Central Nervous System Peripheral T Cell Lymphoma Manifesting as Lymphomatosis Cerebri That Was Misdiagnosed as Neuro-Behçet’s Disease: A Case Report

Background: Lymphomatosis cerebri (LC) is a unique form of primary central nerves lymphoma (PCNSL), which presents as diffuse infiltration of lymphoma cells characteristically in the white matter rather than tumor formation. However, the involvement of central nervous system (CNS) is unclear because of the lack of contrast enhancement. Case Presentation: We treated a 53-year-old woman with LC and brain lesions resembling neuro-Behcet’s disease. She had a past history of acute uveitis and current symptoms of somnolence and gait disturbances progressing for one month. Cranial magnetic resonance imaging (MRI) revealed high signal lesions in the brain stem. Based on her past history and present clinical findings, she was clinically diagnosed with neuro-Behcet’s disease, which was treated with 1 g of methylprednisolone (mPSL) pulse therapy. Repeated mPSL pulse therapy resulted in a minor response, but the cerebral lesions persisted. After a short remission of several months, signal changes of the brain stem lesion recurred and her consciousness level worsened at 4 months after diagnosis. Upon admission to our hospital, positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography revealed abnormal uptake in the systemic lymph nodes (LNs), including the bilateral inguinal LNs. A diagnosis based on a biopsy of the left inguinal LNs was primary central nervous system lymphoma with inguinal LN lesions, manifesting as LC from malignant peripheral T cell lymphoma, not otherwise specified. Four courses of high-dose methotrexate (3.5 g/m2) therapy lead to temporary recovery of consciousness, but there was no improvement in other neurological findings. All nodal lesions tentatively regressed. Serum soluble interleukin-2 receptor (sIL-2R) (normal range: 121–613 U/mL) was constitutively decreased from 8,520 U/mL before chemotherapy to 740 U/mL after chemotherapy. We observed cerebral micro-bleeds in the center of LC lesions during chemotherapy, but no surgical intervention was required. Two months later, LC recurred in the brain, which was fatal. Conclusions: Neuro-Behçet’s disease is difficult to distinguish from LC when other clinical findings, including human leukocyte antigen disparity, serum sIL-2R, or cerebrospinal IL-6, are lacking. LC should be differentiated from CNS lymphoma before corticosteroid therapy

Deep Level Characterization Improved by Laplace Charge Transient Spectroscopy

Deep-level transient spectroscopy (DLTS) has been widely used to electrically characterize the defects in semiconductors. The DLTS spectrum obtained by the rate-window analysis often shows a peak resulting from a transient signal made of two or more exponential signals. In such a case, the energies of the defects responsible for the transient are closely spaced together. The analysis of the transient signal by the inverse Laplace transform is able to resolve a single energy obtained by the rate-window analysis into multiple energies. The charge transient signal is more favored for the inverse Laplace transform than for the capacitance transient signal because the data can be immediately obtained after the pulse by the charge transient spectroscopy (QTS). Using a simulation, the Laplace charge transient spectroscopy has been shown to improve the deep level characterization

Graft-versus-host diseases characterized by effusion: A case of steroid-refractory graft-versus-host disease

Background: Although the biology of steroid-refractory acute GVHD is still unknown, the pathogenesis of steroid-refractory acute GVHD is recognized to be associated with aberrant cytokine milieu. Case presentation: We treated a 41-year-old Japanese male representing a characteristic clinical manifestation among unspecific cases of heterogeneous steroid-refractory acute GVHD. The patient underwent allogeneic bone marrow transplantation due to relapsed neurolymphomatosis. He achieved neutrophil engraftment on day 21 with mild engraftment fever. Acute GVHD occurred on day 56 after transplantation with systemic skin eruptions and precedent body weight gain. Corneal ulceration and gut GVHD symptoms followed the skin lesions sequentially. A biopsy of skin and gut mucosa revealed pathological GVHD. We recognized that the patient presented anasarca symptoms due to acute GVHD. We treated the patient with 1.0 mg/kg corticosteroids (prednisolone) starting on day 68, but his edema worsened. He did not respond to 2.0 mg/kg prednisolone from day 80. He required artificial ventilation on day 80 due to the bilateral massive pleural effusion and died of respiratory failure on day 99 after transplantation. A measurement of serum cytokines before corticosteroid therapy, IL-6 (61.5 pg/mL; normal range: <4.0), VEGF (51 pg/mL; <38.3), IFNγ (0.2 IU/mL; <0.1), and TNF-α (10.5 pg/mL; 0.6–2.8) were elevated. Th2 cytokines, IL-4 (7.2 pg/mL; <6.0) and IL-10 (6.0 pg/mL; <5.0) were also elevated. Conclusions: Our case was prominently characterized by anasarca manifested as follows: systemic edema, massive ascites and pleural effusion. We speculated that acute/chronic GVHD with anasarca has an immunological propensity for proinflammatory and the Th2 cytokine milieu. We advocate that immunological modification by biologic agents such as tocilizumab would be promising theoretically for the treatment of such type of GVHD. Keywords: Graft-versus-host disease, Corticosteroid, Anasarc

ApoE4 Is Associated with Lower Body Mass, Particularly Fat Mass, in Older Women with Cognitive Impairment

A lower body mass is associated with the progression of Alzheimer&rsquo;s disease (AD) and the risk of mortality in patients with AD; however, evidence of genetic determinants of decreased body mass in cognitively impaired older adults is limited. We therefore investigated the genetic effect of APOE-&epsilon;4 on body composition in older adults with mild cognitive impairment (MCI) and early-to-moderate-stage AD. A total of 1631 outpatients (aged 65&ndash;89 years) with MCI and early-to-moderate-stage AD were evaluated for the association between body composition and APOE-&epsilon;4 status. After adjusting for covariates, including cognitive function evaluated with the Mini-Mental State Examination, the presence of the APOE-&epsilon;4 was associated with lower weight (&beta; = &minus;1.116 &plusmn; 0.468 kg per presence, p = 0.017), fat mass (&beta; = &minus;1.196 &plusmn; 0.401 kg per presence, p = 0.003), and percentage of body fat (&beta; = &minus;1.700 &plusmn; 0.539% per presence, p = 0.002) in women but not in men. Additionally, the impact of APOE-&epsilon;4 on measures of body composition in women was more remarkable in MCI than in AD patients. The presence of the APOE-&epsilon;4 allele was associated with lower fat mass, particularly in women with MCI, independent of cognitive decline

Time trends (2012–2020) in glycated hemoglobin and adherence to the glycemic targets recommended for elderly patients by the Japan Diabetes Society/Japan Geriatrics Society Joint Committee among memory clinic patients with diabetes mellitus

ABSTRACT Aims/Introduction To investigate the changes in the glycated hemoglobin (HbA1c) levels and the relative status of the glycemic control related to the new glycemic targets recommended by the Japan Diabetes Society/Japan Geriatrics Society Joint Committee in 2016 in patients with diabetes mellitus visiting a memory clinic from 2012 to 2020. Materials and Methods This cross‐sectional study included 1,436 patients aged ≥65 years with diabetes. Patients were categorized into three categories as follows: category I, intact cognitive function and activities of daily living (ADL); category II, mild cognitive deficits or impaired instrumental ADL; and category III, moderate to severe cognitive impairment or impaired basic ADL. Trends in HbA1c levels, glycemic control status (optimally/poorly/excessively controlled) and proportion of individuals receiving drugs potentially associated with severe hypoglycemia among all patients and categories (I, II or III) from 2012 to 2020 were examined using linear, logistic and multinominal logistic regression models adjusted for confounding factors. Results Between 2012 and 2020, the HbA1c levels, as well as the proportion of patients with poor glycemic control, increased, whereas the proportion of patients with excessive glycemic control and those receiving drugs potentially associated with severe hypoglycemia decreased. Conclusions Increased levels of HbA1c and decreased proportions of individuals under excessive glycemic control might reflect recent treatment strategies that avoid hypoglycemia in older patients. Given the adverse complications associated with hyperglycemia, more flexible and individualized glycemic targets based on comprehensive assessments, including vascular complications and comorbidities, might be necessary

Complete mimicry: a case of alveolar rhabdomyosarcoma masquerading as acute leukemia

Abstract Background A small number of rhabdomyosarcoma (RMS) cases involve the bone marrow. A leukemic presentation of RMS has been reported in a few case series, although almost all cases of leukemic RMS are not completely mimicking leukemia. We encountered a case with RMS cell infiltration of the bone marrow that resembled floating hematological cells. Case presentation We encountered a rare case of a 15-year-old boy with a 2-week history of left femoral pain. Upon admission, he was afebrile with no other symptoms. No apparent cause of femoral pain was detected on an initial examination. Laboratory findings revealed normal white blood cell (WBC) count and hemoglobin concentration, with a platelet count of 10.3 × 104/μL. WBCs included 2.0% metamyelocytes, 4.5% myelocytes, and 0.5% blasts. Lactate dehydrogenase concentration was 1299 U/L, creatine kinase was 437 U/L, and C-reactive protein was 1.25 mg/dL. Bone marrow aspiration demonstrated hypercellular marrow (nucleated cell count 1.84 × 104/μL) and 89.0% of blast-like cells of all nucleated cells. The proliferating cells were negative for myeloperoxidase and esterase, and strongly positive for CD56. Positron emission tomography exhibited extensive accumulation of 18F–fludeoxyglucose with a SUVmax of 7.09. Magnetic resonance imaging revealed T1-low intensity, gadolinium-enhanced, diffuse, and irregular lesions on his pelvis and bilateral femurs. These laboratory and imaging findings suggested hematological malignancy with diffuse bone involvement, suggestive of acute leukemia. However, the pathological diagnosis of bone marrow and basal penile muscle biopsy was alveolar RMS. Karyotype analysis of bone marrow cells revealed the characteristic translocation of t(2;13)(q35;q14). The final diagnosis was alveolar RMS with massive involvement of the bone marrow and the primary site in the perineal muscles. The tumor cells both of the primary site and bone marrow were positive for myogenin. Conclusions A literature review found a misdiagnosed case of completely mimicking leukemic RMS as natural-killer (NK)-cell leukemia. Such a misdiagnosis can have critical consequences. We experienced a rare case of alveolar RMS with symmetrical diffuse bone marrow involvement completely masquerading as acute leukemia. The results of a surface marker study showing that the tumor cells had a near NK-cell phenotype were misleading

Aerobic exercise training-induced irisin secretion is associated with the reduction of arterial stiffness via nitric oxide production in adults with obesity

This study aimed to clarify whether muscle-derived irisin secretion induced by aerobic exercise training is involved in reduction of arterial stiffness via arterial nitric oxide (NO) productivity in obesity. In animal study, 16 Otsuka Long-Evans Tokushima Fatty (OLETF) rats with obesity were randomly divided into 2 groups: sedentary control (OLETF-CON) and 8-week aerobic treadmill training (OLETF-EX) groups. In human study, 15 subjects with obesity completed 8-week aerobic exercise training for 45 min at 60%–70% peak oxygen uptake intensity for 3 days/week. As a result of animal study, carotid-femoral pulse wave velocity (cfPWV) was decreased, and arterial phosphorylation levels of AMP-activated protein kinase (AMPK), protein kinase B (Akt), and endothelial NO synthase (eNOS), circulating levels of nitrite/nitrate (NOx) and irisin, and muscle messenger RNA expression of fibronectin type III domain containing 5 (Fndc5) were increased in the OLETF-EX group compared with OLETF-CON group. In a human study, regular aerobic exercise reduced cfPWV and elevated circulating levels of NOx and irisin. Furthermore, change in circulating irisin levels by regular exercise was positively correlated with circulating NOx levels and was negatively correlated with cfPWV. Thus, aerobic exercise training-induced increase in irisin secretion may be related to reduction of arterial stiffness achieved by NO production via activated arterial AMPK–Akt–eNOS signaling pathway in obesity. Novelty Aerobic exercise training promoted irisin secretion with upregulation of muscle Fndc5 gene expression in rats with obesity. Irisin affected the activation of arterial AMPK–Akt–eNOS signaling by aerobic exercise training. Increased serum irisin level by aerobic exercise training was associated with reduction of arterial stiffness in obese adults.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author