Reduction of cervical vertebra ghost images in panoramic radiography using vertical dual exposure.

PURPOSE: To evaluate the image quality of vertical dual-exposure panoramic radiography (PR), which merges two PR images taken at different focus heights to reduce ghost images of cervical vertebrae (CV) and intervertebral spaces (IVS) in the incisor region. METHODS: PR images of an aluminum block, a CV phantom and a human head phantom were taken at 0 mm and merged with and subtracted from PR images taken at other heights (0, 5, 10, 15, and 20 mm) to create new images, e.g., Merg0 + 15 mm and Sub0 - 10 mm. The subtracted images were analyzed subjectively according to the uniformity on the line profile. Merged images were evaluated subjectively by six raters to determine the influence of the ghost images. RESULTS: Objective evaluation revealed a positional shift in the ghost images according to the height of the focus for both phantoms. In the subjective evaluation, the normal PR (Merg0 + 0 mm) showed the worst score, indicating strong influence of CV and IVS ghost images. CONCLUSION: The vertical dual-exposure PR method, which merges PR images taken at the normal position and a higher X-ray focus, can reduce CV and IVS ghost images in the incisor region.

Significance of timing of therapeutic line on effectiveness of nivolumab for metastatic renal cell carcinoma.

Objectives: This study aimed to clarify the significance of therapeutic timing on the effectiveness of nivolumab for treating metastatic renal cell carcinoma. Marterials and methods: Fifty-eight patients with metastatic renal cell carcinoma treated with nivolumab monotherapy were retrospectively studied. Patients who were treated with nivolumab as second-line therapy were included in the second-line group, while the others were included in the later-line group. The clinicopathological characteristics, effects of nivolumab, and prognoses of these groups were compared. Results: Twenty and thirty-eight patients were included in the second-line and later-line groups, respectively. There were no significant differences in the distribution of International Metastatic Renal Cell Carcinoma Database Consotium risk and other clinicopathological characteristics between the 2 groups. The proportion of patients whose objective best response was progressive disease in the second-line group was significantly lower than that in the later-line group (15% vs. 50%, p = 0.0090). The 50% progression-free survival with nivolumab in the second-line group was significantly better than that in the later-line group (not reached and 5 months, p = 0.0018). Multivariate analysis showed that the second-line setting was an independent predictive factor for better progression-free survival (p = 0.0028, hazard ratio = 0.108). The 50% overall survival after starting nivolumab in the second-line and later-line groups was not reached and 27.8 months, respectively (p = 0.2652). Conclusions: The therapeutic efficacy of nivolumab as second-line therapy is expected to be better than that of later therapy.

Correction of intraoral radiography with dual imaging plates using enlargement of the horizontal direction with division into 12 blocks.

PURPOSE: The dual imaging plate (DIP) method, which synthesizes intraoral radiographs from a front imaging plate (FIP) and a back imaging plate (BIP), produces adequate image quality and allows the radiation dose to be reduced. However, there are slight errors in superimposition and alignment between the FIP and BIP. The aim of this study was to establish positional correction in the DIP method and evaluate the effect. METHODS: Six sets of two imaging plates were used for imaging a mesh plate and a porcine mandible phantom. Subtraction images between FIP and BIP images were synthesized in four steps: correcting horizontal and vertical direction, rotation, enlargement ratio, and enlargement ratio into 12 blocks. Variance of the pixel value on the subtraction images at each step was compared to evaluate the alignment of FIP and BIP images. RESULTS: The variance of the pixel values in the subtraction images was gradually and significantly decreased by each step of image processing (P < 0.01), indicating that the degree of alignment of FIP and BIP images improved during the image processing. CONCLUSION: The present study revealed that it is possible to synthesize more precise DIP images using an additional four-step image processing technique.

Impact of low and high body mass index on predicting therapeutic efficacy and prognosis in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

OBJECTIVE: To evaluate the significance of both low and high body mass index (BMI) as a biomarker in first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). METHODS: The oncological outcome of 235 patients with mRCC treated with TKI from 2007 to 2018 was reviewed retrospectively. All patients received first-line TKI as therapy. We analyzed the relationship between BMI (low and high) and disease control rate. The primary outcome was progression free survival and overall survival, and the association between BMI and survival prognosis was evaluated. RESULTS: The median BMI was 22.5 kg/m2 , and 25 patients (10.7%) had a low BMI (<18.5 kg/m2 ), 158 patients (67.2%) had a normal BMI (18.5-25 kg/m2 ), and 52 patients (22.1%) had a high BMI (≥ 25 kg/m2 ). Patients in the low BMI group had a significantly lower disease control rate, whereas patients in the high BMI group had a significantly higher disease control rate (p = 0.002 and p = 0.030, respectively). A log-rank test showed prognosis to be significantly poorer in the low BMI group and to be significantly better in the high BMI group than that in the normal BMI group. Multivariable Cox regression analysis showed that low BMI was an independent indicator of poor prognosis, whereas high BMI was an independent indicator of favorable prognosis. CONCLUSION: We showed the impact of both low and high BMI on predicting therapeutic efficacy and prognosis in mRCC patients treated with TKI.

Reduction of scratch or dirt artifacts on intraoral radiographs using dual imaging plates in image processing.

OBJECTIVES: Artifacts including scratches and dirt artifacts on the digital intraoral radiographs finally contribute to making inaccurate diagnoses. The aim of this study was to reduce the incidence of artifacts using dual imaging plates (DIPs) in imaging processing. METHODS: Conventional X-rays were taken of a porcine mandible embedded in acrylic resin using a DIP which consists of a front IP (FIP) and a back IP (BIP) with some scratches and dirt. The two images of the FIP and BIP were then synthesized and averaged to obtain a conventional DIP image. The following image processing method was used to make a DIP with artifact reduction (DIP+AR) image. A subtraction image of the FIP and BIP was constructed and the standard deviation (SD) was calculated. If the pixel value was over 3SD on the subtraction images, the pixel value of the DIP was swapped with the value on the opposite side of the non-artifact pixel. The conventional and DIP+AR images were also subjectively evaluated. RESULTS: Image processing to create a DIP+AR image was able to reduce the number of artifacts. Medians of number of artifacts evaluated were 2.00 [interquartile range (IQR), 2.50] in DIP images and 0.67 (IQR, 1.29) in DIP+AR images, indicating a significant reduction of number of artifacts in DIP+AR images. CONCLUSIONS: DIP+AR image processing can reduce the incidence of artifacts caused by scratches and dirt, and could extend the lifespan of the IP and contribute accurate diagnosis in oral radiology.

Impact of modified Glasgow prognostic score on predicting prognosis and modification of risk model for patients with metastatic renal cell carcinoma treated with first line tyrosine kinase inhibitor.

INTRODUCTION AND OBJECTIVES: Intermediate risk group of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria is thought to consist of patients with different prognoses. This study investigated the impact of a pretreated modified Glasgow prognostic score (mGPS), which is defined on the basis of the pretreated serum albumin and C-reactive protein level, on predicting the prognosis of patients with metastatic renal cell carcinoma (mRCC) and its usefulness for the re-stratification of patients into a more improved risk model. MATERIALS AND METHODS: One hundred ninety-six mRCC patients treated with first-line tyrosine kinase inhibitor (TKI) were retrospectively investigated. All patients were classified into either a high-mGPS or a low-mGPS group on the basis of mGPS score upon starting systemic therapy, the overall survival (OS) and cancer specific survival (CSS) rates in each group were compared. We use decision curve analysis and calculate C-index based on OS and CSS to compare IMDC+mGPS model and IMDC model. RESULTS: The categories of favorable, intermediate, and poor risk groups in the IMDC model were assessed in 32, 113, and 51 cases, respectively. The low- and high-mGPS groups consisted of 149 and 47 cases. The median OS in the high- and low-mGPS groups were 38.4 months and 5.6 months, and their median CSSs were 41.0 months and 5.6 months, respectively (P < 0.0001). Multivariate analysis showed that a high mGPS, multiple metastatic organs, and hypercalcemia were independent predictive factors for a worse OS (P = 0.0260). Next, we divided the intermediate risk group into two subgroups using the mGPS score. The OS and CSS for the high-mGPS subgroup were significantly worse than those for the low-mGPS one (P = 0.0024, median OS: 21.0 months and 33.7 months, P = 0.0007, median CSS: 21.0 months and 39.8 months), and there was no significant difference in OS between the high-mGPS subgroup in the intermediate risk group and poor risk group (P = 0.2250). The value of C-index based on OS at IMDC and IMDC+mGPS model were 0.6771 and 0.6967, and those based on CSS were 0.6850 and 0.7080, respectively. In decision curve analysis to evaluate the clinical net benefit using the IMDC+mGPS model compared to the IMDC model, there was no significant difference between the two groups. CONCLUSION: mGPS is useful for establishing a more improved prognostic model that is able to stratify mRCC patients treated with first-line TKI.

Prognostic model of upfront cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors and/or targeted agents.

INTRODUCTION AND OBJECTIVES: The aim of this study was to investigate prognostic factors and to establish a prognostic model using them for upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitor (ICI) and/or tyrosine kinase inhibitor (TKI). MATERIALS AND METHODS: Two hundred eleven patients who were diagnosed as mRCC at initial diagnosis and were treated with TKI and/or ICI were classified into 2 groups: those undergoing CN (upfront CN group, 117 cases) and those who initially underwent systemic therapy (non-upfront CN group, 94 cases). In the upfront CN group, the patients' background and overall survival (OS) were compared with those in the other two groups, and prognostic factors were analyzed. A prognostic model of the upfront CN group was established. RESULTS: The median of the observation period for the upfront CN group was 25 months. The rates of patients with clear cell histology, with a Karnofsky performance status (KPS) of ≥ 80%, with a single metastatic organ, with a normal pretreated C-reactive protein level, and with an intermediate risk according to the International mRCC Database Consortium (IMDC) model were significantly higher than those in the non-upfront CN group (87.2% and 30.9%, p < 0.0001; 92.3% and 77.7%, p = 0.0025; 41.9% and 24.5%, p = 0.0080; 47.9% and 13.8%, p < 0.0001; 66.7% and 45.7%, p = 0.0023, respectively). The 50% OS in the upfront CN group was 33.1 months, significantly better than that in the non-upfront CN group (11.1 months, p < 0.0001), and these results were consistent regardless of their prognostic risk level. Multivariate analysis showed that multiple metastatic organs and a KPS of < 80% were independent predictive factors for OS (hazard ratio: 1.653 and 2.995, p = 0.0339 and 0.0054, respectively). Using these two parameters to stratify the upfront CN group, the 50% OSs in cases with no risk factors, in those with one factor, and in those with two factors were 43.4 months, 29.1 months, and 7.7 months, respectively (p < 0.0001). CONCLUSION: The upfront CN group was able to be stratified by our prognostic model into three subgroups with different prognoses. This model can provide useful information for making decisions in consideration of upfront CN in patients with mRCC.

First-in-human study of blood amyloid ß removal from early Alzheimer's disease patients with normal kidney function.

INTRODUCTION: Amyloid ß (Aß) is a brain protein that causes Alzheimer's disease (AD). This study aimed to verify whether hemadsorption using a hexadecyl-alkylated cellulose bead (HexDC) column removes blood Aß and brain Aß accumulation in mild cognitive impairment/mild AD cases with normal kidney function. METHODS: Two patients with positive Aß on brain imaging underwent HexDC hemadsorption weekly for 6 months. RESULTS: The Aß removal efficiency of HexDC was 87-99%. Aß1-40 /Aß1-42 influx into the blood in one session was 596/56 and 489/48 ng for Case A and Case B, respectively. Although brain Aß accumulation did not clearly change after 6 months of hemadsorption, cognitive functions measured by the two tests were maintained or slightly improved. CONCLUSION: Blood Aß removal was performed in two early AD patients with normal kidney function without adverse events, and it slightly improved or maintained cognitive function.

Preliminary evaluation of dual imaging plate intraoral radiography.

PURPOSE: This study evaluated the contrast-to-noise ratio (CNR), spatial resolution, and subjective quality of dual imaging plates (DIP) intraoral radiography. METHODS: The DIP and conventional single IP (CSIP) methods both used YCR DT-1 imaging plates (Yoshida Co.). The DIP, comprising a front IP (FIP) and back IP (BIP), was constructed. DIP images were synthesized from the FIP and BIP images. An aluminum step phantom was used to measure the CNR. A line pair gauge was used to measure the spatial imaging resolution. A phantom comprising a porcine mandible embedded in acrylic resin was used for subjective evaluation. RESULTS: The CNR of the DIP image was 32% higher than that of the FIP image. The spatial resolution achieved using the FIP, DIP, and CSIP was highly comparable except above 4 line pairs/mm, where that of the CSIP was highest. In subjective evaluation, the noise in the DIP images was significantly lower than in those obtained using the FIP and CSIP. CONCLUSION: The CNR of the DIP was higher than that of the FIP. The decrease in spatial resolution of the DIP was limited. The subjective image quality of the DIP was higher than that of the FIP.

Aß Influx into the Blood Evoked by Different Blood Aß Removal Systems: A Potential Therapy for Alzheimer's Disease.

PURPOSE: Amyloid-ß (Aß) is a brain protein that causes Alzheimer's disease. We have revealed that extracorporeal blood Aß-removal systems evoked a large Aß influx into the blood. This study investigated the system that is more effective in evoking Aß influx. METHODS: Aß removal activities were compared between hexadecyl-alkylated cellulose beads (HexDC) and fragments of polysulfone hollow fibers (PSf-HFs) in mini-columns to eliminate the filtration effect. Then, adsorptive filtration systems were adapted for PSf hemodialyzers to enhance Aß adsorption on micropores in the wall of hollow fibers. Plasma Aß concentrations of patients with renal failure were analyzed during treatment with PSf hemodialyzers alone for 8 h or tandemly connected HexDC and PSf hemodialyzers for 4 h. RESULTS: In the in vitro study, Aß removal efficiency for HexDC was approximately 100% during the 60 min treatment, whereas the removal efficiency for PSf-HF fragments gradually decreased. However, PSf hemodialyzer in adsorptive filtration systems removed Aßs comparably or more than HexDC. Aß influx into the blood increases time-dependently. Concomitant use of HexDC and PSf hemodialyzer evoked a larger Aß1-40 influx than that of PSf hemodialyzer alone. However, Aß1-42 influx by PSf hemodialyzer alone was similar to or a little larger than influx by the combined system. Both systems evoked almost doubled Aß influx than estimated Aßs existing in the normal brain during the 4 h treatment. CONCLUSION: PSf hemodialyzer alone for a longer period and concomitant use of HexDC and PSf hemodialyzer for a shorter time effectively evoked a larger Aß influx. To evoke Aß1-42 influx, PSf hemodialyzer alone was effective enough. These findings of devices and treatment time may lead to optimal clinical settings for therapy and prevention of Alzheimer's disease.

Erratum: Improved prognosis for elderly patients with metastatic renal cell carcinoma in the era of targeted therapy.

[This corrects the article DOI: 10.3892/mco.2020.2020.].

[Postoperative Inguinal Hernia after Robot-Assisted Radical Prostatectomy with Prevention Technique Using Spermatic Cord Isolation].

We retrospectivelyevaluated postoperative inguinal hernias (PIHs) after robot-assisted radical prostatectomy(RARP) with a technique for preventing hernias byspermatic cord isolation. Among the RARPs performed from 2016 to 2018, 191 cases were evaluated 12 or more months after surgery. In all the cases, the peritoneum was isolated from the spermatic cord by5 cm or more as a hernia prevention technique during RARP. We compared the background factors between PIH-positive and PIH-negative groups. The PIH-positive group had a significantlylower bodymass index (BMI) than the PIH-negative group (20.6 kg/m2 vs 23.8 kg/m2, p＝0.0079), but there were no significant differences in other background factors. When patients were classified into three groups byBMI, low (＜21.9 kg/m2), intermediate (21.9 to 25.5 kg/m2), and high (＞25.5 kg/m2), the rate of PIH was 8.5% for the low group, 2.1% for the intermediate group, and 0% for the high group. Our findings suggest that incidences of inguinal hernias after the preventive technique of spermatic cord isolation in RARP, and the BMIs tended to be low in the hernia cases.

Evaluation of the performance, operability, and safety of Plasauto µ, a new type of machine for cell-free and concentrated ascites reinfusion therapy, in a postmarketing clinical study.

Cell-free and concentrated ascites reinfusion therapy (CART) is performed by collecting the ascites from the patient, followed by filtration and concentration. Thereafter, concentrated cell-free ascites is reinfused into the patient intravenously. The new type of machine, Plasauto µ, for managing the process of CART was launched onto the market. We have evaluated the machine through postmarketing clinical study in 17 patients with malignant ascites. The amounts of original and concentrated ascites were 3673 ± 1920 g and 439 ± 228 g, respectively. Recovery rates were acceptable regarding values of total protein, albumin, and IgG that were 55.6% ± 17.3%, 60.2% ± 20.8%, and 58.2% ± 20.5%, respectively. Recovery rates were positively associated with amounts of original ascites and negatively associated with total protein concentration. No adverse events related to the machine were observed. The new type of machine showed preferable performance in processing malignant ascites.

[ROBOT-ASSISTED RADICAL CYSTECTOMY AT HIROSHIMA CITY ASA HOSPITAL -COMPARISON WITH LAPAROSCOPIC RADICAL CYSTECTOMY].

(Objective) We compared the perioperative parameters of robot-assisted radical cystectomy (RARC) and laparoscopic radical cystectomy (LRC) to evaluate the utility of RARC. (Patients and methods) At Hiroshima City Asa Hospital, 25 patients underwent RARC from July 2018 to May 2020 (R group) and 79 patients underwent LRC from July 2012 to June 2018 (L group). We retrospectively compared the patient characteristics, perioperative outcomes, and pathological outcomes between the R group and the L group. (Results) Regarding the patient characteristics, the R group had significantly more neo-adjuvant chemotherapy than the L group (64.0% vs. 32.9%, P=0.009), but the other characteristics did not differ. Between the R group and the L group, there were no significant differences in the total operating time (R group = 400 minutes vs. L group = 421 minutes), estimated blood loss (R group = 228 ml vs. L group = 318 ml), or pathological outcomes. However, there were significantly less postoperative complications in the R group than in the L group (24.0% vs. 52.6%, P=0.020). (Conclusion) This study showed that there might be benefits to introducing RARC into medical centers that perform LRC.

Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor.

BACKGROUND: There are various alternative first-line therapeutic options besides tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). To inform therapeutic decision-making for such patients, this study aimed to identify predictive factors for resistance to TKI. MATERIALS AND METHODS: A total of 239 cases of mRCC patients who received first-line TKI therapy were retrospectively studied. Patients with a radiologic diagnosis of progressive disease within 3 months after initiating therapy were classified as primary refractory cases; the others were classified as non-primary refractory cases. The association between primary refractory cases and age, gender, pathology findings, serum c-reactive protein (CRP) level, metastatic organ status, and 6 parameters defined by the International Metastatic Renal Cell Carcinoma Database Consortium were analyzed. RESULTS: Of 239 cases, 32 (13.3%) received a radiologic diagnosis of progressive disease within 3 months after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, presence of liver metastasis, anemia, and time from diagnosis to treatment interval of less than a year were significantly higher in the primary refractory group. Multivariate analysis showed that sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, and liver metastasis were independently associated with primary refractory disease. A risk-stratified model based upon the number of patients with these factors indicated rates of primary refractory disease of 4.0%, 10.1%, and 45.0% for patients with 0, 1, and 2 or more factors, respectively. CONCLUSIONS: Sarcomatoid differentiation, hypercalcemia, an elevated serum CRP level, and presence of liver metastasis were associated with primary refractory disease in mRCC patients receiving first-line TKI therapy. These results provide clinicians with useful information when selecting a first-line therapeutic option for mRCC patients.

Suppression of inflammation during cell-free concentrated ascites reinfusion therapy using a blood purification device.

In recent years, cell-free concentrated ascites reinfusion therapy has been used to treat patients with malignant ascites. However, concentrated ascites reinfusion therapy involves enrichment and reinfusion of useful proteins and inflammatory cytokines. Therefore, fever is a primary side effect and significant problem for patients with ascites. We removed IL-6, an inflammatory cytokine, by mixing malignant ascites and the hexadecyl group adsorbent from a ß2 -microglobulin-adsorbing column (Lixelle S-15). As a result, the hexadecyl group adsorbent did not adsorb the albumin of malignant ascites but adsorbed 43% of IL-6. To investigate the effect of the hexadecyl group adsorbent on hepatocytes, the adsorbed ascites was added to a human hepatoma cell line (HepG2), and the gene expression levels of albumin and serum amyloid A protein were examined. After absorption, ascites showed significantly suppressed serum amyloid A protein expression and significantly increased albumin gene expression compared to before adsorption. Our results suggest that incorporation of Lixelle to filter and concentrate malignant ascites can suppress inflammatory responses and reduce the inhibition of albumin synthesis in the liver after reinfusion.

Impact of the systemic immune-inflammation index for the prediction of prognosis and modification of the risk model in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

INTRODUCTION: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria are the most representative risk model for patients with metastatic renal cell carcinoma (mRCC). However, the intermediate-risk group of IMDC criteria is thought to include patients with different prognoses because many of the patients are classified into the intermediate-risk group. In this study, we investigated the impact of systemic immune-inflammation index (SII), which is calculated based on neutrophil count, platelet count, and lymphocyte count, on predicting the prognosis in patients with mRCC, and its usefulness for re-classification of patients with a more sophisticated risk model. METHODS: From January 2008 to January 2018, 179 mRCC patients with a pretreatment and SII were retrospectively investigated. All patients were classified into either a high-SII group or a low-SII group based on the cutoff value of a SII at 730, as reported in previous studies; the overall survival (OS) rates in each group were compared. RESULTS: The median age was 65 years old. Males and females comprised 145 and 34 cases, respectively. The categories of favorable-, intermediate-, and poor-risk groups in the IMDC model were assessed in 39, 102, and 38 cases, respectively. The median observation period was 24 months. The low-SII and high-SII groups consisted of 73 and 106 cases, respectively. The 50% OS in the high-SII group was 21.4 months, which was significantly worse than that in the low-SII group (49.7 months; p<0.0001). Multivariate analysis showed that a high SII was an independent predictive factor for a worse OS. Next, we constructed a modified IMDC risk model that included the SII instead of a neutrophil count and a platelet count. By using this modified IMDC model, all cases were re-classified into four groups of 33, 52, 81, and 13 cases with 50% OS of 88.8, 45.9, 29.4, and 4.8 months, respectively. CONCLUSIONS: The SII is useful for establishing a more sophisticated prognostic model that can stratify mRCC patients into four groups with different prognoses.

Improved prognosis for elderly patients with metastatic renal cell carcinoma in the era of targeted therapy.

The present study investigated the outcomes of targeted therapy for elderly patients with metastatic renal cell carcinoma (mRCC). A total of 277 patients with mRCC who were treated with tyrosine kinase inhibitor as a first-line therapy from January 2008 to May 2018 were retrospectively investigated by reviewing clinicopathological data. Patients 75 years or older were classified into the older-aged group (n=55) while all others were classified into the younger-aged group (n=222). The preoperative clinicopathological characteristics and the overall survival (OS) rate for these two groups were subsequently compared. The median age in the older- and younger-aged groups was 78 and 63 years (P<0.0001), respectively. A total of 7, 42 and 6 cases in the older-aged group and 46, 118 and 58 cases in the younger-aged group were classified into favorable, intermediate, and poor risk groups, respectively. The rate of patients with cardiovascular diseases (29.1%) and malignant diseases other than RCC (20.0%) was significantly higher in the older-aged group compared with the younger-aged group (6.8%; P<0.0001 and 7.2%; P=0.0042, respectively). There was a significant improvement in the OS rate for patients beginning targeted therapy after 2011 compared with those starting therapy prior to 2010. The 50% OS rate in patients starting targeted therapy before 2010 and after 2011 was, respectively, 17.1 and 38.6 months for the older-aged group (P=0.0066), while there was no significant difference for the younger-aged group (P=0.1441; 50% OS; 35.9 vs. 30.5 months). The results of the present study indicated that the prognosis for older patients has improved since the introduction of targeted therapy.

Removal of Aß Oligomers from the Blood: A Potential Therapeutic System for Alzheimer's Disease.

PURPOSE: Amyloid-ß protein (Aß) is one of the causative proteins of Alzheimer's disease. We have been developing extracorporeal blood Aß-removal systems as a method for enhancing Aß clearance from the brain. We reported previously that medical adsorbents and hemodialyzers removed Aß monomers from peripheral blood, which was associated with influx of Aß monomers from the brain into the bloodstream. Our intent here was to develop a method to promote clearance of Aß oligomers and to provide an estimate of the molecular size of intact Aß oligomers in plasma. METHODS: Two hollow-fiber devices with different pore sizes (Membranes A and B) were evaluated as removers of Aß oligomers with human plasma in vitro. The concomitant removal of Aß oligomers and monomers was investigated by using Membrane B and hexadecyl alkylated cellulose beads or polysulfone hemodialyzers. Double-filtration plasmapheresis with Membrane A was investigated as an approach for the removal of plasma Aß oligomers in humans. RESULTS: Aß oligomers were effectively removed by both Membranes A and B. The increase of Aß oligomers in plasma was observed just after the removal of plasma Aß oligomers in humans. The intact molecular size of major Aß oligomers in the plasma was estimated to be larger than albumin at approximately 60 kDa or more. Additionally, the concomitant removal of Aß monomers and oligomers evoked dissociation of larger Aß oligomers into smaller ones and monomers. CONCLUSION: Aß oligomers were cleared from plasma both in vitro and in human subjects by using hollow-fiber membranes with large pores, indicating that their intact sizes were mostly larger than 60 kDa. Aß oligomers in peripheral circulation were increased after some clearances in human. Further investigation will determine whether the Aß oligomers detected in circulation after clearance were via influx from the brain.

The third national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from complicated urinary tract infection patients.

The antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using national surveillance data. The data consisted of 881 bacterial strains from eight clinically relevant species. The data were collected for the third national surveillance project from January 2015 to March 2016 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was undertaken with the cooperation of 41 medical institutions throughout Japan. Fluoroquinolone required a MIC90 of 2-64 mg/L to inhibit the 325 Escherichia coli strains tested and the proportion of levofloxacin resistant E. coli strains increased to 38.5% from 29.6% in 2011 and 28.6% in 2008. The proportion of levofloxacin resistant strains of Pseudomonas aeruginosa and Enterococcus faecalis decreased from previous reports and the proportion of multidrug-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae remained low. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, strains with reduced susceptibility to vancomycin (minimum inhibitory concentration, 2 µg/mL) increased to 14.7% from 5.5%. Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (79 of 325 strains, 24.3%), Klebsiella pneumoniae (9 of 177 strains, 7.7%), and Proteus mirabilis (6 of 55 strains, 10.9%). The proportion of extended-spectrum ß-lactamase producing E. coli and K. pneumoniae strains increased from previous surveillance reports.