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Aim: Single-arm, open-label, phase 3 study to evaluate the efficacy and safety of ferric derisomaltose (FDI) for iron deficiency anemia (IDA) in Japanese women with postpartum hemorrhage (PPH)., Methods: Postpartum women aged 20-39 years with serum ferritin <25.0 ng/ml, hemoglobin (Hb) <10.0 g/dl, and blood loss ≥500 ml within 24 h post-delivery were eligible to receive high-dose intravenous FDI. The primary endpoint was the maximum change in Hb concentration by Week 8. Key secondary endpoints included change in iron parameters and percentage of patients with a total Edinburgh Postnatal Depression Score (EPDS) ≥9. Safety assessments included treatment-emergent adverse events (TEAEs) and iron concentrations in maternal milk., Results: All (n = 21 [100.0%]) patients received the predetermined total iron dose by Day 8. Hb concentrations increased rapidly and significantly (p < 0.001) following FDI. Serum ferritin levels also increased rapidly and were maintained near or above the upper limit of normal reference value (250 ng/ml). Following FDI, two (9.5%) patients had a total EPDS score of ≥9. TEAEs occurred in 23 of 42 (54.8%) patients and neonates overall, including 18 of 21 (85.7%) patients and 5 of 21 (23.8%) neonates. TEAEs were mild in all adult patients and four neonates, and moderate in one neonate. Iron concentrations in maternal milk remained within normal reference values. Appropriate patient selection and patient-adjusted dosage selection facilitated safe and effective administration of high-dose (≥1000 mg) FDI., Conclusions: Rapid and sustained improvements in Hb and iron stores occurred following FDI for IDA with PPH, with no new safety signals identified., Clinical Trial Identifier: JapicCTI-194888., (© 2023 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Aims: This study aimed to estimate the utility values of the factors associated with intravenous (IV) iron infusion treatment in Japanese patients with iron-deficiency anemia (IDA) from the patient's perspective., Methods: A conjoint analysis based on online survey data was conducted in May 2022 (registration number: UMIN000047756). Respondents in the main group were selected from the general population (20-69 years). Seven attributes were included in this analysis: waiting time before receiving an IV infusion, pain due to IV infusion, time required for IV infusion, number of IV infusions required to achieve treatment effect, frequency of hypophosphatemia as a side effect of IV infusion, frequency of skin discoloration by the drug solution, and out-of-pocket cost for one IV infusion visit. The utility of each level for each attribute was estimated using a logistic regression model as the difference from non-treatment., Results: The responses were collected from 1,026 people. The utilities decreased with higher pain (-0.189 for pain level of 3.05), longer time for the IV infusion (-0.145 or -0.212 for 5 or 15 min), greater number of required IV infusions (-0.773 or -1.899 for 3 or 25 times), and higher frequency of adverse events (-0.373 or -0.385 for 13.0% or 14.2% of hypophosphatemia incidences; -0.502 for 2.3% of skin discoloration per one infusion)., Limitations: Since this study was based on an online survey, the reliability of the results depends on whether the respondents understood the questions accurately. Further, the respondents were selected from an online panel, potentially affecting finding generalizability., Conclusions: The results indicate that utilities differ depending on the factors associated with IV iron infusion treatment. The findings of this study may be useful for informing future treatments or improving current treatment regimes, supporting the achievement of complete iron repletion for Japanese patients with IDA.

Bacteria in the family Geobacteraceae have been proven to fill important niches in a diversity of anaerobic environments and global biogeochemical processes. Here, three bacterial strains in this family, designated Red875 T , Red259 T , and Red421 T were isolated from river sediment and paddy soils in Japan. All of them are Gram-staining-negative, strictly anaerobic, motile, flagellum-harboring cells that form red colonies on agar plates and are capable of utilizing Fe(III)-NTA, Fe(III) citrate, ferrihydrite, MnO 2 , fumarate, and nitrate as electron acceptors with acetate, propionate, pyruvate, and glucose as electron donors. Phylogenetic analysis based on the 16S rRNA gene and 92 concatenated core proteins sequences revealed that strains Red259 T and Red421 T clustered with the type strains of Geomonas species, whereas strain Red875 T formed an independent lineage within the family Geobacteraceae. Genome comparison based on  average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values clearly distinguished these three strains from other Geobacteraceae members, with lower values than the thresholds for species delineation. Moreover, strain Red875 T also shared low average amino acid identity (AAI) and percentage of conserved proteins (POCP) values with the type species of the family Geobacteraceae. Based on these physiological, chemotaxonomic, and phylogenetic distinctions, we propose that strain Red875 T (=NBRC 114290 T  = MCCC 1K04407 T ) represents a novel genus in the family Geobacteraceae, namely, Geomesophilobacter sediminis gen. nov., sp. nov., and strains Red259 T (=NBRC 114288 T  = MCCC 1K05016 T ) and Red421 T (=NBRC 114289 T  = MCCC 1K06216 T ) represent two novel independent species in the genus Geomonas, namely, Geomonas propionica sp. nov. and Geomonas anaerohicana sp. nov., respectively., Competing Interests: Conflicts of Interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Iron-deficiency anemia (IDA) is the most common form of anemia. It is treated through iron replacement therapy, with oral iron administration as the recommended first-line treatment. However, intravenous (IV) iron formulation is at timed used owing to adverse effects of oral iron administration such as gastrointestinal symptoms. Although saccharated ferric iron oxide had been the only available IV iron formulation in Japan for a long time, ferric carboxymaltose (FCM) has recently been approved. In this review, the characteristics, efficacy, and safety of FCM will be discussed mainly by introducing the results of three clinical trials for FCM conducted in Japan. More effective treatment for patients with IDA might be achieved through the introduction of FCM administration in clinical settings.

Patients with iron deficiency anemia (IDA) need to take oral iron preparations, which serve as the first-line treatment in IDA, for several months in order to replenish body iron stores after the improvement of anemia. However, existing oral iron preparations have concerns regarding its long-term use due to side effects, such as gastrointestinal symptoms. Previous clinical studies have shown that ferric citrate hydrate (FC) exhibits sufficient therapeutic efficacy in patients with IDA and lowers the risks of nausea and vomiting in comparison with existing oral iron preparations. In this study, we evaluated the efficacy and safety of FC administration at doses of 500 and 1,000 mg/day for up to 24 weeks as iron replacement therapy in patients with IDA. The results of this study showed that both the doses of FC improved anemia and iron-deficiency conditions and led to sufficient iron replacement response in most patients with IDA. No safety concerns were identified. Therefore, FC is expected to be a novel oral iron preparation for patients with IDA.

Objectives: This study aimed to investigate the usefulness of contrast-enhanced endoscopic ultrasonography (EUS) with time-intensity curve (TIC) in differentiating pancreatic diseases., Methods: Patients who underwent contrast-enhanced EUS between January 2007 and June 2009 were analyzed retrospectively, including 48 with pancreatic ductal cancer (PC), 14 with autoimmune pancreatitis (AIP), 13 with mass-forming pancreatitis (MFP), and 16 with pancreatic endocrine tumor (PET). After intravenous injection of contrast agent, contrast imaging pattern, TIC-based quantitative evaluation, and diagnostic ability of EUS in combination with TIC to diagnose benignancy or malignancy were assessed., Results: Hypovascular and heterogeneous pattern (42/48) in PC, isovascular and homogenous (21/27) in AIP and MFP, and hypervascular and rapid stained (16/16) in PET were observed. The echo intensity reduction rate from the peak at 1 minute was the greatest in PC followed by MFP, AIP, and PET (P < 0.05). The diagnostic accuracies based on contrast imaging pattern (84.0%) and TIC (88.0%) were higher than those based on B-mode imaging (82.6%) and dynamic computed tomography (81.3%). In EUS in combination with TIC, sensitivity, specificity, and accuracy rose up to 95.8%, 92.6%, and 94.7%, respectively., Conclusions: Contrast-enhanced EUS with the dynamic quantitative analysis preparing TIC increased the diagnostic accuracy for pancreatic diseases.

Background and Aims: Kupffer imaging in contrast-enhanced ultrasonography (CEUS) with Sonazoid, which lasts for 60 min or longer, may be useful in ultrasound-guided percutaneous tumor ablation. The utility of Sonazoid in radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) was investigated in this study., Methods: We analyzed a total of 716 HCC nodules that were detected on dynamic computed tomography in 316 patients. Detectability of these nodules was compared between CEUS and conventional ultrasonography. The effectiveness in the treatment was assessed by comparing the mean numbers of treatment sessions of RFA in patients treated with CEUS and that in historical controls matched for tumor and background conditions., Results: Detectability of tumor nodule was 83.5% in conventional ultrasonography and 93.2% in CEUS (P=0.04). Sixty-nine nodules in 52 patients were additionally detected with CEUS. The number of additionally detected tumor nodules was positively correlated with serum albumin level (P=0.016). The number of RFA sessions was 1.33±0.45 with CEUS as compared to 1.49±0.76 in the historical controls (P=0.0019)., Conclusions: CEUS with Sonazoid is useful for HCC detection in patients with a well-conserved liver function reservoir. The decrease in RFA session numbers indicated the utility of Sonazoid in RFA treatment of HCC., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

An epidemiological study was carried out in natural water supplies of Hokkaido, one of the largest dairy prefectures in Japan. To investigate the prevalence of Cryptosporidium parvum (C. parvum) oocysts water samples were collected from three rivers in the eastern area of Hokkaido from August 1999 to October 2001, and C. parvum oocysts were collected and purified by the ferric sulfate flocculation method. The oocysts were detected using the immunofluorescent assay test (IFAT) and 4', 6-diamidino-2-phenylindole (DAPI) staining. The seasonal change in the number of oocysts detected was observed. Oocysts increased in numbers from the late summer to the early autumn (from August to November), thereafter, they exhibited a trend to decrease until December, when no oocysts could be detected. The maximum number of oocysts detected in the three rivers was 3.50, 5.00 and 3.33 oocysts/l, respectively. The oocyst density in river water changed in relation to the season in 1999, 2000 and 2001. This report first cleared up the seasonal changes in C. parvum oocysts number in river water.

The ethylisocyanide equilibria of all the five known hemoglobins M, namely Hb M Iwate (alpha287 Tyrbeta2), Hb M Boston (alpha258 Tyrbeta2), Hb M Hyde Park (alpha2beta292 Tyr), Hb M Saskatoon (alpha2beta263 tyr), and Hb M Milwaukee-I (alpha2beta267 Glu), were studied both in the half-ferric and fully reduced heme states. In the half-ferric state, no heme-heme interaction was observed for Hb M Iwate, Hb M Boston, and Hb M Hyde Park, but Hb M Saskatoon and Hb M Milwaukee-I show small but definite heme-heme interaction with Hill's n of 1.3. The beta chain mutants, Hb M Hyde Park and Hb M Saskatoon, have almost normal affinity for ethylisocyanide and a normal Bohr effect, whereas the alpha chain mutants, Hb M Iwate and Hb M Boston, have abnormally low affinity and almost no Bohr effect. Hb M Milwaukee-I showed a large Bohr effect and low affinity. These results are consistent qualitatively with those on oxygen equilibria reported previously. In the fully reduced state, in which all four hemes were in the ferrous state and capable of binding ethylisocyanide distinct differences were found in the extent of heme-heme interaction. Namely, the n values for proximal histidine mutants, Hb M Iwate and Hb M Hyde Park, were 1.1 and 1.0, respectively, whereas the distal histidine mutants, Hb M Boston and Hb M Saskatoon, showed high n values of 2.4 and 1.6, respectively. Hb M Milwaukee-I also exhibited a high n value of 2.0 The ethylisocyanide affinity of the four histidine mutants was high compared with that of Hb A, while that for Hb M Milwaukee-I was almost normal. All five Hbs M had approximately normal magnitudes of Bohr effect. In the half-ferric state, the proximal and distal histidine mutants of the same chain showed similar affinity for ethylisocyanide and Bohr effect, rather different from those of the mutants of the opposite chain. These differences seem to be derived from the difference of abnormal bonding of ferric iron to tyrosine or glutamic acid. On the other hand, the reduction of iron, which abolished the abnormal bonding and made all of the chains capable of binding ligand, extinguished the differences of alpha and beta chains, and the effect of amino acid side chains close to iron on ligand binding properties became clear. Proximal histidine, which is considered to trigger the transition between the T and R states, seems to be essential to the heme-heme interaction.