Bioelectrical impedance analysis-derived phase angle as a determinant of protein-energy wasting and frailty in maintenance hemodialysis patients: retrospective cohort study.

BACKGROUND: Phase angle (PA), measured by bioelectrical impedance analysis (BIA) has been studied as indicator of nutritional status or muscle function in hemodialysis (HD) patients. It remains unclear if the phase angle is associated protein-energy wasting (PEW) or frailty, which are common complication in hemodialysis patients. The aim of this study is to determine whether BIA-derived PA is a marker of PEW or frailty in HD patients. METHODS: This retrospective observational study included 116 adult HD patients (35% female, 64 ± 12 years of age) in a single dialysis center. Patients were classified according to the PA quartiles into four groups; 1) first quartile: PA < 3.7°, 2) second quartile: PA 3.7-4.1°, 3) third quartile: PA 4.2-4.9°and 4) forth quartile: PA ≥ 5.0°. International Society of Renal Nutrition and Metabolism (ISRNM) criteria and Japanese version of Cardiovascular Health Study (J-CHS) criteria were used to identify PEW and frailty. RESULTS: The lower PA group was associated with a greater risk of PEW (35% vs. 24% vs. 21% vs. 3%; p = 0.032), frailty (59% vs. 40% vs. 21% vs. 3%; p < 0.001). In multivariate logistic regression analysis, the first quartile group was at a significantly greater risk of both PEW and frailty compared with the fourth quartile group after adjusting for other confounding factors. CONCLUSIONS: Lower PA was associated with a greater risk of PEW and frailty in HD patients.

A case report of cutaneous melanocytoma with CRTC1-TRIM11 fusion: Is CMCT distinct from clear cell sarcoma of soft tissue?

Pathological diagnosis of dermal melanocytic tumors is often problematic owing to histological resemblance. Recently, cutaneous melanocytoma with CRTC1-TRIM11 (CMCT) was added to this category. However, only six cases have been reported so far. We herein present a case of a 77-year-old Japanese man with CMCT. The patient presented a nodule in the right thigh and underwent surgical resection. Histological examination indicated a well-demarcated 6 × 5 mm-sized tumor nodule in the dermis and subcutis. The tumor was amelanotic, consisting of uniform nests and fascicles of spindled, or epithelioid cells. The melanocytic nature was evident by immunohistochemistry. The CRTC1-TRIM11 fusion was detected by TRIM11 immunostaining, chromogenic in situ hybridization, and RT-PCR/direct sequencing. He has been free from the tumor for 1 year after additional resection. The main differential diagnosis of CMCT includes primary and metastatic dermal malignant melanomas (MM) and dermal/subcutaneous clear cell sarcoma (CCS). Additionally, histological overlap with paraganglioma-like dermal melanocytic tumor was considered. Although some investigators argue that CMCT is a variant of CCS, we think it should be separated from CCS, and subcutaneous/dermal CCS should be confined to tumors with EWSR1-ATF1/ CREB1 fusion. However, longer follow-up and more case studies are needed for revealing the true prognosis of CMCT.

Falsely elevated plasma ACTH levels measured by the Elecsys assay related to heterophilic antibody in a case of secondary adrenocortical insufficiency.

A 49-year-old woman with membranous nephropathy was referred to our hospital during the tapering of oral prednisolone, because of suspicion of primary adrenal insufficiency based on a plasma ACTH level of 399.1 pg/mL in the Elecsys assay and a serum cortisol level of 3.1 µg/dL. A rapid ACTH stimulation test revealed a suboptimal response, whereas a prolonged ACTH simulation test showed a sufficient increase in her urinary free cortisol. Also, big ACTH was not detected by gel exclusion chromatography. Therefore, we speculated that ACTH levels were falsely elevated due to some interference substances. Pretreatment of her plasma with either polyethylene glycol precipitation or a heterophilic blocking tube substantially reduced her ACTH values. When either the Immulite ACTH II or the TOSOH II ACTH was tried instead of the Elecsys ACTH, her plasma ACTH values turned out to be lower and appropriate for her clinical status. These results indicated that heterophilic antibodies interfered only with the Elecsys ACTH assay presumably by bridging the capture and tracer antibodies. To our knowledge, this is the first case in which the Elecsys ACTH assay yielded falsely elevated results. Regardless of the measurement system used, if there is a discordance between assay results and clinical findings, it should be considered to adopt additional procedures and/or another assay.

Osteomyelitis and pyomyositis due to Staphylococcus aureus in an osteomalacic adult with multiple fractures.

Multifocal osteomyelitis and pyomyositis usually arise from hematogenous dissemination, especially in patients with immunodeficiency, trauma, or injection drug abuse. We report the case of a 75-year-old man with multifocal pyomyositis and osteomyelitis, which were due to Staphylococcus aureus and were presumably related to multiple fractures. The patient had no risk factors for these hematogenous infections. He was treated with antibiotic therapy for about 80 days and drainage of the abscesses. Regarding the cause of his multipe fractures, he was found to have hypophosphatemia and eventually diagnosed as osteomalacia. To our best knowledge, this case was the first report on multifocal osteomyelitis and pyomyositis around the fracture sites in an osteomalacic adult. Osteomalacia should be considered as one of the differential diagnoses when osteoarticular infection with multifocal fractures is detected.

CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic Targets.

CD70 - a ligand protein of CD27 on lymphocytes - is expressed in a large spectrum of malignancies. It is an attractive target for antibody-based therapy and several clinical trials are currently being conducted. However, there is no evidence regarding the expression of CD70 and its relationship with expression of programmed death ligand-1 (PD-L1) and CD27+ tumor-infiltrating lymphocytes (TIL) in formalin-fixed paraffin-embedded (FFPE) tissues of thymic tumors. FFPE tissues of thymic squamous cell carcinoma (TSCC) (operative specimens, n = 31; biopsy specimens, n = 11), thymoma (n = 60), thymic carcinoid (n = 3), and lung squamous cell carcinoma (LSCC) (n = 30) were analyzed immunohistochemically. Immunoreactivity for CD70 was semi-quantitatively scored according to the proportion of positive tumor cells. Moreover, the densities of CD27-positive intratumoral TIL (iTIL) and stromal TIL of TSCC were assessed and survival was compared. Most TSCC cases (87%; 27/31) were CD70-positive. In contrast, all thymoma and thymic carcinoid cases were CD70-negative. In LSCC cases, CD70-positivity was significantly lower than TSCC cases (20%; 6/30). Biopsy and resected specimens obtained from the same patients demonstrated a consistent staining pattern (6/6 patients). The proportion of CD70-positive TSCC was comparable with those of CD5 (87%) and CD117 (90%). Correlation between CD70 and PD-L1 expression score was observed. There was no significant difference in survival between the CD70-high and CD70-low expression groups. Meanwhile, patients with CD27-positive iTIL-high tumors exhibited better survival than those with iTIL-low tumors. This tendency was weaker in the CD70-high subset. CD70 immunohistochemistry is useful in diagnosing TSCC. CD70 may prevent anti-tumor immunity via CD27. Immunotherapy targeting the CD70-CD27 axis may be a promising option for the treatment of TSCC.

Correlation between anti-thyroid peroxidase antibody levels and diffuse thyroid uptake of 18F-fluorodeoxyglucose in Hashimoto's thyroiditis: a retrospective study.

BACKGROUND: On 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET), diffuse uptake in the thyroid gland is often observed in patients with Hashimoto's thyroiditis. In this study, we evaluated the factors associated with diffuse uptake by comparing Hashimoto's thyroiditis patients with or without diffuse uptake in the thyroid. METHODS: A retrospective study was conducted of 18 patients with Hashimoto's thyroiditis who underwent blood tests, thyroid ultrasonography, and FDG-PET during the period from 2014 to 2015. The patients were divided into two groups: one with diffuse thyroid uptake (group 1, n = 13) and one without diffuse thyroid uptake (group 2, n = 5). Clinical and laboratory parameters, including maximum standardized uptake in the thyroid (SUVmax), which was defined as the higher value obtained in either the right or left thyroid lobe, were compared in the two groups. RESULTS: The frequency of abnormal findings, such as a rough or heterogeneous pattern, was significantly higher in group 1 (p <  0.01), as were anti-thyroid peroxidase (TPO) antibody titers, anti-thyroglobulin (Tg) antibody titers, and SUVmax (p <  0.01). The frequency of hypothyroidism did not differ significantly in the two groups. Anti-TPO and anti-Tg titers were positively correlated with SUVmax (r = 0.856, p <  0.01 and r = 0.821, p <  0.01, respectively); in univariate analysis, anti-TPO titer was predictive of SUVmax (p <  0.01). CONCLUSIONS: The results of the current study suggest that Hashimoto's thyroiditis patients with high titers of anti-thyroid antibodies are likely to exhibit intense diffuse FDG uptake in the thyroid, and that thyroid function may be clearly impaired, even in the presence of mild FDG uptake in the thyroid.

Effects of Intradialytic Resistance Exercise on Protein Energy Wasting, Physical Performance and Physical Activity in Ambulatory Patients on Dialysis: A Single-Center Preliminary Study in a Japanese Dialysis Facility.

Patients under hemodialysis present protein-energy wasting (PEW), which is related with higher mortality rates. The study aimed to determine whether intradialytic resistance exercise training could improve physical performance, physical activity, and PEW in hemodialysis patients. In single center study, 75 hemodialysis patients were enrolled in an intradialytic resistance exercise training consisting of 20 min of adapted leg press, with a gymnastic ball, 3 days/week, during 9 months on the same day of hemodialysis therapy. Physical performance by short physical performance battery (SPPB), physical activity by life space assessment (LSA), and PEW score based on the nomenclature proposed by the International Society of Renal Nutrition and Metabolism in 2008 were assessed at baseline and after 9 months. Intradialytic resistance exercise training significantly improved SPPB score, LSA score, and PEW score (all, P < 0.05). In addition, intradialytic resistance exercise training improved SPPB score in patients with moderate and severe PEW subgroups (P < 0.05), associated with reduced prevalence of the patients with moderate to severe PEW (53% vs. 36%, P < 0.05). Intradialytic resistance exercise training was safe and effective to improve physical performance, physical activity, and PEW in hemodialysis patients.

Predictive significance of thyroid transcription factor-1 expression in patients with non-squamous non-small cell lung cancer with wild-type epidermal growth factor receptor treated with erlotinib.

Little is known on the efficacy of erlotinib treatment in patients expressing wild-type epidermal growth factor receptor (EGFR). This study is a retrospective review of patients with non-squamous, non-small-cell lung cancer (NS-NSCLC) and wild-type EGFR who were treated with erlotinib alone as second- or later-line chemotherapy at the Tokyo Metropolitan Cancer and Infectious Diseases Center of Komagome Hospital (Tokyo, Japan) between December, 2008 and December, 2013. Thyroid transcription factor-1 (TTF-1) was immunohistochemically analyzed in 26 of 53 patients, among whom 20 (77%) and 6 (23%) were considered as TTF-1-positive and -negative, respectively. The median follow-up of these 26 patients was 133 days (range, 26-873 days). The time-to-treatment failure was significantly longer in TTF-1-positive compared with that in TTF-1-negative patients [49.5 vs. 20.0 days; 95% confidence interval (CI): 28-90 vs. 14-74 days, respectively; P=0.01]. The overall survival was significantly better for TTF-1-positive (227 days; 95% CI: 110-366 days) compared with TTF-1-negative patients (P=0.0002). Therefore, the expression of TTF-1 may serve as a useful tool for predicting the efficacy of erlotinib in patients with NS-NSCLC expressing wild-type EGFR.