A case of Adult-onset Acute Flaccid Myelitis Accompanied by Rhombencephalitis which First Presented with Prominent Psychiatric Symptoms and Dysautonomia Mimicking Anti-N-methyl-d-aspartate Receptor Encephalitis.

A 44-year-old woman with a subacute onset of an altered mental status, urinary retention, and fluctuating blood pressure was initially diagnosed with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, meeting the criteria of Graus et al. Cardiac arrest occurred, which required pacemaker placement. She subsequently showed profound flaccid limb paralysis, with magnetic resonance imaging demonstrating focal necrotic lesions localized in the anterior horn of the longitudinal segments of the spinal cord and in the pontine tegmentum. Enteroviruses or autoimmune encephalitis-associated autoantibodies were not detected. We herein report a case of acute flaccid myelitis with profound psychiatric symptoms and dysautonomia, resembling NMDAR encephalitis.

Higher Frequency of Premature Atrial Contractions Correlates With Atrial Fibrillation Detection after Cryptogenic Stroke.

BACKGROUND: Covert atrial fibrillation (AF) is a major cause of cryptogenic stroke. This study investigated whether a dose-dependent relationship exists between the frequency of premature atrial contractions (PACs) and AF detection in patients with cryptogenic stroke using an insertable cardiac monitor (ICM). METHODS: We enrolled consecutive patients with cryptogenic stroke who underwent ICM implantation between October 2016 and September 2020 at 8 stroke centers in Japan. Patients were divided into 3 groups according to the PAC count on 24-hour Holter ECG: ≤200 (group L), >200 to ≤500 (group M), and >500 (group H). We defined a high AF burden as above the median of the cumulative duration of AF episodes during the entire monitoring period. We evaluated the association of the frequency of PACs with AF detection using log-rank trend test and Cox proportional hazard model and with high AF burden using logistic regression model, adjusting for age, sex, CHADS2 score. RESULTS: Of 417 patients, we analyzed 381 patients with Holter ECG and ICM data. The median age was 70 (interquartile range, 59.5-76.5), 246 patients (65%) were males, and the median duration of ICM recording was 605 days (interquartile range, 397-827 days). The rate of new AF detected by ICM was higher in groups with more frequent PAC (15.5%/y in group L [n=277] versus 44.0%/y in group M [n=42] versus 71.4%/y in group H [n=62]; log-rank trend P<0.01). Compared with group L, the adjusted hazard ratios for AF detection in groups M and H were 2.11 (95% CI, 1.24-3.58) and 3.23 (95% CI, 2.07-5.04), respectively, and the adjusted odds ratio for high AF burden in groups M and H were 2.57 (95% CI, 1.14-5.74) and 4.25 (2.14-8.47), respectively. CONCLUSIONS: The frequency of PACs was dose-dependently associated with AF detection in patients with cryptogenic stroke.

Immature stroma and high infiltration of CD15+ cells are predictive markers of poor prognosis in different subsets of patients with pancreatic cancer.

Preoperative treatment is commonly carried out for borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, the relationship between the combination of immune cells in the tumor microenvironment and their intratumoral heterogeneity along with their association with histological findings remains unclear, especially in patients receiving preoperative chemotherapy. We aimed to explore the therapeutic strategies for patients with PDAC with poor prognosis after receiving chemotherapy based on histological and immunological microenvironmental classifications. We investigated the correlation between the prognosis and histological immune microenvironmental factors of patients who initially underwent surgery (n = 100) and were receiving gemcitabine plus nab-paclitaxel (GEM + nabPTX) as preoperative chemotherapy (n = 103). Immune profiles were generated based on immune cell infiltration into the tumor, and their correlation with patient outcomes and histological features was analyzed. Tumor-infiltrating neutrophils (TINs) were identified as independent poor prognostic factors using multivariate analysis in both surgery-first and preoperative chemotherapy groups. The patients were further classified into four groups based on immune cell infiltration into the tumor. Patients with high CD15 infiltration into the tumor and immature stroma at the cancer margins showed the worst prognosis in the preoperative chemotherapy group. The analysis of mRNA expression and immunohistochemical features revealed that CXCR2, the receptor for CXCL8, was correlated with disease-free and overall survival. We inferred that patients with immature stroma at the margins and high infiltration of CD15+ neutrophils within the tumor showed the worst prognosis and they could particularly benefit from treatment with inhibitors targeting CXCR2 or CXCL8.

Association between the controlling nutritional status score and outcomes in ischemic stroke patients with active cancer.

BACKGROUND: The effect of nutritional status on survival in ischemic stroke patients with active cancer remains unclear. METHODS: This study retrospectively evaluated ischemic stroke patients with active cancer admitted to a university hospital in Japan between 2006 and 2016. Patients were followed for 2 years after stroke. The controlling nutritional status (CONUT) score was used to classify undernutrition degree into 4 groups: normal, light, moderate, and severe. Survival rates were compared using the Kaplan-Meier method. Hazard ratio (HR) and 95 % confidence intervals (CIs) for mortality were calculated using Cox regression models. RESULTS: A total of 158 patients (31 % women; median age: 71 years) were analyzed. Of these, 47 % had distant metastasis. The median (interquartile range) National Institute of Health Stroke Scale and CONUT scores were 4 (1-10) and 5 (3-7), respectively. Kaplan-Meier curve indicated that patients with poorer nutritional status had worse outcomes (overall log-rank test, p < 0.001). The univariable Cox regression analysis showed that the HR (95 % CI) for the light, moderate, and severe groups were 1.14 (0.45-2.86), 3.01 (1.27-7.12), and 2.94 (1.10-7.84), respectively. This statistical significance did not persist after adjustment for potential confounders (HR [95 % CI] for the light, moderate, and severe groups were 0.95 [0.36-2.49], 1.56 [0.57-4.28], and 1.34 [0.37-4.92], respectively). Past stroke, distant metastasis, and plasma D-dimer levels on admission were independent predictors of prognosis. CONCLUSIONS: This single-center, retrospective study suggests that nutritional status serves as a prognostic indicator for ischemic stroke patients with active cancer. However, the effect is not statistically independent.

DIRECTEUR: transcriptome-based prediction of small molecules that replace transcription factors for direct cell conversion.

MOTIVATION: Direct reprogramming (DR) is a process that directly converts somatic cells to target cells. Although DR via small molecules is safer than using transcription factors (TFs) in terms of avoidance of tumorigenic risk, the determination of DR-inducing small molecules is challenging. RESULTS: Here we present a novel in silico method, DIRECTEUR, to predict small molecules that replace TFs for DR. We extracted DR-characteristic genes using transcriptome profiles of cells in which DR was induced by TFs, and performed a variant of simulated annealing to explore small molecule combinations with similar gene expression patterns with DR-inducing TFs. We applied DIRECTEUR to predicting combinations of small molecules that convert fibroblasts into neurons or cardiomyocytes, and were able to reproduce experimentally verified and functionally related molecules inducing the corresponding conversions. The proposed method is expected to be useful for practical applications in regenerative medicine. AVAILABILITY AND IMPLEMENTATION: The code and data are available at the following link: https://github.com/HamanoLaboratory/DIRECTEUR.git.

Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double-blind (BLESS) study.

AIMS: Inadequate antidepressant response interrupts effective treatment of major depressive disorder (MDD). The BLESS study evaluates the dosage, efficacy, and safety of brexpiprazole adjunctive therapy in Japanese patients with inadequate antidepressant therapy (ADT) response. METHODS: This placebo-controlled, randomized, multicenter, parallel-group phase 2/3 study randomized Japanese MDD patients (Hamilton Rating Scale for Depression 17-item total score ≥ 14; historical inadequate response to 1-3 ADTs) with inadequate response to 8-week single-blind, prospective SSRI/SNRI treatment to 6-week adjunctive treatment with brexpiprazole 1 mg, 2 mg, or placebo. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline. Secondary endpoints included MADRS response, remission rate, and Clinical Global Impression-Improvement score. Safety was comprehensively evaluated, especially regarding antipsychotic adverse events (AEs). RESULTS: Of 1194 screened patients, 740 were randomized and 736 (1 mg, n = 248; 2 mg, n = 245; placebo, n = 243) had ≥1 baseline/post-baseline MADRS total score. The LSM (SE) change from baseline in MADRS total score at Week 6 by MMRM analysis was -8.5 (0.47) with brexpiprazole 1 mg, -8.2 (0.47) with brexpiprazole 2 mg, and -6.7 (0.47) with placebo (placebo-adjusted LSM difference [95% CI]: 1 mg, -1.7 [-3.0, -0.4]; P = 0.0089; 2 mg, -1.4 [-2.7, -0.1]; P = 0.0312). Secondary efficacy results supported the primary endpoint. Brexpiprazole was generally well tolerated. CONCLUSION: Brexpiprazole 1 mg daily was an appropriate starting dose and both 1 mg and 2 mg daily were effective and well tolerated as adjunctive therapy for Japanese MDD patients not adequately responsive to ADT.

Lentinula Edodes Mycelia extract regulates the function of antigen-presenting cells to activate immune cells and prevent tumor-induced deterioration of immune function.

Immune cell activation is essential for cancer rejection; however, the tumor microenvironment leads to deterioration of immune function, which enables cancer cells to survive and proliferate. We previously reported that oral ingestion of Lentinula Edodes Mycelia (L.E.M.) extract enhances the tumor antigen-specific T-cell response and exerts an antitumor effect in a tumor-bearing mouse model. In this study, we focused on antigen-presenting cells (APCs) located upstream of the immune system, induced a T-cell response, then examined the impact of L.E.M. extract on the APCs. L.E.M. extract enhanced the expression of MHC-I, MHC-II, CD86, CD80, and CD40 in bone marrow-derived dendritic cells (DCs) and strongly induced the production of IL-12. L.E.M.-stimulated DCs enhanced IFN-γ production from CD8+ T cells and induced their differentiation into effector cells. Furthermore, L.E.M. extract promoted IL-12 production and suppressed the production of IL-10 and TGF-ß by transforming bone marrow-derived macrophages into M1-like macrophages. Furthermore, in a B16F10 melanoma inoculation model, DCs in the spleen were decreased and their activation was suppressed by the presence of cancer; however, ingestion of L.E.M. extract prevented this functional deterioration of DCs. In the spleen of cancer-bearing mice, the number of CD11b- F4/80+ macrophages in a hypoactivated state was also increased, whereas L.E.M. extract suppressed the increase of such macrophages. These findings suggest that L.E.M. extract may exhibit an antitumor immune response by regulating the function of APCs to induce cytotoxic T lymphocytes, as well as by suppressing the decline in antigen-presenting cell activity caused by the presence of cancer.

Clinicopathologic Features and Genetic Alterations in Mixed-Type Ampullary Carcinoma.

Mixed-type ampullary carcinoma is a subtype that combines intestinal-type (I-type) and pancreatobiliary-type (PB-type) lesions, but few studies have examined its clinicopathologic features and genetic alterations. The differences in genetic alterations between mixed type and other subtypes, as well as the genetic differences between I-type and PB-type lesions in the mixed type, remain unclear. In this study, we compared the clinicopathologic features and prognosis of 110 ampullary carcinomas classified by hematoxylin and eosin and immunohistochemical staining as follows: 63 PB-type, 35 I-type, and 12 mixed-type carcinomas. A comparative analysis of genetic mutations by targeted sequencing of 24 genes was also performed in 3 I-type cases, 9 PB-type cases, and I and PB-type lesions of 6 mixed-type cases. The mixed subtype had a poorer prognosis than the other subtypes, and there was also a similar tendency in the adjuvant group (n = 22). A total of 49 genetic mutations were detected in all 18 lesions for which genetic alteration was analyzed. No genetic mutations specific to the mixed type were found, and it was not possible to determine genetically whether the mixed type had originally been I or PB type. However, 5 of 6 cases had mutations common to both I and PB-type lesions, and additional mutations were found only in either I or PB-type lesions. In support of this, the mixed type more frequently exhibited genetic heterogeneity intratumorally than the other subtypes. Mixed-type tumors are histologically, immunohistochemically, and genetically heterogeneous, and this heterogeneity is associated with poor prognosis and may affect treatment resistance.

Single-cell RNA-seq analysis identifies distinct myeloid cells in a case with encephalitis temporally associated with COVID-19 vaccination.

Recently accumulating evidence has highlighted the rare occurrence of COVID-19 vaccination-induced inflammation in the central nervous system. However, the precise information on immune dysregulation related to the COVID-19 vaccination-associated autoimmunity remains elusive. Here we report a case of encephalitis temporally associated with COVID-19 vaccination, where single-cell RNA sequencing (scRNA-seq) analysis was applied to elucidate the distinct immune signature in the peripheral immune system. Peripheral blood mononuclear cells (PBMCs) were analyzed using scRNA-seq to clarify the cellular components of the patients in the acute and remission phases of the disease. The data obtained were compared to those acquired from a healthy cohort. The scRNA-seq analysis identified a distinct myeloid cell population in PBMCs during the acute phase of encephalitis. This specific myeloid population was detected neither in the remission phase of the disease nor in the healthy cohort. Our findings illustrate induction of a unique myeloid subset in encephalitis temporally associated with COVID-19 vaccination. Further research into the dysregulated immune signature of COVID-19 vaccination-associated autoimmunity including the cerebrospinal fluid (CSF) cells of central nervous system (CNS) is warranted to clarify the pathogenic role of the myeloid subset observed in our study.

Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis.

DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine with S-adenosyl-L-methionine. Methylation regulates gene expression, serving a variety of physiological and pathophysiological roles. The chemical mechanisms regulating DNMT enzymatic activity, however, are not fully elucidated. Here, we show that protein S-nitrosylation of a cysteine residue in DNMT3B attenuates DNMT3B enzymatic activity and consequent aberrant upregulation of gene expression. These genes include Cyclin D2 (Ccnd2), which is required for neoplastic cell proliferation in some tumor types. In cell-based and in vivo cancer models, only DNMT3B enzymatic activity, and not DNMT1 or DNMT3A, affects Ccnd2 expression. Using structure-based virtual screening, we discovered chemical compounds that specifically inhibit S-nitrosylation without directly affecting DNMT3B enzymatic activity. The lead compound, designated DBIC, inhibits S-nitrosylation of DNMT3B at low concentrations (IC50 ≤ 100 nM). Treatment with DBIC prevents nitric oxide (NO)-induced conversion of human colonic adenoma to adenocarcinoma in vitro. Additionally, in vivo treatment with DBIC strongly attenuates tumor development in a mouse model of carcinogenesis triggered by inflammation-induced generation of NO. Our results demonstrate that de novo DNA methylation mediated by DNMT3B is regulated by NO, and DBIC protects against tumor formation by preventing aberrant S-nitrosylation of DNMT3B.

Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism.

CD4+ memory T cells are central to long-lasting protective immunity and are involved in shaping the pathophysiology of chronic inflammation. While metabolic reprogramming is critical for the generation of memory T cells, the mechanisms controlling the redox metabolism in memory T cell formation remain unclear. We found that reactive oxygen species (ROS) metabolism changed dramatically in T helper-2 (Th2) cells during the contraction phase in the process of memory T cell formation. Thioredoxin-interacting protein (Txnip), a regulator of oxidoreductase, regulated apoptosis by scavenging ROS via the nuclear factor erythroid 2-related factor 2 (Nrf2)-biliverdin reductase B (Blvrb) pathway. Txnip regulated the pathology of chronic airway inflammation in the lung by controlling the generation of allergen-specific pathogenic memory Th2 cells in vivo. Thus, the Txnip-Nrf2-Blvrb axis directs ROS metabolic reprogramming in Th2 cells and is a potential therapeutic target for intractable chronic inflammatory diseases.

RNF43 as a predictor of malignant transformation of pancreatic mucinous cystic neoplasm.

Mucinous cystic neoplasm (MCN) of the pancreas rarely progresses to invasive carcinoma, but few studies have analyzed genomic alterations involved in its malignant transformation. The relationships of ring finger protein 43 (RNF43) mutations with cytological atypia, RNF43 protein expression, and Wnt signaling proteins in MCN remain unclear. This study included 106 MCN cases, classified into 89 low-grade dysplasia (LG), 9 high-grade dysplasia (HG), and 8 invasive carcinoma (INV). We analyzed HG/INV and LG lesions of 9 HG/INV cases and LG lesions of 9 LG cases using targeted sequencing and confirmed the protein expression of RNF43 and ß-catenin. The frequency of RNF43 mutations was significantly higher in HG/INV cases than in LG cases. Furthermore, HG/INV lesions (56%) and LG lesions (33%) of HG/INV cases possessed RNF43 mutation, whereas no such mutation was detected in any LG cases. The expression of RNF43 was reduced in 71% of HG/INV cases and significantly correlated with histological grade and aberrant expression of ß-catenin. In 3 of 5 RNF43-mutated cases, the expression of RNF43 was reduced, but there was no significant correlation between RNF43 mutation and protein expression. MCNs frequently harbored KRAS mutations, at rates of 100% in HG/INV lesions and 50% in LG lesions of HG/INV and LG cases. There was no significant difference in mutation frequency in LG lesions between HG/INV and LG cases. These results suggest that RNF43 mutations may be involved in and predictive of malignant transformation from an early stage of MCN.

An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke.

BACKGROUND: Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. METHODS: We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. RESULTS: Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p < 0.001) and higher extent of NETosis (p = 0.006). Restricted mean survival time analysis revealed that older thrombi were associated with longer puncture-to-reperfusion times (difference: 15.6 minutes longer for older thrombi, p = 0.002). This association remained significant even after adjustment for erythrocyte content and the extent of NETosis (adjusted difference: 10.8 minutes, 95% confidence interval [CI]: 0.6-21.1 minutes, p = 0.039). Compared with fresh thrombi, older thrombi required more device passes before reperfusion (p < 0.001) and were associated with poorer functional outcomes (adjusted common odds ratio: 0.49; 95% CI: 0.24-0.99). CONCLUSION: An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

The long term participation trend for the colorectal cancer screening after the 2011 triple disaster in Minamisoma City, Fukushima, Japan.

Colorectal cancer (CRC) screening is a well-established cancer screening method, and its effectiveness depends on maintaining a high participation rate in the target population. In this study, we analyzed the trends in CRC screening participation rates over 10 years in Minamisoma City, where residents were forced to evacuate after the 2011 triple disaster in Fukushima, Japan. The immunochemical fecal occult blood test is provided as municipal CRC screening. We calculated the annual CRC screening participation rate and analyzed the factors associated with participation in screening. Overall, 4069 (12.3%) and 3839 (11.7%) persons participated in CRC screening in 2009 and 2010, respectively; however, the number decreased significantly to 1090 (3.4%) in 2011 when the earthquake occurred. Over the following 3 years, the rate gradually recovered. Multivariable logistic analysis showed that age < 65 years, living alone, and evacuation were significant associated factors for non-participation after 2011 (p < 0.05). In conclusion, the CRC screening participation rate decreased significantly during the Great East Japan Earthquake but recovered over the next 3 years. Further analysis of factors preventing CRC screening participation and research on the long-term effects of its post-disaster decline are important to consider in assessing the need for intervention in post-disaster cancer screening.

Potential association of prolonged patient interval and advanced anatomic stage in breast cancer patients in the area affected by the 2011 triple disaster in Fukushima, Japan: Retrospective observational study.

ABSTRACT: For five years after the 2011 triple disaster (earthquake, tsunami, and nuclear disaster) in Japan, the proportion of patients with undiagnosed symptomatic breast cancer remained elevated in the coastal area of Fukushima. These individuals experienced a prolonged interval from first symptom recognition to initial medical consultation (hereafter referred to as the patient interval). We aimed to investigate how this prolonged patient interval affected disease staging.Using patient records, we retrospectively extracted females with newly and pathologically diagnosed breast cancer who initially presented to Minamisoma Municipal General Hospital from March 2011 to March 2016. We estimated the proportion with advanced-stage disease (III, IV) according to the patient interval duration (<3 months, 3-12 months, and 12 months plus). A cut-off patient interval value was determined based on the previous evidence with regards to impacts on survival prospects. Logistic regression approaches were used to fulfill the study outcome.The proportion of patients with advanced-stage disease was 10.3% for < 3 months (7/68), 18.2% for 3-12 months (2/11), and 66.7% for more than 12 months (12/18). We found a similar trend using the multivariate logistic regression analyses.Prolongation of the patient interval was associated with advanced-stage disease among female patients with breast cancer.

Evaluation of the emergency medical system in an area following lifting of the mandatory evacuation order after the Fukushima Daiichi Nuclear Power Plant accident: A retrospective cross-sectional observational study.

ABSTRACT: Following the lifting of the evacuation order due to the Fukushima Daiichi Nuclear Power Plant accident, the medical demand and emergency medical system (EMS) in the area where the evacuation orders were lifted have not been well-investigated. This study aimed to evaluate the emergency transportation in such areas and compare the differences with areas that had minimal impact.Using the local EMS transport records, the characteristics of patients who were transferred by an EMS vehicle in Minamisoma City were collected between July 12, 2016 and July 31, 2018, and were compared between former evacuation zones and outside the evacuation zones in the city.The number of emergency transports in the study period in Minamisoma City were 325 cases in the area where the evacuation orders were lifted and 4307 cases in the other areas. The total EMS time was significantly longer in the area where the evacuation order was lifted (48 ±â€Š16 minutes) than in the other areas (40 ±â€Š15 minutes) (P < .001). In the analysis of each component of EMS times, the transport time, which is the time from departure from the patient's location to arrival at a hospital, was significantly longer in the former evacuation zone than in the other areas (16 ±â€Š9 vs 9 ±â€Š9 minutes, P < .001), suggesting that transport time contributed to the longer EMS response times.In areas where the evacuation orders were lifted, the EMS transport time was significantly longer than that in the area outside the former evacuation zone; correspondingly, the total EMS time significantly increased in the former evacuation zone. A plausible reason for this may be the closure of local medical facilities following the evacuation order after the nuclear accident.

Accuracy of post-publication Financial Conflict of Interest corrections in medical research: A secondary analysis of pharmaceutical company payments to the authors of the CREATE-X trial report in the New England Journal of Medicine.

In June 2017, Japanese and Korean authors published the results of the CREATE-X trial in the New England Journal of Medicine (NEJM). After we identified their inadequate disclosures of Financial Conflict of Interests (FCOIs), the authors made a post-publication correction of their FCOIs. The purpose of this study is to evaluate the accuracy of the post-publication corrections by the Japanese authors of the CREATE-X trial. All the Japanese authors of the CREATE-X trial were included in the study. We determined the payments received by these authors in 2016 using publicly available data published by 78 pharmaceutical companies based on the stipulated Japanese transparency guidelines. We retrieved the original and revised versions of the FCOI disclosures as published on the NEJM website, and compared the payments reported by the pharmaceutical companies and the original and revised FCOI disclosures of the authors. Of the 12 authors, nine received payments made by the drug manufacturer involved in the CREATE-X trial. Of these nine, only three (33.3%) originally disclosed their relationships, and another three (33.3%) later disclosed such relationships in the post-publication corrections. Similarly, of the 11 receiving at least one payment from other manufacturers of breast cancer products, none correctly disclosed the payments in the original or the revised disclosure. In the CREATE-X trial, FCOIs with pharmaceutical companies were not properly disclosed by 11 of the 12 Japanese authors, even after the post-publication corrections, which highlights the need to pay more attention to the accuracy of FCOI disclosures in academic publications.

Pharmaceutical company payments to authors of the Japanese guidelines for the management of hypertension.

ABSTRACT: Antihypertensive drugs have been of significant interest to the pharmaceutical industry due to increasing sales opportunities in a global market. The financial relationships between pharmaceutical companies and the Japanese Society of Hypertension (JSH) have a possible influence on clinical practices in Japan. This study examined the distribution of pharmaceutical payments made to the authors of the revised Guidelines for the Management of Hypertension (JSH2019) and the transparency of the Conflict of Interest disclosure that each author made.We retrospectively obtained publicly available data regarding payments made by Japanese pharmaceutical companies to all authors of the JSH2019 in 2016. We also collected data on individual financial disclosure of JSH2019 authors to investigate whether their self-reported financial relationship with companies were compliant to the financial disclosure policy of JSH2019.The total and mean payment values reported by pharmaceutical companies were $4,246,436 and $21,447, respectively. Of the 198 authors, 171 (86.4%) authors received at least 1 payment. Of 74 authors required to disclose their conflict of interest (COI) the authors, one-third failed to follow the COI policy covering the clinical guidelines.Major pharmaceutical companies selling antihypertensive drug products in the Japanese market had a significant financial connection with the JSH2019 authors. Financial relationships between pharmaceutical companies and authors or Japanese medical societies are raising significant concerns about the credibility of clinical guidelines and the potentially biases and undue influences that they may cause, especially with respect to adverse prescription patterns.

Risk Factors and Optimal Methods for Incisional Hernias After Kidney Transplantation: A Single-Center Experience From Asia.

BACKGROUND: For kidney transplant patients, incisional hernia (IH) is a major complication resulting from prolonged pretransplant dialysis, immunosuppressive drugs, and the high prevalence of diabetes. However, there have been relatively few studies of IH after kidney transplantation (KT) in Japan and in the greater Asian population. Additionally, operative methods for IH repair have not been established. METHODS: We retrospectively analyzed 465 consecutive patients who underwent KT at our hospital from April 2013 to March 2019. Patients who underwent incisional hernia repair were included in this study, and the follow-up time was extended to September 2020. We defined severe IH as an IH requiring surgical repair. We examine the risk factors for severe IH among KT patients and also discuss the operative methods of IH repair. RESULTS: During the study period, 7 patients developed severe IH after KT. The cumulative occurrence rate for severe IH was 1.1% 1 year postoperatively. Multivariate logistic regression analyses showed that age at KT and dialysis duration (hazard ratio = 1.112, P = .016; hazard ratio = 1.106, respectively; P = .038) were independent risk factors for severe IH. We used polypropylene mesh for IH repair in all cases, with onlay repair performed in 5 of 7 cases. There was no recurrence or infection after mesh repair during follow-up. CONCLUSIONS: In this study, age at KT and dialysis duration were independent risk factors for severe IH in the Japanese population. Onlay repair with a polypropylene mesh appeared to be a safe and acceptable operation for IH repair after KT.