremental increase in total plasma cholesterol in WT ND, ApoE-/- ND and ApoE-/- CD (P < 0.01).Carotid balloon distension injury in ApoE-/- mice on CD induced enhanced inflammation and proliferation leading to increased neointima. Further applications of this microballoon catheter in genetically modified mice will provide opportunities to elucidate molecular mechanisms of vascular lesion formation in a model that reflects clinical balloon angioplasty. This know-how may pave the way to catheter-based interventions of human microvessels in the peripheral or cerebral circulation.
Cranial magnetic resonance imaging (MRI) examinations were performed in 419 patients with type 2 diabetes mellitus (T2DM) from June to December 2016. The brain white matter lesions were defined by white matter hyperintensity (WMH) in MRI, which was detected in 380 cases (WMH group) and not detected in 39 cases (non-WMH group). The Montreal Cognitive Assessment (MoCA) was used to evaluate the cognitive function. The study showed that there were significant differences in the duration of diabetes, the proportion of hypertension, total cholesterol (TC) and MoCA scores between the two groups (all P<0.05). The age, duration of diabetes, hypertension and glyclated hemoglobin (HbA1c) were significantly correlated with white matter lesions(OR=1.157, 1.116, 5.184, 1.128; P<0.05); and the white matter lesions, age, and body mass index (BMI) were significantly correlated with cognitive dysfunction in diabetic patients (OR=2.137, 1.175, 1.247; P<0.05) . The study result indicates that control of white matter lesions may prevent and improve cognitive dysfunction in T2DM patients.
Key words:
Diabetes mellitus, type 2; Cognitive dysfunction; Leukoencephalopathy
Premixed insulin is currently the most popular insulin starter in China.According to the different ratios of basal and prandial components,premixed insulin analogues could be classified into low-and midmixtures.The former is now mainly used as insulin starter in the patients with type 2 diabetes mellitus after the failure of monotherapy or combination with oral antidiabetic drugs,while the later is usually used as simplified intensive insulin treatment in patients with type 2 diabetes mellitus inadequately controlled on insulin once-or twice-daily.
Key words:
Diabetes mellitus, type 2 ; Low-and mid-mixture ; Premixed insulin analogues
Adopting digital technology to develop online education provides possibilities for equal learning opportunities, personalized learning, and lifelong education. In terms of the measurement for education digitalization,there still needs to be discussed more sufficiently.Thus,focusing on online teaching in open universities, an maturity model to measure education digitalization with four evaluation levels (basic level, apply level, change level, and optimized level) is proposed with the use of Delphi method based on knowledge transfer theory. The model covers five dimensions including teaching environment, teaching context, teaching resource, learners and teachers, with a total of 20 key process behaviors and 38 key practices. In a case study, the maturity model of technology adoption was implemented in an Chinese open universtiy to test the proposed modle.The study included N = 220 questionairs of data collection.Findings confirms the model can be a tool to evaluate the maturity level for online teaching, offering practice implications and guidelines for future implementations of education digitalization.
Antinuclear antibodies (ANAs) predicting the safety and efficacy of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are still a matter of debate considering previous studies showed quite different results based on different ANA cut-off values. Thus, we investigated the associations between different ANA titers and the safety and efficacy of ICIs. Moreover, we also briefly discussed the effects of anti-thyroglobulin (ATG) and anti-thyroid peroxidase (ATPO) on the safety of ICIs.A total of 159 Chinese patients confirmed to have locally-advanced or metastatic NSCLC given ICIs or chemoimmunotherapy in Peking Union Medical College Hospital from January 2015 to December 2020 were analyzed retrospectively and were followed up until December 2020 or death or loss to follow-up. Patients' characteristics were retrieved from medical records. ANAs were detected by the indirect immunofluorescence assay, ATG and ATPO by the electrochemiluminescence immunoassay. The severity of immune-related adverse events (irAEs) was graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) and the efficacy was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).The incidence of irAEs, median progression-free survival (mPFS) of the ANA negative and positive groups were 26.0% vs. 31.4% (P=0.457), 17.7 vs. 10 months (P=0.603) for the cut-off value of 1:80; 26.2% vs. 33.9% (P=0.305), 11.9 vs. 10.6 months (P=0.957) for 1:160; and 25.9% vs. 45.8% (P=0.047), and 11.9 vs. 7.7 months (P=0.471) for 1:320, separately. Besides, ANA titer ≥1:320 was associated with irAEs [odds ratio (OR) =4.9, 95% confidence interval (CI): 1.45-16.52, P=0.01] and the incidence of adverse skin reactions differed greatly between the negative and positive groups (9.7% vs. 32%, P=0.003). Moreover, a total of 52 out of 159 patients were tested for ATG and ATPO. 46 patients were negative and 6 were positive, with the incidence of abnormal thyroid function being 4.3% vs. 50% (P=0.005), respectively.Preexisting ANAs may not correlate with the clinical benefit of immunotherapy in patients with NSCLC but may be associated with adverse skin reactions. Besides, ATG or ATPO has the potential to predict thyroid dysfunction.
A growing number of studies have suggested that transcranial magnetic stimulation (TMS) may represent a novel technique with both investigative and therapeutic potential for autism spectrum disorder (ASD). However, a full spectrum of the adverse effects (AEs) of TMS used in ASD has not been specifically and systematically evaluated.
Abstract Background Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune‐related adverse events (irAEs) remain poorly understood, especially in a real‐world setting. Methods A multicenter observational study was conducted. Medical records of lung cancer patients treated with ICIs at 26 hospitals from January 1, 2015, to February 28, 2021, were retrieved. Types of ICIs included antiprogrammed cell death 1 or antiprogrammed cell death ligand 1 (PD‐L1) monotherapy, anticytotoxic T‐lymphocyte antigen‐4 monotherapy, or combination therapy. Results In total, 1905 patients with advanced lung cancer were evaluated. The median age was 63 (range 28–87) years, and the male/female ratio was 3.1:1 (1442/463). The primary histological subtype was adenocarcinoma (915). A total of 26.9% (512/1905) of the patients developed 671 irAEs, and 5.8% (110/1905) developed 120 grade 3–5 irAEs. Median duration from ICI initiation to irAEs onset was 56 (range 0–1160) days. The most common irAEs were thyroid dysfunction (7.2%, 138/1905), pneumonitis (6.5%, 124/1905), and dermatological toxicities (6.0%, 115/1905). A total of 162 irAEs were treated with steroids and 11 irAEs led to death. Patients with positive PD‐L1 expression (≥1%) and who received first‐line ICI treatment developed more irAEs. Patients who developed irAEs had a better disease control rate (DCR, 71.3% [365/512] vs. 56.0% [780/1145]; p < 0.001). Conclusions The incidence rate of irAEs was 26.9% in a real‐world setting. IrAEs might be related to a better DCR, but clinicians should be more aware of irAE recognition and management in clinical practice.
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