Comparing adverse events of tenecteplase and alteplase: a real-world analysis of the FDA adverse event reporting system (FAERS).

OBJECTIVES: The aim of this study is to monitor, identify, and compare the adverse events (AEs) related to tenecteplase and alteplase, with the objective of exploring the potential safety of tenecteplase for acute ischemic stroke (AIS) and guiding its use to enhance patient safety. METHODS: In order to evaluate the disproportionality of AEs associated with tenecteplase and alteplase in real-world data, four algorithms (ROR, PRR, BCPNN, EBGM) were utilized as measures to detect signals of AEs related to both drugs. Subsequently, Breslow-Day statistical analysis was applied to compare the RORs of the main system organ classes (SOCs) and key preferred terms (PTs) between tenecteplase and alteplase. RESULTS: A statistical analysis was performed utilizing data gleaned from the Food and Drug Administration Adverse Event Reporting System (FAERS) database, encompassing 19,514,140 case reports from 2004Q1 to 2023Q1. There were 1,004 cases where tenecteplase was reported as the primary suspected (PS) and 2,363 tenecteplase-related adverse drug reactions (ADRs) at the PTs level were identified, the two data of alteplase were 10,945 and 25,266, respectively. The occurrence of drug-induced ADRs was analyzed across 27 organ systems, The analysis revealed several expected ADRs, such as Haemorrhage, Hypersensitivity which were consistent with the two drug-labels. It is of note that the signal strengths of 'death,' 'ventricular fibrillation,' 'cardiogenic shock' and 'pneumonia aspiration' at the PT level were markedly higher for tenecteplase than for alteplase, whereas the signal strength of 'angioedema' at the PT level was significantly higher for alteplase in comparison to tenecteplase. Additionally, unexpected significant ADRs associated with ocular adverse reactions and pneumonia aspiration at the PT level were identified, indicating potential AEs not currently mentioned in the drug instructions. CONCLUSION: This study identified and compared signals of ADRs associated with tenecteplase and alteplase, although tenecteplase is as effective as alteplase and has advantages such as ease of use and affordability, it cannot replace alteplase in the treatment of AIS until its safety profile is fully recognized. Additionally, previously unreported ocular ADRs and pneumonia were identified, providing valuable insights into the relationship between ADRs and the use of these thrombolytic drugs. These findings underscore the importance of continuous monitoring and effective detection of AEs to ultimately enhance the safety of AIS patients undergoing thrombolytic therapy.

Development of a prognostic signature based on anoikis-related genes in hepatocellular carcinoma with the utilization of LASSO-cox method.

To develop a signature based on anoikis-related genes (ARGs) for predicting the prognosis of patients with hepatocellular carcinoma (HCC), and to elucidate the molecular mechanisms involved. In this study, bioinformatic algorithms were applied to integrate and analyze 777 HCC RNA-seq samples from the cancer genome atlas and international cancer genome consortium repositories. A prognostic signature was developed via the least absolute shrinkage and selection operator-cox regression method. To evaluate the accuracy of the signature in predicting events, multi-type technical means, such as Kaplan-Meier plots, receiver operating characteristic curve analysis, nomogram construction, and univariate and multivariate Cox regression studies were performed. We investigated the underlying molecular biological mechanisms and immune mechanisms of the signature using gene set enrichment analysis and the CIBERSORT R package, respectively. Meanwhile, immunohistochemical staining acquired from the human protein atlas was used to confirm the differential expression levels of hub genes involved in the prognostic signature. We developed an HCC prognostic signature with a collection of 5 ARGs, and the prognostic value was successfully assessed and verified in both the test and validation cohorts. The risk scores calculated by the prognostic signature were proved to be an independent negative prognostic factor for overall survival. A set of nomograms based on risk scores was established and found to be effective in predicting OS. Further investigation of the underlying molecular biological mechanisms and immune mechanisms indicated that the signature may be relevant to metabolic dysregulation and infiltration of gamma delta T cells in the tumor. The survival prognosis of HCC patients can be predicted by the anoikis-related prognostic signature, and it serves as a valuable reference for individualized HCC therapy.

Comparison of clinical characteristics of first-episode thrombotic thrombocytopenic purpura and TTP-like syndrome: a retrospective cohort study in a level I hematology center in China.

Comparing the characteristics of thrombotic thrombocytopenic purpura (TTP) and TTP-like syndrome patients at admission will allow early differentiation of TTP from TTP-like syndrome and help tailor initial treatment. The medical records of 78 patients with suspected TTP in the Emergency Department of Peking University People's Hospital in the past 5 years were retrospectively analyzed and divided into TTP and TTP-like syndrome groups based on ADAMTS13 activity and ADAMTS13 antibody titer. There were 25 and 53 patients in the TTP group and the TTP-like syndrome group, respectively. The neutrophil-to-lymphocyte ratio (P = 0.025) was tremendously higher, and albumin (P = 0.002) was lower in the TTP-like syndrome group, indicating a more severe inflammation. Compared with the TTP-like syndrome group, the TTP group had an approximately two-fold to three-fold higher prevalence of central nervous system dysfunction (P < 0.001). Also, hemolysis was more substantial in the TTP group as evidenced by higher schistocytes (P < 0.001), reticulocyte (P < 0.001), total bilirubin (P = 0.002), indirect bilirubin (P < 0.001), lactate dehydrogenase (P = 0.007) and cell-free hemoglobin (P < 0.001), simultaneously lower platelet (P < 0.001), haptoglobin (P = 0.044), and ADAMTS13 activity (P < 0.001). The Kaplan-Meier survival analysis showed that the TTP group significantly predicted poor prognosis (log-rank test: X2 = 5.368, P = 0.021). TTP and TTP-like syndrome are two kinds of distinct phenotypes with different hemolysis statuses and illustrated differentiated inflammatory reactions, target organ damage (TOD), and the clinical outcome.

Campylobacter jejuni-Associated Hemophagocytic Lymphohistiocytosis and Guillain-Barre Syndrome: A Case Report.

Campylobacter jejuni (C. jejuni), a Gram-negative bacterium, belongs to microaerobic bacteria. We reported a 21-year-old male patient diagnosed with hemophagocytic lymphohistiocytosis (HLH) due to C. jejuni infection, who presented with multiple clinical manifestations of peripheral nerve injury, such as ophthalmoplegia, facial paralysis, and urinary retention during the treatment. Electromyography showed neurogenic injury and the final diagnosis was Guillain-Barre Syndrome (GBS). After treatment of dexamethasone combined with immunoglobulin, the patient was discharged from the hospital with partial recovery of neurological symptoms.

Serum cystatin C, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, klotho and fibroblast growth factor-23 in the early prediction of acute kidney injury associated with sepsis in a Chinese emergency cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and critical complication of sepsis, and is associated with unacceptable morbidity and mortality. Current diagnostic criteria for AKI was insensitive for early detection. Novel biomarkers including cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), klotho and fibroblast growth factor-23 (FGF-23) can predict AKI earlier and allow immediate interventions. We aimed to determine the diagnostic performance of these biomarkers for detecting AKI in sepsis patients. METHODS: This prospective observational study was conducted between May 2018 and November 2020, enrolling 162 sepsis patients eventually. The AKI was defined in accordance with 2012 KDIGO criteria and we divided patients into non-AKI (n = 102) and AKI (n = 60) groups. Serum levels of several AKI biomarkers were detected by ELISA. The relationship between biomarker levels on admission of AKI was analyzed and discrimination performances comparison were performed. RESULTS: AKI incidence was up to 37.0% (60/162) during hospitalization. Compared with non-AKI group, both serum cystatin C, KIM-1, NGAL and FGF-23 were significantly elevated at admission in septic AKI patients. The areas under the receiver operating curves demonstrated that serum cystatin C had modest discriminative powers for predicting AKI after sepsis, and cystatin C combined with serum creatinine in the prediction of septic AKI increased the diagnostic sensitivity prominently. CONCLUSION: Serum cystatin C, KIM-1, NGAL and FGF-23 levels were both increased in septic AKI patients. Our study provided reliable evidence that cystatin C solely and combined with serum creatinine may accurately and sensitively predict septic AKI of patients on admission.

Acute pancreatitis caused by tigecycline: A case report and literature review.

RATIONALE: There is evidence that tigecycline has broad-spectrum antibiotic activity against a variety of complicated infections. However, adverse effects are inevitable, including gastrointestinal side effects such as nausea, vomiting, and diarrhea; in 2006, acute pancreatitis was also brought into the side-effect list after postmarketing surveillance. Here, we present a case of tigecycline-induced acute pancreatitis. PATIENT CONCERNS: An 87-year-old female patient with urinary tract infection received an intravenous drip of tigecycline for 6 days, after which she developed abdominal distension, vomiting, abdominal pain, and abdominal rigidity. DIAGNOSIS: The patient was suspected to have tigecycline-induced acute pancreatitis. INTERVENTIONS: Tigecycline was discontinued immediately, and the patient received a series of immediate treatments including an indwelling gastric tube for continuous gastrointestinal decompression and inhibition of gastric acid and pancreatic enzyme secretion. OUTCOMES: Following initial interventions, we observed that the patient's symptoms improved significantly, and abdominal distension, vomiting, abdominal pain, and abdominal rigidity were slightly relieved. After 5 days of follow-up, blood lipase and amylase levels decreased to normal levels. Unfortunately, the patient developed convulsions during the use of multiple antibiotics after 1 week and then died of septic shock and acute liver failure. LESSONS: Acute pancreatitis caused by tigecycline is rare. However, in the application of antibiotics, the possibility of adverse effects must be considered, and antibiotics should be used reasonably. If the patient has relevant symptoms, it is necessary to stop using tigecycline immediately, carry out symptomatic treatment, and change to other types of antibiotics for antibacterial treatment.