Wen-Jung Chung

Clinicopathlogical features and prognosis of drug rash with eosinophilia and systemic symptoms : a study of 30 cases in Taiwan

Background  Drug rash with eosinophilia and systemic symptoms (DRESS), a group of non‐blistering severe cutaneous adverse drug reactions (SCADRs), is characterized by skin rash and multiorgan involvement. Details of this reaction have not been reported in the literature so far.

HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis

HLA-A*31:01 was reported to be associated with carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We conducted an international study using consensus diagnosis criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We found that HLA-A*31:01 showed a significant association with CBZ-DRESS in Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0–340)), and the strong association was also found in Chinese (P<0.001; OR (95% CI)=23.0 (4.2–125)). However, HLA-A*31:01 had no association with CBZ-SJS/TEN in neither Chinese nor Europeans. By comparison, HLA-B*15:02 showed a strong association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6–192)). A meta-analysis of this and other published studies confirmed that in all populations, HLA-A*31:01 had an extremely strong association with CBZ-DRESS (P<0.001, a pooled OR (95% CI)=13.2 (8.4–20.8)), but a much weaker association with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4–11.5)). Our data revealed that HLA-A*31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in Europeans. Considering the potential clinical utility, the cost-effectiveness of the combined HLA-A*31:01 and HLA-B*15:02 genetic test to prevent CBZ-SCAR in Chinese needs further investigation.

Severe cutaneous adverse reactions to antiepileptic drugs in Asians

Objective: Ethnicity has been shown to be a contributing risk factor regarding antiepileptic drug (AED)–induced severe cutaneous adverse drug reactions (SCARs). To increase the clinical and epidemiologic information in Asians, we investigated the characteristics, outcome, and tolerability toward alternative drugs for AED-induced SCARs. Methods: A total of 154 patients with AED-induced SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), were analyzed for demographic characteristics, causative AEDs, latent period, organ involvement, complications, and mortality. Tolerability toward alternative AEDs was followed for patients after AED-SCARs episodes. Results: Carbamazepine (CBZ) and phenytoin (PHT) were the most common causative AEDs for SJS/TEN (67.8%) and DRESS (43.6%), respectively. No SCARs case was caused by nonaromatic AEDs, e.g., valproic acid (VPA) and topiramate (TPM). The liver was the most frequently involved internal organ in AED-DRESS, whereas ocular complications were more commonly seen in AED-SJS/TEN. The mortality of AED-SJS/TEN and -DRESS was 6.1% and 7.7%, respectively. By following alternative AED usage of patients after AED-SCARs episodes, we noted that most patients were tolerant of nonaromatic AEDs. One case of oxcarbazepine-SJS had cross-hypersensitivity to lamotrigine (LTG) and further developed into DRESS. Conclusion: CBZ, PHT, and LTG were the major causative AEDs for SCARs. The mortality of PHT-SCARs was higher than CBZ-SCARs due to complicated comorbidity in patients. Nonaromatic AEDs were safe alternatives for patients with aromatic AED-induced SCARs.

A patch testing and cross‐sensitivity study of carbamazepine‐induced severe cutaneous adverse drug reactions

Background  The usefulness of the drug patch testing for Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is still controversial. Recent studies have shown that HLA‐B*1502 is strongly associated with CBZ‐SJS/TEN in Chinese and Southeast Asian populations.

SCORTEN and impaired renal function related to mortality of toxic epidermal necrolysis syndrome patients in the Asian population.

Background  Toxic epidermal necrolysis syndrome (TEN) is a rare, life‐threatening, drug‐related skin reaction with a high mortality rate. To date, only a few studies with insufficient sample sizes have been conducted to analyse SCORTEN in Asian populations with TEN.

Complementary mutations in seipin gene in a patient with Berardinelli–Seip congenital lipodystrophy and dystonia: phenotype variability suggests multiple roles of seipin gene

Berardinelli–Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive disorder characterised by near-complete absence of adipose tissue since birth or early infancy.1 Affected individuals have acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hypertriglycaemia and altered glucose tolerance or diabetes mellitus. 1-Acyl-glycerol phosphate acyltransferase 2 ( AGPAT2 ) and seipin gene were identified as candidate genes of congenital generalised lipodystrophy.2 3 The neurological manifestations in patients with seipin mutations are variable, including silver syndrome, variants of Charcot–Marie–Tooth disease type 2, distal hereditary motor neuropathy type V, spastic paraplegia and mental retardation.2 3 4 5 Herein we report a patient with congenital lipodystrophy who carries a novel compound heterozygous mutation in the seipin gene and presented with dystonia, mental retardation and behaviour change. A 28-year-old man was admitted to the hospital because of progressive gait disturbance for several years. On examination, he had a distinctive appearance of hollow cheeks, apparent muscular hypertrophy, acromegaloid features of face, palms and soles, acanthosis nigricans of axilla and groin, abundant curly scalp hairs and generalised subcutaneous fat loss. In addition, there were torticollis, abnormal posturing of the fingers when the limbs were outstretched, axial dystonia and an abnormal thigh abduction and foot dystonia (in …

Validation of Scoring Systems That Predict Outcomes in Patients With Coronary Artery Disease Undergoing Coronary Artery Bypass Grafting Surgery

Abstract Several risk stratification scores, based on angiographic or clinical parameters, have been developed to evaluate outcomes in patients with left main coronary artery disease (LMCAD) who undergo coronary artery bypass grafting (CABG). This study aims to validate the predictive ability of different risk scoring systems with regard to long-term outcomes after CABG. This single-center study retrospectively re-evaluated the Synergy Between PCI with TAXUS and Cardiac Surgery (SYNTAX) score; EuroSCORE; age, creatinine, and ejection fraction (ACEF) score; modified ACEF score; clinical SYNTAX; logistic clinical SYNTAX score (logistic CSS); and Parsonnet scores for 305 patients with LMCAD who underwent CABG. The endpoints were 5-year rate of all-cause death and major adverse cardio-cerebral events (MACCEs), including cardiovascular (CV) death, myocardial infarction (MI), and stroke and target vessel revascularization (TVR). Compared with the SYNTAX score, other scores were significantly higher in discriminative ability for all-cause death (SYNTAX vs others: P < 0.01). The EuroSCORE ≥6 showed significant outcome difference on all-cause death, CV death, MI, and MACCE (P < .01). Multivariate analysis indicated the SYNTAX score was a non-significant predictor for different outcomes. Adjusted multivariate analysis revealed that the EuroSCORE was the strongest predictor of all-cause death (hazard ratio[HR]: 1.17; P < 0.001), CV death (HR: 1.16; P < 0.001), and MACCE (HR: 1.09; P = 0.01). The ACEF score and logistic CSS were predictive factors for TVR (HR: 0.25, P = 0.03; HR: 0.85, P = 0.01). The EuroSCORE scoring system most accurately predicts all-cause death, CV death, and MACCE over 5 years, whereas low ACEF score and logistic CSS are independently associated with TVR over the 5-year period following CABG in patients with LMCAD undergoing CABG.

Feasibility and Safety of Transulnar Catheterization in Ipsilateral Radial Artery Occlusion

To investigate the postprocedural cardiovascular events and vascular outcomes, including hand ischemia and neurological compromise, after transulnar (TU) catheterization in ipsilateral radial artery occlusion.Previous randomized trials have shown that the transulnar (TU) approach for coronary angiogram and intervention has safety and outcomes similar to those of the transradial (TR) approach. However, the safety of the TU procedure when ipsilateral radial artery occlusion occurs is unknown.We retrospectively reviewed 87 TU cases with ipsilateral radial artery occlusion confirmed by a forearm angiogram. Eighty percent of these patients had a history of ipsilateral radial artery cannulation or surgery. We avoided the use of over-sized sheaths or applied a sheathless approach during surgery.No ulnar artery occlusion was observed by subsequent Doppler ultrasound or pulse oximetry. No patient developed hand ischemia or serious complications requiring surgery or blood transfusion during the follow-up period of 32.2 ± 24.0 months. Review of the preprocedural forearm angiograms showed that 95.7% of the patients possessed significant collaterals supplying flow from the interosseous artery to the occluded radial artery remnant. Thus, the blood circulation to the palmar arch and digital vessels was maintained even when the ulnar artery was temporarily occluded by an in-dwelling ulnar arterial sheath.TU catheterization was safe in patients with coexisting ipsilateral radial artery occlusions and feasible for use in complex intervention procedures. Cautious manipulation of ulnar artery cannulation and hemostasis helped decrease the risk of hand ischemia.

Optimized Collection Protocol for Plasma MicroRNA Measurement in Patients with Cardiovascular Disease

Background. Various microRNAs (miRNAs) are used as markers of acute coronary syndrome, in which heparinization is considered mandatory therapy. Nevertheless, a standard method of handling plasma samples has not been proposed, and the effects of heparin treatment on miRNA detection are rarely discussed. Materials and Method. This study used quantitative polymerase chain reaction (qPCR) analysis to investigate how storage temperature, standby time, hemolysis, and heparin treatment affect miRNA measurement in plasma samples from 25 patients undergoing cardiac catheterization. Results. For most miRNAs, the qPCR results remained consistent during the first 2 hours. The miRNA signals did not significantly differ between samples stored at 4°C before processing and samples stored at room temperature (RT) before processing. miR-451a/miR-23a ratio < 60 indicated < 0.12% hemolysis with 100% sensitivity and 100% specificity. Pretreatment with 0.25 U heparinase I recovered qPCR signals that were reduced by in vivo heparinization. Conclusions. For miRNA measurement, blood samples stored at RT should be processed into plasma within 2 hours after withdrawal and should be pretreated with 0.25 U heparinase I to overcome heparin-attenuated miRNA signals. The miR-451a/miR-23a ratio is a reliable indicator of significant hemolysis.

No correlation between body mass index and 30-day prognostic outcome in Asians with acute ST-elevation myocardial infarction undergoing primary coronary intervention

Background This study investigated whether body mass index (BMI) was a risk factor predictive of 30-day prognostic outcome in Asians with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Material and methods Data regarding the impact of BMI on the prognostic outcome in Asian populations after acute STEMI is scarce. A number of 925 STEMI patients were divided into three groups according to the BMI: normal weight (<25 kg/m2), overweight (≥25.0 to <30.0 kg/m2) and obese (≥30.0 kg/m2). Results The obese group was significantly younger with significantly higher incidences of smoking and diabetes mellitus. The incidences of multi-vessel disease, final thrombolysis in myocardial infarction (TIMI)-3 flow, advanced Killip score, advance congestive heart failure, 30-day mortality and combined 30-day major adverse clinical outcome (MACO) did not differ among the three groups. Multiple regression analysis showed the age, unsuccessful reperfusion and lower left ventricular ejection fraction were most significant and independent predictor of 30-day mortality. Conclusion BMI is not a predictor of 30-day prognostic outcome in Asians with STEMI undergoing primary PCI.