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Objectives: Patients following renal transplantation (RTX) may experience nocturia exacerbation due to polyuria and reduced bladder capacity, thereby impacting the specific quality of life (QOL) associated with nocturia. The present study aims to investigate factors associated with the deterioration of nocturia‐specific QOL in RTX patients. Methods: The study cohort comprised 59 consecutive patients who had undergone successful RTX. Nocturia‐related QOL questionnaires (N‐QOL) were employed to evaluate the specific QOL related to nocturia. The Bother/Concern and Sleep/Energy domains of the N‐QOL were also assessed. The primary outcome measure was to explore factors related to the aggravation of nocturia‐specific QOL in patients post‐RTX. Results: The mean nocturia frequency post‐RTX was 1.3 ± 1.0. Univariate and multivariate analyses revealed a significant reduction in the Bother/Concern domain score associated with increased nocturia (p =.042). Aging significantly decreased the total N‐QOL score and the Sleep/Energy domain score (p =.001 and.0002, respectively). Prolonged duration after RTX significantly reduced the scores of both the Sleep/Energy domain and the Bother/Concern domain (p =.018 and.037, respectively). However, the duration of dialysis prior to RTX was not significantly associated with the total score or subdomains of N‐QOL. Conclusions: Nocturia‐specific QOL affected not only the nocturia itself, but also aging and the prolonged duration after RTX. Thus, comprehensive approaches to the RTX patients were needed to improve the Nocturia‐specific QOL in RTX patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to clarify the relationship between changes in elasticity and anorectal function before and after chemoradiotherapy. Methods: This is a single-center prospective cohort study (Department of Surgical Oncology, The University of Tokyo). We established a technique to quantify internal anal sphincter hardness as elasticity using transanal ultrasonography with real-time tissue elastography. Twenty-seven patients with post-chemoradiotherapy rectal cancer during 2019–2022 were included. Real-time tissue elastography with transanal ultrasonography was performed before and after chemoradiotherapy to measure internal anal sphincter hardness as "elasticity" (hardest (0) to softest (255); decreased elasticity indicated sclerotic changes). The relationship between the increase or decrease in elasticity pre- and post-chemoradiotherapy and the maximum resting pressure, maximum squeeze pressure, and Wexner score were the outcome measures. Results: A decrease in elasticity was observed in 16/27 (59.3%) patients after chemoradiotherapy. Patients with and without elasticity decrease after chemoradiotherapy comprised the internal anal sphincter sclerosis and non-sclerosis groups, respectively. The maximum resting pressure post-chemoradiotherapy was significantly high in the internal anal sphincter sclerosis group (63.0 mmHg vs. 47.0 mmHg), and a majority had a worsening Wexner score (60.0% vs. 18.2%) compared with that of the non-sclerosis group. Decreasing elasticity (internal anal sphincter sclerosis) correlated with a higher maximum resting pressure (r = 0.36); no correlation was observed between the degree of elasticity change and maximum squeeze pressure. Conclusion: Internal anal sphincter sclerosis due to chemoradiotherapy may correlate to anorectal dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the surgical outcomes of para-aortic lymph node (PALN) dissection in patients with colorectal cancer and assessed the prognostic factors related to the survival. Methods: This single-center retrospective study included 31 patients with synchronous or metachronous PALN metastasis from colorectal cancer who underwent PALN dissection between January 2006 and December 2018. Results: Twenty-one patients had synchronous PALN metastasis, and 10 had metachronous PALN metastasis. Seven patients had either simultaneous distant metastasis or a history of distant metastasis other than PALN metastasis at the time of PALN dissection. Eighteen patients underwent adjuvant chemotherapy. The 5-year overall and recurrence-free survival rates were 54.2 and 17.2%, respectively. A multivariable analysis revealed that rectal cancer, metachronous PALN metastasis, and three or more pathological PALN metastases were significantly poor prognostic factors for the recurrence-free survival. Among patients with rectal cancer, lower rectal cancer and lateral pelvic lymph node metastasis were poor prognostic factors for the overall survival. Conclusion: Curative PALN dissection for PALN metastasis from colorectal cancer is feasible with favorable long-term outcomes. A multidisciplinary approach, including surgery and chemotherapy, is needed for colorectal cancer with PALN metastasis to improve the long-term outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Diaphragm ultrasonography is used to identify causes of diaphragm dysfunction. However, its correlation with pulmonary function tests, including maximal inspiratory (MIP) and expiratory pressures (MEP), remains unclear. This study investigated this relationship by measuring diaphragm thickness, thickening fraction (TF), and excursion (DE) using ultrasonography, and their relationship to MIP and MEP. It also examined the influence of age, sex, height, and BMI on these measures. Methods: We recruited healthy Japanese volunteers and conducted pulmonary function tests and diaphragm ultrasonography in a seated position. Diaphragm ultrasonography was performed during quiet breathing (QB) and deep breathing (DB) to measure the diaphragm thickness, TF, and DE. A multivariate analysis was conducted, adjusting for age, sex, height, and BMI. Results: Between March 2022 and January 2023, 109 individuals (56 males) were included from three facilities. The mean (standard deviation) MIP and MEP [cmH2O] were 72.2 (24.6) and 96.9 (35.8), respectively. Thickness [mm] at the end of expiration was 1.7 (0.4), TF [%] was 50.0 (25.9) during QB and 110.7 (44.3) during DB, and DE [cm] was 1.7 (0.6) during QB and 4.4 (1.4) during DB. Multivariate analysis revealed that only DE (DB) had a statistically significant relationship with MIP and MEP (p = 0.021, p = 0.008). Sex, age, and BMI had a statistically significant influence on relationships between DE (DB) and MIP (p = 0.008, 0.048, and < 0.001, respectively). Conclusion: In healthy adults, DE (DB) has a relationship with MIP and MEP. Sex, age, and BMI, but not height, are influencing factors on this relationship. [ABSTRACT FROM AUTHOR]

Background and Purpose: Fraction metabolized (fm) and fraction transported (ft) are important for understanding drug–drug interactions (DDIs) in drug discovery and development. However, current in vitro systems cannot accurately estimate in vivo fm due to inability to reflect the ft by efflux transporters (ft,efflux). This study demonstrates how CYP3A‐mediated DDI for CYP3A/P‐gp substrates can be predicted using Hu‐PXB mice as human liver chimeric mice. Experimental Approach: For estimating human in vitro fm by CYP3A enzyme (fm,CYP3A,in vitro), six drugs, including CYP3A/P‐gp substrates (alprazolam, cyclosporine, docetaxel, midazolam, prednisolone, and theophylline) and human hepatocytes were incubated with or without ketoconazole as a CYP3A inhibitor. We calculated fm,CYP3A,in vitro based on hepatic intrinsic clearance. To estimate human in vivo fm,CYP3A (fm,CYP3A,in vivo), we collected information on clinical DDI caused by ketoconazole for these six drugs. We calculated fm,CYP3A,in vivo using the change of total clearance (CLtotal). For evaluating the human DDI predictability, the six drugs were administered intravenously to Hu‐PXB and SCID mice with or without ketoconazole. We calculated the change of CLtotal caused by ketoconazole. We compared the CLtotal change in humans with that in Hu‐PXB and SCID mice. Key Results: The fm,CYP3A,in vitro was overestimated compared to the fm,CYP3A,in vivo. Hu‐PXB mice showed much better correlation in the change of CLtotal with humans (R2 = 0.95) compared to SCID mice (R2 = 0.0058). Conclusions and Implications: CYP3A‐mediated DDI can be predicted by correctly estimating human fm,CYP3A,in vivo using Hu‐PXB mice. These mice could be useful predicting hepatic fm and ft,efflux. [ABSTRACT FROM AUTHOR]

(1) Background: Although the diagnostic criteria for massive hemorrhage with organ dysfunction, such as disseminated intravascular coagulation associated with delivery, have been empirically established based on clinical findings, strict logic has yet to be used to establish numerical criteria. (2) Methods: A dataset of 107 deliveries with >2000 mL of blood loss, among 13,368 deliveries, was obtained from nine national perinatal centers in Japan between 2020 and 2023. Twenty-three patients had fibrinogen levels <170 mg/dL, which is the initiation of coagulation system failure, according to our previous reports. Three of these patients had hematuria. We used six machine learning methods to identify the borderline criteria dividing the fibrinogen/fibrin/fibrinogen degradation product (FDP) planes, using 15 coagulation fibrinolytic factors. (3) Results: The boundaries of hematuria development on a two-dimensional plane of fibrinogen and FDP were obtained. A positive FDP–fibrinogen/3–60 (mg/dL) value indicates hematuria; otherwise, the case is nonhematuria, as demonstrated by the support vector machine method that seemed the most appropriate. (4) Conclusions: Using artificial intelligence, the borderline criterion was obtained, which divides the fibrinogen/FDP plane for patients with hematuria that could be considered organ dysfunction in massive hemorrhage during delivery; this method appears to be useful. [ABSTRACT FROM AUTHOR]

The surface spectral absorptivity of surface-whitened mortars due to the occurrence of efflorescence (i.e., mortars whose surface was covered with calcium carbonate) was measured, and the relationship between the spectral absorptivity and inspection capability of active thermography inspection was investigated. The spectral absorptivity of mortars increased significantly at a wavelength of approximately 3000 nm regardless of the presence/absence of the discoloration. Experiments for mortar specimens using optical lights with wavelengths in the visible, short wavelength, and medium/long wavelength ranges showed that the heating efficiency and defect detection capability of active thermography inspection were correlated with the surface spectral absorptivity, and were higher when long wavelength light was used as a heater. Defects in the surface-whitened mortar specimen were detected more efficiently when the specimen was heated using a CO2 laser, whose wavelength is in the long wavelength range, than when using an optical light having a wavelength in the visible/short wavelength range. [ABSTRACT FROM AUTHOR]

Abstract Background The difference in prevalence of fatigue among postgraduate trainees between the United States and Japan is unknown. Methods A cross‐sectional survey using Iowa Fatigue Scale was administered on postgraduate trainees in two internal medicine residency programs in New York and five postgraduate residency programs in Japan. Results Of the 393 trainees, 135 (34%) completed the survey. Seventy‐seven (57%) were US trainees. Both fatigue (42% vs 81%) and severe fatigue (4% vs 19%) were more prevalent in Japan (P

Abstract Background Resistance to thyroid hormone (RTH) usually features a syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) without suppression of the typical high thyroid hormone levels. However, some patients with RTH show thyroid-stimulating hormone (TSH) suppression due to thyrotoxicosis. We report a case of painless thyroiditis in a patient with RTH that was misdiagnosed as Graves’ disease because of TSH-suppressed thyrotoxicosis. Case presentation A sixteen-year-old boy consulted a local general physician for fatigue. He had a goiter, and biochemical analysis showed TSH

Objective(s): Impairment of hippocampus function as a center for memory processing occurs due to stress. Centella asiatica L. (Gotu kola) is known to improve memory, intelligence, and neural protection although the precise mechanism is not well understood. This study aimed to investigate the effects of ethanol extracts of C. asiatica toward MAPK expression as down-stream signaling of brain-derived neurotrophic factor (BDNF). Materials and Methods: We performed a chronic electrical stress model on 20 male Sprague Dawley rats (2 months-old, 180–200 g). Rats were divided into four groups: normal control group (Control) which received distilled water, and three treatment groups receiving oral Gotu kola ethanol extracts in oral doses of 150 mg/kg BW (CeA150), 300 mg/kg BW (CeA300), and 600 mg/kg BW (CeA600) over four weeks. Memory acquisition was assessed with Morris water maze. Hippocampus was harvested, then extracted for protein and RNA analysis. MAPK proteins (p38, ERK1/2, JNK) were measured using Western blot, meanwhile, BDNF and TrkB receptor were analyzed with real-time PCR (RT-PCR). Results: CeA600 group revealed improvement of memory performance as shown by reduction in time and distance parameters compared to control during escape latency test. This finding associated with significant elevation of hippocampal BDNF protein and mRNA level with up-regulation of TrkB mRNA expression in CeA600 group compared to control. Western-blot analysis showed significant up-regulation of ERK1/2 protein level in CeA600 group (PConclusion: BDNF signaling through TrkB and ERK1/2 pathway contributes significantly to amelioration of memory performance after C. asiatica treatment in electrical stress model.

Summary: Colorectal surgery is associated with a high risk of perioperative venous thromboembolism (VTE), and this risk is especially high following colorectal cancer resection and surgery for inflammatory bowel disease. Previous analyses of large databases have reported the incidence of postoperative VTE in this population to be approximately 1.1%–2.5%. Therefore, to minimize this risk, patients should be offered appropriate prophylaxis, which may involve a combination of mechanical and pharmacologic prophylaxis with low-dose unfractionated heparin or low molecular weight heparin as recommended by several guidelines. Prior to initiation of treatment, appropriate risk stratification should be performed according to the patients' basic and disease-related as well as procedure-related risk factors, and post-operative factors. Furthermore, a risk-benefit calculation that takes into account patients’ VTE and bleeding risk should be performed prior to starting pharmacologic prophylaxis and to help determine the duration of treatment. Keywords: Colorectal cancer, Inflammatory bowel disease, Laparoscopic surgery, Venous thromboembolism

Summary: Background: It is unclear whether neoadjuvant chemoradiation for lower rectal cancer causes a deterioration in urinary function. This study aimed to prospectively compare the postoperative urinary function of patients with lower rectal cancer treated by surgery after neoadjuvant chemoradiation with that of patients treated with surgery alone. Method: Urinary function was assessed before treatment and 1, 3, and 6 months after surgery by calculating the changes in the scores of the seven items of the International Prostatic Symptom Score (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia) and Quality of life index. Results: Among 123 patients with lower rectal cancer treated with chemoradiotherapy plus surgery and surgery alone between 2014 and 2016, 29 eligible patients in the surgery after neoadjuvant chemoradiation group and 34 eligible patients in the surgery alone group were analyzed. The changes in each item score at 1, 3, and 6 months after surgery were similar between the two treatment groups. The scores of all items were already recovered at 6 months after surgery, except for weak stream and straining in the Surgery + chemoradiotherapy group and nocturia in the Surgery-alone group. Conclusion: Neoadjuvant chemoradiotherapy for lower rectal cancer did not affect postoperative urinary function. Keywords: Rectal cancer, Urinary function, Chemoradiation, Neoadjuvant, International prostatic symptom score

Abstract Background We examined whether inferior thyroid artery peak systolic velocity (ITA-PSV) predicts an increase in levothyroxine (LT4) dosage in pregnant women with Hashimoto’s thyroiditis. Methods Twenty-two women with Hashimoto’s thyroiditis who were planning and later achieved pregnancy or confirmed as pregnant were enrolled in this retrospective longitudinal observational study. ITA-PSV and thyroid volume were measured using ultrasonography. Serum concentrations of free thyroxine (F-T4), free triiodothyronine (F-T3), and thyroid stimulating hormone (TSH) were simultaneously determined. We adjusted LT4 dosage to maintain serum TSH at

Abstract Background The establishment of whole-slide imaging (WSI) as a medical diagnostic device allows that pathologists may evaluate mitotic activity with this new technology. Furthermore, the image digitalization provides an opportunity to develop algorithms for automatic quantifications, ideally leading to improved reproducibility as compared to the naked eye examination by pathologists. In order to implement them effectively, accuracy of mitotic figure detection using WSI should be investigated. In this study, we aimed to measure pathologist performance in detecting mitotic figures (MFs) using multiple platforms (multiple scanners) and compare the results with those obtained using a brightfield microscope. Methods Four slides of canine oral melanoma were prepared and digitized using 4 WSI scanners. In these slides, 40 regions of interest (ROIs) were demarcated, and five observers identified the MFs using different viewing modes: microscopy and WSI. We evaluated the inter- and intra-observer agreements between modes with Cohen’s Kappa and determined “true” MFs with a consensus panel. We then assessed the accuracy (agreement with truth) using the average of sensitivity and specificity. Results In the 40 ROIs, 155 candidate MFs were detected by five pathologists; 74 of them were determined to be true MFs. Inter- and intra-observer agreement was mostly “substantial” or greater (Kappa = 0.594–0.939). Accuracy was between 0.632 and 0.843 across all readers and modes. After averaging over readers for each modality, we found that mitosis detection accuracy for 3 of the 4 WSI scanners was significantly less than that of the microscope (p = 0.002, 0.012, and 0.001). Conclusions This study is the first to compare WSIs and microscopy in detecting MFs at the level of individual cells. Our results suggest that WSI can be used for mitotic cell detection and offers similar reproducibility to the microscope, with slightly less accuracy.

Abstract Background Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by thrombocytosis and a propensity for both thrombotic and hemorrhagic events. ET rarely occurs simultaneously with colorectal cancer. Here, we report a case of colorectal cancer in an ET patient treated using laparoscopic ileocecal resection. Case presentation A 40-year-old woman was admitted to our hospital after presenting with liver dysfunction. She had been previously diagnosed with ET; aspirin and anagrelide had been prescribed. Subsequent examination at our hospital revealed cecal cancer. Distant metastasis was absent; laparoscopic ileocecal resection was performed. Anagrelide was discontinued only on the surgery day. She was discharged on the seventh postoperative day without thrombosis or hemorrhage. However, when capecitabine and oxaliplatin were administered as adjuvant chemotherapy with continued anagrelide administration, she experienced hepatic dysfunction and thrombocytopenia; thus, anagrelide was discontinued. Five days later, her platelet count recovered. Subsequently, anagrelide and aspirin administration was resumed, without any adjuvant chemotherapy. Her liver function normalized gradually in 4 months. One-year post operation, she is well without tumor recurrence or new metastasis. Conclusions To our knowledge, this is the first report of laparoscopic colectomy performed on an ET patient receiving anagrelide. Our report shows that complications such as bleeding or thrombosis can be avoided by anagrelide administration. Contrastingly, thrombocytopenia due to anagrelide intake should be considered when chemotherapy that could cause bone marrow suppression is administered.

Physiologically‐based pharmacokinetic (PBPK) modeling allows assessment of the covariates contributing to the large pharmacokinetic (PK) variability of tacrolimus; these include multiple physiological and biochemical differences among patients. A PBPK model of tacrolimus was developed, including a virtual population with physiological parameter distributions reflecting renal transplant patients. The ratios of predicted to observed dose‐normalized maximum plasma concentration (Cmax), 0–12‐hour area under the concentration–time curve (AUC0–12 hour), and trough plasma concentration (Ctrough) ranged from 0.92‐fold to 1.15‐fold, indicating good predictive performance. The model quantitatively indicated the impact of cytochrome P450 (CYP)3A4 abundance, hematocrit, and serum albumin levels, in addition to CYP3A5 genotype status, on tacrolimus PK and associated variability. Age‐dependent change in tacrolimus trough concentration in pediatric patients was mainly attributed to the CYP3A ontogeny profile. This study demonstrates the utility of PBPK modeling as a tool for mechanistic and quantitative assessment of the impact of patient physiological differences on observed large PK variability.

Abstract Background Sarcopenia has become a serious disorder in modern society. Chronic kidney disease requiring dialysis and diabetes are some of the disorders that accelerate the onset and progression of sarcopenia. We, therefore, investigated the prevalence of sarcopenia in patients undergoing hemodialysis (HD) and confirmed the impact of diabetes mellitus (DM) on this population. Methods This study included 308 patients whose muscle strength and mass had been evaluated using handgrip strength and dual-energy X-ray absorptiometry, respectively. Sarcopenia was defined according to the criteria established by the Asian Working Group on Sarcopenia. In addition, this cohort had been followed up for 9 years. Results The prevalence of sarcopenia was 40% (37% in males and 45% in females) with gender differences being insignificant (p = 0.237). The DM morbidity rate was significantly higher in those with sarcopenia than in those without sarcopenia (41% vs. 27%, p = 0.015). Multivariate regression analyses showed that the presence of DM was an independent contributor to sarcopenia in patients undergoing HD (odds ratio 3.11; 95% confidence interval 1.63–5.93; p

Introduction: Acute and chronic insomnia can exacerbate type 2 diabetes mellitus (T2DM). We investigated suvorexant (an anti-insomnia drug that targets the orexin system) effects on sleep architecture and glucose metabolism in T2DM patients with insomnia. Materials and methods: This 7 day open-label, single-arm, intervention trial included 18 subjects with T2DM and insomnia. After 1 day acclimatization, daily glucose levels, sleep architecture, and autonomic nervous function were evaluated by continuous glucose monitoring (CGM), single-channel electroencephalography, and accelerometry, respectively. Results: Suvorexant treatment for 3 days significantly increased total sleep time and sleep efficiency, with partial suppression of sympathetic nerve activity. CGM-measured 24 h mean glucose level decreased significantly from 157.7 ± 22.9 to 152.3 ± 17.8 mg/dL, especially in the early glucose surge after the midnight nadir (from 28.3 ± 15.0 to 18.2 ± 9.9 mg/dL), and until supper with a significant improvement in homeostasis model assessment of insulin resistance from 4.0 ± 2.8 to 2.9 ± 1.6, respectively. Conclusions: Suvorexant treatment for insomnia of subjects with T2DM significantly improved CGM-measured daily glycemic control, which was associated with changes in sympathomimetic tone and/or improved insulin sensitivity. The amelioration of insomnia may therefore be a target for improving glycemic control in T2DM patients with insomnia. Keywords: Type 2 diabetes mellitus, Therapy for insomnia, Glycemic control, Insulin resistance, Dawn phenomenon, Autonomic nervous function