Assessment of global coagulation function under treatment with emicizumab concomitantly with bypassing agents in haemophilia A with inhibitor (UNEBI Study): multicentre open-label non-randomised clinical trial.

INTRODUCTION: Subcutaneous emicizumab prophylaxis substantially reduces bleeding episodes in patients with haemophilia A (PwHA) and factor VIII inhibitor. However, thrombotic events occurred in some PwHA with inhibitor who had received high cumulative doses of activated prothrombin complex concentrates at their breakthrough bleeds, when they were also given prophylactic emicizumab. After that, although the recommended guidance was proposed for bypassing agents (BPAs) therapy under emicizumab prophylaxis for haemostatic management, detailed investigation(s) is(are) required to elucidate the safe and appropriate dose of BPAs to use concomitantly with emicizumab prophylaxis. METHODS AND ANALYSIS: In the UNEBI Study, 60 PwHA with inhibitor will be enrolled for a maximum duration of 3 years, and samples of 20 events following concomitant use of BPAs with emicizumab will be collected. An 'event' is defined as obtaining blood samples before and after administration of BPA when a breakthrough bleed or a surgical procedure occurs. The coagulation potential in the obtained samples will be measured by global coagulation assays. The primary endpoint is the degree of improvement in the maximum coagulation rate by clot waveform analysis (CWA) before and after administration of fixed-dose BPAs. This parameter obtained from CWA, which is triggered with an optimally diluted mixture of prothrombin time/activated partial thromboplastin time-reagents, is reported to be an excellent marker for assessing the degree of improvement in coagulation potential in emicizumab-treated plasma. ETHICS AND DISSEMINATION: The UNEBI Study was approved by the Japan Certified Review Board of Nara Medical University. The results of the study will be communicated through publication in international scientific journals and presentations at (inter)national conferences. TRIAL REGISTRATION NUMBER: jRCTs051190119.

Quality assessment of cellular and tissue-based products using liquid chromatography-tandem mass spectrometry.

We are currently conducting clinical research on cell sheets for cartilage regeneration. One issue with the future use of chondrocyte sheets as cellular and tissue-based products is quality assessment. Currently, chondrocyte sheets are evaluated using invasive methods that cannot be performed on every sheet produced. We report here on our liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique that allows the noninvasive assessment of every sheet using only 50 µl of culture medium. We found that LC-MS/MS could be used to confirm cell sheet viability through the measurement of glucose and glutamine uptake, to estimate extracellular matrix production by measuring serine consumption, to estimate cell kinetics by measuring cytidine and uracil concentrations, and to estimate melanoma inhibitory activity level by measuring pyridoxal concentration. LC-MS/MS may be useful for the noninvasive assessment of products to be used in regenerative medicine.

A novel immunochromatographic system for easy-to-use detection of group 1 avian influenza viruses with acquired human-type receptor binding specificity.

A switch of viral hemagglutinin receptor binding specificity from bird-type α2,3- to human-type α2,6-linked sialic acid is necessary for an avian influenza virus to become a pandemic virus. In this study, an easy-to-use strip test to detect receptor binding specificity of influenza virus was developed. A biotinylated anti-hemagglutinin antibody that bound a broad range of group 1 influenza A viruses and latex-conjugated α2,3 (blue) and α2,6 (red) sialylglycopolymers were used in an immunochromatographic strip test, with avidin and lectin immobilized on a nitrocellulose membrane at test and control lines, respectively. Accumulation of a sialylglycopolymer-virus-antibody complex at the test line was visualized by eye. The strip test could be completed in 30min and did not require special equipment or skills, thereby avoiding some disadvantages of current methods for analyzing receptor binding specificity of influenza virus. The strip test could detect the receptor binding specificity of a wide range of influenza viruses, as well as small increases in the binding affinity of variant H5N1 viruses to α2,6 sialylglycans at viral titers >128 hemagglutination units. The strip test results were in agreement with those of ELISA virus binding assays, with correlations >0.95. In conclusion, the immunochromatographic strip test developed in this study should be useful for monitoring potential changes in the receptor binding specificity of group 1 influenza A viruses in the field.

Efficacy of propofol sedation for endoscopic submucosal dissection (ESD): assessment with prospective data collection.

OBJECTIVE: The indications for endoscopic treatment in early stage cancer of the digestive tract are expanding with the emergence and technical development of endoscopic submucosal dissection (ESD). ESD requires longer term stable sedation than conventional endoscopic procedures due to the necessity of meticulous control of the devices during the procedure. Propofol has a very short half-life and can be administered continuously, which is advantageous for long-term sedation. Propofol, thus, is likely to be useful for sedation during ESD. METHODS: Fifty consecutive patients who underwent ESD for early gastric cancer with propofol sedation (Group P) and those with midazolam sedation (Group M) were included in this study. Cardiorespiratory suppression rate and the condition of arousal were compared between the groups. A questionnaire survey on the satisfaction of endoscopists, anesthesiologists, endoscopy nurses, and ward nurses with the use of propofol was also carried out. RESULTS: Respiratory suppression was observed in 50% in Group M and in 20% in Group P (p<0.05). Hypotension was seen in 14% and 36% in Groups M and P, respectively (p<0.05). No sedation-related complications were encountered in either of the groups. Arousal rates 1 hour and 3 hours after the procedure were 23% and 60% in group M and 86% and 100% in Group P (p<0.05). As for the questionnaire survey, most respondents, in particular the ward nurses, supported the use of propofol. CONCLUSION: Our data suggest that propofol is safe and useful during ESD as compared with midazolam.

Intraoperative multichannel audio-visual information recording and automatic surgical phase and incident detection.

Identification, analysis, and treatment of potential risk in surgical workflow are the key to decrease medical errors in operating room. For the automatic analysis of recorded surgical information, this study reports multichannel audio visual recording system, and its review and analysis system. Motion in operating room is quantified using video file size without motion tracking. Conversation among surgical staff is quantified using fast Fourier transformation and frequency filter without speech recognition. The results suggested the progression phase of surgical procedure.

Development of the ultra-miniaturized Inertial Measurement Unit WB3 for objective skill analysis and assessment in neurosurgery: preliminary results.

In recent years there has been an ever increasing amount of research and development of technologies and methodologies aimed at improving the safety of advanced surgery. In this context, several training methods and metrics have been proposed, in particular for laparoscopy, both to improve the surgeon's abilities and also to assess her/his skills. For neurosurgery, however, the extremely small movements and sizes involved have prevented until now the development of similar methodologies and systems. In this paper we present the development of the ultra-miniaturized Inertial Measurement Unit WB3 (at present the smallest, lightest, and best performing in the world) for practical application in neurosurgery as skill assessment tool. This paper presents the feasibility study for quantitative discrimination of movements of experienced surgeons and beginners in a simple pick and place scenario.

Ultrasound properties of articular cartilage in the tibio-femoral joint in knee osteoarthritis: relation to clinical assessment (International Cartilage Repair Society grade).

INTRODUCTION: There is a lack of data relating the macroscopic appearance of cartilage to its ultrasound properties. The purpose of the present study was to evaluate degenerated cartilage and healthy-looking cartilage using an ultrasound system. METHODS: Ultrasound properties--signal intensity (a measure of superficial cartilage integrity), echo duration (a parameter related to the surface irregularity) and the interval between signals (that is, time of flight--which is related to the thickness and ultrasound speed of cartilage)--of 20 knees were measured at seven sites: the lateral femoral condyle (site A, anterior; site B, posterior), the medial condyle (site C), the lateral tibial plateau (site D, center; site E, under the meniscus) and the medial tibial plateau (site F, anterior; site G, posterior). The sites were evaluated macroscopically and classed using the International Cartilage Repair Society (ICRS) grading system. RESULTS: The signal intensity of grade 0 cartilage was significantly greater than the intensities of grade 1, grade 2 or grade 3 cartilage. Signal intensity decreased with increasing ICRS grades. The signal intensity was greater at site B than at site C, site D, site F and site G. The signal intensity of grade 0 was greater at site B than at site E. The echo duration did not differ between the grades and between the sites. The interval between signals of grade 3 was less than the intervals of grade 0, grade 1 or grade 2. The interval between signals at site C was less than the intervals at site A, site B, site D, and site E. CONCLUSION: Site-specific differences in signal intensity suggest that a superficial collagen network may be maintained in cartilage of the lateral condyle but may deteriorate in cartilage of the medial condyle and the medial tibial plateau in varus knee osteoarthritis. Signal intensity may be helpful to differentiate ICRS grades, especially grade 0 cartilage from grade 1 cartilage.

Incidence and burden of rotavirus gastroenteritis in Japan, as estimated from a prospective sentinel hospital study.

We assessed the burden of rotavirus infection-related disease, in terms of hospitalization and associated costs, at 3 sentinel hospitals in Akita prefecture, Japan. From January 2001 through December 2002, a total of 443 children <5 years of age were hospitalized for acute gastroenteritis. Of 422 stool specimens collected, 244 (58%) tested positive for rotavirus. Only 7.8% of the rotavirus disease-associated hospitalizations involved infants <6 months of age, whereas most cases of disease (39%) were reported in the second year of life, and 89% of cases had occurred by 36 months of age. The mean severity score for rotavirus gastroenteritis resulting in hospitalization was 16.5, according to the modified 20-point severity scoring system. The average associated direct medical cost was 136,000 yen (1236 US dollars) per case and was similar among the 3 hospitals. The estimated incidence of rotavirus disease-associated hospitalizations among children <5 years of age was 7.9-17.6 hospitalizations/1000 person-years, and the estimated cumulative incidence by 5 years of age was 6.6%. Thus, approximately 1 in 15 children will require hospitalization due to rotavirus diarrhea by their fifth year of life. In Japan, this would mean that 78,000 children <5 years of age would be hospitalized each year, resulting in a direct medical cost of 10 billion yen (96 US dollars million). The burden associated with rotavirus gastroenteritis in Japan is substantial and might be reduced through the introduction of vaccines.

Rank in Self-Defense Forces and risk factors for atherosclerotic disease.

Socioeconomic status is associated with prevalence of and risk for atherosclerotic disease. We investigated the relationship between rank in the Self-Defense Forces (SDFs) and risk factors for atherosclerotic disease among middle-aged, male, SDFs personnel. Subjects were classified into five groups according to their ranks in the SDFs, i.e., class 1 (lowest, n = 289), class 2 (low, n = 170), class 3 (middle, n = 229), class 4 (high, n = 197), and class 5 (highest, n = 89). Low rank was associated with current cigarette smoking, alcohol abstaining, and poorer vegetable consumption. It was also associated with prevalence of type 2 diabetes, elevated gamma-glutamyltransferase activity, and high white blood cell counts. Prevalence of obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, or hyperuricemia was not associated with rank in this population. Rank may be regarded as one of the markers that reflect individual health states among middle-aged male personnel.