Patients In Japan Research Articles

Risk factors of bleeding during rectal cancer surgery in obese patients in Japan.

According to several clinical trials for patients with rectal cancer, laparoscopic surgery significantly reduces intraoperative complications and bleeding compared with laparotomy and demonstrated comparable long-term results. However, obesity is considered one of the risk factors for increased surgical difficulty, including complication rate, prolonged operation time, and bleeding. Patients with clinical pathological stage II/III rectal cancer and a body mass index of ≥25 kg/m2 who underwent laparotomy or laparoscopic surgery between January 2009 and December 2013 at 51 institutions participating in the Japan Society of Laparoscopic Colorectal Surgery were included. These patients were divided into major bleeding (>500 mL) group and minor bleeding (≤500 mL) group. The risk factors of major bleeding were evaluated by univariate and multivariate analyses. This study included 517 patients, of which 74 (19.9%) experienced major bleeding. Patient characteristics did not significantly differ between the two groups. The major bleeding group had a longer operative time (p < 0.001) and a larger tumor size than the minor bleeding group (p = 0.011). In the univariate analysis, age >65 years, laparotomy, operative time >300 min, and multivisceral resection were significantly associated with intraoperative massive bleeding. In the multivariate analysis, age >65 years (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.13-4.82), laparotomy (OR, 20.82; 95% CI, 11.56-39.75), operative time >300 min (OR, 5.39; 95% CI, 1.67-132), and multivisceral resection (OR, 10.72; 95% CI, 2.47-64.0) showed to be risk factors for massive bleeding. Age >65 years, laparotomy, operative time >300 min, and multivisceral resection were risk factors for massive bleeding during rectal cancer surgery in patients with obesity.

Social difficulties and care burden of adult Duchenne muscular dystrophy in Japan: a questionnaire survey based on the Japanese Registry of Muscular Dystrophy (Remudy).

Little is known about the social difficulties and health care needs of adult Duchenne muscular dystrophy (DMD) patients in Japan, as well as the financial and physical stress experienced by their caregivers. This study aimed to clarify the social circumstances surrounding adult DMD patients and assess the degree of involvement of family members in their care and the associated economic burden of the disorder in Japan. Adult DMD patients were identified through the Registry of Muscular Dystrophy (Remudy) in Japan and invited to complete a questionnaire together with a caregiver. Data on health care use, quality of life, work status, informal care, and household expenses were collected to estimate the costs associated with DMD from social and caregiver household perspectives. In total, 234 (63.7%) of 367 adult DMD patients (mean age, 27.4 ± 6.0; range, 20-48years) completed the questionnaire. Of these, 38 (21%) had developmental disorders (mental retardation, autism, and learning disorders), 57 (33%) experienced bullying in school, and 44 (77%) indicated the reason for bullying to be their physical handicap. Employment histories were noted by 72 (31%), although 23 (10%) lost their jobs mainly due to physical difficulties. Of the 234 patients, 164 (74%) lived with their relatives, and 78% of care time was supplied by family members, in particular, their mothers. The mean rate of care work provided by family members was 81%. Household income of families with an adult DMD patient was lower, whereas the rate of living with parent(s) and grandparent(s) was higher, in comparison with the general Japanese population. Adult DMD patients in Japan experience many social difficulties from childhood up to adulthood. As adults, many DMD patients experience bullying and workplace difficulties. Families were found to provide most of the care and financial support for DMD patients. Our results suggest the need to improve public patient care systems, including financial support, to address the physical and economic burdens of care for adult DMD patients in Japan.

Early Diagnosis of Hereditary Angioedema in Japan Based on a US Medical Dataset: Algorithm Development and Validation.

Hereditary angioedema (HAE), a rare genetic disease, induces acute attacks of swelling in various regions of the body. Its prevalence is estimated to be 1 in 50,000 people, with no reported bias among different ethnic groups. However, considering the estimated prevalence, the number of patients in Japan diagnosed with HAE remains approximately 1 in 250,000, which means that only 20% of potential HAE cases are identified. This study aimed to develop an artificial intelligence (AI) model that can detect patients with suspected HAE using medical history data (medical claims, prescriptions, and electronic medical records [EMRs]) in the United States. We also aimed to validate the detection performance of the model for HAE cases using the Japanese dataset. The HAE patient and control groups were identified using the US claims and EMR datasets. We analyzed the characteristics of the diagnostic history of patients with HAE and developed an AI model to predict the probability of HAE based on a generalized linear model and bootstrap method. The model was then applied to the EMR data of the Kyoto University Hospital to verify its applicability to the Japanese dataset. Precision and sensitivity were measured to validate the model performance. Using the comprehensive US dataset, the precision score was 2% in the initial model development step. Our model can screen out suspected patients, where 1 in 50 of these patients have HAE. In addition, in the validation step with Japanese EMR data, the precision score was 23.6%, which exceeded our expectations. We achieved a sensitivity score of 61.5% for the US dataset and 37.6% for the validation exercise using data from a single Japanese hospital. Overall, our model could predict patients with typical HAE symptoms. This study indicates that our AI model can detect HAE in patients with typical symptoms and is effective in Japanese data. However, further prospective clinical studies are required to investigate whether this model can be used to diagnose HAE.

Spontaneous clearance of serum HCV-RNA after splenectomy in a patient with HCV-related liver cirrhosis and portal hypertension: a case report

BackgroundSpontaneous clearance of chronic hepatitis C virus (HCV) is rare in adults. A T-lymphocyte response is thought to be involved in HCV-RNA clearance. Splenectomy reportedly has a beneficial effect on T cell immune function in patients with cirrhosis. To the best of our knowledge, the present report is the first to describe spontaneous clearance of serum HCV-RNA within 1 year after splenectomy in a patient with cirrhosis.Case presentationA 55-year-old man with HCV cirrhosis was transferred to our institution with advanced pancytopenia, splenomegaly, and gastric varices. He had a 1-year history of ascites, edema, and general fatigue. The patient had a Child–Pugh score of 8 and serological type 1 HCV; the HCV-RNA level was 4.7 log IU/mL. Contrast-enhanced computed tomography showed gastric varices and marked splenomegaly (estimated spleen volume of 2175 mL). Esophagogastroduodenoscopy revealed enlarged gastric varices with no red color sign, and the varices were larger than those 1 year prior. He was diagnosed with decompensated HCV-related liver cirrhosis and portal hypertension. We considered direct-acting antiviral (DAA) therapy; however, DAA therapy was not approved in Japan for patients with decompensated cirrhosis at that time. Hand-assisted laparoscopic splenectomy was performed to improve the worsening portal hypertension. Further, we planned the initiation of DAA therapy after surgery, when such therapy would become available. DAA therapy was approved 1 year after splenectomy. At that time, we measured the HCV-RNA level before the initiation of DAA therapy; unexpectedly, however, serum HCV-RNA was not detectable, and the virus continued to disappear during the following 4 years. His liver function (total bilirubin, albumin, and prothrombin time) and pancytopenia improved during the 5 years postoperatively. The serum aspartate and alanine aminotransferase levels normalized between 1 and 5 years postoperatively. Esophagogastroduodenoscopy showed no change in the gastric varices during the 5 years after surgery. The patient remained asymptomatic and continued to do well.ConclusionsWe have presented a case of spontaneous clearance of HCV-RNA after splenectomy in a patient with cirrhosis and portal hypertension. Splenectomy may be associated with disappearance of HCV-RNA based on previous reports. More cases should be accumulated and evaluated.

Genetic diversity among the present Japanese population: evidence from genotyping of human cell lines established in Japan

Japan is often assumed to have a highly homogeneous ethnic population, because it is an island country. This is evident in human cell lines collected from cell banks; however, these genotypes have not been thoroughly characterized. To examine the population genotypes of human cell lines established in Japan, we conducted SNP genotyping on 57 noncancerous cell lines and 43 lung cancer cell lines. Analysis of biogeographic ancestry revealed that 58 cell lines had non-admixed Japanese genotypes, 21 cell lines had an admixture of Japanese and East Asian genotypes, and the remaining 21 cell lines had East Asian genotypes. The proportion of non-admixed Japanese genotypes was similar between lung cancer and noncancerous cell lines, suggesting that patients in Japan may not exclusively have Japanese genotypes. This could influence the incidence of inherited diseases and should be taken into account in personalized medicine tailored to genetic background. The genetic makeup of the present-day Japanese population cannot be fully explained by the ancestral Jomon and Yayoi lineages. Instead, it is necessary to consider a certain level of genetic admixture between Japanese and neighboring Asian populations. Our study revealed genetic variation among human cell lines derived from Japanese individuals, reflecting the diversity present within the Japanese population.

A web-based survey on the occurrence of emotional blunting in patients with major depressive disorder in Japan: Patient perceptions and attitudes.

To determine the prevalence and impact of emotional blunting (EB) in patients with major depressive disorder (MDD) in Japan, and identify treatment needs for EB using patients' perceptions and attitudes. Eligible patients in Japan (aged 18-59 years) who reported a diagnosis of MDD and antidepressant medication use for >3 months were eligible to complete an online survey. The primary outcome was the prevalence of EB, self-reported using a validated screening question. Secondary outcomes included the correlation between EB symptoms (measured by the Oxford Depression Questionnaire [ODQ]) and scores on the Patient Health Questionnaire 9-item (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Work and Social Adjustment Scale (WSAS), and the EuroQol 5-Dimension 5-Levels questionnaire (EQ-5D-5L). Descriptive questions were used to explore patients' perceptions and attitudes toward EB. In total, 3376 patients were included in the analysis (56% male; 48% aged 50-59 years). Overall, 67.1% of patients self-reported symptoms of EB, with 10% rating these as severe. The mean (SD) ODQ total score was 78.2 (21.5), which increased with worsening EB symptoms. There were correlations between ODQ total scores and the PHQ-9, GAD-7, WSAS, and EQ-5D-5L scores (correlation coefficients: 0.67, 0.55, 0.56, -0.51, respectively; all p < 0.0001). Descriptive analyses showed that one-third of patients reporting EB symptoms did not tell their physician, with two-thirds finding these symptoms distressing and likely to affect recovery. EB is an important clinical issue in Japan that needs to be considered alongside functional recovery when managing treatment of patients with MDD.

Sarcopenia as a Robust Predictor of Readmission within 6 Months among Individuals Experiencing Acute Stroke.

Sarcopenia negatively affects the short-term prognosis of hospitalized older adults. However, no evidence currently supports a direct relationship between sarcopenia and readmission among individuals who have experienced an acute stroke. Therefore, we investigated whether sarcopenia is associated with readmission after discharge. This retrospective cohort study included patients who had experienced acute stroke. Sarcopenia was defined as the coexistence of low skeletal muscle mass index (SMI) and grip strength. We applied the log-rank test and Cox proportional hazards regression analysis to analyze whether sarcopenia, low SMI, and low grip strength were associated with readmission within 6 months. Among 228 included patients (mean age, 72.8 years; 146 males), the prevalence of sarcopenia was 24.6% (n=56; male 17.8%; female 36.6%). Cox proportional hazards regression analysis using the propensity score as a covariate revealed that sarcopenia (hazard ratio [HR]=7.21; 95% confidence interval [CI] 1.45-35.8; p=0.016) and low skeletal muscle mass (HR=7.40; 95% CI 1.14-48.1; p=0.036), but not low grip strength (HR=1.42; 95% CI 0.281-7.21; p=0.670), were significantly associated with readmission for stroke within 6 months. Sarcopenia was negatively associated with readmission within 6 months of stroke onset in patients in Japan who had experienced an acute stroke. These findings suggest that the identification of sarcopenia may facilitate prognostic prediction from the acute stage and intervention(s) to prevent rehospitalization.

Differential Effects of Genetic Polymorphism on Comorbid Disease in Metabolic Dysfunction–Associated Steatotic Liver Disease

PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 have been associated with an increased risk of liver-related events (LREs) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we investigated the combined effects of these variants on LREs. The longitudinal multicenter cohort study enrolled 1178 patients with biopsy-proven MASLD. We calculated the genetic risk of hepatic fibrosis and LRE according to the impact of these variants. Patients with genetic fibrosis scores of 2, 3, and 4 or 5 were at greater risk than patients with scores of 0 or 1, with odds ratios of 2.45 (95% CI, 1.27-4.74), 2.14 (95% CI, 1.17-3.94), and 2.54 (95% CI, 1.35-4.77), respectively. Multivariate analysis revealed that PNPLA3 and TM6SF2, but not HSD17B13, were associated significantly with LRE development. The hazard ratio of the genetic high-risk group for LRE was 1.91 (95% CI, 1.20-3.04). The higher risk of LRE development in the genetic high-risk group also was seen in patients with F ≥ 3 or Fibrosis-4 index > 2.67. The hazard ratios of the genetic high-risk group for LRE were greater in patients without obesity, without diabetes, and of younger age compared with patients with obesity, with diabetes, or of older age, respectively. This combination of MASLD-related genetic variants is useful for predicting LREs in Japanese patients with MASLD. The genetic risk according to these variants is useful for LRE risk assessment, especially in patients without metabolic risk factors or in younger patients in Japan.

Treatment Patterns of Biologic Disease-Modifying Antirheumatic Drugs and Janus Kinase Inhibitors in Patients with Rheumatoid Arthritis in Japan: A Claims-Based Cohort Study.

Reports on treatment patterns of biologic disease-modifying antirheumatic drugs (bDMARDs)/Janus kinase inhibitors (JAKi) for rheumatoid arthritis (RA) in clinical practice are still sparse in Japan, especially in combination with conventional synthetic DMARDs (csDMARDs). The aim of this study was to investigate treatment patterns of bDMARD/JAKi in the treatment of RA in real-world clinical practice in Japan. A retrospective cohort study was conducted using the Japanese Medical Data Vision health claims database. The inclusion criteria required a recorded diagnosis of RA, defined by ICD-10 codes, in patients aged 18 years and older on the index date. We analyzed 39,903 RA patients treated with DMARDs from 2008 to 2020. Among analyzed subjects, 10,196 patients (25.6%) were prescribed bDMARDs/JAKi in combination with csDMARDs, and 3067 patients (7.7%) were prescribed these drugs without csDMARDs. Among the bDMARDs/JAKi, tumor necrosis factor inhibitors (TNFi) were the most commonly prescribed DMARD overall, and also the most common first-line therapy, accounting for 60.0% or 45.5% of patients prescribed these drugs in combination with or without csDMARDs, respectively. Switching, temporary discontinuation (restarting with the same agents), and discontinuation of bDMARDs/JAKi were observed in 3150 (30.9%), 1379 (13.5%), and 2025 (19.9%) patients with csDMARDs, and in 849 (27.7%), 513 (16.7%), and 833 (27.2%) patients without csDMARDs, respectively. Real-world treatment trajectories of bDMARDs/JAKi with and without csDMARDs was analyzed in RA patients in Japan between 2008 and 2020. TNFi were the predominant first-line therapy, and likely to be switched to different classes. Understanding the current treatment patterns, including discontinuation, is important to find an optimal treatment strategy for RA patients.

Nationwide epidemiologic survey on incidence of macular dystrophy in Japan.

The aim of this study was to estimate the number of patients in Japan who had visited an ophthalmologist for macular dystrophy of various types, including Best vitelliform macular dystrophy (BVMD), Stargardt disease, occult macular dystrophy (OMD), cone (-rod) dystrophy, X-linked retinoschisis (XLRS), and central areolar choroid dystrophy (CACD). Nationwide epidemiologic survey METHODS: Questionnaires were distributed to 965 major facilities, including all the university hospitals in Japan. The aim of the questionnaire was to determine the number of patients with each type of macular dystrophy who had visited an outpatient clinic during the past 5 years (January 2015 to December 2019). Over 70% of the patients were diagnosed and followed up at university hospitals. The estimated annual number of newly diagnosed cases was as follows: 55.3 for BVMD, 36.7 for Stargardt disease, 35.8 for OMD, 160.6 for cone (-rod) dystrophy, 31.0 for XLRS, 29.8 for CACD, and 174.1 for other types of macular dystrophy. The total number of patients with macular dystrophy diagnosed and followed at major institutions was estimated to be 6651. This was the first nationwide survey of macular dystrophy in Japan and provided an approximate number of affected patients. The diagnosis of macular dystrophy is primarily carried out at facilities with affiliated specialists, such as university hospitals. By examining the incidence of multiple diseases simultaneously, we were able to compare the incidence of each type of macular dystrophy.

Complete sequence of carbapenem-resistant Ralstonia mannitolilytica clinical isolate co-producing novel class D β-lactamase OXA-1176 and OXA-1177 in Japan.

In 2020, the Ralstonia mannitolilytica strain JARB-RN-0044 was isolated from a midstream urine sample of an elderly hospitalized patient in Japan and was highly resistant to carbapenem (i.e., imipenem, meropenem, and doripenem). Whole-genome sequencing revealed that the complete genome consists of two replicons, a 3.5-Mb chromosome and a 1.5-Mb large non-chromosomal replicon which has not been reported in R. mannitolilytica, and referred to as the "megaplasmid" in this study based on Cluster of Orthologous Group of proteins functional analysis. The strain JARB-RN-0044 harbored two novel OXA-60 and OXA-22 family class D β-lactamase genes blaOXA-1176 and blaOXA-1177 on the megaplasmid. Cloning experiments indicated that Escherichia coli recombinant clone expressing blaOXA-1176 gene showed increased minimum inhibitory concentrations (MICs) of imipenem, meropenem, and doripenem, indicating that blaOXA-1176 gene encodes carbapenemase. In contrast, E. coli recombinant clone expressing blaOXA-1177 gene showed increased MICs of piperacillin and cefazolin, but not of carbapenem. Interestingly, the 44.6 kb putative prophage region containing genes encoding phage integrase, terminase, head and tail protein was identified in the downstream region of blaOXA-1176 gene, and comparative analysis with some previously reported R. mannitolilytica isolates revealed that the prophage region was unique to strain JARB-RN-0044. The existence of a highly carbapenem-resistant R. mannitolilytica isolate may raise human health concerns in Japan, where the population is rapidly aging.IMPORTANCERalstonia mannitolilytica is an aerobic non-fermenting Gram-negative rod commonly found in aquatic environments and soil. The bacteria can occasionally cause severe hospital-acquired bloodstream infections in immunocompromised patients and it has been recently recognized as an emerging opportunistic human pathogen. Furthermore, some R. mannitolilytica isolates are resistant to various antimicrobial agents, including β-lactams and aminoglycosides, making antimicrobial therapy challenging and clinically problematic. However, clinical awareness of this pathogen is limited. To our knowledge, in Japan, there has been only one report of a carbapenem-resistant R. mannitolilytica clinical isolate from urine by Suzuki et al. in 2015. In this study, whole-genome sequencing analysis revealed the presence and genetic context of novel blaOXA-1176 and blaOXA-1177 genes on the 1.5 Mb megaplasmid from highly carbapenem-resistant R. mannitolilytica isolate and characterized the overall distribution of functional genes in the chromosome and megaplasmid. Our findings highlight the importance of further attention to R. mannitolilytica isolate in clinical settings.

Validation and Clinical Application of the Japanese Version of the Patient-Reported Experience Measures for Intermediate Care Services: A Cross-Sectional Study.

Older adult patients account for 70% of all hospitalized patients in Japan, and intermediate care based on patient-centered care (PCC) that ensures continuity and quality of care at the interface between home services and acute care services and restores patient's independence and confidence is necessary for them to continue living independently. At present, no concept of intermediate care is established in Japan, and the implementation of PCC has been delayed. Thus, in this study, a Japanese version of the intermediate care evaluation index (patient-reported experience measure (PREM)) was created on the basis of the original PREM developed in the UK, and data in wards with intermediate care functions in Japan were collected to confirm internal consistency and validity from 2020 to 2022. The Japanese version of PREM was found to have a factor structure with two potential factors. Given the clear correlation with the shared decision-making evaluation index, which is the pinnacle of PCC, the theoretical validity of the Japanese version of PREM, which is based on PCC as a theoretical basis, was confirmed.

Comparison of platelet transfusion effectiveness between Helicobacter pylori-positive and -negative immune thrombocytopenia.

Immune thrombocytopenia (ITP) is characterized by early platelet destruction and impaired platelet production. Helicobacter pylori (H. pylori) infection seems to contribute to the pathogenesis in certain ITP patients in Japan. We compared the effectiveness of platelet transfusion in severe ITP in the presence or absence of H.pylori. The median corrected count increment (CCI) at 24 h after platelet transfusion (CCI-24) of the H.pylori-positive ITP patients was higher than that of the H. pylori-negative ITP patients (6463 vs. 754, p < 0.001), and the CCI-1 was also in the same direction but not significant (23 351 vs. 11 578). Multiple regression analyses showed that H. pylori infection was independently associated with CCI-24. Our study suggests that platelet transfusion may be more effective in H. pylori-positive ITP patients.

Financial Burden as a Potential Barrier to Vaccine Completion in Post-hematopoietic Stem Cell Transplant Patients in Japan.

Introduction The administration of routine vaccinations to patients following hematopoietic stem cell transplantation (HSCT) is highly recommended. However, studies examining reasons for not completing vaccination in post-HSCT patients are lacking. Method We reviewed the medical records of patients who sought vaccination following HSCT from January 2012 to December 2018 at the Center for Infectious Diseases, Nara Medical University. Results Information regarding patients' backgrounds, administered vaccines, and reasons for not administering recommended vaccines was collected for the study. Thirty-five patients (22 men and 13 women) with a median time from HSCT to the first visit of 25 months were enrolled. Vaccine coverage was highest for diphtheria, tetanus, and acellular pertussis (DTaP) at 89% (31 patients), followed by 23-valent pneumococcal, measles/rubella/mumps, and Japanese encephalitis at 71% (25 patients), 71% (25 patients), and 63% (22 persons), respectively. However, vaccine coverage for hepatitis B, 13-valent pneumococcal, and Hib was low at 26% (three patients), 11% (four patients), and 40% (14 patients), respectively. The reason for not completing the recommended vaccination series was not provided for most cases; however, the economic barrier was cited for all vaccines. Discussion This study identified several cases in Japan where individuals stopped completing post-HSCT vaccinations due to financial constraints. Larger-scale studies may be necessary in Japan in the future for further investigation.

Abstract 6457: The real-world data of comprehensive genomic profiling tests with tissue specimens from lung cancer patients in Japan

Abstract Introduction: Molecularly targeted therapy improves prognosis of lung cancer patients with specific genomic alterations, and thus it is important to identify actionable genomic alterations leading to appropriate therapy. In Japan, comprehensive genomic profiling (CGP) tests have been covered by insurance since June 2019. 99.7% of the CGP data under insurance coverage have been registered with the nationwide database: Center for Cancer Genomics and Advanced Therapeutics (C-CAT). C-CAT data include CGP test results and clinical information such as companion diagnostic results for EGFR, ALK, ROS1, and BRAF as well as therapeutic history. The aim of this study is to evaluate the usefulness of CGP tests for identifying actionable genomic alterations in real-world lung cancer patients. Methods: Among the 3,240 lung cancer patients registered in the C-CAT database by September 2023, 2,076 non-small cell lung cancer cases were tested using tissue specimens and analyzed retrospectively. The analysis was based on the levels of evidence defined by C-CAT. Level A indicated approved drugs for the particular cancer type, while level C indicated approved drugs or presence of positive clinical trials regardless of cancer type. Level F indicated that the genomic alteration was an oncogenic marker. Results: The cases were divided into two groups: 335 cases with known genomic alterations with positive results from companion diagnostic tests or use of specific inhibitors and 1,741 cases without. Genomic alterations with level A, A to C, and A to F were identified in 430 cases (24.7%), 1174 cases (67.4%), and 1718 cases (98.7%) with unknown genomic alterations, respectively. Genomic alterations with level A included rearrangement of RET (43 of 1741 cases, 2.5%), ALK (14 cases, 0.8%), ROS1 (8 cases, 0.5%), and NTRK1 (2 cases, 0.1%), and mutations of EGFR (124 cases, 7.1%), MET (38 cases, 2.2%), ERBB2 (122 cases, 7.0%), KRAS G12C (66 cases, 3.8%), and BRAF V600E (15 cases, 0.9%). Genomic alterations with level C included mutations in KRAS (185 cases, 10.6%), PIK3CA (99 cases, 5.7%), BRAF (55 cases, 3.2%), and PTEN (32 cases, 1.8%) and amplifications in ERBB2 (147 cases, 8.4%) and MET (68 cases, 3.9%). Among cases with known genomic alterations, ALK and ROS1 fusion genes were not detected in 11 of 49 (22.4%) and 17 of 46 (37.0%), while EGFR and BRAF mutation was not detected in 11 of 218 (5.0%) and 3 of 4 cases (75.0%), respectively. The detection rate of fusion genes was lower than that of mutated genes (70.5% vs 93.7%, p&amp;lt;0.001). Conclusion: In non-small cell lung cancer patients with unknown driver genes, driver oncogenes with corresponding approved therapy were found in a quarter of the patients. CGP tests offer the possibility of increasing the opportunities of receiving new therapies. CGP tests may have a lower detection rate for fusion genes compared with other mutations. Citation Format: Koki Fujii, Momoko Morishita, Michiko Ueki, Hiroaki Ikushima, Hideaki Isago, Kousuke Watanabe, Katsutoshi Oda, Hidenori Kage. The real-world data of comprehensive genomic profiling tests with tissue specimens from lung cancer patients in Japan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6457.

Emergence of multidrug-resistant Pandoraea sputorum in Japan.

Pandoraea is a pathogenic bacterium naturally resistant to various antimicrobials, including colistin. Here, we report the whole-genome sequence of Pandoraea sputorum, which exhibits high-level multidrug resistance, isolated from a hospitalized patient in Japan.

Annual dialysis data report 2020, JSDT renal data registry

BackgroundThe 2020 Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) annual survey was sent to 4493 dialysis facilities in Japan.MethodsQuestionnaires were sent to all facilities that provide patients with dialysis therapy in Japan. Data were collected and compiled to form cross-sectional results of renal replacement therapy from various aspects.ResultsIn total, 4437 facilities (98.8%) responded to the facility questionnaire and 4271 (95.1%) responded to the patient questionnaire. The number of chronic dialysis patients in Japan continues to increase every year, reaching 347,671 at the end of 2020 and giving a prevalence rate of 2754 patients per million population. The mean age was 69.40 years. Diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.5%), followed by chronic glomerulonephritis (25.3%) and nephrosclerosis (12.1%). There were 40,744 incident dialysis patients during 2020, representing a decrease of 141 from 2019. The average age of patients on dialysis was 70.88 years, with diabetic nephropathy being the most common underlying disease (40.7%) second most common was nephrosclerosis (17.5%), which was unchanged from the previous year and surpassed chronic glomerulonephritis (15.0%). There were 34,414 patient deaths in 2020; the crude mortality rate was 9.9%. The main causes of death were heart failure (22.4%), infection (21.5%), and malignancy (9.0%), which were almost the same as the percentages for the previous year. Since 2012, the number of patients treated by hemodiafiltration has increased rapidly; in 2020, the number of patients on this modality was 163,825, accounting for 47.1% of all patients on maintenance dialysis. The number of patients on peritoneal dialysis has been on the rise since 2017, reaching 10,338 in 2020; 20.8% of whom received combined therapy with hemodialysis or hemodiafiltration, showing no change from the previous year. A total of 751 patients were on home hemodialysis at the end of 2020, representing a decrease of 9 from the end of 2018. In 2020, coronavirus disease 2019 (COVID-19) infection and malignancy were added as new items in the survey. Continuing on from the 2019 survey, history of kidney donation for a living-donor transplant was investigated.ConclusionsPresent issues and challenges in renal replacement therapy were identified in the responses to the new questionnaire items included in this survey. A more detailed evaluation with adjustment for patient background factors should clarify the characteristics of the underlying diseases and conditions in dialysis patients.Trial registration The JRDR was approved by the Japanese Society for Dialysis Therapy ethics committee. It was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry on 10 September 2020 and in the UMIN clinical trials registration system (UMIN000018641).

Nationwide data from comprehensive genomic profiling assays for detecting driver oncogenes in non-small cell lung cancer.

Driver oncogenes are investigated upfront at diagnosis using multi-CDx systems with next-generation sequencing techniques or multiplex reverse-transcriptase polymerase chain reaction assays. Additionally, from 2019, comprehensive genomic profiling (CGP) assays have been available in Japan for patients with advanced solid tumors who had completed or were expected to complete standard chemotherapy. These assays are expected to comprehensively detect the driver oncogenes, especially for patients with non-small cell lung cancer (NSCLC). However, there are no reports of nationwide research on the detection of driver oncogenes in patients with advanced NSCLC who undergo CGP assays, especially in those with undetected driver oncogenes at diagnosis. In this study, we investigated the proportion of driver oncogenes detected in patients with advanced NSCLC with undetectable driver oncogenes at initial diagnosis and in all patients with advanced NSCLC who underwent CGP assays. We retrospectively analyzed data from 986 patients with advanced NSCLC who underwent CGP assays between August 2019 and March 2022, using the Center for Cancer Genomics and Advanced Therapeutics database. The proportion of driver oncogenes newly detected in patients with NSCLC who tested negative for driver oncogenes at diagnosis and in all patients with NSCLC were investigated. Driver oncogenes were detected in 451 patients (45.7%). EGFR was the most common (16.5%), followed by KRAS (14.5%). Among the 330 patients with undetected EGFR, ALK, ROS1, and BRAF V600E mutations at diagnosis, 81 patients (24.5%) had newly identified driver oncogenes. CGP assays could be useful to identify driver oncogenes in patients with advanced NSCLC, including those initially undetected, facilitating personalized treatment.

In vitro activity of tedizolid against 43 species of Nocardia species

The purpose of the present study was to evaluate the in vitro activity of tedizolid against several clinically significant species of Nocardia by comparing with that of linezolid. A total of 286 isolates of Nocardia species, including 236 clinical isolates recovered from patients in Japan and 50 strains (43 species) purchased from NITE Biological Resource Center, were studied. Antimicrobial susceptibility testing was performed using the broth microdilution method. For the 286 Nocardia isolates, the minimal inhibitory concentration (MIC)50 and MIC90 values of tedizolid were 0.25 and 0.5 μg/ml, and those of linezolid were 2 and 2 μg/ml, respectively. The distribution of the linezolid/tedizolid ratios (MICs of linezolid/MICs of tedizolid) showed that tedizolid had four- to eight-fold higher activity than linezolid in 96.1% (275/286) of Nocardia isolates. Both the tedizolid and linezolid MIC90 values for Nocardia brasiliensis were two-fold higher than those for the other Nocardia species. Both tedizolid and linezolid had low MIC values, 0.25–1 μg/ml and 0.5–4 μg/ml, respectively, even against nine isolates (five species) that were resistant to trimethoprim/sulfamethoxazole. One Nocardia sputorum isolate showed reduced susceptibility to tedizolid (4 μg/ml). Bioinformatics analysis suggests different resistance mechanisms than the oxazolidinone resistance seen in enterococci and staphylococci.

Long-term prognosis after stapled and hand-sewn ileal pouch–anal anastomoses for familial adenomatous polyposis: a multicenter retrospective study

PurposeThe long-term prognosis of stapled and hand-sewn ileal pouch–anal anastomoses in familial adenomatous polyposis patients in Japan remains unknown. This study aimed to compare the overall survival in familial adenomatous polyposis patients who underwent stapled or hand-sewn ileal pouch–anal anastomosis.MethodsThis multicenter retrospective study was conducted at 12 institutions in Shizuoka Prefecture, Japan. The clinical outcomes of 53 eligible familial adenomatous polyposis patients who underwent stapled (n = 24) and hand-sewn (n = 29) ileal pouch–anal anastomosis were compared.ResultsThe median follow-up duration was 171.5 months. The incidence of adenoma in the remnant rectum or anal transitional zone and metachronous rectal cancer was significantly more common in stapled ileal pouch–anal anastomosis (adenoma: stapled, 45.8%, vs. hand-sewn, 10.3%, p = 0.005; metachronous rectal cancer: 29.2%, vs. none, p = 0.002). The number of deaths was remarkably higher in stapled ileal pouch–anal anastomosis (p = 0.002). Metachronous rectal cancer was the most common cause of death. Overall survival was worse in stapled ileal pouch–anal anastomosis than in hand-sewn ileal pouch–anal anastomosis (120 months, 90.7% vs. 96.6%; 240 months, 63.7% vs. 96.6%; p = 0.044). Cox regression analysis revealed the independent effects of preoperative advanced colorectal cancer and stapled ileal pouch–anal anastomosis on overall survival.ConclusionStapled ileal pouch–anal anastomosis negatively affected the overall survival of familial adenomatous polyposis patients. Therefore, hand-sewn ileal pouch–anal anastomosis is recommended for better prognosis in these patients.