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NUP98::DDX10 is a rare fusion gene associated with acute myeloid leukemia (AML), for which the prognosis and indication for allogeneic hematopoietic stem cell transplantation are unknown. A 48-year-old woman was diagnosed with AML harboring NUP98::DDX10. The results of quantitative RT-PCR of the fusion mRNA as a minimal residual disease (MRD) marker guided the treatment. In August 2019, the patient achieved hematological remission following standard remission induction therapy with idarubicin and cytarabine. After four cycles of consolidation therapies, MRD was detected, and she underwent allogeneic stem cell transplantation in May 2020. As MRD persisted in June, the immunosuppressant was stopped and three cycles of azacitidine were administered. Despite this, a hematological relapse occurred in January 2021 that was resistant to high-dose cytarabine and an investigational agent. She died as a result of the disease's progression. Thus, a second thought should be given to the timing of transplantation, the bridging, and the intervention for relapse after transplantation. The cases must be accumulated.

Patients with acute leukemia who are unable to achieve complete remission prior to allogeneic hematopoietic stem cell transplantation (SCT) have dismal outcomes with relapse rates well in excess of 60%. Haplo-identical SCT (haplo-SCT) may allow enhanced graft-versus-leukemia (GVL) effects by virtue of HLA class I/II donor-host disparities but typically requires intensive immune-suppression with post-transplant cyclophosphamide (PT-Cy) to prevent lethal graft-versus-host disease (GVHD). Here we demonstrate in preclinical models that glucocorticoid administration from day -1 to +5 inhibits alloantigen presentation by professional recipient antigen presenting cells in the gastrointestinal tract and prevents donor T-cell priming and subsequent expansion therein. In contrast, direct glucocorticoid signaling of donor T-cells promotes chemokine and integrin signatures permissive of preferential circulation and migration into the bone marrow, promoting donor T-cell residency. This results in significant reductions in GVHD whilst promoting potent GVL effects (relapse in recipients receiving glucocorticoids, vehicle or PT-Cy was 12%, 56% and 100% respectively). Intriguingly, patients with acute myeloid leukemia not in remission that received unmanipulated haplo-SCT and peri-transplant glucocorticoids also had an unexpectedly low relapse rate at 1 year (32%: 95% CI, 18%-47%) with high overall survival at 3 years (58%: 95% CI, 38-74%). These data highlight a potentially simple and effective approach to prevent relapse in patients with otherwise incurable leukemia that could be studied in prospective randomized trials.

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.

Chronic active Epstein-Barr virus infection (CAEBV) is critical owing to lethal complications such as hemophagocytic lymphohistiocytosis (HLH), multiple organ failure, and malignant lymphoma. Here we present two cases of CAEBV who developed rapid and life-threatening disease progression after cytotoxic chemotherapy. Case 1: In a 34-year-old male, CAEBV recurred after 4-month remission obtained by initial therapy with etoposide, cyclosporine, and prednisolone. Accordingly, cord blood transplantation was planned. A day after administering high-dose melphalan as the conditioning, he developed respiratory failure, pancytopenia, and hyperferritinemia. He died 3 days later. Case 2: A 53-year-old female attained remission after initial therapy for CAEBV. After 1 month, she relapsed, and high-dose cytarabine (HDAC) was administered. A day after HDAC administration, she suddenly developed respiratory failure, which was followed by multiple organ failure. She died 3 days later. Thus, planned strategy for prompt allogeneic hematopoietic stem cell transplantation is necessary to prevent disease progression and control cytokinemia before cytotoxic chemotherapy for CAEBV.

A 64 year-old woman with steroid-dependent immune thrombocytopenia developed anemia. Esophagogastroduodenoscopy revealed the presence of a tumor, which was diagnosed to be diffuse large B-cell lymphoma, in the second portion of the duodenum. 18F-fluorodeoxy glucose positron emission tomography showed an increased uptake mass in the pelvic cavity as well as in the duodenum. Though the duodenal tumor disappeared after 4 cycles of chemotherapy, the pelvic mass did not shrink in size. As a result, laparoscopic resection of the pelvic tumor was performed and the tumor was histologically diagnosed to be a gastrointestinal stromal tumor. Subsequently, the patient was treated with 2 more cycles of the chemotherapy. Eventually, thrombocytopenia completely resolved.

Though tonsillectomy is one of the most common surgical procedures in otorhinolaryngology generally for benign diseases and mainly for young people, uncontrollable perioperative bleeding associated with tonsillectomy is a rare but potentially life-threatening event. We report herein on a case of a 19-year-old female with uncontrollable hemorrhage during a tonsillectomy, which was controlled through selective embolization. To the best of our knowledge, this is the first report on endovascular treatment in the management of tonsillectomy-associated intraoperative uncontrollable hemorrhage rather than postoperative bleeding. Selective embolization for perioperative bleeding during a tonsillectomy is considered as an efficient and important therapeutic option in the definitive treatment of this life-threatening occurrence. We also reviewed patients who underwent tonsillectomy in our hospital in the past five years. The ratio of postoperative hemorrhage was 11.8%. All patients with post-tonsillectomy hemorrhage were classified as grade 1 bleeding (spontaneous cessation).

In this study, we investigated for a period of 8 years, 884 patients who underwent swallowing rehabilitation in our hospital, and evaluated the factors affecting resumption of oral intake of food. We found that the number of patients undergoing swallowing rehabilitation in our hospital increased over time. Of the included patients, 82.8% were ≥70 years of age and men were more frequent than women (p=0.004). At the end of the rehabilitation, 56.3% patients' main nutrition route was oral. Most (60.5%) patients required30 days of rehabilitation. We evaluated correlation between the states of patients at starting point of swallowing rehabilitation and the result of the rehabilitation. The patients having a desire for eating were significantly more successful in regaining oral intake of food than those without the desire (p0.001) and those with desire unknown (p0.001). We classified the patients as per the Japan Coma Scale into four groups: alert, 1 digit, 2 digits, and 3 digits; the 3-digit group was significantly less successful in resumption of oral ingestion compared to all other groups (p0.001). Based on the activities of daily living (ADL), we classified the patients into four groups: supine position, possible to semi-sitting group (get-up more than 30°), possible to sit-up group, and possible more than transferring by oneself group. It was proved that the supine position group was significantly less successful in regaining oral intake of food compared to all other groups (p0.001). Multivariate analysis showed that the strongest correlation for regaining oral ingestion was desire for eating (p0.001), followed by ADL and level of consciousness. In conclusion, we found that the number of patients undertaking swallowing rehabilitation in our hospital is increasing, and that factors such as desire for eating, ADL, and level of consciousness significantly influence the resumption of oral intake of food.

Paradoxical vocal cord motion (PVCM) during vocal cord dysfunction (VCD) generally occurs spasmodically and transiently. After we had experienced 36 cases of VCD and successfully treated with conservative treatment including "pursed lips inspiration" method, we experienced a boy who had persistent PVCM. It was observed his PVCM vanished when he breathed in through pursed lips, while it appeared again when he stopped pursed lips inspiration. An airway reflex has been reported where the negative pressure in the subglottic space resulting from the inspiratory effort against a narrowed glottis activates the vocal cord adductor. VCD is considered to have both acceleration of laryngeal closure reflex against airway stimuli and active adductive movement of vocal cords against negative pressure in the subglottic space as underlying factors. The pursed lips inspiration method enables VCD patients not only to accomplish slow and light breathing but also to decrease the difference in the pressure between the supra--and subglottic space by occluding the nasal cavity and voluntary puckering up of the mouth which generate negative pressure in the supraglottic space. This is the first report of the pursed lips inspiration method as a treatment for VCD. Pursed lips inspiration is a simple method which is easy to perform anytime, anywhere without any special equipment, and is considered to be worth trying for VCD.

We report herein on a 15-year-old girl with Takayasu's arteritis (TA) in the early pre-pulseless phase who presented with left neck pain and fever. Laboratory examination revealed a high level of C-reactive protein (CRP) and an elevated erythrocyte sedimentation rate (ESR). Findings of ultrasonography, computed tomography (CT), and magnetic resonance imaging and angiography (MRI, MRA) demonstrated a thickening of the left carotid artery but neither stenosis nor dilation of the large vessels. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) after twenty days duration of fever revealed an accumulation of 18F-fluorodeoxyglucose not only in the left carotid artery but also the wall of the ascending aorta, aortic arch, thoratic aorta, and part of abdominal aorta, which led to the diagnosis of TA in the early pre-pulseless phase. The patient was treated with prednisolone resulting in a marked improvement in both the clinical symptoms and laboratory parameters within a couple of weeks. Stenosis of the left carotid artery was found in MRI, MRA following four months and a definitive diagnosis was reached. We suggest early diagnosis of TA may permit early treatment and improve the prognosis.

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.

Juzen-taiho-to (JTT, TJ-48), a Japanese herbal medicine that improves immune function, was found to be effective in otitis-prone in children.To evaluate the efficacy of JTT against intractable and recurrent infections in immature immune systems, we administered JTT to otitis-prone infants and investigated clinical changes before and during JTT administration.Twenty-four otitis-prone infants were administered JTT at 0.10-0.14 g/kg/day twice a day for 3 months. We compared clinical course, such as frequency of acute otitis media (AOM), duration of fever and antibiotics administration, and hospital visits for the periods before and during JTT administration.Medication compliance rate was 87.5%, and administration of JTT led to remission in 95.2% patients. No apparent side effects were observed. The frequency of AOM decreased significantly (Wilcoxon signed rank test, p=0.000) with JTT. The duration of fever (p=0.000) and administration of antibiotics (p=0.001), as well as the number of hospital visits (p=0.001) and emergent hospital visits (p=0.000) showed significant decreases after JTT administration. After the end of the JTT period, 14 of 21 (66.7%) patients started to take it again, as they experienced purulent otitis media and/or other infections after discontinuation. The frequency of AOM increased significantly after stopping JTT (p=0.004) and decreased again with JTT resumption (p=0.005).

Immunoglobulin light chain (AL) amyloidosis is a systemic disorder caused by depositions of insoluble amyloid fibrils that are composed of fragments of monoclonal light chains produced by abnormal plasma cells. The prognosis is reported to be poor; median survival time (MST) is 1–2 years overall, and is 6 months in patients with cardiac involvement. We here report the treatment outcomes of 24 patients with AL amyloidosis at our hospital between January 2008 and December 2012, including 11 patients with cardiac involvement. MST from the diagnosis was significantly shorter (9.8 months) in patients with cardiac involvement. Of these, patients who achieved a decrease of B-type natriuretic peptide (BNP) to

Primary mediastinal (thymic) B-cell lymphoma (PMBL) is resistant to treatment when compared with diffuse large B-cell lymphoma (DLBCL). Moreover, the optimal first -line treatment of PMBL has not yet been determined. Herein, we report a case of PMBL that was successfully treated with the dose adjusted (DA) etoposide, prednisolone, vincristine, doxorubicin, and cyclophosphamide with rituximab (EPOCH-R) regimen. A-29-year-old woman was referred to our hospital with an anterior mediastinal tumor. Eight months before admission, she had visited a clinic for pain in the chest and back, but no abnormalities were found. Subsequently, her chest pain got worse, and she went to another clinic, where she was detected with an anterior mediastinal tumor and was referred to our hospital. Tumor biopsy with a thoracoscope was performed, and a diagnosis of PMBL was made. The tumor diameter was 90 mm, with invasion to the lungs and superior vena cava. The tumor had a clinical stage of IEA, and the International Prognostic Index (IPI) was low risk. She was treated with the DA-EPOCH-R regimen for 8 courses, and a complete response was achieved. A recent retrospective study of DA-EPOCH-R treatment without radiotherapy for PMBL was recently published. It showed that the event-free survival rate was 93% and the overall survival rate was 97% during a median 5-year follow-up. Thus, DA-EPOCH-R may be a potential standard treatment for PMBL.

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.

The data accumulated from epidemiological studies suggests that individuals with elevated blood levels of homocysteine have an increased risk of cardiovascular disease. However, little is known of the food factor that may affect the homocysteine status, except for folate and B-vitamins. Here, we tested the effect of dietary phenolics (i.e., anthocyanin of food colorant) administration on plasma homocysteine concentration in a rat study, since a profound effect on the methionine metabolism was speculated from the 3',4'-catechol skeletal structure of anthocyanin. Female Sprague-Dawley rats (body weight 100 g) orally ingested a single dose of anthocyanin mixture (total 100 mg) composed of cyanidin-3-glucoside (50mg), cyanidin-3-sambubioside (48 mg), and cyanidin-3,5-diglucoside (2 mg). The total homocysteine in the plasma collected 90-240 min after anthocyanin intake was 1.4 to 1.8-fold (5.2-6.7 micromol/L) higher than the basal homocysteine level (3.7 micromol/L). In the liver and kidney, anthocyanin significantly affects sulfur amino acid (S-adenosylmethionine, SAM, and S-adenosylhomocysteine, SAH) levels, both of which are precursors of plasma homocysteine, and the SAH/SAM ratio showed a significant increase in the liver and kidney. Accordingly, these results suggest that dietary anthocyanin stimulates homocysteine synthesis from SAH in the liver and kidney, and the homocysteine yielded transfers into the blood stream. The intake of anthocyanin and its structural homologues may have an effect on the metabolic regulation of sulfur amino acids and possibly increase the risk of vascular disease in humans.

High-dose melphalan with autologous stem cell transplantation (HDM/ASCT) is a promising treatment option for eligible patients with systemic immunoglobulin light chain (AL) amyloidosis. We present the results of ASCT following risk-adapted melphalan conditioning on the basis of criteria proposed by our group, including B-type natriuretic peptide (BNP). Ten patients with primary systemic AL amyloidosis treated at our institute were evaluated. A full dose of melphalan (200 mg/m(2)) was administered to patients who met all the following: performance status, 0 or 1; number of organs involved, 2 or less; serum creatinine, 1.5 mg/dL or less; EF 50 % or more and BNP 200 pg/mL or less; otherwise 140 mg/m(2). The hematologic complete response was achieved in four and organ response was seen in two patients. The median event-free survival (EFS) of all patients was 21.5 months, and median overall survival (OS) was 47.0 months. EFS and OS were significantly longer for patients who received 200 mg/m(2) of melphalan than for those who received lower dose (EFS: not reached vs. 13.9 months, P = 0.0217; OS: not reached vs. 13.8 months, P = 0.0186). No treatment-related mortality within 100 days from ASCT was observed. Evaluation of cardiac diastolic function may contribute to safer HDM/ASCT and improve outcome of AL amyloidosis.

Objective To determine the efficacy and safety of garenoxacin, a new generation of quinolone antimicrobial agent, in the treatment of adult upper respiratory tract infections. Methods A total of 113 subjects were enrolled in this study. Garenoxacin (400 mg/day) was administered to patients with pharyngolaryngitis, tonsillitis, and otitis media for 5–7 days and to those with sinusitis for 7–10 days. Clinical symptoms and findings were examined and quantitatively evaluated using a scoring system. Results We found 80 to 100% improvement rate in symptoms and findings for each infection. In addition, we found significant improvement in subjective evaluations from patient questionnaires even in the early stage of the treatment. X-ray examination for acute sinusitis demonstrated that the clinical efficacy was 84% (27/32) and 76% (19/25) patients were already improved within seven days. Among the detected 84 bacteria, 75 (89%) were identified as the major pathogenic bacteria of respiratory tract infections such as Streptococcus pneumoiae (27 strains) and Haemophillus influenzae (14 strains). Garenoxacin administration completely eradicated bacteria in 53 out of 54 cases (98%). There were 8 adverse events (8.3%) including 3 diarrhea cases (3.1%). Conclusion These results suggest that garenoxacin is a highly effective and safe antimicrobial agent in the treatment of community-acquired upper respiratory infections. Additionally, garenoxacin did not induce the growth of resistant bacteria because of its strong antimicrobial activity.

金沢大学医薬保健研究域医学系, We report the first case of three delayed complications following irradiation for laryngeal carcinoma: bilateral vocal cord immobility, obstruction of esophagus and spontaneously ruptured pseudoaneurysm of common carotid artery. Medial fixation of bilateral vocal cords and stenosis of cervical esophagus were noted at 28 years after radiotherapy. Spontaneous rupture of a pseudoaneurysm bulging into the hypopharynx and obstruction of the esophagus occurred at 35 years after irradiation. The life-threatening hemorrhage was successfully treated by microcoil embolization of the common carotid artery. The relationship between these complications and irradiation is also discussed. © 2008 Elsevier Ireland Ltd. All rights reserved.

The laryngeal mask airway (LMA) is regarded as a safer supraglottic airway for general anesthesia compared with conventional endotracheal tubes. We report a case of bilateral vocal cord palsy temporarily observed after using the LMA, which required urgent tracheotomy. Severe swelling of the arytenoid suggested that bilateral recurrent laryngeal nerve palsy was caused by prolonged compression on the pyriform fossa. One month later, vocal cord movements were fully recovered. It should be noted that bilateral vocal cord palsy is a possible complication associated with use of the LMA.

We report 2 cases of clinical signs and symptoms consistent with idiopathic carotidynia, evaluating and following up the appearance of carotidynia on CT and ultrasonography. Subjects were a 22-year-old woman and an 82-year-old man reporting pain and mass on the left side of the neck. They had abnormal soft-tissue infiltration surrounding the symptomatic carotid artery centered at the distal common carotid and carotid bifurcation in CT and ultrasonography. Their symptoms were resolved within 2 weeks. Repeat CT and ultrasonography after resolution of symptoms showed an absence of the previous abnormality. Few reports have described radiological findings in carotidynia, and CT and ultrasonography enable the evaluation of patients with suspected carotidynia and of most common entities in the differential diagnosis of carotidynia, including aneurysm, aneurysmal dissection, thrombosis, lymphadenitis, submandibular gland disease, and head and neck tumors.

Matrix metalloproteinase 2 (MMP-2) plays a crucial role in invasion and metastasis of malignant tumors. Membrane type 1-MMP (MT1-MMP) was originally identified as an activator of MMP-2. Tissue inhibitor of MMP-2 (TIMP-2) was identified as an inhibitor of MMP-2 and MT1-MMP. However, TIMP-2 was reported to be essential for cell-mediated activation of MMP-2 and thus, the contribution of TIMP-2 to tumor invasion has remained controversial. This study was designed to analyze the role of TIMP-2 for activation of MMP-2 and its prognostic value in tongue squamous cell carcinoma (SCC). Expression of MMP-2, MT1-MMP and TIMP-2 protein was analyzed by immunohistochemistry, and their association with clinical factors was evaluated in 51 patients treated surgically for tongue SCC. Expression of MMP-2, MT1-MMP and TIMP-2 was significantly correlated with local and distant metastatic tumor recurrence and poor prognosis (MMP-2 and MT1-MMP, p < 0.0001; TIMP-2, p = 0.0002). Activation of MMP-2, analyzed by gelatin zymography in 17 fresh specimens, was remarkably associated with expression of MMP-2 (r = 0.779, p < 0.0001), MT1-MMP (r = 0.674, p < 0.0022) and TIMP-2 (r = 0.858, p < 0.0001). Increased expression of TIMP-2, as well as MMP-2 and MT1-MMP, was an important prognostic factor in patients with tongue SCC.