Genetic Variants at the APOE Locus Predict Cardiometabolic Traits and Metabolic Syndrome: A Taiwan Biobank Study.

Several apolipoprotein genes are located at the APOE locus on chromosome 19q13.32. This study explored the genetic determinants of cardiometabolic traits and metabolic syndrome at the APOE locus in a Taiwanese population. A total of 81,387 Taiwan Biobank (TWB) participants were enrolled to undergo genotype−phenotype analysis using data from the Axiom Genome-Wide CHB arrays. Regional association analysis with conditional analysis revealed lead single-nucleotide variations (SNVs) at the APOE locus: APOE rs7412 and rs429358 for total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol levels; CLPTM1 rs3786505 and rs11672748 for LDL and HDL cholesterol levels; and APOC1 rs438811 and APOE-APOC1 rs439401 for serum triglyceride levels. Genotype−phenotype association analysis revealed a significant association of rs429358 and rs438811 with metabolic syndrome and of rs7412, rs438811, and rs439401 with serum albumin levels (p < 0.0015). Stepwise regression analysis indicated that CLPTM1 variants were independently associated with LDL and HDL cholesterol levels (p = 3.10 × 10−15 for rs3786505 and p = 1.48 × 10−15 for rs11672748, respectively). APOE rs429358 and APOC1 rs438811 were also independently associated with metabolic syndrome (p = 2.29 × 10−14) and serum albumin levels (p = 3.80 × 10−6), respectively. In conclusion, in addition to APOE variants, CLPTM1 is a novel candidate locus for LDL and HDL cholesterol levels at the APOE gene region in Taiwan. Our data also indicated that APOE and APOC1 variants were independently associated with metabolic syndrome and serum albumin levels, respectively. These results revealed the crucial role of genetic variants at the APOE locus in predicting cardiometabolic traits and metabolic syndrome.

Evaluating the benefit of adjuvant radiotherapy after extensive lymph node dissection for gastric cancer: a single-institute retrospective study.

OBJECTIVE: This study aimed to evaluate whether adjuvant radiotherapy (RT) can improve the treatment outcome of patients with locally advanced gastric cancer who underwent extensive lymph node dissection (ELND). MATERIALS AND METHODS: This retrospective study included patients with gastric cancer pathological stages IIA-IIIC at Taipei Tzu Chi Hospital between 2008 and 2015. Patients (a) aged >80 years, (b) with distant metastasis at diagnosis, (c) with coexisting malignancies, (d) who did not complete the prescribed RT course, and (e) who died 1 month after surgery were excluded. Among 420 patients diagnosed with gastric cancer, 98 were included. RESULTS: The median follow-up was 24.5 months. Of 39 patients who underwent adjuvant RT, 38 also received adjuvant chemotherapy (CT). Of 59 patients who did not receive adjuvant RT, only 34 received adjuvant CT. ELND was performed in 67.3% of the patients. The 5-year overall survival (OS) rate was 40%. In the univariate analyses, adjuvant CT regimen, 5-fluorouracil + leucovorin, was associated with worst outcome, while TS-1 was associated with better survival outcome (P = 0.018). The number of involved lymph nodes was strongly related to the OS and disease-free survival (DFS) (P < 0.001). We tried using different numbers of involved lymph nodes as a cutoff point and found that adjuvant RT significantly improved both OS and DFS in patients whose involved lymph nodes were ≥4 (OS, P = 0.017; DFS, P = 0.015). In multivariate analyses, better DFS was associated with negative surgical margin (P = 0.04), earlier disease stage (P = 0.001), adjuvant radiotherapy (P = 0.045), and adjuvant CT regimen TS-1 (P = 0.001). CONCLUSION: Adjuvant RT could improve DFS of patients with locally advanced gastric cancer with or without ELND. When the number of involved lymph nodes is ≥4, adjuvant RT is strongly suggested.

Janus kinase 2 V617F mutation in an unrelated peripheral blood stem cell donor.

Polycythemia vera (PV) is relatively uncommon in early adulthood, and evidence about the prevalence of the Janus kinase 2 (JAK2) V617F mutation in the general population is limited. Here, we report a previously healthy volunteer peripheral blood stem cell (PBSC) donor who developed symptomatic PV with the JAK2 V617F mutation 2 years after PBSC mobilization and harvest. The characteristic mutation was identified retrospectively in the blood sample of the donor at the confirmation typing stage, which was before granulocyte colony-stimulating factor injection. This report presents a safety issue for both donor and recipient of hematopoietic stem cell transplantation. Clinicians should be aware of this during health workup and postdonation follow-up of unrelated PBSC donors. Any abnormal and/or equivocal laboratory data, especially during the donor workup stage, should not be overlooked.

Hoarseness: an unusual complication of port-A catheter perforation.

BACKGROUND: A port-A catheter implantation for cancer patients is popular as a route for chemotherapy. Potential complications exist, such as perforation during chemotherapeutic agent infusion, especially when the port-A tip is incorrectly positioned or when it is in long-term use. CASE REPORT: We report on a patient who presented with hoarseness as a result of port-A catheter perforation-related mediastinitis subsequent to chemotherapeutic agent infusion through the catheter. CONCLUSIONS: Hoarseness is a rare complication of port-A perforation and extravasation. To avoid perforation, the tip of the catheter should be located in a high-flow vessel, such as the distal superior vena cava rather than higher in the caval vein, to prevent a locally increased concentration of drugs. We also recommend that a venogram be arranged if extravasation is suspected.

Association between white blood cell count and components of metabolic syndrome.

BACKGROUND: Components of metabolic syndrome (MetS) were found to be associated with several inflammatory factors including white blood cell count (WBCC), which is an easily available test in clinical practice. In the present study, the relationships between WBCC and MetS components were investigated in children. METHODS: A total of 288 Taiwanese children, under 10 years old, with normal WBCC, were enrolled in the study. They were divided into quartiles according to WBCC (lowest, WBCC1; highest, WBCC4). The mean values of each MetS component for every group were compared in boys and girls separately. Multivariate linear regression between the WBCC and the MetS components after adjusting for age and body mass index (BMI) were also evaluated. RESULTS: In group comparison, only the high-density lipoprotein-cholesterol (HDL-C) was found to be significantly lower in WBCC4 in boys. Other components were not different. After multivariate linear regression, WBCC was negatively correlated to HDL-C and positively to BMI in boys. Although not significant, similar relationships were also observed in girls. Interestingly, borderline positive correlation was noted between triglyceride (TG) and WBCC in girls. CONCLUSION: BMI was positively and HDL-C was negatively related to WBCC in boys. A similar trend could also be observed in girls but without significance. Borderline significant correlation between TG and WBCC was noted in girls. These findings suggest that cardiovascular risks might commence even in childhood. Early detection of children with these abnormalities may help to prevent cardiovascular disease and diabetes in adolescence or even adulthood.

The impact of metabolic syndrome on insulin sensitivity, glucose sensitivity, and acute insulin response after glucose load in early-onset type 2 diabetes mellitus: Taiwan Early-Onset Type 2 Diabetes Cohort Study.

Diabetic patients with metabolic syndrome (MetS) have higher lifetime risks for cardiovascular disease, especially in early-onset type 2 diabetes mellitus (EODM). Increased insulin resistance (IR) and impaired insulin secretion are important pathophysiologies in diabetic patients. Therefore, the effects of MetS on IR and insulin secretion in EODM were investigated. Forty-eight EODM (mean age, 22.8 +/- 0.6 years) patients were enrolled in this study. Two grouping criteria were used: the first was whether the patient had MetS or not (MetS+ or Met-, with 31 and 17 patients, respectively); and the second was the number of MetS components each group had, that is, MetS (1,2) with 1 to 2, MetS (3) with 3, and MetS (4,5) with 4 to 5 components (17, 17, and 14 patients in each group, respectively). A frequently sampled intravenous glucose tolerance test was performed to measure insulin sensitivity, glucose sensitivity, acute insulin response after glucose load, and disposal index. Severe IR was noted with both homeostasis model assessment and frequently sampled intravenous glucose tolerance test both in MetS+ and MetS-. However, significantly higher acute insulin response after glucose load and disposal index were noted in MetS+ and MetS (4,5) than in Met-, MetS (1,2), and MetS (3), respectively. Early-onset type 2 diabetes mellitus patients with MetS had similar IR to those without MetS. This may be due to early deterioration of insulin action in these subjects. In addition, insulin secretion was higher in subjects with more MetS components, suggesting that EODM patients with MetS had better preserved ability of beta-cell compensation for IR than those without MetS.

Impaired glucose tolerance and impaired fasting glucose share similar underlying pathophysiologies.

Both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states. IGT was defined as having normal fasting plasma glucose (< 6.1 mmol/l) and abnormal 2-hr post-challenge plasma glucose. IFG was defined as having abnormal fasting plasma and normal 2-hr post-challenge plasma glucose (< 7.8 mmol/l). To explore whether these two abnormalities share similar underlying pathophysiologies, we evaluated risk factors of IGT and IFT using the models of factor analysis. The present study included 107 subjects with IGT and 52 with IFG. An oral glucose tolerance test and insulin suppression test, which could quantify insulin resistance, were performed on separate days. The risk factors include waist-to-hip ratio (WHR), triglycerides, high-density lipoprotein (HDL)-cholesterol, blood pressure, and fasting plasma glucose, which are associated with metabolic syndrome and insulin resistance. Factor analysis is a commonly used statistical method that could reduce a large number of risk factors into smaller numbers of groups, also called dimension. Accordingly, the complicated data could be interpreted more easily, since the related risk factors are grouped in one dimension. The results showed that the risk factors of IGT and IFG have similar grouping patterns. Triglyceride, insulin resistance, and HDL-cholesterol were grouped in one dimension (the lipid dimension), while WHR, mean blood pressure and fasting plasma glucose were grouped in another dimension (the metabolic dimension). In conclusion, except for WHR, the grouping patterns of the components in both IGT and IFG were nearly identical. These results suggest that IGT and IFG may share similar pathophysiologies.

Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital.

OBJECTIVES: To describe the immunological responses and clinical outcome of coronavirus (SARS) infected healthcare workers (HCW) who had been administered with convalescent plasma as a treatment. METHODS: Convalescent plasma (500 mL) was obtained from each of three SARS patients and transfused into the three infected HCW. Donors were blood type O and seronegative for hepatitis B and C, HIV, syphilis and human T-cell lymphotropic virus types I and II (HTLV-I and -II). Serum antibody (IgG) titre was >640. Apharesis was performed with a CS 3000 plus cell separator followed by the forming of the convalescent phase plasma. As part of the routine check with donated plasma, the convalescent plasma was confirmed free of residual SARS-CoV by RT-PCR. Serial serum samples obtained from the recipients of the convalescent plasma were collected to undertake real-time quantitative RT-PCR for SARS-CoV for direct measurement of viral concentration. Specific immunoglobulin IgM and IgG concentrations were titrated using an antigen microarray developed in-house. RESULTS: Viral load dropped from 495 x 10(3), 76 x 10(3) or 650 x 10(3) copies/mL to zero or 1 copy/mL one day after transfusion. Anti-SARS-CoV IgM and IgG also increased in a time-dependent manner following transfusion. All three patients survived. One HCW became pregnant subsequently, delivering 13 months after discharge. Positive anti-SARS-CoV IgG was detected in the newborn. Passive transfer of anti-SARS-CoV antibody from the mother was considered as a possibility. CONCLUSIONS: All infected HCW whose condition had progressed severely and who had failed to respond to the available treatment, survived after transfusion with convalescent plasma.

Transfusion-related acute lung injury--a report of two and the possible role of steroid.

Transfusion-related acute lung injury (TRALI) is a rare but potentially fatal clinical syndrome associated with transfusion. Dyspnea, hypoxemia, hypotension, and fever are the typical symptoms which mimic those of the adult respiratory distress syndrome (ARDS). The onset of TRALI is usually within 4-6 hours after transfusion. According to literature, TRALI is possibly underdiagnosed and underreported. Differential diagnosis includes fluid overload, allergy and sepsis. No definite protocol except supportive treatment is recommended up to now. We present two cases of TRALI and discuss the possible mechanisms and the role of steroid therapy.