Preliminary validation of the Virtual Kitchen Challenge as an objective and sensitive measure of everyday function associated with cerebrovascular disease.

Preliminary validity of a computer-based test of everyday function (Virtual Kitchen Challenge [VKC]) was examined against brain-imaging markers of cerebrovascular disease and in contrast to conventional neuropsychological and self-report measures. Twenty community-dwelling older adults (n = 6 mild cognitive impairment) performed simulated breakfast and lunch tasks using a computer touchscreen (VKC). Automated measures (completion time, proportion time off screen, etc.) were computed during training and test conditions. White matter hyperintensity (WMH) volumes from brain magnetic resonance imaging and conventional measures of cognition and function also were obtained. VKC completion time and proportion time off screen improved significantly from training to test and were significantly associated with WMH volume (r > 0.573). VKC measures and WMH were not significantly correlated with conventional cognitive or self-report measures. The VKC holds promise as a valid measure of subtle functional difficulties in older adults that is sensitive to change and cerebrovascular pathology, highlighting its potential for clinical trials. Highlights: Virtual Kitchen Challenge (VKC) scores showed significant improvement from training to test conditions.VKC scores (completion time and proportion of time off screen) were associated with a neuroimaging biomarker of brain health (white matter hyperintensities).

A Case of GATA3 Positive Pleomorphic Liposarcoma, Epithelioid Variant: A Diagnostic Pitfall.

Pleomorphic liposarcoma is a rare malignant adipocytic tumor showing undifferentiated pleomorphic sarcoma morphology with various degrees of epithelioid features. It is sometimes difficult to distinguish from carcinoma metastasis. Immunohistochemical panel is very important for differential diagnosis; however, there is a risk that unexpected staining could lead to misinterpretation. We report a pleomorphic liposarcoma, epithelioid variant, in an 88-year-old man, with tricky-positive staining for GATA3. Histological examination revealed a tumor with epithelioid morphology. The tumor consists of solid sheets of epithelioid tumor cells with focal aggregates of pleomorphic lipoblasts. Immunohistochemically, the adipocytic tumor cell areas were positive for S100 protein, and the epithelioid tumor cells showed CAM 5.2 positivity. GATA3 was diffusely positive. The combination of CAM 5.2 and GATA3 staining suggested the possibility of metastatic cancer, but systemic clinical examinations did not detect any presence of a primary tumor, including urinary bladder, breasts, and salivary glands. The pathological diagnosis of pleomorphic liposarcoma, epithelioid variant, was made because of the presence of malignant lipoblasts. Our report may contribute for differential diagnosis of pleomorphic liposarcoma, epithelioid variant, with unexpected positive immunoreaction for GATA3.

Case Report: Extraskeletal osteosarcoma with preceding myositis ossificans.

Extraskeletal osteosarcoma (EO) is a soft tissue sarcoma characterized by the production of bone matrix by neoplastic cells. Benign osteoid in EO, leading to a diagnostic dilemma, is rarely encountered. Herein, for the first time, we present a case with cytogenetically confirmed EO combined with or preceding myositis ossificans (MO). A 21-year-old man had a mildly painful swelling in his left knee. Imaging studies demonstrated a 39-mm mass with peripheral mineralization and cystic change on the posterolateral side of the left fibular head. He was clinically suspected of having either MO or a malignancy, such that wide resection was performed. Macroscopically, the mass was grayish to brown. In the cut section, multiple cystic lesions in addition to solid components were noted. Histopathologically, the solid components demonstrated diffuse proliferation of pleomorphic tumor cells with osteoclast-like giant cells. The malignant tumor cells formed osteoid. In the periphery, the mass was benign, showing mature bone tissue and focally non-malignant woven bone with fibroblasts, compatible with zonation. Fluorescence in situ hybridization (FISH) demonstrated split signals of the USP6 gene. These findings suggested EO with preceding MO. Although the pathogenesis remains to be elucidated, the observed USP6 rearrangement might contribute to both the diagnosis of EO with preceding MO and an understanding of the underlying histopathology.

Familial Paget's disease of bone with ocular manifestations and a novel TNFRSF11A duplication variant (72dup27).

INTRODUCTION: Paget's disease of bone (PDB) is a skeletal disorder characterized by disorganized bone remodeling due to abnormal osteoclasts. Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) gene encodes the receptor activator of nuclear factor kappa B (RANK), which has a critical role in osteoclast function. There are five types of rare PDB and related osteolytic disorders due to TNFRSF11A tandem duplication variants so far, including familial expansile osteolysis (84dup18), expansile skeletal hyperphosphatasia (84dup15), early-onset familial PDB (77dup27), juvenile PDB (87dup15), and panostotic expansile bone disease (90dup12). MATERIALS AND METHODS: We reviewed a Japanese family with PDB, and performed whole-genome sequencing to identify a causative variant. RESULTS: This family had bone symptoms, hyperphosphatasia, hearing loss, tooth loss, and ocular manifestations such as angioid streaks or early-onset glaucoma. We identified a novel duplication variant of TNFRSF11A (72dup27). Angioid streaks were recognized in Juvenile Paget's disease due to loss-of-function variants in the gene TNFRSF11B, and thought to be specific for this disease. However, the novel recognition of angioid streaks in our family raised the possibility of occurrence even in bone disorders due to TNFRSF11A duplication variants and the association of RANKL-RANK signal pathway as the pathogenesis. Glaucoma has conversely not been reported in any case of Paget's disease. It is not certain whether glaucoma is coincidental or specific for PDB with 72dup27. CONCLUSION: Our new findings might suggest a broad spectrum of phenotypes in bone disorders with TNFRSF11A duplication variants.

Imaging of spinal chordoma and benign notochordal cell tumor (BNCT) with radiologic pathologic correlation.

Benign notochordal cell tumor (BNCT) and chordoma are neoplasms of notochordal differentiation. BNCT represents notochordal rests, commonly an incidental lesion present in the spine in 19% of cadaveric specimens. BNCTs are often radiographically occult. CT of BNCT frequently reveals patchy sclerosis between areas of maintained underlying trabeculae. BNCT demonstrates marrow replacement on T1-weighted MR images with high signal intensity on T2-weighting. BNCTs are frequently smaller than 35 mm and lack significant enhancement, bone destruction, cortical permeation, or soft tissue components. Biopsy or surgical resection of BNCT is usually not warranted, although imaging surveillance may be indicated. Chordoma is a rare low-grade locally aggressive malignancy representing 1-4% of primary malignant bone tumors. Chordoma is most frequent between the ages of 50-60 years with a male predilection. Clinical symptoms, while nonspecific and location dependent, include back pain, numbness, myelopathy, and bowel/bladder incontinence. Unfortunately, lesions are often large at presentation owing to diagnosis delay. Imaging of chordoma shows variable mixtures of bone destruction and sclerosis, calcification (50-70% at CT) and large soft tissue components. MR imaging of chordoma reveals multilobulated areas of marrow replacement on T1-weighting and high signal intensity on T2-weighting reflecting the myxoid component within the lesion and areas of hemorrhage seen histologically. Treatment of chordoma is primarily surgical with prognosis related to resection extent. Unfortunately, complete resection is often not possible (21-75%) resulting in high local recurrence incidence (19-75%) and a 5-year survival rate of 45-86%. This article reviews and illustrates the clinical characteristics, pathologic features, imaging appearance spectrum, treatment, and prognosis of BNCT and spinal chordoma.

An autopsy case of pulmonary arterial hypertension in an elderly patient with multimorbidity: a case report.

BACKGROUND: There is an increasing number of elderly patients with pulmonary arterial hypertension (PAH), and their characteristics differ from those of young or middle-aged patients with this condition. CASE SUMMARY: A 73-year-old woman with a history of myocardial infarction and cardiovascular risk factors was admitted to the hospital with 2-week exertional dyspnoea. Her initial diagnosis was heart failure with preserved ejection fraction, but the symptoms persisted despite receiving treatment with diuretics. Additional tests showed a significant decrease in diffusing capacity of carbon monoxide and findings suggestive of severe pulmonary hypertension (PH). Contrast-enhanced computed tomography of the chest, and pulmonary angiography, showed no narrowing or obstruction of the pulmonary arteries. Right heart catheterization revealed haemodynamic data implying pre-capillary PH. Her condition gradually deteriorated to World Health Organization functional class IV, and sequential combination therapy with tadalafil, macitentan, and selexipag was initiated with a PAH diagnosis; however, she died 1 month later. Pathological findings in autopsy were consistent with PAH, and some parts of the lungs revealed the presence of obstructive and interstitial lung disease. DISCUSSION: The majority of elderly patients with PAH might have multimorbidity. However, there is no specific treatment strategy. It is associated with diagnostic delay and worse prognosis; therefore, early suspicion and comprehensive tests, including right heart catheterization, are essential for better management.

Subchondral insufficiency fracture of the knee: review of current concepts and radiological differential diagnoses.

Subchondral insufficiency fracture of the knee (SIFK) is a common cause of knee joint pain in older adults. SIFK is a type of stress fracture that occurs when repetitive and excessive stress is applied to the subchondral bone. If the fracture does not heal, the lesion develops into osteonecrosis and results in osteochondral collapse, requiring surgical management. Because of these clinical features, SIFK was initially termed "spontaneous osteonecrosis of the knee (SONK)" in the pre-MRI era. SONK is now categorized as an advanced SIFK lesion in the spectrum of this disease, and some authors believe the term "SONK" is a misnomer. MRI plays a significant role in the early diagnosis of SIFK. A subchondral T2 hypointense line of the affected condyle with extended bone marrow edema-like signal intensity are characteristic findings on MRI. The large lesion size and the presence of osteochondral collapse on imaging are associated with an increased risk of osteoarthritis. However, bone marrow edema-like signal intensity and osteochondral collapse alone are not specific to SIFK, and other osteochondral lesions, including avascular necrosis, osteochondral dissecans, and osteoarthritis should be considered. Chondral lesions and meniscal abnormalities, including posterior root tears, are also found in many patients with SIFK, and they are considered to be related to the development of SIFK. We review the clinical and imaging findings, including the anatomy and terminology history of SIFK, as well as its differential diagnoses. Radiologists should be familiar with these imaging features and clinical presentations for appropriate management.

A desmoplastic fibroblastoma that developed in the anterior mediastinum: a case report.

BACKGROUND: Desmoplastic fibroblastoma (also known as collagenous fibroma) is a benign, slowly growing soft-tissue tumor. Most desmoplastic fibroblastomas develop in the limbs, neck, or trunk. A mediastinal origin is quite rare. CASE PRESENTATION: A 32-year-old Asian female was referred to us for the diagnosis and treatment of an anterior mediastinal tumor. The tumor was 80 mm in the largest diameter and was located on the pericardium. No invasion was evident. She underwent resection of the tumor via video-assisted thoracoscopic resection. The tumor was totally encapsulated, and its pedicle was on the pericardium. The resected specimen was very rigid, making it difficult to remove from the intercostal space. Histologically, the tumor was composed of a paucicellular dense collagenous tissue. Mitosis was rarely observed, and cellular atypia was not evident, suggesting that the tumor was benign. We diagnosed the tumor as a desmoplastic fibroblastoma by morphology and immunohistochemistry. CONCLUSIONS: Desmoplastic fibroblastoma of the mediastinum is an extremely rare disease. Preoperative diagnosis is difficult. Early surgical resection is suitable for diagnosis and treatment planning.

Androgen Receptor Predicts First and Multiple Recurrences in Non-Muscle Invasive Urothelial Carcinoma of the Bladder.

The aim of this study is to investigate the role of androgen receptor (AR) expression on clinicopathologic characteristics, first recurrence free survival (RFS), progression free survival (PFS) and multiple recurrences in non-muscle invasive bladder cancer (NMIBC). AR expression in 40 paraffin-embedded specimens of primarily diagnosed NMIBC after transurethral resection was examined by immunohistochemistry using a monoclonal AR antibody. Associations between AR expression and clinicopathologic features and prognosis were statistically assessed. Multivariate Cox proportional hazards model was applied for evaluating predictive factors on RFS and PFS. For multiple recurrences, we used the Andersen-Gill model. AR was positive in 20/40 (50%) cases. Twenty-three patients (57.5%) had no recurrence, 10 (25.0%) had one recurrence, and 7 (17.5%) experienced more than one recurrence. AR expression and clinicopathologic features were not significantly correlated (P >0.05). Univariate analyses showed that AR expression was significantly associated with RFS and PFS (P <0.05). Via multivariate analyses, positive AR expression was significantly associated with lower risk of first recurrence (hazard ratio (HR) = 0.265; 95% confidence interval (95% CI) = 0.084-0.829; P = 0.022). Multivariate analysis of PFS was not feasible in our cohort. Using the multivariate Andersen-Gill model, positive AR expression in the primary tumor was an independent factor predicting lower risk of multiple recurrences (HR = 0.387, 95% CI = 0.161-0.927, P = 0.033). Androgen receptor expression is associated with first and multiple recurrences in NMIBC.

The Virtual Kitchen Challenge: preliminary data from a novel virtual reality test of mild difficulties in everyday functioning.

Background: Efficient, objective measures of mild functional difficulties are lacking. Preliminary data from a novel, non-immersive virtual reality, performance-based task (Virtual Kitchen Challenge; VKC) were obtained to address this gap. Methods: 14 older and 21 younger adults completed cognitive tests and two everyday tasks (breakfast, lunch) in the VKC with virtual objects and a touch-screen and in the Real Kitchen with real objects (order counterbalanced). Automated performance measures were obtained from the VKC program and human coders scored VKC and Real Kitchen videos for errors. Results: Older adults made more errors than younger adults on the VKC and Real Kitchen, with similar error patterns across measures. VKC automated measures were significantly related to measures from human coders, performance on the Real Kitchen, and cognitive test scores. Conclusion: The VKC is a valid and highly efficient performance-based measure of subtle functional difficulties with great potential for future clinical and research applications.

Optimal body mass index cut-point for predicting recurrence-free survival in patients with non-muscle-invasive urothelial carcinoma of bladder.

In Japanese patients with non-muscle-invasive urothelial carcinoma of the bladder, the impact of body mass index (BMI) on recurrence following transurethral resection of bladder tumor (TURBT) is unclear. The present study retrospectively examined data collected from 50 patients diagnosed with primary urothelial carcinoma of the bladder (pTa, pTis, and pT1) who had previously undergone TURBT surgery. Two BMI cut-off points for predicting disease recurrence were evaluated: i) A threshold generated through receiver operating characteristic (ROC) curve analysis; ii) the World Health Organization BMI index (24 kg/m2) for overweight status in Japanese populations. Univariate and multivariate analyses were applied to assess individual variables (BMI included) and the effect they had on recurrence-free survival (RFS). Median RFS and BMI values of 19.72 months (range, 3.13-72.13 months) and 23.37 kg/m2 (range, 14.72-36.84 kg/m2), respectively, were recorded. In multivariate analyses, higher continuous BMI was significantly associated with shorter RFS (P=0.019). Based on a ROC-generated BMI cut-off point (23.4 kg/m2), patients were ranked with either a high (≥23.4 kg/m2) or low (<23.4 kg/m2) BMI status. Multivariate analysis indicated that BMI values >23.4 kg/m2 were significantly associated with shorter RFS (P=0.028). Intravesical Bacillus Calmette-Guérin treatment and history of upper-tract urothelial carcinoma were also independently associated (P=0.044 and P=0.010, respectively). However, BMI values >24 kg/m2 (customary cut-off point) had no significant impact on RFS (P=0.066). Thus, a higher BMI status was revealed to be independently predictive of shorter RFS in Japanese patients undergoing TURBT for urothelial carcinoma of the bladder. A greater number of samples are required in order to determine optimal BMI cut-off points in Japanese patients and to investigate whether weight reduction intervention may improve prognosis.

[Unruptured Arteriosclerotic Aneurysm in the Distal Middle Cerebral Artery:A Case Report].

We report a rare case of an unruptured cerebral aneurysm in the left distal middle cerebral artery(MCA). A 76-year-old woman was referred to our department for unruptured cerebral aneurysms detected incidentally by magnetic resonance angiography. A left carotid angiogram revealed a saccular aneurysm arising in an arterial trunk unrelated to the branching zone of the distal MCA. The patient underwent an operation for trapping and excision of the saccular aneurysm in the distal MCA followed by end-to-end anastomosis. Histological analysis revealed an aneurysmally-dilated artery exhibiting thickened fibrous intima with foci of calcification and fragmented internal elastic lamina. Neither dissection nor infection were observed. The histological findings suggested that the aneurysm in this case was associated with arteriosclerotic change. Considering the medical history of the patient, we conclude that aging and hypertension are factors of the development of the cerebral aneurysm in our case, although the aneurysm is located in the distal MCA in which it is considered to low hemodynamic stress. We report this extremely rare case with a literature review.

The potential of virtual reality-based training to enhance the functional autonomy of Alzheimer's disease patients in cooking activities: A single case study.

Impairments in performing activities of daily living occur early in the course of Alzheimer's disease (AD). There is a great need to develop non-pharmacological therapeutic interventions likely to reduce dependency in everyday activities in AD patients. This study investigated whether it was possible to increase autonomy in these patients in cooking activities using interventions based on errorless learning, vanishing-cue, and virtual reality techniques. We recruited a 79-year-old woman who met NINCDS-ADRDA criteria for probable AD. She was trained in four cooking tasks for four days per task, one hour per day, in virtual and in real conditions. Outcome measures included subjective data concerning the therapeutic intervention and the experience of virtual reality, repeated assessments of training activities, neuropsychological scores, and self-esteem and quality of life measures. The results indicated that our patient could relearn some cooking activities using virtual reality techniques. Transfer to real life was also observed. Improvement of the task performance remained stable over time. This case report supports the value of a non-immersive virtual kitchen to help people with AD to relearn cooking activities.

Analysis of the Infiltrative Features of Chordoma: The Relationship Between Micro-Skip Metastasis and Postoperative Outcomes.

BACKGROUND: Chordomas are very rare primary malignant bone tumors that arise commonly from the sacrum (50-60%) and clivus (25-35%). Chordomas have a high rate of recurrence. The authors confirmed a unique histologic infiltration pattern of chordomas that resembles a skip-metastatic lesion in normal tissue around tumor, which they named "micro-skip metastasis." This study aimed to examine the correlations between the clinicopathologic features of chordomas, including micro-skip metastasis, and the clinical outcomes, including overall survival, local recurrence-free survival, and distant metastasis-free survival. METHODS: The study analyzed histopathologic and clinical data from patients with sacral chordomas who underwent en bloc resection from July 1991 through July 2014. Cases with a minimum follow-up period shorter than 20 months after resection were excluded. Kaplan-Meier survival analyses with log-rank tests were performed for overall survival, metastasis-free survival, and recurrence-free survival. RESULTS: The study retrospectively reviewed 40 patients. The mean follow-up period was 98.2 months (range 22-297 months). The local recurrence rate was 41.3%. Micro-skip metastases, observed in 17 patients (42.5%), were associated with a significantly increased risk of local recurrence (p = 0.023) but not with overall survival or distant metastasis-free survival. Poorer overall survival was associated with histologic vascular invasion (p = 0.030) and a greater maximum tumor diameter (p = 0.050). CONCLUSIONS: The presence of micro-skip metastasis was associated with a higher rate of local recurrence. The maximum tumor diameter and the presence of histologic vascular invasion were associated with poorer overall survival.

Notochordal Tumors: An Update on Molecular Pathology with Therapeutic Implications.

Recent molecular investigations of chordoma show common expression of various receptor tyrosine kinases and activation of downstream signaling pathways contributing to tumor growth and progression. The transcription factor brachyury (also known as T) is important in notochord differentiation, and germline duplication of the gene is often found in familial chordomas. Nuclear expression of brachyury is consistent in chordoma and in benign notochordal cell tumor. Based on the molecular evidence, targeting of several kinds of molecular agents has been attempted for the treatment of uncontrolled chordomas and achieved partial response or stable condition in many cases.

High-Frequency Continuous Pulsed Magnetic Stimulation Does Not Adversely Affect Development on Whole Body Organs in Female Sprague-Dawley Rats.

OBJECTIVES: To conduct histopathological studies on various organs in three different groups of female rats for adverse effects of pulsed magnetic stimulation (MS). Blood tests and body and organ weights were also studied. METHODS: A high-frequency continuous magnetic stimulator was used (SMN-X, Nihon Kohden, Tokyo). Thirty-four female Sprague-Dawley rats (SPF) were randomly divided into three groups: treatment (MS) groups with 12 and 36 stimulations (seven rats in each); sham groups exposed only to sounds of stimulation for 12 and 36 times; (seven rats in each); and control groups with no stimulation or sound during the same periods of 12 and 36 stimulations (five rats in each). The MS group received magnetic stimulation at the maximum output level (560 mT peak) at 10 Hz for 25 min once daily for 5 days a week. After treatment various organs including genital organs were removed for histological and endocrinological examinations. RESULTS: No changes were seen in body and organ weights and daily behaviors among the three groups. No adverse influence of magnetic stimulation was noted on histopathological examinations of liver, spleen, kidney, lung, heart, thymus, urinary bladder, skeletal muscle and bone marrow. No intragroup changes were seen among the three groups with regard to endocrinological findings including blood cell counts, adrenocorticotropic hormone (ACTH), estrogen and progesterone levels. CONCLUSIONS: Pulsed magnetic stimulation exerted no apparent adverse effect on the various organs, hormone levels, body weight, and daily behaviors in female rats.

Melorheostosis with recurrent soft-tissue components: a histologically confirmed case.

Melorheostosis is a very rare disorder characterized by irregular cortical thickening seen on radiographs. In this paper, we present a case of melorheostosis with microscopically confirmed soft-tissue components. The patient was a 51-year-old man who complained of severe pain in the lateral aspect of his right knee. The excision of an ossified soft-tissue lesion relieved intractable pain that had lasted 20 years. Microscopically, the cortex of the affected fibula was composed of thick compact bone and the soft-tissue component consisted of dense compact bone without endochondral ossification. The presence of soft-tissue osseous nodules around the joints is one of the specific conditions for melorheostosis and should be differentiated from synovial chondromatosis. The ossified soft-tissue lesion in our patient is to our knowledge the first reported case of the histologically confirmed soft-tissue component of melorheostosis, which differs from that of synovial chondromatosis.

An Unusual Presentation of Adult Tethered Cord Syndrome Associated with Severe Chest and Upper Back Pain.

Adult tethered cord syndrome (ATCS) is a rare entity that usually presents with multiple neurological symptoms, including lower extremity pain, backache, lower extremity muscle weakness, and bowel/bladder disturbances. Prompt surgical treatment is often necessary to avoid permanent sequelae. We report a 63-year-old man with sudden-onset severe right chest and upper back pain, followed by urinary retention. His initial workup included computed tomography of the abdomen and pelvis, which showed a presacral mass. His symptom-driven neurological workup focused on the cervical and thoracic spine, the results of which were normal. Pelvic radiographs and magnetic resonance imaging of the lumbosacral spine showed spina bifida occulta, meningocele, and presacral masses consistent with a teratomatous tumor. His symptoms, except for urinary retention, improved dramatically with surgical treatment. The excised specimen contained a teratomatous lesion plus an organized hematoma. Hematoma formation was suspected as the trigger of his sudden-onset right chest and upper back pain.