The incidence of hypersensitivity reaction (HR) to carboplatin has been reported to increase after repeated use of the drug. However, a reliable ex vivo test to predict HR to carboplatin is not currently available. We evaluated the clinical usefulness of measuring basophil CD203c to predict carboplatin-related HR in this prospective case-control study conducted at Mie University Hospital between October 2009 and September 2010. Eleven patients had history of carboplatin-related HR within the past 3 years, and 19 had no history of HR after receiving more than 5 courses of carboplatin therapy. Six of these 19 patients developed carboplatin-related HR during the study period. The CD203c basophils (%) and the mean fluorescence intensity (MFI) were analyzed on a flow cytometer and compared between patients with and without HR. Changes in the CD203c expression on basophils before and after HR were also assessed in patients who developed HR during the study period. The median CD203c basophils (%) and ΔMFI after 30-min exposure to 50 µg/mL carboplatin were significantly higher in patients with HR (3.5% and ΔMFI 9.0) compared with those without (2.2% and ΔMFI 0.4) (p<0.05). In particular, these values were significantly higher in patients with grade 4 anaphylaxis (10.6% and ΔMFI 22.0). All five patients who developed grade 2-4 anaphylaxis during the study period had high CD203c basophils (%) and/or increased ΔMFI on the day before HR. The results suggest that basophil CD203c may be a promising biomarker for the prediction of severe carboplatinrelated anaphylaxis.

The mucosal cutting biopsy technique is a useful diagnostic modality for the diagnosis of gastric GIST and for selection of the appropriate treatment.

BackgroundMagnesium oxide (MgO), an antacid and laxative, is widely used in Japan to treat constipation and peptic ulcers. Because serum Magnesium (Mg) levels are elevated in elderly and/or patients with renal failure, its periodic monitoring is recommended for patients prescribed MgO, in order to prevent MgO-induced hypermagnesemia. However, there is little information regarding the factors contributing to the development of MgO-induced hypermagnesemia. In the present study, we retrospectively investigated the risk factors of hypermagnesemia in patients prescribed MgO.MethodsData of 3258 patients hospitalized in Mie University Hospital between October 2015 and September 2017, who were prescribed MgO tablets, were extracted from the electronic medical records. According to the inclusion and exclusion criteria, 320 of the 3258 patients were enrolled in this study. Hypermagnesemia was defined as serum Mg levels ≥2.5 mg/dL (by the Common Terminology Criteria for Adverse Events version 4.0). Uni- and multivariate analyses were performed to identify risk factors for the development of hypermagnesemia in patients prescribed MgO using the following variables: age, estimated glomerular filtration rate, blood urea nitrogen levels, MgO dose, duration of MgO administration, and co-administrated proton pump inhibitors, H2 blocker (famotidine), vitamin D3 drugs, and diuretics.ResultsSeventy-five patients out of 320 (23%) developed grade 1 and grade 3 hypermagnesemia, with the occurrence of grade 1 and grade 3 in 62 (19%) and 13 (4%) patients, respectively. Multivariate logistic regression analyses indicated 4 independent risk factors for hypermagnesemia comprising estimated glomerular filtration rate ≤ 55.4 mL/min (odds ratio (OR): 3.105, P = 0.001), blood urea nitrogen ≥22.4 mg/dL (OR: 3.490, P < 0.001), MgO dose ≥1650 mg/day (OR: 1.914, P = 0.039), and duration of MgO administration ≥36 days (OR: 2.198, P = 0.012). The occurrence rate of hypermagnesemia was elevated in accordance with these risk factors.ConclusionsThese results suggest that a periodic monitoring of serum Mg levels is strongly recommended in MgO prescribed patients, especially in those with multiple risk factors for hypermagnesemia. The present findings provide useful information for the safe management of MgO therapy.Electronic supplementary materialThe online version of this article (10.1186/s40780-019-0133-7) contains supplementary material, which is available to authorized users.

Background and Aim: Newly developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. We conducted surveillance of subjects with Barrett's esophagus using this ultrathin transnasal endoscopy. In Japan the lower margin of the lower esophageal palisade vessels is defined the gastroesophageal junction in deep inspiration. We diagnose Barrett's esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. Methods and Results: Barrett's esophagus was confirmed in 116 out of 135 subjects (85.9%), with 17 cases of short-segment Barrett's esophagus (SSBE) and 99 of ultra-shortsegment Barrett's esophagus. Close observation of the Barrett's esophagus mucosal structural pattern using narrow band imaging revealed 29 cases with an oval or round pattern, 29 with a long straight pattern, 47 with a villous pattern, 8 with a cerebriform pattern, and 6 with an irregular pattern according to Goda classification. Mucosal biopsies from all subjects with SSBE are examined. Histological examination revealed intestinal metaplasia in only eight subjects. We grouped the oval/round and long straight patterns as closed type, and the villous, cerebriform, and irregular patterns as open type. Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between intestinal metaplasia and the open-type pattern. Conclusion: We consider this new ultrathin transnasal endoscopy to be a useful technique for surveillance of Barrett's esophagus, especially SSBE.

Basophil activation was observed in patients with a history of carboplatin-induced severe hypersensitivity reaction (HR). However, the precise mechanism by which carboplatin induces basophil activation and the associated surrogate markers remains to be elucidated. To investigate whether IgE-dependent mechanisms, including the overexpression of FcεRI, participate in carboplatin-induced basophil activation, 13 ovarian cancer patients were enrolled: 5 with a history of carboplatin-induced severe hypersensitivity reaction within the past 2 years, and 8 with no such history. The expression levels of FcεRI, IgE, and CD203c on basophils were measured using a flow cytometer. Immunoglobulin E-dependent basophil activation was evaluated by testing for IgE passive sensitization using lactic acid, and by testing for phosphatidylinositol 3-kinase inhibition, using wortmannin. In three patients positive for carboplatin hypersensitivity, pretreatment with wortmannin almost completely inhibited carboplatin-induced basophil activation (P < 0.05). In a healthy control subject, whose own IgE showed no response to carboplatin, acquired reactivity to carboplatin when exposed to plasma from patients positive for carboplatin hypersensitivity. This did not occur when the same experiment was carried out using plasma from the patients negative for carboplatin hypersensitivity. Moreover, pretreatment with omalizumab, a monoclonal anti-IgE antibody, almost completely blocked carboplatin-induced basophil activation in the plasma of patients positive for carboplatin hypersensitivity. On further investigation, the HR-positive group had significantly higher levels of FcεRI compared with the negative group (P < 0.05). In conclusion, an IgE-dependent mechanism incorporating FcεRI overexpression participates in carboplatin-induced severe HR. These results establish the relevance of monitoring the pharmacodynamic changes of basophils to prevent carboplatin-induced severe HR.