Valproic acid (VPA) is a widely used antiepileptic drug (AED). When carbapenems are concomitantly used with VPA, the serum levels of VPA may decrease and aggravate seizures. The aim of this study was to evaluate the risk factors associated with decreased serum VPA levels and clinical outcome in patients being treated with a combination of carbapenems and VPA. Fifty-four adult patients who were treated with VPA for epileptic seizures concomitant with carbapenems for the treatment of infections were evaluated in this study. Serum VPA levels were measured before and during combination therapy with VPA and carbapenems, and the change in serum VPA levels was calculated. The risk factors related to the decrease in serum VPA levels and clinical outcomes were evaluated. Our results show that VPA concentrations were reduced to subtherapeutic levels after the introduction of carbapenems. The reduction in VPA concentrations was found within 24 hours of the start of treatment with carbapenems. VPA levels continuously declined while the combination of treatments was used, which aggravated epileptic seizures in 48% of the patients. Renal disease and enzyme-inducing AEDs were risk factors that contributed to the severity of reduced serum VPA levels during combined treatment with carbapenems. This study suggests that clinicians need to be aware of the reduction of VPA concentrations to subtherapeutic levels and the aggravation of seizures while patients are treated with a combination of carbapenems and VPA.

McLaren et al.(1) recently used whole-exome sequencing to show that GNPAT p.D519G (rs11558492) is associated with a high-iron phenotype in HFE C282Y homozygous men. Three other studies examined this association in different Caucasian populations with conflicting results. (2)(3)(4) However, the role of GNPAT in the absence of iron overload or in the HFE wild-type population remains unclear.Here, we investigated iron indices before and after iron supplementation and their association with genetic polymorphisms. This study was approved by the ethics committee, and informed consent was obtained from all participants. We screened healthy reproductive-age women and excluded those with renal insufficiency, anemia, gastrointestinal bleeding, or chronic inflammation and those that were pregnant or breastfeeding; thus, 83 healthy female volunteers were eligible for analysis. Participants fasted overnight, and baseline iron parameters were measured at 8 AM. They were then administered sodium ferrous citrate (element iron, 100 mg), and blood was sampled 2 hours later. Data are presented in Table 1.Regarding TMPRSS6 rs855791, iron parameters at baseline or after iron challenge did not significantly differ between genotypes. For GNPAT rs11558492, 64 participants were wild type (A/A) and 19 carried variants (18 A/G and 1 G/G). The G allele frequency was 12% (20 of 166), similar to 14% in the general population in 1000 Genomes (chi-square test: P 5 0.416). Fasting serum iron levels were higher in subjects with GNPAT variants than in wild-type subjects (131.2 vs. 110.5 lg/dL; P 5 0.045), but there was no significant difference in fasting transferrin saturation (TS; 38.2% vs. 33.7%; P 5 0.153). After iron supplementation, serum iron levels and TS were both significantly higher in GNPAT variants (iron, 320.2 vs. 284.5 lg/dL; P 5 0.025; TS, 85.8% vs. 78.9%; P 5 0.040). Furthermore, multivariate analysis showed that the GNPAT genotype was an independent factor associated with baseline iron levels (P 5 0.045; adjusted R 2 5 0.037); the factors analyzed included age,

Genome wide studies have associated TMPRSS6 rs855791 (2321 C>T) with iron status and hepcidin. It is unclear whether this polymorphism affects iron absorption. In nonanemic Taiwanese women (n=79, 44 TT variant, 35 CC variant), we administered standardized rice-based test meals containing 4 mg of labeled 57Fe or 58Fe as FeSO4 on alternate days. Fractional iron absorption was measured by erythrocyte incorporation of the tracers 14 days after administration. Compared to the CC variant, in the TT variant serum iron and transferrin saturation were lower (P=0.001; P

Our report demonstrates CLS as an unusual adverse effect of bortezomib. As bortezomib use may become more common, clinicians should be aware of this novel but potentially life-threatening adverse effect. Based on our experience, timely management with steroids is important in dealing with this complication.