Multi-target anticancer drugs have a more comprehensive and extensive range of action,and there is an uncertain risk in the combination of two drugs.A case of acute toxicity induced by erlotinib combined with cabozantinib is reported in this article.
Anilides ; adverse effects ; Drug Eruptions ; etiology ; Drug Therapy, Combination ; adverse effects ; Erlotinib Hydrochloride ; adverse effects ; Humans ; Myocardial Infarction ; chemically induced ; Pyridines ; adverse effects

BACKGROUND: There is scanty evidence concerning the ability of Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) and Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (ACUITY-HORIZONS) scores to predict out-of-hospital bleeding risk after percutaneous coronary interventions (PCIs) with drug-eluting stents (DES) in patients receiving dual antiplatelet therapy. We aimed to assess and compare the long-term prognostic value of these scores regarding out-of-hospital bleeding risk in such patients. METHODS: We performed a prospective observational study of 10,724 patients undergoing PCI between January and December 2013 in Fuwai Hospital, China. All patients were followed up for 2 years and evaluated through the Fuwai Hospital Follow-up Center. Major bleeding was defined as Types 2, 3, and 5 according to Bleeding Academic Research Consortium Definition criteria. RESULTS: During a 2-year follow-up, 245 of 9782 patients (2.5%) had major bleeding (MB). CRUSADE (21.00 [12.00, 29.75] vs. 18.00 [11.00, 26.00], P < 0.001) and ACUITY-HORIZONS (9.00 [3.00, 14.00] vs. 6.00 [3.00, 12.00], P < 0.001) risk scores were both significantly higher in the MB than non-MB groups. Both scores showed a moderate predictive value for MB in the whole study cohort (area under the receiver-operating characteristics curve [AUROC], 0.565; 95% confidence interval [CI], 0.529-0.601, P = 0.001; AUROC, 0.566; 95% CI, 0.529-0.603, P < 0.001, respectively) and in the acute coronary syndrome (ACS) subgroup (AUROC: 0.579, 95% CI: 0.531-0.627, P = 0.001; AUROC, 0.591; 95% CI, 0.544-0.638, P < 0.001, respectively). However, neither score was a significant predictor in the non-ACS subgroup (P > 0.05). The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup. CONCLUSIONS CRUSADE and ACUITY-HORIZONS scores showed statistically significant but relatively limited long-term prognostic value for out-of-hospital MB after PCI with DES in a cohort of Chinese patients. The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup.
Acute Coronary Syndrome ; therapy ; Aged ; Angina, Unstable ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; adverse effects ; Postoperative Hemorrhage ; chemically induced ; diagnosis ; epidemiology ; surgery ; Practice Guidelines as Topic ; Prognosis ; Prospective Studies ; Research Design ; Risk ; Risk Assessment ; Treatment Outcome

Objective The benefit of short-term dual antiplatelet therapy (DAPT) following second-generation drug-eluting stents implantation has not been systematically evaluated. To bridge the knowledge gap, we did a meta-analysis to assess the efficacy of ≤6 months versus ≥12 months DAPT among patients with second-generation drug-eluting stents.Methods We searched online databases and identified randomized controlled trials that assess the clinical impact of short-term DAPT (≤6 months) published before March 3, 2016. The efficacy endpoints included the incidence of all-cause death, myocardial infarction, cerebrovascular accidents, and definite or probable stent thrombosis. Safety endpoint defined as major bleeding was also evaluated and discussed.Results We included 5 trials that randomized 9473 participants (49.8%, short-term DAPT duration vs. 50.2%, standard duration). A total of 9445 (99.7%) patients reported the efficacy endpoints, and the safety endpoint was available from 4 studies (n=8457). There was no significant difference in efficacy endpoints between short-term and standard DAPT duration (≥12 months) [risk ratio (RR) 0.96; 95% confidence intervals (CI), 0.80-1.15]. Short-term DAPT duration did not significantly increase the individual risk of all-cause death, myocardial infarction, cerebrovascular accidents, or definite or probable stent thrombosis. Although short-term DAPT obviously reduced risk of major bleeding compared with standard DAPT (RR 0.53; 95% CI, 0.29-0.96), significant publication bias was found when accessing the safety endpoint of the 4 studies (Egger's test, P=0.009).Conclusions The efficacy of short-term DAPT was comparable with that of standard duration DAPT. DAPT less than 6 months may be appropriate for patients receiving second-generation drug-eluting stents implantation.
Drug-Eluting Stents ; Humans ; Myocardial Infarction ; chemically induced ; Platelet Aggregation Inhibitors ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Stroke ; chemically induced ; Thrombosis ; chemically induced ; Time Factors

To investigate the effects of triptolide on inflammation and apoptosis induced by focal cerebral ischemia/reperfusion in rats.The rat model of focal cerebral ischemia/reperfusion injury was established according to Longa's method. A total of 80 SD rats were randomly divided into 5 groups:normal control, sham group, DMSO group, middle cerebral artery occlusion (MCAO) group, and MCAO with tripolide treatment group. TTC staining was used to examine the site and volume of cerebral infarction, and Longa score was employed for neurological disorders measurement. Number of astrocytes was measured by fluorescence staining, and neuronal apoptosis was determined by TUNEL staining. The expressions of inducible nitric oxide synthase(iNOS), cyclooxygenase 2(COX-2) and NF-κB proteins were detected by immunohistochemistry, and the expression of iNOS, COX-2 mRNA was detected by real-time PCR.Compared with DMSO group and MCAO group, brain edema was improved (80.03±0.46)% (<0.05), infarct volume was reduced (8.3±1.4)% (<0.01), Longa score was decreased (1.38±0.20,<0.05) in triptolide treatment group. Meanwhile triptolide also dramatically reduced the number of GFAP-positive astrocytes (<0.05), alleviated protein expression of COX-2 (91.67±1.31), iNOS (95.24±5.07) and NF-κB (75.03±2.06) triggered by MCAO (all<0.05), and induced a down-regulation of cell apoptosis as showed by TUNEL assay (64.15±3.52,<0.05).Triptolide can reduce the cerebral infarction volume, attenuate brain edema and ameliorate the neurological deficits induced by cerebral ischemia-reperfusion injury rats, indicating that it might be used as a potential anti-inflammatory agent.
Animals ; Apoptosis ; drug effects ; Astrocytes ; Brain Edema ; drug therapy ; Brain Injuries ; chemically induced ; drug therapy ; Brain Ischemia ; chemically induced ; Cyclooxygenase 2 ; drug effects ; Diterpenes ; pharmacology ; Down-Regulation ; drug effects ; Epoxy Compounds ; pharmacology ; Infarction, Middle Cerebral Artery ; chemically induced ; drug therapy ; Inflammation ; drug therapy ; Male ; NF-kappa B ; drug effects ; Nitric Oxide Synthase Type II ; drug effects ; Phenanthrenes ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; chemically induced ; drug therapy

Acute Disease ; Anaphylaxis ; drug therapy ; Epinephrine ; administration & dosage ; adverse effects ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnosis ; etiology ; Thrombosis ; chemically induced ; complications

No abstract available.
Coronary Angiography ; Electrocardiography ; Flowers ; Honey/*poisoning ; Humans ; Inferior Wall Myocardial Infarction/*chemically induced/diagnosis/therapy ; Male ; Middle Aged ; Plant Nectar ; Predictive Value of Tests ; *Rhododendron ; Risk Factors ; Toxins, Biological/*poisoning

BACKGROUNDMonosodium L-glutamate (MSG) is a food flavour enhancer and its potential harmfulness to the heart remains controversial. We investigated whether MSG could induce cardiac arrhythmias and apoptosis via the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor.

METHODSMyocardial infarction (MI) was created by ligating the coronary artery and ventricular arrhythmias were monitored by electrocardiogram in the rat in vivo. Neonatal rat cardiomyocytes were isolated and cultured. Cell viability was estimated by 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazoliumromide (MTT) assay. Calcium mobilization was monitored by confocal microscopy. Cardiomyocyte apoptosis was evaluated by acridine orange staining, flow cytometry, DNA laddering, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.

RESULTSMSG (i.v.) decreased the heart rate at 0.5 g/kg and serious bradycardia at 1.5 g/kg, but could not induce ventricular tachyarrhythmias in normal rats in vivo. In rats with acute MI in vivo, however, MSG (1.5 g/kg, i.v.) induced ventricular tachyarrhythmias and these arrhythmias could be prevented by blocking the AMPA and N-methyl-d-aspartate (NMDA) receptors. Selectively activating the AMPA or NMDA receptor induced ventricular tachyarrhythmias in MI rats. At the cellular level, AMPA induced calcium mobilization, oxidative stress, mitochondrial dysfunction and apoptosis in cultured cardiomyocytes, especially when the AMPA receptor desensitization were blocked by cyclothiazide. The above toxic cellular effects of AMPA were abolished by AMPA receptor blockade or by H2O2 scavengers.

CONCLUSIONSMSG induces bradycardia in normal rats, but triggers lethal tachyarrhythmias in myocardial infarcted rats probably by hindering AMPA receptors. AMPA receptor overstimulation also induces cardiomyocyte apoptosis, which may facilitate arrhythmia.

Animals ; Apoptosis ; drug effects ; Arrhythmias, Cardiac ; chemically induced ; Calcium ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; DNA Fragmentation ; drug effects ; Glutamic Acid ; toxicity ; Male ; Microscopy, Confocal ; Myocardial Infarction ; chemically induced ; Rats ; Rats, Wistar ; Receptors, AMPA ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sodium Glutamate ; toxicity ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ; toxicity

Capecitabine is an orally available chemotherapeutic agent that is converted to 5-fluorouracil (5-FU) after absorbtion. Capecitabine and its active metabolite, 5-FU, have cardiotoxic effects with reported instances of acute coronary syndromes caused due to coronary vasospasm. However, these agents exert toxic effects on cardiovascular system and beyond vasospasm provacation. We report a 46-year-old patient diagnosed as acute inferior infarction who is treated with capecitabine for 3 months due to metastatic breast carcinoma, in whom thrombotic coronary occlusion was observed in angiography. This case demonstrates that apart from vasospasm, coronary thrombosis could be observed after capecitabine treatment, with a possible direct effect of this drug.
Capecitabine ; Coronary Thrombosis ; chemically induced ; Coronary Vasospasm ; chemically induced ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Fluorouracil ; adverse effects ; analogs & derivatives ; therapeutic use ; Humans ; Middle Aged ; Myocardial Infarction ; chemically induced

OBJECTIVETo compare the safety of intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) in ischemic patients under the guidance of CT and multi-mode MRI.

METHODSThe clinical, laboratory, and radiologic data from 113 consecutive hyperacute ischemic patients who received intravenous rtPA therapy from June 2009 to October 2011 was retrospectively reviewed. The rate of hemorrhagic transformation (HT) and the clinical outcome between CT and multi-mode MRI was compared. Etiological subgroups were classified according to Chinese ischemic stroke subclassification (CISS).

RESULTSAmong 113 patients treated with intravenous rtPA, the mean age was 66 ±12 years, 74(65.5%) were man, the pretreatment National Institutes of Health Stroke Scale score (NIHSS) was 12.4 ±6.5, and time from symptom onset to therapy was 259.7 ±131.7 min. Postlytic radiological HT was found in 34 patients (30.1%). Symptomatic ICH occurred in 9 patients (8%). Logistic regression analysis suggested that multi-mode MRI was an independent predictor of reduced risk of HT.

CONCLUSIONThe risk of hemorrhagic complications is lower in patients receiving intravenous thrombolytic therapy with rtPA guided by multi-mode MRI than those guided by CT scan.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Brain Infarction ; drug therapy ; Cerebral Hemorrhage ; chemically induced ; prevention & control ; Female ; Humans ; Logistic Models ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Recombinant Proteins ; administration & dosage ; adverse effects ; therapeutic use ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; adverse effects ; Tissue Plasminogen Activator ; administration & dosage ; adverse effects ; therapeutic use ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVETo investigate the clinical features and prognosis of rhabdomyolysis related to seizure attacks and use of statin.

METHODSThe medical records of 3 patients with established diagnosis of rhabdomyolysis were analyzed and the related literatures were reviewed.

RESULTSAll the 3 patients had seizure attacks and/or used statin before the onset of rhabdomyolysis. Two of the patients complained of back pain, and all the 3 patients had dark-colored urine. Serum levels of creatine kinase (CK) were markedly increased by over 50 times above the normal upper limit. CK level kept increasing even after proper interventions, till reaching the peak level about 3 days later. The patients improved rapidly with full recovery thereafter, and CK became normal in 2 weeks. None of the patients had renal failure.

CONCLUSIONSeizure attacks and use of statin are common risk factors for non-traumatic rhabdomyolysis. Caution needs to be taken when prescribing statin to patients with recent seizure attacks. Special attention should be given to such early symptoms as muscle pain, weakness and dark-colored urine, and CK level monitoring is advisable in such cases.

Cerebral Infarction ; drug therapy ; Creatine Kinase ; blood ; Epilepsy ; complications ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; adverse effects ; therapeutic use ; Lovastatin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Rhabdomyolysis ; chemically induced ; enzymology ; etiology ; Simvastatin ; adverse effects ; therapeutic use