Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity: Prespecified Subgroup Analysis of the ANNEXA-4 Study in Japan.

AIMS: Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been approved for clinical use in several countries, including Japan, based on the results from the phase 3 trial ANNEXA-4. We aimed to assess the efficacy and safety of andexanet alfa treatment in FXa inhibitor-related acute major bleeding in patients enrolled for ANNEXA-4 in Japan. METHODS: This prespecified analysis included patients enrolled at Japanese sites in the prospective, open-label, single-arm ANNEXA-4 trial. Eligible patients had major bleeding within 18 hours of oral FXa inhibitor administration. The coprimary efficacy endpoints were percent change in anti-FXa activity and proportion of patients achieving excellent or good hemostatic efficacy 12 hours post-treatment. RESULTS: A total of 19 patients were enrolled, all of whom had intracranial hemorrhage; 16 patients were evaluable for efficacy. Median percent reduction in anti-FXa activity from baseline to nadir was 95.4% in patients taking apixaban, 96.1% in patients taking rivaroxaban, and 82.2% in patients taking edoxaban. Overall, 14/16 patients (88%) achieved excellent or good hemostasis (apixaban, 5/5; rivaroxaban, 6/7; edoxaban, 3/4). Within 30 days, treatment-related adverse events (AEs) and serious AEs occurred in 2 and 5 patients, respectively. One patient died during follow-up, and 2 patients experienced thrombotic events. CONCLUSION: Treatment with andexanet alfa rapidly reduced anti-FXa activity with favorable hemostatic efficacy in Japanese patients with acute major bleeding. Serious AEs of thrombotic events during rapid reversal of anti-FXa activity arose as particular safety concerns in this population as with previous studies.

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.

Muscle strength rather than appendicular skeletal muscle mass might affect spinal sagittal alignment, low back pain, and health-related quality of life.

Sarcopenia is defined as decreasing in muscle strength and mass, and dynapenia is defined as decreasing in muscle strength and maintained muscle mass. This study elucidated the prevalence and characteristics of sarcopenia and dynapenia and evaluate in elderly spinal disorders patients. 1039 spinal disorders patients aged ≥ 65 years were included. We measured age, grip strength, muscle mass, spinal sagittal alignment parameters, low back pain (LBP) scores and health-related quality of life (HR-QoL) scores. Based on the previous reports, patients were categorised into normal group: NG, pre-sarcopenia group: PG, dynapenia group: DG, and sarcopenia group: SG. Pre-sarcopenia, dynapenia, and sarcopenia were found in 101 (9.7%), 249 (19.2%), and 91 (8.8%) patients, respectively. The spinal sagittal alignment parameters, trunk muscle mass, LBP, and HR-QoL scores were significantly worse in DG and SG compared with those in PG and NG. Spinal alignment, trunk muscle mass, and clinical outcomes, including LBP and HR-QoL scores, were maintained in the PG and poor in the DG and SG. Thus, intervention for muscle strength may be a treatment option for changes of spinal sagittal alignment and low back pain.

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.

Spinal Epidural Hematoma Due to Venous Congestion Caused by Nutcracker Syndrome.

The causes of spinal epidural hematoma (SEH) have been attributed to coagulopathy, trauma, vascular anomalies, and so forth. The incidence of vascular anomalies shown by digital subtraction angiography has been reported to be 15%, and most cases have been reported to be spinal epidural arteriovenous fistulae. SEH has rarely been caused by venous congestion. We report a case of SEH in a 78-year-old male who presented to our emergency department with sudden-onset back pain, followed by complete paraplegia with bladder and rectal disturbance. Magnetic resonance imaging revealed a dorsally placed extradural hematoma extending from T10 to L1. An urgent laminectomy from T11 to L2 was performed. Computed tomography angiography (CTA) performed 1 week after the operation showed compression of the left renal vein between the aorta and superior mesenteric artery with dilation of the surrounding veins, including the spinal epidural venous plexus, at the same level as the hematoma. This was diagnosed as Nutcracker syndrome (NCS), which was consistent as a cause of SEH. The patient's symptoms gradually improved, and after 6 months, he regained normal strength in his lower extremities, but bladder and rectal disturbance remained and required intermittent self-catheterization. We chose conservative treatment for NCS, and SEH did not recur until the patient died of a cause unrelated to SEH or NCS. SEH could occur secondary to venous congestion including NCS. We emphasize the importance of investigating venous return to evaluate the etiology of SEH, which can be clearly visualized using CTA.

Clinical feasibility of transfer to combined therapy with peritoneal dialysis and hemodialysis for patients on peritoneal dialysis: A prospective multicenter study in Japan.

INTRODUCTION: Although combined therapy with peritoneal dialysis (PD) and hemodialysis (HD) is widespread in Japan, its clinical utility has been reported only in retrospective or before-and-after test lacking a control group. METHODS: We conducted a prospective, multicenter, observational cohort study of 176 incident PD patients and compared patient survival and changes in clinical parameters between patients on different dialysis modalities. RESULTS: During a median follow-up of 41 months, 47 patients transferred to combined therapy and 35 patients transferred directly to HD. Patients transferred to combined therapy had a significantly better survival than those transferred directly to HD. However, we could not establish this difference in a multivariate analysis because only six patients died among these groups. The decreases in urea nitrogen and serum creatinine were more prominent among patients directly transferred to HD. CONCLUSION: This is the first report revealing clinical feasibility of transfer to combined therapy for PD patients.

Quantitative sonographic assessment of quadriceps muscle thickness for fall injury prediction in patients undergoing maintenance hemodialysis: an observational cohort study.

BACKGROUND: Accidental fall risk is high in patients undergoing maintenance hemodialysis. Falls are associated with fatal injury, comorbidities, and mortality. Risk assessment should be a primary component of fall prevention. This study investigated whether quadriceps muscle thickness measured using ultrasonography can predict fall injury among dialysis patients. METHODS: Using an observational cohort study design, 180 ambulatory hemodialysis patients were recruited from 2015 to 2016 from four dialysis clinics. The sum of the maximum quadriceps muscle thickness on both sides and the average of the maximum thigh circumference and handgrip strength after hemodialysis were calculated. Patients were stratified according to tertiles of quadriceps muscle thickness. Fall injury was surveyed according to the patient's self-report during the one-year period. RESULTS: Among the 180 hemodialysis patients, 44 (24.4%) had fall injuries during the 12-month follow-up period. When the quadriceps muscle thickness levels were stratified into sex-specific tertiles, patients in the lowest tertile were more likely to have a higher incidence of fall injury than those in the higher two tertiles (0.52 vs. 0.19 and 0.17 fall injuries/person-year). After adjusting for covariates, lower quadriceps muscle thickness was found to be an independent predictor of fall injury (hazard ratio [95% confidence interval], 2.33 [1.22-4.52], P < 0.05). Receiver operating characteristic curves were constructed to determine the optimal cutoffs of quadriceps muscle thickness, thigh circumference, and handgrip strength that best predicted fall injury (quadriceps muscle thickness, 3.37 cm and 3.54 cm in men and women; thigh circumference, 44.6 cm and 37.2 cm in men and women; and handgrip strength, 23.3 kg and 16.5 kg in men and women). Using these cutoff values, the areas under the curve were 0.662 (95% CI, 0.576-0.738), 0.625 (95% CI, 0.545-0.699), and 0.701 (95% CI, 0.617-0.774), for quadriceps muscle thickness, thigh circumference, and handgrip strength, respectively. Quadriceps muscle thickness was a more precise predictor of fall injury than thigh circumference and had similar diagnostic performance as handgrip strength tests in dialysis patients. CONCLUSIONS: Quadriceps muscle thickness can be measured easily at the bedside using ultrasonography and is a precise predictor of fall injury in patients undergoing maintenance hemodialysis.

Treatment Outcomes of Stent-Assisted Coil Embolization for Ruptured Vertebral Artery Dissecting Aneurysms: The Preservation of Branches May Improve the Prognosis.

Objective: Subarachnoid hemorrhage due to ruptured vertebral artery dissecting aneurysm (rVADA) is associated with a high frequency of acute rebleeding and requires early treatment following onset. Parent artery occlusion (PAO) or stent-assisted coiling (SAC) embolization is selected as a treatment option according to the individual patient condition. This report is a retrospective examination evaluating the treatment outcomes for rVADA. Methods: The subjects were 20 rVADA patients (16 men and 4 women) who underwent endovascular treatment at our institution. The mean patient age was 52.9 years. Ten patients each were allocated to the PAO group and SAC group. We evaluated and compared the following parameters: presence of hemorrhagic complications, presence of ischemic complications, requirement of retreatment, and Glasgow Outcome Scale (GOS) after 90 days. Results: The reasons for selecting SAC were contralateral occlusion or a small diameter in three patients, the posterior inferior cerebellar artery (PICA) involvement in three patients, perforating artery from dissected lesion in five patients, and anterior spinal artery in one patient. There was no rebleeding in any patient. Symptomatic ischemic complications were observed in four patients in the PAO group and in one in the SAC group. Hyper-intense lesions in the brainstem on MRI DWI were noted in five patients in PAO group and in one in the SAC group. Retreatment was required for three patients in the PAO group and for four in the SAC group. Favorable outcomes (GOS 4, 5) after 90 days were observed for three patients in the PAO group and for eight patients in the SAC group (p = 0.0257). Conclusion: SAC that can preserve branches is a useful treatment option for rVADA. Further studies on a greater number of subjects are required to establish the optimal dose of antiplatelet agents and anticoagulants, and for stent selection.

Association of gait speed and grip strength with risk of cardiovascular events in patients on haemodialysis: a prospective study.

BACKGROUND: Gait speed (GS) and handgrip strength (HGS), both factors associated with frailty and sarcopenia, are reportedly associated with CV events in the general population. However, little is known about the impact of these factors on the outcome of patients on dialysis. This study aimed to evaluate whether evaluation of GS and HGS could be associated the onset of fatal/non-fatal cardiovascular (CV) events in patients on haemodialysis (HD). METHODS: One-hundred-eighty-two patients with end-stage renal disease (ESRD) undergoing HD at four dialysis clinics in April 2015 provided written informed consent to participate in the study. We excluded patients who had physical disability, were unable to walk without help, or had recently experienced CV events. Usual GS over a 4-m walk and HGS were measured at baseline, and 173 patients (men, 124; women, 49) were divided into sex-specific quartiles according to GS and HGS and were followed-up for fatal/non-fatal CV events for a median of 2 years. We examined the association of GS and HGS with CV events and determined cut-off values using Cox regression analysis adjusted for age, sex, HD duration, history of CVD, and diabetes. RESULTS: During the follow-up period, 46 CV events occurred. Both physical performance factors were significantly associated with CV events. Low GS (< 0.82 m/s for men and 0.81 m/s for women) and weak HGS (< 29.0 kg for men and 19.7 kg for women) were associated with CV events. For low vs. high GS, the hazard ratio (HR) for CV events was 2.29 [95% confidence interval (CI): 1.20-4.33; P = 0.01], and for low vs. high HGS, the HR was 2.15 [95% CI: 1.00-5.04; P < 0.05]. These HRs remained significant after adjusting for confounding factors, such as sex, age, dialysis vintage, history of CV disease, and diabetes. CONCLUSIONS: Slow GS and weak HGS in patients on HD were suggested to be independent predictors of fatal/non-fatal CV events.

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.

Simultaneous Determination of Inorganic Anions and Cations in Water and Biological Samples by Capillary Electrophoresis with a Capacitive Coupled Contactless Conductivity Detector Using Capillary Filling Method.

An analytical method for concurrent analysis of inorganic anions and cations has been developed using a capillary electrophoresis (CE)-capacitively coupled contactless conductivity detector (C4D) system. Although hydrodynamic and electrokinetic injection techniques have been widely used in CE, we employed a capillary filling method (CFM) for the analysis of inorganic ions. The procedure is relatively simple and has the advantage that CMF does not require pressure control and vial exchange. Three anions (chloride, sulfate, nitrate) and five cations (ammonium, potassium, sodium, magnesium, calcium) were successfully separated and detected at ppm levels within 80 s using a 9 mM histidine/15 mM malic acid (pH 3.6) containing 50 mM N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate as background electrolyte. Applying this analytical condition, the electroosmotic flow is negligible and anions and cations were migrated concurrently to different polarities according to their electrophoretic mobility. Obtained raw data showed stepwise increases in detected conductivity due to the migration of sample components, which expresses as peak profiles by differentiation of electropherograms. The RSD values of the peak area and migration times for the anions and cations were satisfactory and were less than 5.15 and 2.04%, respectively. The developed method was applied for the analysis of inorganic anions and cations in commercial mineral waters, tap water, urine, and exhaled breath condensate. These results indicate that the CE-C4D system with CFM is suitable for the rapid analysis of inorganic anions and cations in various samples.

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.

Combined therapy with peritoneal dialysis and hemodialysis: a multicenter retrospective observational cohort study in Japan.

BACKGROUND/AIMS: Combining peritoneal dialysis (PD) and hemodialysis (HD) has been common treatment option in Japan. METHODS: In this retrospective, multicenter, observational study, the clinical characteristics and outcomes of 104 patients (57 ± 11 years, males 72%) who had switched from PD alone to combined therapy with PD and HD were studied. Clinical parameters were measured at baseline and after 3 months of combined therapy. RESULTS: At baseline, urine volume, dialysate-to-plasma ratio of creatinine (D/P Cr), and total Kt/V were 150 ml/day (range: 0-2,000 ml/day), 0.67 ± 0.11, and 1.8 ± 0.4, respectively. During the first 3 months of combined therapy, body weight, urine volume, serum creatinine level, and D/P Cr decreased, whereas hemoglobin levels increased. CONCLUSIONS: In patients where PD does not result in acceptable outcomes, combined therapy with PD and HD may have potential benefits in terms of dialysis adequacy and hydration status. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=368389

Rotatable reagent cartridge for high-performance microvalve system on a centrifugal microfluidic device.

Recently, microfluidic lab-on-a-CD (LabCD) has attracted attentions of researchers for its potential for pumpless, compact, and chip-inclusive on-site bioassay. To control the fluids in the LabCD, microvalves such as capillary, hydrophobic, siphon, and sacrificial valves have been employed. However, no microvalve can regulate more than one channel. In a complicated bioassay with many sequential mixing, washing, and wasting steps, thus, an intricate fluidic network with many microchannels, microvalves, and reservoirs is required, which increases assay costs in terms of both system development and chip preparation. To address this issue, we developed a rotatable reagent cartridge (RRC), which was a column-shaped tank and has several rooms to store different reagents. By embedding and rotating the RRC in the LabCD with a simple mechanical force, only the reagent in the room connected to the following channel was injected. By regulating the angle of the RRC to the LabCD, conservation and ejection of each reagent could be switched. Our developed RRC had no air vent hole, which was achieved by the gas-permeable gap between the bottle and cap parts of the RRC. The RRC could inject 230 nL-10 µL of reagents with good recoveries more than 96%. Finally, an enzymatic assay of L-lactate was demonstrated, where the number of valves and reservoirs were well minimized, significantly simplifying the fluidic system and increasing the channel integratability. Well quantitative analyses of 0-100 µM L-lactate could easily be carried out with R(2) > 0.999, indicating the practical utility of the RRC for microfluidic bioanalysis.

Development of an on-site measurement system for salivary stress-related substances based on microchip CE.

Secretory immunoglobulin A (sIgA) in saliva has been suggested to be a potential marker of chronic, long-term stress due to suppression of the immune system. A rapid point-of-care testing platform for stress measurement based on immunoassay and capillary electrophoresis (CE) separation was -developed using a poly(methyl methacrylate) (PMMA) chip and a laboratory-built microchip CE system. A method for the quantitative determination of sIgA in human saliva is introduced.

Assessment of body composition using dry mass index and ratio of total body water to estimated volume based on bioelectrical impedance analysis in chronic kidney disease patients.

OBJECTIVE: Body mass index (BMI) is commonly used for assessment of nutritional status. However, changes in BMI in chronic kidney disease (CKD) patients are affected not only by muscle and fat but also by fluid volume. The ratio of extracellular water (ECW(BIA)) to total body water (TBW(BIA)) in multifrequency bioelectrical impedance analysis is commonly used for assessing abnormal fluid status. This study reexamines ECW(BIA)/TBW(BIA) and evaluates the reliability of TBW(BIA)/TBW(watson) and dry mass index (DMI) in the assessment of fluid and nutritional status. DESIGN, SETTING, AND SUBJECTS: TBW(BIA), intracellular water (ICW(BIA)), and ECW(BIA) were measured in 45 randomly selected CKD patients. Participants were surveyed for age, gender, BMI, blood pressure, serum albumin, estimated glomerular filtration rate, and proteinuria. DMI was calculated by the formula ([weight--TBW(BIA)]/height(2)) and TBW(BIA)/TBW(watson) using an anthropometric formula (Watson). Fluid and nutritional status were assessed using ECW(BIA)/TBW(BIA), TBW(BIA)/TBW(watson), and DMI. RESULTS: TBW(BIA)/TBW(watson) positively correlated with weight, BMI, and diastolic blood pressure and negatively correlated with age and serum albumin level. In contrast, ECW(BIA)/TBW(BIA) correlated with ICW deficit, aging, and body weight loss. On the basis of DMI and TBW(BIA)/TBW(watson), participants were categorized as follows: 1 obese patient with hypovolemia and 2 with euvolemia; 17 overweight patients with hypovolemia (n = 6), euvolemia (n = 8), or hypervolemia (n = 3); 24 patients of optimal weight with hypovolemia (n = 10), euvolemia (n = 9), or hypervolemia (n = 5); and 1 underweight patient with euvolemia. CONCLUSIONS: A combination of DMI, BMI, and TBW(BIA)/TBW(watson) makes it possible to include assessment of fluid volume to the physique index. In addition, ECW(BIA)/TBW(BIA) is not a reliable marker of edematous state in CKD patients.