Interaction of BMI and respiratory status in obstructive sleep apnea, a cross-sectional COPD study.

This cross-sectional study of 136 patients with chronic obstructive pulmonary disease (COPD) investigated the mechanism underlying overlap syndrome, defined as coexisting COPD and obstructive sleep apnea (OSA). OSA was defined as a respiratory event index (REI) ≥ 5 events/h, determined using type-3 portable monitors. The mean REI was 12.8 events/h. Most participants (60.1%) had mild OSA (REI: 5-15 events/h). The REI was positively correlated with forced expiratory volume in one second (%FEV1) (r = 0.33, p < 0.001), body mass index (BMI) (r = 0.24, p = 0.005), and fat-free mass index (r = 0.31, p = 0.005), and negatively correlated with residual volume divided by total lung capacity (r = -0.27, p = 0.003). Receiver-operating characteristic curve analysis revealed an optimal BMI cutoff of 21.96 kg/m2 for predicting moderate/severe OSA. A BMI ≥ 21.96 kg/m2 was associated with OSA among participants with %FEV1 ≥ 50%, but not those with %FEV1 < 50%. This study revealed an interaction between airflow limitation and hyperinflation, nutritional status, and OSA.

Anti-N-methyl-d-aspartate receptor encephalitis preceded by meningitis lasting up to 60 days.

Long-lasting meningitis complicated by N-methyl-d-aspartate receptor (NMDAR) encephalitis has not been discussed widely in the literature. Herein, we present two cases of anti-NMDAR encephalitis preceded by meningitis. The patients had 60- and 22-day periods of preceding meningitis, which improved with intravenous methylprednisolone and plasmapheresis. No tumors were detected in either of the patients. Although meningitis preceding anti-NMDAR encephalitis is not rare, our patients, especially those who had it for a duration of 60 days, had longer durations of meningitis. This manuscript foregrounds that anti-NMDAR encephalitis might be included in the differential diagnosis of long-lasting meningitis.

Therapeutic Response to Single-Inhaler Triple Therapies in Moderate-to-Severe COPD.

BACKGROUND: COPD is characterized by progressive and irreversible air flow limitations. Single-inhaler therapies (SITTs) incorporating an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting ß2-agonist have been shown to effectively alleviate symptoms and improve lung function. Fluticasone-furoate/umeclidinium/vilanterol (F/U/V) and budesonide/glycopyrronium/formoterol (B/G/F) are available as SITT in Japan. However, the clinical differences between these 2 combinations and the predictors of their proper use have not been established. This study aimed to identify the subject characteristics that could predict the effectiveness of inhaler therapy. METHODS: We assessed the pulmonary function test results of subjects with COPD before and one month after using F/U/V and B/G/F as SITT. Subjects with a difference of 100 mL or more in the FEV1 after treatment with pre-SITT were extracted and divided into the F/U/V effect and no-effect group and B/G/F effect and no-effect group to examine the factors associated with positive outcomes with each inhaler. RESULTS: F/U/V and B/G/F significantly improved the inspiratory capacity (IC), %IC, FVC, and %FEV1 when compared to pre-intervention values (P < .001, P = .001, P = .007, P = .009, respectively, for F/U/V; and P = .006, P = .008, P = .038, P = .005, respectively, for B/G/F). Factors associated with FEV1 improvement in F/U/V included lower %IC (odds ratio 0.97 [95% CI 0.94-0.99], P = .03) and a higher modified Medical Research Council (mMRC) dyspnea score (2.36 [1.27-4.70], P < .01). In addition, a higher %IC (1.03 [1.00-1.06], P = .02) and lower mMRC dyspnea score (0.55 [0.28-0.99], P = .041) were predictors for the effectiveness of B/G/F. CONCLUSIONS: Our results showed that SITT significantly improved the IC, %IC, FVC, and %FEV1 when compared to pre-intervention and that F/U/V was more effective in subjects with severe symptoms, whereas B/G/F was more effective in subjects with mild symptoms.

Identification of TCR repertoires in functionally competent cytotoxic T cells cross-reactive to SARS-CoV-2.

SARS-CoV-2-specific CD8+ T cells are scarce but detectable in unexposed healthy donors (UHDs). It remains unclear whether pre-existing human coronavirus (HCoV)-specific CD8+ T cells are converted to functionally competent T cells cross-reactive to SARS-CoV-2. Here, we identified the HLA-A24-high binding, immunodominant epitopes in SARS-CoV-2 spike region that can be recognized by seasonal coronavirus-specific CD8+ T cells from HLA-A24+ UHDs. Cross-reactive CD8+ T cells were clearly reduced in patients with hematological malignancy, who are usually immunosuppressed, compared to those in UHDs. Furthermore, we showed that CD8+ T cells in response to a selected dominant epitope display multifunctionality and cross-functionality across HCoVs in HLA-A24+ donors. Cross-reactivity of T-cell receptors isolated from them exhibited selective diversity at the single-cell level. Taken together, when stimulated well by immunodominant epitopes, selective pre-existing CD8+ T cells with high functional avidity may be cross-reactive against SARS-CoV-2.

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).

Phase II study of dose-adjusted gemcitabine, dexamethasone, cisplatin, and rituximab in elderly relapsed diffuse large B-cell lymphoma patients.

High-dose chemotherapy and autologous stem cell transplantation (ASCT) are too toxic for elderly patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Therefore, effective and tolerable regimens for elderly patients are urgently needed. The present phase II study assessed the efficacy and safety of dose-adjusted therapy with gemcitabine, dexamethasone, cisplatin, and rituximab (GDP-R) in this population. ASCT-ineligible elderly patients with relapsed or refractory DLBCL received dose-adjusted GDP-R in each 28-day cycle for up to six cycles. The primary endpoint was overall response rate (ORR), and secondary endpoints were complete response (CR) rate, progression-free survival (PFS), and safety. Thirty-three patients were enrolled and received dose-adjusted GDP-R. The median age was 75 years (range: 68-87 years). The ORR was 82.8% (90% confidence interval [CI], 67.1-93.0%), with a CR rate of 58.6% (90% CI, 41.7-74.1%). At a median follow-up of 20.9 months, the 2-year PFS rate was 46.8% (90% CI, 30.7-61.5%) and the 2-year overall survival rate was 63.2% (90% CI, 45.8-76.3%). The most frequently observed grade 4 adverse events were neutropenia (63.6%), thrombocytopenia (57.6%), and lymphocytopenia (39.4%). Dose-adjusted GDP-R is a promising salvage regimen for ASCT-ineligible elderly patients with relapsed DLBCL after rituximab-containing chemotherapy and warrants further investigation.

A Case of Crossed Logopenic Primary Progressive Aphasia in a Dextral Patient with Underlying Frontotemporal Dementia.

A 61-year-old dextral woman was admitted to the hospital with difficulty finding words. Neurological examinations confirmed that her speech was affected by frequent pauses and occasional phonological paraphasia without cognitive deficits. We detected atrophy, hypoperfusion, and hypometabolism in the right perisylvian and parietal regions, expanding to the right anterior temporal lobes and right inferior frontal gyrus (opercular region) by magnetic resonance imaging, single-photon emission computed tomography, and fluorodexyglucose-positron emission tomography (PET), respectively. Amyloid-PET did not identify the accumulation of amyloid beta (Aß) in the bilateral cerebral cortices. We herein report a case of crossed aphasia with Aß-negative logopenic primary progressive aphasia that was likely the result of frontotemporal lobar degeneration.

Unsuppressed serum albumin levels may jeopardize the clinical relevance of the international staging system to patients with light chain myeloma.

The international staging system (ISS) is the most commonly used risk-stratification system for patients with multiple myeloma (MM) and is determined by serum albumin and ß2-microglobulin levels. In the two determinants, ß2-microglobulin levels are frequently observed to be elevated in patients with myeloma, particularly in those with renal impairment. In comparison with patients with intact immunoglobulin myeloma, patients with LC myeloma do not necessarily show decreased levels of serum albumin. The clinical impact of ISS in patients with LCMM, in particular the distinction between ISS I and II, may be complicated due to non-decreased levels of serum albumin in both stages. Accordingly, we have attempted to assess clinical relevance of the ISS in patients with LC myeloma. The clinical data of 1899 patients with MM diagnosed between January 2001 and December 2012 were collected from 38 affiliated hospitals of the Japanese Society of Myeloma. Significant difference was not found between stage I (n = 72) and stage II (n = 92) in LC myeloma patients (n = 307). The mean serum albumin concentration of patients with LC myeloma was within the reference range but higher than that of patients with IgG + IgA myeloma (n = 1501), which complicates the distinction between ISS stage I and II myeloma. Patients with LC myeloma had low frequencies of t(4; 14) and high frequency of elevated lactate dehydrogenase, and despite a relevant amount of missing data in our registry (R-ISS stage I; n = 11, stage II; n = 32, and stage III: n = 18), the information included in the R-ISS scoring system seems to be more accurate than ISS to obtain a reliable risk stratification approach in non-ISS stage III LC myeloma patients.

Long-term clinical follow-up of a patient with non-paraneoplastic cerebellar ataxia associated with anti-mGluR1 autoantibodies.

The clinical features of cerebellar ataxia associated with anti-metabotropic glutamate receptor 1 (mGluR1) autoantibodies, a rare autoimmune-mediated cerebellar ataxia, remain to be elucidated. Here, we describe a patient with non-paraneoplastic cerebellar ataxia associated with anti-mGluR1 autoantibodies, who was followed up over 5 years. She presented with relapses and remissions of subacute progressive cerebellar ataxia that were responsive to immunotherapy. Although serum anti-mGluR1 autoantibodies were continuously detected and cerebellar atrophy gradually progressed, repeated intravenous immunoglobulin therapy and oral immunosuppressants ensured cerebellar ataxia remained at almost the same level during the observation period.

Diagnosing Corticobasal Syndrome Based on the Presence of Visual Hallucinations and Imaging with Amyloid Positron Emission Tomography.

A 61-year-old woman was admitted to our hospital due to memory difficulties, visual hallucinations, and slowly progressing motor difficulties in the limbs. A clinical examination revealed bradykinesia, gait disturbance, left-side-dominant rigidity, ideomotor apraxia, dressing apraxia, left-sided spatial agnosia, impaired visuospatial ability, and executive dysfunction. Her symptoms were unresponsive to levodopa, and corticobasal syndrome (CBS) was diagnosed. One year later, amyloid positron emission tomography revealed amyloid beta accumulation in the bilateral cerebral cortices; at this point, CBS with underlying Alzheimer's disease pathology (CBS-AD) was diagnosed. Visual hallucinations may help differentiate CBS with corticobasal degeneration (CBS-CBD) from other pathologies, including CBS-AD.

Comparison of cerebrospinal fluid profiles in Alzheimer's disease with multiple cerebral microbleeds and cerebral amyloid angiopathy-related inflammation.

Brain magnetic resonance imaging (MRI) of patients with Alzheimer's disease (AD) sometimes reveals multiple cerebral microbleeds (CMBs) and confluent white matter hyperintensities (WMHs) similar to those observed in cerebral amyloid angiopathy-related inflammation (CAA-I). To determine whether there might be common pathophysiological mechanisms underlying the MRI findings of multiple CMBs and confluent WMHs, we investigated the cerebrospinal fluid (CSF) profiles of 38 AD, five amnestic mild cognitive impairment (MCI), and six CAA-I patients. The AD and MCI patients were divided into groups of patients with (n = 10) or without (n = 33) multiple CMBs (n ≥ 2) on T2*-gradient echo sequences of brain MRI. We compared the CSF profiles of AD and MCI patients with or without multiple CMBs, and CAA-I patients. The brain MRIs of the patients with multiple CMBs revealed severe degrees of WMHs compared with the patients without multiple CMBs. The levels of CSF anti-amyloid ß autoantibody and interleukin 8, and CSF/serum albumin ratios and immunoglobulin G indexes, were significantly higher in CAA-I patients than the other groups. However, there were no significant differences in the CSF profiles of patients with or without multiple CMBs. Our study provides evidence for different pathophysiological mechanisms underlying these differential MRI findings in AD and CAA-I.

Reduction in the numbers of drugs administered to elderly in-patients with polypharmacy by a multidisciplinary review of medication using electronic medical records.

AIM: Polypharmacy is a major problem for elderly patients in developed countries. We investigated whether a multidisciplinary medication review using electronic medical records could reduce the number of drugs administered to elderly patients receiving polypharmacy. METHODS: The present study included 432 elderly patients (188 women, 244 men; 267 patients aged 65-74 years and 165 patients aged ≥75 years) who were admitted to and discharged from the Department of Neurology and Geriatrics, Gifu University Hospital, between 2004 and 2011; those who died at the hospital were excluded. The names, categories, and numbers of orally administered drugs at admission and discharge were examined retrospectively using electronic medical records. The histories of continuous oral immunotherapy use at the hospital, falls during the 2 years before hospital admission and the presence of fall risk factors were also evaluated. P-values <0.05 were considered statistically significant. RESULTS: On average 1.14 ± 3.07 fewer types of drugs were given to patients at discharge than at admission in patients receiving polypharmacy (P < 0.001). However, the number of drugs given to patients undergoing continuous oral immunotherapy increased by 1.67 ± 3.47 (P < 0.001). The number of drugs was reduced in 33.1% of fallers, and 36.3% of non-fallers. In both fallers and non-fallers, there was a reduction in drug categories associated with falls. CONCLUSIONS: Multidisciplinary medication review using electronic medical records could significantly reduce the numbers of drugs taken by elderly inpatients receiving polypharmacy, including drugs associated with falls, in both fallers and non-fallers Geriatr Gerontol Int 2017; 17: 653-658.

DEC2 is a negative regulator for the proliferation and differentiation of chondrocyte lineage-committed mesenchymal stem cells.

Differentiated embryo chondrocyte 2 (DEC2) is a basic helix-loop-helix-Orange transcription factor that regulates cell differentiation in various mammalian tissues. DEC2 has been shown to suppress the differentiation of mesenchymal stem cells (MSCs) into myocytes and adipocytes. In the present study, we examined the role of DEC2 in the chondrogenic differentiation of human MSCs. The overexpression of DEC2 exerted minimal effects on the proliferation of MSCs in monolayer cultures with the growth medium under undifferentiating conditions, whereas it suppressed increases in DNA content, glycosaminoglycan content, and the expression of several chondrocyte-related genes, including aggrecan and type X collagen alpha 1, in MSC pellets in centrifuge tubes under chondrogenic conditions. In the pellets exposed to chondrogenesis induction medium, DEC2 overexpression downregulated the mRNA expression of fibroblast growth factor 18, which is involved in the proliferation and differentiation of chondrocytes, and upregulated the expression of p16INK4, which is a cell cycle inhibitor. These findings suggest that DEC2 is a negative regulator of the proliferation and differentiation of chondrocyte lineage-committed mesenchymal cells.

Lineage switch with t(6;11)(q27;q23) from T-cell lymphoblastic lymphoma to acute monoblastic leukemia at relapse.

We present a patient with T-cell lymphoblastic lymphoma (T-LBL) harboring t(6;11)(q27;q23) that converted to acute monoblastic leukemia at relapse. A 27-year-old man developed T-LBL with a mediastinal mass. He exhibited several recurrences in the central nervous system and marrow. A fifth relapse occurred in the marrow, with 42.8% blasts with CD4, CD5, CD7, CD10, CD33, CD34, HLA-DR and cytoplasmic (cy) CD3. While achieving complete remission with nelarabine, sixth relapse occurred in the marrow with 6.8% blasts, which had characteristics of monoblastic features, 2 months later. Marrow blasts were positive for myeloperoxidase, CD4, CD33, CD56, CD64, and HLA-DR, but were negative for cyCD3, CD5, CD7, CD10, and CD34. Marrow cells at both the 5th lymphoid and 6th myeloid relapses had t(6;11)(q27;q23) and the same MLL-MLLT4 fusion transcript. In addition, the MLL-MLLT4 fusion sequences documented in the initial mediastinal cells were the same as seen in peripheral blood cells at the 6th relapse. The patient continues 7th remission after one course of gemtuzumab ozogamicin therapy followed by cord blood transplantation for more than 3 years. Sequential phenotypic and cytogenetic studies may yield valuable insights into the mechanism of leukemic recurrence and possible implications for treatment selection.

Psychological Transformation by an Intervention to Facilitate Benefit Finding Among People With Chronic Mental Illness in Japan.

PURPOSE: This study aimed to preliminarily explore the psychological transformation effected by a newly developed intervention program for facilitating benefit finding among individuals with chronic mental illness in Japan. DESIGN AND METHODS: An intervention study with three weekly group sessions was implemented, and qualitative data on the participants' experience of benefit finding were obtained by a questionnaire survey and analyzed using content analysis technique. FINDINGS: Of the 31 participants, 23 responded that they realized some sort of benefit finding through the intervention. PRACTICE IMPLICATIONS: The program component in question may contribute to enhanced benefit finding for people with chronic mental illness while longitudinal studies involving more participants are desirable.

Effectiveness of a program to facilitate recovery for people with long-term mental illness in Japan.

Recovery is defined as the process of developing new meaning and purpose in life as one grows beyond the catastrophic effects of mental illness. This study aimed to develop a program to facilitate recovery and examine its effectiveness in a randomized controlled trial. The program was developed with three components that enhance benefit finding, personal meaning, and a sense of happiness. Sixty-three participants with long-term mental illness were randomly allocated to the intervention group (n = 32) or the control group (n = 31). The intervention group attended eight 2-h group sessions, with one held every week. Recovery was assessed at baseline, post-intervention, and at a three-month follow-up. In the per-protocol analysis, after excluding those who dropped out, the intervention group showed significant improvement in recovery compared with the control group (P < 0.05). In the intention-to-treat analysis, a repeated measures analysis of variance did not show any significant intervention effect (time × group) (P > 0.05). The program had the potential to facilitate recovery.

Late-onset patients with sporadic amyotrophic lateral sclerosis in Japan have a higher progression rate of ALSFRS-R at the time of diagnosis.

OBJECTIVE: The population in Japan is aging at a faster rate than in other countries in the world. It is speculated that the number of patients with late-onset amyotrophic lateral sclerosis (ALS) will increase even more in the future. However, few studies have been undertaken on the characteristics of patients with late-onset ALS in Japan. This study sought to investigate the clinical features of patients with late-onset ALS compared with those with early-onset ALS using the progression rate (ΔFS). METHODS: Forty-five patients with sporadic ALS were divided into 2 groups: 23 patients with early-onset of ALS (<65 years; early onset) and 22 patients with late-onset ALS (≥65 years; late onset). Every patient was followed up from the time of initial diagnosis to the primary endpoint (death or time culminating in death without tracheostomy or ventilation assistance including noninvasive positive pressure ventilation) or for at least 48 months after initial diagnosis. RESULTS: ΔFS in the patient group with late onset was significantly higher than that of the group with early onset (p=0.010). Survival of patients with late onset was significantly decreased compared to that of patients with early onset (p=0.031). CONCLUSION: Our finding suggested that patients with late-onset ALS showed more rapid disease progression than those with early-onset ALS using ΔFS.

Neuromyelitis optica in Japanese sisters.

We report cases of Japanese sisters with neuromyelitis optica (NMO). The elder sister was 25, when she was diagnosed with right optic neuritis. After 3 months, she developed left optic neuritis and myelitis. At age 27, she had the second relapse, but she has been free from episodes thereafter. The younger sister was 26, when she was diagnosed with optic neuritis. Thus far, she has 9 relapses, comprising both myelitis and optic neuritis. Both sisters had normal brain MRI scans, longitudinally extensive transverse myelitis over 3 vertebral segments, and positive results for anti-aquaporin-4 antibody (AQAP4Ab). They fulfilled the Wingerchuk criteria for definite NMO. Both sisters shared some immunogenetic factors, but they were not exposed to the same environmental factors after their early twenties. The final disability status was almost the same in both cases, and both showed a very benign course. These data suggest that genetic factors affect the age at onset and environmental factors may affect the frequency of relapse.