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BACKGROUND AIMS: An intensified conditioning regimen incorporating medium-dose etoposide (VP16) is an option for patients with acute lymphoblastic leukemia (ALL). However, the prognostic impacts of the addition of VP16 to cyclophosphamide (CY) and total body irradiation (TBI) in patients with Philadelphia chromosome-positive (Ph+) ALL with regard to minimal residual disease (MRD) status have not been elucidated. METHODS: The authors retrospectively compared the outcomes of patients with Ph+ ALL who underwent allogeneic transplantation following VP16/CY/TBI (n=101) and CY/TBI (n=563). RESULTS: At 4 years, the VP16/CY/TBI group exhibited significantly better disease-free survival (DFS) (72.6% versus 61.7%, P=0.027) and relapse rate (11.5% versus 21.1%, P=0.020) and similar non-relapse mortality (16.0% versus 17.2%, P=0.70). In subgroup analyses, the beneficial effects of the addition of VP16 on DFS were more evident in patients with positive MRD status (71.2% versus 48.4% at 4 years, P=0.022) than those with negative MRD status (72.8% versus 66.7% at 4 years, P=0.24). Although MRD positivity was significantly associated with worse DFS in patients who received CY/TBI (48.4% versus 66.7%, P < 0.001), this was not the case in those who received VP16/CY/TBI (71.2% versus 72.8%, P=0.86). CONCLUSIONS: This study demonstrated the benefits of the addition of VP16 in Ph+ ALL patients, especially those with positive MRD status. VP16/CY/TBI could be a potential strategy to overcome the survival risk of MRD positivity.

The alkylating agent busulfan is commonly used as conditioning in allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML). However, a consensus has not yet been reached regarding the optimal busulfan dose in cord blood transplantation (CBT). Therefore, we conducted this large nationwide cohort study to retrospectively analyze the outcomes of CBT in patients with AML receiving busulfan at intermediate (6.4 mg/kg i.v.; BU2) or higher (12.8 mg/kg i.v.; BU4) doses within a fludarabine/i.v. busulfan (FLU/BU) regimen. Among 475 patients who underwent their first CBT following FLU/BU conditioning between 2007 and 2018, 162 received BU2 and 313 received BU4. Multivariate analysis identified BU4 as a significant factor for longer disease-free survival (hazard ratio [HR], .85; 95% confidence interval [CI], .75 to .97; P = .014) and a lower relapse rate (HR, .84; 95% CI, .72 to .98; P = .030). No significant differences were observed in non-relapse mortality between BU4 and BU2 (HR, 1.05; 95% CI, .88-1.26; P = .57). Subgroup analyses showed that BU4 provided significant benefits for patients who underwent transplantation while not in complete remission (CR) and those age

There are limited data comparing myeloablative conditioning with fludarabine/busulfan (Flu/Bu4) and reduced-intensity conditioning with fludarabine/busulfan (Flu/Bu2) in patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed nationwide registry data and compared the outcomes of adult patients with MDS receiving Flu/Bu4 and Flu/Bu2 by propensity score (PS) matching. Patients who met the following criteria were eligible for enrollment: (1) age ≥16 years; (2) diagnosis of de novo MDS; (3) first allo-HSCT between 2006 and 2018; (4) related bone marrow transplantation (BMT) or peripheral blood stem cell transplantation from an HLA-matched donor, unrelated BMT from an HLA-matched or HLA-1 allele-mismatched donor, or unrelated cord blood transplantation; and (5) receiving Flu/Bu4 or Flu/Bu2 as a conditioning regimen. Flu/Bu4 comprised intravenous busulfan (total dose, 12.8 mg/kg) combined with fludarabine (total dose, 125-180 mg/m

Objective Recurrent acute otitis media (AOM) in young children is rapidly increasing worldwide. Repeated antibiotic use leads to antibiotic-resistant pathogen development. Complementary and alternative medicine approaches have been suggested as a supplemental treatment option to conventional antimicrobial medicine. This randomized, parallel-group, open-label, non-herbal medicine controlled trial assessed the efficacy of a traditional Japanese herbal medicine, juzen-taiho-to (JTT) for AOM prevention in otitis-prone children. Methods Children prone to recurrent AOM aged 6–48 months were recruited from 26 otolaryngology clinics in Japan and received conventional AOM treatment based on Japanese guidelines with or without 2 daily oral doses of JTT (0.10–0.25 g/kg/day). The mean number of AOM episodes, coryza episodes, and duration of total antibiotic administration per month were compared during 3-month intervention. Results At least one episode of AOM was diagnosed in 71% of JTT-group and 92% of control participants during follow-up. JTT administration reduced the frequency of AOM episodes by 57% compared with children who received conventional treatment alone (0.61 ± 0.54 vs. 1.07 ± 0.72 AOM instances/month; P = 0.005) and also significantly decreased number of coryza episodes ( P = 0.015) and total antibiotic administration ( P = 0.024). Conclusions This is the first report of recurrent AOM prevention by herbal medication. JTT appears to effectively prevent recurrent AOM in children. Subsequent double-blind studies are needed to confirm the beneficial effects of JTT on recurrent AOM and upper respiratory tract infections.

金沢大学医薬保健研究域医学系, Although it appears very uncommon in adult COM, Mycobacterium abscessus should be considered as a possible cause of a chronically draining ear. Multi-antibiotic chemotherapy including high-dose clarithromycin can effectively treat adult COM cased by M. abscessus. The first case report of adult chronic otitis media (COM) caused by M. abscessus is described here. A 61-year-old woman presented persistent otorrhea for 2 months, despite treatment with standard antimicrobial drugs. Physical examination revealed a small perforation of the tympanic membrane and edematous middle ear mucosa. Mycobacterial cultures and PCR yielded non-tuberculous mycobacteria (NTM); M. abscessus. Intravenous panipenem/betamipron and amikacin and oral clarithromycin were administered for 36 days. Computed tomography of the temporal bone showed improved aeration in the tympanic cavity, but soft tissue shadow remained unchanged in the mastoid 31 days after starting medication. She therefore underwent tympano-mastoidectomy at 36 days. At surgery, inflammation remained in the middle ear, and edematous pale mucosal tissue was noted around the stapes and ossicular chain. Histopathologic examination showed inflammation and granulation tissue, but no caseating necrosis or acid-fast bacilli. After surgery the symptoms resolved and remained well without evidence of infection recurrence 12 months after the operation. © 2010.

金沢大学医薬保健研究域医学系, Objective: Resistant strains of non-typeable Haemophilus influenzae (NTHi) are one of the principal causes of recurrent acute otitis media (otitis prone), rhinosinusitis, and pneumonia in young children. β-Lactamase-nonproducing ampicillin-resistant (BLNAR) strains are particularly common in Japan, and β-lactamase-producing amoxicillin-clavulanate resistant (BLPACR) strains are now emerging. We investigated the nasopharyngeal carriage status of these resistant strains among children attending a same day care center during a 10-year period. Methods: From 1999 to 2008, we obtained nasopharyngeal swab specimens from young children attending a same day care center and examined the incidence of resistant strains of NTHi. Antimicrobial resistance of NTHi was identified based on PCR analysis of mutation of the penicillin binding protein (PBP) genes. Pulsed-field gel electrophoresis (PFGE) was performed to examine the clonal relationship of each resistant strain. Results: The prevalence of resistant strains of NTHi among the children attending this day care has significantly increased during the past 10 years and most of this day care children recently have resistant strains with PBP gene mutations in their nasopharynx. Genetically BLPACR (gBLPACR) strains have rapidly increased since 2007 and PFGE analysis demonstrated that all gBLPACR were clonally identical. This is the first report of apparent clonal dissemination of gBLPACR strains of NTHi occurring in a certain environment such as day care. Conclusions: The rapidly increasing prevalence of resistant strains, in particular gBLPACR, in this day care center may predict a high incidence of these resistant bacteria from clinical isolates in the near future and potential serious medical problems worldwide. © 2010 Elsevier Ireland Ltd.

In the Japanese population, the second premolars are the secondmost- frequently impacted teeth in the mandible, after the third molars. Although some papers have reported on the treatment of impacted mandibular second premolars caused by abnormal tilting of the tooth germ, there has been little information regarding bilateral horizontal impaction with distal inclination. The purpose of the present report is to describe the treatment course of a rare and severe case of an 11-year, 8-month-old girl without any obvious etiologies whose bilateral mandibular second premolars were inclined to the distal direction at approximately 90 degree angles, with the root formation developed to an approximately half length. After extraction of the retained primary molars, traction was performed in the treatment of the affected teeth. The affected premolars had fully erupted and achieved occlusion one year after the beginning of intervention. In conclusion, it was considered that the present case could obtain a successful outcome by limited traction since no clinical anomalies or discomfort was detectable during the one year of retention.

An aberrant internal carotid artery (ICA) is a rare vascular anomaly and causes to objective pulsatile tinnitus and retrotympanic mass. In the past, it was often diagnosed during ear surgery or biopsy, which may lead to massive bleeding. We present a case of 37-year-old woman complaining of pulsatile tinnitus. The tinnitus was objectively audible at the right ear through an otoscope. Previously, MRA plays a pivotal role in the evaluation of the aberrant ICA. But in this case, the resolution of magnetic resonance angiography (MRA) was not enough to portray the course of the ICA, because dephasing of the spins due to turbulence may cause loss of the signal intensity on MRA. Computed tomography (CT) of the temporal bone revealed aberrant internal carotid artery passing through the middle ear. It is important to diagnose approximately this anomaly using with combination of high-resolution CT, MRI, and MRA.