Clinical and molecular features of patients with IDH1 wild-type primary glioblastoma presenting unexpected short-term survival after gross total resection.

BACKGROUND: This study investigated the factors influencing short-term survivors (STS) after gross total resection (GTR) in patients with IDH1 wild-type primary glioblastoma. METHODS: We analyzed five independent cohorts who underwent GTR, including 83 patients from Kitasato University (K-cohort), and four validation cohorts of 148 patients from co-investigators (V-cohort), 66 patients from the Kansai Molecular Diagnosis Network for the Central Nervous System tumors, 109 patients from the Cancer Genome Atlas, and 40 patients from the Glioma Longitudinal AnalySiS. The study defined STS as those who had an overall survival ≤ 12 months after GTR with subsequent radiation therapy, and concurrent and adjuvant temozolomide (TMZ). RESULTS: The study included 446 patients with glioblastoma. All cohorts experienced unexpected STS after GTR, with a range of 15.0-23.9% of the cases. Molecular profiling revealed no significant difference in major genetic alterations between the STS and non-STS groups, including MGMT, TERT, EGFR, PTEN, and CDKN2A. Clinically, the STS group had a higher incidence of non-local recurrence early in their treatment course, with 60.0% of non-local recurrence in the K-cohort and 43.5% in the V-cohort. CONCLUSIONS: The study revealed that unexpected STS after GTR in patients with glioblastoma is not uncommon and such tumors tend to present early non-local recurrence. Interestingly, we did not find any significant genetic alterations in the STS group, indicating that such major alterations are characteristics of GB rather than being reliable predictors for recurrence patterns or development of unexpected STS.

Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons.

There are sex differences in somatosensory sensitivity. Circulating estrogens appear to have a pronociceptive effect that explains why females are reported to be more sensitive to pain than males. Although itch symptoms develop during pregnancy in many women, the underlying mechanism of female-specific pruritus is unknown. Here, we demonstrate that estradiol, but not progesterone, enhances histamine-evoked scratching behavior indicative of itch in female rats. Estradiol increased the expression of the spinal itch mediator, gastrin-releasing peptide (GRP), and increased the histamine-evoked activity of itch-processing neurons that express the GRP receptor (GRPR) in the spinal dorsal horn. The enhancement of itch behavior by estradiol was suppressed by intrathecal administration of a GRPR blocker. In vivo electrophysiological analysis showed that estradiol increased the histamine-evoked firing frequency and prolonged the response of spinal GRP-sensitive neurons in female rats. On the other hand, estradiol did not affect the threshold of noxious thermal pain and decreased touch sensitivity, indicating that estradiol separately affects itch, pain, and touch modalities. Thus, estrogens selectively enhance histamine-evoked itch in females via the spinal GRP/GRPR system. This may explain why itch sensation varies with estrogen levels and provides a basis for treating itch in females by targeting GRPR.

Association between prior-night sleep and next-day fatigue in older adults: a daily diary study.

BACKGROUND: Fatigue is known as an element of frailty. Sleep problems (e.g., short sleep duration and low sleep quality) can increase fatigue, but the day-to-day relationship between sleep and fatigue has not been studied well in older adults. Using a daily diary method, this study examined the within- and between-person associations between sleep and fatigue in older adults. METHODS: The study recruited 56 Japanese community dwellers (age: 82-86 years; female: 37.5%). Participants responded to a daily diary questionnaire at the end of each day. Over seven days, time in bed and satisfaction were measured after waking up, whereas fatigue was assessed before going to bed. We included person-level covariates (demographic factors, and physical and mental health) and day-level covariates (time in study, and positive and negative emotions). Multilevel models were estimated to examine within- and between-person associations. RESULTS: At the within-person level, on days following short and long time in bed and days following low levels of sleep satisfaction, individuals felt higher levels of fatigue compared with usual days. At the between-person level, no statistically significant differences in fatigue were observed between individuals with long and short time in bed. CONCLUSIONS: The findings suggest that prior-day sleep is associated with next-day fatigue in older adults. Long and short sleep duration and low sleep quality can lead to fatigue. Considering that sleep is a modifiable health behavior, appropriate management of sleep behavior may reduce fatigue.

Functional Outcomes of Microsurgical Resection for Cavernous Malformations of the Brainstem.

Long-term functional outcomes of microsurgical resection for cavernous malformations of the brainstem (CMB) have been largely unknown. Favorable outcomes after CMB surgery might be related to the achievement of complete resection and mRS at 1 month after the surgery. Preoperative sensory, cerebellar, trigeminal nerve, and lower cranial nerve symptoms tended to improve after surgery.We evaluated 25 consecutive patients with CMB surgically treated at our center between 2006 and 2021. The subjects included 11 men and 14 women, with ages ranging from 13 to 61 years (mean ± SD = 37 ± 12 years). Modified Rankin Scale (mRS) scores and neurological symptoms of the patients were evaluated before surgery, 1 month after surgery, and at the final follow-up at the outpatient clinic. The mean number of previous hemorrhages was 7 ± 1.0 and the mean lesion size was 21 ± 8 mm. The mRS scores on admission and at the final follow-up were 2.9 points and 1.7 points, respectively. The mRS scores at the final follow-up were significantly improved compared to those on admission. There was no statistical difference between the preoperative mRS and mRS at 1 month after the operation. Multivariable analysis indicated that mRS scores at 1 month after surgery were the most significant predictive factors for favorable outcomes. Complete resection was achieved in 24 of 33 operations. Incomplete resection was significantly related to the frequency of subsequent recurrent hemorrhage and high mRS scores at the final follow-up. Preoperative sensory, cerebellar, trigeminal nerve, and lower cranial nerve symptoms improved significantly after surgery.

A surgical case of pediatric spinal medulloepithelioma.

Embryonal tumor with multilayered rosettes (ETMR), C19MC-altered was introduced to the World Health Organization classification of central nervous system tumors in 2016. It is characterized by amplification or fusion of the chromosome 19 microRNA cluster (C19MC) locus at 19q13.42. Medulloepithelioma also an ETMR but lacks C19MC alteration. We report a rare case of spinal medulloepithelioma in a 2-year-old boy and review the literature.

Sweep imaging with Fourier transform as a tool with MRI for evaluating the effect of teriparatide on cortical bone formation in an ovariectomized rat model.

BACKGROUND: Teriparatide (TPTD) is a drug for osteoporosis that promotes bone formation and improves bone quality. However, the effects of TPTD on cortical bone are not well understood. Sweep imaging with Fourier transform (SWIFT) has been reported as a useful tool for evaluating bound water of cortical bone, but it has yet to be used to investigate the effects of TPTD on cortical bone. This study aimed to evaluate the consequences of the effect of TPTD on cortical bone formation using SWIFT. METHODS: Twelve-week-old female Sprague-Dawley rats (n = 36) were reared after ovariectomy to create a postmenopausal osteoporosis model. They were divided into two groups: the TPTD and non-TPTD groups. Rats were euthanized at 4, 12, and 24 weeks after initiating TPTD treatment. Tibial bones were evaluated using magnetic resonance imaging (MRI) and bone histomorphometry. In MRI, proton density-weighted imaging (PDWI) and SWIFT imaging were performed. The signal-to-noise ratio (SNR) was calculated for each method. The same area evaluated by MRI was then used to calculate the bone formation rate by bone histomorphometry. Measurements were compared using the Mann-Whitney U-test, and a P-value of < 0.05 was considered significant. RESULTS: PDWI-SNR was not significantly different between the two groups at any time point (P = 0.589, 0.394, and 0.394 at 4, 12, and 24 weeks, respectively). Contrarily, SWIFT-SNR was significantly higher in the TPTD group than in the non-TPTD group at 4 weeks after initiating treatment, but it was not significantly different at 12 and 24 weeks (P = 0.009, 0.937, and 0.818 at 4, 12, and 24 weeks, respectively). The bone formation rate assessed by histomorphometry was significantly higher in the TPTD group than in the non-TPTD group at all timepoints (P < 0.05, all weeks). In particular, at 4 weeks, the bone formation rate was markedly higher in the TPTD group than in the non-TPTD group (P = 0.028, 1.98 ± 0.33 vs. 0.09 ± 0.05 µm3/µm2/day). CONCLUSIONS: SWIFT could detect increased signals of bound water, reflecting the effect of TPTD on the cortical bone. The signal detected by SWIFT reflects a marked increase in the cortical bone formation rate.

Subcellular dynamics of estrogen-related receptors involved in transrepression through interactions with scaffold attachment factor B1.

Estrogen-related receptor (ERR), a member of the nuclear receptor superfamily, consists of three subtypes (α, ß, γ) and has strong homology with estrogen receptor. No endogenous ligands have been identified for ERRs, but they play key roles in metabolic, hormonal, and developmental processes as transcription factors without ligand binding. Although subnuclear dynamics are essential for nuclear events including nuclear receptor-mediated transcriptional regulation, the dynamics of ERRs are poorly understood. Here, we report that ERRs show subcellular kinetic changes in response to diethylstilbestrol (DES), a synthetic estrogen that represses the transactivity of all three ERR subtypes, using live-cell imaging with fluorescent protein labeling. Upon DES treatment, all ERR subtypes formed discrete clusters in the nucleus, with ERRγ also displaying nuclear export. Fluorescence recovery after photobleaching analyses revealed significant reductions in the intranuclear mobility of DES-bound ERRα and ERRß, and a slight reduction in the intranuclear mobility of DES-bound ERRγ. After DES treatment, colocalization of all ERR subtypes with scaffold attachment factor B1 (SAFB1), a nuclear matrix-associated protein, was observed in dot-like subnuclear clusters, suggesting interactions of the ERRs with the nuclear matrix. Consistently, co-immunoprecipitation analyses confirmed enhanced interactions between ERRs and SAFB1 in the presence of DES. SAFB1 was clarified to repress the transactivity of all ERR subtypes through the ERR-response element. These results demonstrate ligand-dependent cluster formation of ERRs in the nucleus that is closely associated with SAFB1-mediated transrepression. Taken together, the present findings provide a new understanding of the pathophysiology regulated by ERR/SAFB1 signaling pathways and their subcellular dynamics.

Novel metabolic system for lactic acid via LRPGC1/ERRγ signaling pathway.

Lactic acid (LA) is a byproduct of glycolysis resulting from intense exercise or a metabolic defect in aerobic processes. LA metabolism is essential to prevent lactic acidosis, but the mechanism through which LA regulates its own metabolism is largely unknown. Here, we identified a LA-responsive protein, named LRPGC1, which has a distinct role from PGC1α, a key metabolic regulator, and report that LRPGC1 particularly mediates LA response to activate liver LA metabolism. Following LA stimulation, LRPGC1, but not PGC1α, translocates from the cytoplasm to the nucleus through deactivation of nuclear export signals, interacts with the nuclear receptor ERRγ, and upregulates TFAM, which ensures mitochondrial biogenesis. Knockout of PGC1 gene in HepG2 hepatocarcinoma cells decreased the LA consumption and TFAM expression, which were rescued by LRPGC1 expression, but not by PGC1α. These LRPGC1-induced effects were mediated by ERRγ, concomitantly with mitochondrial activation. The response element for LRPGC1/ERRγ signaling pathway was identified in TFAM promoter. Notably, the survival rate of a mouse model of lactic acidosis was reduced by the liver-targeted silencing of Lrpgc1, while it was significantly ameliorated by the pharmacological activation of ERRγ. These findings demonstrate LA-responsive transactivation via LRPGC1 that highlight an intrinsic molecular mechanism for LA homeostasis.

Scaffold attachment factor B: distribution and interaction with ERα in the rat brain.

Scaffold attachment factor (SAFB) 1 and its homologue SAFB2 are multifunctional proteins that are involved in various cellular mechanisms, including chromatin organization and transcriptional regulation, and are also corepressors of estrogen receptor alpha (ERα). Both SAFBs are expressed at high levels in the brain. However, the distributions of SAFB1 and SAFB2 have yet to be characterized in detail and it is unclear whether both proteins interact with ERα in the brain. In this study, we investigated the expression and distribution of both SAFBs and their interaction with ERα in adult male rat brain. Immunohistochemical staining showed that SAFB1 and SAFB2 have a similar distribution pattern and are widely expressed throughout the brain. Double-fluorescence immunohistochemical and immunocytochemical analyses in primary cultures showed that the two SAFB proteins are localized in nuclei of neurons, astrocytes, and oligodendrocytes. Of note, SAFB2 was also found in cytoplasmic regions in these cell lineages. Both SAFB proteins were also expressed in ERα-positive cells in the medial preoptic area (MPOA) and arcuate and ventromedial hypothalamic nuclei. Co-immunoprecipitation experiments revealed that both SAFB proteins from the MPOA reciprocally interact with endogenous ERα. These results indicate that, in addition to a role in basal cellular function in the brain, the SAFB proteins may serve as ERα corepressors in hormone-sensitive regions.

Status of growth plates can be monitored by MRI.

BACKGROUND: Growth plate injuries and disorders cause premature closure, resulting in shortened or deformed limbs. Quantitative assessment by MRI might monitor the status of the growth plate and may assist in the prediction of these deformations. PURPOSE: To investigate whether the status of the growth plate can be monitored by quantitative evaluation using MRI of the noninjured region of the growth plate in a physeal injury model. STUDY TYPE: Prospective, longitudinal. ANIMAL MODEL: A 3.0-mm drill was used to create an injury to the central region of the right proximal tibial growth plate in 5-week-old male Japanese white rabbits (N = 18). The left tibia served as the control. FIELD STRENGTH/SEQUENCE: 7.04T, T2 -weighted imaging, diffusion-weighted imaging. ASSESSMENT: Eight of 18 rabbits underwent MRI, proton density-weighted imaging, and T2 -weighted and diffusion-weighted imaging. T2 and apparent diffusion coefficient (ADC) maps were generated for each image. The growth plate height and the T2 and ADC values of the noninjured region were measured. Two rabbits were sacrificed at 2, 4, 6, 8, and 10 weeks postinjury. Proximal tibial bones were evaluated using microcomputed tomography, histological, and immunohistological methods. STATISTICAL TESTS: Data were compared using repeated-measures analysis of variance followed by Tukey post-hoc multiple comparison. RESULTS: Growth plate height decreased at 10 weeks postinjury (P = 0.018) on the injured side. T2 values were greater at 2 weeks postinjury (P = 0.0478) and decreased at 8 and 10 weeks (P = 0.0226, P = 0.0470, respectively) on the injured side. ADC values increased at 6 weeks on the lateral side (P = 0.0304) and decreased at 8 weeks and 10 weeks postinjury (P < 0.01) on the medial and injured sides, respectively. DATA CONCLUSION: Quantitative MRI can help monitor the status of the growth plate and capture its changes early. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:133-143.

Relationships between recurrence patterns and subventricular zone involvement or CD133 expression in glioblastoma.

INTRODUCTION: We previously reported that CD133 expression correlated with the recurrence pattern of glioblastoma (GBM). Subventricular zone (SVZ) involvement may also be associated with distant recurrence in GBM. Therefore, we herein investigated whether the combined analysis of SVZ involvement and CD133 expression is useful for predicting the pattern of GBM recurrence. MATERIALS AND METHODS: We retrospectively analyzed 167 cases of GBM. Tumors were divided into four groups based on spatial relationships between contrast-enhanced lesions (CEL) and the SVZ or cortex (Ctx) on MRI. The initial recurrence pattern (local/distant) was obtained from medical records. To identify factors predictive of recurrence, we examined CD133 expression by immunohistochemical, clinical (age, sex, KPS, Ki-67 labeling index, surgery, and MRI characteristics), and genetic (IDH1, MGMT, and BRAF) factors. RESULTS: The CD133 expression rate was higher in SVZ-positive tumors than in SVZ-negative tumors (P = 0.046). Distant recurrence was observed in 21% of patients, and no significant difference was noted in recurrence patterns among the four groups. However, strong CD133 expression was associated with a shorter time to distant recurrence in univariate, multivariate, and propensity-matched scoring analyses (P < 0.0001, P = 0.001, and P = 0.0084, respectively). In the combined analysis, distant recurrence was the most frequent (70%) in group III (SVZ-negative, Ctx-positive) GBM and those with high CD133 expression rates (≥ 15%). CONCLUSION: An integrated analysis of CD133 expression and MRI-based tumor classification may be useful for predicting the recurrence pattern of GBM.

Determination of the lingual border of lower complete dentures: How to use a silicone impression material?

OBJECTIVES: This study aimed to clarify the efficacy of a border-moulding procedure with low-flow silicone impression material compared with a conventional compound to complete denture fabrication. It also aimed to evaluate the influence of various functional tasks during the lingual-side moulding procedure regarding the depth and width of the border. METHODS: Ten dentate subjects (three men, seven women; average age 30 years) were enrolled in this study after giving informed consent. A specially designed custom impression tray for the mandibular lingual side was fabricated for each subject. With the tray and heavy-body-type silicone material, lingual border moulding was performed that included four functional tasks: tongue protrusion (TP), licking the upper lip with the tongue (UL), swallowing (SW), and placing the tongue tip to the palate (PP). RESULTS: Within the limitations of this study, the results suggested that heavy-body silicone impression material is satisfactory for use in the border-moulding procedure, giving reproducible results. CONCLUSION: There were no significant differences among the functional tasks regarding the depth and width of the lingual flange except for swallowing, which exhibited the largest values.

[Diffuse Leptomeningeal Glioneuronal Tumor with Subarachnoid Hemorrhage:A Case Report].

Diffuse leptomeningeal glioneuronal tumor(DLGNT)is a rare primary neoplasm of the central nervous system, and is a condition that is newly listed in the 2016 World Health Organization(WHO)classification of tumors of the central nervous system. We report an adult case of DLGNT that was characteristically merged with subarachnoid hemorrhage. A 46-year-old woman reported persistent dizziness upon walking. MRI of the brain revealed a diffuse, infiltrating lesion with high intensity on FLAIR around the cerebellopontine angle to the lateral ventricle and in the leptomeninges of the spinal cord. The lesion on the cerebellopontine angle showed high intensity on T1 weighted images with contrast enhancement. Since diffuse glioma and meningeal carcinomatosis were suspected, we performed an endoscopic biopsy for the lesion in the right lateral ventricle. Although the tumor was tentatively diagnosed as WHO grade II diffuse astrocytoma, a definitive diagnosis could not be obtained. One month after surgery, the patient presented with acute headache and dizziness. CT showed subarachnoid hemorrhage in the cerebellopontine angle. To decompress the intracranial pressure and prevent re-bleeding, and to obtain enough tissue samples for definitive diagnosis, we removed the enhanced lesion and hematoma at the cerebellopontine angle. Tumor tissue was composed of oligodendroglial-like cells and was positive for GFAP, Olig2, synaptophysin, and S100 protein, although it was negative for IDH1R132H. Fluorescent in situ hybridization showed KIAA1566-BRAF fusion; however, neither 1p loss nor 1p19q co-deletion was observed. Together with histological and radiological findings, the tumor was ultimately diagnosed as DLGNT. The patient received maintenance chemotherapy with temozolomide, and the tumor was stable at 18 months after surgery.

[Optic Neuropathy Secondary to Compression by the Internal Carotid Artery Concomitant with an Inflammatory Granuloma:A Case Report].

A 77-year-old man presented with a 6-month history of progressive right optic neuropathy secondary to compression by the ipsilateral internal carotid artery(ICA). We performed anterior clinoidectomy and optic canal unroofing. Subsequently, we wrapped the ICA with a polytetrafluoroethylene tape, pulled the vessel laterally, and sutured the tape to the dura mater at the anterior skull base for optimal decompression. An inflammatory mass lesion was observed around the ICA, which led to further compression of the optic nerve. Histopathological examination of the resected specimen showed an inflammatory granuloma. The patient's visual field deficit showed partial improvement postoperatively. Transposition using a tape might be an effective surgical alternative for compressive optic neuropathy.

[A Case of Invasive Lobular Carcinoma of Accessory Mammary Gland That Was Difficult for Evaluate for Lesion Spread].

A 48-year-old female discovered a mass in her left axilla. A thorough examination resulted in a diagnosis of left invasive lobular carcinoma(ILC)of the accessory mammary gland with wide ductal spread. Considering the wide ductal spread, massive resection of the left axilla mass, left lymph node dissection, and a latissimus dorsi musculocutaneous flap procedure were performed. However, histological analysis revealed ILC measuring 80×50 mm with lymph node metastases(5/23)and extensive cancer spread, resulting in a positive surgical margin. It is important to recognize the characteristics of ILC, axillary accessory breast cancer, and the axilla in a treatment strategy.

Lack of posterior occlusal support predicts the reduction in walking speed in 80-year-old Japanese adults: A 3-year prospective cohort study with propensity score analysis by the SONIC Study Group.

OBJECTIVE: To investigate the association between posterior occlusal support by residual teeth and the reduction in walking speed in 80-year-old Japanese adults using propensity score matching. BACKGROUND DATA DISCUSSING THE PRESENT STATUS OF THE FIELD: Previous studies have demonstrated an association between oral status and motor function; however, most of these studies had a cross-sectional design. MATERIAL AND METHOD: This study included 353 community-dwelling Japanese people aged 79-81 years. Low walking speed was defined as ≤0.8 m/s, and participants with a low walking speed at baseline were excluded. The participants were divided into two groups: with or without posterior occlusal support by residual teeth at baseline. Propensity score matching was used to reduce the effects of bias by matching participants with and without posterior occlusal support according to similar background factors at baseline. Conditional logistic regression was conducted to determine low walking speed at the 3-year follow-up, which included posterior occlusal support as an independent variable with matching data. RESULTS: Before matching for posterior occlusal support, significant differences existed between the groups in terms of sex, years of education, height, weight and grip strength. However, after matching, there was no significant difference between the groups in any characteristic. Logistic regression analysis showed that posterior occlusal support is a significant variable (odds ratio = 1.88; P = 0.04) associated with reduced walking speed. CONCLUSION: Lack of posterior occlusal support at baseline independently predicted the incidence of reduced walking speed over 3 years.

Depressive-Like Behaviors Are Regulated by NOX1/NADPH Oxidase by Redox Modification of NMDA Receptor 1.

Involvement of reactive oxygen species (ROS) has been suggested in the development of psychiatric disorders. NOX1 is a nonphagocytic form of NADPH oxidase whose expression in the nervous system is negligible compared with other NOX isoforms. However, NOX1-derived ROS increase inflammatory pain and tolerance to opioid analgesia. To clarify the role of NOX1 in the brain, we examined depressive-like behaviors in mice deficient in Nox1 (Nox1-/Y). Depressive-like behaviors induced by chronic social defeat stress or administration of corticosterone (CORT) were significantly ameliorated in Nox1-/Y Generation of ROS was significantly elevated in the prefrontal cortex (PFC) of mice administrated with CORT, while NOX1 mRNA was upregulated only in the ventral tegmental area (VTA) among brain areas responsible for emotional behaviors. Delivery of miRNA against NOX1 to VTA restored CORT-induced depressive-like behaviors in wild-type (WT) littermates. Administration of CORT to WT, but not to Nox1-/Y, significantly reduced transcript levels of brain-derived neurotrophic factor (bdnf), with a concomitant increase in DNA methylation of the promoter regions in bdnf Delivery of miRNA against NOX1 to VTA restored the level of BDNF mRNA in WT PFC. Redox proteome analyses demonstrated that NMDA receptor 1 (NR1) was among the molecules redox regulated by NOX1. In cultured cortical neurons, hydrogen peroxide significantly suppressed NMDA-induced upregulation of BDNF transcripts in NR1-expressing cells but not in cells harboring mutant NR1 (C744A). Together, these findings suggest a key role of NOX1 in depressive-like behaviors through NR1-mediated epigenetic modification of bdnf in the mesoprefrontal projection.SIGNIFICANCE STATEMENT NADPH oxidase is a source of reactive oxygen species (ROS) that have been implicated in the pathogenesis of various neurological disorders. We presently showed the involvement of a nonphagocytic type of NADPH oxidase, NOX1, in major depressive disorders, including behavioral, biochemical, and anatomical changes in mice. The oxidation of NR1 by NOX1-derived ROS was demonstrated in prefrontal cortex (PFC), which may be causally linked to the downregulation of BDNF, promoting depressive-like behaviors. Given that NOX1 is upregulated only in VTA but not in PFC, mesocortical projections appear to play a crucial role in NOX1-dependent depressive-like behaviors. Our study is the first to present the potential molecular mechanism underlying the development of major depression through the NOX1-induced oxidation of NR1 and epigenetic modification of bdnf.

Treatment outcomes of hypofractionated radiotherapy combined with temozolomide followed by bevacizumab salvage therapy in glioblastoma patients aged > 75 years.

BACKGROUND: The optimal treatment for elderly patients with glioblastoma has not been established. METHODS: We retrospectively analyzed the safety and efficacy of hypofractionated radiotherapy (45 Gy/15 fr) combined with temozolomide (TMZ) followed by bevacizumab (BEV) salvage treatment in 18 glioblastoma patients aged > 75 years. RESULTS: All of the patients received safe hypofractionated radiotherapy and concomitant TMZ (75 mg/m2), and 14 of 18 patients received maintenance TMZ. We administered BEV to 17 of 18 patients because their Karnofsky Performance Status scores declined and/or recurrence was detected. During the follow-up period (median duration: 17.5 months, range 3-33 months), 12 patients died of their disease. While the median progression-free survival period was 2.5 months, the median overall survival period was 20 months. Adverse events (National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4) occurred in 5 patients. CONCLUSION: Hypofractionated radiotherapy combined with TMZ and BEV salvage treatment was found to be safe and effective in glioblastoma patients aged > 75 years.

Rapidly progressive renal failure due to tubulointerstitial infiltration of peripheral T-cell lymphoma, not otherwise specified accompanied by uveitis: a case report.

BACKGROUND: Rapid decline in renal dysfunction due to primary renal lymphoma, or secondary renal lymphoma by infiltration from a primary origin, is extremely rare. There are notably few reports indicating infiltration of T-cell lymphoma into the kidney. CASE PRESENTATION: A 61-year-old woman with a sudden body rash and liver dysfunction was brought to our hospital presenting with a dull headache and blurred vision. Laboratory tests revealed rapidly progressive renal failure. Histological examination of the kidney and skin indicated infiltration of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Infiltration of PTCL-NOS to the liver and spleen, and presence of Uveitis masquerade syndrome were suspected. Imaging showed that the lesion was limited to extralymphatic organs. Renal function was improved with administration of steroids, including pulse steroid therapy, before administering cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) therapy. CONCLUSIONS: This is the first reported case of rapidly progressive renal failure caused by perivascular tubulointerstitial nephritis with the direct invasion of PTCL-NOS. In our case, a single steroid dose showed dramatic results with respect to renal symptoms.

Early detection of osteoarthritis in rabbits using MRI with a double-contrast agent.

BACKGROUND: Articular cartilage degeneration has been evaluated by magnetic resonance imaging (MRI). However, this method has several problems, including its time-consuming nature and the requirement of a high magnetic field or specialized hardware. The purpose of this study was to sequentially assess early degenerative changes in rabbit knee articular cartilage using MRI with a new double-contrast agent. METHODS: We induced osteoarthritis (OA) in the right knee of rabbits by anterior cruciate ligament transection and partial medial meniscectomy. Proton density-weighted images and T2-calculated images were obtained before and after contrast agent injection into the knee. The signal intensity ratio (SIR) values on the proton density-weighted images were calculated by dividing the signal intensity of the articular cartilage by that of joint fluid. Six rabbits were examined using MRI at 2 (designated 2-w OA) and 4 weeks (4-w OA) after the operation. Histological examination was performed 4 weeks after the operation. One rabbit was histologically examined 2 weeks after the operation. The control consisted of six rabbits that were not subjected to the operation. The SIR values, T2 values and the thicknesses of the cartilage of the 2-w OA, 4-w OA and the control before and after contrast agent injection were analyzed. The Mankin score and OARSI (Osteoarthritis Research Society International) score were used for the histological evaluation. RESULTS: Significant differences in the SIR and T2 values of the medial and lateral condyles of the femur were found between the control and the 4-w OA only after contrast agent injection. No significant differences were found in the SIR and T2 values before contrast agent injection between the control, the 2-w OA and 4-w OA. The thickness of the articular cartilage revealed no significant differences. In the histological assessment, the Mankin score and OARSI score sequentially increased from the control to the 4-w OA. CONCLUSION: We evaluated the SIR and T2 values of the knees in a rabbit OA model and a control model using a new double-contrast agent. MRI with this agent enabled OA detection earlier than using conventional MRI.