An autopsy case of macroglobulinemia complicated with syndrome of inappropriate secretion of ADH (SIADH) like hyponatremia, hypopituitarism and AL amyloidosis.

An 88-year-old male patient with macroglobulinemia was admitted to our hospital because of severe hyponatremia and unconsciousness. Laboratory findings showed decreased inhibition of antidiuretic hormone (ADH) and he was diagnosed with syndrome of inappropriate secretion of ADH (SIADH). Hyponatremia improved with only limitation of water intake and the patient was followed up on a continuing outpatient basis. However, soon after discharge from hospital, his legs started swelling with edema and hyponatremia worsened. He was re-admitted due to a fall at home. Hyponatremia was observed at re-admission. A CRH challenge test showed partial dysfunction of ACTH secretion. Corticosteroid therapy was performed, but the patient subsequently died from pneumonia. Pathological findings at autopsy revealed invasion of plasma cells and amyloid depositions in multiple organs, including the pituitary, adrenal cortex, heart, liver, kidney, lymph nodes and bone marrow. Consistent with these results, fibrosis was observed in the anterior lobe of the pituitary, suggesting that the autopsy findings were related to the clinical observations and diagnosis. This is the first reported case of macroglobulinemia complicated with multiple hormone dysfunction.

A mixed-method systematic review of unmet care and support needs among Japanese cancer survivors.

PURPOSE: To synthesize published studies regarding Japanese cancer survivors' needs/unmet needs of care/support, change of unmet needs over time, and preferred care/support providers. METHODS: A mixed-method systematic review was conducted. MEDLINE, PsycINFO, CINAHL, and Ichu-shi were searched from inception to May 2022. Quantitative and qualitative studies were separately analyzed using narrative synthesis and meta-ethnography. Each finding was synthesized using a line of argument. RESULTS: Twenty-four studies (13 quantitative and 11 qualitative studies) were included. Six quantitative studies reported unmet needs in survivors of adolescent and young adult (n=1) and adulthood (n=5) cancer. No longitudinal studies regarding changes in unmet needs were identified. One study reported that adults preferred care/support providers. The quantitative studies identified more help in physical (48.2-51.0%, n=2) and psychological issues (17.4-78.8%, n=5), information (27.9-58.0%, n=3), and healthcare services (25.3-67.1%, n=2) among adults. The qualitative studies emphasized more tailor-made information about life events for young cancer survivors. More empathic and trustworthy interactions with surrounding people, including healthcare professionals, were demanded, regardless of age. A line of argument illustrated that cancer survivors had insufficient resources for activities and empowerment to face life with cancer at all phases. CONCLUSIONS: Japanese cancer survivors' unmet needs are diverse. More information and resources for psychological care/support and local healthcare services post-treatment are needed, which may hinder the optimal transition to survivorship. IMPLICATIONS FOR CANCER SURVIVORS: The synthesized evidence should be utilized to implement a comprehensive care/support system in practice and educate people surrounding cancer survivors, regardless of age.

Effectiveness of a Volunteer Training Program on the Learning Support of Children in Hospice Palliative Care.

BACKGROUND: Volunteers are expected to play a key role in children's hospice. However, there is a lack of information about how to cultivate effective volunteer training programs. OBJECTIVE: To verify the effect of a training program on volunteers' confidence in providing learning support and sharing experiences with children with life-threatening conditions and their families in a children's hospice. METHODS: In this pre-post study, participants were 48 undergraduate and graduate students from 3 universities in Japan. They received 5 lectures on children's hospice learning support. They evaluated the training program by rating their self-confidence in meeting each of the 15 program goals on a questionnaire. RESULTS: An exploratory factor analysis of the questionnaire yielded 12 goals in 4 factors: understanding of one's own and others' mental state, accommodating the learning needs of children with life-threatening conditions, understanding and accommodating the physical state of children with life-threatening conditions, and understanding the significance of children's hospice. A paired t test revealed that participants' self-confidence had increased significantly in 3 of these 4 factors after the program. However, the score for accommodating the learning needs of children with life-threatening conditions decreased but not significantly. CONCLUSION: Although it needs some improvements, the program was effective for improving volunteers' self-confidence in and understanding of learning support and sharing experiences with children with life-threatening conditions.

Mycophenolate mofetil treatment in a patient with recurrent lymphocytic hypophysitis.

Lymphocytic hypophysitis (LHP) is a relatively rare disease characterised by lymphocytic infiltration of the pituitary gland, resulting in pituitary dysfunction. LHP is generally responsive to corticosteroid therapy, but cases with recurrence require clinicians to select second-line therapy. We report here the case of a 58-year-old patient with LHP who developed panhypopituitarism and bitemporal hemianopia. He responded to prednisolone 40 mg/day but relapsed during tapering. The prednisolone dose was increased again and mycophenolate mofetil (MMF) was added. Thereafter, over the course of 1 year, prednisolone was tapered to 8 mg/day without relapse. Because of the rarity of LHP, there are no standard treatment protocols that support the choice of a specific immunosuppressive drug. MMF was effective for recurrent LHP in our case. Further accumulation of cases is needed to establish the standard treatment for this disease.

Bacteremia Possibly Caused by Helicobacter cinaedi and Associated with Painful Erythema in Rheumatoid Arthritis with Malignant Lymphoma.

We herein report the case of a 69-year-old woman with rheumatoid arthritis (RA) and malignant lymphoma who developed Helicobacter cinaedi bacteremia after starting rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. She had a recurrent fever and painful erythema for 13 months before the diagnosis was made. This delayed diagnosis was attributable to the underlying RA, which typically presents with various cutaneous manifestations and elevated C-reactive protein levels. The erythema on the thighs, abdomen, and left forearm improved following treatment with intravenous aminobenzyl penicillin; she received antibiotics for six weeks. This case emphasizes the importance of recognizing this opportunistic infection in immunocompromised patients.

Pharmacological inhibition of tankyrase induces bone loss in mice by increasing osteoclastogenesis.

Tankyrase is a poly (ADP-ribose) polymerase that leads to ubiquitination and degradation of target proteins. Since tankyrase inhibitors suppress the degradation of AXIN protein, a negative regulator of the canonical Wnt pathway, they effectively act as Wnt inhibitors. Small molecule tankyrase inhibitors are being investigated as drug candidates for cancer and fibrotic diseases, in which the Wnt pathways are aberrantly activated. Tankyrase is also reported to degrade the adaptor protein SH3BP2 (SH3 domain-binding protein 2). We have previously shown that SH3BP2 gain-of-function mutation enhances receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in murine bone marrow-derived macrophages (BMMs). Although the interaction between tankyrase and SH3BP2 has been reported, it is not clear whether and how the inhibition of tankyrase affects bone cells and bone mass. Here, we have demonstrated that tankyrase inhibitors (IWR-1, XAV939, and G007-LK) enhanced RANKL-induced osteoclast formation and function in murine BMMs and human peripheral blood mononuclear cells through the accumulation of SH3BP2, subsequent phosphorylation of SYK, and nuclear translocation of NFATc1. Tankyrase inhibitors also enhanced osteoblast differentiation and maturation, represented by increased expression of osteoblast-associated genes accompanied by the accumulation of SH3BP2 protein and enhanced nuclear translocation of ABL, TAZ, and Runx2 in primary osteoblasts. Most importantly, pharmacological inhibition of tankyrase in mice significantly decreased tibia and lumbar vertebrae bone volumes in association with increased numbers of osteoclasts. Our findings uncover the role of tankyrase inhibition in bone cells and highlight the potential adverse effects of the inhibitor on bone.

POEMS syndrome in a patient with rheumatoid arthritis.

Multiple myeloma has been reported to be associated with rheumatoid arthritis (RA). POEMS syndrome is a rare variant of multiple myeloma and is characterised by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. We report the case of a 67-year-old patient with RA who developed numbness and tingling in both legs due to polyneuropathy. CT showed a massive right pleural effusion and a sclerotic lesion in the right ninth rib. Histopathological examination of the rib revealed IgA lambda-type plasmacytoma. Serum vascular endothelial growth factor was extremely high at 5530 pg/mL. We made a diagnosis of POEMS syndrome. A literature search of the PubMed database identified only two documented cases of POEMS syndrome in patients with RA. Neuropathies are reportedly more frequent in patients with RA than in the general population. Rheumatologists should consider POEMS syndrome in patients with RA and neurological symptoms.

Successful treatment using rituximab in a patient with refractory polymyositis complicated by scleroderma renal crisis.

Corticosteroids are the first-line treatment for patients with inflammatory myopathies. Myositis can be a clinical feature of scleroderma (polymyositis-scleroderma overlap syndrome), and treatment of this syndrome is a challenge for clinicians because moderate to high doses of corticosteroids are considered a risk factor for development of acute kidney injury in affected patients. We report here the case of a 56-year-old woman with scleroderma who developed polymyositis and was successfully treated with rituximab. Initial treatment of the polymyositis with prednisolone 40 mg/day was rapidly tapered to 2.5 mg/day due to development of scleroderma renal crisis, for which four weekly infusions of rituximab (500 mg; off-label) were given. She responded well to rituximab in addition to prednisolone 2.5 mg/day. Rituximab may improve inflammatory myopathies, even in cases where high-dose corticosteroids should be avoided due to complications. Rituximab should be considered as a treatment option in cases of refractory polymyositis.

Group cognitive remediation therapy for younger adolescents with anorexia nervosa: a feasibility study in a Japanese sample.

OBJECTIVE: Cognitive remediation therapy (CRT) aims to increase patients' cognitive flexibility by practicing new ways of thinking as well as facilitating bigger picture thinking, supporting patients with relevant tasks and encouraging an awareness of their own thinking styles. CRT has been applied in the treatment of adult anorexia nervosa (AN), and has been shown to be effective and acceptable. In adolescents, CRT has been piloted on both individual and group format. However, no studies are published in CRT for adolescents with AN in a Japanese sample. The objectives of this study were to assess the feasibility, to estimate effect sizes for the purpose of designing a larger study, and to assess the acceptability of a CRT group for younger adolescents with AN in a Japanese sample. METHODS: Group CRT interventions were carried out with a total of seven adolescents with AN. Neuropsychological and psychological assessments (motivation, self-efficacy and depression) were administered before and after the group intervention. The participants completed worksheets (documents of participants' thinking about their thinking style and the relation of the skills that they learnt through each session to real-life) and questionnaires after the group. RESULTS: There were small effect sizes differences between the part of the pre and post neuropsychological tests and the pre and post ability to change (motivation). There were medium effect sizes differences between the pre and post depressive symptoms and importance to change (motivation). There was a large effect size shown between the pre and post weights. All participants were able to reflect on their own thinking styles, such as having difficulty with changing feelings and the tendency to focus on details in real-life. Adolescents' feedback was positive, and the rate of dropout was low. CONCLUSION: CRT groups could be feasible and acceptable for younger adolescents with AN in a Japanese sample. Trial registration UMIN No. 000020623. Registered 18 January 2016.

Corticoid therapy for overlapping syndromes in an HIV-positive patient.

Human immunodeficiency virus (HIV) infection disturbs the host's immune function and often coexists with various autoimmune and/or systemic rheumatic diseases with manifestations that sometimes overlap with each other. We herein present the case of a 43-year-old Japanese man infected with HIV who exhibited elevated serum creatine kinase and transaminases levels without any symptoms. He was diagnosed with autoimmune hepatitis, polymyositis and Sjögren's syndrome and received combined antiretroviral therapy (cART); however, the laboratory abnormalities persisted. We successfully administered cART with the addition of oral prednisolone, and the patient's condition recovered without side effects related to the metabolic or immunosuppressive effects of these drugs.

Sudden onset of diabetes with ketoacidosis in a patient treated with FK506/tacrolimus.

We report a 43-year-old man who presented diabetic ketoacidosis 1 year after receiving kidney transplantation. He was a recipient of renal transplantation treated with metyl-prednisolone and tacrolimus regimen. The serum level of tacrolimus was 12.4 ng/ml, and he showed hyperphagia before a month of admission. A week before admission, he was aware of polydipsia, polyuria, and general fatigue. He visited our hospital and was found to have severe hyperglycemia (925 mg/dl), significant ketosis and mild metabolic acidosis (pH 7.341), although he had not been diagnosed as diabetes mellitus. He administrated in our hospital, and was treated with insulin for 5 weeks. He was not obese (BMI = 18.2 kg/m(2)) and had no family history of type 2 diabetes. He was finally treated with diet therapy alone. The 24 h urine C-peptide secretion on the third hospital day was low (8.4 microg per day). However, no autoantibodies against pancreatic islets were positive, and his insulin secretion was recovered at discharge suggesting that he was not type 1 diabetes. Although, tacrolimus has been reported to cause or worsen diabetes mellitus, the present case suggests that it could cause severe decrease in insulin secretion which leading to diabetic ketoacidosis in lean subject without previous history of diabetes mellitus.

Ezetimibe improves glucose metabolism by ameliorating hepatic function in Japanese patients with type 2 diabetes.

UNLABELLED: Aims/Introduction: Several experimental studies have shown that ezetimibe improves steatosis and insulin resistance in the liver. This suggests that ezetimibe may improve glucose metabolism, as well as lipid metabolism, by inhibiting hepatic lipid accumulation. Therefore, we compared HbA1c levels after 3 months ezetimibe treatment with baseline levels in patients with type 2 diabetes and examined the factors associated with reductions in HbA1c following ezetimibe administration. MATERIALS AND METHODS: Lipid profiles, hepatic function, and HbA1c were assessed before and after 3 months treatment with 10 mg/day ezetimibe in 96 patients with type 2 diabetes and hypercholesterolemia. Regression analysis was used to investigate associations between metabolite levels and the percentage change in HbA1c. RESULTS: Low-density lipoprotein-cholesterol was significantly lower after 3 months treatment compared with baseline, and HbA1c decreased in approximately 50% of patients. Univariate linear regression analyses showed that changes in HbA1c were significantly associated with serum alanine aminotransferase (ALT), the aspartate aminotransferase (AST)/ALT ratio, and age. Two-tailed chi-square tests revealed that serum ALT ≥35 IU/L and an AST/ALT ratio <1.0 were significantly associated with decreases in HbA1c following ezetimibe administration. CONCLUSIONS: The results of the present study indicate that ezetimibe may improve glucose metabolism. Serum ALT levels and the AST/ALT ratio were useful predictors of a glucose metabolism response to ezetimibe. This trial was registered with UMIN (no. UMIN000005307). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00147.x, 2011).

Enhanced expression of PDX-1 and Ngn3 by exendin-4 during beta cell regeneration in STZ-treated mice.

Progenitor cells exist in the adult pancreas and transform to endocrine cells in pathological conditions. To address the mechanism of beta cell regeneration, mice were treated with streptozotocin (STZ group) or streptozotocin and exendin-4 (STZ + Ex-4 group), and the expression of PDX-1, Ngn3, insulin, IRS-2, and Foxo1 was investigated. PDX-1 mRNA was upregulated biphasically and induction of Ngn3 mRNA occurred shortly after the first increase of PDX-1 expression, a pattern similar to that observed during embryogenesis. PDX-1-positive cells appeared only in islet-like cell clusters (ICCs) in STZ group, but they appeared both in ducts and ICCs in STZ + Ex-4 group. Ngn3-positive cells emerged in ICCs but not in ducts. Therefore, regeneration seemed to occur mainly from intra-islet stem/progenitor cells. Exendin-4 upregulated PDX-1 expression which paralleled increased IRS-2 expression and translocation of Foxo1 from nucleus to cytoplasm. Further analysis of beta cell regeneration should help in the design of novel therapy for diabetes.