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An 8.0‐kg 8‐year‐old male dachshund was presented for surgical treatment of suspected pituitary‐dependent hyperadrenocorticism with portal vein thrombosis. Advanced diagnostic imaging revealed a thrombus in the splenic and portal veins. For the portal vein thrombus, CT angiography showed an enhanced timing delay in the lateral right and caudate liver lobes. Blood tests showed a marked increase in the liver panel, including total bile acid. Brain MRI revealed a pituitary mass, suggesting pituitary‐dependent hyperadrenocorticism. The mass was completely resected. The preoperative antithrombotic therapy of rivaroxaban (0.66 mg/kg, PO, once per day) and clopidogrel sulphate (1.66 mg/kg, PO, once per day) was continued postoperatively. Six months after resection of the pituitary mass, the thrombus had disappeared. Further studies are required to prove a causal association between the disappearance of the thrombus and the treatments provided. [ABSTRACT FROM AUTHOR]

Objectives The objectives of this study were to establish a magnetic resonance imaging-based classification system for canine hyperadrenocorticism according to pituitary gland extension, determine indications for trans-sphenoidal hypophysectomy, and clarify the prognosis for each disease grade. Methods A 5-point classification system (Grades 1 to 5) was developed based on tumour extension in dorsal and cranio-caudal directions. Cases were then classified as Type A: no arterial circle of Willis or cavernous sinus involvement and Type B: cases in which these blood vessels were involved. Results Medical records and magnetic resonance imaging data of 37 cases with hyperadrenocorticism were reviewed. Thirty-three cases underwent surgery; 4 Grade 5 cases did not have appropriate indications for surgery, and other therapies were used. Complete resection was achieved for 3, 3, 22 and 1 Grade 1A, 2A, 3A and 3B cases, respectively. Resection was incomplete in 1, 1 and 2 Grade 3A, 3B and 4B cases, respectively. Remission was achieved in 29 cases. Recurrence occurred in 4 cases, all of which were classified as Grade 3. Clinical Significance Dogs with Type A, Grade 1 to 3 hyperadrenocorticism had a good prognosis following trans-sphenoidal hypophysectomy. Grade 3B, 4 and 5 cases may not be suitable for this surgery. [ABSTRACT FROM AUTHOR]

Background. Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported. Methods. We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low-dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed. Results. Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04). Conclusions. Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV. [ABSTRACT FROM AUTHOR]

Background Intestinal microbial ecology is actively regulated by Paneth cell-derived antimicrobial peptides, α-defensins. Graft-versus-host disease ( GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation ( SCT). We previously demonstrated that Paneth cells are targeted by GVHD, and their expression of antimicrobial peptide α-defensins is impaired, leading to a loss of physiological diversity among the microflora and development of bloodstream infection. Herein, we evaluated whether fecal levels of α-defensins could be surrogate marker of intestinal dysbiosis. Methods We directly measured α-defensin cryptdin-1 (Crp1) in fecal pellets of mice with GVHD by using a novel enzyme-linked immunosorbent assay. Results Fecal levels of Crp1 were significantly decreased in mice with GVHD but unchanged in mice without GVHD after SCT. These were correlated with intestinal flora diversity. Conclusion We demonstrate a link between reduced secretion of Paneth cell α-defensins and dysbiosis of intestinal flora in GVHD. Fecal levels of α-defensins could be surrogate markers for intestinal microbial homeostasis. [ABSTRACT FROM AUTHOR]

Introduction: Dabigatran is an oral intake thrombin inhibitor for preventive administration against stroke accompanied by atrial fibrillation. Although dabigatran causes prolonged activated partial thromboplastin time (APTT), the effect of dabigatran on each coagulation factor and coagulation factor inhibitor remains to be investigated. Our aim was to analyze the influence of dabigatran on coagulation factors and coagulation factor inhibitors. Methods: We administered dabigatran to 40 patients. In 26 of these 40, we analyzed the activity of several coagulation factors and their inhibitors. We used Fisher's exact test to determine statistical significance. Results: The activities of many coagulation factors changed during the dabigatran therapy. Factor II levels decreased in all patients showing prolongation of partial thromboplastin (PT) and APTT. The antifactor VIII inhibitor was positive in the majority of patients with prolonged PT and APTT, while activities of protein C, protein S, and antifactor IX inhibitor were not associated with PT and APTT prolongation. Conclusion: Dabigatran affects the activities of many coagulation factors, including factors II, V, VIII, and IX, as well as the antifactor VIII inhibitor. [ABSTRACT FROM AUTHOR]

Background Reactivation of hepatitis B virus ( HBV) infection, reverse seroconversion ( RS), is a serious complication after allogeneic stem cell transplantation (allo HSCT). We previously conducted a post-transplant hepatitis B vaccine intervention trial and demonstrated the vaccine efficacy in preventing HBV- RS. This report is an update of the hepatitis B vaccine study. Methods In this trial, 21 patients were enrolled and received a standard 3-dose regimen of hepatitis B vaccine after discontinuation of immunosuppressants, whereas 25 transplant recipients with previous HBV infection did not receive the vaccine and served as controls. Results None of the 21 patients in the vaccine group developed HBV- RS and 12 controls developed HBV- RS in median follow-up periods of 60 months (range 13-245). HBV vaccine resulted in a positive value of hepatitis B surface antibody ( HBsAb) titer in 9 patients, while HBsAb remained negative in 12 patients. Presence of a high titer of HBsAb before vaccination was associated with conversion into HBsAb positivity after vaccination. Conclusion These results demonstrated the long-term effects of HBV vaccine for preventing HBV- RS after allo HSCT. Of note, no HBV- RS occurred, even in patients who did not achieve conversion into HBsAb positivity after vaccination. [ABSTRACT FROM AUTHOR]

Background Systolic dysfunction is associated with poor outcomes in dogs with myxomatous mitral valve disease. However, assessment of systolic variables by conventional echocardiographic methods is difficult in these dogs because of mitral regurgitation ( MR). Hypothesis We hypothesized that assessment of systolic function by dobutamine stress may identify systolic dysfunction in dogs with MR, and that 2-dimensional speckle-tracking echocardiography (2D- STE) could quantitatively evaluate myocardial function. Animals Anesthetized dogs with experimentally induced MR. Methods Dogs were examined for systolic myocardial deformations using 2D- STE during dobutamine infusion before and 3 and 6 months after MR induction. We evaluated peak systolic rotation and rotation rate in each basal and apical view; peak systolic torsion and torsion rate were also calculated. Results Invasive peak positive first derivatives of left ventricular pressure (dp/dt) were significantly decreased in dogs 6 months after induction of MR compared with pre- MR results. After 3 and 6 months of MR, dogs had diminished peak systolic torsion values and torsion rates in response to dobutamine infusion compared with pre- MR results (3 months, P < .001 and P = .006; 6 months, P = .003 and P = .021). These results were significantly correlated with overall invasive dp/dt ( r = 0.644, P < .001; r = 0.696, P < .001). Conclusions and Clinical Importance Decreased torsion during dobutamine infusion in dogs with MR may reflect latent systolic dysfunction. Dobutamine infusion, therefore, may be useful for the assessment of systolic function in dogs with MR. [ABSTRACT FROM AUTHOR]

Introduction Cord blood ( CB) is being increasingly used as a source of hematopoietic stem cells for transplantation to treat diseases of the blood and immune systems, and there is an urgent need to expand CB banking worldwide. CB processing requires costly machinery or a clean room that hampers wider application of CBT particularly in the developing countries. Methods We developed a novel filtration system using a nonchemical-coated and nonwoven polyester fabric filter, which traps cells through affinity and does not require centrifugation or potentially toxic chemicals. Results Cell processing with the device resulted in minimum cell loss of total cells and CD34+ cells, without impairing the ability of CD34+ cells to engraft and differentiate both in vivo and in vitro. Conclusion CB processing with this device is simple, cost-effective, and nontoxic without requiring costly equipment will thus facilitate international CB banking, which helps in meeting the increasing worldwide demand for CB for allogeneic hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

An 11-year-old spayed female miniature dachshund was evaluated for a 2-month history of chronic vomiting. Abdominal ultrasonography revealed a heterogeneous mass in the pyloric region. Contrast upper gastrointestinal radiography demonstrated impairment of gastric outflow. Endoscopic examination revealed multiple polyps at the gastric pylorus. The pyloric polyps were variable in size, sessile-shaped and pedunculated. Initially, endoscopic polypectomy was attempted, but all the polyps could not be completely resected. Thus, endoscopic polypectomy with argon plasma coagulation was performed to cauterise the lesions. The histopathological diagnosis of the lesions was inflammatory polyps, and a moderate number of Helicobacter spp. was revealed. After the argon plasma coagulation treatment, the dog did not vomit, and improvement of clinical signs was maintained for 13 months. Endoscopic polypectomy with argon plasma coagulation may be useful for mixtures of sessile and pedunculated polyps. The present report may provide a basis for further studies of argon plasma coagulation treatment for canine gastrointestinal polyps. [ABSTRACT FROM AUTHOR]

Objectives To evaluate left ventricular geometry in dogs with various stages of myxomatous mitral valve disease. Methods Ninety-seven dogs with myxomatous mitral valve disease classified by the International Small Animal Cardiac Health Council system and 20 weight- and age-matched healthy dogs. Left ventricular long-axis to short-axis ratio, sphericity index in end-diastole and end-systole, left ventricular wall thickness to internal dimension ratio and relative wall thickness were assessed. Results The diastolic sphericity index was lower in classes Ib, II and III than in healthy dogs (P=0·003, P<0·001 and P<0·001) and was also lower in class III than in classes Ia, Ib and class II dogs (P<0·001, P<0·001 and P=0·002). The relative wall thickness was lower in classes II and III than in class Ia (P=0·003 and P<0·001), class Ib (P=0·004 and P<0·001), and healthy dogs (P<0·001 and P<0·001) and was also lower in class III than in class II (P=0·005). Clinical Significance Sphericity index and relative wall thickness are simple methods for assessing left ventricular geometry using two-dimensional echocardiography that may be useful in myxomatous mitral valve disease dogs as part of risk stratification. [ABSTRACT FROM AUTHOR]

Background Left ventricular torsional motion plays an important role for effective pump function. However, noninvasive clinical assessment of torsional deformations by two-dimensional speckle-tracking echocardiography (2D- STE) in dogs with myxomatous mitral valve disease ( MMVD) has not been reported. Hypothesis Left ventricular torsion is determined by the native orientation of the helical myocardial fibers, such that it might provide better assessment of myocardial function than conventional methods. Animals Sixty-seven client-owned dogs with MMVD were classified into 3 classes based on the International Small Animal Cardiac Health Council classification and 16 weight- and age-matched healthy dogs. Methods Dogs were examined for myocardial deformations by 2D- STE and were evaluated for peak systolic rotation and rotation rate at each basal and apical view. Dogs also were evaluated for peak systolic torsion and torsion rate. Results Peak systolic torsion was higher in class II than in class I ( P < .001) dogs. Peak systolic torsion was lower in class III than in class II ( P = .001) dogs and controls ( P = .003). Conclusions and Clinical Importance Torsional deformations assessed by 2D- STE differed among clinical classes of MMVD. Myocardial torsional deformations by 2D- STE may provide more detailed assessment of contractile function in dogs with MMVD. [ABSTRACT FROM AUTHOR]

Long-term analysis of infectious complication after high-dose immunosuppressive therapy with CD34-selected autologous hematopoietic stem cell transplantation for patients with severe autoimmune diseases (AD) was performed. Theoretically, CD34 selection can reduce the risk of reinfusion of autoreactive lymphocytes. However, it is also associated with a significant reduction in T cells, natural killer cells, and monocytes, which in turn may compromise immune reconstitution, thereby increasing the risk of infection. Moreover, AD compromises host immunity and causes organ damage resulting in dysfunction of the cutaneous or mucosal barrier. In this study, the incidence rate of infections is reported in 14 patients who underwent high-dose (200 mg/kg) cyclophosphamide therapy followed by reinfusion of CD34-selected autologous peripheral blood stem cells. Bacterial complication occurred in 3 of 14 (21%) patients. Cytomegalovirus reactivation and adenovirus hemorrhagic cystitis were observed in 9 (64%) and 2 (14%) patients, respectively. As for late infectious complications, 7 patients (50%) developed dermatomal varicella zoster virus infection. No infection-related mortality was seen in this case series. Because the risk for infections approaches that seen in allogeneic transplant recipients, infection surveillance, diagnostic workup, and prophylactic strategies similar to those applicable to allogeneic recipients are warranted. [ABSTRACT FROM AUTHOR]

To assess infectious complications associated with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced- and conventional-intensity conditioning regimens (RIC, n=91; CIC, n=54, respectively), we retrospectively analyzed data from 145 consecutive patients with cGVHD after allogeneic HSCT from a human leukocyte antigen-matched related or unrelated donor. In the present retrospective analysis, 57% (83/145) of patients with cGVHD developed infections, with a mortality rate of 27% (22/83). The incidences of bacteremia ( n=28), central venous catheter-related infections ( n=11), bacterial pneumonia ( n=4), invasive aspergillosis ( n=7), and adenoviral hemorrhagic cystitis ( n=8) were significantly higher in patients with prednisolone dose ≥1 mg/kg at the time of diagnosis of cGVHD. The present results suggest that infections associated with cGVHD, especially after high-dose prednisolone, are predictive of poor outcome regardless of whether the patient received RIC or CIC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Allogeneic peripheral blood progenitor cell (PBPC) transplantation requires granulocyte-colony-stimulating factor (G-CSF) administration to mobilize PBPCs in healthy donors. The effects of G-CSF on pulmonary functions, however, have not been clearly elucidated in PBPC donors. STUDY DESIGN AND METHODS: Respiratory status by measurements of arterial blood gas was prospectively evaluated serially in 25 healthy donors (9 men, 16 women; age, 18-61 years) administered a dose of 10 microg per kg for 5 days. RESULTS: White blood cell (WBC) counts increased in all the subjects after G-CSF administration; means on Days 0, 3, and 5 were 6 x 10(9), 33.4 x 10(9), and 33.6 x 10(9) per L, respectively. The mean PaO(2) values on the respective days were 93.1, 85.8, and 81.8 mmHg, and these changes were significant (p < 0.0001), remaining significant after adjustment for the WBC count. Levels of both PaCO(2) and AaDO(2) were significantly higher after G-CSF administration than those before G-CSF administration (p < 0.0001 and p = 0.0004, respectively). SaO(2) was significantly decreased after G-CSF administration (p = 0.0002). Age was identified as a significant predictive factor for the increase of AaDO(2) and PaO(2) decline. These observations clearly indicate that the gas exchange was significantly affected during G-CSF administration in healthy PBPC donors. CONCLUSION: Considering an increasing use of PBPC mobilization by G-CSF, careful monitoring of the respiratory status is important to ensure safety of PBPC donors, especially elderly donors. [ABSTRACT FROM AUTHOR]

Background: Enumeration of CD34+ cells in peripheral blood (PB) before apheresis predicts the number of CD34+ cells collected, although flow cytometric techniques used are complex and expensive. In an attempt to determine the optimal timing for peripheral blood progenitor cell (PBPC) collection, the usefulness of circulating immature cell (CIC) counts in PB was evaluated.Study Design and Methods: CIC counts in PB and CD34+ cell counts in the apheresis product from 249 collections were assessed, and the relationship between these two parameters was evaluated by with the Pearson rank correlation analysis, the Fisher exact test, and the U-test.Results: CIC counts were correlated significantly with the number of CD34+ cells per kg of patient's body weight in the apheresis product (Pearson rank correlation analysis: r = 0.635, p < 0.0001). When a level of 1 x 10(9) CICs per L was selected as a cutoff value, the sensitivity and specificity for collecting more than 1 x 10(6) CD34+ cells per kg of body weight were 75.7 and 85.5 percent, respectively.Conclusion: The present study strongly suggests that the number of CICs in PB may estimate the number of CD34+ cells collected. The data indicate that CIC counts above 1 x 10(9) per L can be used as a good predictor for PBPC collections containing more than 1 x 10(6) CD34+ cells per kg of body weight in a single apheresis procedure. [ABSTRACT FROM AUTHOR]

T. Aoki, K. Kamezaki, T. Miyamoto, K. Nagafuji, Y. Mori, T. Yamauchi, K. Takenaka, H. Iwasaki, N. Harada, N. Shimono, T. Teshima, K. Akashi. Cord blood stem cell transplantation in a patient with disseminated mucormycosis and acute myelogenous leukemia. Transpl Infect Dis 2010: 12: 277–279. All rights reserved [ABSTRACT FROM AUTHOR]

Here we report the case of a 43-year-old Japanese woman with acute myelogenous leukemia who underwent 2 unrelated cord blood transplantations (UCBT), terminating in fatal disseminated tuberculosis (TB). The patient did not achieve remission despite intensive chemotherapy, and subsequently underwent UCBT with a standard conditioning regimen. However, engraftment was not achieved. Fifty days after the first UCBT, the patient underwent a second UCBT with a reduced-intensity conditioning regimen. She developed a pre-engraftment immune reaction, which responded well to prednisolone, and engraftment was documented. However, 50 days after the second UCBT, the patient presented with high fever and developed pneumonia despite antibiotic and antifungal treatments. Thereafter, Mycobacterium tuberculosis was detected in blood cultures and specimens of bronchoalveolar lavage, thus indicating disseminated TB. Despite anti-tuberculous treatment, she died on day 85. TB should always be considered as a possible diagnosis when treating febrile immunocompromised patients. [ABSTRACT FROM AUTHOR]

An abstract of the article "The Internalization of 3-Deoxyglucosone in Human Umbilical Vein Endothelial Cells," by H. Sakiyama, M. Takahashi, T. Yamamoto, T. Teshima and N. Taniguchi is presented.

Belumosudil mesylate is a selective Rho-associated coiled-coil kinase 2 inhibitor with immunomodulatory and antifibrosis effects. This multicenter, open-label, single-arm study evaluated belumosudil 200 mg once daily as second or subsequent line of therapy (LOT) in 21 Japanese patients ≥12 years of age with steroid-dependent/steroid-resistant chronic graft-versus-host disease (cGVHD). The primary endpoint of best overall response rate (ORR) at 24 weeks after enrollment of the last patient was 85.7% (95% confidence interval [CI]: 63.7-97.0), and the lower limit of the 95% CI exceeded the pre-defined threshold of 25%. The Kaplan-Meier estimate of duration of response rate at 24 weeks was 75% (95% CI: 46-90); 13/18 responders (72.2%) had a sustained response for ≥20 weeks. The median time to response was 4.1 weeks (range 3.90-8.10); ORR was 47.6% at 4 weeks and 75.0% at 24 weeks; best ORR was 80% for joints/fascia, 66.7% for the mouth, and 54.5% for skin. Overall, 57.1% of patients had clinically meaningful symptom improvement at least once; the median duration of symptom improvement was 22.2 weeks (range 4.0-51.3). Corticosteroid dose reductions were recorded for 57.1% of patients. Median failure-free and overall survival were not reached. Treatment-emergent adverse events occurred in 85.7% of patients (most commonly diarrhea, 19.0%), of which 38.1% were drug-related. There were no drug-related discontinuations or deaths. In summary, belumosudil 200 mg once daily as second or subsequent LOT in Japanese patients with steroid-dependent/steroid-resistant cGVHD was effective, with no new safety concerns., (© 2024 Wiley Periodicals LLC.)

Prolonged SARS-CoV-2 infection in immunocompromised individuals has been scattered, but the details remain unclear. We conducted a prospective study with 26 COVID-19 patients with haematological malignancies to determine viral shedding kinetics and characteristics. We obtained nasopharyngeal swabs from the patients 21-28 days post-onset for a PCR test and performed virus isolation from the PCR-positive samples. A viable virus was detected in five patients (19.2%), all of whom had malignant lymphoma. Those patients had significantly lower CD4 + T-cell counts than the PCR-negative patients. A comparison of previous chemotherapy showed that anti-CD20 antibodies and bendamustine may be risk factors for prolonged viral shedding., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Recent advances in next-generation sequencing (NGS) have enabled the detection of subclinical minute FLT3-ITD. We selected 74 newly diagnosed, cytogenetically normal acute myeloid leukaemia (AML) samples in which FLT3-ITD was not detected by gel electrophoresis. We sequenced them using NGS and found minute FLT3-ITDs in 19 cases. We compared cases with clinically relevant FLT3-ITD (n = 37), cases with minute FLT3-ITD (n = 19) and cases without detectable FLT3-ITD (n = 55). Molecular characteristics (location and length) of minute FLT3-ITD were similar to those of clinically relevant FLT3-ITD. Survival of cases with minute FLT3-ITD was similar to that of cases without detectable FLT3-ITD, whereas the relapse rate within 1 year after onset was significantly higher in cases with minute FLT3-ITD. We followed 18 relapsed samples of cases with clinically FLT3-ITD-negative at diagnosis. Two of 3 cases with minute FLT3-ITD relapsed with progression to clinically relevant FLT3-ITD. Two of 15 cases in which FLT3-ITD was not detected by NGS relapsed with the emergence of minute FLT3-ITD, and one of them showed progression to clinically relevant FLT3-ITD at the second relapse. We revealed the clonal dynamics of subclinical minute FLT3-ITD in clinically FLT3-ITD-negative AML. Minute FLT3-ITD at the initial AML can expand to become a dominant clone at relapse., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)