Myelodysplastic syndrome accompanied by basophilia and eosinophilia with t(5;12)(q31;p13)

The t(5;12)(q31not, vert, similar35;p12not, vert, similar13) is rare among cytogenetically categorized myeloid diseases. Here we describe a case of myelodysplastic syndrome (MDS) with basophilia followed by leukocytosis, basophilia, and eosinophilia with t(5;12)(q31;p13).A 44-year-old man was referred to Tsukuba University Hospital in August 2005, due to severe anemia and thrombocytopenia. Peripheral blood examination showed hemoglobin 4.5 g/dL, with mean corpuscular volume 109 fL, platelets 73 × 109/L, and white blood cells 4.9 × 109/L with 23% basophils, 3% eosinophils, and 0% blasts. Bone marrow was slightly hypocellular, with trilineage dysplasia. Cytogenetic examination of the bone marrow cells revealed a normal karyotype, 46,XY. A diagnosis of myelodysplastic syndrome–refractory anemia with excess blasts type 2 (MDS-RAEB2) was made according to the WHO classification

Venetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan

Background: In a Phase 3 international clinical trial (VIALE-C), venetoclax plus low-dose cytarabine improved the response rate and overall survival versus placebo plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia who were ineligible for intensive chemotherapy. After the enrollment period of VIALE-C ended, we conducted an expanded access study to provide preapproval access to venetoclax in combination with low-dose cytarabine in Japan. Methods: Previously, untreated patients with acute myeloid leukemia who were ineligible for intensive chemotherapy were enrolled according to the VIALE-C criteria. Patients received venetoclax (600 mg, Days 1–28, 4-day ramp-up in Cycle 1) in 28-day cycles and low-dose cytarabine (20 mg/m2, Days 1–10). All patients took tumor lysis syndrome prophylactic agents and hydration. Safety endpoints were assessed. Results: Fourteen patients were enrolled in this study. The median age was 77.5 years (range = 61–84), with 78.6% over 75 years old. The most common grade ≥ 3 treatment-emergent adverse event was neutropenia (57.1%). Febrile neutropenia was the most frequent serious adverse event (21.4%). One patient developed treatment-related acute kidney injury, leading to discontinuation of treatment. Two patients died because of cardiac failure and disease progression that were judged not related to study treatment. No patients developed tumor lysis syndrome. Conclusions: The safety outcomes were similar to those in VIALE-C without new safety signals and were well managed with standard medical care. In clinical practice, more patients with severe background disease are expected, in comparison with in VIALE-C, suggesting that it is important to carefully manage and prevent adverse events

Tokyo Guidelines 2018 management bundles for acute cholangitis and cholecystitis

Management bundles that define items or procedures strongly recommended in clinical practice have been used in many guidelines in recent years. Application of these bundles facilitates the adaptation of guidelines and helps improve the prognosis of target diseases. In Tokyo Guidelines 2013 (TG13), we proposed management bundles for acute cholangitis and cholecystitis. Here, in Tokyo Guidelines 2018 (TG18), we redefine the management bundles for acute cholangitis and cholecystitis. Critical parts of the bundles in TG18 include the diagnostic process, severity assessment, transfer of patients if necessary, and therapeutic approach at each time point. Observance of these items and procedures should improve the prognosis of acute cholangitis and cholecystitis. Studies are now needed to evaluate the dissemination of these TG18 bundles and their effectiveness. Free full articles and mobile app of TG18 are available at: . Related clinical questions and references are also include

Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis

The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also include

In vivo regulation of erythropoiesis by chemically inducible dimerization of the erythropoietin receptor intracellular domain.

Erythropoietin (Epo) and its receptor (EpoR) are required for the regulation of erythropoiesis. Epo binds to the EpoR homodimer on the surface of erythroid progenitors and erythroblasts, and positions the intracellular domains of the homodimer to be in close proximity with each other. This conformational change is sufficient for the initiation of Epo-EpoR signal transduction. Here, we established a system of chemically regulated erythropoiesis in transgenic mice expressing a modified EpoR intracellular domain (amino acids 247-406) in which dimerization is induced using a specific compound (chemical inducer of dimerization, CID). Erythropoiesis is reversibly induced by oral administration of the CID to the transgenic mice. Because transgene expression is limited to hematopoietic cells by the Gata1 gene regulatory region, the effect of the CID is limited to erythropoiesis without adverse effects. Additionally, we show that the 160 amino acid sequence is the minimal essential domain of EpoR for intracellular signaling of chemically inducible erythropoiesis in vivo. We propose that the CID-dependent dimerization system combined with the EpoR intracellular domain and the Gata1 gene regulatory region generates a novel peroral strategy for the treatment of anemia

CID Dose- and Transgene Expression Level-dependent Colony Formation of <i>G1HRD-idEpoRic</i> Bone Marrow Cells.

<p>(A) Increased CFU-E—derived colony formation in response to incremental doses of CID or rHuEPO. Bone marrow MNCs from line A transgenic mice were used. (B) The bone marrow MNCs of 3 independent transgenic mouse lines were cultured in methylcellulose medium supplemented with CID (1.0 nmol/mL) or rHuEPO (2.0 U/mL) for 3 days, and the numbers of CFU-E—derived colonies were counted. Note that the numbers of CFU-E—derived colonies correlate tightly with the expression levels of the transgene (line A > line B > line C, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119442#pone.0119442.g001" target="_blank">Fig. 1C</a>). These assays were performed in triplicate and repeated 3 times. The results are shown as the mean ± standard deviations.</p

Enlargement of the Spleen Red Pulp by the CID-idEpoRic System.

<p>(A) Gross appearance of enlarged spleens after the injection of the vehicle, CID (10 mg/kg), or rHuEPO (300 U/kg) for 9 consecutive days. (B–G) Hematoxylin and eosin staining of the spleen sections from vehicle- (B, E), CID- (C, F), or rHuEPO-treated (D, G) line A transgenic mice. E, F, and G show higher magnification views. The enucleated red blood cells were observed in the spleen red pulps of CID- and rHuEPO-treated mice (F, G). (H–J) The spleen sections from vehicle- (H), CID- (I), or rHuEPO-treated (J) mice were stained with an anti-ß-globin antibody. ß-globin-positive (brown signals) erythroid cells were expanded in the spleens of CID- (I) or rHuEPO-treated (J) transgenic mice. The scale bars indicate 1.0 cm (A), 200 μm (B–D, H–J), and 80 μm (E–G).</p

Blood Biochemical Profiles after Oral Administration of CID.

<p>Biochemical indices of the <i>G1HRD-idEpoRic</i> transgenic mice (Tg, line A) were measured 1 day after oral administration of 100 mg/kg CID for 10 consecutive days. As controls, age-matched (8–16 weeks of age) wild-type (WT) and vehicle-treated mice were used. The values represent the mean ± standard error of 4 mice for each group. AST, asparagine transferase; ALT, alanine transferase; BUN, blood urea nitrogen.</p><p>Blood Biochemical Profiles after Oral Administration of CID.</p