Miliary tuberculosis-associated hemophagocytic lymphohistiocytosis with a high level of soluble interleukin-2 receptor successfully treated with concomitant recombinant thrombomodulin: A case report.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disease characterized by a highly inflammatory state due to the abnormal activation of T lymphocytes and macrophages. Miliary tuberculosis (MTB) is a rare cause of HLH and its clinical appearances occasionally resembles that of intravascular lymphoma (IVL). A 76-year-old woman presented with persistent fever and fatigue. Abnormal laboratory findings showing thrombocytopenia (13,000/µL), hypofibrinogenemia (101 mg/dL), hyperferritinemia (2,312 ng/mL), and markedly elevated soluble interleukin-2 receptor (sIL-2R) level (32,200 U/mL), in addition, hemophagocytosis in the bone marrow (BM) smear, were suggestive of IVL-associated HLH. The pathology of the BM biopsy specimen showed granuloma with non-caseous necrosis, and culture tests using sputum, gastric fluid, urine, and peripheral and bone marrow blood revealed the presence of Mycobacterium tuberculosis, leading to the final diagnosis of MTB-associated HLH. Anti-TB medications and corticosteroids were administered, but thrombocytopenia, hypofibrinogenemia, and hyperferritinemia persisted. Concomitant use of recombinant thrombomodulin (rTM) enabled regression of clinical status. In this case, BM biopsy served as the diagnosis of MTB-associated HLH, although IVL-associated HLH is initially suspected by an extremely high level of sIL-2R. Furthermore, this case report informs that using rTM could improve the outcomes of MTB-associated HLH.

Implications of the Onset of Sweating on the Sweat Lactate Threshold.

The relationship between the onset of sweating (OS) and sweat lactate threshold (sLT) assessed using a novel sweat lactate sensor remains unclear. We aimed to investigate the implications of the OS on the sLT. Forty healthy men performed an incremental cycling test. We monitored the sweat lactate, blood lactate, and local sweating rates to determine the sLT, blood LT (bLT), and OS. We defined participants with the OS during the warm-up just before the incremental test as the early perspiration (EP) group and the others as the regular perspiration (RP) group. Pearson's correlation coefficient analysis revealed that the OS was poorly correlated with the sLT, particularly in the EP group (EP group, r = 0.12; RP group, r = 0.56). Conversely, even in the EP group, the sLT was strongly correlated with the bLT (r = 0.74); this was also the case in the RP group (r = 0.61). Bland-Altman plots showed no bias between the mean sLT and bLT (mean difference: 19.3 s). Finally, in five cases with a later OS than bLT, the sLT tended to deviate from the bLT (mean difference, 106.8 s). The sLT is a noninvasive and continuous alternative to the bLT, independent of an early OS, although a late OS may negatively affect the sLT.

Relationship between hip joint proximity area and sagittal balance parameters: an upright computed tomography study.

PURPOSE: A close relationship between sagittal spinal alignment and hip osteoarthritis (OA) has been documented. This study aimed to examine the relationship between hip joint proximity area and sagittal balance parameters in healthy subjects. METHODS: This prospective study enrolled 47 healthy volunteers who underwent 320-detector row upright computed tomography. Acquired data were reconstructed in a virtual three-dimensional space. The proximity area was determined by < 1 mm of the Hausdorff distance between the acetabulum and the femoral head. Volunteers were divided into the anterior and posterior proximity groups depending on the position of the closest area. Sagittal balance parameters [sagittal vertical axis (SVA), T1 spinopelvic inclination (T1-SPi), T1-pelvic angle, pelvic tilt, sacral slope, pelvic incidence, lumbar lordosis, thoracic kyphosis), offset distance between the centre of the acoustic meati (CAM) and C7 plumb line (CAM-C7-offset), and offset distance between the CAM and hip axis (HA) (CAM-HA-offset)] were compared between the two groups using independent sample t test. RESULTS: The anterior proximity group (n = 24) had higher SVA (p = 0.016) and T1-Spi (p = 0.015) than the posterior proximity group (n = 23). CAM-HA-offset was higher in the posterior than in the anterior proximity group (p < 0.000). There was no difference in other parameters (p > 0.05). CONCLUSION: The anterior proximity group had a positive anterior spinal balance; the posterior proximity group may have a more posterior gravity line than the hip joint centre. The anterior spinal balance may contribute to the anterior loading of the hip joint, with known relation with the initiation and onset of hip OA.

Effects of alternating heat and cold stimulation at different cooling rates using a wearable thermo device on shoulder muscle stiffness: a cross-over study.

BACKGROUND: A small, wearable thermo device that uses Peltier elements for programmed heat and cold stimulation has been developed recently and is expected to be applied in conventional contrast bath therapy. This study was aimed to examine improvements in trapezius muscle hardness and subjective symptoms resulting from alternating heat and cold stimulation, with different rates of cooling. METHODS: This cross-over study included four conditions. Twenty healthy young male individuals (age, 22.3 ± 4.5 years) participated in this study. These four interventions targeted the unilateral trapezius muscle of the dominant arm after a 15-min typing task. Specifically, heat and cold stimulations were applied at different ratios (the heating/cooling rate of 3:1, 3:2, and 3:3) or not applied. Each intervention was separated by at least one week. Skin temperature at the stimulation area was recorded using a data logger. Outcome measures included muscle hardness (measured using a portable tester) and subjective symptoms (muscle stiffness and fatigue). Each item was assessed at three time points: baseline, after typing, and after the intervention. RESULTS: Two-way analysis of variance with repeated measures found an interaction effect for muscle hardness between four conditions (3:1, 3:2, 3:3, and no) and three time points (p < 0.05). Only in the 3:1 condition were the post-intervention values lower than those after typing (p < 0.01). There was also an interaction effect for subjective muscle stiffness (p < 0.05); the values after the intervention in the 3:1 condition were lower than those after intervention in the no stimulation condition (p < 0.01). There was no significant relationship between changes in muscle hardness and changes in subjective symptoms in the 3:1 condition. CONCLUSIONS: Our results demonstrate that alternating heat and cold stimulations with a different cooling rate could affect the degree of improvement in muscle hardness and subjective symptoms. In particular, the 3:1 condition has the possibility to improved muscle hardness within the condition and subjective muscle stiffness between conditions. TRIAL REGISTRATION: UMIN000040620. Registered 1 June 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046359.

Rare earth element identification and quantification in millimetre-sized Ryugu rock fragments from the Hayabusa2 space mission.

Millimetre-sized primordial rock fragments originating from asteroid Ryugu were investigated using high energy X-ray fluorescence spectroscopy, providing 2D and 3D elemental distribution and quantitative composition information on the microscopic level. Samples were collected in two phases from two sites on asteroid Ryugu and safely returned to Earth by JAXA's asteroid explorer Hayabusa2, during which time the collected material was stored and maintained free from terrestrial influences, including exposure to Earth's atmosphere. Several grains of interest were identified and further characterised to obtain quantitative information on the rare earth element (REE) content within said grains, following a reference-based and computed-tomography-assisted fundamental parameters quantification approach. Several orders of magnitude REE enrichments compared to the mean CI chondrite composition were found within grains that could be identified as apatite phase. Small enrichment of LREE was found for dolomite grains and slight enrichment or depletion for the general matrices within the Ryugu rock fragments A0055 and C0076, respectively. Supplementary Information: The online version contains supplementary material available at 10.1186/s40623-022-01705-3.

Sweep Pulse Excitation Method for Enhancing Photoacoustic Elastic Waves at Different Laser Irradiation Parameters.

Laser remote sensing using a sweep pulse excitation method, in which a laser beam is irradiated at the same repetition frequency as the natural frequency, for enhancing photoacoustic elastic waves through resonance effect has been studied. The sweep pulse excitation method, which is based on the principle of detecting natural frequency fluctuations, such as hammering tests, can detect natural frequencies in the audible sound region with low average laser power and contribute to the convenience and low cost of an installation strength diagnosis of fastening bolts. In this study, we investigated the dynamics of the swept excitation method for optimization by evaluating the dependence of the laser irradiation conditions (pulse width, spot size, and average power) on different metal disc samples. We discovered that the magnitude of the photoacoustic elastic wave is proportional to the absorption of laser power, and the spatiotemporal dynamics can be explained through thermal diffusion phenomena. These findings contribute to the development of laser-sensing technology based on photoacoustic elastic waves.

Realtime Monitoring of Local Sweat Rate Kinetics during Constant-Load Exercise Using Perspiration-Meter with Airflow Compensation System.

Epidermal wearable sweat biomarker sensing technologies are likely affected by sweat rate because of the dilution effect and limited measurement methods. However, there is a dearth of reports on the local sweat rate (LSR) monitored in real-time during exercise. This explorative study investigated the feasibility of real-time LSR monitoring and clarified LSR kinetics on the forehead and upper arm during constant-load exercise using a perspiration meter with an airflow compensation system. This observational cross-sectional study included 18 recreationally trained males (mean age, 20.6 ± 0.8 years). LSR on the forehead and upper arm (mg/cm2/min) were measured during a constant-load exercise test at 25% of their pre-evaluated peak power until exhaustion. The LSR kinetics had two inflection points, with a gradual decrease in the incremental slope for each section. After the second flexion point, the LSR slope slightly decreased and was maintained until exhaustion. However, the degree of change varied among the participants. Although the ratio of forehead LSR to upper arm LSR tended to decrease gradually over time, there was little change in this ratio after a second flexion point of LSR in both. These findings suggest possible differences in LSR control between the forehead and upper arm during constant-load exercise to prolonged exhaustion.

Constant Load Pedaling Exercise Combined with Electrical Muscle Stimulation Leads to an Early Increase in Sweat Lactate Levels.

A novel exercise modality combined with electrical muscle stimulation (EMS) has been reported to increase cardiovascular and metabolic responses, such as blood lactate concentration. We aimed to examine the effect of constant load pedaling exercise, combined with EMS, by non-invasively and continuously measuring sweat lactate levels. A total of 22 healthy young men (20.7 ± 0.8 years) performed a constant load pedaling exercise for 20 min at 125% of the pre-measured ventilatory work threshold with (EMS condition) and without (control condition) EMS stimulation. Blood lactate concentration was measured by blood samples obtained from the earlobe every minute. Sweat lactate was monitored in real time using a sensor placed on the forearm. The sweat lactate threshold (sLT) was defined as the point of increase in sweat lactate. sLT occurred significantly earlier in the EMS condition than in the control condition. In the single regression analysis, the difference in sLT between the two conditions, as the independent variable, was a significant predictor of the difference in blood lactate concentrations at the end of the exercise (p < 0.05, r = −0.52). Sweat lactate measurement may be a noninvasive and simple alternative to blood lactate measurement to determine the effectiveness of exercise combined with EMS.

Comparison of bacterial culture results of preoperative synovial fluid and intraoperative specimens in patients with joint infection.

OBJECTIVES: The details of relationship between bacterial culture results of preoperative and intraoperative specimens in same patients with native joint septic arthritis (NJSA) and periprosthetic joint infection (PJI) are unknown. This study aims to reveal the difference of culture results of preoperative synovial fluid and intraoperative specimens and evaluate the risk factors for detecting different species intraoperatively from preoperative synovial fluid. METHODS: This study included 55 joints diagnosed with 16 NJSA and 39 PJI. Bacterial culture positive rates and identified bacterial species were compared between preoperative synovial fluid and intraoperative tissue/synovial fluid. We also examined the presence or absence of sinus tracts and antimicrobial agents as risk factors in patients with different bacterial species in intraoperative specimens from preoperative synovial fluid. RESULTS: The culture positive rates were not significantly different between preoperative synovial fluid and intraoperative specimens. Different bacterium were detected in 10.9% joints by intraoperative tissue and 14.6% joints by intraoperative synovial fluid. The positive rate of sinus tract was significantly higher in patients with different bacterial species (62.5%) than without different bacterial species (12.8%, p < 0.01). Conversely, antimicrobial agent was not significantly difference. CONCLUSION: This study demonstrated that different bacterium from preoperative culture results were detected in 10-15% joints by intraoperative specimens in NJSA and PJI. The sinus tract was a risk factor for identifying different bacterial species in the intraoperative specimens. Therefore, in cases of sinus tract, it is necessary to examine multiple specimens of both intraoperative tissue and synovial fluid for increasing the detection rate.

Machine Learning-Based Diagnosis in Laser Resonance Frequency Analysis for Implant Stability of Orthopedic Pedicle Screws.

Evaluation of the initial stability of implants is essential to reduce the number of implant failures of pedicle screws after orthopedic surgeries. Laser resonance frequency analysis (L-RFA) has been recently proposed as a viable diagnostic scheme in this regard. In a previous study, L-RFA was used to demonstrate the diagnosis of implant stability of monoaxial screws with a fixed head. However, polyaxial screws with movable heads are also frequently used in practice. In this paper, we clarify the characteristics of the laser-induced vibrational spectra of polyaxial screws which are required for making L-RFA diagnoses of implant stability. In addition, a novel analysis scheme of a vibrational spectrum using L-RFA based on machine learning is demonstrated and proposed. The proposed machine learning-based diagnosis method demonstrates a highly accurate prediction of implant stability (peak torque) for polyaxial pedicle screws. This achievement will contribute an important analytical method for implant stability diagnosis using L-RFA for implants with moving parts and shapes used in various clinical situations.

Ultrasonography-detected synovitis of hand is associated with the presence of synovitis in the forefoot of patients with rheumatoid arthritis.

BACKGROUND: In rheumatoid arthritis, forefoot disease activity can lead to joint damage, pain, and disability during weight-bearing activities; therefore, the evaluation and control of forefoot disease activity is important. We aimed to investigate an association between the prevalence of abnormalities in the forefoot based on ultrasonography (US) and the clinical and US findings related to arthritis and identify factors related to the presence of synovitis in the forefoot of RA patients. METHODS: In total, 810 metatarsophalangeal joints of 81 rheumatoid arthritis patients were examined using US. Patients were assigned to either a forefoot synovitis group (n = 22), with foot synovitis detected using US, or a non-forefoot synovitis group (n = 59). We assessed associations between clinical parameters and US finding of the hand and US finding of the metatarsophalangeal joints. RESULTS: The following were significantly higher in forefoot synovitis group than in non-forefoot synovitis group: swollen joint count [P < 0.001]; Disease Activity Score 28 based on C-reactive protein [P < 0.05]; clinical disease activity index [P < 0.001]; and total Power Doppler score of the hand [P < 0.001]. Receiver-operating characteristic analysis for total Power Doppler scores of the hand to suggest the presence of synovitis in the metatarsophalangeal joints showed that a total Power Doppler score of the hand of ≥5 was associated with synovitis in the metatarsophalangeal joints, with a sensitivity of 68% and a specificity of 85% (odds ratio = 11.9). CONCLUSION: Total Power Doppler scores of the hand had a good valuable score for suggesting the presence of synovitis in metatarsophalangeal joints of rheumatoid arthritis patients.

A randomized, double-blind, placebo-controlled, phase 3 study of tivantinib in Japanese patients with MET-high hepatocellular carcinoma.

A previous randomized phase 2 study of hepatocellular carcinoma revealed that the c-Met inhibitor tivantinib as second-line treatment significantly prolonged progression-free survival in a subpopulation whose tumor samples highly expressed c-Met (MET-high). Accordingly, this phase 3 study was conducted to evaluate the efficacy of tivantinib as a second-line treatment for Japanese patients with MET-high hepatocellular carcinoma. This randomized, double-blind, placebo-controlled study was conducted at 60 centers in Japan. Hepatocellular carcinoma patients with one prior sorafenib treatment and those with MET-high tumor samples were eligible for inclusion. Registered patients were randomly assigned to either the tivantinib or placebo group at a 2:1 ratio and were treated with twice-a-day oral tivantinib (120 mg bid) or placebo until the discontinuation criteria were met. The primary endpoint was progression-free survival while the secondary endpoints included overall survival and safety. Between January 2014 and June 2016, 386 patients provided consent, and 195 patients were randomized to the tivantinib (n = 134) or placebo (n = 61) group. Median progression-free survival was 2.8 (95% confidence interval: 2.7-2.9) and 2.3 (1.5-2.8) mo in the tivantinib and placebo groups, respectively (hazard ratio = 0.74, 95% confidence interval: 0.52-1.04, P = .082). Median overall survival was 10.3 (95% confidence interval: 8.1-11.6) and 8.5 (6.2-11.4) mo in the tivantinib and placebo group, respectively (hazard ratio = 0.82, 95% confidence interval: 0.58-1.15). The most common tivantinib-related grade ≥3 adverse events were neutropenia (31.6%), leukocytopenia (24.8%), and anemia (12.0%). This study did not confirm the significant efficacy of tivantinib as a second-line treatment for Japanese patients with MET-high hepatocellular carcinoma. (NCT02029157).

Reliability of Trapezius Muscle Hardness Measurement: A Comparison between Portable Muscle Hardness Meter and Ultrasound Strain Elastography.

Prolonged computer work and smartphone use can cause stiffness of the neck and shoulder muscles, including the trapezius muscle. Hence, muscle hardness quantification is clinically beneficial. The present study aimed to examine the reliability of trapezius muscle hardness measurement using a portable muscle hardness meter and ultrasound strain elastography. Overall, 20 healthy young men participated in this study. Prior to measurement, the participant's subjective symptoms, particularly shoulder muscle stiffness, were rated using an 11-point verbal scale. Furthermore, hardness of the right and left upper trapezius muscles was assessed. In the strain elastography assessment, muscle hardness was evaluated using strain ratio. Results showed that, in quantifying upper trapezius muscle hardness, both portable muscle hardness meter and strain elastography had an excellent intra-tester reliability (>0.9). However, the correlation coefficients between muscle hardness values assessed using a muscle hardness meter and those evaluated with strain elastography did not significantly differ, and the scores for subjective shoulder stiffness did not correspond to muscle hardness values. Therefore, the hardness of the trapezius muscle does not directly reflect the subjective shoulder stiffness. Future studies should thoroughly examine the location of the shoulder stiffness, and check whether it is accompanied by local pain or tenderness.

Early diagnosis of septic arthritis using synovial fluid presepsin: A preliminary study.

Therapeutic outcomes for septic arthritis vary greatly depending on the span of time between disease-onset and surgery. The most important factor is making an early and definitive diagnosis; however, some cases may be difficult to diagnose. We investigated presepsin, a biomarker of sepsis, to determine whether or not presepsin in synovial fluid would be useful for the diagnosis of septic arthritis. We selected 18 patients with septic arthritis including periprosthetic joint infections (SA group) and 28 patients with osteoarthritis (OA group). We measured the concentrations of synovial fluid presepsin, blood presepsin and procalcitonin (PCT) in the two groups. We compared the sensitivities and specificities of synovial fluid presepsin, blood presepsin and PCT. Synovial fluid and blood presepsin and blood PCT were all significantly higher in the SA group. Synovial fluid presepsin exhibited both 100% sensitivity and 100% specificity in the SA group, which were higher rates than those for blood presepsin and PCT. We found that synovial fluid presepsin is markedly elevated in case of septic arthritis, and therefore, it has potential as a new biomarker of septic arthritis.

Laser Resonance Frequency Analysis: A Novel Measurement Approach to Evaluate Acetabular Cup Stability During Surgery.

Artificial joint acetabular cup stability is essential for successful total hip arthroplasty. However, a quantitative evaluation approach for clinical use is lacking. We developed a resonance frequency analysis (RFA) system involving a laser system that is fully contactless. This study aimed to investigate the usefulness of laser RFA for evaluating acetabular cup stability. First, the finite element method was performed to determine the vibration mode for analysis. Second, the acetabular cup was press-fitted into a reamed polyurethane cavity that replicated the human acetabular roof. The implanted acetabular cup was vibrated with pulse laser irradiation and the induced vibration was detected with a laser Doppler vibrometer. The time domain signal from the vibrometer was analyzed by fast Fourier transform to obtain the vibration frequency spectrum. After laser RFA, the pull-down force of the acetabular cup was measured as conventional implant fixation strength. The frequency of the first highest amplitude between 2 kHz and 6 kHz was considered as the resonance peak frequency, and its relationship with the pull-down force was assessed. The peak frequency could predict the pull-down force (R2 = 0.859, p < 0.000). Our findings suggest that laser RFA might be useful to measure acetabular cup stability during surgery.

Intermineral oxygen three-isotope systematics of silicate minerals in equilibrated ordinary chondrites.

High precision oxygen three-isotope ratios were measured for four mineral phases (olivine, low-Ca and high-Ca pyroxene, and plagioclase) in equilibrated ordinary chondrites (EOC) using a secondary ion mass spectrometer. Eleven EOCs were studied that cover all groups (H, L, LL) and petrologic types (4, 5, 6), including S1-S4 shock stages, as well as unbrecciated and brecciated meteorites. SIMS analyses of multiple minerals were made in close proximity (mostly <100 µm) from several areas in each meteorite thin section, to evaluate isotope exchange among minerals. Oxygen isotope ratios in each mineral become more homogenized as petrologic type increases with the notable exception of brecciated samples. In type 4 chondrites, oxygen isotope ratios of olivine and low-Ca pyroxene are heterogeneous in both δ18O and Δ17O, showing similar systematics to those in type 3 chondrites. In types 5 and 6 chondrites, oxygen isotope ratios of the four mineral phases plot along mass dependent fractionation lines that are consistent with the bulk average Δ17O of each chondrite group. The δ18O of three minerals, low-Ca and high-Ca pyroxene and plagioclase, are consistent with equilibrium fractionation at temperatures of 700-1000°C. In most cases the δ18O values of olivine are higher than those expected from pyroxene and plagioclase, suggesting partial retention of premetamorphic values due to slower oxygen isotope diffusion in olivine than pyroxene during thermal metamorphism in ordinary chondrite parent bodies.

Preclinical and first-in-human phase I studies of KW-2450, an oral tyrosine kinase inhibitor with insulin-like growth factor receptor-1/insulin receptor selectivity.

Numerous solid tumors overexpress or have excessively activated insulin-like growth factor receptor-1 (IGF-1R). We summarize preclinical studies and the first-in-human study of KW-2450, an oral tyrosine kinase inhibitor with IGF-1R and insulin receptor (IR) inhibitory activity. Preclinical activity of KW-2450 was evaluated in various in vitro and in vivo models. It was then evaluated in a phase I clinical trial in 13 patients with advanced solid tumors (NCT00921336). In vitro, KW-2450 inhibited human IGF-1R and IR kinases (IC50 7.39 and 5.64 nmol/L, respectively) and the growth of various human malignant cell lines. KW-2450 40 mg/kg showed modest growth inhibitory activity and inhibited IGF-1-induced signal transduction in the murine HT-29/GFP colon carcinoma xenograft model. The maximum tolerated dose of KW-2450 was 37.5 mg once daily continuously; dose-limiting toxicity occurred in two of six patients at 50 mg/day (both grade 3 hyperglycemia) and in one of seven patients at 37.5 mg/day (grade 3 rash). Four of 10 evaluable patients showed stable disease. Single-agent KW-2450 was associated with modest antitumor activity in heavily pretreated patients with solid tumors and is being further investigated in combination therapy with lapatinib/letrozole in patients with human epidermal growth factor receptor 2-postive metastatic breast cancer.

Phase 1/2 study of KRN330, a fully human anti-A33 monoclonal antibody, plus irinotecan as second-line treatment for patients with metastatic colorectal cancer.

KRN330 is a recombinant, fully-human monoclonal antibody directed against A33, a surface differentiation antigen that is uniformly expressed in 95 % of colorectal cancers. A previous Phase 1 study of single-agent KRN330 identified a maximum tolerated dose (MTD) of 3 mg/kg q2w and preliminary evidence of clinical activity among patients with advanced and metastatic colorectal cancer (mCRC). This Phase 1/2 trial sought to assess the safety and activity of second-line KRN330 plus irinotecan in patients with mCRC. Patients with mCRC who showed disease progression after FOLFOX/CapOx received intravenous doses of KRN330 (0.5 or 1.0 mg/kg qw or q2w) plus irinotecan (180 mg/m(2)) in a standard 3 + 3 dose escalation. The MTD of KRN330 with irinotecan in 19 patients was 0.5 mg/kg qw in the Phase 1 study with gastrointestinal effects and neutropenia being the predominant dose-limiting toxicities. In the Phase 2 study, the most frequent treatment-related Grade ≥3 toxicities in 44 patients were fatigue (15.9 %), neutropenia (13.6 %), leukopenia (6.8 %), diarrhea (4.5 %), and dehydration (4.5 %). Objective response rate (ORR) was 4.5 % and disease control rate was 45.5 % for the intent-to-treat population. Median progression-free survival was 87 days (95 % CI, 43-136 days). The prespecified ORR of KRN330 plus irinotecan was not met. Further investigation of KRN330 plus other agents may be warranted.

Influence of Diffusion Time and Temperature on Restricted Diffusion Signal: A Phantom Study.

PURPOSE: Diffusion MRI is a physical measurement method that quantitatively indicates the displacement of water molecules diffusing in voxels. However, there are insufficient data to characterize the diffusion process physically in a uniform structure such as a phantom. This study investigated the transitional relationship between structure scale, temperature, and diffusion time for simple restricted diffusion using a capillary phantom. METHODS: We performed diffusion-weighted pulsed-gradient stimulated-echo acquisition mode (STEAM) MRI with a 9.4 Tesla MRI system (Bruker BioSpin, Ettlingen, Germany) and a quadrature coil with an inner diameter of 86 mm (Bruker BioSpin). We measured the diffusion coefficients (radial diffusivity [RD]) of capillary plates (pore sizes 6, 12, 25, 50, and 100 µm) with uniformly restricted structures at various temperatures (10ºC, 20ºC, 30ºC, and 40ºC) and multiple diffusion times (12-800 ms). We evaluated the characteristics of scale, temperature, and diffusion time for restricted diffusion. RESULTS: The RD decayed and became constant depending on the structural scale. Diffusion coefficient fluctuations with temperature occurred mostly under conditions of a large structural scale and short diffusion time. We obtained data suggesting that temperature-dependent changes in the diffusion coefficients follow physical laws. CONCLUSION: No water molecules were observed outside the glass tubes in the capillary plates, and the capillary plates only reflected a restricted diffusion process within the structure.We experimentally evaluated the characteristics of simple restricted diffusion to reveal the transitional relationship of the diffusion coefficient with diffusion time, structure scale, and temperature through composite measurement.

Effects of preceding antiplatelet agents on severity of ischemic stroke in patients with a history of stroke.

INTRODUCTION: Antiplatelet agents are effective for secondary prevention of ischemic stroke and can reduce the severity of first-ever ischemic stroke. However, it is uncertain if prophylactic antiplatelet therapy reduces the severity of recurrent ischemic stroke. The aim of this study was to determine the effect of preceding antiplatelet treatment on the severity of thrombotic stroke (TS) in patients with a prior history of stroke. METHODS: From a prospective hospital registry of 1338 consecutive patients with acute ischemic stroke, we identified patients with a prior history of stroke who were admitted for cardioembolic stroke (CE); TS including large-artery atherosclerosis, small vessel occlusion, and branch atheromatous disease; or other cause or cryptogenic stroke (OCS). Cases in each subtype were categorized based on preceding medication: antiplatelet agents (AP) and none (N). Severity of stroke (National Institutes of Health Stroke Scale: NIHSS) on admission was compared between AP and N cases. RESULTS: The total cohort of 252 patients included 83 with CE, 102 with TS, and 67 with OCS. After excluding those with prior anticoagulants, the median NIHSS on admission was lower in AP cases than in N cases (3 vs. 5, p = 0.002). In multivariate analysis, preceding AP treatment was independently associated with minor stroke (NIHSS ≤4) on admission in CE group (OR 8.48, 95% CI 1.71-62.9, p = 0.008) and TS group (OR 4.24, 95% CI 1.44-13.4, p = 0.009). CONCLUSION: Preceding antiplatelet treatment in patients with a prior history of stroke may reduce the severity of subsequent thrombotic and cardiogenic stroke.