Targeted therapy is one of the important methods of treatment for non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) have the characteristics of high efficacy and low toxicity, and are used in the precise treatment in NSCLC patients with gene mutation. Common gene mutations include genes encoding epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Different patients have different responses to TKIs. Monitoring the blood concentration of TKIs can help better predict the clinical outcome (efficacy/toxicity) and optimize the treat strategies. In this paper, the relevant literature at home and abroad in the past 10 years are searched, and the relationship between the blood trough concentration of EGFR-TKI and ALK-TKI commonly used in clinic and the efficacy/toxicity are reviewed.

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.

Targeted therapy is one of the important methods of treatment for non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) have the characteristics of high efficacy and low toxicity, and are used in the precise treatment in NSCLC patients with gene mutation. Common gene mutations include genes encoding epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Different patients have different responses to TKIs. Monitoring the blood concentration of TKIs can help better predict the clinical outcome (efficacy/toxicity) and optimize the treat strategies. In this paper, the relevant literature at home and abroad in the past 10 years are searched, and the relationship between the blood trough concentration of EGFR-TKI and ALK-TKI commonly used in clinic and the efficacy/toxicity are reviewed.

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.

With the application of immune checkpoint inhibitors (ICIs), the acute kidney injury (AKI) caused by ICIs has attracted increasingly extensive attention. The incidence of ICIs-induced AKI is 0.8%-29%, which can occur weeks or months after the first drug use or even after drug withdrawal. The typical renal histopathological features of AKI are acute tubulointerstitial nephritis, and glomerulopathy can also be seen. The risk factors include combined application of ICIs, the use of proton pump inhibitors, and having chronic kidney diseases, etc. After the diagnosis of AKI, it is necessary to decide whether to reduce the dose or stop using ICIs and start glucocorticoid treatment or add other immunosuppressive drugs according to the degree of disease and the specific situation of the patient. In case of level 3-4 AKI, ICIs shall be permanently discontinued.

Objective:To explore the characteristics and factors affecting the occurrence of renal injury in patients with abnormal biochemical indexes of renal function after the use of immune checkpoint inhibitors (ICIs), and to provide reference for selection of clinical treatment regimen.Methods:Patients who were treated with immune checkpoint inhibitors researched and developed independently in China including camrelizumab, sintilimab, tislelizumab, and toripalimab from March 1, 2021 to February 28, 2022 and showed estimated glomerular filtration rate (eGFR) <90 ml/(min·1.73 m 2) and/or serum creatinine (Scr)>105 μmol/L were retrieved from the China Hospital Pharmacovigilance System. The clinical data including general information, anti-tumor treatment regimen, laboratory test results, and concomitant medications were collected. Patients were divided into kidney injury group and non-kidney injury group, and all the clinical characteristics were compared between the 2 groups, the influencing factors of kidney injury were analyzed using a binary logistic regression model, the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated. Results:A total of 222 patients were entered in the analysis, including 170 males and 52 females, with a median age of 67 (36, 85) years. Of them, 144 patients were treated with carrilizumab, 38 with sindilizumab, 31 with tirelizumab, and 9 with treprolizumab; 29 patients (13.1%) developed kidney injury, including 26 cases of grade 1 and 3 cases of grade 2 renal injuries; the time of renal injury occurrence was 19-355 days after the first application of ICIs, and the median time was 108 days. After diagnosed of kidney injury, 13 out of 29 patients stopped ICIs, of which 6 had recovered kidney function and 7 had no improvement; 16 patients continued the ICIs treatment, of which 10 patients had recovered or improved kidney function and 6 had no improvement. The clinical characteristics of patients in the 2 groups were compared, and 10 variables including age, gender, baseline renal function, previous use of carboplatin, previous radiotherapy, combined chemotherapy containing cisplatin, combined paclitaxel chemotherapy, combined tyrosine kinase inhibitor (TKI) anti-vascular therapy, combined proton pump inhibitors, and combined radiotherapy were screened for the binary logistic regression analysis. The results showed that female ( OR=3.046, 95% CI: 1.149-8.077), ≤65 years ( OR=3.649, 95% CI: 1.435-9.274), combined TKI anti-vascular therapy ( OR=4.773, 95% CI: 1.496-15.227), and combined radiotherapy ( OR=8.655, 95% CI: 1.268-59.076) were independent risk factors for the development of kidney injury. Conclusions:The incidence of kidney injury in patients with eGFR <90 ml/(min·1.73 m 2) and/or Scr >105 μmol/L after using ICIs is 13.1%. In these patients, female, ≤65 years, combined TKI anti-vascular therapy, and combined radiotherapy may be risk factors for the development of ICI-associated kidney injury.

With the application of immune checkpoint inhibitors (ICIs), the acute kidney injury (AKI) caused by ICIs has attracted increasingly extensive attention. The incidence of ICIs-induced AKI is 0.8%-29%, which can occur weeks or months after the first drug use or even after drug withdrawal. The typical renal histopathological features of AKI are acute tubulointerstitial nephritis, and glomerulopathy can also be seen. The risk factors include combined application of ICIs, the use of proton pump inhibitors, and having chronic kidney diseases, etc. After the diagnosis of AKI, it is necessary to decide whether to reduce the dose or stop using ICIs and start glucocorticoid treatment or add other immunosuppressive drugs according to the degree of disease and the specific situation of the patient. In case of level 3-4 AKI, ICIs shall be permanently discontinued.

Objective:To explore the characteristics and factors affecting the occurrence of renal injury in patients with abnormal biochemical indexes of renal function after the use of immune checkpoint inhibitors (ICIs), and to provide reference for selection of clinical treatment regimen.Methods:Patients who were treated with immune checkpoint inhibitors researched and developed independently in China including camrelizumab, sintilimab, tislelizumab, and toripalimab from March 1, 2021 to February 28, 2022 and showed estimated glomerular filtration rate (eGFR) <90 ml/(min·1.73 m 2) and/or serum creatinine (Scr)>105 μmol/L were retrieved from the China Hospital Pharmacovigilance System. The clinical data including general information, anti-tumor treatment regimen, laboratory test results, and concomitant medications were collected. Patients were divided into kidney injury group and non-kidney injury group, and all the clinical characteristics were compared between the 2 groups, the influencing factors of kidney injury were analyzed using a binary logistic regression model, the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated. Results:A total of 222 patients were entered in the analysis, including 170 males and 52 females, with a median age of 67 (36, 85) years. Of them, 144 patients were treated with carrilizumab, 38 with sindilizumab, 31 with tirelizumab, and 9 with treprolizumab; 29 patients (13.1%) developed kidney injury, including 26 cases of grade 1 and 3 cases of grade 2 renal injuries; the time of renal injury occurrence was 19-355 days after the first application of ICIs, and the median time was 108 days. After diagnosed of kidney injury, 13 out of 29 patients stopped ICIs, of which 6 had recovered kidney function and 7 had no improvement; 16 patients continued the ICIs treatment, of which 10 patients had recovered or improved kidney function and 6 had no improvement. The clinical characteristics of patients in the 2 groups were compared, and 10 variables including age, gender, baseline renal function, previous use of carboplatin, previous radiotherapy, combined chemotherapy containing cisplatin, combined paclitaxel chemotherapy, combined tyrosine kinase inhibitor (TKI) anti-vascular therapy, combined proton pump inhibitors, and combined radiotherapy were screened for the binary logistic regression analysis. The results showed that female ( OR=3.046, 95% CI: 1.149-8.077), ≤65 years ( OR=3.649, 95% CI: 1.435-9.274), combined TKI anti-vascular therapy ( OR=4.773, 95% CI: 1.496-15.227), and combined radiotherapy ( OR=8.655, 95% CI: 1.268-59.076) were independent risk factors for the development of kidney injury. Conclusions:The incidence of kidney injury in patients with eGFR <90 ml/(min·1.73 m 2) and/or Scr >105 μmol/L after using ICIs is 13.1%. In these patients, female, ≤65 years, combined TKI anti-vascular therapy, and combined radiotherapy may be risk factors for the development of ICI-associated kidney injury.

Objective:To analyze clinical characteristics of cutaneous delayed-type hypersensitivity caused by injection of equine tetanus antitoxin (TAT) or equine anti-tetanus immunoglobulin F (ab′) 2. Methods:Clinical data were collected from 181 outpatients or inpatients with cutaneous delayed-type hypersensitivity caused by injection of equine TAT or anti-tetanus immunoglobulin from 2008 to 2020, and retrospectively analyzed.Results:Before the injection of equine TAT or anti-tetanus immunoglobulin, skin test was negative in 171 (94.47%) of the 181 patients, and the 10 (5.53%) patients with positive skin test responses received desensitization injection. Among the 181 patients, there were 118 males and 63 females aged from 11 to 68 years, with the disease duration of 1 to 7 days and alatency period of 4 to 14 days. There was no significant difference in the clinical manifestations between the patients receiving injection of TAT (130 cases) and those receiving injection of equine anti-tetanus immunoglobulin (51 cases) . Urticaria-like rashes were the main clinical manifestation, and infiltrative erythema occurred at the injection site in 12 patients, of whom 10 developed generalized urticaria all over the body. Of the 181 patients, 163 (90.06%) presented with generalized skin rashes, and 56 (30.94%) had systemic symptoms such as chest tightness, fever, etc, of whom 15 (26.79%) had a history of allergies and 6 with severe symptoms had no history of allergies. Thirty-four (18.78%) patients had single or multiple laboratory abnormalities, such as increased white blood cell counts, elevated C-reactive protein level and urinary glucose, and presence of occult blood in urine. All cases responded well to the treatment with antihistamines and glucocorticoids. The treatment duration ranged from 3 to 10 days, and the outcome was good.Conclusion:TAT-or anti-tetanus immunoglobulin-induced cutaneous delayed-type hypersensitivity may still occur in patients with a negative skin test or after desensitization treatment, and mainly manifests as urticaria-like rashes.