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Definitive chemoradiotherapy (CRT) is the standard treatment for patients with locally advanced esophageal cancer (EC) who refuse surgery as the initial therapy. However, poor survival, a high incidence of late toxicities, and severe complications after salvage surgery remain issues to be resolved. This single-arm multicenter trial (JCOG0909) aimed to confirm the efficacy of CRT modifications, including salvage treatment for reducing CRT-related toxicities and facilitating salvage treatment for improved survival.Patients with clinical stage II/III EC (International Union Against Cancer sixth edition, non-T4) were eligible. Chemotherapy comprised cisplatin (75 mg/mOverall, 96 patients were enrolled, and 94 were included in the efficacy analysis. A complete response was achieved in 55 patients (59%). Salvage endoscopic resection and salvage surgery were performed in 5 (5%) and 25 patients (27%), respectively. R0 resection by salvage surgery was achieved in 19 patients (76%). Five patients (20%) showed grade 3 or 4 early operative complications, and 9 patients (9.6%) showed grade 3 late toxicities during the long-term follow-up. The 3-year OS was 74.2% (90% confidence interval, 65.9%-80.8%).The combination of definitive CRT and salvage treatment has lower CRT-related toxicities and yields good OS, thus making it a promising novel treatment option for patients with locally advanced EC.

This cross-sectional study aimed to examine the relationships between lip seal strength, tongue pressure, and daytime sleepiness in Japanese workers. A self-administered questionnaire which comprised the Epworth Sleepiness Scale (ESS) was completed by 496 workers, and excessive daytime sleepiness was defined by an ESS score of 11 or over. Lip seal strength and tongue pressure were measured in all participants, and multiple regression analyses were performed to examine the effects of lip seal strength and tongue pressure on daytime sleepiness. The median ESS score was 5.0 (25th and 75th percentiles: 2.0 and 8.0), and 42 (8.5%) workers had excessive daytime sleepiness. The median lip seal strength was 13.5 N (11.4, 16.3), and the tongue pressure was 41.7 kPa (35.2, 48.3). Workers with higher ESS scores had significantly lower levels of lip seal strength than those without, following adjustments for age and body mass index (BMI) values (β (95% confidence interval): −0.043 [−0.081, −0.004]). However, tongue pressure was not significantly associated with ESS score after adjustments for age and/or BMI. These results suggest that maintaining moderate lip seal strength may help prevent excessive daytime sleepiness in Japanese workers regardless of age or BMI.

Background: This cross-sectional study aimed to examine the relationship between lip seal strength, tongue pressure, and daytime sleepiness, among Japanese workers. Methods: A self-administered questionnaire composed of Epworth Sleepiness Scale (ESS) was conducted on 496 workers, and excessive daytime sleepiness defined by an ESS score of 11 or over. Lip seal strength and tongue pressure were measured in all participants, and multiple regression analyses were performed to examine the effects of lip seal strength and tongue pressure on daytime sleepiness. Results: The median ESS score was 5.0 (25th, 75th percentile: 2.0, 8.0), and 60 (12.1%) workers with excessive daytime sleepiness. The median lip-seal strength was 13.5 N (11.4, 16.3) and tongue pressure was 41.7 kPa (35.2, 48.3). Workers with excessive daytime sleepiness had significantly lower lip seal strength than did those without after adjustment for age and body mass index (BMI) (β (95% confidence interval): –0.043 [–0.081, –0.004]). However, tongue pressure was not significantly associated with excessive daytime sleepiness after adjustment for age and/or BMI. Conclusions: These results suggest that maintaining moderate lip-seal strength may help prevent excessive daytime sleepiness in Japanese workers regardless of age or BMI.

Summary of patients with EBV-associated lymphoproliferative diseases and CCR4 expression.

Purpose: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is an Epstein–Barr virus (EBV)–associated lymphoma for which a new chemotherapeutic regimen called SMILE (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide) recently showed promising results.Experimental Design: The amount of EBV-DNA was prospectively measured in whole-blood and plasma samples by real-time quantitative PCR from 26 patients registered in the SMILE phase II study.Results: Before treatment, the EBV-DNA was detected in 22 samples of whole blood with a median number of 3,691 copies/mL (range: 0–1.14 × 107), but 15 samples of plasma with a median of 867 copies/mL (range: 0–1.27 × 107). Results of these 2 measurements of EBV-DNA well correlated (R2 = 0.994, P < 0.001). The overall response rate to SMILE was significantly higher in patients with less than 105 copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, P = 0.007) and in patients with less than 104 copies/mL of EBV-DNA in plasma (95% vs. 29%, P = 0.002). The incidence of grade 4 toxicity of SMILE other than leukopenia/neutropenia was significantly higher in patients with 105 copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, P = 0.007) than that of others and in patients with 104 copies/mL or more in plasma (86% vs. 26%, P = 0.002).Conclusions: These findings suggest that whole blood is more sensitive for clinical use than plasma. The EBV-DNA amount in whole blood was useful for predicting tumor response, toxicity, and prognosis after SMILE chemotherapy for ENKL. Clin Cancer Res; 18(15); 4183–90. ©2012 AACR.

Supplemental Figure Legend from mTOR Inhibitors Induce Cell-Cycle Arrest and Inhibit Tumor Growth in Epstein–Barr Virus–Associated T and Natural Killer Cell Lymphoma Cells

Supplementary Figure 1. Densitometoric analysis of immunoblotting. Supplementary Figure 2. Rapamycin inhibits proliferation of T and NK cell lines. Supplementary Figure 3. CCI-779 induces inhibition of cell proliferation by G1 cell cycle arrest in Epstein-Barr virus (EBV)-positive T and NK cell lines. Supplementary Figure 4. CCI-779 inhibits tumor growth and proliferation in the murine xenograft model. CCI-779 inhibits growth of subcutaneous xenograft tumors in NOG mice.

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PDF file - 86K, 4.Correlation of EBER positivity and EBV-DNA levels in whole blood or plasma

Purpose: Epstein–Barr virus (EBV) infects B cells, as well as T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoid malignancies. In various tumor cells, mTOR performs an essential function together with Akt with regard to cell growth. We investigated the effects of mTOR inhibitors on EBV-associated T- and NK-cell lymphomas.Experimental Design: We investigated the Akt/mTOR activation pathway in EBV-positive and -negative T- and NK-cell lines (SNT13, SNT16, Jurkat, SNK6, KAI3, and KHYG1). We evaluated the antitumor effects of mTOR inhibitors (rapamycin and its analogue, CCI-779) against these cell lines in culture and in a murine xenograft model that was established by subcutaneous injection of SNK6 cells into NOG mice.Results: All EBV-positive and -negative T- and NK-cell lines tested displayed activation of the Akt/mTOR pathway, and treatment with mTOR inhibitors suppressed mTOR activation. The inhibitors induced G1 cell-cycle arrest and inhibited cell proliferation in T- and NK-cell lines. Overall, T cell lines were more sensitive to rapamycin, but there were no significant differences between EBV-positive and -negative cell lines. Treatment with rapamycin did not affect lytic or latent EBV gene expression. Intraperitoneal treatment with CCI-779 significantly inhibited the growth of established tumors in NOG mice and reduced the EBV load in peripheral blood.Conclusion: These results suggest that inhibition of mTOR signaling is a promising new strategy for improving treatment of EBV-associated T- and NK-cell lymphoma. Clin Cancer Res; 20(21); 5412–22. ©2014 AACR.

Purpose: Epstein–Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells, and T- and NK-cell lymphoproliferative diseases (T/NK-LPD) that are refractory to conventional chemotherapies may develop. To identify a molecular-targeted therapy for EBV-associated T/NK-LPDs, we investigated whether CC chemokine receptor 4 (CCR4) was expressed on EBV-infected T and/or NK cells and whether a humanized anti-CCR4 monoclonal antibody, mogamulizumab, was effective.Experimental Design: CCR4 expression was examined in various cell lines. In vitro, the effects of mogamulizumab on cell lines were evaluated in the presence of peripheral blood mononuclear cells from volunteers. In vivo, the effects of mogamulizumab were evaluated using a murine xenograft model. CCR4 expression was examined on EBV-infected cells from patients with EBV-associated T/NK-LPDs. Ex vivo, the effects of mogamulizumab were evaluated using patient lymphocytes.Results: CCR4 expression was confirmed in most EBV-positive T and NK cell lines. Mogamulizumab induced antibody-dependent cellular cytotoxicity (ADCC) activity against CCR4-positive cell lines, and inhibited the growth of EBV-positive NK-cell lymphomas in a murine xenograft model. Furthermore, CCR4 was expressed on EBV-infected cells in 8 of 17 patients with EBV-associated T/NK-LPDs. Interestingly, CCR4 was positive in 5 of 5 patients with hydroa vacciniforme, a photodermatosis caused by the clonal expansion of EBV-infected γδT cells. EBV-positive γδT cells were obtained from a patient with hydroa vacciniforme and subjected to an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. The γδT cells that were positive for CCR4 were killed by mogamulizumab via ADCC.Conclusions: These results indicate that mogamulizumab may be a therapeutic option against EBV-associated T/NK-LPDs. Clin Cancer Res; 20(19); 5075–84. ©2014 AACR.

Background The Safari study (UMIN000015168) was a retrospective, multicenter study in which 1072 consecutive cases of estrogen receptor-positive advanced breast cancer treated using 500 mg fulvestrant were registered. We previously reported the relationship between the patient factors and overall survival after the diagnosis using the same cases and the same factors for the analysis of time to treatment failure in patients with estrogen receptor-positive advanced breast cancer. The current study is an ad hoc analysis that focused on the relationship between the patient factors and overall survival after recurrence by adding factors generally associated with overall survival after recurrence. Methods The overall survival after recurrence in patients with estrogen receptor-positive human epidermal growth factor receptor 2 negative recurrent breast cancer was analyzed via univariate and multivariate analyses with a Cox proportional hazards model. Results A total of 598 cases were used for the analysis of overall survival after recurrence. Multivariate analysis revealed that favorable overall survival (median, 6.4 years) was significantly correlated with long time from recurrence to fulvestrant use (≥3 years), low nuclear or histological grade (G3 vs. G1), long time to treatment failure of initial palliative endocrine therapy (≥12 months) and long time to initial palliative chemotherapy (≥2 years). Conclusion The results of this study indicate that sequential endocrine monotherapy may be a useful treatment option for patients with estrogen receptor-positive/human epidermal growth factor receptor 2 negative recurrent breast cancer who have been successfully treated with initial long-term palliative endocrine therapy.

Primary human herpesvirus 6 (HHV-6) infection is sometimes accompanied by acute encephalopathy with reduced subcortical diffusion (AED) in immunocompetent children. We investigated exosomal microRNA (miRNA) expression profiles in cerebrospinal fluid (CSF) and sera of patients with HHV-6-associated AED (n = 5) and febrile seizure (FS) (n = 5) using high-throughput sequencing. A total of 176 and 663 miRNAs were identified in CSF and serum exosomes, respectively. Comparative analysis determined that some miRNAs (miR-381-3p, miR-155) were exclusively expressed in the CSF exosomes of AED but not of FS patients, suggesting their potential application as novel diagnostic biomarkers for AED.

We undertook genomic analyses of Japanese patients with stage I esophageal squamous cell carcinoma (ESCC) to investigate the frequency of genomic alterations and the association with survival outcomes. Biomarker analysis was carried out for patients with clinical stage T1bN0M0 ESCC enrolled in JCOG0502 (UMIN000000551). Whole-exome sequencing (WES) was performed using DNA extracted from formalin-fixed, paraffin-embedded tissue of ESCC and normal tissue or blood sample. Single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) were identified. We then evaluated the associations between each gene alteration with a frequency of 10% or more and progression-free survival (PFS) using a Cox regression model. We controlled for family-wise errors at 0.05 using the Bonferroni method. Among the 379 patients who were enrolled in JCOG0502, 127 patients were successfully analyzed using WES. The median patient age was 63 years (interquartile range, 57-67 years), and 78.0% of the patients ultimately underwent surgery. The 3-year PFS probability was 76.3%. We detected 20 genes with SNVs, indels, or amplifications with a frequency of 10% or more. Genomic alterations in FGF19 showed the strongest association with PFS with a borderline level of statistical significance of P = .00252 (Bonferroni-adjusted significance level is .0025). Genomic alterations in FGF4, MYEOV, CTTN, and ORAOV1 showed a marginal association with PFS (P .05). These genomic alterations were all CNAs at chromosome 11q13.3. We have identified new genomic alterations associated with the poor efficacy of ESCC (T1bN0M0). These findings open avenues for the development of new potential treatments for patients with ESCC.

PURPOSE We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)–positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1). METHODS The phase III KAITLIN study ( NCT01966471 ) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor–negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). Adjuvant radiotherapy/endocrine therapy was permitted. Coprimary end points were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations with hierarchical testing. RESULTS The median follow-up was 57.1 months (interquartile range, 52.1-60.1 months) for AC-THP (n = 918) and 57.0 months (interquartile range, 52.1-59.8 months) for AC-KP (n = 928). There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP. Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities [12.5%]). Similar rates of grade ≥ 3 (55.4% v 51.8%) and serious adverse events (23.3% v 21.4%) occurred with AC-THP and AC-KP, respectively. KP decreased clinically meaningful deterioration in global health status versus THP (stratified HR, 0.71; 95% CI, 0.62 to 0.80). CONCLUSION The primary end point was not met. Both arms achieved favorable IDFS. Trastuzumab plus pertuzumab plus chemotherapy remains the standard of care for high-risk HER2-positive EBC.

Lip seal strength and tongue pressure are related to sarcopenia in older adults and are directly linked to the quality of life of workers after retirement. This study examined lip seal strength and tongue pressure among Japanese male workers by age. A self-administered questionnaire survey including alcohol consumption and smoking was conducted on 454 male workers. Height, weight, lip seal strength, and tongue pressure were also measured and then stratified by age (20s, 30s, 40s, 50s, and 60s and over). The mean (25th, 75th percentiles) lip seal strength and tongue pressure for all workers were 13.7 N (11.6, 16.4) and 41.7 kPa (35.2, 48.2), respectively. Both lip seal strength and tongue pressure were lowest in the 20s, at 12.1 N (9.6, 14.0) and 40.6 kPa (33.4, 47.6), respectively. The multiple regression analysis adjusted for smoking showed a significant positive association between lip seal strength and BMI for the 20s, 50s, and 60s and over, and a significant positive association between tongue pressure and BMI for the 30s, 40s, 50s, and 60s and over. To maintain oral health in older adults, it may be useful to measure workers’ lip seal strength and tongue pressure and intervene at an earlier stage.

Purpose Adolescent and young adult cancer patients (AYAs) often experience profound psychological distress, with various unmet supportive care needs that can be alleviated with appropriate screening and attention by healthcare workers. The Distress Thermometer and Problem List-Japanese version (DTPL-J) is our previously developed screening tool to facilitate individual support of AYAs. This study evaluated the feasibility and preliminary effectiveness of a psychosocial support program based on the DTPL-J for AYAs in clinical practice. Methods This multicenter, retrospective, observational study included 19 of 126 wards and 9 of 75 outpatient clinics at 8 institutions in Japan. Over 200 patients were expected to participate during the eligibility period. Patients participated in a support program at least once, and approximately once a month based on the DTPL-J results. The program was evaluated using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) implementation framework. Results The screening rate of the 361 participants was 90.3%, suggesting high feasibility. Distress Thermometer scores, the number of supportive care needs, and the rates of AYAs with high distress were significantly reduced 1 month after screening (p Conclusion Analysis using the RE-AIM suggested the sufficient feasibility and preliminary effectiveness of a psychosocial support program based on the DTPL-J for AYAs. Trial registration University Hospital Medical Information Network (UMIN CTR) UMIN000042857. Registered 25 December 2020—Retrospectively registered.

Background Congenital cytomegalovirus (CMV) infection (cCMV) can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Oral valganciclovir (VGCV) therapy has been reported to improve long-term audiological and neurodevelopmental outcomes in patients with cCMV. The levels of CMV DNA in whole blood have been monitored in previous studies. However, quantitative methods using whole blood have not been standardized. Recently, the plasma viral load has been standardized and widely used in CMV-associated diseases. Methods CMV viral loads in whole blood and plasma were serially measured in 24 patients with a confirmatory diagnosis of cCMV during oral VGCV therapy using an in-house real-time PCR assay. Plasma samples were assayed using the Cobas 6800 system (Roche Diagnostics) in addition to an in-house assay. Results Plasma CMV viral loads were remarkably decreased at the end of therapy compared to before therapy. A significant correlation of CMV levels between whole blood and plasma was observed (Spearman’s ρ = 0.566). The levels of CMV DNA before therapy were significantly correlated with the period of decreasing the viral loads to below the detection limit, not only in whole blood (Spearman’s ρ = 0.901) but also in plasma (Spearman, ρ = 0.804). Finally, CMV viral loads between the in-house assay and commercially available standardized assay in 75 plasma samples with positive PCR results for CMV were compared; a significant correlation was observed between the results of both assays. Conclusions There was a significant correlation between the two assays (Spearman, ρ = 0.882), suggesting that CMV plasma viral loads measured by the standardized assay are widely used to monitor the levels of CMV DNA in patients with cCMV during oral VGCV therapy.

Objective: This study examined the impact of Japan’s state of emergency on trends in diabetes care during the coronavirus disease 2019 (COVID-19) pandemic. Design: A descriptive and retrospective study. Setting: Showa University Hospital, Japan. Participants: Patients with diabetes who received medical treatment from 2018 to 2020. Determinants of interest: Number of patients with diabetes visiting the hospital per week. To examine the impact of the Japan’s state of emergency, the number of hospital visitations by patients with diabetes was summarized from 28 weeks of data for each year, from calendar week 8 to calender week 35. Results: Compared with the mean of 2018 and 2019, no significant difference was found between the three periods (before, during, and after the state of emergency). However, the numbers of patients from both inside and outside Tokyo increased at 7 weeks after the state of emergency was lifted. Conclusions: A significant increase in the numbers of patients with diabetes was seen compared with the same period in 2018 and 2019, suggesting that the state of emergency may have hindered diabetes care. Therefore, patients with diabetes should receive continuous follow-up regarding their diabetes care, keeping a close eye on relvent measurements.

Respiratory distress is common in neonates admitted to neonatal intensive care units. Additionally, infectious diseases such as intrauterine infections or vertical transmission are important underlying causes of respiratory failure. However, pathogens often cannot be identified in neonates, and there are many cases in which antibacterial drugs are empirically administered. Next-generation sequencing (NGS) is advantageous in that it can detect trace amounts of bacteria that cannot be detected by culturing or bacteria that are difficult to cultivate. However, there are few reports on the diagnosis of infectious diseases using NGS in the neonatal field, especially those targeting respiratory distress. The purpose of our study was to investigate the microorganisms associated with neonatal respiratory distress and to determine whether less invasive collection specimens such as plasma and gastric fluid are useful. Neonates were prospectively recruited between January and August 2020 from Nagoya University Hospital. The inclusion criteria were as follows: 1) admission to the neonatal intensive care unit; 2) respiratory distress presentation within 48 h of birth; and 3) suspected infection, collection of blood culture, and administration of antibiotics. Plasma samples and blood cultures were simultaneously collected. Gastric fluid samples were also collected if the patient was not started on enteral nutrition. Information on the patients and their mothers were collected from the medical records. DNA was extracted from 140 µL of plasma and gastric fluid samples. DNA sequencing libraries were prepared, and their quality was analyzed. DNA libraries were sequenced using high-throughput NGS. The NGS data of plasma and gastric fluid samples were analyzed using the metagenomic pipeline PATHDET, which calculated the number of reads assigned to microorganisms and their relative abundance. Putative pathogens were listed. Overall, 30 plasma samples and 25 gastric fluid samples from 30 neonates were analyzed. Microorganism-derived reads of gastric fluid samples were significantly higher than those of plasma samples. Transient tachypnea of the newborn was the most common cause of respiratory distress with 13 cases (43%), followed by respiratory distress syndrome with 7 cases (23%). There were 8 cases (29%) of chorioamnionitis and 7 cases (25%) of funisitis pathologically diagnosed. All blood cultures were negative, and only two gastric fluid cultures were positive for group B Streptococcus (Patient 15) and Candida albicans (Patient 24). Putative pathogens that met the positive criteria for PATHET were detected in four gastric fluid samples, one of which was group B Streptococcus from Patient 15. In the gastric fluid sample of Patient 24, Candida albicans were detected by NGS but did not meet the positive criteria for PATHDET. Cluster analysis of the plasma samples divided them into two study groups, and the indicator genera of each cluster (Phormidium or Toxoplasma) are shown in Figure 1. Clinical findings did not show any significant differences between the two groups. Cluster analysis of the gastric fluid samples divided them into three study groups, and the indicator genera of each cluster (Ureaplasma, Nostoc, and Streptococcus) are shown in Figure 2. The incidence rate of chorioamnionitis was significantly higher in Ureaplasma group than in the other two groups. Gastric fluid may be useful for assessing neonatal patients with respiratory distress. To the best of our knowledge, this was the first study to reveal that the presence of Ureaplasma in the gastric fluid of neonates with respiratory distress was associated with chorioamnionitis. The early diagnosis of intra-amniotic infections using gastric fluid and its treatment may change the treatment strategy for neonatal respiratory distress. Screening for Ureaplasma in neonates with respiratory distress may reduce the need for empirical antibiotic administration. Further research is required to confirm these findings.

Background Infantile central nervous system infections (CNSIs) can be life-threatening and severe sequelae can be observed in encephalitis and bacterial meningitis. The causative microorganism is unknown in > 40% of patients with aseptic infections. This study aimed to analyze metagenome for detection of pathogen, and transcriptome for host reaction of infection in a single cerebrospinal fluid (CSF) sample using two different next-generation sequencing (NGS) platforms, Illumina and Nanopore. Methods Twenty-eight CNSIs patients (< 12 months), treated between June 2012 and April 2020, were enrolled. A total of 49 clinical samples (28 CSF and 21 blood) from 28 patients were collected. Extracted RNA, which was obtained from 23 CSF in sufficient quantities, was sequenced using both Nanopore and Illumina platforms to compare their performances in the detection of pathogens. Human-derived reads subtracted during pathogen detection were used for host transcriptomic analysis from both Nanopore and Illumina sequencing. All the extracted DNA from 28 CSF and 21 blood, was sequenced using Illumina sequencer for the detection of pathogens. Data analysis was performed on the in-house PATHDET pipeline. A flowchart for pathogen detection and transcriptome analysis Pathogen detection was performed on the in-house PATHDET pipeline and transcriptome analysis was performed by using the secondary outputs. Results RNA sequencing of CSF samples in 23 cases revealed potential viral pathogens in 10 cases: coxsackievirus B5 (4 cases), coxsackievirus B4 (3 cases), coxsackievirus B2 (1 case), echovirus E7 (1 case), and human parechovirus 3 (1 case). DNA sequencing was performed in 28 cases using Illumina sequencing, and Proteus mirabilis (1 case, consistent with the culture test) and human parvovirus B19 (1 case) were detected. The results of Nanopore sequencing and Illumina sequencing were consistent. However, the mapping coverage and depth to the detected pathogen genome of Nanopore sequencing was superior to that of Illumina sequencing. MX1, ISG15, and OAS1 were differentially expressed genes in patients with identified pathogens via metagenomic NGS, both the Nanopore and Illumina sequencing, and were associated with antiviral roles in innate immunity. A pie chart for patients with central nervous system infections (CNSIs) Results of next-generation sequencing (NGS) and the detected pathogen candidates using DNA/RNA workflows. Performance of Nanopore and Illumina sequencing for pathogen genome mapping The sequencing output, which is 100,000 reads randomly extracted from original sequencing reads, was mapped to the pathogen reference genome to determine (A) mapping coverage and (B) mapping depth. Volcano plot of all genes analyzed in Nanopore and Illumina sequencing Volcano plots showing differentially expressed genes in the cerebrospinal fluid between identified-pathogen and unidentified-pathogen samples from (A) Nanopore sequencing and (B) Illumina RNA sequencing. Conclusion The use of Nanopore sequencing for metagenomic diagnostics of CSF samples should help to understand both pathogens and host immune responses of CNSI and could shed light on the pathogenesis of these infections. Disclosures All Authors: No reported disclosures.

Alcohol consumption is a major risk factor for esophageal cancer. In Asia, heavy drinkers are considered to have a higher risk of esophageal cancer than nondrinkers and light drinkers. However, no study has shown an association between alcohol reduction and the morbidity of esophageal cancer in Asian heavy drinkers. Therefore, this study investigated the significance of reducing alcohol consumption to prevent esophageal cancer in Asian heavy drinkers by conducting a systematic review and meta-analysis. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 1995 to December 2020. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effects model. I2 statistics were used to detect heterogeneity. This study included 21 articles in the qualitative synthesis. Light drinkers and heavy drinkers were categorized based on alcohol consumption amount as ≤ 25 ethanol g/day and ≥ 66 ethanol g/day, respectively, as described in many previous studies, and five cohort studies were eligible for this meta-analysis. The HR of esophageal cancer among heavy drinkers versus nondrinkers was 4.18 (95% CI 2.34–7.47, I2 = 74%). On the other hand, the HR of esophageal cancer among light drinkers was 1.82 compared with nondrinkers (95% CI 1.57–2.10, I2 = 0%). Heavy drinkers have a higher esophageal cancer incidence than light drinkers and nondrinker. It is possible that alcohol reduction may decrease the risk of esophageal cancer in Asian heavy drinkers.

Background This was a Japanese subpopulation analysis of MONARCH 2, a double-blind, randomized, placebo-controlled, phase 3 study of abemaciclib plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). Methods Eligible women had progressed on (neo)adjuvant endocrine therapy (ET), ≤ 12 months from end of adjuvant ET, or on first-line ET for ABC, and had not received chemotherapy for ABC. Patients were randomized 2:1 to receive abemaciclib or placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), pharmacokinetics (PK), health-related quality of life (HRQoL), and safety. Results In Japan, 95 patients were randomized (abemaciclib, n = 64; placebo, n = 31). At final PFS analysis (February 14, 2017), median PFS was 21.2 and 14.3 months, respectively, in the abemaciclib and placebo groups (hazard ratio: 0.672; 95% confidence interval: 0.380–1.189). Abemaciclib had a higher objective response rate (37.5%) than placebo (12.9%). PK and safety profiles for Japanese patients were consistent with those of the overall population, without clinically meaningful differences across most HRQoL dimensions evaluated. The most frequent adverse events in the abemaciclib versus placebo groups were diarrhea (95.2 versus 25.8%), neutropenia (79.4 versus 0%), and leukopenia (66.7 versus 0%). At a second data cutoff (June 20, 2019), median OS was not reached with abemaciclib and 47.3 months with placebo (hazard ratio: 0.755; 95% confidence interval: 0.390–1.463). Conclusions Results of the Japanese subpopulation were consistent with the improved clinical outcomes and manageable safety profile observed in the overall population. Clinical trial registration NCT02107703; U.S. National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT02107703.

Objective: This study examined the impact of Japan’s state of emergency on trends in diabetes care during the coronavirus disease 2019 (COVID-19) pandemic. Design: A descriptive and retrospective study. Setting: Showa University Hospital, Japan. Participants: Patients with diabetes who received medical treatment from 2018 to 2020. Determinants of interest: Number of patients with diabetes visiting the hospital per week. To examine the impact of the Japan’s state of emergency, the number hospital visiting by patients with diabetes was summarized from 28 weeks of data, from calendar week 8 to week 35, for each year. Results: Compared with the mean of 2018 and 2019, no significant difference was found between the three periods (before, during, and after the state of emergency). However, the numbers of patients from both inside and outside Tokyo increased at 7 weeks after the state of emergency was lifted. Conclusions: A significant increase in the numbers of patients with diabetes was seen compared with the same period in 2018 and 2019, suggesting that the state of emergency may have hindered diabetes care. Therefore, patients with diabetes should be followed up continuous of diabetes care while keeping a close eye on measures.

The study aim was to clarify the essential competencies for psychologists in palliative care teams. A nationwide, multicentre cross-sectional survey was conducted. A 32-item questionnaire assessing endorsement of potential competencies was completed by 70 patients and/or families, 101 consulting personnel, 747 members of palliative care teams and 203 mental health providers. All 32 competencies were judged as essential. Of the 32 items, 9 and 28 items were endorsed by >95% and 80% of participants, respectively. The most frequently endorsed essential competency was ability to coordinate with other professionals in palliative care teams. Some competencies considered essential seemed specific to oncology and medical settings. The results suggest the need for specific guidance for psychologists working in palliative care teams and the development of clinical oncology training programmes and/or systems for psychologists.

Human parvovirus B19 (PVB19) infection causes neurological manifestations, including encephalitis, meningitis, and neuropathy, but facial nerve palsy is rare. Moreover, no case of facial nerve palsy related to PVB19 infection that was diagnosed by PCR and serology has been reported. A 19-month-old boy without the medical history developed facial nerve palsy and was treated with prednisolone and valacyclovir. On the 19th day, erythema appeared on his body, and the PVB19-specific IgM and PVB19 DNA were detected in the serum, leading to the diagnosis of infectious erythema associated with PVB19 infection. This case indicates that PVB19 may be one of the causative agents of facial nerve palsy.

BackgroundAt present non-invasive fibrosis markers are not available for assessment of liver fibrosis in children with chronic hepatitis C. MethodsSixty-three children with chronic hepatitis C were included. Changes in Wisteria floribunda agglutinin-positive Mac-2 binding protein (M2BPGi) levels were evaluated in l3 of 27 treatment-naive patients during the observation period of the natural course of disease (median 4, range 3-6 years). Changes during treatment were evaluated in 27 of 36 patients for 4 (2-9) years of post-treatment follow-up. ResultsThere were significant differences in the levels of M2BPGi between the control group and HCV F0 group (P=0.002) and between the control group and HCV F1 group (PConclusionsOur study shows new findings that M2BPGi may be useful to predict the presence of a mild degree of fibrosis in children with chronic hepatitis C and such a mild fibrosis may be quickly resolved by antiviral therapies.

Background JCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015. Methods Individual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities. Results The 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less). Conclusions The dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem.

Natural Killer T (NKT) cells are unique lymphocyte lineage that present both NK and T cell phenotype. NKT cells hold strong direct cytotoxic ability toward tumor cells through glycolipid/CD1d complex on tumor cells, NKT cells secrete large amounts of IFNγ and stimulate CD8 and NK cells as indirect cytotoxic effects. To elicit NKT cells responses in cancer patients, adoptive transfer of α-galactosyl ceramide (αGalCer) loaded APCs was exploited in a decade. I summarized anti-tumor effects and immune reaction treated with this therapy in recent 3 years. Methods: For αGalCer loaded APCs, CD14-monocyte (MO) or mature dendritic cells (DC) was used. Monocytes isolated by leukapheresis were purified ether plastic adherence or CD14-positive selection. Plastic adherent monocytes were cultured for 6 days for differentiation into DC, then for an additional day for maturation with αGalCer loading. CD14-Mo was cultured for 2 days with GM-CSF and αGalCer. After cultivation, all cells were frozen and stored in liquid nitrogen until use. For tumor treatment, patients were injected αGalCer-DC at least 4 times via SC with 2 weeks interval or injected at least twice with αGalCer-CD14-Mo intravenously with 3-4 weeks interval. We evaluated safety and efficacy of αGalCer-APCs immunotherapy by CTCAE, tumor maker, RECIST and immunological analysis. Fifty patients were enrolled in this immunotherapy between 2020-2022. Results: In all cases, we could not observe any therapy-related adverse effects above CTCAE Grade 2. Several anti-tumor effects such as tumor marker reduction and/or tumor regression including CR were observed in 60.6% of evaluated cases. In the cases with iv injection of αGalCer-CD14-Mo, CD3+CD56+ circulating NKT (cNKT) cells were significantly increased after the therapy. In the cases with subcutaneous injection of αGalCer-DC, NK number was significantly increased. Also, cNKT cells and CD8 cells were increased with tendency of significance after the therapy. We obtained CR case in chemotherapy naïve DLBCL patient by αGalCer-DC therapy. After 6 injections, multiple LN swelling was disappeared completely. In another cases, breast cancer with axillary LN metastasis, we obtained rapid tumor regression with αGalCer-DC SC injection. In the case combined αGalCer-APCs with some cytotoxic chemotherapy or conventional radiation immune responses were abolished. In the cases combined αGalCer-APCs with taxane, platinum, gemcitabine-based chemotherapy, immune responses were clearly observed. Conclusion: αGalCer-APCs infusion efficiently promote cNKT response. cNKT response was clearly related with immune responses such as CD8/NK upregulation and anti-tumor effects. Immune responses induced by the therapy seemed to be abolished by combined conventional radiotherapy or several cytotoxic chemotherapies. αGalCer-APCs infusion might be promising for cancer therapy. Citation Format: Yoshinori Ito. Anti-tumor effects and immunological responses by aGalCer loaded antigen presenting cell infusion in the patients with malignant tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3186.

Background Trastuzumab deruxtecan (T-DXd, DS-8201) is an antibody-drug conjugate with a HER2 antibody, tetrapeptide-based cleavable linker, and a novel topoisomerase I inhibitor payload. DESTINY-Breast01 (NCT03248492) is an open-label, international, multicenter, phase 2 study of T-DXd in patients with HER2 positive metastatic breast cancer (MBC) and supported regulatory approval in the US and Japan. Updated longer-term safety and efficacy results are presented here. Methods All patients were required to have MBC that progressed on or after T-DM1. 253 patients were enrolled and 184 received T-DXd 5.4 mg/kg, representing the primary analysis set. The primary endpoint was ORR. Additional endpoints included duration of response, PFS, and OS. Results Patients had received a median of 6 previous lines of treatment for MBC. In this updated data cutoff (8 June 2020) compared to the prior data cutoff (1 Aug 2019), median duration of follow-up has increased from 11.1 to 20.5 mo; 37 patients (20.1%) remain on treatment. Confirmed ORR was 61.4% (12 CRs) with a median duration of response of 20.8 mo; the disease control rate was 97.3% (95% CI, 93.8-99.1). The updated mPFS was 19.4 mo (95% CI, 14.1 mo-NE). Estimated OS was 85% (95% CI, 79%-90%) at 12 months and 74% (95% CI, 67%-80%) at 18 months. The preliminary mOS is 24.6 mo (estimated at 35% maturity with only 17 patients at risk at 24 months). The safety profile of T-DXd was similar as that previously reported; with an additional 9 mo follow-up, only 3 new cases of T-DXd-related interstitial lung disease (ILD) were reported. Results are summarized in the table below. Conclusion Consistent with prior results, T-DXd demonstrated high rates of durable responses in a heavily pretreated population of patients with MBC. From this single-arm, phase 2 study, the PFS and immature OS results are encouraging; these endpoints will be further evaluated in the ongoing randomized controlled studies of T-DXd. For patients who remained on treatment for this longer duration (double that of the previous report), the rate of discontinuation or ILD did not notably increase. Continued attention to pulmonary symptoms and careful monitoring is warranted. Updated Results for DESTINY-Breast011 Aug 2019 datacut8 Jun 2020 datacutPatients remaining on treatment, n/N (%)79/184 (42.9%)37/184 (20.1%)Median duration of follow-up11.1 months20.5 monthsORR60.9%61.4%CR6.0%6.5%PR54.9%54.9%SD36.4%35.9%Duration of response, median (95% CI)14.8 months (13.8-16.9)20.8 months (15.0-NE)PFS, median (95% CI)16.4 months (12.7-NE)19.4 months (14.1-NE)OSMedian (95% CI)NE (NE-NE)24.6 months (23.1-NE)Point estimate at 12 mo (95% CI)86.2% (79.8-90.7)85% (79-90)Point estimate at 18 mo (95% CI)–74% (67-80)SafetyPatients with a TEAE, n (%)183 (99.5%)183 (99.5%)Grade ≥3105 (57.1%)113 (61.4%)Associated with discontinuation28 (15.2%)34 (18.5%)Associated with death10 (5.4%)10 (5.4%)Drug-related ILD per ILD adjudication committeea25 (13.6%)28 (15.2%)Grade 5 drug-related ILD per ILD adjudication committee4 (2.2%)5 (2.7%)a1 grade 1 and 1 grade 3 event are pending adjudication and are not included. Citation Format: Shanu Modi, Cristina Saura, Toshinari Yamashita, Yeon Hee Park, Sung-Bae Kim, Kenji Tamura, Fabrice Andre, Hiroji Iwata, Yoshinori Ito, Junji Tsurutani, Joohyuk Sohn, Neelima Denduluri, Christophe Perrin, Kenjiro Aogi, Eriko Tokunaga, Seock-Ah Im, Keun Seok Lee, Sara A Hurvitz, Javier Cortes, Caleb Lee, Yali Liu, Lin Zhang, Javad Shahidi, Antoine Yver, Jose Baselga, Ian E Krop. Updated results from DESTINY-breast01, a phase 2 trial of trastuzumab deruxtecan (T-DXd ) in HER2 positive metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-06.

We report conjugated polymers consisting of boron formazanate in the main chains. By employing typical donor-type comonomers, such as fluorene and bithiophene, copolymers were prepared with the Mig...

Background Surgery is recommended for patients with high-risk submucosal invasive rectal cancer (SM-RC) after local resection but affects the quality of life due to stoma placement or impaired anal function; therefore, alternative treatment approaches are needed to prevent local metastasis. The purpose of this study was to assess the short-term safety of adjuvant chemoradiotherapy with capecitabine in patients with high-risk submucosal invasive rectal cancer after local resection. Methods This single-arm, multicenter, phase II trial included patients undergoing local resection for high-risk submucosal invasive rectal cancer within 12 weeks prior to enrollment. High-risk submucosal invasive rectal cancer was defined as the presence of at least one of the following factors: poor differentiation of adenocarcinoma, submucosal invasion depth > 1 mm, presence of lymphovascular invasion and grade-2 or -3 tumour budding. Protocol treatment comprised 45.0 Gy radiotherapy with conventional fractionation and 1650 mg/m2 capecitabine given twice daily until radiotherapy completion. The primary endpoint was treatment completion rate with an expected rate of 95% and a threshold of 80%. Results Twenty-nine patients from six institutions were enrolled between May 2015 and February 2018. One patient was ineligible. Twenty-three patients completed treatment, with a completion rate of 82% (80% confidence interval, 69–91%); the remaining five patients completed treatment with protocol deviation. The median relative dose intensity of capecitabine was 100% (range, 58–100%). Common adverse events included radiation dermatitis (54%), anal pain (39%) and anal mucositis (29%). No grade-3 or higher adverse events were reported. Conclusions Adjuvant chemoradiotherapy using capecitabine demonstrated acceptable short-term safety profiles in patients with high-risk submucosal invasive rectal cancer after local resection., Adjuvant chemoradiotherapy using capecitabine demonstrated acceptable short-term safety profiles in patients with high-risk submucosal invasive rectal cancer after local resection.

Background Myocarditis is an inflammatory disease of the myocardium, which leads to cardiac dysfunction and heart failure. Previous studies have suggested that complex cross-talk between innate and adaptive immune responses is involved in the pathogenesis of acute myocarditis. Immunohistochemistry is the current standard method for the evaluation of infiltrating immune cells, however, it is difficult to investigate and quantify many immune cell populations using this technique. Methods Endomyocardial biopsy samples of five pediatric patients with myocarditis were analyzed by cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT), a computational method for quantifying cell fractions from tissue gene expression profiles. CIBERSORT results were then compared with immunohistochemistry analyses. Results Significant results of immune infiltrate deconvolution were obtained in four patients with fulminant myocarditis by CIBERSORT analysis. Among 22 immune cell types, 19 cell types were detected in one or more patients. Activated NK cells were the most prevalent population in two patients, whereas activated memory CD4+ T cells and M2 macrophages were the most prevalent population in one patient each. Overall CIBERSORT results were consistent with those of immunohistochemistry, although some discrepancies were observed. Conclusions Infiltrating immune cell subsets detected by CIBERSORT analysis can reflect the time course of innate and adaptive immune responses in acute myocarditis. CIBERSORT may have the potential to characterize the detail of infiltrating immune cells in myocardial tissues and provide novel insights into the pathogenesis of acute myocarditis.

Oral fluoropyrimidines, such as S-1, have been shown to have a role in controlling disease progression in metastatic breast cancer. We examined adjuvant treatment with S-1 in patients with oestrogen receptor (ER)-positive and HER2-negative primary breast cancer.We did a multicentre, open-label, randomised, controlled, phase 3 trial in 139 sites (137 hospitals and two clinics). Eligible patients were women aged 20-75 years with histologically diagnosed stage I to IIIB invasive breast cancer (intermediate to high risk of recurrence). Patients were temporarily registered at participating institutions and biopsy or surgical samples were collected and sent for central pathological assessment. Patients received 5 years of standard adjuvant endocrine therapy (selective oestrogen receptor modulators with or without ovarian suppression and aromatase inhibitors) with or without 1 year of S-1. Oral S-1 80-120 mg/day was administered twice a day for 14 days with 7 days off. Randomisation (1:1) using the minimisation method was done with six stratification factors (age, axillary lymph node metastasis at surgery or sentinel lymph node biopsy, preoperative or postoperative (neoadjuvant or adjuvant) chemotherapy, preoperative endocrine therapy, proportion of ER-positive cells, and study site). The primary endpoint was invasive disease-free survival, in the full analysis set (all randomly assigned patients, excluding those with significant protocol deviations). The safety analysis set consisted of all patients who received at least one dose of study treatment. Here, we report the results from the interim analysis at the data cutoff date Jan 31, 2019. This trial is registered with Japan Registry of Clinical Trials, jRCTs051180057, and the University hospital Medical Information Network, UMIN000003969.Between Feb 1, 2012, and Feb 1, 2016, 1930 patients were enrolled in the full analysis set, 957 (50%) received endocrine therapy plus S-1 and 973 (50%) received endocrine therapy alone. Median follow-up was 52·2 months (IQR 42·1-58·9). 155 (16%) patients in the endocrine therapy alone group and in 101 (11%) patients in the endocrine therapy plus S-1 group had invasive disease-free survival events (hazard ratio 0·63, 95% CI 0·49-0·81, p=0·0003). As the primary endpoint was met at interim analysis, the trial was terminated early. The most common grade 3 or worse adverse events were decreased neutrophil count (72 [8%] of 954 patients in the endocrine therapy plus S-1 group vs seven [1%] of 970 patients in the endocrine therapy alone group), diarrhoea (18 [2%] vs none), decreased white blood cells (15 [2%] vs two [1%]), and fatigue (six [1%] vs none). Serious adverse events were reported in nine (1%) of 970 patients in the endocrine therapy alone group and 25 (3%) of 954 patients in the endocrine therapy plus S-1 group. There was one (1%) possible treatment-related death in the endocrine therapy plus S-1 group due to suspected pulmonary artery thrombosis.These data suggest that this combination of S-1 with endocrine therapy could be a potential treatment option for this intermediate and high-risk group of patients with ER-positive, HER2-negative primary breast cancer.Public Health Research Foundation (Japan), Taiho Pharmaceutical.

Background Infantile central nervous system infections (CNSIs) can be life-threatening and cause severe sequelae. However, the causative microorganism remains unknown in >40% of patients with aseptic infections. This study aimed to analyze the metagenome for detection of pathogens and the transcriptome for host immune responses during infection in a single cerebrospinal fluid (CSF) sample using 2 different next-generation sequencing (NGS) platforms, Nanopore and Illumina. Methods Twenty-eight CNSIs patients ( Results RNA metagenomic sequencing using both sequencing platforms revealed putative viral pathogens in 10 cases. DNA sequencing using the Illumina sequencer detected 2 pathogens. The results of Nanopore and Illumina RNA sequencing were consistent; however, the mapping coverage and depth to the detected pathogen genome of Nanopore RNA sequencing were greater than those of Illumina. Host transcriptomic analysis of Nanopore sequencing revealed highly expressed genes related to the antiviral roles of innate immunity from pathogen-identified cases. Conclusions The use of Nanopore RNA sequencing for metagenomic diagnostics of CSF samples should help to elucidate both pathogens and host immune responses of CNSI and could shed light on the pathogenesis of these infections.

Artificial intelligence algorithms utilizing deep learning are helpful tools for diagnostic imaging. A deep learning-based automatic detection algorithm was developed for rib fractures on computed tomography (CT) images of high-energy trauma patients. In this study, the clinical effectiveness of this algorithm was evaluated. A total of 56 cases were retrospectively examined, including 46 rib fractures and 10 control cases from our hospital, between January and June 2019. Two radiologists annotated the fracture lesions (complete or incomplete) for each CT image, which is considered the “ground truth.” Thereafter, the algorithm’s diagnostic results for all cases were compared with the ground truth, and the sensitivity and number of false positive (FP) results per case were assessed. The radiologists identified 199 images with a fracture. The sensitivity of the algorithm was 89.8%, and the number of FPs per case was 2.5. After additional learning, the sensitivity increased to 93.5%, and the number of FPs was 1.9 per case. FP results were found in the trabecular bone with the appearance of fracture, vascular grooves, and artifacts. The sensitivity of the algorithm used in this study was sufficient to aid the rapid detection of rib fractures within the evaluated validation set of CT images.

Accurate tracer accumulation evaluation is difficult owing to the partial volume effect (PVE). We proposed a novel semi-quantitative approach for measuring the accumulation amount by examining the approximate image. Using a striatal phantom, we verified the validity of a newly proposed method to accurately evaluate the tracer accumulations in the caudate and putamen separately. Moreover, we compared the proposed method with the conventional methods.The left and right caudate/putamen regions and the whole brain region as background were identified in computed tomography (CT) images obtained by single-photon emission computed tomography (SPECT)/CT and acquired the positional information of each region. SPECT-like images were generated by assigning assumed accumulation amounts to each region. The SPECT-like image, approximated to the actual measured SPECT image, was examined by changing the assumed accumulation amounts assigned to each region. When the generated SPECT-like image most approximated the actual measured SPECT image, the accumulation amounts assumed were determined as the accumulation amounts in each region. We evaluated the correlation between the count density calculated by the proposed method and the actual count density of theThe correlation coefficients between the actual count density and the SPECT count densities were 0.997, 0.973, 0.951, 0.950, and 0.996 for the proposed method, CT-guide method, GTM method, RBV method, and Southampton method, respectively. The correlation of the proposed method was significantly higher than those of the other methods.The proposed method could calculate accurate accumulation amounts in the caudate and putamen separately, considering the PVE.