Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

Transition from spin glass to paramagnetism in the magnetic properties of PrAu2Si2.

It is unexpected that a spin-glass (SG) transition, which generally occurs only in systems with some form of disorder, was observed in the ThCr2Si2-type compound PrAu2Si2at a temperature of ∼3 K. This puzzling phenomenon was later explained based on a novel dynamic frustration model that does not involve static disorder. We present the results of re-verification of the reported SG behaviors by measuring the physical properties of three polycrystalline PrAu2Si2samples annealed under different conditions. Indeed, in the sample annealed at 827 °C for one week, a SG transition does occur at a temperature ofTf∼ 2.8 K as that reported previously in the literature. However, it is newly found that the SG effect is actually more pronounced in the as-cast sample, and almost completely disappears in the well-annealed (at 850 °C for four weeks) sample. The annealing effect observed in PrAu2Si2, that is, SG to paramagnetism transition is discussed by comparing with earlier results reported on the same system and other isomorphic compounds.

Magnetic and transport properties of new ternary uranium-based germanide U2Rh3Ge5.

A new ternary uranium germanide U2Rh3Ge5 has been successfully synthesized and investigated by means of magnetic susceptibility χ(T, H), isothermal magnetization M(T, H), electrical resistivity ρ(T), and specific heat C(T, H) measurements. This compound is found to crystallize in the U2Co3Si5-type orthorhombic structure. The low-field χ(T) shows a clear peak at T N = 41.5 K corresponding to an antiferromagnetic transition. The M(H) curve measured up to 70 kOe exhibits an H-linear behavior at 2 K with very small induced magnetic moments, while it shows upward curvature with increasing temperature, implying the possible presence of a metamagnetic transition in high-field region above 70 kOe. As the temperature decreases, ρ(T) increases slowly at T > T N and decreases rapidly at T < T N, which can be understood based on a semiconductor-like narrow band gap model (or the c-f hybridization effect) and an antiferromagnetic spin-wave model, respectively. No evidence of heavy-fermion behavior or superconductivity transition is observed at temperatures as low as 0.4 K. The obtained experimental results are discussed by comparing with those reported for the isomorphic compound U2Ir3Si5 and the quasi-isomorphic compound U2Rh3Si5.

Propionimicrobium lymphophilum and Actinotignum schaalii bacteraemia: a case report.

Propionimicrobium lymphophilum is an anaerobic Gram-positive bacillus that exists in human skin and urinary tract. The pathogenicity is, however, not well known. Only two cases of urinary tract infection have been described recently. In the case presented here, the bacterium was isolated, concomitant with Actinotignum schaalii, from blood culture of a patient with fever and difficulty of urination. The bacteria were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA sequencing. The case was successfully treated with ampicillin/sulbactam.

Small femoral offset is a risk factor for lateral femoral cutaneous nerve injury during total hip arthroplasty using a direct anterior approach.

INTRODUCTION: Lateral femoral cutaneous nerve (LFCN) injury is a risk specific to the direct anterior approach (DAA) for total hip arthroplasty (THA). However, prevention strategies have not been established. This study aimed to identify the predisposing factors determining LFCN injury during THA via a DAA. HYPOTHESIS: Patients with LFCN injury after THA via DAA would demonstrate predisposing factors. MATERIAL AND METHODS: LFCN injury was identified using a patient questionnaire. Potential factors predisposing to LFCN injury were identified in four categories in patient records: patient factors (age, sex, BMI, diagnosis and range of hip motion), surgical factors (surgical time and surgeon's experience of the DAA), preoperative radiographic factors (neck-shaft angle, femoral offset, acetabular offset, total offset and length of muscle on computed tomography axial image) and radiographic changes (differences between each offset pre- and post-surgery). Multivariate analysis was performed to identify risk factors for LFCN injury during this surgery. RESULTS: After application of inclusion and exclusion criteria, 102 hips (28 with LFCN injury; 74 without) in 102 patients (17 males, 85 females; mean age 66.0 years [range, 26-88 years]) were included. Univariate analysis of patients with and without LFCN injury revealed that small preoperative femoral offset and short preoperative long axis of the tensor fascia lata were statistically significant risk factors for LFCN injury (P=0.004, and P=0.01, respectively). Multivariate analysis showed that small preoperative femoral offset was the only independent risk factor for LFCN injury (odds ratio, 0.895; 95% Confidence Interval, 0.817-0.981; P=0.0018). DISCUSSION: Smaller femoral offset was a significant risk factor for LFCN injury following THA via a DAA. Our recommendations are that careful attention should be paid to the skin-fascia incision and subcutaneous exposure, and that excessive retraction of the sartorius muscle and tensor fascia lata should be avoided, to reduce the risk of LFCN injury in patients with a small femoral offset. LEVEL OF EVIDENCE: IV, retrospective historical cohort study.

Targeting Oct1 genomic function inhibits androgen receptor signaling and castration-resistant prostate cancer growth.

Androgen receptor (AR) functions as a ligand-dependent transcription factor to regulate its downstream signaling for prostate cancer progression. AR complex formation by multiple transcription factors is important for enhancer activity and transcriptional regulation. However, the significance of such collaborative transcription factors has not been fully understood. In this study, we show that Oct1, an AR collaborative factor, coordinates genome-wide AR signaling for prostate cancer growth. Using global analysis by chromatin immunoprecipitation sequencing (ChIP-seq), we found that Oct1 is recruited to AR-binding enhancer/promoter regions and facilitates androgen signaling. Moreover, a major target of AR/Oct1 complex, acyl-CoA synthetase 3 (ACSL3), contributes to tumor growth in nude mice, and its high expression is associated with poor prognosis in prostate cancer patients. Next, we examined the therapeutic effects of pyrrole-imidazole polyamides that target the Oct1-binding sequence identified in the center of the ACSL3 AR-binding site. We observed that treatment with Oct1 polyamide severely blocked the Oct1 binding at the ACSL3 enhancer responsible for its transcriptional activity and ACSL3 induction. In addition, Oct1 polyamides suppressed castration-resistant tumor growth and specifically repressed global Oct1 chromatin association and androgen signaling in prostate cancer cells, with few nonspecific effects on basal promoter activity. Thus, targeting Oct1 binding could be a novel therapeutic strategy for AR-activated castration-resistant prostate cancer.

Changes in the immune cell population and cell proliferation in peripheral blood after gemcitabine-based chemotherapy for pancreatic cancer.

PURPOSE: Regulatory T cells (Tregs) play a role in the immunosuppressive state in pancreatic cancer patients. We aimed to evaluate the changes of immune cells population including Tregs caused by gemcitabine (GEM)-based chemotherapy. METHODS: Fifty-three patients with pancreatic cancer were enrolled in this study, of which 32 received GEM- based chemotherapy. Blood samples were collected before and at least 2 weeks after the last dose of chemotherapy. The peripheral blood mononuclear cells (PBMCs) were subjected to flow cytometry analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Other lymphocytes and NK cell markers were also measured. The proliferative capacity of PBMCs stimulated with anti-CD3 was analyzed using H(3) thymidine. RESULTS: The percentage and number of Tregs were significantly decreased after chemotherapy (p = 0.032, p = 0.003, respectively). The other immune cells and the proliferative capacity did not change. CONCLUSION: This study showed that GEM-based chemotherapy produced an immunomodulatory effect via the depletion of Tregs.

Intraurethral condylomata acuminata associated with genital piercings.

A 33-year-old man was referred to our institution with papillary masses at the urethral meatus and difficulty urinating. Genital examination showed two piercings on the frenulum, which were penetrating the external urethra. Endoscopic examination revealed papillary tumours over the entire circumference of the penile urethra and the piercing site. The tumours were resected transurethrally. Microscopic examination revealed condylomata acuminata. Human papillomavirus types 6 and 66 were detected in the lesions. Retrograde urethral viral infection is rare because of the protection provided by the mucosal immune system. Genital piercing may have facilitated spread of the human papillomavirus into the urethra.

Cellular therapies for the treatment of non-union: the past, present and future.

Non-union fracture is a pathological condition having some impairment of the cellular part of the repair: a reduction of MSC and of the osteoblastic activation. Non union is therefore a good indication for cell-based therapies using stem cells. We described the rational of this treatment and described the technique of autologous bone marrow concentrate implantation that was until now used. With the development of stem cell research and regenerative medicine, we believed that therapy based on cytotherapy has great potential. In this review, clinical applications of cytotherapy are summarized and analyzed. Current problems and future challenges are discussed.

Associations between six classical HLA loci and rheumatoid arthritis: a comprehensive analysis.

Although the HLA region contributes to one-third of the genetic factors affecting rheumatoid arthritis (RA), there are few reports on the association of the disease with any of the HLA loci other than the DRB1. In this study we examined the association between RA and the alleles of the six classical HLA loci including DRB1. Six HLA loci (HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) of 1659 Japanese subjects (622 cases; 488 anti-cyclic citrullinated peptides (CCP) antibody (Ab) positive (82.6%); 103 anti-CCP Ab negative (17.4%); 31 not known and 1037 controls) were genotyped. Disease types and positivity/negativity for CCP autoantibodies were used to stratify the cases. Statistical and genetic assessments were performed by Fisher's exact tests, odds ratio, trend tests and haplotype estimation. None of the HLA loci were significantly associated with CCP sero-negative cases after Bonferroni correction and we therefore limited further analyses to using only the anti CCP-positive RA cases and both anti-CCP positive and anti-CCP negative controls. Some alleles of the non-DRB1 HLA loci showed significant association with RA, which could be explained by linkage disequilibrium with DRB1 alleles. However, DPB1*02:01, DPB1*04:01 and DPB1*09:01 conferred RA risk/protection independently from DRB1. DPB1*02:01 was significantly associated with the highly erosive disease type. The odds ratio of the four HLA-loci haplotypes with DRB1*04:05 and DQB1*04:01, which were the high-risk HLA alleles in Japanese, varied from 1.01 to 5.58. C*07:04, and B*15:18 showed similar P-values and odds ratios to DRB1*04:01, which was located on the same haplotype. This haplotype analysis showed that the DRB1 gene as well as five other HLA loci is required for a more comprehensive understanding of the genetic association between HLA and RA than analyzing DRB1 alone.

Triglyceride-rich lipoproteins in chronic kidney disease patients undergoing maintenance haemodialysis treatment.

OBJECTIVE: Plasma triglyceride (TG) levels were reported to be high in chronic kidney disease (CKD) patients undergoing haemodialysis (HD) treatment. One of the atherogenic causes of hypertriglyceridemia is the increase in TG-rich lipoprotein remnants, which are equivalent to remnant-like particle cholesterol (RLP-C). Here, we compared the plasma levels of TG, a representative indicator of TG-rich lipoproteins and RLP-C, as well as the TG/RLP-C ratio between CKD patients undergoing HD and controls, in an effort to elucidate the atherogenicity of TG-rich lipoproteins in CKD patients on HD. MATERIALS AND METHODS: Plasma lipid and apo(lipo)protein levels and the TG/RLP-C ratio were compared between 49 CKD patients undergoing HD and 627 controls. Blood sampling for lipid and apoprotein analysis was performed in a 12-h fasting state. Controls were divided into four subgroups according to TG level (from highest to lowest). RLP-C and apo(lipo)proteins were measured using the immunoprecipitation method and turbidimetric immunoassay, respectively. In addition, a comparison between HD patients and age-, gender-, and plasma TG level-matched controls was performed. RESULTS: Plasma TG levels were 107 ± 70 (mean ± SD) mg/dl in HD patients and 115 ± 72 mg/dl in controls. Plasma RLP-C levels were 6.7 ± 4.5 mg/dl in HD patients and 4.6 ± 3.5 mg/dl in the controls (p < 0.0001). RLP-C levels decreased in descending order from the highest to the lowest TG group in controls. RLP-C levels were higher in HD patients than in controls with plasma TG levels of < 150 mg/dl (p < 0.0001). TG/RLP-C ratios were 19.0 ± 12.0 in HD patients and 25.9 ± 9.5 in controls (p < 0.0001). This ratio was significantly lower in HD patients than in all four TG subgroups. The comparison between HD patients and age-, gender-, plasma TG-matched controls revealed identical results. CONCLUSION: Plasma RLP-C levels were high, and the TG/RLP-C ratio was low in CKD patients undergoing HD treatment. These findings indicate that total plasma TG-rich lipoprotein levels were not increased, but the distribution of plasma TG-rich lipoproteins were skewed towards remnant fractions in CKD patients undergoing HD treatment; these plasma TG-rich lipoproteins appear to be more atherogenic than those in controls.

Incidence and clinical features of priapism in Japan: 46 cases from the Japanese diagnosis procedure combination database 2006-2008.

We investigated the incidence and clinical features of priapism in Japan, using a national administrative claims database, the Diagnosis Procedure Combination database. Priapism patients were identified using the International Classification of Diseases and Related Health Problems, 10th Revision code, N483 (priapism). Verified patient characteristics included age, comorbidities and management of priapism. Among 6.93 million inpatients, 46 patients with priapism were identified. Four had two admissions each for repeated events. The median age was 41.5 years (range, 11-89 years). A total of 21 patients had comorbidities; 3 had haematological malignancies, 4 had haemodialysis, 1 had a renal transplant, 2 had neurological problems, 4 had non-haematological malignancies, 3 had trauma and 6 had psychoses (2 cases had two comorbidities). All patients with non-haematological malignancies were over the age of 70 years, indicating that close attention is required to search for associated malignancies in elderly patients. The medical treatments included 6 vascular embolizations, 11 Winter method surgeries and 18 other operations. The incidence was estimated to be 0.13 (95% confidence interval, 0.097-0.17) per 100,000 person-years. This incidence was lower than that reported in other parts of the world.

Lower incidence of inguinal hernia after radical prostatectomy using open gasless endoscopic single-site surgery.

Inguinal hernia is one of the long-term complications requiring surgical interventions after retropubic radical prostatectomy (RRP), and its incidence has been reported to range from 12 to 21%. The number of open gasless laparoendoscopic single-site surgery, especially minimum incision endoscopic radical prostatectomy (MIES-RRP) is increasing in Japan. The incidence of post-operative inguinal hernia was compared between conventional RRP and MIES-RRP. The medical records of 333 patients who underwent conventional RRP (n=214) or MIES-RRP (n=119) with pelvic lymphadenectomy at our hospital were retrospectively evaluated. There were no significant differences between the two groups in age, pre-operative PSA levels, or previous major abdominal surgery (cholecystectomy, gastrectomy and colectomy), appendectomy or inguinal hernia repair. MIES-RRP was carried out with a 5-8-cm lower abdominal midline incision. Inguinal hernia developed postoperatively in 41 (19%) of the 214 men undergoing conventional RRP during mean follow-up of 58 months (range: 7-60 months). In contrast, 7 (5.9%) of the 119 men receiving MIES-RRP, developed inguinal hernia during mean follow-up of 21 months (range: 13-31 months). The hernia-free survival was significantly higher after MIES-RRP than after conventional RRP (P=0.037). Our results suggest that MIES-RRP is less associated with post-operative inguinal hernia than conventional RRP.

miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression.

Recent advances in cancer biology reveal that microRNAs (miRNAs) are involved in the regulation of cancer-related genes, or they function as tumor suppressors or oncogenes. In prostate cancer, evidence has accumulated for the contribution of the androgen-dependent gene network to tumor growth, although the precise functions of miRNAs in prostate cancer remain to be investigated. Here, we identified androgen-responsive miRNAs by the short RNA sequencing analysis in LNCaP prostate cancer cells. Among 10 miRNAs with known sequences, we have determined that miR-148a reduces the expression of cullin-associated and neddylation-dissociated 1 (CAND1), a negative regulator of SKP1-Cullin1-F-box (SCF) ubiquitin ligases, by binding to the 3'-untranslated region of CAND1 mRNA. CAND1 knockdown by small interfering RNA promoted the proliferation of LNCaP cells. Our study indicates the potential contribution of miR-148a to the growth of human prostate cancer.

Maximum tumor diameter: a simple independent predictor for biochemical recurrence after radical prostatectomy.

Previous studies have suggested that maximum tumor diameter (MTD) is a predictor of PSA recurrence or biochemical recurrence (BCR) in prostate cancer after radical prostatectomy (RP). The significance of MTD in BCR prediction was evaluated using RP specimens of 364 patients with a BCR of 18% (n=66) during a mean follow-up of 37.4 months (range: 10-109 months). MTD was defined as the largest diameter of the largest tumor, and its median MTD was 15 mm (range: 0.9-50 mm). MTD was significantly associated with pre-operative PSA levels, pathological T stage, Gleason's score and positive surgical margin. In a univariate analysis, pathological T stage, Gleason's score, positive surgical margin and MTD were associated significantly with the risk of BCR. Patients with >20 mm MTD had a significantly higher risk of BCR than did those with < or =20 mm MTD (P<0.001). Cox multivariate models indicated that pathological stage, Gleason's score, positive surgical margin and MTD were independent prognostic factors for BCR. MTD would be a useful tool for predicting BCR, as calculation of MTD is a simple and reliable measure.

Inguinal lymph node metastases are recognized with high frequency in rectal adenocarcinoma invading the dentate line. The histological features at the invasive front may predict inguinal lymph node metastasis.

AIM: Inguinal lymph node (ILN) metastasis occurs with high frequency in some of the patients with lower rectal cancer. The aim of this study was to identify risk factors for ILN metastasis in patients with low rectal adenocarcinoma. METHOD: We retrospectively analysed 156 patients with lower rectal adenocarcinoma who underwent radical resection (R0) at a single institution. RESULTS: Twenty-five (16%) patients had a tumour that invaded the dentate line, seven of whom had ILN metastasis. Invasion of the dentate line was significantly associated with a high rate of ILN metastasis, worse prognosis and local recurrence than with a tumour not invading the dentate line (P = 0.03). A Cox proportional hazard regression analysis revealed the histological characteristics at the invading front (Hif) also to be a risk factor for ILN metastasis. CONCLUSION: Tumours which invade the dentate line have a high rate of ILN metastases and worse cancer specific end-points. The presence of poorly differentiated or mucinous adenocarcinoma components is an indication for bilateral groin irradiation.

Unconventional superconductivity of NpPd(5)Al(2).

The high quality single crystals of NpPd(5)Al(2) with the body-centered tetragonal structure were grown by the Pb flux method. NpPd(5)Al(2) was found to be the first Np-based heavy fermion superconductor with the relatively high critical temperature T(sc) = 4.9 K. The upper critical field H(c2) is large and highly anisotropic. Corresponding to the heavy electronic state, the initial slope of H(c2) is large, but H(c2) at low temperatures is suppressed by the magnetic field, indicating a strong Pauli paramagnetic effect and the first-order transition at H(c2). These results imply that NpPd(5)Al(2) is located at the proximity of the antiferromagnetic ordering, which might be hidden by the superconductivity. The d-wave superconductivity with a spin singlet state is most likely realized in NpPd(5)Al(2).

Field-angle-dependent specific heat measurements and gap determination of a heavy fermion superconductor URu2Si2.

To identify the superconducting gap structure in URu2Si2, we perform field-angle-dependent specific heat measurements for the two principal orientations in addition to field rotations, and a theoretical analysis based on microscopic calculations. The Sommerfeld coefficient gamma(H)'s in the mixed state exhibit a distinctly different field dependence. This comes from point nodes and the substantial Pauli paramagnetic effect of URu2Si2. These two features combined give rise to a consistent picture of superconducting properties, including a possible first order transition of Hc2 at low temperatures.

Ordered fullerene nanocylinders in large-diameter carbon nanotubes.

A new ordered fullerene phase encapsulated by large-diameter CNTs is systematically investigated by combining a growth technique by chemical vapour deposition, high-resolution transmission electron microscopy and molecular-dynamics simulations. In contrast to fullerenes in smaller (1-2 nm) diameter CNTs, where fullerenes are packed in linear or helical chains, fullerenes form a nanoscale cylinder in double-walled CNTs with diameters of ∼4 nm. The fullerenes were shown to form a nanocylinder with a side wall that resembled the (111) plane of solid C(60). This ordered phase is different from peapods or fullerene solids known so far, and a result of the interaction between the CNT wall and fullerenes. This finding will open up a new field of fullerene science.

The secretory leukocyte protease inhibitor (SLPI) suppresses cancer cell invasion but promotes blood-borne metastasis via an invasion-independent pathway.

An invasion-independent pathway has been proposed as a novel mechanism in blood-borne metastasis, where tumour cells enveloped by sinusoidal tumour vessels enter the circulation without vascular invasion. We previously identified the secretory leukocyte protease inhibitor (SLPI) as a candidate gene responsible for this pathway. In this study, the functional role of SLPI in metastatic dissemination was investigated. We transfected the SLPI gene into a poorly metastatic clone of the MCH66 mouse mammary tumour cell line. Over-expression of SLPI promoted in vivo growth and spontaneous metastasis to the lung, whereas it suppressed invasive activity in vitro. The inoculated tumours of SLPI-transfectants exclusively induced a sinusoidal vasculature and subsequently produced endothelial-coated tumour emboli, which are morphological indices of the invasion-independent pathway. In addition, exogenous SLPI inhibited the migration activity through Matrigel of both tumour cells and human umbilical vein endothelial cells (HUVECs). In vivo angiogenesis assays also demonstrated that SLPI suppressed the migration of newly formed blood vessels. These results suggest that an anti-migratory effect of SLPI on tumour-associated endothelial cells may induce vascular remodelling to form a sinusoidal architecture, and consequently promote invasion-independent metastasis. This study provides a new model for metastasis, based on the mechanism regulated by anti-invasive factors, such as SLPI.