Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

PURPOSE: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay. EXPERIMENTAL DESIGN: FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. RESULTS: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL. CONCLUSIONS: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

Posterior Spinal Fusion Surgery for Neuromuscular Disease Patients with Severe Scoliosis Whose Cobb Angle Was over 100 Degrees.

Background and objectives: Patients with neuromuscular diseases usually have progressive neuromuscular scoliosis (NMS), requiring invasive surgery. Some patients present with severe scoliosis at the time of consultation and are difficult to treat. Posterior spinal fusion (PSF) surgery combined with anterior release and pre- or intraoperative traction would be effective for severe spinal deformities but would be invasive. This study aimed to evaluate the outcomes of PSF-only surgery for patients with severe NMS with a Cobb angle > 100°. Materials and Methods: Thirty NMS patients (13 boys and 17 girls; mean age 13.8 years) who underwent PSF-only surgery for scoliosis with a Cobb angle > 100° were included. We reviewed the lower instrumented vertebra (LIV), duration of surgery, blood loss, perioperative complications, preoperative clinical findings, and radiographic findings, including Cobb angle and pelvic obliquity (PO) in the sitting position pre- and postoperatively. The correction rate and correction loss of the Cobb angle and PO were also calculated. Results: The mean duration of surgery was 338 min, intraoperative blood loss was 1440 mL, preoperative %VC was 34.1%, FEV1.0 (%) was 91.5%, and EF was 66.1%. There were eight cases of perioperative complications. The Cobb angle and PO correction rates were 48.5% and 42.0%, respectively. We divided the patients into two groups: the L5 group, in which the LIV was L5, and the pelvis group, in which the LIV was the pelvis. The duration of surgery and PO correction rate in the pelvis group were significantly higher than those in the L5 group. Conclusions: Patients with severe NMS demonstrated severe preoperative restrictive ventilatory impairments. PSF surgery without anterior release or any intra-/preoperative traction showed satisfactory outcomes, including acceptable scoliosis correction and improved clinical findings, even in patients with extremely severe NMS. Instrumentation and fusion to the pelvis for severe scoliosis in patients with NMS showed good PO correction and low correction loss of Cobb angle and PO, but a longer duration of surgery.

Pediatric internal auditory canal cavernous hemangioma with rapid progression of sensorineural hearing loss: illustrative case.

BACKGROUND: Cavernous hemangioma of the internal auditory canal is extremely rare and is characterized by symptoms such as vertigo, sensorineural hearing loss, and facial nerve dysfunction. OBSERVATIONS: A health examination on an 11-year-old female in the fifth grade revealed hearing loss in the left ear. She also had dizziness that had persisted for approximately 1 year. Pure-tone audiometry revealed sensorineural hearing loss in her left ear. Rightward horizontal and rotatory nystagmus was detected. Facial paralysis was not present. Magnetic resonance imaging showed a lesion that was suspected to be hemangioma. The authors selected a left suboccipital retrosigmoid approach. The tumor showed a berry-tufted appearance throughout the cerebellopontine angle. The seventh cranial nerve penetrated the tumor and partly circulated outside the tumor with marked adhesion. The authors partially resected the tumor to avoid damaging the facial nerve. A histological examination identified cavernous hemangioma. LESSONS: The fundamental treatment for cavernous hemangioma of the internal auditory canal is complete surgical removal; however, any surgical intervention may result in hearing loss and facial paralysis. The extent of surgery needs to be decided intraoperatively based on the balance between preoperative symptoms and postoperative complications.

Changes in erythropoiesis-stimulating agent responsiveness after transfer to combined therapy with peritoneal dialysis and hemodialysis for patients on peritoneal dialysis: A prospective multicenter study in Japan.

INTRODUCTION: Inadequate dialysis and fluid overload are corrected after starting combined therapy with peritoneal dialysis (PD) and hemodialysis (HD). However, the effects on anemia management has not been elucidated. METHODS: We conducted a prospective, multicenter, observational cohort study of 40 PD patients (age, 60 ± 10 years; male, 88%; median PD duration, 28 months) starting combined therapy and investigated changes in several clinical parameters, including erythropoiesis-stimulating agent (ESA) resistance index (ERI). RESULTS: ERI decreased significantly during 6 months after switching to combined therapy (from 11.8 [IQR 8.0-20.4] units/week/kg/(g/dL) to 7.8 [IQR 3.9-18.6] units/week/kg/(g/dL), p = 0.047). Body weight, urinary volume, serum creatinine and the dialysate-to-plasma creatinine ratio (D/P Cr) decreased, whereas hemoglobin and serum albumin increased. In subgroup analysis, the changes in ERI were not affected by cause for starting combined therapy, PD holiday and D/P Cr. CONCLUSION: Although detailed mechanism was unclear, ESA responsiveness improved after switching from PD alone to combined therapy.

Synergistic deterioration of prognosis associated with decreased grip strength and hyporesponse to erythropoiesis-stimulating agents in patients undergoing hemodialysis.

INTRODUCTION: We examined the combined effect of erythropoietin (EPO) hyporesponsiveness and low handgrip strength (HGS) on the prognosis of patients undergoing hemodialysis (HD). METHODS: We recruited patients with chronic kidney disease (CKD) Stage 5, who were undergoing HD at our dialysis clinic between January 2015 and March 2015 (n = 182). Patients of ≥20 years of age and who had been undergoing HD for ≧3 months at enrollment were eligible for inclusion. Seven patients treated with epoetin-ß pegol were excluded. First, the erythropoietin resistance index (ERI) and HGS were measured. The patients were stratified by the ERI of 9.44 (U/kg/week/g/dL), and by the HGS of 28 kg for men and 18 kg for women. We then observed death and cardiovascular disease (CVD), composite endpoint (deaths or CVD) for a median of 2 years. RESULTS: A total of 175 patients (male, n = 122; female, n = 53; age, 34-92 years) were included in the analysis. During the observation period of 24 months, 57 events (14 deaths and 43 CVD) were observed. High ERI and low HGS were associated with a high incidence of endpoints compared to low ERI and high HGS. Among the four groups classified by ERI and HGS values, the highest risk group was the high ERI/low HGS group (HR: 4.20 95% CI 2.12-8.33). CONCLUSIONS: EPO hyporesponsiveness combined with low HGS were found to be significant predictors of a poor outcome, and the synergistic effects of the two factors had stronger predictive ability than either single factor.

Clival Metastasis of Hepatocellular Carcinoma with an Initial Histopathological Diagnosis of Atypical Pituitary Adenoma.

Histologically, hepatocellular carcinoma (HCC) and atypical pituitary adenoma are similar, posing a potential clinical problem. A 76-year-old woman, whose past medical history was significant for hepatitis C virus (HCV), positivity without liver cirrhosis was presented with abducens nerve (CN VI) palsy. Contrast-enhanced magnetic resonance imaging (MRI) showed a clival tumor with infiltration of the right cavernous sinus. Subtotal resection was performed using a right anterior petrosal approach. Histological diagnosis was pituitary adenoma. Thirty-four days after the operation, MRI imaging showed residual tumor growth without any liver masses on computed tomography (CT). The patient underwent a second operation using an endoscopic transnasal transsphenoidal approach. Histological examination of the specimen gave a positive reaction for α -fetoprotein. Repeat whole-body CT showed an enhanced liver mass. Based on these findings, the lesion was diagnosed as metastatic HCC. The patient died of liver failure 6 months later. In this case, tumor diagnosis was difficult because of the histological similarity of HCC and pituitary adenoma, and the fact that the clival tumor grew prior to presentation of the liver mass on CT. This case emphasizes the importance of comparing the pathological diagnosis with the patient's clinical course.

Intrasellar Symptomatic Salivary Gland Rest with Inflammations.

BACKGROUND: Instances of ectopic salivary gland tissue within the pituitary gland are rare, they are mostly asymptomatic, and the underlying pathophysiology of symptomatic cases is unclear. We report a case of intrasellar salivary gland rest that presented clinical symptoms and clearly related to inflammatory changes. CASE DESCRIPTION: In the present case, headache, bitemporal hemianopia, and hormone abnormality led to the detection of ectopic salivary gland tissue within the pituitary gland of a 24-year-old man. Imaging revealed a well-circumscribed intrasellar cystic lesion having a diameter of major axis of 16 mm, for which tumorectomy was performed using the nasal approach. The tumor was cystic with stringy content. Pathologic findings revealed that the lesion was composed principally of secretions lacking cell components, whereas the salivary gland tissue was found in the cyst wall. Dilated ducts due to the leakage of secretions were also observed. Acute and chronic inflammation was present around the salivary gland. CONCLUSIONS: Not only are instances of symptomatic ectopic salivary glands rare, but this was also the first case detected to be caused by the pathophysiology involving the leakage of secretions from an ectopic salivary gland and associated inflammation. We report this case to help elucidate the pathophysiology of the condition.

[Biomarkers of stress and fatigue].

A questionnaire based survey has been commonly used for the assessment of psychological stress and stress-related diseases. Development of a quantitative approach using a non-invasive sample (i.e., saliva, hair or nails) is highly desirable to measure chronic stress. This paper gives a brief explanation of subjective and objective (i.e., physiological signals, and biological markers) methods for stress assessment. Furthermore, it focuses particularly on the current knowledge about the biomarker candidates of chronic psychological stress and chronic fatigue syndrome (CFS). Psychological stress is known to stimulate the autonomic nervous, endocrine, and immune systems. Since chronic stress is associated with suppression of a variety of immune parameters, some immune markers are potentially useful.

Expression of ACE and ACE2 in individuals with diabetic kidney disease and healthy controls.

BACKGROUND: Angiotensin-converting enzyme (ACE) 2 (ACE2) is expressed mainly in the heart and kidney and forms angiotensin-1-7 from angiotensin II. ACE2 might act in a counterregulatory manner to ACE. There is little information about renal ACE and ACE2 expression in human diabetic nephropathy. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Kidney tissue from 20 patients with type 2 diabetes and overt nephropathy and 20 healthy kidney donors. PREDICTOR: Diabetes status. OUTCOMES & MEASUREMENTS: Renal expression of ACE and ACE2 assessed by means of immunohistochemistry and in situ hybridization. Correlation between ACE and ACE2 expression and levels of various biochemical parameters. RESULTS: Decreased ACE2 and increased ACE expression in both the tubulointerstitium and glomeruli resulted in a significant (P < 0.001) increase in ACE/ACE2 ratio in patients with diabetes with overt nephropathy compared with controls, although ACE messenger RNA in the tubulointerstitium did not significantly increase. ACE/ACE2 ratio correlated positively with values for mean blood pressure, fasting blood glucose, serum creatinine, proteinuria, and hemoglobin A(1c) and inversely with estimated glomerular filtration rate (P < 0.001). LIMITATIONS: Inclusion of small number of human renal biopsy specimens with structural distortion of cortical tissue. CONCLUSIONS: The high ACE/ACE2 ratio in kidneys of patients with type 2 diabetes with overt nephropathy may contribute to renal injury.

Quantitative analysis of sulfur-related metabolites during cadmium stress response in yeast by capillary electrophoresis-mass spectrometry.

The objective of this research is to establish an evaluation system of metabolites by capillary electrophoresis-mass spectrometry (CE-MS) in response to chemical stress using the unicellular genome model, yeast (Saccharomyces cerevisiae strain S288C). A method previously reported by Soga et al. was modified and validated for the determination of sulfur-related metabolites, 23 cationic metabolites, in yeast extract. A mixture of 5 mM formic acid in 50% (v/v) 2-propanol was used for the sheath liquid to improve the detection sensitivity. Moreover, washing of CE capillary with 0.1M ammonia solution between successive runs enhanced the reproducibility. After analytical validation, the method was applied to the metabolomic analysis of yeast cells in response to cadmium (Cd) stress. Under Cd exposure, some interesting observations were obtained, particularly the depletion of glycine and the strong accumulation of L-gamma-glutamylcysteine in yeast cells.

The role of von Hippel-Lindau protein in the differentiation of neural progenitor cells under normoxic and anoxic conditions.

Von Hippel-Lindau protein (pVHL) normally functions to cause ubiquitin-mediated degradation of hypoxia-inducible factor-1alpha (HIF-1alpha) under normoxic but not under hypoxic conditions, and induces neuronal differentiation of neural progenitor cells. However, the role of pVHL in the differentiation of neural progenitor cells under either condition has not been fully elucidated. Herein, we show that under the anoxic condition the expression of pVHL and neuronal markers in neural progenitor cells was inhibited, while HIF-1alpha was induced. In addition, neural progenitor cells expressing pVHL following gene transfer showed distinct neuronal differentiation and no induction of HIF-1alpha under the normoxic condition but not under the anoxic condition. In conclusion, neuronal differentiation induced by pVHL is associated with degradation of HIF-1alpha and occurs normally under the normoxic condition but not under the anoxic condition. Differentiation of neuronal progenitor cells may thus depend on oxygen density.

Simultaneous separation and on-line concentration of amitrole and benzimidazole pesticides by capillary electrophoresis with a volatile migration buffer applicable to mass spectrometric detection.

This study used capillary electrophoresis (CE) to investigate the simultaneous separation and on-line concentration of five pesticides: amitrole (AMT), carbendazim (MBC), 2-aminobenzimidazole (ABI), thiabendazole (TBZ) and 1,2-diaminobenzene (DAB). A volatile migration buffer was used for the investigation because of the applicability to mass spectrometric (MS) detection. They were separated completely at pH 4.0 as a result of changing pH using formic acid-ammonium formate buffer. Values of the dissociation constant for MBC and DAB estimated from the changes in the mobility with pH showed good agreement with values in the literature. Dissociation constants for AMT and TBZ were estimated. Limits of detection (LODs) for the analytes were on the ppm level with UV detection under the optimized separation condition. On-line concentration by simple stacking mode was not effective except to 2-aminobenzimidazole because of the peak tailing. The addition of formic acid to sample matrix improved the peak shapes. That improvement may be attributed to transient isotachophoretic effect. The concentration factors obtained from the comparison of the LODs were in the range of 7.6-27-fold. This concentration method was applied preliminarily to CE with MS detection.