An 82-year-old female patient with atrial fibrillation and heart failure was treated with dabigatran etexilate 110 mg twice daily for 6 years. Two months ago, the patient′s lower limb edema was aggravated and urine output was reduced. Considering the worsening of the patient′s heart failure, torasemide tablets and spironolactone tablets were given, but her symptoms were not improved. Two days ago, the patient had scattered petechiae on the whole skin, tarry stools, and reduced urine (200 ml daily). Laboratory tests showed hemoglobin (Hb) 63 g/l, prothrombin time (PT) 39.5 s, activated partial thromboplastin time (APTT) 117.2 s, thrombin time (TT) >300 s, and international normalized ratio (INR) 3.64; the fibrinogen (Fib) could not be measured. Coagulation dysfunction and gastrointestinal bleeding caused by dabigatran etexilate were considered. Dabigatran etexilate was discontinued, and intravenous infusion of idarucizumab injection (2.5 g) was given twice. Then gastrointestinal bleeding in the patient disappeared and laboratory tests showed PT 12.7 s, APTT 42.4 s, TT 18.8 s, INR 1.18, and Fib 2.67 g/L. After 8 days, the patient′s cardiac function was improved, the skin ecchymosis subsided, and laboratory tests showed Hb 84 g/L, PT 14 s, APTT 37.8 s, TT 41.2 s, INR 1.3, Fib 2.26 g/L, and negative fecal occult blood test.

A 35-year-old male patient with type 2 diabetes mellitus was treated with metformin and dapagliflozin orally for a long time. Due to poor glycemic control and overweight, the treatment was adjusted to subcutaneous injection of semaglutide 0.25 mg once a week plus 1 metformin and empagliflozin tablet orally twice daily. The patient experienced abdominal bloating and significant satiety after the first dose, which did not attract attention, and metformin and empagliflozin tablets were not discontinued. Three days later, he developed persistent epigastric pain, and laboratory tests indicated blood ketone body (β-hydroxybutyrate) 4.70 mmol/L. Despite treatments with lansoprazole, anisodamine, metoclopramide, and dezocine, the symptoms was not alleviated. Gastrointestinal decompression was performed, which led to a slight improvement in abdominal pain. An immediate abdominal CT scan revealed gastric retention. The patient′s gastric retention was considered to be associated with the administration of semaglutide. The following day′s laboratory tests indicated carbon dioxide combining power 2.36 mmol/L, suggesting the occurrence of diabetic ketoacidosis, which was hypothesized to be related to empagliflozin. The original hypoglycemic regimen was discontinued, insulin pump therapy was given with blood glucose level monitoring, and fasting, gastrointestinal decompression, fluid resuscitation, and acid suppression was applied. The patient′s symptoms were significantly improved, and the ketone body levels gradually decreased. After 3 days of treatments, the patient began to eat, and after 6 days, he returned to a normal diet without further abdominal pain or bloating. The ketone body levels and carbon dioxide combining power returned to normal, and the hypoglycemic regimen was adjusted to lispro insulin plus acarbose.

Janus kinase inhibitors (JAKi) are a kind of small molecule targeted drugs used to treat a variety of immune-mediated inflammatory diseases by inhibiting the excessive response of a variety of cytokines. Currently, JAKi has shown good clinical efficacy, but it also has risk of major adverse cardiovascular events (MACE). The specific mechanism of JAKi-caused MACE is still unclear. This paper reviews the pharmacological molecular mechanisms and classification of JAKi and the research progress of MACE related to the JAKi (tolvaptan, baricitinib, ruxolitinib, upadacitinib, and abrocitinib) that have been approved for marketing in China. The risk factors that lead to MACE, including age, combined cardiovascular disease and inflammatory diseases, types of JAKi, dosage forms, and treatment duration are analyzed, so as to provide reference for the clinical rational use of JAKi and better prevention of MACE related to JAKi.

A 46-year-old female patient received Tongtian oral solution 10 ml thrice daily combined with Yangxue Qingnao pills 2.5 g thrice daily for migraine. After 10 days of treatments, the patient developed yellow urine. After 12 days of treatments, the patient stopped using Tongtian oral solution by herself. After continuing to take Yangxue Qingnao pills for 5 days, the patient developed symptoms of yellowish skin and sclera, and 10 days later, Yangxue Qingnao pills were discontinued by herself. The next day of discontinuing the Yangxue Qingnao pills, the patient experienced abdominal distension. The laboratory tests showed alanine aminotransferase (ALT) 1 454 U/L, aspartate aminotransferase (AST) 1 429 U/L, gamma glutamyltransferase (GGT) 290 U/L, alkaline phosphatase (ALP) 176 U/L, total bilirubin (TBil) 94.2 μmol/L, and total bile acid (TBA) 365.9 μmol/L. Based on the patient′s medical history, laboratory test results, and auxiliary examinations, drug-induced liver injury was diagnosed, which might be related to Tongtian oral solution and Yangxue Qingnao pills. After one week of Yangxue Qingnao pills withdrawal, the patient′s symptoms of yellowish skin and sclera were improved and urine color became lighter, with ALT 495 U/L, AST 202 U/L, GGT 181 U/L, ALP 120 U/L, TBil 24.6 μmol/L, and TBA 15.6 μmol/L. After 7 days of treatments such as magnesium isoglycyrrhizinate, hepatocyte growth-promoting factor, and ademetionine, the patient′s condition was significantly improved. The above-mentioned drugs were discontinued and switched to bicyclol 25 mg thrice daily orally. Eight days later, the patient′s liver function indicators had basically returned to normal.

Drug-induced neurological disorders (DINDs) refer to the central or peripheral nervous system disease caused by drugs. DINDs account for a large proportion of adverse drug reactions/events in China, and its onset is complex to some extent. Common DINDs include epilepsy, movement disorders, stroke, peripheral neuropathy, spinal cord injury, cognitive impairment and so on. Usually, DINDs have characters of gradual development and late-onset reactions, and it is difficult to associate their clinical manifestations with drugs, leading to misdiagnosis and poor prognosis in clinic. To reduce the neurotoxicity of drugs, multidisciplinary cooperation should be strengthened, and individualized treatment plans for high-risk people and closer monitoring should be implemented for timely identification and diagnose. At the same time, relevant researches on DINDs should be strengthened in the clinic to cope with the complexity and long-term prognosis challenges of the diseases.

A 66-year-old male patient with esophageal cancer progressed after concurrent radiotherapy and chemoradiotherapy, and received immunotherapy combined with chemotherapy (intravenous infusion of sintilimab 200 mg on day 1, tegafur gimeracil oteracil potassium 50 mg orally twice daily from day 1 to 14), with 21 days as a cycle. After 13 days of treatments, diarrhea appeared, and gradually worsened with abdominal pain and a small amount of mucous bloody stools. Colonoscopy showed diffuse swelling and punctiform hemorrhagic erosion of the mucosa of the colon and rectum. Histopathological examination of the ascending colon and sigmoid colon showed regular arrangement of glands, infiltration of lymphocytes, neutrophils and eosinophils in the interstitium, and formation of crypt abscesses, which were considered to be immune-associated colitis caused by sintilimab. After discontinuing the use of sintilimab and administering low-dose methylprednisolone (24 mg orally twice daily) for 3 days, the patient′s symptoms were completely relieved. The dose of methylprednisolone was reduced gradually and discontinued within 4 weeks. The patient did not rechallenge immune checkpoint inhibitors and continued maintenance therapy with tegafur gimeracil oteracil potassium, and no diarrhea recurred

With the aging of the population and the increasing number of patients with thromboembolic diseases, oral anticoagulants are more and more widely used. Anticoagulant-related nephropathy (ARN) is a significant adverse reaction in the treatment with oral anticoagulants, generally considered to be a form of acute kidney injury caused by excessive anticoagulation. The mechanisms involved may include glomerular hemorrhage, obstruction of renal tubules by red cell casts, and damage to tubular epithelial cells. Abnormalities in coagulation function and renal function are the main risk factors for ARN; older age, diabetes mellitus, and cardiovascular diseases such as hypertension and heart failure also increase the risk of ARN occurrence. ARN should be managed based on individual patient characteristics. Benefits and risks of treatment should be carefully considered when choosing oral anticoagulants; renal function should be closely monitored during treatments to detect potential risks early. In case of ARN, it is advised to promptly adjust the anticoagulant therapy and provide symptomatic supportive treatments. In severe cases, treatments with methylprednisolone combined with hemodialysis can be employed.

Objective:To explore the effect of concomitant amiodarone on the bleeding risk in atrial fibrillation patients treated with dabigatran etexilate.Methods:This study was a retrospective cohort study. The clinical data of hospitalized patients with atrial fibrillation who took dabigatran etexilate in Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology from July 1, 2022 to June 30, 2023 were collected. Patients were divided into concomitant amiodarone group and non concomitant amiodarone group according to whether they were treated with oral amiodarone. Propensity score matching (PSM) was performed at a 1∶1 ratio in patients between the 2 groups according to patient's gender, age, main basic diseases and the number of basic diseases, baseline liver and kidney function, dosage of dabigatran etexilate, etc. The incidence of bleeding events was compared between the 2 groups.Results:A total of 878 patients were included in the study, including 568 males (64.7%) and 310 females (35.3%), with a age of 67 (59, 74) years. There were 252 patients (28.7%) in the concomitant amiodarone group and 626 patients (71.3%) in the non concomitant amiodarone group. Within 3 months of follow-up, the incidence of bleeding events in patients of concomitant and non concomitant amiodarone groups were 19.0% (48/252) and 21.2% (133/626), respectively, which were 19.0% (48/252) and 16.7% (40/239) after PSM, respectively, with no significant difference (all P>0.05). The main type of bleeding in patients of both groups was mild bleeding events [62.5% (30/48) vs. 67.5% (27/40)], and bleeding was more common in the gums, skin, and nose. There was no statistically significant difference in incidence of the bleeding types and bleeding sites of patients between the 2 groups (all P>0.05). Conclusions:Compared with patients with atrial fibrillation when treated with dabigatran etexilate and without concomitant amiodarone, the bleeding risk of patients with amiodarone did not significantly increased in the short term. The bleeding events during treatment of dabigatran etexilate were mainly mild bleeding, but clinical vigilance was still necessary.

Objective:To mine the risk signal of acute kidney injury (AKI) induced by different oral anticoagulant drugs (OACs) in various populations and provide a reference for clinical use of OACs.Methods:Reports of AKI induced by OACs and non-OACs in the US Food and Drug Administration Adverse Event Reporting System database from the 1st quarter of 2004 to the 3rd quarter of 2023 were collected. The relationship between the drugs mentioned above and the AKI in patients were analyzed by methods of reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN). When the number of reports of the target adverse event (AE) for the target drug was ≥3, and the lower limit of the 95% confidence interval ( CI) of ROR was >1 or the lower limit of the 95% CI of the information component ( IC025) was >0, it indicated a statistically significant association between the target drug and the target AE. Results:A total of 12 402 AKI reports related to OACs were collected, including 1 313 for warfarin, 3 086 for dabigatran, 4 730 for rivaroxaban, 2 918 for apixaban, and 365 for edoxaban; 454 378 AKI reports were related to non-OACs. The overall analysis of OACs showed an ROR (lower limit of 95% CI) of 1.791 (1.759) and an IC ( IC025) of 0.813 (0.787) for AKI caused by OACs. Analysis of individual OACs showed that warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban all posed risks for AKI, with ROR (lower limit of 95% CI) of 1.220(1.156), 2.386(2.302), 2.044(1.986), 1.375(1.326), 3.003(2.706), respectively, and IC ( IC025) of 0.284(0.204), 1.231(1.178), 1.010(0.968), 0.452(0.399), 1.560(1.407), respectively. Edoxaban had the highest ROR and IC values, while warfarin had the lowest. Subgroup analysis showed that in the <18 years subgroup, neither warfarin nor rivaroxaban showed a risk of AKI; the ROR method did not show dabigatran to have a risk of AKI, but the BCPNN method did. In the 18-45 years subgroup, both methods showed that apixaban did not have a risk of AKI, while all other OACs did. In the 45-64 years subgroup, all OACs showed a risk of AKI. In the ≥65 years subgroup, warfarin and apixaban posed risks for AKI. Gender subgroup analysis showed that both methods indicated a risk of AKI with warfarin in males; all OACs showed a risk of AKI in females. Conclusions:OAC has a statistically significant risk of AKI, among which edoxaban has the highest risk intensity and warfarin has the lowest. Different OACs have different risks of AKI in patients with different ages.

Objective:To mine the risk signals of adverse events (AE) of satralizumab for treatment of neuromyelitis optica spectrum disorder (NMOSD) and provide reference for safe use of the drug in clinic.Methods:AE reports on satralizumab from the 1st quarter of 2020 to the 4th quarter of 2023 were collected by searching US Food and Drug Administration Adverse Event Reporting System (FAERS) database. AEs were classified and standardized according to the preferred term (PT) and system organ class (SOC) of Medical Dictionary for Regulatory Activities version 26.1. Reporting odds radio (ROR) method and Bayesian confidence progressive neural network (BCPNN) method were used to mine the AE risk signals. An AE with ≥3 reports, lower limit of the 95% confidence interval ( CI) of ROR >1, and the information component ( IC) of BCPNN method minus 2 times of standard deviation ( IC-2 SD) >0 were defined as a risk signal. Descriptive analysis on the signals was performed. Results:A total of 526 AE reports were collected, 39 risk signals (PT) were mined by ROR and BCPNN methods, involving 13 SOCs. Among the 39 PTs, 11 were adverse reactions recorded in the label, including blood triglycerides increased, hepatic function abnormal, cellulitis, and etc. Twenty-eight PTs were not recorded in the label, 11 of which involved infections and infestations. The top 5 PTs in signal intensity were atypical mycobacterium infection, pyelonephritis, compression fracture, spinal compression fractures, and lymphocyte count decreased. The top 5 PTs in number of reports were urinary tract infection, pneumonia, corona virus disease 2019, sepsis, and herpes zoster.Conclusion:In addition to the blood triglycerides increased, hepatic function abnormal, cellulitis, and other AEs recorded in the label, NMOSD treatment with satralizumab may also cause atypical mycobacterial infection, pyelonephritis, compression fracture and other AEs not recorded in the label, which clinical physicians should be vigilant.