Computer model of IL-6-dependent rheumatoid arthritis in F759 mice.

The interleukin-6 (IL-6) amplifier, which describes the simultaneous activation of signal transducer and activator of transcription 3 (STAT3) and NF-κb nuclear factor kappa B (NF-κB), in synovial fibroblasts causes the infiltration of immune cells into the joints of F759 mice. The result is a disease that resembles human rheumatoid arthritis. However, the kinetics and regulatory mechanisms of how augmented transcriptional activation by STAT3 and NF-κB leads to F759 arthritis is unknown. We here show that the STAT3-NF-κB complex is present in the cytoplasm and nucleus and accumulates around NF-κB binding sites of the IL-6 promoter region and established a computer model that shows IL-6 and IL-17 (interleukin 17) signaling promotes the formation of the STAT3-NF-κB complex followed by its binding on promoter regions of NF-κB target genes to accelerate inflammatory responses, including the production of IL-6, epiregulin, and C-C motif chemokine ligand 2 (CCL2), phenotypes consistent with in vitro experiments. The binding also promoted cell growth in the synovium and the recruitment of T helper 17 (Th17) cells and macrophages in the joints. Anti-IL-6 blocking antibody treatment inhibited inflammatory responses even at the late phase, but anti-IL-17 and anti-TNFα antibodies did not. However, anti-IL-17 antibody at the early phase showed inhibitory effects, suggesting that the IL-6 amplifier is dependent on IL-6 and IL-17 stimulation at the early phase, but only on IL-6 at the late phase. These findings demonstrate the molecular mechanism of F759 arthritis can be recapitulated in silico and identify a possible therapeutic strategy for IL-6 amplifier-dependent chronic inflammatory diseases.

Identifying Active Progeny Virus Particles in Formalin-Fixed, Paraffin-Embedded Sections Using Correlative Light and Scanning Electron Microscopy.

Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tissue blocks is routinely used to identify virus-infected cells. However, detecting virus particles in FFPE sections using light microscopy is difficult because of the light diffraction resolution limitations of an optical microscope. In this study, light microscopy and field emission scanning electron microscopy were performed to observe 3-dimensional virus particles in FFPE sections in a nondestructive manner using NanoSuit or osmium conductive treatment methods. The virus particles in FFPE sections were immunostained with specific antibodies against the surface antigens of the viral particles and stained with 3,3'-diaminobenzidine. A metal solution (0.2% gold chloride or 2% osmium tetroxide) was applied to enhance the 3,3'-diaminobenzidine-stained area. This procedure is nondestructive for FFPE sections and is a simpler method than transmission electron microscopy. To validate the applicability of this technique, we performed 3-dimensional imaging of the virus particles of different sizes, such as human papillomavirus, cytomegalovirus, and varicella-zoster virus. Furthermore, ultrathin sections from the FFPE sections that were observed to harbor viral particles using field emission scanning electron microscopy were prepared and assessed using transmission electron microscopy. In the correlative areas, transmission electron microscopy confirmed the presence of large numbers of virus particles. These results indicated that the combination of marking viral particles with 3,3'-diaminobenzidine/metal staining and conductive treatment can identify active progeny virus particles in FFPE sections using scanning electron microscopy. This easy correlative imaging of field emission scanning electron microscopy of the identical area of FFPE in light microscopy may help elucidate new pathological mechanisms of virus-related diseases.

Comparison between the diagnostic performance of vessel fractional flow reserve and nonhyperemic pressure ratio for functionally significant coronary stenosis severity as assessed by fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs) have been widely used to assess the functional severity of coronary stenosis. However, their measurement requires using a pressure wire, making their use in all patients difficult. The recently developed vessel fractional flow reserve (vFFR), derived from three-dimensional quantitative coronary angiography, is expected to serve as a surrogate for pressure wire assessment. METHODS: This retrospective study was conducted on patients with intermediate coronary stenosis who underwent FFR and NHPR measurements. The vFFR and NHPR values were compared for diagnosing coronary stenosis as defined by an FFR of ≤0.80, and the number of patients not requiring wire-based assessment was estimated. RESULTS: In a total of 90 lesions from 74 patients (median [SD] age 75 [12] years; men 80%), the median FFR was 0.78 (0.72-0.84), and 57% of these lesions (N = 51) exhibited an FFR of ≤0.80. vFFR provided high discrimination for coronary stenosis (area under the curve 0.80, 95% confidence interval 0.70-0.90), which was comparable to that of NHPRs (p = 0.42). High diagnostic accuracy was consistently observed across a variety of clinical presentations (i.e., old age, diabetes, target coronary artery, and left ventricular hypertrophy) (pinteraction > 0.05). In total, 55 lesions (61%) demonstrated positive or negative likelihood of coronary stenosis when vFFR was <0.73 (specificity 90%) or >0.87 (sensitivity 88%), respectively. CONCLUSION: vFFR demonstrated excellent diagnostic performance for detecting functionally significant coronary stenosis as evaluated by FFR. vFFR may be used as a surrogate for pressure wire assessment.

Evaluation of Lower-Limb Kinematics during Timed Up and Go (TUG) Test in Subjects with Locomotive Syndrome (LS) Using Wearable Gait Sensors (H-Gait System).

Few studies have dealt with lower-limb kinematics during the timed up and go (TUG) test in subjects with locomotive syndrome (LS). This study aimed to evaluate the characteristics of lower-limb kinematics during the TUG test in subjects with LS using the wearable sensor-based H-Gait system. A total of 140 participants were divided into the non-LS (n = 28), the LS-stage 1 (n = 78), and LS-stage 2 (n = 34) groups based on the LS risk test. Compared with the non-LS group, the LS-stage 1 and LS-stage 2 groups showed significantly smaller angular velocity of hip and knee extension during the sit-to-stand phase. The LS-stage 2 group showed significantly smaller peak angles of hip extension and flexion during the walking-out phase compared to the non-LS group. These findings indicate that the evaluation of the lower-limb kinematics during the TUG test using the H-Gait system is highly sensitive to detect LS, compared with the evaluation of the lower-limb kinematics when simply walking.

Nutrient Solution Flowing Environment Affects Metabolite Synthesis Inducing Root Thigmomorphogenesis of Lettuce (Lactuca sativa L.) in Hydroponics.

The principal difference between hydroponics and other substrate cultivation methods is the flowing liquid hydroponic cultivation substrate. Our previous studies have revealed that a suitable flowing environment of nutrient solution promoted root development and plant growth, while an excess flow environment was unfavorable for plants. To explain the thigmomorphogenetic response of excess flow-induced metabolic changes, six groups of lettuce (Lactuca sativa L.), including two flow conditions and three time periods, were grown. Compared with the plants without flow, the plants with flow showed decreased root fresh weight, total root length, root surface area, and root volume but increased average root diameter and root density. The roots with flow had more upregulated metabolites than those without flow, suggesting that the flow may trigger metabolic synthesis and activity. Seventy-nine common differential metabolites among six groups were screened, and enrichment analysis showed the most significant enrichment in the arginine biosynthesis pathway. Arginine was present in all the groups and exhibited greater concentrations in roots with flow than without flow. It can be speculated from the results that a high-flowing environment of nutrient solution promotes arginine synthesis, resulting in changes in root morphology. The findings provide insights on root thigmomorphogenesis affected by its growing conditions and help understand how plants respond to environmental mechanical forces.

Regional differences in the prevalence of oral allergy syndrome among Japanese children: A questionnaire-based survey.

BACKGROUND: Oral allergy syndrome (OAS) is characterized by an immediate allergic reaction that mainly or partially affects the oral mucosa, pharynx, or lips, and it is usually caused by ingesting fresh fruits or vegetables. Most patients with OAS also have allergic rhinitis due to pollen. As allergic rhinitis is increasingly prevalent in the Japanese population and the age at disease development is decreasing, morbidity associated with OAS among the younger population is likely to increase. However, there is little information about the prevalence of this disease among Japanese children, specifically the influences of residency in regions with different environments. OBJECTIVE: To investigate the prevalence of OAS and seasonal allergic rhinitis (SAR) among Japanese children and evaluate the relationship between OAS and SAR. METHODS: We administered a questionnaire-based survey among children aged 7-15 years, living in 4 cities in central Japan. RESULTS: The questionnaires were administered to 4103 children and completed by 3365 (82.0%). Overall, 524 children (15.6%) reported OAS-like symptoms after ingesting fruits or vegetables. The prevalence of seasonal SAR and oral symptoms significantly differed among the 4 cities. The total prevalence of oral symptoms co-occurring with SAR was 24.4%, which was significantly higher than the prevalence of symptoms occurring without SAR (10.2%, p < 0.001). CONCLUSIONS: Herein, oral symptoms were more likely to occur in patients with SAR than in those without SAR. The prevalence of SAR and food-induced oral symptoms significantly differed among the regions, suggesting they might be affected by regional differences in lifestyles and flora.

Relationships between Changes in Muscle Shear Modulus, Urinary Titin N- Terminal Fragment, and Maximum Voluntary Contraction Torque after Eccentric Exercise of the Elbow Flexors.

The study aimed to investigate the relationships between the shear modulus of the biceps brachii (BB) and brachialis muscle (BA) and the total of the two (BB+BA), and urinary titin N-terminal fragment (UTF), maximum voluntary isometric contraction (MVC), and other indirect markers. Fifteen healthy men performed five sets of 10 eccentric contractions using a dumbbell corresponding to 50% of MVC at 90° measured at baseline. The elbow joint of the left arm was extended from 90° to 180° (180° = full extension) in 5 s in the exercise, and was returned with support from the examiner to prevent concentric contraction. Shear modulus of BB and BA were measured by ultrasound shear wave elastography, and UTF, MVC, and range of motion of the elbow joint (ROM) were recorded before; immediately after; and 1, 24, 48, 72, 96, and 168 h after the exercise. After calculating the shear modulus of BB and BA, two values were added (BB+BA). The shear modulus peaked at 48 h, UTF peaked at 96 h, MVC and ROM changed largest at immediately, and muscle soreness peaked at 48 h post-exercise. Significant (p < 0.05) relationships were found between changes in BB shear modulus and BA shear modulus (r = 0.874), BB+BA shear modulus (r = 0.977), UTF (r = 0.681), and MVC (r = -0.538). Significant (p < 0.05) relationships were also observed between changes in BA shear modulus and BB+BA shear modulus (r = 0.957), UTF (r = 0.682), MVC (r = -0.522), and ROM (r = -0.600). Moreover, significant (p < 0.05) relationships were observed between changes in BB+BA shear modulus and UTF (r = 0.703), MVC (r = -0.549), and ROM (r = -0.547). These results indicate that shear modulus of each muscle (i.e., BB and BA) provide more precise information about muscle damage than UTF, MVC and ROM.

Bone biopsy findings in patients receiving long-term bisphosphonate therapy for glucocorticoid-induced osteoporosis.

INTRODUCTION: Bisphosphonates (BPs) have been shown to reduce the incidence of vertebral fractures during the first year or two of glucocorticoid (GC) treatments and are therefore recommended as a first-line treatment for GC-induced osteoporosis (GIO). However, there are theoretical concerns about the long-term use of BPs in low-turnover osteoporosis caused by chronic GC therapy. MATERIALS AND METHODS: We analyzed the trabecular microarchitecture, bone metabolism, and material strength of iliac crest bone biopsy samples from 10 female patients with rheumatoid arthritis who received an average of 6.7 years of BP therapy for GIO (GIOBP group), compared with those of 10 age- and bone mineral density (BMD)-matched non-rheumatoid arthritis postmenopausal women (reference group). RESULTS: Patients in the GIOBP group had a significantly greater fracture severity index, as calculated from the number and the extent of vertebral fractures compared with the reference patients. Micro-computed tomography analysis showed that the degree of mineralization and trabecular microarchitecture were significantly lower in the GIOBP group than in the reference patients. Patients in the GIOBP group exhibited lower bone contact stiffness, determined by micro-indentation testing, than in the reference group. The contact stiffness of the bone was negatively correlated with the fracture severity index and the daily prednisolone dosage. Immunohistochemistry and serum bone turnover markers showed decreased osteoclastic activity, impaired mineralization, and an increased fraction of empty lacunae in the GIOBP group. CONCLUSION: Our findings indicate that patients receiving long-term BP for GIO are still at high risk for fragility fractures because of poor bone quality.

Evaluation of gait characteristics in subjects with locomotive syndrome using wearable gait sensors.

BACKGROUND: Individuals with locomotive syndrome (LS) require nursing care services owing to problems with locomotion and the musculoskeletal system. Individuals with LS generally have a reduced walking speed compared with those without LS. However, differences in lower-limb kinematics and gait between individuals with and without LS are not fully understood. This study aimed to clarify the characteristics of the gait kinematics of individuals with LS using wearable sensors. METHODS: We assessed 125 participants (mean age 73.0 ± 6.7 years) who used a public health promotion facility. Based on the 25-question Geriatric Locomotive Function Scale (GLFS-25), these participants were grouped into the non-LS (GLFS-25 < 7), LS-stage 1 (GLFS-25 7-16), and LS-stage 2 (GLFS-25 ≥ 16) groups (larger GLFS-25 scores indicate worse locomotive ability). Spatiotemporal parameters and lower-limb kinematics during the 10-m walk test were analyzed by the "H-Gait system", which is a motion analysis system that was developed by the authors and is based on seven inertial sensors. The peak joint angles during the stance and swing phases, as well as the gait speed, cadence, and step length were compared among all groups. RESULTS: There were 69 participants in the non-LS group, 33 in the LS-stage 1 group, and 23 in the LS-stage 2 group. Compared with the non-LS group, the LS-stage 2 group showed significantly smaller peak angles of hip extension (9.5 ± 5.3° vs 4.2 ± 8.2°, P = 0.002), hip flexion (34.2 ± 8.8° vs 28.5 ± 9.5°, P = 0.026), and knee flexion (65.2 ± 18.7° vs 50.6 ± 18.5°, P = 0.005). The LS-stage 1 and LS-stage 2 groups had a significantly slower mean gait speed than the non-LS group (non-LS: 1.3 ± 0.2 m/s, LS-stage 1: 1.2 ± 0.2 m/s, LS-stage 2: 1.1 ± 0.2 m/s, P < 0.001). CONCLUSIONS: The LS-stage 2 group showed significantly different lower-limb kinematics compared with the non-LS group, including smaller peak angles of hip extension, hip flexion, and knee flexion. It would be useful to assess and improve these small peak joint angles during gait for individuals classified as LS-stage 2.

[Validation Study on Migration Test for Plastic Food Utensils, Containers, and Packaging].

Migration test of food utensils, containers, and packaging is an important test method for confirming the safety and their compliance to the standards. However, there is little report on inter-laboratory study which was performed to evaluate the entire migration test, including migration operations and quantification. An interlaboratory study was performed participating 22 laboratories using 8 types of model synthetic resin samples containing 10 substances with a wide range of Log Pow values to evaluate the accuracy of the entire migration test. As a result, most of HorRat (r) values met the target criteria (0.3

Changes in Muscle Shear Modulus and Urinary Titin N-Terminal Fragment after Eccentric Exercise.

This study aimed to investigate the relationship between the muscle shear modulus of the biceps brachii, urinary titin N-terminal fragment (UTF), and other damage markers after eccentric exercise. Seventeen healthy males performed five sets of ten eccentric exercises with dumbbells weighing 50% of the maximum voluntary contraction (MVC) at the elbow joint. Muscle shear modulus with range of interest set to only biceps brachii muscle measured by ultrasound shear wave elastography, UTF, MVC, range of motion (ROM), and soreness (SOR) were recorded before, immediately after, and 1, 24, 48, 72, 96, and 168 h after eccentric exercise. Each marker changed in a time course pattern, as found in previous studies. The peak shear modulus showed a moderate negative correlation with peak MVC (r = -0.531, P < 0.05) and a strong positive correlation with peak UTF (r = 0.707, P < 0.01). Our study results revealed a significant relationship between muscle strength, shear modulus measured by ultrasound SWE, and titin measured by UTF, as a non-invasive damage marker after eccentric exercise to track changes in EIMD.

Swelling-activated ClC-3 activity regulates prostaglandin E2 release in human OUMS-27 chondrocytes.

Articular chondrocytes are exposed to dynamic osmotic environments during normal joint loading, and thus, require effective volume regulatory mechanisms. A regulatory volume decrease (RVD) is one of the mechanisms for protecting chondrocytes from swelling and damage. Swelling-activated Cl- currents (ICl,swell) are responsible for the RVD, but the molecular identity in chondrocytes is largely unknown. In this study, we reveal that in human OUMS-27 chondrocytes, ICl,swell can be elicited by hypoosmotic stimulation (180 mOsm) and be inhibited by classical Cl- channel blockers, 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) and niflumic acid, and be attenuated by siRNA knockdown of ClC-3. Our molecular analyses revealed that ClC-3A is expressed as a major splice variant in both human articular chondrocytes and OUMS-27 cells. The onset and early phase of RVD following hypoosmotic stress in OUMS-27 cells were affected by DIDS and ClC-3 knockdown. Hypoosmotic stimulation caused Ca2+ influx and subsequent release of prostaglandin E2 (PGE2) in OUMS-27 cells, and both of these responses were reduced by DIDS and ClC-3 knockdown. These results strongly suggest that ClC-3 is responsible for ICl,swell and RVD under the hypoosmotic environments. It is likely that ClC-3 is associated with the pathogenesis of cartilage degenerative diseases including osteoarthritis via PGE2 release.

Efficacy of combination-chemotherapy with pirarubicin, ifosfamide, and etoposide for soft tissue sarcoma: a single-institution retrospective analysis.

BACKGROUND: The standard chemotherapy regimens for soft tissue sarcoma are doxorubicin-based. This retrospective study aimed to assess the efficacy and safety of pirarubicin, ifosfamide, and etoposide combination therapy for patients with this disease. METHODS: Between 2008 and 2017, 25 patients with soft tissue sarcoma were treated with pirarubicin (30 mg/m2, 2 days), ifosfamide (2 g/m2, 5 days), and etoposide (100 mg/m2, 3 days) every 3 weeks. The primary endpoint was overall response, and the secondary endpoint was adverse events of this regimen. RESULTS: Responses to this regimen according to RECIST criteria were partial response (n = 9, 36%), stable disease (n = 9, 36%) and progressive disease (n = 7, 28%). During the treatment phase, frequent grade 3 or worse adverse events were hematological toxicities including white blood cell decreases (96%), febrile neutropenia (68%), anemia (68%), and platelet count decreases (48%). No long-term adverse events were reported during the study period. CONCLUSION: This regimen was comparable to previously published doxorubicin-based combination chemotherapy in terms of response rate. Although there were no long-lasting adverse events, based on our results, severe hematological toxicity should be considered.

Analysis of 122 triplet and one quadruplet pregnancies after single embryo transfer in Japan.

RESEARCH QUESTION: What is the prevalence of triplet and quadruplet pregnancies after single embryo transfer (SET) in Japan. DESIGN: A retrospective observational study was conducted on 274,605 pregnancies after 937,848 SET cycles in registered assisted reproductive technology (ART) data from the Japanese ART national registry database between 2007 and 2014. A questionnaire survey of ART centres was also conducted. Data on pregnancies with embryo division into three or more after SET were analysed. RESULTS: According to the Japanese ART national registry database, SET resulted in 109 triplet pregnancies (0.04% of pregnancies), and the questionnaire reports from 31 centres revealed 33 triplet and one quadruplet pregnancies. After exclusion of 20 duplicated cases, 122 triplet and one quadruplet pregnancies included 46 monochorionic (one gestational sac [37.4%]), 18 dichorionic (two gestational sacs [14.6%]) and 59 trichorionic pregnancies (three gestational sacs [48.0%]). Compared with singleton pregnancies, patients with monozygotic triplet or quadruplet pregnancies were less frequently diagnosed with unexplained infertility (P = 0.004), more often received gonadotrophin injections for ovarian stimulation in 39 cases with information available (P = 0.021) and underwent more blastocyst transfers and assisted hatching (P = 0.002 and P < 0.001, respectively). The proportion of live birth, defined as at least one baby born, excluding induced abortion, was 64.6% (73/116 pregnancies) of monozygotic triplet or quadruplet pregnancies. CONCLUSIONS: Combined Japanese ART national registry and survey data revealed 122 triplet and one quadruplet pregnancies, the majority after cryopreserved embryo transfer. Most were conceived after blastocyst transfer and often after assisted hatching, which are potential risk factors for zygotic splitting.

Expression of Leucine-rich Repeat-containing Protein 32 Following Lymphocyte Stimulation in Patients with Non-IgE-mediated Gastrointestinal Food Allergies.

The lymphocyte stimulation test (LST) facilitates the diagnosis of non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs). However, LSTs require large volumes of blood and prolonged culture durations. Recently, we found that IL2RA mRNA expression in peripheral blood mononuclear cells (PBMCs) of patients with non-IgE-GI-FAs increased after a 24 h stimulation with milk proteins. We designated this gene expression test as the instant peripheral blood allergen stimulation test (iPAST). In this study, we investigated whether other activated T cell-associated genes are superior to IL2RA in the iPAST for the supplementary diagnosis of non-IgE-GI-FAs. After incubating PBMCs with milk proteins for 24 h, the mRNA levels of three genes, LRRC32, TNFRSF4, and CD69, were assessed using quantitative RT-PCR. The diagnostic significance of the mRNA expression was evaluated by analyzing the receiver operating characteristic (ROC) curve. Upon stimulation with α-casein, κ-casein, α-lactalbumin, or a mixture of four milk protein components (Pmix), LRRC32 expression in the PBMCs of 16 patients with non-IgE-GI-FAs was found to be higher than that in their 17 control counterparts, whereas TNFRSF4 and CD69 levels remained unaltered. Except for ß-lactoglobulin and cow's milk (CM), the area under the ROC curve (AUC) for LRRC32 mRNA expression upon stimulation was >0.7, which validated the diagnostic ability of this test. Notably, α-casein and Pmix had higher AUC scores of 0.820 and 0.842, respectively, than other antigens. iPAST assessed by LRRC32 as well as IL2RA may be useful for the supplementary diagnosis of non-IgE-GI-FAs as an alternative to LSTs and provide insight into the pathogenesis of non-IgE-GI-FAs.

Local dissemination of osteosarcoma observed after massage therapy: a case report.

BACKGROUND: Limited evidence is available regarding the dissemination of tumor tissues due to compression during massage therapy, a routine procedure in patients with various symptoms in Asian countries. CASE PRESENTATION: A 12-year-old male presented at a massage clinic with pain and swelling of his left knee, which worsened the same night. Consistent with conventional osteosarcoma, radiography revealed cortical bone destruction, osteoblastic changes, and periosteal reactions. Magnetic resonance imaging revealed a tumor in the distal femur, an extraskeletal mass, and an infiltrative lesion in the intramuscular and neurovascular areas surrounding the distal femur; this was considered as hemorrhage and dissemination of the tumor tissue. 18Fluorine-labelled fluorodeoxyglucose-positron emission tomography and computed tomography revealed multiple metastases in the spine, liver, and lung. Consistent with osteosarcoma, histopathological examination revealed tumor cell proliferation with extensive pleomorphism and mitoses. Despite undergoing chemotherapy, radiation therapy, and hip disarticulation, the patient died due to multiple metastases 13 months after the initial diagnosis. CONCLUSIONS: The present case suggests association of massage therapy with the local dissemination of tumor tissues, although influence of massage therapy on metastatic lesions remains unclear. Massage therapists should be aware of the possibility for dissemination of hidden malignancies due to the procedure.

The Incidence and Risk Factors of Venous Thromboembolism in Patients with Inflammatory Bowel Disease: A Prospective Multicenter Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) has been shown to be more frequent in inflammatory bowel disease (IBD) than in the general population in Western studies. However, the actual state of VTE in Asian IBD remains poorly understood. AIMS: To reveal the incidence of VTE in IBD patients in Japan. METHODS: Eighty-five patients admitted to 3 gastroenterology centers were registered from 2013 to 2018. The incidence of VTE in patients with IBD (n = 42) was prospectively compared to that among patients with other digestive diseases (n = 43). The presence of VTE was surveyed using contrast-enhanced computed tomography and/or ultrasonography at admission and at 1-2 weeks after admission. The patient characteristics and laboratory data of IBD patients with or without VTE were compared to determine the risk factors for VTE. RESULTS: The incidence of VTE with IBD was 16.7%, which was significantly more frequent than with other digestive diseases (2.3%; p = 0.0296). In IBD patients, VTE was detected in 6 of 22 patients with ulcerative colitis (27.2%) but in only 1 of 20 patients with Crohn's disease (5.0%). VTE was diagnosed at admission in 4 IBD patients and 2 weeks after admission in 3 IBD patients. The risk factors of VTE in IBD were the presence of an indwelling central venous catheter, a low level of total protein, a low activated partial thromboplastin time, and a high level of fibrinogen degradation products. CONCLUSION: VTE was frequently detected in Japanese IBD patients both at and after admission. Adequate screening and prophylaxis for VTE is deemed necessary in IBD.

Two Medullary Hemorrhage Cases Complicated by Respiratory Distress in the Early Phase.

Medullary hemorrhage is quite rare among brain stem hemorrhage cases, thus the clinical course remains unclear. In the medulla oblongata, respiratory centers are located and previous reports indicate that medullary lesions have possible relationship with acute respiratory distress syndrome. This kind of respiratory failure is commonly caused by neurogenic pulmonary edema (NPE), which is defined as noncardiac noninfectious acute respiratory distress syndrome with changes in intracranial condition including cerebrovascular events. However, to date, very few reports have described cases with medullary hemorrhage accompanied by NPE. We experienced 2 patients with medullary hemorrhages. A 65-year-old man presented with sudden onset of headache, whose head computed tomography showed right medullary hemorrhage. Another 76-year-old woman was transferred because of sudden limb weakness and diagnosed with left medullary hemorrhage. Digital subtraction angiography showed the presence of arteriovenous fistula in the medulla oblongata and drainer veins in the second case. Both cases were complicated by acute pulmonary edema in the early phase, suggesting the possible association of the medullary hemorrhage with NPE.

Left Ventricular Mass Influences Relationship Between Filling Pressure and Early-Diastolic Ratio of Inflow Velocity to Mitral Annular Velocity (E/e').

BACKGROUND: Early-diastolic mitral annular velocity (e') and the ratio of early-diastolic left ventricular (LV) inflow velocity (E) to e' (E/e') have been widely used as indexes of LV relaxation and filling pressure, respectively. However, many recent studies have demonstrated that they are not reliable in various clinical settings. We thus investigated the factors influencing these echocardiographic parameters in a multicenter study.Methods and Results:The study group comprised 69 patients, referred for cardiac catheterization, and enrolled in 5 university hospitals. Time constant (τ) and LV mean diastolic pressure (LVMDP) were measured using a micromanometer-tipped catheter. Although e' only weakly correlated with τ (r=-0.35, P<0.01), E/e' modestly correlated with LVMDP (r=0.48, P<0.001). Multivariable analysis revealed that hypertension (ß=-0.33, P<0.01) and LV ejection fraction (LVEF) (ß=0.44, P<0.001) were the independent determinants of e', and LV mass index (LVMI) (ß=0.37, P<0.001) and LVMDP (ß=0.47, P<0.001) were those of E/e'. Additionally, E/e' significantly correlated with LVMDP in patients with normal LVMI (r=0.74, P<0.001) but not in those with increased LVMI. CONCLUSIONS: The coincidence of hypertension and LVEF affected the relationship between LV relaxation and e', whereas LVMI altered the relationship between LV filling pressure and E/e'. Thus, clinical conditions associated with an increase in LVMI, such as LV hypertrophy and LV dilatation, should be considered when estimating the filling pressure from E/e'.

Efficacy of radio-hyperthermo-chemotherapy as salvage therapy for recurrent or residual malignant soft tissue tumors.

BACKGROUND: Recurrence after wide excision or residual tumor after an unplanned excision of a malignant soft tissue sarcoma (STS) is a complex problem, due to a higher recurrence rate and poorer survival rate compared with primary resection. Regional hyperthermia was used, with the expectation that it will enhance the anti-tumor effects of chemotherapy and radiotherapy. This study aimed to assess the efficacy of neoadjuvant concomitant radiotherapy, hyperthermia, and chemotherapy (RHC) for salvage of recurrent or residual malignant STS. METHODS: We identified 64 patients with recurrent or residual STS treated between 1994 and 2013. After excluding those with low-grade malignancy, with recurrent bone tumor in the soft tissues, with truncal STS, and who declined to participate, 23 patients (7 with recurrence and 16 with residual tumor) underwent RHC. The histologic diagnoses were undifferentiated pleomorphic sarcoma (n = 11), synovial sarcoma (n = 3), leiomyosarcoma and myxoid liposarcoma (n = 2 each), and other histologic types. As primary outcomes, the 5-year overall survival (OS), distant metastasis-free survival (D-MFS), and local control (LC) rates were evaluated by Kaplan-Meier analysis. RESULTS: The median follow-up period was 112.3 months. The 5-year OS, D-MFS, and LC were 86.4%, 77.4%, and 86.7%, respectively. In the univariate analysis, tumor depth was considered as a negative prognostic factor for OS and D-MFS, and a positive margin was also a negative prognostic factor for OS, D-MFS LC with retained on Cox proportional hazards model in OS, and D-MFS. CONCLUSION: RHC is an effective option for salvage treatment of recurrent and residual STS.