Hiroshi Kawabata

We reviewed 70 patients with prolonged activated partial thromboplastin time (aPTT) who underwent cross‑mixing tests (CMT) at our hospital. Median age was 70 years, median aPTT was 65.8 s, and 41 (58.5%) underwent CMT for preoperative screening. Visual CMT showed 13 deficiency‑pattern, 4 inhibitor‑pattern, and 53 lupus anticoagulant (LAC)‑pattern cases. Direct oral anticoagulants (DOACs) explained one deficiency‑pattern and two LAC‑pattern cases. All inhibitor‑pattern patients presented with bleeding and were diagnosed with acquired hemophilia A (AHA). Based on additional tests, including dilute Russell’s viper venom time, LAC was considered the cause of aPTT prolongation in 59 cases (84.3%). No congenital hemophilia was identified. In CMT, an increase in aPTT after incubation in 50% mixed plasma clearly differentiated AHA (> 30 s) from LAC (< 25 s). All preoperative cases were ultimately attributed to LAC or DOACs; 37 patients proceeded to surgery without abnormal bleeding. These findings suggest that most preoperative aPTT prolongations seen in community practice are due to LAC, whereas AHA is rare. CMT provides same‑day results and is useful for rapidly excluding AHA in preoperative evaluation.

A 79-year-old woman was admitted to our hospital with a persistent fever, malaise, and anemia requiring frequent transfusions. A peripheral blood smear revealed erythrocyte agglutination and a high titer of cold agglutinins. Imaging examination revealed pulmonary emboli and multiple subacute cerebral infarctions. Despite the absence of lymphadenopathy or splenomegaly, the diagnosis of intravascular large B-cell lymphoma (IVLBCL) was confirmed through random skin biopsies. Immunochemotherapy successfully induced remission of her fever and anemia with normalization of her cold agglutinin titer. This case highlights that cold agglutinin syndrome can be associated with aggressive lymphomas, including IVLBCL.

A 65-year-old man with generalized lymphadenopathy was diagnosed with classical Hodgkin lymphoma-Mixed cellularity via left cervical lymph node biopsy. Initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine led to complete metabolic remission (CMR); however, recurrence developed after 6 months. Brentuximab vedotin induced partial remission followed by systemic relapse after 10 months. Nivolumab led to a second CMR, but disease progression persisted over nearly 4 years, despite treatment adjustments and local radiotherapy. Eventually, the patient was diagnosed with diffuse large B-cell lymphoma during routine esophagogastroduodenoscopy. Four courses of rituximab-CHOP therapy led to a CMR. This case highlights the importance of performing re-biopsies to detect the recurrence or progression of lymphoma.

Iron is an essential trace metal, vital for various physiologic processes, but excess levels can harm health. Maintaining iron homeostasis is critical, with hepcidin playing a key role. The isoform hepcidin-25 exerts the most significant influence on iron metabolism, making its serum levels a valuable diagnostic tool. However, mass-spectrometry and other conventional measurement methods can be difficult to perform, and some immunoassays lack reliability. In this study, we employed a recently developed latex agglutination method integrated with a readily available automated analyzer to quantify serum hepcidin-25 levels in both volunteers recruited from personnel of our hospital (n = 93) and patients with various hematological disorders (n = 112). Our findings unveiled a robust positive correlation between serum hepcidin-25 and ferritin, as well as C-reactive protein levels, in both volunteers and patients. Among the patients with hematological disorders, there was a noteworthy negative correlation between hepcidin-25 levels and hemoglobin concentrations, as well as reticulocyte counts. Interestingly, the hepcidin-25/ferritin ratio was remarkably low in patients with hemolytic anemia and myelodysplastic syndromes with ring sideroblasts. Our findings suggest that quantifying serum hepcidin-25 and the hepcidin-25/ferritin ratio using this method may be valuable for screening of hematopoietic diseases and other iron metabolism disorders.

Iron-deficiency anemia (IDA) associated with gastrointestinal diseases is the second most common etiology of IDA in Japan, and is most often caused by gastrointestinal bleeding. A multicenter, single-arm (2 groups), open-label, phase III study was conducted to assess the efficacy and safety of ferric derisomaltose (FDI) when administered by intravenous (IV) bolus injection (n = 30) or drip infusion (n = 10) in Japanese patients with IDA associated with gastrointestinal diseases. The primary endpoint, which was the mean maximum change in hemoglobin (Hb) concentration from baseline, was 4.33 (95% confidence interval, 3.82–4.83) g/dL in the overall population (4.27 [3.83–4.71] g/dL in the bolus injection group and 4.49 [2.69–6.29] g/dL in the drip infusion group). Treatment-emergent adverse events (TEAEs) were reported in 24 patients (60.0%) in the overall population (18 patients [60.0%] in the bolus injection group and 6 patients [60.0%] in the drip infusion group). No serious treatment-related TEAEs or unexpected safety findings were reported during the study. These findings reveal a favorable efficacy and safety profile for FDI when administered by IV bolus injection or drip infusion in Japanese patients with IDA associated with gastrointestinal diseases.

Purpose To examine whether the machine learning (ML) analyses using clinical and pretreatment 2-deoxy-2-[¹⁸F]fluoro-d-glucose positron emission tomography ([¹⁸F]-FDG-PET)–based radiomic features were useful for predicting prognosis in patients with hypopharyngeal cancer. Procedures This retrospective study included 100 patients with hypopharyngeal cancer who underwent [¹⁸F]-FDG-PET/X-ray computed tomography (CT) before treatment, and these patients were allocated to the training (n=80) and validation (n=20) cohorts. Eight clinical (age, sex, histology, T stage, N stage, M stage, UICC stage, and treatment) and 40 [¹⁸F]-FDG-PET–based radiomic features were used to predict disease progression. A feature reduction procedure based on the decrease of the Gini impurity was applied. Six ML algorithms (random forest, neural network, k-nearest neighbors, naïve Bayes, logistic regression, and support vector machine) were compared using the area under the receiver operating characteristic curve (AUC). Progression-free survival (PFS) was assessed using Cox regression analysis. Results The five most important features for predicting disease progression were UICC stage, N stage, gray level co-occurrence matrix entropy (GLCM_Entropy), gray level run length matrix run length non-uniformity (GLRLM_RLNU), and T stage. Patients who experienced disease progression displayed significantly higher UICC stage, N stage, GLCM_Entropy, GLRLM_RLNU, and T stage than those without progression (each, pAUC=0.860, accuracy=0.800; validation: AUC=0.803, accuracy=0.700). In the logistic regression model, 5-year PFS was significantly higher in patients with predicted non-progression than those with predicted progression (75.8% vs. 8.3%, pp=0.045). Conclusions The logistic regression model constructed by UICC, T and N stages and pretreatment [¹⁸F]-FDG-PET–based radiomic features, GLCM_Entropy, and GLRLM_RLNU may be the most important predictor of prognosis in patients with hypopharyngeal cancer.

A multicenter, randomized, open-label, phase III study was conducted to compare the efficacy and safety of intravenous ferric derisomaltose (FDI) versus saccharated ferric oxide (SFO) in Japanese patients with iron deficiency anemia associated with menorrhagia. FDI can be administered as a single dose up to 1000 mg, whereas SFO has a maximum single dose of 120 mg. The primary endpoint, which was the maximum change in hemoglobin concentration from baseline, was noninferior for the FDI group compared with the SFO group. The incidence of treatment-emergent adverse events was lower in the FDI group (66.2%) than in the SFO group (90.8%). Notably, the incidence of serum phosphorus level < 2.0 mg/dL was significantly lower in the FDI group (8.4%) than in the SFO group (83.2%), and severe hypophosphatemia (≤ 1.0 mg/dL) occurred in 6.7% of SFO‑treated patients compared with none in the FDI group. The percentage of patients who achieved the cumulative total iron dose during the 8-week treatment period was higher in the FDI group (92.8%) than in the SFO group (43.2%). The study met its primary endpoint, and also demonstrated the tolerability of a high dose of FDI per infusion, with a lower incidence of hypophosphatemia.

Various systems for predicting the prognosis of patients with myelodysplastic syndromes (MDS) have been developed. However, associations between performance status (PS) and prognosis of MDS require further investigation. To objectively assess the impact of PS on survival, we examined laboratory findings associated with PS, including serum levels of C-reactive protein (CRP), albumin (ALB), and total cholesterol (CHOL). Patients (n = 123; male 86, female 37; median age 74 yrs.) diagnosed with MDS or myelodysplastic/myeloproliferative neoplasms at Kanazawa Medical University Hospital between 2010 and 2020 were enrolled and grouped by cutoff values determined by receiver operating characteristic analysis: 0.44 mg/dL for CRP, 4.0 g/dL for ALB, and 120 mg/dL for CHOL. The median follow-up period was 17.6 months. Kaplan–Meier analysis revealed that overall survival (OS) in the high CRP, low ALB, and low CHOL groups was significantly shorter than in the low CRP, high ALB, and high CHOL groups, respectively. Multivariable analysis revealed that elevated serum CRP was an independent prognostic risk factor independent of gender, bone marrow blast percentage, and cytogenetics.