2022 Volume 24 Issue 3 Published: 28 March 2022
  

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  • Xing Yue, Dong Mei
    Abstract ( ) PDF ( )
    Immune checkpoint inhibitors (ICI) is a class of high-profile immunotherapy drugs for tumor, which has showed remarkable efficacy in the treatment of a variety of malignant tumors. However, ICI can also induce a series of immune-related adverse events (irAE), which are common in endocrine system with an incidence of about 40%. The irAE in endocrine system has obvious impacts on the efficacy of ICI for primary diseases and quality of life in patients, which may even be life-threatening. It is suggested that the diagnosis and treatment of irAE in endocrine system should be improved through further strengthening the research on the mechanism, diagnosis, and differential diagnosis of irAE, constructing multidisciplinary teams on diagnosis and treatment, and performing whole process management of tumor patients treated with ICI.
  • Niu Xiaoqiang, Wang Yiran, Wang Huimin, Zhou Wenya, Hu Xiaoling
    Abstract ( ) PDF ( )
    Objective To explore the occurrence and clinical characteristics of thyroid dysfunction caused by camrelizumab. Methods The subjects were selected from all malignant tumor patients who were treated with camrelizumab during hospitalization in Heping Hospital Affiliated to Changzhi Medical College from June 2020 to September 2021. The electronic medical records of patients who met the inclusion criteria were collected, and the general conditions, camrelizumab application, combined medication, and the thyroid function test results before and after the application of camrelizumab were collected. The causality between drugs and injuries in patients who developed thyroid dysfunction was assessed using Naranjo′s causality assessment scale. The clinical characteristics of thyroid dysfunction were analyzed based on the medical records that had evaluation results of "certainly" or "probably". Results A total of 71 patients were included in the analysis, and 22 patients (31.0%) developed camrelizumab-related thyroid dysfunction (causality assessment results were all "probably"). When thyroid dysfunction was found for the first time, hypothyroidism and hyperthyroidism were diagnosed in 11 patients, respectively, and 3 patients with hyperthyroidism developed into hypothyroidism later. The incidences of hypothyroidism and hyperthyroidism were 19.7% and 11.3% respectively. Among the 22 patients, 15 were male and 7 were female, aged 47-78 years; 10 patients were with lung cancer, 4 with gastric cancer, 3 with esophageal cancer, 2 with liver cancer, 2 with breast cancer, and 1 with peritoneal omental mesothelioma; 3 patients were treated with camrelizumab monotherapy, and 19 were treated with camrelizumab combined with chemotherapy and/or targeted drug therapy. Thyroid dysfunction all occurred in the first to sixth cycles of camrelizumab treatment, of which 15 (68.2%) in the first to third cycles. Of the 11 patients with initial diagnose of hypothyroidism, 6 had no obvious symptoms, 5 had fatigue (1 was complicated with apathy), and 4 were subclinical hypothyroidism; the severity was grade 1 in 4 cases and grade 2 in 7 cases. None of the 11 patients with initial diagnose of hyperthyroidism had significant symptoms, and 5 of them had subclinical hyperthyroid. All of the 11 cases were grade 1 in severity, 3 developed into hypothyroidism after 3, 6, and 7 cycles of camrelizumab treatment, which was grade 2 in severity. None of the 22 patients discontinued camrelizumab. No intervention was given to the patients with grade 1 hypothyroidism and hyperthyroidism, of which 3 patients with hyperthyroidism returned to normal on their own and the remaining showed no obvious changes in their thyroid function. Ten patients with grade 2 hypothyroidism received thyroid hormone replacement therapy; thyroid function was normal in 2 patients, improved in 5 patients, and without obvious changes in 3 patients. Conclusions Thyroid dysfunction is a very common adverse reaction of camrelizumab, which can present as both hypothyroidism and hyperthyroidism, and initial hyperthyroidism can evolve to hypothyroidism. Thyroid dysfunction was mostly grade 1-2 in severity and the drug does not need to be discontinued generally. Patients with grade 2 hypothyroidism should be given thyroid hormone replacement therapy.
  • Peng Jing, Wu Mingli, Ren Xiaolei, Jiang Kaijie, Li Lanfang, Liu Zhen, Wei Tiantian, Meng Luhua, Wang Meixia, Ban Bo
    Abstract ( ) PDF ( )
    Objective To analyze the risk of diabetes mellitus related to immune checkpoint inhibitors (ICI). Methods The adverse event (AE) reports on fulminant type 1 diabetes mellitus (FT1DM), type 1 diabetes mellitus (T1DM), diabetic ketoacidosis (DKA), which were related to duvalizumab, pabolizumab, nivolumab, and atezolizumab in the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021, were collected.The correlation between the 4 drugs and FT1DM, T1DM,and DKA were evaluated using proportional reporting odds ratio (PRR) method.AE with reports ≥3, PRR value≥2, and χ2≥4 were judged to have statistical correlations with drugs. The greater the PRR value, the stronger the correlation between AE and drugs and the stronger the risk signals. Results A total of 1-468 AE reports on diabetes mellitus were collected, 53, 386, 957, and 72 of which were related toduvalizumab, pabolizumab, nivolumab, and atezolizumab, respectively. For duvalizumab, pabolizumab, nivolumab, and atezolizumab, the PRR reflecting the correlation with FT1DM were 21.97 (χ2=40.71), 71.50 (χ2=3-531.21), 294.30 (χ2=4-3915.75), and 33.58 (χ2=279.70), respectively; the PRR reflecting correlation with T1DM were 12.12 (χ2=162.08), 21.04 (χ2=3391.17), 20.99 (χ2=5816.11), and 9.71 (χ2=224.81), respectively; the PRR reflecting correlation with DKA were 6.93 (χ2=161.26), 4.78 (χ2=426.52), 6.82 (χ2=1797.15), and 3.04 (χ2=41.84), respectively. The 4 drugs were statistically correlated with their corresponding AE. The order of risk signal intensity for corresponding AE was FT1DM > T1DM > DKA. The order of risk signal intensity for FT1DM were nivolumab > pabolizumab > duvalizumab > atezolizumab, for T1DM were pabolizumab ≈ nivolumab > duvalizumab > atezolizumab, for DKA were duvalizumab ≈ nivolumab > pabolizumab > atezolizumab. Conclusions Duvalizumab, pabolizumab, nivolumab, and atezolizumab all can cause diabetes mellitus. The risk signal intensity was the strongest for FT1DM, followed by T1DM and DKA in order.
  • Han Junwei, Li Yuanping, Cheng Yao, Wang Xiaocheng, Zhou Min, Song Jianbo
    Abstract ( ) PDF ( )

    Objective To systematically evaluate the risk of severe gastrointestinal events in patients with cancer caused by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR- TKI). Methods Randomized controlled trials of VEGFR-TKI in the treatment of tumors were collected by searching relevant databases at home and abroad (up to March 2, 2019). The patients who were treated with a VEGFR-TKI were enrolled into the trial group, and those who received placebo or another VEGFR-TKI were enrolled into the control group. The outcomes included the incidence of serious gastrointestinal events. The Jadad scoring method was used to assess the quality of included studies. The Review Manager 5.3-software was used for direct meta-analysis on the risk of severe gastrointestinal events. Stata 13.0-software and linear mixed model based on frequency framework were used for network meta-analysis on severe gastrointestinal events at the highest risk. The results were expressed by relative risk (RR) and its 95% confidence interval (CI). Results A total of 38-studies were included in the analysis, all of which were high-quality studies (Jadad score 4-7), comprising a total of 15-217 patients (9-130 in the trial group and 6-087 in the control group). The results of direct meta-analysis showed that the risks of severe diarrhea, severe anorexia, and severe nausea in the trial group were higher than those in the control group respectively, and the differences were statistically significant [6.8% (602/8-894) vs. 0.7% (49/6-584), RR=6.62 (95%CI: 5.00-8.76), P<0.001; 2.5% (201/7-937) vs. 0.7% (41/5-831), RR=2.14 (95%CI: 1.40-3.25), P<0.001; 1.5% (92/6-343) vs. 0.4% (21/4-870), RR=1.95 (95%CI: 1.23-3.12), P=0.005]; the risk of severe diarrhea was the highest [6.8% (602/8-894)]. There was no significant difference in the risk of severe vomiting and severe abdominal pain compared with the control group [1.4% (79/5-788) vs. 0.7% (32/4-428), RR=1.49 (95%CI: 0.90-2.47), P=0.120; 1.7% (82/4-766) vs. 1.1% (40/3-628), RR=1.35 (95%CI: 0.84-2.16), P=0.210]. The results of network meta-analysis on risk of severe diarrhea events showed that the relative risks of severe diarrhea caused by varieties of VEGFR-TKI were axitinib>anlotinib>cabozantinib≈vandetanib≈sunitinib≈lenvatinib≈sorafenib≈pazopanib>regorafenib>fruquintinib>apatinib in the order. Conclusion The application of VEGFR-TKIs, especially axitinib, can increase the risk of severe diarrhea in patients with tumors, which deserves clinical attention and vigilance.

  • Xu Yichun, Liu Chen, Shen Jianghua, Zhang Lan, Chu Yanqi
    Abstract ( ) PDF ( )
    Contrast induced acute kidney injury (CI-AKI) is a serious complication after contrast- enhanced CT scanning. Since the incidence of CI-AKI after contrast-enhanced CT scanning is very low, it is particularly important to screen the high-risk population of CI-AKI for targeted prevention using the risk assessment model. In this paper, 6 risk prediction models for CI-AKI after contrast-enhanced CT scanning are retrieved by searching the literature at home and abroad, including Herts′ prediction equation, Kim′s nomogram prediction model, Huang′s scoring prediction model, Moos′s risk factor prediction model, Jeon′s risk scoring prediction model, and Baek′s risk scoring model for CI-AKI prognosis in patients with chronic kidney disease. The predictive factors involved in the 6 models include estimated glomerular filtration rate, serum creatinine, and serum albumin before contrast-enhanced CT scanning, patient′s age, history of diabetes mellitus, hypertension, and chronic kidney disease, development of acute hypotension or congestive heart failure, and repeated use of contrast. Baek′s risk scoring model is used to predict the development and outcome of CI-AKI in patients with chronic kidney disease after contrast-enhanced CT scanning, while the other 5 models are prediction models for the risk of CI-AKI after contrast-enhanced CT scanning. However, the performance indicators of these 6 models are incomplete and lack of external verification by other researchers.
  • Ni Chunyan
    Abstract ( ) PDF ( )
    A 72-year-old male patient received anti-infectious treatments with piperacillin sodium and tazobactam sodium, moxifloxacin, and posaconazole, and expectorant treatment with acetylcysteine for pulmonary infection after lung transplantation; original antirejection therapy with tacrolimus and mycophenolate mofetil was continued. Before treatments, serum creatinine was 98-μmol/L and blood urea nitrogen was 3.4-μmol/L. On the 5th day of treatments, the trough blood concentration of tacrolimus increased to 22.9-μg/L, serum creatinine increased to 497-μmol/L, and blood urea nitrogen increased to 17.91-mmol/L. During the consultation, the clinical pharmacists learned that the patient used posaconazole and tacrolimus in combination. They also understood that posaconazole could inhibit the activity of liver cytochrome P450 (CYP) 3A4, while tacrolimus was mainly metabolized by CYP3A4 by searching the literature. Then it is considered that the acute kidney injury caused by tacrolimus occurred due to the increase of blood concentration following the simultaneous application of tacrolimus and posaconazole. Clinical pharmacists recommended that posaconazole was replaced by caspofungin and the dose of tacrolimus was reduced. The clinician adopted the above recommendations and the patient was given continuous venous-venous hemofiltration meantime. Eight days later, the patient′s serum creatinine level gradually decreased to 334-μmol/L, blood urea nitrogen was 7.6-mmol/L, and urine volume was 200-ml. Then hemodialysis was performed 3 times a week; 1 month later, the patient′s serum creatinine was 115-μmol/L, and blood urea nitrogen was 7.2-mmol/L.
  • Zhao Xue, Li Fan, Zhang Yanli, Zhang Xiao, Cao Junling
    Abstract ( ) PDF ( )
    A 41-year-old female patient received long-term treatment with metformin, glimepiride, sitagliptin, and acarbose for type 2 diabetes mellitus. Due to elevated blood-glucose, the hypoglycemic regimen was adjusted to metformin, acarbose, and dulaglutide (1.5-mg, subcutaneously injected once a week). After each injection of dulaglutide, the patient had severe anorexia but no intervention was given because that the patient could tolerate. Empagliflozin 10-mg orally once daily were added 3 days after the first injection and then the dose was adjusted to 10-mg next day. The day after the fourth injection, the patient developed dizziness, nausea, vomiting, general fatigue, etc. Laboratory tests showed blood glucose 20-mmol/L, arterial blood pH 7.22, partial pressure of carbon dioxide 22.1-mmHg, bicarbonate concentration 8.8-mmol/L, standard bicarbonate 12-mmol/L, total carbon dioxide content 10-mmol/L, ketone body in urine (+++), and urine sugar (++++). Diabetic ketoacidosis was diagnosed. Considering that severe anorexia after the application of dulaglutide caused serious insufficient carbohydrate intake and then empagliflozin- induced diabetic ketoacidosis was stimulated, the 2 drugs were discontinued and symptomatic and supportive treatments were given. Five days later, laboratory tests showed post-lunch blood glucose 10.1-mmol/L, ketone body in urine (+), negative urine sugar, and urine pH 5.5. Empagliflozin 5-mg once daily was added and laboratory tests showed carbon dioxide binding capacity of the blood 23.2-mmol/L, urine ketones (+++), urine sugar (++++), and uric acidity 5.0 four days later. The patient insisted on leaving the hospital. After discharge, she was treated with recombinant insulin glargine, acarbose, and empagliflozin. At 1 month of follow-up, symptoms of diabetic ketoacidosis did not recur.
  • Wei Huabo, Zhang Junguo, Tan Bing, Dong Yang
    Abstract ( ) PDF ( )
    A 65-Year-old male patient with squamous cell lung cancer received chemotherapy with paclitaxel (210-mg by an IV infusion on day 1) and carboplatin (0.5 g by an IV infusion on day 1; 21 days was a cycle) and targeted therapy with apatinib (0.25 g orally once daily). About 1 hour after the first oral administration of apatinib, the patient developed dyspnea, chest tightness, followed by limb numbness and fatigue. About 1 hour after the second administration, the above symptoms recurred, accompanied by lower limb pain, speak disability, and arrhythmia. The symptoms were considered to be related to apatinib. The drug was stopped and the treatments including noninvasive ventilator assisted breathing, antiallergic, antispasmodic, and antiasthmatic were given. Five days later, the above symptoms disappeared.
  • Cheng Shuqiao, Yin Tao
    Abstract ( ) PDF ( )
    A 52-year-old female patient with gastrointestinal stromal tumor received imatinib 0.4 g once daily after surgery. Approximately 5 months of imatinib treatment, the patient developed nausea, vomiting, fatigue, and yellowish skin. Laboratory tests showed alanine aminotransferase (ALT) 388-U/L, aspartate aminotransferase (AST) 336-U/L, and total bilirubin (TBil) 32-μmol/L. Drug-induced liver injury was considered and imatinib was discontinued. Further examination showed albumin 29.5-g/L, HBV DNA 3.57×106 IU/ml, and prothrombin activity (PTA) 21%. Abdominal enhanced CT showed peritoneal effusion. The patient was a chronic HBV carrier with negative e antigen (more than 20 years). Combined with the above examination results, the patient was diagnosed as acute-on-chronic liver failure, which is probably to be caused by HBV reactivation induced by imatinib. After 24 days of treatments with antivirus drugs, liver-protective drugs, and artificial extracorporeal liver support, the patient′s ALT was 25-U/L, AST was 39-U/L, TBil was 165-μmol/L, and HBV DNA was 659 IU/ml. About 5 months later, the patient′s liver function returned to normal, with HBV DNA 262 IU/ml.
  • Liu Donghua, Xing Xiaomin, Yang Xue, Liang Yu, Zhao Jun, Liu Xuelian, Yu Jing, Liu Yuefen
    Abstract ( ) PDF ( )
    A 25-year-old male patient received intravenous infusion of tegacyclin 50-mg once per 12-hours from the 3rd day after renal transplantation because the bacterial culture of the donor kidney preservation solution showed carbapenem resistant Acinetobacter baumannii. On the 4th day after using tegacyclin, the patient developed epigastric pain, which was improved after gastric protection treatment. On the 8th day of medication, the patient developed persistent severe pain in his left lower abdomen. On the 9th day of medication, laboratory tests showed amylase 1-188-U/L and lipase 699-U/L. Pancreatic ultrasonic examination suggested acute edematous pancreatitis. Acute pancreatitis was diagnosed, which was considered to be related to tigecycline. Tigecycline was stopped. An IV infusion of octreotide acetate injection 0.6-mg dissolved in 0.9% sodium chloride injection 50 ml twice daily was given and diet was prohibited at the same time. Five days later, his symptoms of abdominal pain was improved significantly, pancreatic amylase decreased to 69-U/L, and lipase decreased to 646-U/L.
  • Zhang Juan, Wang Yinglin, Zhao Quan
    Abstract ( ) PDF ( )
    A 44-year-old male patient with type 2 diabetic ketosis received intravenous injection of 3.375 g piperacillin sodium and tazobactam sodium once every 8 hours for urinary tract infection. The patient′s platelet count (PLT) was 288×109/L before treatment. After 5 days of treatment, the patient′s PLT increased to 729×109/L. Secondary thrombocytosis was diagnosed, which was considered to be related to piperacillin sodium and tazobactam sodium. The drug was stopped and replaced by levofloxacin 0.5 g once daily orally. Five days later, the patient′s PLT decreased to 491×109/L; 14 days later, the PLT decreased to 280×109/L.
  • Liang Yu, Meng Zhen, Liu Donghua, Cang Huaiqin, Ji Hongyan, Yang Xue, Quan Xianghua
    Abstract ( ) PDF ( )
    A 64-year-old male patient with gastric adenocarcinoma received chemotherapy with oxaliplatin (250-mg intravenous infusion on day 1) and tegafur gimeracil oteracil potassium (60-mg orally twice daily on day 1 to day 14, 21 days as a cycle). One month later, he was given nivolumab immunotherapy (240-mg intravenous infusion on day 1, 14 days as a cycle). On the 2nd day of the 4th cycle of nivolumab treatment (the 44th day after the first dose), the patient developed diarrhea with watery stools, 3 to 4 times a day, accompanied by mild abdominal pain; 3 days later, the diarrhea worsened, showing dark red bloody stools, covered with pus moss, up to 10 times a day, accompanied by obvious abdominal pain. According to colonoscopy and histological examination results, ulcerative colitis (initial onset, total colon, active stage, and severe) was diagnosed, which was considered as a grade 3 immune-related colitis induced by nivolumab. After suspension of chemotherapy and immunotherapy, and administration of glucocorticoids and octreotide, the patient′s abdominal pain and diarrhea were gradually improved. On the 45th day of nivolumab withdrawal, the patient received chemotherapy with oxaliplatin and tegafur gimeracil oteracil potassium again, and colitis did not recur.
  • Du Xueting, Zhu Xiaoli, Gao Lingna, Sun Hongshuang, Ma Hongfang
    Abstract ( ) PDF ( )
    A 66-year-old female patient regularly received nifedipine sustained release tablets 20-mg twice daily and captopril 25-mg once daily by mouth for 2 years due to hypertension. Low blood glucose (3.0-mmol/L) appeared in recent 1 year, frequent hypoglycemic coma occurred in recent 4 months. Laboratory tests showed minimum fasting glucose 1.6-mmol/L, insulin 12 mU/L, C-peptide 1.78-nmol/L, and positive anti-insulin antibody. Insulin autoimmune syndrome was considered, which might be associated with captopril. Then captopril was stopped, nifedipine sustained-release tablets was continued, irbesartan hydrochlorothiazide was added, and prednisone 30-mg orally once daily was given at the same time. In addition, the patient was asked to adjust diet, including low carbohydrate and eating less and often. After stopping captopril for 3 days, her blood glucose was between 4.3 to 11.2-mmol/L, and hypoglycemia did not recur.
  • Wang Min, Zhang Li
    Abstract ( ) PDF ( )
    A 63-year-old male patient underwent coronary CT angiography and intravenous injection of 100-ml of iopromide. About 2-minutes after finishing the examination, the patient felt chest tightness, shortness of breath, general discomfort, redness of skin, and scattered rash, followed by transient disturbance of consciousness and urinary incontinence. Two to 3-minutes later, the patient regained consciousness, and was restless; the blood pressure was 51/35-mmHg. Electrocardiogram showed ST segment elevation in leads I, AVL, and V1-V5 and increase of troponin, creatine kinase, and brain natriuretic peptide precursors. After antiallergy, antishock, fluid replacement, volume expansion, and antiplatelet treatments, electrocardiogram was normal and blood pressure was 132/78-mmHg. After retrospective analysis of cases and literature review, it was considered that the patient had Kounis syndrome resulted by iopromide-induced anaphylactic shock.
  • Li Jinfeng, Hou Jia, Miao Xiaojin, Wang Quan, Li Fengjun, Zhang Yuan
    Abstract ( ) PDF ( )
    A 59-year-old male patient received targeted drug recombinant human endostatin injection 15-mg intravenously once daily for 14 days for poorly differentiated adenocarcinoma of lung with brain metastasis. On the 17th day after drug withdrawal, erythema and pruritus appeared on the neck and chest, and then the erythema quickly spread to the whole body, with blisters and extensive epidermal exfoliation, accompanied by pruritus, pain, and mild fever. Toxic epidermal necrolysis caused by recombinant human endostatin was considered. High-dose of glucocorticoid and human immunoglobulin were given and 2 weeks later, the skin lesions healed basically.