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Objective:To investigate the clinical characteristics of patients with malignant tumors and immune checkpoint inhibitors (ICI) related multisystem adverse events as well as therapeutic efficacy of ICI.Methods:The general data, immune-related adverse events (irAE) type, onset time, severity and ICI efficacy of patients with malignant tumors who developed irAE after receiving ICI in China-Japan Friendship Hospital between January 2019 and November 2021 were retrospectively analyzed. All patients were divided into multisystem irAE group and single system irAE group according to whether patients with more than 1 organ or system developed irAE for once. The occurrence of irAE was summarized, and the clinical characteristics of patients were compared. Progression-free survival analysis was not performed owing to the pause of immunotherapy caused by some irAE, so the efficacy of ICI was evaluated by using ICI treatment duration (TD).Results:A total of 47 patients with malignant tumors and irAE were included in this study, with 70 times of irAE in total. The median onset time was 90 d (35 d, 196 d). Among them, 12 patients (25.53%) developed multisystem irAE (32 times of irAE in total); the other 35 patients (74.47%) developed single system irAE (38 times of irAE in total). Cutaneous toxicity for 7 times, thyroid toxicity for 7 times and pulmonary toxicity for 5 times were the most frequent among multisystem irAE group; pulmonary toxicity for 13 times, thyroid toxicity for 12 times and cutaneous toxicity for 5 times were the most frequent among single system irAE group. There were no statistically significant differences in the proportion of patients stratified by age, gender, the combination of other treatments and different body mass between the two groups (all P > 0.05). The median follow-up time was 20 months (9-40 months). The median TD of ICI was 16.00 months (95% CI 3.62-31.22 months) in multisystem irAE group and 4.60 months (95% CI 4.12-11.30 months) in single system irAE group; TD in multisystem irAE group was longer than that in single system irAE group, and the difference was statistically significant ( HR = 0.413, 95% CI 0.202-0.844, P = 0.038). Conclusions:The efficacy of ICI in patients with malignant tumors and multisystem irAE is better than that in those with single system irAE. It suggests that the better efficacy of ICI may be associated with greater risk of irAE. There is no significant difference in the clinical features between multisystem irAE and single system irAE.
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OBJECTIVE To provide reference for safe use of bevacizumab in tumor patient. METHODS Retrospective analysis was performed for a case of tracheomediastinal fistula caused by bevacizumab after radiotherapy in which clinical pharmacist participated. Retrieved from PubMed ，Elsevier Science Direct ，Springer Link ，Wiley Oline Library ，CNKI and Wanfang database ，the cases of respiratory fistula caused by bevacizumab were collected ，and the causes of respiratory fistula were analyzed. RESULTS & CONCLUSIONS Referring to relevant literatures ，combined with the formation position of fistula and considering its correlation with the use time of bevacizumab ，considering that it may be bevacizumab related tracheomediastinal fistula，clinical pharmacists recommended that patients stopped bevacizumab and underwent stent implantation. The patient refused to implant stent for personal reasons ，but the tracheomediastinal fistula improved 3 months after drug withdrawal. Combined with the data of 16 patients with respiratory fistula caused by bevacizumab ，it could be inferred that the use of bevacizumab on the basis of radiotherapy may be the cause of tracheomediastinal fistula ；the mechanism may be related to bevacizumab inhibiting angiogenesis and affecting wound healing. This suggests that for patients who have received radiotherapy ，clinical pharmacists should strengthen medication monitoring and medication education when using bevacizumab ；clinical pharmacists should not only pay attention to the common adverse reactions such as hypertension and bleeding caused by the drug ，but also pay attention to rare but life-threatening adverse reactions such as respiratory fistula ，so as to ensure the safety of drug use.
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Objective The aim of this study was to investigate the mechanism underlying pruritus by comparing the epidermal growth factor receptor inhibitor(EGFRI)-erlotinib mouse model with the substance P(SP)-induced pruritus mouse model. Methods Two randomized groups of mice were treated with erlotinib or SP to induce pruritus. Behavioral and skin manifestations were observed. Pathological images and neurokinin 1 receptor(NK-1R)expression of the skin were determined. Concentration of interleukin(IL)-31, IL-33, histamine, leukotriene B4, and SP was analyzed by enzyme-linked immunosorbent assay. Nitric oxide was analyzed by colorimetry. Results Transient pruritus induced by erlotinib appeared 2 to 5 days after treatment. In contrast, continuous pruritus was observed during the first hour, but was then gradually relieved. These two shared similar scratching behavior. Concentration of neurotransmitters showed similar trends in changes among the erlotinib group and SP group. Immunohistochemical expression was also consistent between the erlotinib group and SP group. Conclusions Erlotinib-associated pruritus is related to release of signaling factors through the SP/NK-1R signaling pathway.
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Objective To correlate the expression levels of interferon inducible genes (IFIGs) with disease activity and clinical features in systemic lupus erythematosus (SLE) patiems,.Methods Peripheral blood cells obtained from 67 SLE patients and 23 healthy donors (HDs) were subjected to real-time PCR to measure the transcriptional levels of five IFIGs (OAS-1,Mx-1,Ly6e,IFIT1 and IFIT4).Interferon scores were calculated and were compared between various groups of SLE patients as well as between patients and controls;ISRE lucife:rase reporter gene activity was measured in 17 of 67 patients and correlated with interferon score.Results Interferon scores were strongly correlated with ISRIE reporter gene aetivity,which represented for the type Ⅰ interferon activity in serum.The expression.levels of IFIGs and jinterferon scores were significantly elevated in SLE patients compared with HDs (P＜0.0001).Interferon scores were correlated positively with SLEDAI-2K(P=0.0006) and negatively with C3 levels(P=0.0162).Interferon scores were also significantly elevated in SLE patients with a positive anti-Sm or anti-RNP autoantibodies.Clonclusion The interferon score may be regarded as a good indicator for serum type I interferon activity in SLE and serves as a new hiomarker for disease activity in SLE patients.
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Objective To explore the association between the signal transducer and activator of transcription 4 (STAT4) gene polymorphism and Chinese Han systemic lupus erythematosus patients. Methods Pyrosequencing technique was used to genotype the 3 single nucleotide polymorphisms (SNP) in the samples of patients and normal individuals. Results Not only these 3 SNPs, but also the haplotypes composed by them showed significant difference between the SLE patients and normal individuals[rs11889341:P=0.012 02, OR (95%CI)=1.22( 1.044～1.424); rs7574865:P=0.003 454, 0R(95%CI)=1.25(1.076～1.451 ); rs8179673: P=0.004 275, OR (95%CI)=1.274 (1.079～1.505)]. Conclusion rs11889341, rs7574865 and rs8179673 of STAT4 are associated with the pathogenesis of Chinese Han SLE, and the STAT4 gene is a susceptibile gene for SLE in a few racial cohorts.
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Objective To correlate the chemokine score with disease activity,organ damages and clinical features in systemic lupus erythematosus (SLE) patients.Methods Peripheral blood cells obtained from 60 SLE patients,20 rheumatoid arthritis (RA) patients and 23 healthy donors (HDs) were subjected to real-time PCR to measure the transcriptional levels of seven chemokines (RANTES,MCP-1,CCL19,MIG,IP-10,CXCL11,and IL-8).Chemokine scores were calculated and were compared between various groups of SLE patients as well as between patients and controls.Results Chemokine scores were significantly elevated in SLE patients compared with RA patients and HDs (P=0.0112 and P=0.0019,respectively).Chemokine scores were correlated positively with SLEDAI (P=0.0061) and negatively with C3 levels (P=0.003).Compared to patients without lupus nephritis (LN),chemokine scores were elevated in SLE patients with active LN,especially when their daily prednisone dosage was less than 30 mg (P=0.0418 and P=0.002,respectively).Chemokine scores were also associated with cumulative organ damage (SLICC damage index [SDI]＞0) and positive anti-Sm and anti-RNP autoantibodies.Conclusion The chemokine score may serve as a new biomarker for disease activity and organ damage in SLE patients.
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Objective To study the clinical value of cerebrospinal fluid cytology(csfc)and specific stain in tuberculous meningitis(TBM)-purulent meningitis(PM)and cryptococcal meningitis(CM).Methods The csfc data of 179 patients with TBM,PM and CM were retrospectively analyzed.The samples collected from all of these patients were analyzed by csfc May-Grunwald-Giemsa(MGG)staining,aricine blue staining and Indian ink staining. And the cytospin smears from 70 TBM were simultaneously stained by the immunofluorescence(IF)and immunocytological method to demonstrate the presence of mycobacterial antigen.Results ①TBM group showed a mixed-cell response.At the early stage of disease,the proportion of neutrophilic granulocyte reached 80%,and then reduced gradually.Lyumphoidocyte reaction was the most obvious in 1～2 months.The immunofluorescence(IF)and immunocytological method present a sensitivity of 82.9%and 85.7%,respectively.②Neutrophilic granulocyte was the most cell at acute stage of PM,and it descended quickly once treated with effective antibiotics.③The positive rates to detect CM with csfc MGG,aricine and Indian ink staining were 83.3%,81.8%,and 76.5%,respectively.Conclusion Dynamic observation on cerebrospinal fluid cytology is helpful to boost the differential diagnosis of intracranial infection.
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Objective:To study the effects of Astragalus Root Injection(a traditional Chinese herb medicine) on oxaliplatin-induced apoptosis of hippocampal neurons. Motheds: The primary culture of hippocampus neurons from SD rats (aged within 24h) were treated with different concentrations of oxaliplatin( L-OHP) (0, 3, 5 and 10 ?g/mL) and Astragalus Root Injection (0.05, 0.2 and 0.5 g/mL). The apoptosis of the neurons and the nerve growth factor(NGF)level were analyzed. Results: Astragalus Root Injection dose-dependently decreased neuronal cell apoptosis induced by oxaliplatin (P
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<p><b>OBJECTIVE</b>To evaluate Amifostin's effect on protecting kidney from cisplatinum (DDP) injury and its adverse reactions and safety.</p><p><b>METHODS</b>193 Patients were divided into two groups randomly: 102 in group A (treatment group) and 91 in group B (control group). Indexes such as blood routine, blood calcium, liver function, blood urea nitrogen (BUN), cretinine (C), and urinary N-acetyl-beta-D-glucosaminidase (NAG)/C and micro-albumin (MAB/C) were monitored at different intervals before or after treatment.</p><p><b>RESULTS</b>In the two courses of treatment in both groups, the deviation (D) values of MAB/C before treatment and on D2 in group A were lower than those in grop B (P < 0.05), so were those before treatment and on D4, D6, D10 and D14 (P < 0.01). The D-values of NAG/C before treatment and on D4, D6, D10 and D14 in the first course of group A were obviously lower than those on the corresponding days in group B (P < 0.01), so were those before treatment and on D2, D4, D6, D10 and D14 in the second course (P < 0.01).</p><p><b>CONCLUSION</b>The reduction of MAB/C and NAG/C by Amifostin in group A demonstrates that: Amifostin is able to effectively protect the renal function, regardless of the type of tumor. In contrast with group B, Amifostin in group A shows no protection for tumor in lung cancer and ovarian cancer. The main side effects of Amifostin are mild hypotension, nausea, vomiting and hypocalcemia in some patients.</p>