Effect of High-Dose Drug-Coated Balloon Repetition After Drug-Coated Balloon Failure.

PURPOSE: Although the optimal treatment for femoropopliteal (FP) drug-coated balloon (DCB) restenosis lesions remains debatable, the effectiveness of DCB repetition for DCB restenosis has been reported. However, the optimal DCB repetition strategy is not yet established. Thus, this study aimed to compare the clinical outcomes of high-dose DCB repetition with those of low-dose DCB repetition for FP DCB restenosis lesions. MATERIALS AND METHODS: This single-center, observational study used a clinical database of 677 consecutive patients undergoing FP endovascular intervention for symptomatic peripheral artery disease between December 2018 and December 2021. Of these patients, 89 cases treated with DCB repetition for FP DCB restenosis lesions were analyzed. The primary endpoint was recurrent restenosis (re-restenosis) and the secondary endpoints were recurrent target-lesion revascularization (TLR), re-occlusion, and major adverse limb events (MALE) obtained using propensity score matching. Interaction analysis was also performed to explore the effects of the baseline characteristics on the association between high- and low-dose DCB with restenosis risk. RESULTS: After propensity score matching, high-dose DCB demonstrated a significantly higher freedom from re-restenosis compared with low-dose DCB repetition at 1 year (90.4% vs 40.9%, p=0.034). In addition, freedom from re-TLR and MALE at 1 year was significantly higher in the high-dose DCB group (95.0% vs 53.3%, p=0.025; 95.0% vs 54.7%, p=0.025, respectively). Conversely, freedom rates from re-occlusion were not significantly different between the 2 groups (100.0% vs 84.0%, p=0.99). No baseline characteristics or perioperative outcomes had any significant interaction effect on the association of high-dose DCB versus low-dose DCB with restenosis risk. CONCLUSION: For FP DCB restenosis lesions, high-dose DCB repetition offered more favorable outcomes than low-dose DCB repetition. CLINICAL IMPACT: This study revealed that for femoropopliteal drug-coated balloon (DCB) restenosis lesions, high-dose DCB repetition obtained more favorable outcomes than low-dose DCB repetition. In addition, there was no significant interaction effect on the association of high- versus low-dose DCB with re-restenosis risk for the baseline characteristics and perioperative outcomes. This finding might be also a reason for choosing high-dose DCB repetition for FP DCB restenosis lesions in daily clinical practice.

Feasibility of an intensified myeloablative conditioning regimen consisting of busulfan, fludarabine, cytarabine, and total body irradiation before single cord blood transplantation in elderly patients.

The optimal conditioning regimen for stem cell transplantation in elderly patients remains to be established. We developed a novel preparative regimen using fludarabine 180 mg/m2, intravenous busulfan 12.8 mg/m2, cytarabine 8 g/m2, and 4-Gy total body irradiation before cord blood transplantation (CBT) in patients older than 55 years with various hematological malignancies. All but one patient received graft-versus-host disease (GVHD) prophylaxis consisting of cyclosporine (CsA) and short-term methotrexate (sMTX). Thirty-three patients were included in this study, with a median age of 64 years (range 56-70). The disease risk index was high or very high in 67% of patients, and 73% had a disease status other than complete remission. The probabilities of overall survival and disease-free survival at 3 years were 60 and 57%, respectively. The cumulative incidences of relapse and non-relapse mortality at 3 years were 18 and 25%, respectively. Regimen-related toxicities were generally tolerable. Disease-free survivors (n = 20) stopped immunosuppressants at a median of 7.4 months (range 2.6-25.0), in all cases by the time of the last follow-up. In conclusion, this highly myeloablative conditioning regimen resulted in a high probability of disease-free, GVHD-free, immunosuppressant-free survival after single CBT.(190 words).

Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome.

Rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) is the cause of Asian alcohol flushing response after drinking. ALDH2 detoxifies endogenous aldehydes, which are the major source of DNA damage repaired by the Fanconi anemia pathway. Here, we show that the rs671 defective allele in combination with mutations in the alcohol dehydrogenase 5 gene, which encodes formaldehyde dehydrogenase (ADH5FDH ), causes a previously unidentified disorder, AMeD (aplastic anemia, mental retardation, and dwarfism) syndrome. Cellular studies revealed that a decrease in the formaldehyde tolerance underlies a loss of differentiation and proliferation capacity of hematopoietic stem cells. Moreover, Adh5-/-Aldh2 E506K/E506K double-deficient mice recapitulated key clinical features of AMeDS, showing short life span, dwarfism, and hematopoietic failure. Collectively, our results suggest that the combined deficiency of formaldehyde clearance mechanisms leads to the complex clinical features due to overload of formaldehyde-induced DNA damage, thereby saturation of DNA repair processes.

Dynamic viscoelasticity measurement under alternative torque using electromagnetically spinning method with quadruple electromagnets.

In this study, we developed a novel type of rheological measurement system. Here, a spherical probe is driven to rotate periodically by applying torques using quadruple electromagnets in a noncontact manner. Moreover, this system is an enhancement of our electromagnetically spinning (EMS) viscometer, which is widely used for measuring rheological flow curves in various industrial fields. The quadruple EMS method provides the frequency spectrum of viscoelasticity, in addition to shear viscosity, in a steady flow by switching the operation modes of the driving torque. We show the results obtained for Newtonian fluids and viscoelastic materials and demonstrate the validity of the system.

[Diffuse large B-cell lymphoma developed newly after 9-year remission of a follicular lymphoma].

Follicular lymphoma (FL) occasionally transforms into diffuse large B-cell lymphoma (DLBCL). This is generally associated with a poor prognosis, necessitating more potent chemotherapy as salvage treatment. However, de novo DLBCL, but not DLBCL transformed from FL, can be treated as primary DLBCL. We encountered a 63-year-old woman who developed DLBCL after a 9-year remission following treatment of FL. To differentiate DLBCL transformed from FL and de novo DLBCL, VDJ gene rearrangements in IgH were examined by PCR using biopsy specimens from both lymphomas. The results revealed the two lymphomas to be different clones. Thus, she was diagnosed with primary DLBCL. Therefore, routine chemotherapy and radiation therapy were conducted for the primary DLBCL with a limited stage, achieving complete remission. Treatment based on the clonality assessment of VDJ gene rearrangements is potentially useful for treating late relapse of B-cell lymphoma according to the pathological conditions of patients.

Primary T-cell high-grade lymphoma of the feline uterus.

A 12-year-old female American shorthair cat presented with a one-month history of hematuria and general lethargy. Abdominal ultrasonography revealed complete thickening of the left uterine wall. At a diagnostic laparotomy, a large mass arising from the left uterine horn was discovered, and ovariohysterectomy was performed. Histological diagnosis revealed a T-cell high-grade lymphoma of the uterus. After the ovariohysterectomy, the patient achieved complete remission and was maintained by combination chemotherapy from 14 days after surgery. However, relapse occurred in the urinary bladder wall on day 287, and the patient died of postrenal acute renal failure on day 310. This is the first report of a feline case of primary uterine lymphoma that was treated with ovariohysterectomy followed by systemic chemotherapy.

Rituximab Monotherapy and Rituximab-Containing Chemotherapy Were Effective for Paraneoplastic Pemphigus Accompanying Follicular Lymphoma, but not for Subsequent Bronchiolitis Obliterans.

A 60-year-old male patient suffered from mild exertional dyspnea, wheezing, and systemic blisters. He was diagnosed with paraneoplastic pemphigus (PNP) with follicular lymphoma in the pancreas head and pelvic cavity. He was first treated with eight cycles of rituximab; his blisters and erosions gradually improved and highly elevated levels of auto-antibodies related to PNP gradually decreased to normal levels. However, obstructive and restrictive respiratory failure still progressed. Computed tomography of the inspiratory and expiratory phases revealed obstructive pulmonary disorder, leading to a diagnosis of bronchiolitis obliterans (BO). The patient underwent plasma exchange and was repeatedly treated with rituximab monotherapy and rituximab-containing chemotherapies, but died 7 months after the diagnosis of BO. Early introduction of rituximab-containing regimens may be necessary to prevent the development of BO accompanying PNP. However, when a diagnosis of PNP-related BO is made, lung transplantation may also be considered for patients in whom rituximab-containing regimens are effective for PNP.

[Acquired pure red cell aplasia in a patient with B cell chronic lymphocytic leukemia after fludarabine therapy].

A 67-year-old woman was diagnosed with chronic lymphocytic leukemia (CLL) in October 2001. In August 2004, she received chemotherapy consisting of fludarabine and cyclophosphamide (FC therapy). After three cycles of FC therapy, the number of tumor cells was markedly decreased. However, anemia progressed. She was diagnosed with pure red cell aplasia (PRCA) by bone marrow examination and was successfully treated with cyclosporin A (CsA). In October 2008, anemia progressed with the exacerbation of CLL and she received three cycles of fludarabine therapy. Although the number of tumor cells diminished, the anemia did not improve. She was diagnosed with PRCA recurrence and was again successfully treated with CsA. PRCA is a rare complication in patients with CLL and has been attributed to T cell-mediated mechanisms. Six cases with PRCA that developed after fludarabine therapy for CLL have already been reported. Fludarabine therapy may be toxic to Treg, resulting in the loss of self-tolerance. It is important to consider the possibility of PRCA in patients with progressive anemia after fludarabine therapy for CLL.

[Clinical assessment of CD4/8 ratio of bone marrow lymphocytes in acquired pure red cell aplasia].

We have reviewed 6 patients with acquired PRCA and investigated CD4/8 ratio in the bone marrow lymphocytes prior to treatment with cyclosporin A (CsA). CsA, as a remission induction therapy, produced CR in 3/6 patients, and PR+NR in 3/6 patients. CD4/8 ratio in CR group was high compared to PR+NR group. Moreover, the number of reticulocyte and hemoglobin concentration in CR group was high in comparison with PR+NR group. In acquired PRCA, CD4/8 ratio in the bone marrow lymphocytes may correlate with the disease status and the outcome of CsA treatment.

A high sIL-2R/ferritin ratio is a useful marker for the diagnosis of lymphoma-associated hemophagocytic syndrome.

Lymphoma-associated hemophagocytic syndrome (LAHS), which is the major subtype of adult-onset secondary hemophagocytic lymphohistiocytosis (HLH), has a poor outcome. Although the early diagnosis and treatment of LAHS contributes to a better outcome, the lack of mass formation and the absence of distinct lymph node enlargement often delay the diagnosis of underlying lymphoma. A recent study, which statistically analyzed HLH cases in the literature, showed that the serum soluble interleukin-2 receptor (sIL-2R)/ferritin ratio could be used as a marker to diagnosis of LAHS. To verify this finding, we retrospectively analyzed the laboratory findings of 21 patients with HLH (10 benign disease-associated HLH and 11 LAHS). No significant differences were observed in the levels of LDH or CRP levels. The mean sIL-2R levels (units per milliliter) were significantly higher in the LAHS group (4,176 vs. 13,451, p = 0.0031), and ferritin levels (nanogram per milliliter) were higher in the benign disease-associated HLH group (20,462 vs. 2,561, p = 0.0031). Consequently, the mean serum sIL-2R/ferritin ratio of patients with LAHS was markedly higher than that of patients with benign disease-associated HLH (0.66 vs. 8.56, p = 0.0004). Thus, the results of this study demonstrated that the serum sIL-2R/ferritin ratio is a very useful marker for diagnosing of LAHS, which was further supported by clinical case analysis. Further studies to clarify the pathophysiology of secondary HLH caused by various triggers are needed.

[Cytomegalovirus mononucleosis complicated with peripheral facial palsy].

A 36-year-old woman was admitted to our hospital for further examination of an acute febrile illness with liver dysfunction. A peripheral blood smear displayed atypical lymphocytes. Cytomegalovirus (CMV) mononucleosis was diagnosed based on the detection of CMV-specific IgM and conventional CMV pp65 antigen. The physical examination on admission revealed signs of lower motor neuron right facial palsy. There were no significant cerebrospinal fluid findings, nor were there other neurological abnormalities. After receiving a short-course of oral corticosteroids, the patient gradually recovered from the facial paralysis. A one-month follow-up examination indicated that she had fully recovered neurologically, showing disappearance of CMV-DNA and a significant increase in the anti-CMV IgG titer. To our knowledge, there has been only one previous report describing CMV as the cause of an isolated facial palsy combined with CMV mononucleosis.

[Effective treatment with tranexamic acid for chronic disseminated intravascular coagulation associated with aortic dissection].

An 82-year-old female with a history of aortic dissection was admitted to our hospital for evaluation of thrombocytopenia and a bleeding tendency. Blood coagulation test data demonstrated that the patient had disseminated intravascular coagulation (DIC) secondary to aortic dissection. We initiated anti-fibrinolytic therapy with tranexamic acid. After this anti-fibrinolytic therapy, thrombocytopenia and the levels of fibrinogen and fibrinogen degradation products improved. In addition, we reviewed 7 other patients who were treated with tranexamic acid for DIC associated with aortic dissection. Anti-fibrinolytic therapy with tranexamic acid is effective for treating DIC secondary to aortic dissection.

Blood viscometer applying electromagnetically spinning method.

Viscosity is an important parameter which affects hemodynamics during extracorporeal circulation and long-term cardiac support. In this study, we have aimed to develop a novel viscometer with which we can easily measure blood viscosity by applying the electromagnetically spinning (EMS) method. In the EMS method, we can rotate an aluminum ball 2 mm in diameter indirectly in a test tube with 0.3 ml sample of a liquid by utilizing the moment caused by the Lorentz force as well as separate the test tube from the viscometer body. First, we calibrated the EMS viscometer by means of liquid samples with known viscosities and computational fluid dynamics. Then, when we measured the viscosity of 9.4 mPa s silicone oil in order to evaluate the performance of the EMS viscometer, the mean viscosity was found to be 9.55 ± 0.10 mPa s at available shear rates from 10 to 240 s(-1). Finally, we measured the viscosity of bovine blood. We prepared four blood samples whose hematocrit levels were adjusted to 23, 45, 50, and 70% and a plasma sample without hemocyte components. As a result, the measurements of blood viscosities showed obedience to Casson's equation. We found that the viscosity was approximately constant in Newtonian silicone oil, whereas the viscosity decreased with increasing shear rate in non-Newtonian bovine blood. These results suggest that the EMS viscometer will be useful to measure blood viscosity at the clinical site.

Superoxide dismutase and catalase activities in the seminal plasma of normozoospermic and asthenozoospermic Beagles.

We measured the blood plasma testosterone (T) levels and superoxide dismutase (SOD) and catalase activities in the seminal plasma of the ejaculates of 5 normal (2-5 years old) and 5 asthenozoospermic (AZ-) (3-5 years old) Beagles. Sperm ejaculated by AZ-dogs was incubated for 3 hr in Eagle's MEM only (controls) or Eagle's MEM containing 100 units/ml of SOD or catalase. Sperm motility was examined during incubation. The mean (+/- SE) plasma T level of the AZ-dogs (1.2 +/- 0.2 ng/ml) was significantly lower than in the normal dogs (2.5 +/- 0.2 ng/ml) (P<0.005). The mean (+/- SE) seminal plasma SOD and catalase activities (18.8 +/- 1.9 and 0.5 +/- 0.1 unit/g protein, respectively) were significantly lower in the AZ-dogs than in the normal dog (43.3 +/- 2.5 and 2.2 +/- 0.4 unit/g protein, respectively) (P<0.001 and 0.01, respectively). The motility of sperm incubated in Eagle's MEM containing SOD or catalase was significantly higher than that of control sperm incubated in only Eagle's MEM after 2 or 3 hr of incubation (P<0.05). The results of this study indicate that poor T secretion by the testes and low antioxidant enzyme activities are related to AZ in the dog.