An optimal promoter regulating cytokine transgene expression is crucial for safe and effective oncolytic virus immunotherapy.

In general, ensuring safety is the top priority of a new modality. Although oncolytic virus armed with an immune stimulatory transgene (OVI) showed some promise, the strategic concept of simultaneously achieving maximum effectiveness and minimizing side effects has not been fully explored. We generated a variety of survivin-responsive "conditionally replicating adenoviruses that can target and treat cancer cells with multiple factors (m-CRAs)" (Surv.m-CRAs) armed with the granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene downstream of various promoters using our m-CRA platform technology. We carefully analyzed both therapeutic and adverse effects of them in the in vivo syngeneic Syrian hamster cancer models. Surprisingly, an intratumor injection of a conventional OVI, which expresses the GM-CSF gene under the constitutively and strongly active "cytomegalovirus enhancer and ß-actin promoter", provoked systemic and lethal GM-CSF circulation and shortened overall survival (OS). In contrast, a new conceptual type of OVI, which expressed GM-CSF under the cancer-predominant and mildly active E2F promoter or the moderately active "Rous sarcoma virus long terminal repeat", not only abolished lethal adverse events but also prolonged OS and systemic anti-cancer immunity. Our study revealed a novel concept that optimal expression levels of an immune stimulatory transgene regulated by a suitable upstream promoter is crucial for achieving high safety and maximal therapeutic effects simultaneously in OVI therapy. These results pave the way for successful development of the next-generation OVI and alert researchers about possible problems with ongoing clinical trials.

Benefits of Collaboration Between the Wound, Ostomy, and Continence Nurse and Orthopedic Surgeon When Treating Skin Defects After Soft Tissue Sarcoma Resection: A Retrospective Case-Control Study.

PURPOSE: The purpose of this study was to evaluate the benefits of collaborative management between orthopedic surgery and WOC nurses in patients undergoing resection of subcutaneous sarcomas. DESIGN: Retrospective case-control study. SUBJECTS AND SETTING: The sample comprised 25 patients who underwent wide resection for soft tissue sarcoma, followed by 2-stage split-thickness skin grafting. Data collection occurred between January 2015 and April 2021 in a university hospital based in Kagoshima, Japan. For comparison, we categorized these patients into 2 groups: intervention group participants were managed by an orthopedic surgeon and a WOC nurse; nonintervention group members were managed without WOC nurse participation. METHODS: Patient background and treatment-related information was retrospectively collected from medical records and compared between the WOC nurse intervention group and the nonintervention group, including maximum tumor diameter, surgical time, maximum skin defect diameter, length of hospital stay, and time from surgery to complete wound healing. RESULTS: The average length of hospital stay was significantly shorter in the WOC nurse intervention group compared with the nonintervention group (38.3 days, SD = 8.0 vs 47.1 days, SD = 10.2; P = .023). CONCLUSION: Collaborative wound management with a WOC nurse resulted in a shorter hospital length of stay when compared to traditional management with WOC nurse involvement. Based on these findings, we assert that WOC nurses provide an important bridge between postoperative wound management in patients undergoing resection of subcutaneous sarcomas.

Association between Regular Exercise and Self-Rated Health and Sleep Quality among Adults in Japan during the COVID-19 Pandemic.

Regular exercise may be associated with better self-rated health and sleep status. However, this correlation among various age groups, such as young, middle-aged, and older people, as well as during the COVID-19 pandemic, has not been examined. This study examined the correlation between regular exercise and self-rated health and sleep quality among adults in Japan during the COVID-19 pandemic. Data were collected using an online survey conducted between February 26 and 27, 2021. A total of 1410 adults in Japan (age range, 20-86 years) completed the online survey. Regular exercise was divided into: (1) more than 30 min of moderate exercise a day, (2) more than 2 days per week, and (3) continuous for 1 year or longer. Self-rated health and sleep quality were assessed using the Likert scale. After adjusting for multiple confounders, regular exercise was correlated with decreased poor self-rated health and poor sleep quality in middle-aged adults; however, no significant correlation was observed among young and older adults. The promotion of regular exercise among middle-aged people during the COVID-19 pandemic may contribute to better self-rated health and sleep quality status.

Normal aging induces PD-1-enriched exhausted microglia and A1-like reactive astrocytes in the hypothalamus.

Hypothalamic aging is considered to be critical for systemic aging, and the accumulation of "exhausted glial cells" in the hypothalamus may contribute to brain dysfunction. In this study, we used normal aging mice and investigated aging-specific transcriptional identities of microglia and astrocytes in the hypothalamus. We confirmed that normal aging promoted anxiety, induced impairment of motor coordination and reduced physical strength of muscle in mice. To investigate the senescence of hypothalamic glial cells, we isolated CD11b-positive microglia and ACSA-2-positive astrocytes from the hypothalamus of aged mice using magnetic-activated cell sorting (MACS). The mRNA level of p16INK4A was dramatically increased in the hypothalamic microglia of aged mice compared to young mice. Furthermore, the expression of programmed cell death 1 (PD-1) as well as A1-like astrocyte mediators in the hypothalamic microglia was dramatically induced by aging, indicating that normal aging may produce PD-1-enriched "exhausted microglia" in the hypothalamus. Furthermore, neuroinflammatory A1-like reactive astrocytes with a p16INK4A-positive senescent state were predominantly detected in the hypothalamus of aged mice. Exhausted microglia were also detected in the prefrontal cortex of aged mice, whereas astrocytic neuroinflammation was milder than that observed in the hypothalamus, even with p16INK4A-positive senescence. These results suggest that the production of PD-1-enriched exhausted and senescent microglia and neuroinflammatory A1-like reactive astrocytes in the hypothalamus may partly contribute to aging-related emotional and physical dyscoordination.

Neurotensin receptor 1 is a new therapeutic target for human undifferentiated pleomorphic sarcoma growth.

Undifferentiated pleomorphic sarcoma (UPS) is the second most common soft tissue sarcoma. For patients with unresectable or metastatic disease, chemotherapies are considered, but in many cases they are not curative. There is a need to identify specific molecular dysregulations that can be therapeutic targets. We focused on neurotensin receptor 1 (NTSR1), which belongs to the G-protein-coupled receptor. NTSR1 expression was upregulated in specimens from patients with UPS. Real-time polymerase chain reaction showed that expression of NTSR1 messenger RNA was 5- to 7-fold increased in UPS cells compared with myoblasts. Western blot showed a high expression of NTSR1 protein in UPS cell lines. Knockdown of NTSR1 prevented UPS cell proliferation and invasion. We confirmed that SR48692, an inhibitor of NTSR1, exhibited antitumor activities in UPS cells. The combination index showed that SR48692 and standard chemotherapeutic drugs prevented UPS cell proliferation synergistically. Mouse xenograft models showed that SR48692 inhibited extracellular signal-regulated kinase phosphorylation and enhanced the response to standard chemotherapeutic drugs. Inhibition of NTSR1 improved the effect of standard chemotherapeutic drugs for UPS. SR48692 may be a new drug for targeted UPS therapy.

Tranilast enhances the effect of anticancer agents in osteosarcoma.

Tranilast [N­(3',4'­dimethoxycinnamoyl)­anthranilic acid], initially developed as an antiallergic drug, also exhibits a growth inhibitory effect on various types of cancer. Osteosarcoma is treated mainly with high­dose methotrexate, doxorubicin, cisplatin and ifosfamide; however, 20­30% of patients cannot be cured of metastatic disease. We investigated whether tranilast enhances the anticancer effects of chemotherapeutic drugs and analyzed its mechanism of action in osteosarcomas. Tranilast inhibited proliferation of HOS, 143B, U2OS and MG­63 osteosarcoma cells in a dose­dependent manner, as well as enhancing the effects of cisplatin and doxorubicin. The average combination index at effect levels for tranilast in combination with cisplatin was 0.57 in HOS, 0.4 in 143B, 0.39 in U2OS and 0.51 in MG­63 cells. Tranilast and cisplatin synergistically inhibited the viability of osteosarcoma cells. In flow cytometric analysis, although tranilast alone did not induce significant apoptosis, the combination of tranilast and cisplatin induced early and late apoptotic cell death. Expression of cleaved caspase­3, cleaved poly(ADP­ribose) polymerase and p­H2AX was enhanced by tranilast in combination with cisplatin. Tranilast alone increased expression of p21 and Bim protein in a dose­dependent manner. Cell cycle analysis using flow cytometry demonstrated that the combination of tranilast and cisplatin increased the number of cells in the G2/M phase. Compared with cisplatin alone, the combination increased levels of phospho­cyclin­dependent kinase 1 (Y15). In the 143B xenograft model, tumor growth was significantly inhibited by combined tranilast and cisplatin compared with the controls, whereas cisplatin alone did not significantly inhibit tumor growth. In conclusion, tranilast has a cytostatic effect on osteosarcoma cells and enhances the effect of anticancer drugs, especially cisplatin. Enhanced sensitivity to cisplatin was mediated by increased apoptosis through G2/M arrest. Since tranilast has been clinically approved and has few adverse effects, clinical trials of osteosarcoma chemotherapy in combination with tranilast are expected.

Synergistic effect of arsenic trioxide, vismodegib and temozolomide on glioblastoma.

The treatment of glioblastoma is a critical health issue, owing to its resistance to chemotherapy. The current standard of treatment is surgical resection, followed by adjuvant radiotherapy and temozolomide treatment. Long­term local treatment of glioblastoma is rarely achieved and the majority of the patients undergo relapse. Resistance to temozolomide emerges from numerous signalling pathways that are altered in glioblastoma, including the Hedgehog signalling pathway. Hence, further research is required to identify effective treatment modalities. We investigated the effect of vismodegib, arsenic trioxide and temozolomide on glioblastoma in vitro and in vivo to apply our findings to the clinical setting. WST­1 assay revealed that glioblastoma proliferation was inhibited following treatment with these drugs either in single or in combination; this synergistic effect was confirmed by CalcuSyn software. Western blot analysis revealed an increase in the expression of cleaved caspase­3 and γH2AX. Furthermore, there was marked inhibition and decreased tumour growth in mice that received combination therapy, unlike those that received single agent or vehicle treatment. Our results revealed that the combination of arsenic trioxide/vismodegib and temozolomide may be an attractive therapeutic method for the treatment of glioblastoma.

TGF-ß Promotes the Proliferation of Microglia In Vitro.

The activation and proliferation of microglia is characteristic of the early stages of brain pathologies. In this study, we aimed to identify a factor that promotes microglial activation and proliferation and examined the in vitro effects on these processes. We cultured microglial cell lines, EOC 2 and SIM-A9, with various growth factors and evaluated cell proliferation, death, and viability. The results showed that only transforming growth factor beta (TGF-ß) caused an increase in the in vitro proliferation of both microglial cell lines. It has been reported that colony-stimulating factor 1 promotes the proliferation of microglia, while TGF-ß promotes both proliferation and inhibition of cell death of microglia. However, upon comparing the most effective doses of both (assessed from the proliferation assay), we identified no statistically significant difference between the two factors in terms of cell death; thus, both have a proliferative effect on microglial cells. In addition, a TGF-ß receptor 1 inhibitor, galunisertib, caused marked inhibition of proliferation in a dose-dependent manner, indicating that inhibition of TGF-ß signalling reduces the proliferation of microglia. Therefore, galunisertib may represent a promising therapeutic agent for the treatment of neurodegenerative diseases via inhibition of nerve injury-induced microglial proliferation, which may result in reduced inflammatory and neuropathic and cancer pain.

PEG10 counteracts signaling pathways of TGF-ß and BMP to regulate growth, motility and invasion of SW1353 chondrosarcoma cells.

Recently, we reported highly active transforming growth factor (TGF)-ß and bone morphogenetic protein (BMP) signaling in human chondrosarcoma samples and concurrent downregulation of paternally expressed gene 10 (PEG10). PEG10 expression was suppressed by TGF-ß signaling, and PEG10 interfered with the TGF-ß and BMP-SMAD pathways in chondrosarcoma cells. However, the roles of PEG10 in bone tumors, including chondrosarcoma, remain unknown. Here, we report that PEG10 promotes SW1353 chondrosarcoma cell growth by preventing TGF-ß1-mediated suppression. In contrast, PEG10 knockdown augments the TGF-ß1-induced motility of SW1353 cells. Individually, TGF-ß1 and PEG10 siRNA increase AKT phosphorylation, whereas an AKT inhibitor, MK2206, mitigates the effect of PEG10 silencing on cell migration. SW1353 cell invasion was enhanced by BMP-6, which was further increased by PEG10 silencing. The effect of siPEG10 was suppressed by inhibitors of matrix metalloproteinase (MMP). BMP-6 induced expression of MMP-1, -3, and -13, and PEG10 lentivirus or PEG10 siRNA downregulated or further upregulated these MMPs, respectively. PEG10 siRNA increased BMP-6-induced phosphorylation of p38 MAPK and AKT, whereas the p38 inhibitor SB203580 and MK2206 diminished SW1353 cell invasion by PEG10 siRNA. SB203580 and MK2206 impeded the enhancing effect of PEG10 siRNA on the BMP-6-induced expression of MMP-1, -3, and -13. Our findings suggest dual functions for PEG10: accelerating cell growth by suppressing TGF-ß signaling and inhibiting cell motility and invasion by interfering with TGF-ß and BMP signaling via the AKT and p38 pathways, respectively. Thus, PEG10 might be a molecular target for suppressing the aggressive phenotypes of chondrosarcoma cells.

The histone deacetylase inhibitor LBH589 inhibits undifferentiated pleomorphic sarcoma growth via downregulation of FOS-like antigen 1.

Undifferentiated pleomorphic sarcoma (UPS) is the second most frequent soft tissue sarcoma. Because of its resistance to chemotherapy, UPS patients are treated with surgical resection and complementary radiotherapy. However, since standard chemotherapy has not been established, unresectable or metastatic cases result in a poor prognosis. Therefore, the identification of a more effective therapy for UPS patients is needed. The development and progression of malignant tumors involve epigenetic alterations, and histone deacetylases (HDAC) have become a promising chemotherapeutic target. In this study, we investigated the potential effects and mechanisms of an HDAC inhibitor, LBH589, in UPS cells. We confirmed that LBH589 exhibits potent antitumor activities in four human UPS cell lines (GBS-1, TNMY-1, Nara-F, and Nara-H) and IC50 values ranged from 7 to 13 nM. A mouse xenograft model showed that LBH589 treatment effectively suppressed tumor growth. FACS analysis showed that LBH589 induced apoptosis and G2/M cell cycle arrest. Among apoptosis-related proteins, the expressions of Bcl-2 and Bcl-xL were decreased and the expression of Bak and Bim increased. Among cell cycle-related proteins, reductions of CDK1, p-CDK1, cyclin B1, Aurora A, and Aurora B were observed after LBH589 treatment. RNA microarray identified the FOS-like antigen 1 (FOSL1) gene as a downregulated gene in response to LBH589 in UPS cells. While knockdown of FOSL1 decreased UPS cell proliferation, overexpression induced cell proliferation. Our results show that LBH589 could be a promising chemotherapeutic agent in the treatment of UPS and downregulation of the FOSL1 gene could be the new molecular target of UPS treatment.

Risk Factors for Surgical Site Infection after Soft-Tissue Sarcoma Resection, Including the Preoperative Geriatric Nutritional Risk Index.

Malignant soft-tissue sarcoma resection is associated with a relatively high incidence of surgical site infection (SSI). The known risk factors for SSI following soft-tissue sarcoma resection include tumor size and location, prolonged surgery, and massive blood loss. The geriatric nutritional risk index (GNRI) was used as a tool to help predict the occurrence of SSI after major surgery. We investigated the utility of the GNRI as a predictor of SSI following soft-tissue sarcoma resection. We retrospectively reviewed 152 patients who underwent surgical resection of soft-tissue sarcoma in our institute, and found that the incidence of SSI was 18.4% (28/152). The SSI and non-SSI groups significantly differed regarding surgical time, diameter of the skin incision, maximum tumor diameter, instrumentation, presence of an open wound, preoperative chemotherapy, preoperative C-reactive protein concentration, and GNRI. Binomial logistic regression analysis showed that the risk factors for SSI following soft-tissue sarcoma surgery were male sex, larger skin incision diameter, larger maximum tumor diameter, presence of an open wound, and lower GNRI. Our findings indicate that malnutrition is a risk factor for SSI after soft-tissue sarcoma resection, and suggest that appropriate assessment and intervention for malnutrition may reduce the incidence of SSI.

Association between bone mineral density, muscle volume, walking ability, and geriatric nutritional risk index in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Hemodialysis patients are at risk for bone loss and sarcopenia, characterized by reduced muscle mass and limited mobility/function. Osteoporosis and sarcopenia both increase the risk of hospitalization and death in affected individuals. Malnutrition also occurs as a complication of hemodialysis and has been identified as a risk factor for osteoporosis and sarcopenia. In this study, we examined the relationship between osteoporosis, muscle volume, walking ability, and malnutrition in hemodialysis patients. METHODS AND STUDY DESIGN: Forty-five hemodialysis patients were evaluated. Bone mineral density (BMD) and muscle volume were measured by dual-energy X-ray absorptiometry. Muscle volume and strength were evaluated using lean mass index (LMI), handgrip strength, and walking ability. The time required for a patient to walk 10 meters was measured to evaluate walking ability. The geriatric nutritional risk index (GNRI) was used to assess malnutrition. RESULTS: Multiple linear regression analysis showed that older age, female sex, lower LMI, and higher total type I procollagen N-terminal propeptide were correlated with lower BMD of lumbar spine. Higher age and lower LMI were correlated with lower BMD of the femoral neck. Female sex and lower GNRI were correlated with lower LMI. Longer duration of hemodialysis was correlated with lower walking ability. CONCLUSIONS: Our findings suggest that muscle preservation is required to maintain both lumbar spine and femoral neck BMD. Similarly, nutritional management is necessary to maintain BMD via preservation of muscle volume. Complementary nutritional therapies are needed to improve osteoporosis and sarcopenia in high-risk hemodialysis patients.

Clinical outcomes of arthroscopic rotator cuff repair: a retrospective comparison of double-layer, double-row and suture bridge methods.

BACKGROUND: The suture-bridge (SB) method has recently become the mainstream means of repairing full-thickness rotator cuff tears. However, in some patients the deep and superficial layers have moved in different directions because of delamination of their rotator cuffs. In such cases, a simple suture (double-layer, double-row [DD] method) is used to repair the superficial and deep layers separately. The purpose of this study was to analyze the clinical outcomes and re-tear rates of the DD and SB methods, with patients selected according to the condition of their torn cuffs. METHODS: We retrospectively registered 74 patients with full-thickness rotator cuff tears that had been repaired arthroscopically, 35 shoulders by the DD and 39 by the SB method. Mean ages were 66.1 years in the DD and 62.9 years in the SB group. We evaluated clinical status before and after surgery (Japanese Orthopedic Association [JOA] scores) and re-tear rate. The Wilcoxon signed-ranks test was used to compare JOA scores and active ROM between before and after surgery in each group. Mann-Whitney's U test was used for comparing JOA scores, active ROM, re-tear rates, size of tear, duration of follow-up, sex, and presence of subscapular muscle repair between the DD and SB groups. A hazard ratio of less than 5% was considered to denote significance. RESULTS: JOA scores improved significantly in the DD and SB groups from preoperative means of 63.4 and 63.3 points, respectively, to postoperative means of 91.8 and 92.1 points, respectively. The active flexural ROM improved significantly from means of 110.1° and 100.0°, respectively, to postoperative means of 142.3° and 142.7°, respectively; the differences between groups were not significant. Re-tear occurred in 5.9% of the DD (two of 34 shoulders) and 7.9% of the SB group (three of 38 shoulders); its incidence did not differ significantly between the two groups. CONCLUSIONS: Both the DD and SB methods achieve satisfactory clinical outcomes that do not differ significantly. Our results suggest that careful selection of operative method on the basis of the delamination pattern in patients undergoing RCT may reduce the re-tear rate after utilizing the SB method.

Validation of Different Nutritional Assessment Tools in Predicting Prognosis of Patients with Soft Tissue Spindle-Cell Sarcomas.

Predicting outcomes in patients with soft tissue sarcoma (STS) is challenging. To improve these predictions, we retrospectively analyzed common nutritional assessment systems, including Glasgow prognostic score (GPS), Geriatric Nutritional Risk Index (GNRI), neutrophil⁻lymphocyte ratio (NLR), platelet⁻lymphocyte ratio (PLR), and controlling nutritional (CONUT) score against outcomes in 103 patients with STS, of whom 15 (14.6%) died within 1 year of diagnosis. GPS, GNRI, NLR, PLR, and CONUT scores significantly differed between patients who died within one year and patients who lived longer. Binomial logistic regression analysis showed that male sex, older age at diagnosis, higher GPS, higher stage, and unresectable STS were risk factors for death within a year of diagnosis. Overall survival was evaluated by Cox proportional hazards models, which correlated higher NLR, higher PLR, larger maximum diameter of tumor, higher stage, and unresectable STS with poor prognosis. We next examined prognostic factors in the 93 patients with resectable STS, and found male sex, higher GPS, and higher stage were correlated with poor prognosis in these patients. Our findings suggest that GPS, NLR, and PLR are simple predictors of outcome in patients with STS. Nutritional therapies might improve their GPS and prognosis.

Utility of intraoperative monitoring with motor-evoked potential during the surgical enucleation of peripheral nerve schwannoma.

Although it is thought that the surgical enucleation of schwannomas can be easily performed, certain patients present with postoperative neurological symptoms. The present study examined the utility of intraoperative motor-evoked potential (MEP) in predicting neurological deficits following the surgical enucleation of peripheral nerve schwannoma. The current study included 23 patients and MEP was performed using transcranial electrical stimulation. In three cases, the MEP decreased to <50% of the preoperative value; however, in two cases that involved the peroneal nerve and tibial nerve, results appeared to be false positives induced by a tourniquet during surgery. In another case, the MEP was completely lost following enucleation of the tumor from the sciatic nerve, which recovered to 61% of the original MEP within 10 min. This patient presented with common peroneal palsy postoperatively. By contrast, another case involving the lumbar nerve root and in which there was reversible postoperative motor loss, the MEP did not change intraoperatively. Postoperative neurological deficit occurred in 22% of patients in the present study, which is similar to that of previous reports. The present study also demonstrated that even if a nerve is not transected or injured, traction or compression of a peripheral nerve may induce ischemia, which can be monitored using MEP. Although MEP alone was not able to predict postoperative transient sensory or motor deficits, the combination of MEP with other methods of neurological monitoring may improve accuracy and should be investigated in future studies.

Lumbar spine epidural abscess and facet joint septic arthritis due to Streptococcus agalactiae: a case report.

BACKGROUND: Here we report a rare case of lumbar spine epidural abscess and facet joint septic arthritis caused by Streptococcus agalactiae, which had spread to the iliopsoas muscles, leading to urine retention. CASE PRESENTATION: A 68-year-old woman with low back pain experienced a sudden onset of bilateral lower limb weakness, it was followed 14 days later by urine retention. At consultation, magnetic resonance imaging and identification of serum ß-hemolytic streptococci provided a diagnosis of Streptococcus agalactiae infection. She was started on antibiotics. Despite diminishing signs of inflammation, preoperative MRI showed an epidural mass at T12-L4 compressing the cord and involving the paravertebral muscles as well. Group B beta-hemolytic streptococci were detected in both urine and blood. Because of bilateral lower limb weakness and urine retention, T12-L4 hemilaminectomy was performed. The L3/L4 intertransverse ligament resected and abscess drained. Histopathology revealed that inflammatory cells had invaded the facet joint. Group B beta-hemolytic streptococci were identified, confirming the diagnosis. The patient continued with the antibiotics postoperatively, and her health rapidly improved. CONCLUSION: Lumbar spine epidural abscess and facet joint septic arthritis caused by Streptococcus agalactiae is a clinical emergency, with significant morbidity and mortality especially with delayed diagnosis. A delay in both diagnosis and aggressive treatment can lead to not only severe neurological deficit but also to septicaemia, multiorgan failure, and even death.

Hypertrophic spinal pachymeningitis associated with human T-cell lymphotrophic virus-1 infection and Sjogren's syndrome: A case report and brief literature review.

INTRODUCTION: Reports of hypertrophic spinal pachymeningitis associated with human T-cell lymphotrophic virus-1 (HTLV-1) infection and Sjogren's syndrome in the English literature are still very rare. PRESENTATION OF CASE: We hereby present a case of a 78-year-old female with a history of lower extremity weakness after a fall, which fully resolved after conservative treatment. However, the symptoms recurred 4 years later, and the patient became unable to walk. The patient had no superficial or deep sensation below the level of T9, and she also had urinary retention. Magnetic resonance imaging showed that hypertrophic dura mater was compressing the spinal cord from T2 to T10. Blood testing revealed increased anti-HTLV-1 antibody, rheumatoid factor, elevation of anti-SS-A antibody and antinuclear antibody. The cerebrospinal fluid contained markedly elevated levels of total protein and cell numbers. Biopsy of the labial gland of the lip revealed chronic sialadenitis. DISCUSSION: In collaboration with a neurologist, we diagnosed this patient with hypertrophic spinal pachymeningitis associated with HTLV-1 infection and Sjogren's syndrome. We performed laminectomy at the affected spinal levels, resected the thickened dura, and maintained the patient on steroid therapy. The patient attained a marked recovery; she could walk with a cane and her urinary retention was improved. CONCLUSION: For the management of HSP associated with HTLV-1 and SS, we recommend surgical decompression with subsequent prolonged steroid therapy and prolonged close monitoring to achieve a good long-term outcome.

Whole-tumor apparent diffusion coefficient (ADC) histogram analysis to differentiate benign peripheral neurogenic tumors from soft tissue sarcomas.

BACKGROUND: Apparent diffusion coefficient (ADC) histogram analyses have been used to differentiate tumor grades and predict therapeutic responses in various anatomic sites with moderate success. PURPOSE: To determine the ability of diffusion-weighted imaging (DWI) with a whole-tumor ADC histogram analysis to differentiate benign peripheral neurogenic tumors (BPNTs) from soft tissue sarcomas (STSs). STUDY TYPE: Retrospective study, single institution. SUBJECTS: In all, 25 BPNTs and 31 STSs. FIELD STRENGTH/SEQUENCE: Two-b value DWI (b-values = 0, 1000s/mm2 ) was at 3.0T. ASSESSMENT: The histogram parameters of whole-tumor for ADC were calculated by two radiologists and compared between BPNTs and STSs. STATISTICAL TESTS: Nonparametric tests were performed for comparisons between BPNTs and STSs. P < 0.05 was considered statistically significant. The ability of each parameter to differentiate STSs from BPNTs was evaluated using area under the curve (AUC) values derived from a receiver operating characteristic curve analysis. RESULTS: The mean ADC and all percentile parameters were significantly lower in STSs than in BPNTs (P < 0.001-0.009), with AUCs of 0.703-0.773. However, the coefficient of variation (P = 0.020 and AUC = 0.682) and skewness (P = 0.012 and AUC = 0.697) were significantly higher in STSs than in BPNTs. Kurtosis (P = 0.295) and entropy (P = 0.604) did not differ significantly between BPNTs and STSs. DATA CONCLUSION: Whole-tumor ADC histogram parameters except kurtosis and entropy differed significantly between BPNTs and STSs. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Association between Bone Mineral Density of Femoral Neck and Geriatric Nutritional Risk Index in Rheumatoid Arthritis Patients Treated with Biological Disease-Modifying Anti-Rheumatic Drugs.

Treatment of rheumatoid arthritis (RA) with biological disease-modifying anti-rheumatic drugs (bDMARDs) induces rapid remission. However, osteoporosis and its management remains a problem. The Geriatric Nutritional Risk Index (GNRI) evaluates the risk of malnutrition-related complications in elderly patients and has been shown to be a significant predictor of many diseases. We evaluated the correlation between GNRI and RA activity. In addition, risk factors for femoral neck bone loss were evaluated in RA patients treated with bDMARDs. We retrospectively examined the medical records of 146 patients with RA, collecting and recording the patients' demographic and clinical characteristics. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Inverse correlations were observed between GNRI and disease duration, disease activity score-28 joint count serum C-reactive protein (CRP), simple disease activity index, modified health assessment questionnaire score and CRP. GNRI showed correlation with femoral neck BMD and femoral neck BMD ≤ 70% of young adult men (YAM). Multiple regression analysis showed that female sex, increased age and lower GNRI were risk factors for lower BMD of the femoral neck. Multivariate binomial logistic regression analysis showed that female sex (odd ratio: 3.67) and lower GNRI (odd ratio: 0.87) were risk factors for BMD ≤ 70% of YAM. Because the GNRI is a simple method, it might be a simple predictor for RA activity and BMD status in RA patients. Complementary nutritional therapies might improve RA activity and osteoporosis in RA patients who have undergone treatment with bDMARDs.