Fumiaki Kiyomi

Heterogeneous clinical features in patients with pulmonary fibrosis showing histology of pleuroparenchymal fibroelastosis

BACKGROUND The histological pattern of pleuroparenchymal fibroelastosis (PPFE) is well defined, but its clinical features remain unclear. METHODS We retrospectively examined the predominantly involved lung-fields (based on abnormal opacities on computed tomography [CT] images), and the initial value and annual decline of respiratory function in patients with pulmonary fibrosis presenting with histologically confirmed PPFE. RESULTS Thirteen female and nine male subjects were included. Eleven interpreters independently analyzed 231 CT image series. One-third of the CT series (78/231) was interpreted as demonstrating equal involvement of the upper and lower lung fields, i.e., six out of 21 patients had equal involvement of the upper and lower lung fields, based on a majority decision of the interpreters. The residual volume/total lung capacity (RV/TLC) was increased and correlated inversely with forced vital capacity (FVC) at the initial measurement. FVC followed two patterns of decline over time: a gradual decline over a follow-up period of more than 6 years (-55mL/year, R(2)=0.799), and a relatively rapid decline over a shorter period (-364mL/year, R(2)=0.855) as determined by mixed-effect linear regression. CONCLUSIONS The predominantly involved sites seen on CT images of PPFE were not limited to the upper lobes. In some cases, upper lung fields were predominantly involved, but in other cases, both upper and lower lung fields were equally involved. Two patterns of FVC decline exists: a rapid decline over a short period and a slow decline over a longer period, suggesting that the disease follows a heterogeneous clinical course.

A single-arm Phase II validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: the AVOID trial

Background Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%–20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions. Patients and methods The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX) or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of hypersensitivity reactions. Results Hypersensitivity reactions occurred in three patients (4.1%); all three experienced a cutaneous reaction (grade 1 erythema). None of the 73 patients developed respiratory symptoms, ocular symptoms, or anaphylaxis. Grade 3 or higher hemotoxicity occurred in 13.7% of the patients and grade 3 or higher nonhematological toxicity occurred in 13.7%. The response rate to treatment was 64.4%. Conclusion The coinfusion of dexamethasone and oxaliplatin effectively reduced oxaliplatin-induced hypersensitivity reactions in patients with colorectal cancer. This approach should be considered for all patients treated with oxaliplatin, allowing treatment to be completed as planned.

Comparison of intra-individual coefficients of variation on the paired sampling data when inter-individual variations are different between measures

BackgroundPain intensities of patients are repeatedly measured by Visual Analog Scale (VAS) and Pain Vision (PV) in a clinical research. Two measurements by VAS and PV are performed at the same time. In order to evaluate within patient consistency, intra-individual coefficient of variations (CVs) are compared between measures assuming that the pain status of each patient is stable during the research period. The correlated samples and different inter-individual variation due to different scales of the measures should be taken into account in statistical analysis. The adjustment of covariates will improve the estimation of population mean values of the measures.MethodsIn this paper, statistical approach to compare the intra-individual CVs is proposed. The approach consists of two steps: (1) estimating population mean values and intra-individual variances of the pain intensities by measure in a mixed effect model framework, (2) computing intra-individual CVs and comparing them between measures. The mixed effect model includes measure and some variables as fixed effects and subject by measure as a random effect. The different inter-individual variations between measures and their covariance reflect the paired sampling in the variance component. The confidence interval of the difference of intra-individual CVs is constructed using the asymptotic normality and the delta method. Bootstrap method is available if sample size is small.ResultsThe proposed approach is illustrated using pain research data. Measure (VAS and PV), age and sex are included in the model as fixed effects. The confidence intervals of the difference of intra-individual CVs between measures are estimated by the asymptotic theory and by bootstrap using a subgroup resampling, respectively. Both confidence intervals are similar.ConclusionThe proposed approach is useful to compare two intra-individual CVs taking it into account to reflect the paired sampling, different inter-individual variations between measures and some covariates. Although the inclusion of covariates did not improve the goodness-of-fit in the illustration, the proposed model with covariates will improve the accuracy and/or precision if covariates truly influence response variable. This approach can be applicable with small modification to various situations.

C-myc and its Main Ubiquitin Ligase, Fbxw7, Influence Cell Proliferation and Prognosis in Adult T-cell Leukemia/lymphoma

Smoldering-type and chronic-type adult T-cell leukemia/lymphomas (ATLL) patients have relatively indolent clinical courses, but often progress into aggressive lymphoma-type and acute-type disease. We examined the roles of transcription factor C-MYC and its ubiquitin ligase FBXW7 in tumor tissues from 137 patients with ATLL. Immunohistochemical tests showed ≥50% of lymphoma cells in 78.7% (48/61) of lymphoma-type, and 64.9% (24/37) of acute-type samples expressed C-MYC, significantly higher than was seen in smoldering-type (3.6%) and chronic-type (9.1%) samples (P<0.01). Real-time polymerase chain reaction showed C-MYC mRNA expression in lymphoma-type and acute-type samples were significantly higher than in smoldering-type (P<0.01). C-MYC expression was highly correlated with its mRNA levels (&rgr;=0.65, P<0.0001), chromosomal amplification and duplication (&rgr;=0.3, P=0.045) and MIB1 labeling index (&rgr;=0.69, P<0.0001). Expression of FBXW7 protein and mRNA in lymphoma-type samples were significantly lower than those of smoldering-type (P<0.01 for each), and both were inversely correlated with C-MYC (protein: &rgr;=−0.4, P=0.0002; mRNA: &rgr;=−0.31, P=0.015). Seven patients with smoldering-type or chronic-type ATLL converted to acute-type, in 4 of whom C-MYC expression increased from <50% to ≥50%. Patients with ≥50% C-MYC or MIB1 had significantly worse prognosis than those with <50% C-MYC (P=0.0004) or MIB1 (P<0.0001), as did those with ≥7.5 C-MYC mRNA scores (P=0.033); whereas significantly better prognosis was associated with ≥50% FBXW7 protein (P=0.0006) or ≥0.17 FBXW7 mRNA (P=0.016). C-MYC and FBXW7 affect ATLL proliferation and progression, and low FBXW7 may increase C-MYC expression. C-MYC was a critical prognostic factor in ATLL patients.

Increased biofilm formation ability and accelerated transport of Staphylococcus aureus along a catheter during reciprocal movements

Staphylococcus spp. is a major cause of device-related infections. However, the mechanisms of deep-tissue infection by staphylococci from the skin surface remain unclear. We performed in vitro experiments to determine how staphylococci are transferred from the surface to the deeper layers of agar along the catheter for different strains of Staphylococcus aureus with respect to bacterial concentrations, catheter movements, and biofilm formation. We found that when 5-mm reciprocal movements of the catheter were repeated every 8h, all catheter samples of S. aureus penetrated the typical distance of 50mm from the skin to the epidural space. The number of reciprocal catheter movements and the depth of bacterial growth were correlated. A greater regression coefficient for different strains implied faster bacterial growth. Enhanced biofilm formation by different strains implied larger regression coefficients. Increased biofilm formation ability may accelerate S. aureus transport along a catheter due to physical movements by patients.

Relationship between the Carotid Plaque T1 Relaxation Time and the Plaque-to-Muscle Signal Intensity Ratio on Black-Blood Magnetic Resonance Imaging Scans

BACKGROUND Black-blood magnetic resonance imaging (BB-MRI) is useful for the characterization and assessment of carotid artery plaques. The plaque-to-muscle signal intensity (SI) ratio (plaque/muscle ratio [PMR]) is used widely to evaluate plaques. However, the correlation between the PMR and the T1 relaxation time needs to be determined. We measured the T1 relaxation time of carotid plaques using T1 mapping and compared the results with the PMR on BB-MRI scans. METHODS Between April 2014 and July 2015, 20 patients with carotid artery stenosis were treated by carotid artery stenting. All patients underwent preoperative magnetic resonance plaque imaging. The ratio of the plaque SI to the sternocleidomastoid muscle was calculated on T1-weighted BB-MRI scans. T1 mapping was performed in the region where the vessel was narrowest using the inversion recovery technique. The T1 relaxation time was recorded to determine whether there was a correlation with the PMR. RESULTS The plaque T1 value was 577.3 ± 143.2 milliseconds; the PMR value obtained on BB-MRI scans was 1.23 ± .27. There was a statistically significant decrease in the T1 value as the PMR increased (P < .0001). CONCLUSIONS As the T1 relaxation time was well correlated with the PMR on BB-MRI scans, the evaluation of vulnerable plaques using the PMR was reliable and convenient.

1056: THE EFFICACY OF THE POLIMYXIN B IMMOBILIZED FIBER COLUMN DIRECT HEMOPERFUSION FOR SEPTIC SHOCK

Crit Care Med 2015 • Volume 43 • Number 12 (Suppl.) baseline and after CSE exposure. The NALP3-ubiquitin binding was increased by more than 50% after CSE exposure when densitometrically controlled for input loading. Conclusions: CSE decreases NALP3 protein levels by increasing its degradation, not by decreasing new protein synthesis. The underlying mechanism is most likely increased ubiquitin-mediated proteasomal processing. Our findings provide potential mechanistic insights for smoking-related immunosuppression, and this may uncover unique opportunities to develop therapeutic strategies to modulate cytokine signaling, and subsequently, inflammation associated with sepsis development.

Bacterial contamination upon the opening of injection needles

IntroductionTwo opening methods are used for injection needle products: the “peel-apart method” where the adhesive surface of the packaging mount is peeled off, and the “push-off top method,” where the needle hub is pressed against the mount to break it. However, the risks of bacterial contamination as a result of opening method remain unknown. The aim of our study was to evaluate the bacterial contamination of needle hubs upon the opening of injection needles by the peel-apart or push-off top method under various conditions.MethodsBacterial contamination upon the opening of injection needles was examined in two materials, paper and plastic. Various concentrations of Staphylococcus aureus were applied to the mount and were maintained under wet or dry conditions. Injection needles were opened using the peel-apart or push-off top method. Needle hub contamination was examined using agar medium colony counting. Clinically assumed conditions (the hands and saliva of anesthesiologists) were also evaluated. Data were statistically examined using the Cochran-Mantel-Haenszel, Jonckheere, and Fisher’s exact tests.ResultsThe lateral surfaces of needle hubs were contaminated using the push-off top method, but not by the peel-apart method, in a manner that was dependent on S. aureus concentrations. No significant differences were observed between mount materials. Needle hub contamination was significantly more severe for the wet than for the dry opening portion. The clinically assumed condition study revealed that the lateral and bottom surfaces of the needle hub were contaminated significantly more in the saliva contamination group than in the dry and wet hand groups.ConclusionsThe bacterial contamination of needle hubs may occur upon the opening of injection needles when the push-off top method is used and may be affected by hands contaminated with saliva under clinical conditions.

Poorly Differentiated Clusters Predict a Poor Prognosis for External Auditory Canal Carcinoma

Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is rare and offers a poor prognosis; more accurate prognostic biomarkers are required. Our laboratory recently demonstrated that tumor budding, characterized by tumor cell clusters (< 5 cells), and laminin 5-γ2 staining of SCC of the EAC are associated with shorter survival. However, clusters composed of ≥ 5 tumor cells are also found in the stroma. Previous reports of colorectal cancer suggest that poorly differentiated clusters (PDCs) are a negative prognostic indicator. Here, we report on the association between PDCs and prognosis in SCC of the EAC. PDCs and tumor budding were histopathologically and immunohistochemically (cytokeratin AE1/AE3) analyzed in 31 cases of pre-treatment biopsy SCC of the EAC. Clusters in the stroma composed of < or ≥ 5 cancer cells were defined as tumor budding or PDCs, respectively. Entire tumors were initially scanned to identify greatest PDC density. Tumors with low or high PDC density were classified as low- and high-grade, respectively. Patients with high-grade PDCs had a significantly poorer outcome than those with low-grade. Even in cases of low-grade tumor budding, those with high-grade PDCs had a poor prognosis. Multivariate analysis results indicated that high-grade PDCs were associated with poor prognosis. PDC grade can provide a more accurate prognosis than tumor budding in SCC of the EAC.

Comparison of accuracy of presepsin and procalcitonin concentrations in diagnosing sepsis in patients with and without acute kidney injury

BACKGROUND Levels of the biomarkers presepsin and procalcitonin are affected by renal function. We evaluated the accuracies of presepsin and procalcitonin levels for diagnosing sepsis in patients with and without acute kidney injury (AKI). METHODS We evaluated patients with presepsin and procalcitonin data, and classified them into AKI and non-AKI groups based on the Kidney Disease Improving Global Outcomes criteria. Each group was then subdivided according to sepsis status for each stage of AKI. Receiver operating characteristic curve analyses were used to investigate the accuracies of biomarker levels for diagnosing sepsis. RESULTS In the non-AKI group, the area under the curves (AUCs) for procalcitonin and presepsin levels were 0.897 and 0.880, respectively (p = .525) and optimal cut-off values were 0.10 ng/ml (sensitivity: 85.1%, specificity: 79.1%) and 240 pg/ml (sensitivity: 80.9%, specificity: 83.2%), respectively. In the stage 3 subgroup, the AUC for procalcitonin (0.946) was significantly higher than that for presepsin (0.768, p < .001). The optimal cut-off values for diagnosing sepsis were 4.07 ng/ml (sensitivity: 87.2%, specificity: 93.5%) for procalcitonin and 500 pg/ml (sensitivity: 89.7%, specificity: 59.7%) for presepsin. CONCLUSIONS In patients with severe AKI, the accuracy of the diagnosis of sepsis with procalcitonin was significantly higher than with presepsin.