2024 Volume 26 Issue 4 Published: 23 April 2024
  

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  • Cui Shijun, Guo Jianming, Tong Zhu, Guo Lianrui, Gu Yongquan
    Abstract ( ) PDF ( )
    Objective To explore the long-term efficacy and safety of gene therapy with pUDK- hepatocyte growth factor (pUDK-HGF) for rest pain and ulcers caused by critical limb ischemia. Methods Long-term follow-up were conducted through outpatient and telephone on patients who completed the pUDK-HGF Phase Ⅱ randomized double-blind placebo-controlled trial. The occurrence of tumors was observed, and tumor markers detection, fundus examination, visual analogue scale (VAS), and lower limb CT angiography (CTA) were performed according to voluntary principle. The results were analyzed descri- ptively and statistically. Results A total of 53 patients were included in the analysis, of which 15 (28.3%) were in the placebo group and 38 (71.7%) were in the pUDK-HGF treatment group in the Phase Ⅱ clinical trial. The median follow-up time was 2.8 years, ranging from 1.7 to 3.5 years. During the follow-up period, no tumor was found in the 53 patients. Among the 38 patients in the pUDK-HGF treatment group, 18 underwent comprehensive examination and evaluation, including tumor markers, fundus and CTA examination, and patients with resting pain underwent VAS evaluation. Among them, 1 patient had transient mild elevation of carcinoembryonic antigen, and no abnormal tumor markers were found in the other 17 patients; no proliferative retinal vasculopathy was found in the fundus examination. At the end of the phase Ⅱ clinical trial (out-group), 3 were effective and 2 were ineffective of the 5 patients with rest pain; at the end of this follow-up period, 4 were evaluated as effectiveness and 1 as ineffectiveness according to CTA, and 5 were all evaluated as effectiveness according to VAS. Of the 13 patients with ulcer, 9 were evaluated as effectiveness and 4 were as ineffectiveness according to CTA at out-group; 10 were evaluated as effectiveness and 3 were as ineffectiveness at the end of this follow-up. Conclusions pUDK-HGF had relatively good safety in the treatment of rest pain and ulcers caused by critical limb ischemia. No risk of carcinogenesis and proliferative retinal vasculopathy has been found, and the long-term efficacy of pUDK-HGF is good.
  • Fan Caixia, Xu Kun, Li Hongyan, Liu Wenqi, Zhu Zongfa, Li Zhengrong, Bi Yunyan, Zhang Shilin, Zhu Xiaosong, Wang Shiming
    Abstract ( ) PDF ( )
    Objective To investigate the effect of intravenous application of furosemide on occurrence of cardiac surgery-associated acute kidney injury (CSA-AKI) in patients after cardiac surgery. Methods The electronic medical records of patients undergoing cardiac surgery in Linyi People′s Hospital from January 2014 to December 2022 were collected and retrospectively analyzed. According to whether CSA-AKI occurred after surgery, the patients were divided into AKI group and non-AKI group and the clinical characteristics between the 2 groups were compared. Multivariate logistic regression was used to analyze the influencing factors of CSA-AKI, and the odds ratio (OR) and its 95% confidence interval (CI) were calculated. Results A total of 2-633 patients were enrolled in the analysis, including 1-601 males (60.8%) and 1-032 females (39.2%). The age was (62.8±8.9) years, ranging from 18 to 85 years. Among the 2-633 patients, 491 (18.6%) developed CSA-AKI. Multivariate logistic regression analysis showed that after adjusting for factors such as the type of operation, intraoperative cardiopulmonary bypass, hypertension, diabetes mellitus, hypoalbuminemia, NYHA cardiac function class Ⅲ/Ⅳ, intraoperative/postoperative aortic balloon counterpulsation, preoperative serum creatinine level, operation duration, and the number of vasoactive drugs used after the operation, postoperative intravenous application of furosemide was still independently associated with the occurrence of CSA-AKI (OR=2.161, 95%CI: 1.720-2.715, P<0.001). Conclusions The incidence of CSA-AKI in patients enrolled in this study was 18.6%. Intravenous use of furosemide after cardiac surgery can increase the risk of CSA-AKI.
  • Ji Wen, Wang Shuping, Tang Zhenguo, Zhang Wen
    Abstract ( ) PDF ( )
    Objective To explore the clinical characteristics of cardiotoxicity due to 5-hydroxytryptamine 3 receptor (5-HT3) antagonists. Methods Relevant databases at home and abroad (up to June 20, 2023) were searched and case literature of cardiotoxicity induced by 5-HT3 receptor antagonist were collected. Relevant information of patients, medication status (drug name, usage and dosage, indication, combined drugs), occurrence of cardiotoxicity, evaluation of the association between 5-HT3 receptor antagonists and cardiotoxicity, intervention measures and outcomes were extracted and analyzed descriptively and statistically. Results A total of 23 case reports, 22 in English and 1 in Chinese, were enrolled in the analysis. There were 26 patients, 6 males and 20 females, and the age ranged from 8 to 60 years, with an average of 40 years. The reasons for drug use were perioperative antiemesis in 19 patients, chemotherapy antiemesis in 2 patients, and other reasons in 5 patients. Ondansetron was used in 19 patients, dolasetron in 4 patients, granisetron, tropisetron and palonosetron in 1 patient each. Except for 1 patient with overdose by self-medication, the dosage in 25 patients was within the recommended range in labels. A total of 50 case time of cardiotoxicity occurred in 26 patients, mainly including tachycardia (12 cases), electrocardiogram (ECC) changes (11 cases), bradycardia (9 cases), cardiac arrest (1 case), and myocardial infarction (1 case), etc. Twenty-one patients experienced cardiotoxicity after initial medication, of which 8 occurred immedia- tely after the initial medication, 5 patients occurred after ≥2 times of medication. After the occurrence of cardiotoxicity, 26 patients stopped 5-HT3 receptor antagonists successively, of which 24-stopped the drug immedia- tely and received symptomatic treatments, 1 stopped the drug after 8 days of medication without other intervention, and 1 stopped the drug and received symptomatic treatment after the symptoms aggravated. After drug withdrawal and/or symptomatic treatments, the mentioned symptoms disappeared and ECC returned to normal in 25 patients. Of them, 22 patients had a recovery time of ≤48-hours, while the other 3 patients had their ECG returned to normal at 1 week, 2 weeks, and 2 months, respectively; one patient died due to ineffective treatment for ventricular fibrillation. Conclusions The cardiotoxicity induced by 5-HT3 receptor antagonists mostly occurs after the initial medication, and mainly manifests as tachycardia, bradycardia, ECG changes, etc. Most patients have a good prognosis after timely drug withdrawal and symptomatic treatments, and in severe cases, it can lead to death.
  • Zhang Hong, Chen Lei, Wang Qi, Wang Xiaojuan
    Abstract ( ) PDF ( )
    Objective To explore the occurrence, clinical characteristics and influencing factors of hypoglycemia induced by somatostatin in patients with acute pancreatitis (AP). Methods The electronic medical records of AP patients treated with somatostatin in Fuyang people′s Hospital from May 1, 2019 to September 10, 2023 were collected. Patients with hypoglycemia caused by somatostatin were screened out, and the clinical characteristics of these patients were retrospectively analyzed. Patients were divided into hypoglycemia group and non-hypoglycemia group according to whether somatostatin-related hypoglycemia occurred. The clinical characteristics in patients of the 2 groups were compared and the influencing factors of somatostatin related hypoglycemia were analyzed using multivariate logistic regression method. The effect sizes were the odds ratio (OR) and its 95% confidence interval (CI). Results A total of 353 patients were included in the analysis and 33 patients were diagnosed with somatostatin-related hypoglycemia, with an incidence of 9.3%. Of the 33 patients, 22 (66.7%) were male and 11 (33.3%) were female, aged (52±20) years. Thirty-three patients experienced a total of 66-hypoglycemic events, of which 17 (51.5%) had multiple episodes (≥2). The median blood glucose of 66-hypoglycemic events was 2.7-mmol/L, ranging from 1.8 to 3.8-mmol/L. Fifty-six times of hypoglycemia occurred during somatostatin treatment in 30 patients (90.9%), with a median time of 3 (2, 4) days for the first occurrence of somatostatin, and 39.3% (22/56) and 21.4% (12/56) of hypoglycemia episodes occurred in the first half of the night (18:00 to 23:59) and the second half of the night (0:00 to 5:59), respectively. Ten times of hypoglycemia occurred 4-7 days after somatostatin withdrawal in 3 patients (9.1%). Multivariate logistic regression analysis showed that diabetes mellitus was an independent risk factor for the occurrence of somatostatin related hypoglycemia in patients with AP (OR=6.574, 95%CI: 1.911-22.430, P=0.003), while high serum total protein and parenteral nutrition support were protective factors (OR=0.940, 95%CI: 0.885-0.998,P=0.043; OR=0.405, 95%CI: 0.166-0.990, P=0.047). Conclusions Patients with AP should be alert to the occurrence of hypoglycemia during somatostatin treatment and within 1 week after drug withdrawal, especially at night. Diabetes mellitus and low serum total protein were independent risk factors for the occurrence of somatostatin-related hypoglycemia in patients with AP, while parenteral nutrition support was a protective factor.
  • Fan Liyuan, Li Mengge, He Yifu, Xing Yufei, Yang Ying, Ding Conglan
    Abstract ( ) PDF ( ) Supplementary files
    Objective To improve the skin toxicity management model of tumor targeted drugs based on evidence-based practice method and apply it to clinical practice. Methods Using the evidence- based practice method of Joanna Briggs Institute, evidence of skin toxicity management of tumor targeted drugs was formed by searching relevant guidelines and evidence-based medical literature at home and abroad, and conducting interviews and surveys with nurses and patients. Based on the evidence and in consultation with evidence-based medicine, nursing and clinical experts, the evidence was transformed into management improvement plans, and the skin toxicity checklist and care checklist were developed. The improvement scheme was applied to clinical practice, the training of nurses was strengthened, the nursing process was standardized and improved, and various forms of health education were provided to patients. Patients with skin toxicity who received targeted drug therapy in the Department of Oncology of Anhui Cancer Hospital from May to August 2023 were collected. Implementation of various management indicators by nurses before and after management improvement were compared. The occurrence and severity of skin toxicity in patients were compared to verify the effect of the improvement. Results A total of 35 tumor patients with skin toxicity to targeted drugs were entered, including 26 males and 9 females, with age (60±10) years. Compared with before, the implementation rate of the 5 indicators after the management improvement, including the evaluation of skin toxicity and risk factors by nurses using the common terminology criteria for adverse events version 5.0, the qualified status of related nursing documents, the health education of skin care, and regular follow-up of patients, were significantly increased (from 0-31.4% up to 80%-100%), the differences were statistically significant (all P<0.05). After improvement, the incidence and severity of skin rash, skin dryness, skin reaction of hands and feet, and paronychia were significantly reduced, the score of skin care knowledge questionnaire was significantly increased [6.00(5.00, 8.00) vs. 8.00(7.00, 9.00), P=0.002], and the dermatology life quality index was significantly decreased [8.00(6.00, 9.00) vs. 6.00(5.00,8.00), P=0.033]. The differences in anxiety and depression scores were not statistically significant (both P>0.05). Conclusion The skin toxicity management of targeted drugs based on JBI evidence-based practice method can standardize the clinical nursing practice of nurses, improve the severity of skin toxicity in tumor patients, and improve their quality of life.
  • Wang Xinglong, Hu Qingyuan, Bai Jie, Song Zhihui
    Abstract ( ) PDF ( )
    Objective To investigate the risk of adverse event (AE) associated with inclisiran and to provide reference for the safe use in clinical practice. Methods The AE reports in the US FDA Adverse Event Reporting System (FAERS) database from the 4th quarter of 2004 to the 2nd quarter of 2023 with inclisiran as the primary suspect drug were collected. AE was standardized and classified using the preferred terminology (PT) and the system organ class (SOC) of the Medical Dictionary for Regulatory Activities 26.0. AE risk signal mining was performed using the report odds ratio (ROR) method and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method. PT that was considered as an AE risk signal in both methods were defined as AE risk signals [ROR method: ≥3 reports  and the lower limit of the 95% confidence interval (CI) of the ROR>1; MHRA comprehensive standard method: ≥3 reports、PRR ≥2 and χ2≥4]. A descriptive statistical analysis was performed. Results A total of 1 888 AE reports were collected with inclisiran as the primary suspect drug, involving 1-888 patients and 835 PTs. The AE was predominantly reported in the United States (88.7%, 1 675/1 888), and predominantly by the consumer (62.1%, 1 171/1 886); there were a total of 484 reports (25.6%) about serious AE. Excluding non-drug and indication-related PTs, 85 PTs (involving 15 SOCs) met the criteria in both the ROR method and the MHRA comprehensive standard method, and defined as AE risk signals. The top 5 PTs ranked by the number of reports were arthralgia (248 cases), injection site pain (237 cases), limb pain (170 cases), myalgia (158 cases), and diarrhea (132 cases); the top 5 PTs ranked by the signal intensity included bladder discomfort (ROR=28.87, PRR=28.85), injection site discomfort (ROR=24.48, PRR=24.40), sinus pain (ROR=23.20, PRR=23.19), injection site vesicles (ROR=17.63, PRR=17.61), and injection site rash (ROR=12.51, PRR=12.45). Among the top 20 PTs ranked according to the number of reports and signal intensity respectively, 8 and 13 PTs were not documented in domestic and international specifications, of which myalgia and hypoacusis had more reports and stronger signal intensity. Conclusion The main AE  of inclisiran in the US FAERS database were injection site reactions, followed by musculoskeletal-related AEs (arthralgia, myalgia, and myospasm, etc.) and infection-related AEs (such as urinary tract infections and bronchitis), which require clinical attention.
  • Yang Yanni, Li Shuxia, Zhang Xiaojuan, Jin Weijun, Chen Minghao
    Abstract ( ) PDF ( )
    Objective To actively monitor and analyze the safety of levofloxacin and sodium chloride injection produced by Guangzhou Green Cross Pharmaceutical Co., Ltd (generic drug). and levofloxacin and sodium chloride injection produced by Daiichi Sankyo (Beijing) Pharmaceutical Co., Ltd (original drug). Methods The data in this study came from the adverse drug reaction reports on levofloxacin and sodium chloride injection voluntarily monitored and reported to the National Adverse Drug Reaction Monitoring System Database by the First Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial People′s Hospital, and the First Affiliated Hospital of Ji'nan University from October 1, 2022, to September 30, 2023. The information on patients′ age, gender, medication use, primary disease, time from medication to the occurrence of adverse reactions, clinical manifestations, treatment and prognosis of adverse reactions, and the occurrence of serious adverse reactions were collected. The incidence of adverse reactions was calculated. Results A total of 30 adverse reaction reports involving levofloxacin and sodium chloride injection were collected, involving 30 patients. In the generic drug group, there were 21 cases, including 8 males and 13 females, aged from 20 to 91 years with a median age of 43 years; 2 cases of serious adverse reactions were reported. In the original drug group, there were 9 cases, including 3 males and 6 females, aged from 20 to 96 years with a median age of 56 years; no serious adverse reactions were reported. In the generic drug group, a total of 36 adverse reactions occurred in 21 patients, while in the original drug group, a total of 13 adverse reactions occurred in 9 patients. These adverse reactions involved the skin and appendages, digestive system, nervous system, musculoskeletal system, urinary system, and medication site, with skin itching and rash being the most common allergic reactions (15 case time in the generic drug group, accounting for 41.7%; 6 case time in the original drug group, accounting for 46.2%). Two cases of serious adverse reactions occurred in the generic drug group, and both were anaphylactic shock. After discontinuation of the drug, switching to other antibiotics, and symptomatic treatments, 5 cases in the generic drug group were cured, 15 cases were improved, and 1 case was unknown. In the original research drug group, 2 cases were cured and 7 cases were improved. There were no deaths in either the generic or original drug groups. The incidence of adverse reactions in outpatients and/or inpatients in the generic drug group was 0.07% (21/29 557), while that in the original research drug group was 0.08% (9/10 686). There was no statistically significant difference between the 2 groups (χ2=0.183, P=0.669). Conclusion The results of active monitoring show that there is no significant difference in safety between the generic and original drugs of levofloxacin and sodium chloride injection.
  • Zhang Tai, Wu Qiang, Wang Jin, Zhang Yunli
    Abstract ( ) PDF ( )
    Dextran 40 is a commonly used pharmaceutical excipient and can be used as formulations of dry powder for injection. But it has antigenic properties that can trigger severe allergic reactions. Therefore, injections containing the excipient dextran 40 may have additional safety risks that are not easily recognized in the clinic. Dextran 40-associated allergic reactions may also interfere with the diagnosis of certain diseases and limit the choice of therapeutic drugs. Revision of the relevant instructions and improvement of the clinical dosing process can help reduce the risk of injections containing the excipient dextran 40 in clinical use. Physicians and pharmacists should expand their clinical and pharmacological thinking to evaluate the antigenicity of the excipient dextran 40 as an independent influence factor in the rational and safe use of medication. Identification individual cases of adverse events caused by this excipient and taking measures to minimize adverse events caused by this excipient in different drugs can help effectively reduce the risk of drug safety of the relevant formulations.
  • Yuan Heqing, Gao Lu, Shao Xiying
    Abstract ( ) PDF ( )
    Ado-trastuzumab emtansine (T-DM1) is a conjugate of trastuzumab and emtansine, which is one of the options for adjuvant therapy of residual invasive lesions after neoadjuvant therapy and rescue treatment of advanced breast cancer in patients with human epidermal growth factor receprot 2(HER2) mutation. Thrombocytopenia is one of the common adverse reactions of T-DM1. The incidence of all grade of thrombocytopenia was 3.6%-38.2%, and the incidence of grade 3 and above of thrombocytopenia was 0.4%-14.3% during treatment. The risk of thrombocytopenia is higher in Asian populations, patients with prior therapy of platinum, and those with a baseline platelet count of ≤200×109/L. The mechanism of thrombocytopenia caused by T-DM1 is not clear. Attention should be paid to monitoring platelet count during treatment, and patients with thrombocytopenia should be treated according to the severity.
  • Guo Ningning, Fang Gaofei
    Abstract ( ) PDF ( )
    A 64-year-old female patient received treatments such as antibacterial, analgesic, etc. due to local swelling and blisters caused by application of domestically made drug for external use for knee joint pain. After 7 days, local skin redness and swelling appeared, with scattered rashes. Anti-allergic treatments including intravenous infusion of calcium gluconate and oral desloratadine cirate were given. On the second day, the patient developed a wheal like rash all over her body, and intravenous infusion of anti-allergic drugs were continued. On the same day, the patient′s skin symptoms were improved. The patient′s systemic rash worsened again after 1.5-hours of reapplication of desloratadine cirate, and the next day, angioneurotic edema appeared. Desloratadine cirate was stopped, dexamethasone, promethazine, and other symptomatic treatments were continued. Four days later, the patient′s symptoms completely disap- peared.
  • Fan Kongli, Fu Guangwei, Sang Xisheng
    Abstract ( ) PDF ( )
    A 64-year-old female patient with bilateral knee joint pain received Hehe pills 10 g twice daily by herself. After 2 months of treatment, she stopped taking the medicine. On the 10th day after discontinuation of medication, yellowish skin, mucosa, and sclera appeared. Laboratory tests showed alanine aminotransferase 274-U/L, aspartate aminotransferase 274-U/L, alkaline phosphatase 713-U/L, total bilirubin 412.7-mmol/L, direct bilirubin 216.2-mmol/L. Severe liver injury caused by Hehe pills was considered. Symptomatic and supportive treatments including liver protection and jaundice reduction, and bilirubin adsorption were given. One month later, the yellowish skin, mucosa, and sclera in the patient were significantly improved, and 2 months later, liver function returned to normal. The patient′s liver injury was most likely related to the Aconiti Kusnezoffii Radix, Aconiti Radix, Olibanum, and Myrrha contained in Hehe pills.
  • Xu Qian, Wu Wei, Wang Chunhui
    Abstract ( ) PDF ( )
    A 65-year-old male patient received immunotherapy combined with targeted therapy (nivolumab 360-mg intravenously on day 1 and anlotinib 12-mg orally once daily from day 1 to day 14, 21 days as a cycle) for tumor recurrence after radical gastrectomy for gastric cancer. Hypothyroidism and hand-foot syndrome occurred during the 7th cycle of treatment, then anlotinib was discontinued, and levothyroxine sodium 50-μg once daily was given. On the 9th cycle of nivolumab treatment, the patient developed unexplained fatigue, and laboratory tests showed that adrenocorticotropic hormone (ACTH) (8: 00-am) 19.5-ng/L, cortisol (8: 00-am) 191-nmol/L, thyrotropin 19.3 mU/L, and free thyroxine 11.5-pmol/L. The dosage of levothyroxine sodium increased to 100-μg/d orally once daily. After that, the levels of ACTH and cortisol in the patient continued to decline, which was considered to be immune-related hypophysitis caused by nivolumab. Nivolumab was stopped and cortisol replacement therapy was given. Eleven days later, the patient′s fatigue symptom was alleviated. At 1 year follow-up, laboratory tests showed that the level of cortisol gradually returned to normal, but ACTH was still less than 1.5-ng/L, suggesting that the damage of pituitary gland in the patient caused by nivolumab was irreversible.
  • Liao Ziqiong, Dong Shujie, Zhao Rongsheng
    Abstract ( ) PDF ( )
    A 63-year-old female patient with multiple systemic metastases from lung adeno- carcinoma was treated with befotertinib (75-mg orally once daily) and other symptomatic supportive treatments. Before treatments, her platelet count (PLT) was 177×109/L. After 35 days of medication, the patient had a transient loss of consciousness with chest tightness and shortness of breath. Computed tomography pulmonary angiography showed multiple embolism in bilateral pulmonary arteries. Laboratory tests showed that D-dimer was 35.16-g/L, and PLT was 34×109/L. The pulmonary embolism and throm- bocytopenia were considered to be caused possibly by befotertinib. Befotertinib was stopped, and enoxaparin sodium injection and rivaroxaban were given successively for anticoagulation. Thirteen days later, the chest tightness and shortness of breath were significantly improved, D-dimer was 0.57-g/L, and the PLT was 123×109/L.
  • Yuan Ting, Weng Wenhan, Zhao Yang, Yu Zhiying
    Abstract ( ) PDF ( )
    A 52-year-old male patient with small cell lung cancer developed symptoms of systemic skin redness, edema, and blisters of varying sizes in multiple parts of the body (neck, chest, and feet) 10 days after receiving chemotherapy with TC regimen (albumin paclitaxel and carboplatin) combined with serplulimab for immunotherapy. It is suspected to be toxic epidermal necrolysis caused by serplulimab. After discontinuing serplulimab and receiving symptomatic treatments such as methylprednisolone, loratadine, ebastine, and adjuvant topical mucosal protection for 10 days, the dermatitis basically subsided and the ruptured blisters were scabby. The patient switched to anlotinib and did not receive immunotherapy again.