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Purpose: Laparoscopic hepatectomy (LH) is reported to cause less bleeding than open hepatectomy (OH) in obese patients; however, there are no reports addressing this issue in terms of body size-corrected bleeding. Methods: The subjects of this study were 31 obese and 149 non-obese patients who underwent LH and 32 obese and 245 non-obese patients who underwent OH. Bleeding corrected for body surface area (C-BL) was compared between the obese and non-obese patients who underwent each procedure. A multivariate analysis for increased C-BL was performed using the median C-BL for each procedure. Results: The median C-BL tended to be higher in the obese patients than in the non-obese patients who underwent LH, but there was no significant difference (72 vs. 42 mL/m2, P = 0.050). However, it was significantly higher in the obese patients than in the non-obese patients who underwent OH (542 vs. 333 mL/m2, P = 0.002). In a multivariate analysis, for OH, sectionectomy or more (OR 3.20, P < 0.001) and a high BMI (OR 2.76, P = 0.018) were found to be independent risk factors, whereas for LH, a high BMI was not (OR 1.58, P = 0.301). Conclusions: Obesity was identified as a risk factor for increased bleeding with body size correction for OH, but the risk was reduced for LH. [ABSTRACT FROM AUTHOR]

Background: Some aspects regarding the use of antiplatelet agents after coil embolization for subarachnoid hemorrhage during admission remain unclear. This study used diagnostic procedure combination (DPC) data to investigate the safety and prognostic effects of aspirin monotherapy and aspirin and P2Y12 inhibitor combination therapy on bleeding events. Methods: This cross-sectional study used Japanese DPC data to assess patients who were hospitalized with subarachnoid hemorrhage and received aspirin monotherapy and aspirin and P2Y12 inhibitor combination therapy between April 2016 and March 2020 (n = 4421). The aspirin monotherapy (A group, n = 2848) and aspirin and P2Y12 inhibitor combination therapy (AP group, n = 1573) groups were compared. The primary and secondary endpoints were the incidence of bleeding events and proportion of patients with a modified Rankin Scale (mRS) score ≤ 2 at discharge, respectively. Data was analyzed using multivariable adjusted logistic regression (significance level, 5%). Results: The adjusted odds ratio in AP group, with A group as the reference, for bleeding events and the proportion of patients with mRS score ≤ 2 at discharge were 0.97 (95% confidence interval [95% CI]: 0.75–1.26, p = 0.839) and 1.09 (95% CI: 0.92–1.29, p = 0.302), respectively. Conclusions: There are no differences in the incidence of bleeding events or good clinical outcomes (mRS score ≤ 2 at discharge) between aspirin monotherapy and aspirin and P2Y12 inhibitor combination therapy. [ABSTRACT FROM AUTHOR]

Flash-induced absorption changes in the Soret region arising from the [PD1PD2]+ state, the chlorophyll cation radical formed upon light excitation of Photosystem II (PSII), were measured in Mn-depleted PSII cores at pH 8.6. Under these conditions, TyrD is i) reduced before the first flash, and ii) oxidized before subsequent flashes. In wild-type PSII, when TyrD● is present, an additional signal in the [PD1PD2]+-minus-[PD1PD2] difference spectrum was observed when compared to the first flash when TyrD is not oxidized. The additional feature was "W-shaped" with troughs at 434 nm and 446 nm. This feature was absent when TyrD was reduced, but was present (i) when TyrD was physically absent (and replaced by phenylalanine) or (ii) when its H-bonding histidine (D2-His189) was physically absent (replaced by a Leucine). Thus, the simple difference spectrum without the double trough feature at 434 nm and 446 nm, seemed to require the native structural environment around the reduced TyrD and its H bonding partners to be present. We found no evidence of involvement of PD1, ChlD1, PheD1, PheD2, TyrZ, and the Cytb559 heme in the W-shaped difference spectrum. However, the use of a mutant of the PD2 axial His ligand, the D2-His197Ala, shows that the PD2 environment seems involved in the formation of "W-shaped" signal. [ABSTRACT FROM AUTHOR]

Background: Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant disorder that can affect multiple organs. Although gastrointestinal manifestations, such as neurofibromas and gastrointestinal stromal tumors (GISTs), can occur, appendiceal neurofibromas are extremely rare, with no documented cases of their occurrence following other gastrointestinal lesions. Herein, we report a case of an appendiceal neurofibroma following the resection of multiple small intestinal GISTs. Case presentation: A 68-year-old man with NF1 presented with melena and was diagnosed with anemia due to bleeding from multiple small intestinal GISTs. Laparoscopic three partial resection of the small intestine was performed to control the bleeding. Histopathologic examination revealed the proliferation of spindle cells that are positive for c-kit and Discovered on GIST-1, confirming the diagnosis of GIST. Two years later, a follow-up computed tomography (CT) scan revealed a progressively enlarging mass in the appendix with suspected invasion into the small intestine. Positron emission tomography/CT showed fludeoxyglucose accumulation in the tumor. Therefore, considering the possibility of malignancy, laparoscopic ileocecal resection with lymph node dissection was performed. Postoperatively, melena was observed, but the anemia did not progress and improved with fasting and hemostatic therapy. The patient was eventually discharged on postoperative day 8. Histopathologic examination revealed spindle cell proliferation with positivity for S-100, confirming the diagnosis of neurofibroma. Conclusions: Patients with NF1 can develop a variety of gastrointestinal lesions. Appendiceal neurofibroma can be difficult to diagnose preoperatively and differentiate from malignancy. Hence, surgical resection should be considered. [ABSTRACT FROM AUTHOR]

Background: Ampulla of Vater carcinoma (AVC) stage T3 was subdivided according to the degree of pancreatic invasion into T3a (≤ 0.5 cm) and T3b (> 0.5 cm) by the 8th edition of the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) cancer staging system. However, the differences in clinicopathological features and survival outcomes between the two categories have not been well discussed. Patients and Methods: We retrospectively analyzed 133 consecutive patients who underwent pancreatoduodenectomy for AVC at our institution between 2002 and 2020. Clinicopathological features and survival outcomes of patients with AVC were analyzed, with a focus on the depth of pancreatic invasion. In addition, the survival outcomes of patients with T3 AVC were compared with those of patients with resectable pancreatic head carcinoma (R-PhC) who underwent pancreatoduodenectomy during the same period. Results: The overall survival (OS) in patients with T3b AVC (n = 12) was significantly worse than that in patients with T3a AVC (n = 39) [median survival time (MST) 9.2 vs. 74.5 months, p < 0.001). A multivariate analysis identified T3b tumor (hazard ratio 5.64, p = 0.009) as an independent prognostic factor. The OS of patients with T3a AVC was significantly better than that of patients with R-PhC who received adjuvant chemotherapy (n = 276, MST 35.0 months, p = 0.007). In contrast, the OS of patients with T3b AVC tended to be worse than that of patients with R-PhC managed without adjuvant chemotherapy, although this difference was not statistically significant (n = 163; MST, 17.5; p = 0.140). Conclusions: AVC with > 0.5 cm invasion into the pancreas was associated with poor survival and represented advanced tumor progression to systemic disease. [ABSTRACT FROM AUTHOR]

Mutation profiling by next-generation sequencing (NGS) has facilitated understanding of the molecular pathogenesis of acute myeloid leukemia (AML), and has been incorporated into the new disease classification (International Consensus Classification; ICC) and risk classification (European LeukemiaNet [ELN] 2022; ELN2022). We compared disease subtypes between the previous disease classification (4th edition of the WHO classification; WHO-4) and the ICC in 91 patients with AML diagnosed at our institution. We also compared disease risk classifications using the previous risk classification (ELN2017) and the ELN2022. Targeted sequencing of bone marrow samples was conducted at Kyoto University. We found that entities under AML with recurrent genetic abnormalities were well-established, with almost no change from the WHO-4 to the ICC. In contrast, 16.7% of cases of AML, not otherwise specified in the WHO-4 were reclassified into AML with mutated TP53, and 36.7% were reclassified into AML with myelodysplasia-related gene mutations or cytogenetic abnormalities per the ICC. Meanwhile, the ELN2017 and ELN2022 showed no difference in concordance indexes in multivariate Cox regression analysis for progression-free and overall survival. The superiority of the ELN2022 over the ELN2017 could not be confirmed in our single-center retrospective study, and further investigation including multicenter prospective studies is needed. [ABSTRACT FROM AUTHOR]

IoT sensors are crucial for visualizing multidimensional and multimodal information and enabling future IT applications/services such as cyber-physical spaces, digital twins, autonomous driving, smart cities and virtual/augmented reality (VR or AR). However, IoT sensors need to be battery-free to realistically manage and maintain the growing number of available sensing devices. Here, we provide a novel sensor design approach that employs metasurfaces to enable multifunctional sensing without requiring an external power source. Importantly, unlike existing metasurface-based sensors, our metasurfaces can sense multiple physical parameters even at a fixed frequency by breaking classic harmonic oscillations in the time domain, making the proposed sensors viable for usage with limited frequency resources. Moreover, we provide a method for predicting physical parameters via the machine learning-based approach of random forest regression. The sensing performance was confirmed by estimating the temperature and light intensity, and excellent determination coefficients larger than 0.96 were achieved. Our study affords new opportunities for sensing multiple physical properties without relying on an external power source or requiring multiple frequencies, which markedly simplifies and facilitates the design of next-generation wireless communication systems. Metasurface-based sensors provide a battery-free sensing solution for maintaining numerous IoT devices with little human resources. However, the conventional method exploited resonant mechanisms associated with multiple physical parameters through different frequencies, although available frequencies were strictly limited. We report the first sensor design approach using circuit-based metasurfaces that offer a higher degree of freedom to design time-varying scattering profiles associated with multiple physical properties at a single frequency. Our prototype detects light intensity and temperature with an excellent determination coefficient above 0.96 via a machine-learning technique. [ABSTRACT FROM AUTHOR]

In cancer genome analysis, identifying pathogenic alterations and assessing their effects on oncogenic processes is important. Although whole exome sequencing (WES) can effectively detect such changes, driver alterations could not be identified in 27.8% of the cases, according to a previous study. The objectives of the present study were to evaluate the utility of whole genome sequencing (WGS) and clarify its differences with WES in terms of driver alteration detection. For this purpose, WGS analysis was conducted on 177 driverless WES samples, selected from 5,480 fresh frozen samples derived from 5,140 Japanese patients with cancer. These samples were selected as primary tumor, both WES and transcriptome profiling were performed, estimated tumor content of ≥ 30%, and no driver alterations were identified by WES. WGS identified driver and likely driver alterations in 68.4 and 22.6% of the samples, respectively. The most frequent alteration type was oncogene amplification, followed by tumor suppressor gene deletion and small variants located outside the coding region. In the remaining 9.0% of samples, no such signals were identified; therefore, further investigations are required. The current study clearly demonstrated the role and utility of WGS in identifying genomic alterations that contribute to tumorigenesis. [ABSTRACT FROM AUTHOR]

Purpose: Early-stage spondylolysis (ESS) is a common cause of acute low back pain (LBP) in adolescents. When treating patients with ESS, early diagnosis is essential, yet difficult without magnetic resonance imaging. This study evaluates a self-reported questionnaire for detecting ESS. Methods: We evaluated a total of 69 adolescents (≤ 18 years old) with acute LBP (≤ 1 month) with plain radiography, magnetic resonance imaging and a questionnaire including the following parameters: exercise frequency per week, daily training time, the necessity for stopping sports activity, pain-producing situations, pain quality, pain response to hyperextension or hyperflexion, pain location, and pain extent. Patients with obvious pathological findings other than ESS (e.g., disk herniation or infection) were excluded. The correlation of each question and gender, regarding ESS was determined, to evaluate the value of the originally developed questionnaire. Results: 24 out of 69 patients were diagnosed with ESS (ESS group), with a mean age of 13.9 years old and 21 males and 3 females in the group. 45 patients had NS-LBP, with a mean age of 14.6 years old, and 28 males and 17 females in the group. Correlation analyses showed weak associations between ESS and higher frequency of exercise per week, longer training time per day, and pain-producing situations. There was also a moderate association between ESS and male gender. Conclusion: Exercise frequency, training time, pain-provoking situations, and gender could be important factors to detect ESS within this questionnaire. [ABSTRACT FROM AUTHOR]

Objectives: Social jetlag (SJL), the discrepancy between an individual's inherent circadian rhythm and external social schedule, is associated with obesity. This study aimed to investigate whether SJL also influences body weight and body fat loss during dieting. Methods: This was an observational study from 2015 to 2018 with participants who had joined an exercise and nutrition program at a private personal training gym. Data from 11,829 individuals provided by the gym along with their sleep logs were analyzed. Differences in change in body mass index (BMI) and body fat percentage (%body fat) were compared by the degree of SJL. Regression was conducted for the change in BMI and %body fat on SJL, adjusted for gender, age, engagement duration in the program, initial BMI, initial %body fat, chronotype, and dietary intakes. Results: The subjects comprised 3,696 men and 8,133 women with a mean age of 40.4 years. Greater SJL was associated with a lower efficacy of BMI and %body fat reduction. The change in BMI (+ 0.56 / hour: SJL) and %body fat (+ 1.40 / hour: SJL) was associated with SJL after adjusting for each variable including dietary intake. Conclusion: SJL was associated with the effect of exercise and nutrition instruction on BMI and body fat reduction, even after adjustment for covariates related to dietary intake. Maintaining consistent sleep–wake rhythms may be crucial for enhancing the efficacy of weight loss programs. [ABSTRACT FROM AUTHOR]

Abstract Inosine monophosphate dehydrogenase (IMPDH) is a rate‐limiting enzyme in de novo guanine nucleotide synthesis pathway. Although IMPDH inhibitors are widely used as effective immunosuppressants, their antitumor effects have not been proven in the clinical setting. Here, we found that acute myeloid leukemias (AMLs) with MLL‐fusions are susceptible to IMPDH inhibitors in vitro. We also showed that alternate‐day administration of IMPDH inhibitors suppressed the development of MLL‐AF9‐driven AML in vivo without having a devastating effect on immune function. Mechanistically, IMPDH inhibition induced overactivation of Toll‐like receptor (TLR)‐TRAF6‐NF‐κB signaling and upregulation of an adhesion molecule VCAM1, which contribute to the antileukemia effect of IMPDH inhibitors. Consequently, combined treatment with IMPDH inhibitors and the TLR1/2 agonist effectively inhibited the development of MLL‐fusion AML. These findings provide a rational basis for clinical testing of IMPDH inhibitors against MLL‐fusion AMLs and potentially other aggressive tumors with active TLR signaling.

Eight peaks of coronavirus disease 2019 (COVID-19) outbreak occurred in Japan, each associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. The National Epidemiological Surveillance of Infectious Diseases (NESID) analyzed viral genome sequences from symptomatic patients and submitted the results to GISAID. Meanwhile, commercial testing services occasionally sequence samples from asymptomatic individuals. We compared a total of 1248 SARS-CoV-2 full-genome sequences obtained from the SB Coronavirus Inspection Center Corp. (SBCVIC) during Japan's seventh wave, which was dominated by Omicron variants, with 1764 sequences obtained in Japan from GISAID during the same period using chronological phylogenies and molecular transmission networks. The number of SBCVIC sequences was consistent with the number of cases reported by NESID. The SBCVIC detected a shift in the PANGO lineage from BA.2 to BA.5 earlier than that of GISAID. BA.2 lineages from the SBCVIC were distributed at different locations in the transmission network dominated by GISAID entries, whereas BA.5 lineages from SBCVIC and GISAID often formed distinct subclusters. Test-based sentinel surveillance of asymptomatic individuals may be a more manageable approach compared to notifiable disease surveillance; however, it may not necessarily capture all infection populations throughout Japan. [ABSTRACT FROM AUTHOR]

Purpose: Oral mucositis is a severe adverse event in patients undergoing chemotherapy and radiotherapy that may lead to the termination of cancer treatment. This study aimed to elucidate the relationship between salivary inflammatory mediators and oral mucositis in patients undergoing chemotherapy. Methods: This prospective cohort study included 167 patients who underwent chemotherapy at our institution between June 2020 and November 2023. We evaluated the association between chemotherapy-induced oral mucositis and salivary inflammatory mediators using multiple comparison tests and logistic regression analyses. Results: Of the 167 patients, 67 (40.1%) had oral mucositis. Dunn’s multiple comparison test revealed that interleukin-6 was significantly higher in oral mucositis of grades 2 and ≥ 3 (P < 0.01) and tumor necrosis factor (TNF)-α was significantly higher in oral mucositis of grades 3–4 (P < 0.01). Logistic regression analysis showed that the risk of oral mucositis was significantly higher for tumor necrosis factor (TNF)-α > 4.4 pg/mL than for TNF-α ≤ 4.4 pg/mL (adjusted odds ratio, 2.4; 95% confidence interval, 1.1–5.3; P = 0.03). Conclusion: Saliva is useful in evaluating inflammation in patients with chemotherapy-induced oral mucositis. Furthermore, TNF-α may be a predictive marker for the severity of oral mucositis in patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The prognostic impact of positive peritoneal lavage cytology (CY+) in patients with perihilar cholangiocarcinoma (PHC) remains unclear. The present study investigated the clinical significance of primary tumor resection of CY+ PHC. Methods: We retrospectively evaluated 282 patients who underwent surgery for PHC between September 2002 and March 2022. The patients' clinicopathological characteristics and survival outcomes were compared between the CY negative (CY−) resected (n = 262), CY+ resected (n = 12), and CY+ unresected (n = 8) groups. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival. Results: The expected residual liver volume was significantly higher in the CY+ resected group (61%) than in the CY− resected (47%) and CY+ unresected (37%) groups (p = 0.004 and 0.007, respectively). The CY+ resected group had a higher administration rate of postoperative therapy than the CY− resected group (58% vs. 16%, p = 0.002). Overall survival of the CY+ resected group was similar to that of the CY− resected group (median survival time [MST] 44.5 vs. 44.6, p = 0.404) and was significantly better than that of the CY+ unresected group (MST 44.5 vs. 17.1, p = 0.006). CY positivity was not a prognostic factor according to a multivariate analysis in patients with primary tumor resection. Conclusions: The CY+ resected group showed better survival than the CY+ unresected group and a similar survival to that of the CY− resected group. Resection of the primary tumor with CY+ PHC may improve the prognosis in selected patients. [ABSTRACT FROM AUTHOR]

Introduction: Symptom status and treatment changes among patients with chronic obstructive pulmonary disease (COPD) using inhaler treatment in real-world clinical settings are not well understood, particularly according to class of treatment. We investigated the proportion of symptomatic patients among those with COPD using inhaler treatment, based on COPD Assessment Test (CAT) scores in clinical practice, and changes in inhaler treatments and symptoms at 1-year follow-up. Methods: This was a retrospective analysis of data from a multicenter, prospective cohort study conducted at medical institutions with respiratory specialists in Japan. The primary endpoint was the proportion of patients with CAT scores ≥ 10 or < 10 in each inhaler treatment group at registration. Results: Of 414 patients in the full analysis set, 76 (18.4%), 261 (63.0%), and 77 (18.6%) were using long-acting muscarinic antagonist (LAMA), LAMA + long-acting β2-agonist (LABA), and inhaled corticosteroids (ICS) + LABA, respectively, at registration. The proportions of patients with CAT scores ≥ 10 or < 10 per inhaler treatment group at registration, respectively, were 32.9% and 67.1% in the LAMA group, 55.0% and 45.0% in the LAMA + LABA group, and 50.0% and 50.0% in the ICS + LABA group. Most patients (> 75%) in each inhaler treatment group showed no change in inhaler treatment at 1 year, regardless of their CAT score at registration. Approximately 70–80% of patients with CAT scores ≥ 10 at registration still had CAT scores ≥ 10 at 1 year; 10–30% of patients with CAT scores < 10 at registration had CAT scores ≥ 10 at 1 year. Conclusion: In real-world Japanese clinical practice, a considerable proportion of patients have persistent symptoms (CAT score ≥ 10) despite using mono or dual inhaler treatment; > 75% of symptomatic patients with COPD using inhaler treatment did not undergo treatment escalation at 1-year follow-up and remained symptomatic. Trial Registration: ClinicalTrials.gov identifier, NCT05903989. [ABSTRACT FROM AUTHOR]

Photoisomerization is a key photochemical reaction in microbial and animal rhodopsins. It is well established that such photoisomerization is highly selective; all-trans to 13-cis, and 11-cis to all-trans forms in microbial and animal rhodopsins, respectively. Nevertheless, unusual photoisomerization pathways have been discovered recently in microbial rhodopsins. In an enzymerhodopsin NeoR, the all-trans chromophore is isomerized into the 7-cis form exclusively, which is stable at room temperature. Although, the 7-cis form is produced by illumination of retinal, formation of the 7-cis form was never reported for a protonated Schiff base of all-trans retinal in solution. Present HPLC analysis of retinal oximes prepared by hydroxylamine reaction revealed that all-trans and 7-cis forms cannot be separated from the syn peaks under the standard HPLC conditions, while it is possible by the analysis of the anti-peaks. Consequently, we found formation of the 7-cis form by the photoreaction of all-trans chromophore in solution, regardless of the protonation state of the Schiff base. Upon light absorption of all-trans protonated retinal Schiff base in solution, excited-state relaxation accompanies double-bond isomerization, producing 7-cis, 9-cis, 11-cis, or 13-cis form. In contrast, specific chromophore-protein interaction enforces selective isomerization into the 13-cis form in many microbial rhodopsins, but into 7-cis in NeoR. [ABSTRACT FROM AUTHOR]

A 73-year-old Japanese man with a history of distal biliary cancer treated by pancreatoduodenectomy developed pancreatic acinar cell carcinoma (PACC) treated by remnant pancreatectomy and adjuvant chemotherapy. Thirteen months after surgery, multiple liver metastases developed and FOLFOX chemotherapy was initiated. Based on the PACC diagnosis and a positive family history for breast and ovarian cancer genetic testing was performed which revealed a pathogenic germline BRCA2 variant (c.8629G > T, p.Glu2877Ter). Olaparib therapy was initiated and the metastases responded well (partial response). PACC is a BRCA2-associated cancer which may respond well to PARP inhibitors. [ABSTRACT FROM AUTHOR]

Purpose: Despite their similar clinical characteristics, appendiceal diverticulitis (AD) and acute appendicitis (AA) are pathologically distinct. This study compared the clinical features of AD and AA and identified relevant risk factors. Methods: Patients who underwent appendectomy with a preoperative diagnosis of either AD or AA were categorized based on histopathological findings. The two groups were compared in terms of various clinical factors. Results: Among the 854 patients included in the study, a histopathological evaluation revealed 49 and 805 cases of AD and AA, respectively. A univariate analysis demonstrated that AD was more prevalent than AA among older, taller, and heavier males. A multivariate analysis revealed that male sex, a white blood cell (WBC) count < 13.5 × 103/μL, an eosinophil count ≥ 0.4%, and a mean corpuscular volume (MCV) ≥ 91.6 fL were significant factors differentiating AD from AA. In addition, pathological AD emerged as an independent risk factor for abscess and/or perforation. Conclusions: AD was associated with an older age, robust physique, and significant risk of abscess and/or perforation despite a low WBC count. In addition to imaging modalities, the preoperative factors of male sex, a WBC count < 13.5 × 103/μL, an eosinophil count ≥ 0.4%, and a MCV ≥ 91.6 fL may be useful for distinguishing AD from AA. [ABSTRACT FROM AUTHOR]

Psychological research on human motivation repeatedly observed that approach goals (i.e., goals to attain success) increase task enjoyment and intrinsic motivation more strongly than avoidance goals (i.e., goals to avoid failure). The present study sought to address how the reward network in the brain—including the striatum and ventromedial prefrontal cortex—is involved when individuals engage in the same task with a focus on approach or avoidance goals. Participants reported stronger positive emotions when they focused on approach goals, but stronger anxiety and disappointment when they focused on avoidance goals. The fMRI analyses revealed that the reward network in the brain showed similar levels of activity to cues predictive of approach and avoidance goals. In contrast, the two goal states were associated with different patterns of activity in the visual cortex, hippocampus, and cerebellum during success and failure outcomes. Representation similarity analysis further revealed shared and different representations within the striatum and vmPFC between the approach and avoidance goal states, suggesting both the similarity and uniqueness of the mechanisms behind the two goal states. In addition, the distinct patterns of activation in the striatum were associated with distinct subjective experiences participants reported between the approach and the avoidance conditions. These results suggest the importance of examining the pattern of striatal activity in understanding the mechanisms behind different motivational states in humans. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to clarify the responsiveness and minimal clinically important difference (MCID) of the 6-minute walk distance (6MWD) from before and 1 week after surgery in patients with colorectal cancer (CRC). Methods: This retrospective cohort study enrolled 97 patients with primary CRC scheduled for surgery. An anchor-based approach estimated the MCID of the 6MWD, with postoperative physical recovery and EuroQol 5-dimension 5L questionnaire assessments serving as anchors. Effect size (ES) and standardized response mean (SRM) of the 6MWD were calculated to evaluate responsiveness, and the receiver operating characteristic (ROC) curve was used to estimate the MCID of the 6MWD. Results: Of the 97 patients, 72 were included in the analysis. The absolute value of ES and SRM of the 6MWD were 0.69 and 0.91, respectively. The ROC curve indicated that the optimal cut-off values for estimating the MCID of the 6MWD were -60 m (area under the curve [AUC] = 0.753 [95% CI: 0.640−0.866]) and -75 m (AUC = 0.870 [95% CI: 0.779−0.961]) at each anchor. Conclusion: From before to 1 week after surgery, the responsiveness of the 6MWD was favorable, and the MCID of the 6MWD was -75 to -60 m in patients with CRC. [ABSTRACT FROM AUTHOR]

The international prognostic index (IPI) system has been widely used to predict prognosis in diffuse large B-cell lymphoma (DLBCL). However, this system categorizes DLBCL patients into four risk groups, and cannot optimize individualized prognosis. In addition, other clinicopathological factors, such as molecular aberrations, are not incorporated into the system. To partly overcome these weak points, we developed nomograms to predict individual patient survival. We also incorporated MYD88L265P and CD79BY196 mutations into the nomograms since these mutations are associated with a worse prognosis and their signaling pathways have been highlighted as a therapeutic target. We analyzed 302 DLBCL cases for which multivariate analysis by Cox proportional hazard regression was performed. Nomograms for progression-free survival (PFS) and overall survival (OS) were constructed and assessed by a concordance index (C-index). The nomograms were also evaluated using an open external dataset (n = 187). The MYD88L265P and/or CD79BY196 (MYD88/CD79B) mutation was detected in 62/302 patients. The nomograms incorporating IPI factors exhibited a C-index of 0.738 for PFS and a C-index of 0.765 for OS. The nomograms incorporating IPI factors and the MYD88/CD79B mutation showed a C-index of 0.745 for PFS and a C-index of 0.769 for OS. The nomograms we created were evaluated using an external dataset and were well validated. The present nomograms incorporating IPI factors and the MYD88/CD79B mutation have sufficient discrimination ability, and may effectively predict prognosis in DLBCL patients. The prognostic models we have presented here may help clinicians personalize prognostic assessments and clinical decisions. [ABSTRACT FROM AUTHOR]

The preference for colours has profound impacts on the fitness of visually oriented species, influencing the search for food resources and mates of better quality while also modulating various physiological and behavioural features. Such processes may be more important to sexually dimorphic species, especially coloured ones since visual signals play an important role in intra- and intersexual communication. Amazon small streams vary widely regarding the amount of dissolved organic carbon resulting in black (red-biased) and clear (mostly transparent) water types. The sailfin tetra Crenuchus spilurus is a small sexually dimorphic species composed of two main genetic lineages that live in black and clear water types. Recently, we have shown that the female sexual preference for male ornaments colouration differs between individuals inhabiting black and clear water types. Females from black waters do not choose males primarily based on colouration under strongly red-biased lighting, but females from clear waters do, which suggests that the importance of red colours for sexual behaviour differs between lineages of the sailfin tetra. Here, we evaluated the sailfin tetra female environmental colour preference through the choice between a red and a full spectrum illuminated environments. Females from black waters and clear waters preferred red-lightened environments. Such results suggest that the females are attracted to the red colouration outside the context of mating, irrespective of the prevailing lighting condition of their native environment. This preference for red illuminated environments may be important for several processes, including physiological and behavioural features. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the recovery of the Japanese orthopedic association back pain evaluation questionnaire (JOABPEQ) scores and 6 min walk distance (6MWD) in patients after surgery for lumbar spinal stenosis and identified the items among 25 questions of JOABPEQ that showed recovery. Methods: A total of 227 patients (average age 71.5 years; SD: 7.5; 121 men) were included from a single center. The outcome measures were JOABPEQ, visual analog scale (VAS), and 6MWD and obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Mixed-model repeated measures were used to compare the variables at each time point between the surgery groups. Results: The JOABPEQ, VAS, and 6MWD scores generally improved at 1 month postoperatively compared with those obtained preoperatively, and some parameters further improved at 3 months. However, improvement in the lumbar spine dysfunction item of JOABPEQ was delayed, showing improvement at 3 months postoperatively for decompression surgery (average score: pre, 64.6; 3 months, 78.5) and 6 months postoperatively for fusion surgery (average score: Pre, 64.3; 6 months, 77.1). Responses to the individual JOABPEQ questions generally improved after surgery. No significant changes in lumbar spine dysfunction occurred in the fusion group. Conclusion: Our results demonstrated the early postoperative recovery course of JOABPEQ and 6MWD. In the fusion group, significant changes in lumbar spine dysfunction started at 6 months postoperatively. These findings could help medical staff explain postoperative recovery to patients after lumbar spinal stenosis surgery and in their decision making regarding surgery. [ABSTRACT FROM AUTHOR]

Common extrahepatic metastasis sites of hepatocellular carcinoma (HCC) are the lungs, adrenal glands, and bones. Herein, we report a rare case of metastatic gastric, pancreatic, and renal tumors from HCC simultaneously, and review the relevant literature. A 75-year-old woman presented with right hypochondralgia, appetite loss, and weight loss. Computed tomography revealed suspected metastatic liver, lung, and renal tumors. A blood test revealed a leukocyte count of 26,210/μL and a high inflammatory reaction. As sepsis was suspected, the patient was referred to our hospital. Gadolinium–ethoxybenzyl–diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging revealed a hypovascular liver tumor that was suspected to be metastatic. Upper gastrointestinal endoscopy revealed two suspected metastatic gastric tumors. Liver and gastric tumor biopsies revealed poor carcinoma in both. The patient's condition gradually worsened and she died on day 8 of the illness. Based on autopsy findings, the patient was finally diagnosed with metastatic gastric and renal tumors originating from HCC. Additionally, a metastatic pancreatic tumor originating from the HCC was identified during autopsy. The pathological diagnosis of the pulmonary lesion was primary lung adenocarcinoma. In conclusion, HCC should be suspected in cases with multiple metastases of unknown primary lesions. [ABSTRACT FROM AUTHOR]

Lymph node metastasis, primarily caused by the migration of oral squamous cell carcinoma (OSCC) cells, stands as a crucial prognostic marker. We have previously demonstrated that EP4, a subtype of the prostaglandin E2 (PGE2) receptor, orchestrates OSCC cell migration via Ca2+ signaling. The exact mechanisms by which EP4 influences cell migration through Ca2+ signaling, however, is unclear. Our study aims to clarify how EP4 controls OSCC cell migration through this pathway. We find that activating EP4 with an agonist (ONO-AE1-473) increased intracellular Ca2+ levels and the migration of human oral cancer cells (HSC-3), but not human gingival fibroblasts (HGnF). Further RNA sequencing linked EP4 to calmodulin-like protein 6 (CALML6), whose role remains undefined in OSCC. Through protein-protein interaction network analysis, a strong connection is identified between CALML6 and calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), with EP4 activation also boosting mitochondrial function. Overexpressing EP4 in HSC-3 cells increases experimental lung metastasis in mice, whereas inhibiting CaMKK2 with STO-609 markedly lowers these metastases. This positions CaMKK2 as a potential new target for treating OSCC metastasis. Our findings highlight CALML6 as a pivotal regulator in EP4-driven mitochondrial respiration, affecting cell migration and metastasis via the CaMKK2 pathway. EP4 receptor enhances OSCC cell migration through increased Ca2+ signaling, linking to CALML6 and the CaMKK2 pathway. This process promotes mitochondrial function and metastasis, with CaMKK2 emerging as a potential target for OSCC treatment. [ABSTRACT FROM AUTHOR]

In this paper, we prove the existence of a reservoir that has a finite-dimensional output and makes the reservoir computing model universal. Reservoir computing is a method for dynamical system approximation that trains the static part of a model but fixes the dynamical part called the reservoir. Hence, reservoir computing has the advantage of training models with a low computational cost. Moreover, fixed reservoirs can be implemented as physical systems. Such reservoirs have attracted attention in terms of computation speed and energy consumption. The universality of a reservoir computing model is its ability to approximate an arbitrary system with arbitrary accuracy. Two sufficient reservoir conditions to make the model universal have been proposed. The first is the combination of fading memory and the separation property. The second is the neighborhood separation property, which we proposed recently. To date, it has been unknown whether a reservoir with a finite-dimensional output can satisfy these conditions. In this study, we prove that no reservoir with a finite-dimensional output satisfies the former condition. By contrast, we propose a single output reservoir that satisfies the latter condition. This implies that, for any dimension, a reservoir making the model universal exists with the output of that specified dimension. These results clarify the practical importance of our proposed conditions. [ABSTRACT FROM AUTHOR]

The purpose of this study is to clarify whether swallowing function can be inferred from grip strength. Based on the diagnostic criteria of sarcopenia, patients were divided into two groups according to grip strength, and it was analyzed whether there was a difference in the evaluation index for swallowing function between the two groups. Among the cases requesting evaluation of swallowing function from June 10, 2020 to October 28, 2020, 83 cases (mean age: 71.7 years, 59 males and 24 females) who received assessment tests and swallowing endoscopy were included. According to the diagnostic criteria for grip strength in the Asian working group in Sarcopenia, less than 28 kgf and 18 kgf were defined as the weak group for men and women, respectively. Hyodo scores, repeated salivary swallowing tests (RSST), maximum vocalization time (MPT), and dysphagia severity classification (DSS) were compared between the two groups. Of the 83 patients, 29 and 54 were in the normal group and weak group, respectively. In all indicators, the normal group showed significantly better results than the weak group: Hyodo score (2.4 vs. 4.0, p < 0.01), RSST (4.1 times vs. 2.4 times, p < 0.01), MPT (12.1 s vs. 5.9 s, p < 0.001), DSS (4.5 vs. 5.9, p < 0.001), respectively. In multiple regression analysis with DSS as the dependent variable, grip strength was a significant independent variable of DSS even after adjusting for age, gender, and body mass index. Grip strength assessment based on sarcopenia criteria can be a useful tool for estimating swallowing function. [ABSTRACT FROM AUTHOR]

Disruption of a link or set of links due to disasters degrades the performance of a transport network. In particular, if all commonly used routes are disrupted, users will be forced to take huge detours. This paper introduces a new concept called "stem of path" (SoP), which represents a set of links capable of capturing the variety of paths between two nodes. The SoP is derived through the enumeration of the minimum cuts weighted by the link selection probability between origin–destination pairs. An application in the Sioux Falls network confirms that SoP is a set of links that, when disrupted, increases the travel time between two nodes. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prognostic impact and predictors of persistent renal dysfunction in acute kidney injury (AKI) after an emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). A total of 877 patients who underwent emergency PCI for AMI were examined. AKI was defined as serum creatinine (SCr) ≥ 0.3 mg/dL or ≥ 50% from baseline within 48 h after PCI. Persistent AKI was defined as residual impairment of SCr ≥ 0.3 mg/dL or ≥ 50% from baseline 1 month after the procedure. The primary outcome was the composite endpoints of death, myocardial infarction, hospitalization for heart failure, stroke, and dialysis. AKI and persistent AKI were observed in 82 (9.4%) and 25 (2.9%) patients, respectively. Multivariate Cox proportional hazards analysis demonstrated that persistent AKI, but not transient AKI, was an independent predictor of primary outcome (hazard ratio, 4.99; 95% confidence interval, 2.30–10.8; P < 0.001). Age > 75 years, left ventricular ejection fraction < 40%, a high maximum creatinine phosphokinase MB level, and bleeding after PCI were independently associated with persistent AKI. Persistent AKI was independently associated with worse clinical outcomes in patients who underwent emergency PCI for AMI. Advanced age, poor cardiac function, large myocardial necrosis, and bleeding were predictors of persistent AKI. [ABSTRACT FROM AUTHOR]

The relationship between oral functions and dementia was examined in 7384 older adults (age ≥ 75 years) who visited a dental clinic in Gifu, Japan. Participants without dementia in a baseline survey in April 2018 were followed until March 2021. As oral functions, chewing function, tongue and lip function, and swallowing function were assessed by self-administered questionnaire, by oral diadochokinesis test, and by repetitive saliva swallowing test, respectively. The presence of systemic diseases was based on data obtained from the National Database of Health Insurance of Japan. At follow-up, 415 (6%) participants were diagnosed with dementia. Multivariate logistic regression analyses showed the presence of dementia at follow-up was associated with female (odds ratio [OR] 1.386; 95% confidence interval [CI] 1.117–1.719), age (OR 1.078; CI 1.056–1.101), regular dental checkups (absence; OR 1.452; CI 1.180–1.788), brushing frequency ≥ twice/day (absence; OR 1.510; CI 1.194–1.911), decayed teeth (presence; OR 1.328; CI 1.071–1.648), swallowing function (poor; OR 1.484; CI 1.135–1.939) at baseline. It was found that poor swallowing function was associated with the future onset of dementia. [ABSTRACT FROM AUTHOR]

Mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) are rare tumors recently characterized by the presence of both neuroendocrine and non-neuroendocrine components within the same tumor tissue. Although MiNEN found their place in the WHO classification for various organs, this composite tumor in the head and neck region remains exceptionally rare. We present a case of primary oral MiNEN in a 64-year-old male located on the left side of lower gingiva. Biopsy raised suspicion of neuroendocrine carcinoma (NEC) and the patient underwent partial mandibulectomy. The resected specimen showed two distinct components of NEC and squamous cell carcinoma (SCC) with the confirmation of immunohistochemical markers. There has been no sign of recurrence nor metastasis 6 years after the surgery. In addition, we have conducted a review of published cases with potential relevance to this entity, resulting in five cases. The diverse terminology reinforces the need for a standardized classification system of oral/head and neck MiNENs. [ABSTRACT FROM AUTHOR]

Background: Approximately a decade has passed since the addition of venous thromboembolism to the list of significant adverse reactions of antipsychotic drugs. However, only a few studies have investigated the relationship between antipsychotic use and venous thromboembolism in the Japanese population. Purpose: We aimed to evaluate the risk of recurrent venous thromboembolism in users of antipsychotic drugs and update the evidence on venous thromboembolism in the Japanese population. Methods: A cross-sectional retrospective analysis of data from a large Japanese claims database, managed by Medical Data Vision Co. Ltd., was conducted. Adult patients who experienced venous thromboembolism between October 2014 and September 2018 in acute care hospitals were identified. The risk of recurrent venous thromboembolism was evaluated with logistic regression using demographic variables. The data of patients using antipsychotic drugs within specific therapeutic classes were also evaluated. Results: We included 8960 patients (mean age, 69 years; 59.2% female). Recurrent venous thromboembolism was observed in 686 patients (7.7%). The risk of recurrent venous thromboembolism was significantly higher in younger patients [< 65 years: reference; 65–74 years: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66–0.99, p = 0.04; ≥ 75 years: OR 0.77, 95% CI 0.64–0.94, p = 0.01], those with history of surgery (OR 1.39, 95% CI 1.18–1.65, p = 0.01), and anticoagulant users (OR 2.25, 95% CI 1.46–3.48, p = 0.01) and was significantly lower in the presence of comorbidities (OR 0.68, 95% CI 0.58–0.81, p< 0.01) and fractures (OR 0.49, 95% CI 0.26–0.94, p = 0.03). Long-term antipsychotic drug prescriptions (> 14 days) were associated with a higher risk of venous thromboembolism than short-term prescriptions (≤ 14 days) (OR 1.56, 95% CI 1.04–2.34, p = 0.03). Conclusions: In patients with a history of venous thromboembolism, particular attention should be paid to recurrence in younger patients. If antipsychotic drugs are prescribed for > 14 days to patients with a history of venous thromboembolism, they should be administered carefully, guided by reported findings. Further evaluations using different databases or populations are required to generalize the findings of this study. [ABSTRACT FROM AUTHOR]

During the hibernation season, Arctic ground squirrels (AGS) experience extreme temperature fluctuations (body temperature, Tb, as low as − 3 °C), during which they are mostly physically inactive. Once Tb reaches ~ 15 °C during interbout arousals, hibernators recruit skeletal muscle (SkM) for shivering thermogenesis to reach Tb of ~ 35 °C. Polyunsaturated fatty acids (PUFA) in the diet are known to influence SkM function and metabolism. Recent studies in the cardiac muscle of hibernators have revealed that increased levels of ω-6 and the ω-6:ω-3 PUFA ratio correlate with sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and hibernation status. We hypothesized that diet (increased ω-6:ω-3 PUFA ratio) and torpor status are important in the regulation of the SERCA pump and that this may improve SkM performance during hibernation. Ex vivo functional assays were used to characterize performance changes in SkM (diaphragm) from AGS fed the following diets. (1) Standard rodent chow with an ω-6:ω-3 ratio of 5:1, or (2) a balanced diet with an ω-6:ω-3 ratio of 1:1 that roughly mimics wild diet. We collected diaphragms at three different stages of hibernation (early torpor, late torpor, and arousal) and evaluated muscle function under hypothermic temperature stress at 4 °C, 15 °C, 25 °C, and 37 °C to determine functional resilience. Our data show that torpid animals fed standard rodent chow have faster SkM relaxation when compared to the balanced diet animals. Furthermore, we discovered that standard rodent chow AGS during torpor has higher SkM relaxation kinetics, but this effect of torpor is eliminated in balanced diet AGS. Interestingly, neither diet nor torpor influenced the rate of force development (rate of calcium release). This is the first study to show that increasing the dietary ω-6:ω-3 PUFA ratio improves skeletal muscle performance during decreased temperatures in a hibernating animal. This evidence supports the interpretation that diet can change some functional properties of the SkM, presumably through membrane lipid composition, ambient temperature, and torpor interaction, with an impact on SkM performance. [ABSTRACT FROM AUTHOR]

In many sexually reproducing organisms, oocytes are fundamentally fertilized with one sperm. In Caenorhabditis elegans, chitin layer formation after fertilization by the EGG complex is one of the mechanisms of polyspermy block, but other mechanisms remain unknown. Here, we demonstrate that MARC-3, a membrane-associated RING-CH-type ubiquitin ligase that localizes to the plasma membrane and cortical puncta in oocytes, is involved in fast polyspermy block. During polyspermy, the second sperm entry occurs within approximately 10 s after fertilization in MARC-3-deficient zygotes, whereas it occurs approximately 200 s after fertilization in egg-3 mutant zygotes defective in the chitin layer formation. MARC-3 also functions in the selective degradation of maternal plasma membrane proteins and the transient accumulation of endosomal lysine 63-linked polyubiquitin after fertilization. The RING-finger domain of MARC-3 is required for its in vitro ubiquitination activity and polyspermy block, suggesting that a ubiquitination-mediated mechanism sequentially regulates fast polyspermy block and maternal membrane protein degradation during the oocyte-to-embryo transition. In many sexually reproducing animals, the oocyte fuses with only one sperm during fertilization. Here, the authors show that C. elegans MARC-3, a membrane-associated RING-CH-type ubiquitin ligase, regulates polyspermy block after fertilization and maternal membrane protein degradation during the oocyte-to-embryo transition. [ABSTRACT FROM AUTHOR]

We present the results of 27 Al-nuclear magnetic resonance (NMR) studies of Si-substituted PrTi 2 Al 20 in order to clarify the magnetic and electronic properties at low temperatures and the change by Si substitution for Al from a microscopic point of view. From the analyses of the Knight shift, the hyperfine coupling constants on 27 Al in PrTi 2 (Si 0.1 Al 0.9 ) 20 are slightly larger than those of PrTi 2 Al 20 . The nuclear spin-lattice relaxation rate 1 / T 1 does not exhibit any anomaly around 2.0 K, in contrast to the results associated with the quadrupolar ordering in PrTi 2 Al 20 . The analysis of 1 / T 1 at high temperatures reveals that the c – f hybridization may be reduced by Si substitution for Al. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the most aggressive and deadly brain tumors; however, its current therapeutic strategies are limited. Selenoprotein P (SeP; SELENOP, encoded by the SELENOP gene) is a unique selenium-containing protein that exhibits high expression levels in astroglia. SeP is thought to be associated with ferroptosis sensitivity through the induction of glutathione peroxidase 4 (GPX4) via selenium supplementation. In this study, to elucidate the role of SeP in GBM, we analyzed its expression in GBM patients and found that SeP expression levels were significantly higher when compared to healthy subjects. Knock down of SeP in cultured GBM cells resulted in a decrease in GPX1 and GPX4 protein levels. Under the same conditions, cell death caused by RSL3, a ferroptosis inducer, was enhanced, however this enhancement was canceled by supplementation of selenite. These results indicate that SeP expression contributes to preserving GPX and selenium levels in an autocrine/paracrine manner, i.e., SeP regulates a dynamic cycling-selenium storage system in GBM. We also confirmed the role of SeP expression in ferroptosis sensitivity using patient-derived primary GBM cells. These findings indicate that expression of SeP in GBM can be a significant therapeutic target to overcome anticancer drug resistance. [ABSTRACT FROM AUTHOR]

Wave phenomena can be artificially engineered by scattering from metasurfaces, which aids in the design of radio-frequency and optical devices for wireless communication, sensing, imaging, wireless power transfer and bio/medical applications. Scattering responses vary with changing frequency; conversely, they remain unchanged at a constant frequency, which has been a long-standing limitation in the design of devices leveraging wave scattering phenomena. Here, we present metasurfaces that can scatter incident waves according to two variables—the frequency and pulse width—in multiple bands. Significantly, these scattering profiles are characterized by how the frequencies are used in different time windows due to transient circuits. In particular, by using more than one frequency with coupled transient circuits, we demonstrate variable scattering profiles in response to unique frequency sequences, which can break a conventional linear frequency concept and markedly increase the available frequency channels in accordance with a factorial number of frequencies used. Our proposed concept, which is analogous to frequency hopping in wireless communication, advances wave engineering in electromagnetics and related fields. Metasurfaces show variable scattering with frequency sequence. This frequency-hopping response breaks a conventional linear frequency concept and markedly expands available frequency channels from a linear number to its factorial number. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the association between prolonged preoperative sedentary time (ST) and postoperative ileus (POI) after adjusting for confounders in patients with colorectal cancer (CRC). Methods: This single-center retrospective study enrolled 155 consecutive patients who underwent surgery for primary CRC. A diagnosis of POI was made by the surgeons if the Clavien-Dindo classification (CD) grade is ≥ 2 within 30 days after surgery. Preoperative ST was assessed using the International Physical Activity Questionnaire usual week short version (Japanese version). Patients were classified into two groups (ST < 6 h/day and ST ≥ 6 h/day) based on results from the questionnaire, and data were analyzed using a propensity score-matching strategy to adjust for confounders. In addition, receiver operating characteristic (ROC) curve analysis was performed to identify the optimal cutoff value of preoperative ST for predicting POI. Results: Of the 155 patients, 134 were included in the analysis. POI occurred in 16 (11.9%) patients of overall patients and 11 (12.5%) of the 88 matched patients. The logistic regression analysis after propensity score-matching showed that prolonged preoperative ST (ST ≥ 6 h/day) was associated with POI (odds ratio 5.40 (95% confidence interval: 1.09 − 26.60), p = 0.038). The ROC curve analysis indicated that the optimal cutoff value of preoperative ST for predicting POI was 6 h/day. Conclusion: Prolonged preoperative ST is a risk factor for POI in patients with CRC. Therefore, reducing preoperative ST may play an important role in preventing POI. [ABSTRACT FROM AUTHOR]

Background: Assessing right ventricular (RV) function is paramount for risk stratification, which remains challenging in patients with tricuspid regurgitation (TR). We assessed RV–pulmonary artery (PA) coupling and its predictability of outcomes after transcatheter tricuspid valve repair (TTVR). Methods: Study participants comprised patients undergoing transcatheter tricuspid valve repair to treat symptomatic TR from June 2015 to July 2021. We calculated an RV–PA coupling ratio using a formula, which is dividing tricuspid annular plane systolic excursion (TAPSE) by echocardiographically estimated (ePASP) or invasively measured PASP (iPASP) at baseline. The primary outcome was all-cause mortality or heart failure rehospitalization within one year. Results: The study participants (n = 206) were at high surgical risk (EuroSCORE II: 7.4 ± 4.8%). The primary outcome occurred in 57 patients within one year. The c-statistics for the outcome were 0.565 (95% CI 0.488–0.643) for TAPSE/ePASP and 0.695 (95% CI 0.631–0.759) for TAPSE/iPASP. The correlation between the ePASP and iPASP was attenuated in patients with massive/torrential TR compared to those with severe TR (interaction p = 0.01). In the multivariable Cox proportional model, TAPSE/iPASP was inversely associated with the risk of the primary outcome (per 0.1-point increase: adjusted-HR 0.67, 95% CI 0.56–0.82, p < 0.001), independent of baseline demographics. According to the TAPSE/iPASP quartiles (i.e., ≤ 0.316; 0.317–0.407; 0.408–0.526; ≥ 0.527), the event-free survival was 43.4%, 48.3%, 77.9%, and 85.4% at one year after TTVR. Conclusion: RV–PA coupling predicts one-year mortality and heart failure rehospitalization after TTVR in patients with TR. The predictability is improved if invasively-measured PA pressure is included. Assessing right ventricular (RV) function is paramount for risk stratification. The present analysis confirms that RV–PA coupling, measured as TAPSE/PASP, predicts one-year mortality and heart failure rehospitalization in patients undergoing TTVR. There is a significant interaction between TR severity and the correlation of ePASP with iPASP, and therefore the correlation is attenuated in patients with massive to torrential TR. The predictability of RV–PA coupling is improved if PA pressure is measured invasively and included in the formula. [ABSTRACT FROM AUTHOR]

Background: Obesity and underweight represent classical risk factors for outcome in patients treated for cardiovascular disease. This study describes the impact of different body mass index (BMI) categories on 1-year clinical outcome in patients with tricuspid regurgitation (TR) undergoing transcatheter-edge-to-edge repair (TEER). Methods: We analyzed 211 consecutive patients (age 78.3 ± 7.2 years, 55.5% female, median EuroSCORE II 9.6 ± 6.7) with tricuspid regurgitation undergoing TEER from June 2015 until May 2021. Patients were prospectively enrolled in our single center registry and were retrospectively analyzed. Patients were stratified according to body mass index (BMI) into 4 groups: BMI < 20 kg/m2 (underweight), BMI 20.0 to < 25.0 kg/m2 (normal weight), BMI 25.0 to > 30.0 kg/m2 (overweight) and BMI ≥ 30 kg/m2 (obese). Results: Kaplan–Meier survival curves demonstrated inferior survival for underweight and obese patients, but comparable outcomes for normal and overweight patients (global log rank test, p < 0.01). Cardiovascular death was significantly higher in underweight patients compared to the other groups (24.1% vs. 7.0% vs. 6.3% vs. 6.4%; p < 0.01). Over all, there were comparable rates of bleeding, stroke and myocardial infarction. Multivariable Cox regression analysis (adjusted for age, gender, coronary artery disease, chronic obstructive pulmonary disease, tricuspid annular plane systolic excursion, left-ventricular ejection fraction) confirmed underweight (HR 3.88; 95% CI 1.64–7.66; p < 0.01) and obesity (HR 3.24; 95% CI 1.37–9.16; p < 0.01) as independent risk factors for 1-year all-cause mortality. Conclusions: Compared to normal weight and overweight patients, obesity and underweight patients undergoing TEER display significant higher 1-year all-cause mortality. [ABSTRACT FROM AUTHOR]

Background: Transcatheter mitral valve replacement (TMVR) has emerged as alternative to transcatheter edge-to-edge repair (TEER) for treatment of mitral regurgitation (MR); however, the role of TMVR with the Tendyne system among established treatments of MR is not well defined. We assessed characteristics and outcomes of patients treated with the Tendyne system in the current clinical practice. Methods: We reviewed patients who underwent cardiac computed tomography and were judged eligible for the Tendyne system. Results: A total of 63 patients were eligible for TMVR with the Tendyne system. Of these, 17 patients underwent TMVR, and 46 were treated by TEER. Patients treated with the Tendyne system were more likely to have a high transmitral pressure gradient and unsuitable mitral valve morphology for TEER than those treated with TEER. TMVR with the Tendyne system reduced the severity of MR to less than 1 + in 94.1% of the patients at discharge and achieved a greater reduction in left ventricular (LV) end-diastolic volume at the 30-day follow-up compared with TEER. In contrast, patients treated with the Tendyne system had a higher 30-day mortality than those treated with TEER, while the mortality between 30 days and one year was comparable between Tendyne and TEER. Conclusions: Among patients eligible for the Tendyne system, approximately a quarter of the patients underwent TMVR with the Tendyne system, which led substantial reduction of MR and LV reverse remodeling than TEER. In contrast, the 30-day mortality rate was higher after TMVR with the Tendyne compared to TEER. [ABSTRACT FROM AUTHOR]

Aims: We aimed to identify patients who would benefit from basal insulin-supported oral therapy (BOT) with a glinide and an α-glucosidase inhibitor (a fixed-dose combination tablet of mitiglinide 10 mg and voglibose 0.2 mg) in Japanese type 2 diabetic patients. Methods: Patients who were hospitalized to improve hyperglycemia received basal–bolus insulin therapy. After the reduction of glucose toxicity, a 75 g oral glucose tolerance test and a glucagon test were performed. Thereafter, the basal–bolus insulin therapy was switched to BOT with mitiglinide, followed by further addition of voglibose. Interstitial glucose levels were continuously monitored throughout the study period. Diurnal glucose profile was recorded and analyzed. Patients were divided into two groups according to whether their percentage of time in range (TIR, 70–180 mg/dL) under BOT with mitiglinide/voglibose was higher than 70% or not, and the differences in clinical characteristics between the groups were analyzed. Results: Twenty patients were enrolled, and 19 of them completed the study. BOT with mitiglinide/voglibose achieved ≥ 70% of TIR in thirteen patients. The area under the curve of serum C-peptide levels during the oral glucose tolerance test was significantly higher in the patients with ≥ 70% of TIR. The daily insulin dosages and blood glucose profiles were comparable between the two groups. Conclusions: The efficacy of BOT with mitiglinide/voglibose depended on residual insulin secretory abilities. This therapy would be a useful therapeutic option for patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]