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Sung-Soo Kim,1,* Sojung Won,2,* Ha Eun Lee,2 Seung Hyun Ryu,2 Dong Joon Choi,2 Sung Ig Cho,2 Byoung Joo Gwag,2 Hwa-Young Youn,3 Jin Hwan Lee2 1VIP Animal Medical Center KR, Seoul, 02830, Republic of Korea; 2GNT Pharma, Yongin, Gyeonggi, 17096, Republic of Korea; 3Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea*These authors contributed equally to this workCorrespondence: Jin Hwan Lee, GNT Animal Health Business Unit, Yongin, Gyeonggi, 17096, Republic of Korea, Tel +82 10 8878 0456, Fax +82 31 8005 9931, Email jhlee@gntpharma.comPurpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 selective inhibitors are the most widely used drugs to treat pain. Conventional NSAIDs and COX-2 selective inhibitors, however, cause several side effects such as gastric damage, kidney damage, and cardiovascular problems. Our previous study showed that 2-acetoxy-5-(2-4-(trifluoromethyl)-phenethylamino)-benzoic acid ie, flusalazine (also known as ND-07), which exerts dual actions by serving both as an anti-inflammatory agent and a free radical scavenger, is an effective and safe treatment for severe inflammatory diseases in mice. The goal of the present study was to examine the potential analgesic action and safety of flusalazine in mice models of pain.Methods and Results: Flusalazine showed a significant analgesic effect in an acetic acid-induced abdominal constriction model. Likewise, total paw licking was reduced significantly in neurogenic (early stage) and inflammatory (late stage) pain induced by formalin in flusalazine-treated mice. In the tail immersion test, flusalazine significantly increased tail withdrawal time at 2 h after its administration. Also, the formation of paw edema in the flusalazine-treated group was significantly inhibited in a carrageenan-induced inflammatory pain model. Gastric damage was not induced by flusalazine even up to 1000 mg/kg, while aspirin and indomethacin caused critical gastric bleeding.Conclusion: These findings suggest that flusalazine’s safety profile and analgesic effects have high translational potential for the clinical treatment of patients experiencing pain.Keywords: analgesic effect, aspirin, flusalazine, indomethacin, NSAIDs

Doo Yong Park,1 Yeon Soo Kim,1,2 Seung Ho Ryu,3 Yu Sun Jin11Department of Physical Education, College of Education, Seoul National University, Seoul, Republic of Korea; 2Department of Physical Education, College of Education, Republic of Korea & Institute of Sport Science, Seoul National University, Seoul, Republic of Korea; 3Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaBackground: A significant discovery was recently made in which participation in physical activity and sedentary behavior, two contrasting lifestyles, was found to be related to the frequency of hyperuricemia diagnosis. The purpose of this study was to identify the association between sedentary behavior and physical activity levels in South Korean men and women diagnosed with hyperuricemia.Methods: This study included 161,064 healthy men and women participants who had obtained a complete health examination. Physical activity levels and sitting time were assessed by the validated International Physical Activity Questionnaire Short Form Korean version. The presence of hyperuricemia in the subjects was determined by measuring serum uric acid (SUA) concentration (SUA ≥6 mg/dL [male], SUA ≥7 mg/dL [female]). Logistic regression analysis, adjusting other confounding factors, was conducted to identify the association of sedentary behavior and physical activity levels with hyperuricemia (p

Abstract Aims Interleukin‐16 (IL‐16) has been reported to mediate left ventricular myocardial fibrosis and stiffening in patients with heart failure with preserved ejection fraction (HFpEF). We sought to elucidate whether IL‐16 has a distinct impact on pathophysiology and prognosis across different subphenotypes of acute HFpEF. Methods and results We analysed 211 patients enrolled in a prospective multicentre registry of acute decompensated HFpEF for whom serum IL‐16 levels after stabilization were available (53% female, median age 81 [interquartile range 75–85] years). We divided this sub‐cohort into four phenogroups using our established clustering algorithm. The study endpoint was all‐cause death. Patients were subclassified into phenogroup 1 (‘rhythm trouble’ [n = 69]), phenogroup 2 (‘ventricular‐arterial uncoupling’ [n = 49]), phenogroup 3 (‘low output and systemic congestion’ [n = 41]), and phenogroup 4 (‘systemic failure’ [n = 52]). After a median follow‐up of 640 days, 38 patients had died. Among the four phenogroups, phenogroup 2 had the highest IL‐16 level. The IL‐16 level showed significant associations with indices of cardiac hypertrophy, diastolic dysfunction, and congestion only in phenogroup 2. Furthermore, the IL‐16 level had a significant predictive value for all‐cause death only in phenogroup 2 (C‐statistic 0.750, 95% confidence interval 0.606–0.863, P = 0.017), while there was no association between the IL‐16 level and the endpoint in the other phenogroups. Conclusions Our results indicated that the serum IL‐16 level had a significant association with indices that reflect the pathophysiology and prognosis of HFpEF in a specific phenogroup in acute HFpEF.

Abstract Proposed in 1954, Alisov’s climate classification (CC) focuses on climatic changes observed in January–July in large-scale air mass zones and their fronts. Herein, data clustering by machine learning was applied to global reanalysis data to quantitatively and objectively determine air mass zones, which were then used to classify the global climate. The differences in air mass zones between two half-year seasons were used to determine climatic zones, which were then subdivided into continental or maritime climatic regions or according to east–west climatic differences. This study renews Alisov’s CC for the first time in almost 70 years and employs data-driven machine learning to establish a standard for causal CC based on air masses.

Introduction: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical procedure for ulcerative colitis (UC). Intestinal ischemia may occur if the main blood vessels are ligated at an early stage of this surgery. Considering that the blood flow in the large intestine can be maintained by preserving the middle colic artery, we have used a new IPAA method: ligating the middle colic artery immediately before removal of the specimens ('M-method'). Here, we evaluated the M-method's clinical outcomes. Methods: Between April 2009 and December 2021, 13 patients underwent a laparoscopy-assisted IPAA procedure at our institution. The conventional method was used for six patients, and the M-method was used for the other seven patients. We retrospectively analyzed the cases' clinical notes. Results: The M-method's rate of postoperative complications (Clavien-Dindo classification grade II or more) was significantly lower than that of the conventional method (14.2% vs. 83.3%). The M-method group's postoperative stay period was also significantly shorter (average 16.4 days vs. 55.5). There were significant differences in the albumin value and the ratio of the modified GPS score 1 or 2 on the 7th postoperative day between the M- and conventional methods (average 3.15 vs. 2.5, average 4/7 vs. 6/6). However, it is necessary to consider the small number of cases and the uncontrolled historical comparison. Conclusion: Late ligation of the middle colic artery may be beneficial for patients' post-surgery recovery and can be recommended for IPAAs in UC patients.

Background Neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) are novel inflammation markers. Their combined usefulness for estimating the prognosis of patients with heart failure with preserved ejection fraction (HFpEF) admitted for acute decompensated heart failure remains elusive. Methods and Results We investigated 1026 patients registered in the Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction. Both NLR and PLR values were measured at the time of admission. Comorbidity burden was defined as the number of occurrences of 8 common comorbidities of HFpEF. The primary end point was cardiac death. The patients were stratified into 3 groups based on the optimal cut‐off values of NLR and PLR on the receiver operating characteristic curve analysis for predicting cardiac death (low NLR and PLR, either high NLR or PLR, and both high NLR and PLR). After a median follow‐up of 429 days, 195 patients died, with 85 of these deaths attributed to cardiac causes. An increased comorbidity burden was significantly associated with a higher proportion of patients with high NLR (>4.5) or PLR (>193), or both. High NLR and PLR values were independently associated with cardiac death, and a combination of both values was the strongest predictor (hazard ratio, 2.66 [95% CI, 1.51–4.70], P=0.0008). A significant difference was found in the rate of cardiac death among the 3 groups stratified by NLR and PLR values. Conclusions The combination of NLR and PLR is useful for the prediction of postdischarge cardiac death in patients with acute HFpEF. Registration URL: ClinicalTrials.gov; Unique identifier: UMIN000021831.

Silica–graphite filler was prepared via two-step grafting procedure by grafting silica particles onto the expanded graphite. In the first step, isocyanatopropyltriethoxysilane was chemically introduced onto the silica aggregates, which was followed by grafting onto the expanded graphite via urethane linkage in the second step. Successful grafting of silica aggregates onto the graphite was corroborated using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The presence of a thin graphene layer on silica aggregates corroborated using transmission electron microscopy confirmed the grafting of silica aggregates onto the graphite surface. Styrene–butadiene rubber (SBR) composites with various silica–graphite loadings were prepared by melt processing technique to generate pristine silica and silica–graphite-filled elastomeric composites. Rheometric cure studies revealed that the torque difference (Δ S) increased with pristine silica loading, when compared to the unfilled SBR system, and this effect is more pronounced on loading silica–graphite filler. Improvements in mechanical properties such as modulus and tensile strength were observed with increasing loading of silica particles and this effect is more pronounced on loading silica–graphite fillers, indicating that this is due to the rise in the elastomer–filler interactions in the silica–graphite-loaded SBR systems. This fact was further corroborated using bound rubber content and equilibrium swelling ratios of the unvulcanized and vulcanized SBR composites. [ABSTRACT FROM AUTHOR]

Abstract The world is becoming longer-lived, and the number of elderly colorectal cancer patients is increasing. It is very important to identify simple and inexpensive postoperative predictors in elderly colorectal cancer patients. The geriatric nutritional risk index (GNRI) is a marker of systemic nutrition and is associated with poor survival in various kinds of cancers. A few reports have investigated recurrence factors using preoperative GNRI with CRC (colorectal cancer) patients. This study aimed to investigate whether preoperative GNRI is associated with recurrence-free survival (RFS) and overall survival (OS) in elderly patients with CRC. This study retrospectively enrolled 259 patients with Stage I–III CRC who were more than 65 years old and underwent curative surgery at a single institution in 2012–2017. We classified them into low GNRI (RFS: ≤ 90.5, OS ≤ 101.1) group and high GNRI (RFS: > 90.5, OS > 101.1) group. Multivariable analyses showed low GNRI group was an independent risk factor for 3-year RFS (P = 0.006) and OS (P = 0.001) in the patients with CRC. Kaplan–Meier analysis showed 3-year RFS and 3-year OS were significantly worse in the low GNRI group than in high GNRI group (p = 0.001, 0.0037). A low-preoperative GNRI was significantly associated with a poor prognosis in elderly CRC patients.

Abstract Aims At present, the clinical significance of admission hyperglycaemia in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. This study was designed to evaluate the relationship between admission hyperglycaemia and clinical outcome in HFpEF patients, especially in non‐diabetic patients. Methods and results We enrolled 486 non‐diabetic HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure from the PURSUIT‐HFpEF registry, a prospective, multicentre observational study. We divided non‐diabetic patients into two groups, an admission hyperglycaemia group whose blood glucose on admission was ≥7.0 mmol/L (148 patients) and a normoglycaemic group whose blood glucose on admission was

Abstract Aims The impacts of high density lipoprotein cholesterol (HDL‐C) as an anti‐inflammatory and C reactive protein (CRP) as inflammatory properties on the pathogenesis of heart failure were reported. At present, the clinical significance of the HDL‐C/CRP ratio in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. Methods and results We examined the data on 796 consecutive HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure from the PURSUIT‐HFpEF registry, a prospective, multicentre observational study. We calculated the HDL/CRP ratios and evaluated the relationship between the values and clinical outcomes, including degree of cardiac function. The mean follow‐up duration was 420 ± 346 days. All‐cause death occurred in 118 patients, of which 51 were cardiac deaths. HDL/CRP ≤ 4.05 was independently and significantly associated with all‐cause death (odds ratio = 1.84, 95% CI: 1.06–3.20, P = 0.023), and HDL/CRP ≤ 3.14 was associated with cardiac death by multivariate Cox proportional hazard analysis (odds ratio = 2.86, 95% CI: 1.36–6.01, P = 0.003). HDL‐C/CRP ratio significantly correlated with the product of the left atrial volume and left ventricular mass index as well as the tricuspid annular plane systolic excursion by multiple regression analysis (standardized beta‐coefficient = −0.085, P = 0.034 and standardized beta‐coefficient = 0.081, P = 0.044, respectively). Conclusions HDL‐C/CRP ratio was a useful marker for predicting all‐cause death and cardiac death and correlated with left ventricular diastolic function and right ventricular systolic function in HFpEF patients.

Abstract Aims Heart failure (HF) readmissions with preserved ejection fraction (HFpEF) are increasing in the elderly, which is a major socioeconomic problem. We investigated the clinical impact of HF readmissions (HFR) on octogenarians with HFpEF. Methods and results We enrolled consecutive octogenarians (≥80 years old) from June 2016 to February 2020 in PURSUIT‐HFpEF registry. We divided them into HFR group readmitted for HF during the follow‐up period and non‐HF readmission (non‐HFR) group. We evaluated the impact of HFR on all‐cause mortality, cardiac death, and quality of life (QOL). Additionally, we evaluated the factors at discharge correlated with HFR. HFR group comprised 116 patients (21.4%). Among all‐cause deaths, 40 patients suffered cardiac deaths (48.2%). The Kaplan–Meier analysis revealed a similar prognosis between HFR and non‐HFR groups as well as similar incidences of HF deaths. The QOL scores had significantly deteriorated by 1 year later in the HFR group (0.71 ± 0.19 vs. 0.59 ± 0.21, P

Background Stent thrombosis (ST) remains a significant medical issue. In particular, longer‐term mortality and clinical predictors after ST occurrence have yet to be elucidated. Methods and Results This was a multicenter, retrospective, observational study. A total of 187 definite ST cases from January 2008 to December 2017 were enrolled, and the long‐term clinical outcomes were investigated. The primary outcome measure was the cumulative mortality after ST occurrence. In addition, independent predictors of mortality were assessed. Among the stent types causing ST, bare‐metal stent, first‐generation drug‐eluting stent, second‐generation drug‐eluting stent, and third‐generation drug‐eluting stent comprised 31.0%, 19.3%, 36.9%, and 6.4% of cases, respectively. Median duration from stent implantation to ST was 680.5 (interquartile range, 33.8–2450.5) days. Cumulative mortality was 14.6%, 17.4%, 21.2%, 24.4%, and 33.8% at 1, 2, 3, 5 and 10 years, respectively. The cumulative mortality did not significantly differ by type of stent, and mortality of late ST was higher than that of early ST and very late ST; however, it did not reach statistical significance after the multivariate analysis. Independent predictors of mortality were hemodialysis (hazard ratio [HR], 7.80; 95% CI, 3.07–19.81; P

Abstract Aim Stage II‐IV colorectal cancers are subdivided according to TNM categories. However, stage I cases are a single category, despite the inclusion of both T1 and T2 cases, which may have different outcomes. The aim of this study was to evaluate the usefulness of subdividing stage I colorectal cancers by T category. Methods From 1984 to 2015, 844 patients with stage I colorectal cancer (T1: 446, T2: 398) underwent colorectal resection with lymph node dissection at three hospitals. The long‐term survival and recurrence rates were compared between T1 and T2. A Cox regression analysis was used to evaluate the risk factors associated with cancer recurrence. Results A comparison of the T1 and T2 groups revealed significant differences in 5‐year overall (95.9% vs 91.4%, P = .008), recurrence‐free (94.8% vs 87.1%, P = .0007), and cancer‐specific survival (97.6% vs 93.6%, P = .004), and in the overall (2.5% vs 6.8%, P = .003), local (0.2% vs 1.5%, P = .04), and lymph node recurrence rates (0.2% vs 1.5%, P = .04). All local and lymph node recurrences were associated with lower rectal cancer, and this difference was significant. The Cox multivariate analysis identified male sex (P = .01, hazard ratio: 4.00, 95% confidence interval: 1.38‐11.55), T2 (P = .02, hazard ratio: 2.98, 95% confidence interval: 1.17‐7.60), and venous invasion (P = .03, hazard ratio: 2.38, 95% confidence interval: 1.12‐5.10) as risk factors for recurrence. Conclusions The subdivision of stage I colorectal cancer according to T category clearly reflected the long‐term outcomes.

Abstract Background Although there are reports linking ulcerative colitis (UC) to prostate cancer (PC), those reports are of PC patients who were previously diagnosed with UC. There are no reports of the development of UC during radiotherapy. Here we describe the first case of a patient who developed UC during radiotherapy for PC. The UC progressed rapidly and required emergency surgery. Case presentation A 61-year-old Japanese man underwent a prostate biopsy at another hospital due to a high prostate-specific antigen level and was diagnosed with PC. Goserelin and bicalutamide treatment was initiated in 2019, and intensity-modulated radiotherapy (total of 60 Gy/20 Fr) was administered in 2020. Diarrhea began during the radiotherapy and bleeding began post-radiotherapy. He was admitted to another hospital 14 days after the end of the radiotherapy, and colonoscopy revealed a deep ulcer in the colon, which led to the suspicion of UC. He was transferred to our hospital, and colonoscopy showed a widespread map-like ulcer, pseudopolyposis, and very easy bleeding in the colon. We diagnosed severe UC, and it worsened rapidly with uncontrollable bleeding, which we considered an indication for surgery. Emergency surgery (a total colectomy and ileostomy creation) was performed. The specimens confirmed an extensively spreading ulcer throughout the colon. The pathological report was UC in the active phase. The postoperative course was good. Conclusions When a patient exhibits diarrhea while undergoing radiotherapy for PC, clinicians should be aware of the possibility of UC in addition to radiation colitis, and colonoscopy should be considered.

Abstract Background and Aims There are two types of serum uric acid‐lowering agents, the xanthine oxidoreductase (XO) inhibitor and non‐XO inhibitor. We investigated whether febuxostat, XO inhibitor, could produce more favorable effects on coronary endothelial function (CEF) and renal function than benzbromarone, non‐XO inhibitor, in hyperuricemic coronary artery disease (CAD) patients. Methods We divided 21 hyperuricemic patients with stenting for left anterior descending (LAD) or left circumflex (LCX) artery into patients started on febuxostat (F group) and those on benzbromarone (B group). After 8 months, all patients underwent CEF evaluations (acetylcholine provocation test) and optical coherence tomography (OCT) for non‐culprit vessels (e.g. if patients received LAD stenting, we evaluated LCX). We compared the diameter ratio induced by acetylcholine and baseline (CEF ratio), thin‐cap fibroatheroma and calcified plaque by OCT, uric acid, oxidative stress biomarkers, and renal function including estimated glomerular filtration rate (eGFR) between F and B groups. Creatinine 2 days after stenting was measured to evaluate contrast‐induced nephropathy (CIN). Results Change of eGFR was significantly lower in F group (n= 11) than B group over 8 months while the other parameters including CEF ratio were similar. F group showed favorable effects for CIN. Conclusion In conclusion, 8‐months of febuxostat, XO inhibitor, does not significantly protect CEF but can protect the renal function including CIN in hyperuricemic patients with CAD compared to benzbromarone, non‐XO inhibitor.

Introduction Bilateral renal cell carcinomas with different histological types are rare. We report herein the first description of bilateral renal carcinomas with clear cell renal cell carcinoma and mucinous tubular and spindle cell carcinoma occurring synchronously. Case presentation A 62‐year‐old man was referred to our hospital with bilateral renal tumors. The tumors on each side showed different findings from both contrast‐enhanced computed tomography and magnetic resonance imaging. The tumors were partially resected. Histopathological and immunohistochemical examination of the left renal tumor diagnosed clear cell renal carcinoma. Histopathological and immunohistochemical examination of the right renal tumor diagnosed mucinous tubular and spindle cell carcinoma. Conclusion We encountered a case with clear cell renal cell carcinoma and mucinous tubular and spindle cell carcinoma occurring simultaneously in bilateral kidneys.

Abstract Background Small bowel obstruction (SBO) is a common postoperative complication of ulcerative colitis (UC). There have been a few recent reports of afferent limb syndrome (ALS) as a rare occurrence in cases of SBO. We present a case of ALS with recurrent SBO that was successfully managed surgically. Case presentation When this male patient was 55 years old, he underwent laparoscopy-assisted anus-preserving total proctocolectomy, the creation of a J-type ileal pouch, ileal pouch-anal canal anastomosis (IPAA), and creation of ileostomy for intractable UC. Three months later, ileostomy closure was performed. The first onset of SBO was observed 5 months after ileostomy closure. SBO occurred repeatedly, and the patient was hospitalized nine times in approximately 2 years. Each SBO was improved by non-surgical treatment. A computed tomography (CT) scan revealed that the afferent limb was narrowing and twisted, and gastrografin enema confirmed narrowing at the proximal portion of the pouch inlet. Endoscopy showed a sharp angulation at the pouch inlet. We suspected ALS and decided on a surgical policy and performed pouchopexy and ileopexy to the retroperitoneum by suturing with excision of the remaining blind end of the ileum. Endoscopy 3 days after surgery showed neither twist nor stricture in the fixed ileal pouch or the afferent limb. At the time of writing, the patient remains free of SBO symptoms. Conclusion Clinicians should consider ALS when examining a patient with recurrent intermittent SBO after IPAA surgery. When ALS is suspected, the patient is indicated for surgery such as surgical pexy.

Abstract Background Enlarged left atrium (LA) is an established predictor of recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI), but occasionally recurrences of AF/atrial tachycardia (AT) are experienced in patients with normal left atrial diameter. Therefore, the predictors of AF recurrence and AF triggers were evaluated in patients with normal LA. Methods We enrolled 168 patients with normal LA (

Abstract Background The term “mesenteric inflammatory veno-occlusive disease (MIVOD)” is used to describe an ischemic injury resulting from phlebitis or venulitis that affects the bowel or mesentery in the absence of arteritis. MIVOD is difficult to diagnose because of its rarity and frequent confusion with other diseases. The incidence and etiology of MIVOD remain unclear; only a few cases have been reported. We describe a case of the successful surgical management of a patient with MIVOD with characteristic images. Case presentation A 65-year-old Japanese man visited a hospital with the chief complaint of abdominal pain in January 2018. CT showed edema and thickening of the intestinal wall from the descending colon to the rectum. The patient was admitted to the hospital. Suspected diagnoses were enteritis, ulcerative colitis, amyloidosis, vasculitis, malignant lymphoma, and venous thrombus, but no definitive diagnosis was obtained. The patient was transferred to our hospital for the treatment of stenosis (located from the descending colon to the rectum) and bowel obstruction. An emergency transverse colostomy was performed. The sigmoid colon and mesentery were too rigid and edematous to resect. Colonic hemorrhage occurred 2 weeks after the surgery. With radiology intervention, coiling for the arteriovenous fistula in the descending colon was performed, and hemostasis was obtained. A colonoscopy at 6 months post-surgery showed neither ulceration nor stenosis in the rectum, indicating that the rectum could be preserved in the next surgery. However, severe stenosis in the descending and sigmoid colon remained unchanged. Ten months after the transverse colostomy, we performed a subtotal colectomy and ileorectal anastomosis, and an ileostomy was created. The sigmoid colon and mesentery were not so rigid compared to the first surgery’s findings, and we were able to resect intestine and mesentery. Histopathology revealed phlebitis and venulitis, fibrinoid necrosis, and normal arteries, meeting the diagnostic criteria for MIVOD. Postoperatively, the patient showed no recurrence for 8 months. Conclusion Clinicians should consider MIVOD when examining a patient with intestinal ischemia. When MIVOD is suspected, the patient is indicated for surgery based on an accurate diagnosis and good prognosis.

Abstract Aim The factors correlated with prognosis in heart failure with mid‐range ejection fraction (HFmrEF) is unclear, especially for acute heart failure (AHF) with HFmrEF. Thus, we investigated the factors correlated with the improvement in the ejection fraction (EF) over 1 year in AHF patients with HFmrEF. Methods and results In Acute Heart Failure Registry in the Osaka Rosai Hospital, we examined 159 consecutive HFmrEF patients out of 1051 HF patients who were admitted to our hospital for AHF from January 2015 to December 2017. We divided them into improved EF (IM) group whose EF improved (≧10%) and non‐IM group who had no improvement. We compared the baseline characteristics, echocardiographic data, medications, examinations for ischaemia, invasive treatments, and clinical outcomes between IM group and non‐IM group. IM group consisted of 21 patients (20%). IM group had a significantly more de novo heart failure, higher serum albumin (Alb), lower EF, smaller left ventricular dimension during diastole, more frequent coronary angiogram during hospitalization, and coronary intervention. Multivariate analysis revealed that Alb, left ventricular dimension during diastole, and coronary angiogram performed during hospitalization were independently associated with the improvement in the EF. In addition, IM group had less rehospitalizations over 1 year and a greater reduction in the B‐type natriuretic peptide level during the follow‐up than non‐IM group. Conclusions In AHF patients with HFmrEF, we should evaluate for any ischaemic heart disease during hospitalization, especially in patients with non‐enlarged left ventricular and non‐reduced serum Alb. AHF patients with HFmrEF who showed improvement in the EF tended to have better prognosis than those without improvement.

Abstract Background Intussusception is a relatively common condition seen in children. In comparison, adult intussusception is rare and usually occurs as a complication in patients with organic diseases. It is responsible for 1% of all bowel obstructions, in most of intussusceptions a malignant tumor is involved. Herein, we present an extremely unusual case of intussusception that occurred as a complication at the site of a functional end-to-end anastomosis. Case presentation A 57-year-old female patient was diagnosed with tumors in the ascending and descending colon and was referred to our department. Laparoscopic hemicolectomy and laparoscopic descending colectomy were performed. The mechanical intestinal obstruction occurred on the 9th day postoperatively, and computed tomography scan revealed intussusception at the site of the ileocolic anastomosis. Endoscopic reduction was attempted, but the procedure was challenging. Surgery was then performed and revealed that the site of ileocolic anastomosis firmly adhered to the side wall and right retroperitoneum. However, the intestine in the oral side of the anastomosis was not fixed. Examination of the anastomotic site revealed that the ileum had passed through the anastomosis and prolapsed into the transverse colon. The ileocolic anastomosis was resected. End-to-end anastomosis was performed, and surgery was then completed. No neoplastic lesions were observed in the resected tissue of the lead point of intussusception. The postoperative clinical course was favorable, and the patient was discharged on the 11th day after the second round of surgery. Conclusions There are no reports the anastomosis is involved as part of the intussception, as observed in the present case. Intussusception should thus be considered as one of the causes of postoperative mechanical intestinal obstruction.

The distribution of compressive strength in thick concrete members exposed to various environments in a nuclear power plant undergoing decommissioning is investigated. X-ray diffraction data, scanning electron microscopy analysis, and chemical analysis data reveal that rock-forming minerals in the aggregate had reacted and portlandite had been consumed to form calcium alumino silicate hydrates (C-A-S-H) when evaporable water content was sufficient. In addition, the study confirms Al-tobermorite formation in modern concrete after 16.5 years of elevated temperature conditions ranging from 40 to 55 °C. It is concluded that an appropriate aggregate and binder combination for the concrete enhances the compressive strength of thick concrete members thanks to the reaction of rock-forming minerals with portlandite, and also strengthens the chemical stability through the formation of Al-tobermorite under elevated temperature conditions and sufficient evaporable water content.

Background: The neutrophil-to-lymphocyte ratio (NLR) has been proposed as an indicator of a systemic inflammatory response. There are baseline differences in the inflammation status between paroxysmal atrial fibrillation (PAF) and persistent AF (PerAF). The NLR changes and late recurrences of AF (LRAF) after ablation depending on the AF type remain unknown. Methods: Consecutive AF patients undergoing pulmonary vein isolation (PVI) by radiofrequency catheter ablation were enrolled from September 2014 to June 2018. The peripheral blood leukocyte NLR 1 day before and 36–48 h after PVI were measured. First, the relationship between NLR changes after to before ablation (ΔNLR) and ERAFs/LRAFs in PAF and PerAF patients were investigated to exclude the baseline inflammation status and evaluate catheter ablation induced inflammation. Second, the clinical impact of the NLR for predicting LRAFs was evaluated. Results: There hundred sixty-nine PAF and 264 PerAF patients from Osaka Rosai AF registry were enrolled. The ratio of ERAFs/LRAFs in PAF and PerAF patients were 26.8%/22.5% and 39.4%/29.9%, respectively. In PAF and PerAF patients, the ΔNLR was significantly higher with ERAF than no-ERAF (p = 0.022 and p = 0.010, respectively). In PAF patients, the ΔNLR was significantly higher with LRAF than no-LRAF (p = 0.017), while with PerAF, the ΔNLR did not significantly differ between LRAFs and no-LRAFs. In PAF, the ΔNLR was independently and significantly associated with LRAFs after PVI (p = 0.029). Conclusion: The ΔNLR was significantly higher only in PAF patients with LRAFs than no-LRAFs, but not in PerAF patients. The ΔNLR was useful for predicting LRAFs after PVI in PAF patients.

Abstract Background A tumor composed exclusively or predominantly of human melanin black 45 (HMB45)-positive epithelioid cells is called a perivascular epithelioid cell tumor (PEComa). We report a very rare case of a PEComa of the greater omentum. Case presentation MRI conducted to examine the orthopedic disease of the patients, a 49-year-old Japanese woman, also identified a tumor in her pelvis. A CT scan revealed a tumor mass on the right side of the pelvic floor and clear nutrient vessels originating from the splenic and celiac arteries. An omental primary tumor or accessory spleen was thus suspected, and tumor resection was performed. The tumor was a light brown solid tumor with a smooth margin, measuring 5.2 × 3.8 × 3.5 cm. Histopathologically, the tumor was composed mainly of spindle and epithelioid cells, and large and small blood vessel formation was observed. In the immunohistochemical staining, tumor cells were positive for human melanin black 45 (HMB-45) and Melan-A and partially positive for alpha-smooth muscle actin. The final diagnosis was PEComa of the greater omentum. Conclusions Although omental PEComa is very rare, it should be considered as a differential disease of an omental primary tumor.

Objectives: The protective efficacy of an absorptive adhesion prevention product (SeprafilmⓇ) against bowel obstruction (BO) during open surgery was demonstrated in a large-scale randomized controlled clinical trial in Europe and America. However, the efficacy of Seprafilm against BO in laparoscopic surgery remains uncertain. The objective of this study was to clarify the protective efficacy of Seprafilm against BO after laparoscopic surgery for colorectal cancer. Methods: From 2009 to 2016, 1328 laparoscopic colorectal resections were performed for colorectal cancer. From 2009, Seprafilm was used for preventing BO in laparoscopic colorectal surgery. The incidence of BO and short-term results were compared between the Seprafilm and non-Seprafilm groups after propensity score matching. Results: Propensity scoring generated 270 matched patients per group for the comparisons between the Seprafilm and non-Seprafilm groups. The two groups showed no significant differences regarding patients' backgrounds. Among all patients, 73.1% (19/26) of BO occurred within 30 days after the surgery. Significantly lower incidences of all grade (2.6% vs. 7.0%; p = 0.016) and grade 2 + 3a (1.5% vs. 5.2%; p = 0.017) BO were observed in the Seprafilm group than in the non-Seprafilm group; no significant difference regarding grade 3b BO (1.1% vs. 1.9%; p = 0.476) was found. A significant difference in BO within 30 days was also noted between the two groups (1.9% vs. 5.2%, p = 0.036). There were no significant differences between the groups regarding anastomotic leakage and deep surgical site infection. Conclusions: Seprafilm was useful for preventing BO, requiring decompression therapy of the bowel, after laparoscopic colorectal surgery without increasing adverse events.

Woven coronary artery anomaly is a rare congenital anomaly, and intravascular ultrasound and optical coherence tomography are useful for the diagnosis. We performed both imaging techniques for woven coronary artery anomaly and evaluated which was superior. We concluded that optical coherence tomography was the preferred imaging modality in this case. (Level of Difficulty: Intermediate.)

We performed orbital atherectomy in the left circumflex artery through a stent that jailed the circumflex artery ostium. The orbital atherectomy catheter was entrapped within the stent and the stent was avulsed during catheter withdrawal. We should consider this potential complication when performing orbital atherectomy in a jailed side branch. (Level of Difficulty: Advanced.)

Background Newer implantable cardioverter defibrillators can monitor intracardiac ECGs , but their ability to detect ischemia is unclear. This study investigated the usefulness of implantable cardioverter defibrillators with an ST‐monitoring function in coronary artery disease patients. Methods and Results We conducted a prospective study of implantable cardioverter defibrillator patients with the ST‐monitoring function. One hundred seventy‐three patients who received implantable cardioverter defibrillators for primary or secondary prevention of sudden cardiac death. All patients underwent medical examinations at least every 6 months, with standard 12‐lead ECGs and device checks that included analysis of the ST‐monitoring function. Myocardial perfusion imaging or coronary angiography was performed during the follow‐up. The mean follow‐up duration was 23.3±7.7 months. Significant ST changes occurred in 15 patients (8.7%), of whom 14 were asymptomatic. The incidence of angina pectoris was significantly higher in the ST change (+) group than that in the ST change (−) group (28.6% versus 7.2%, P=0.03). In the patients who underwent myocardial perfusion imaging, the sensitivity, specificity, and negative predictive value of the ST‐monitoring feature to detect ischemia were 75.0%, 72.5%, and 93.5%, respectively. The sensitivity, specificity, and negative predictive value of the ST‐monitoring feature to predict residual stenosis evaluated using coronary angiography were 76.9%, 83.5%, and 97.5%, respectively. The percentage of patients with a septal right ventricular lead was significantly lower in the ST change (+) group than in the ST change (−) group (13.5% versus 33.5%, P=0.01). Conclusions If intracardiac ECGs ST changes are detected, it is necessary to use additional modalities even in asymptomatic patients. Clinical Trial Registration URL: upload.umin.ac.jp. Unique identifier: UMIN000011824.

Introduction: Bepridil is effective for atrial fibrillation (AF), but it can induce torsades de pointes. Thus we examined the efficacy and safety of bepridil when started at 100 mg/day for AF after failed electrical cardioversion (EC). Methods and Results: We studied 28 consecutive patients (58 ± 12 years old) with failed EC. After administration of bepridil, we examined the time to restore the sinus rhythm, the duration of the maintained sinus rhythm. Our patients were divided into the two groups and various clinical factors were compared, including medication and echocardiographic and electrocardiographic parameters: the SR group who maintained sinus rhythm during followup period and the AF group who still had AF. Sixteen patients (57%) could maintain sinus rhythm (SR group). Adverse arrhythmic events were not observed. There were no significant differences in any clinical factors between the two groups before and after bepridil. Conclusions: Bepridil was effective and safe for persistent AF with failed EC.

Chemically modified nucleotides have been developed and applied into SELEX procedure to find a novel type of aptamers to fit with targets of interest. In this study, we directly performed chemical modification of 5-(N-benzylcarboxyamide)-2'-deoxyuridine (called 5-BzdU) in the AS1411 aptamer, which binds to the nucleolin protein expressed in cancer cells. Forty-seven compounds of AS1411-containing Cy3-labeled 5-BzdU (called Cy3-(5-BzdU)-modified-AS1411) were synthesized by randomly substituting thymidines one to twelve in AS1411 with Cy3-labeled 5-BzdU. Both statistically quantified fluorescence measurements and confocal imaging analysis demonstrated at least three potential compounds of interest: number 12, 29 and 41 that significantly increased the targeting affinity to cancer cells but no significant activity from normal healthy cells. These results suggest that the position and number of substituents in AS1411 are critical parameters to improve the aptamer function. In this study, we demonstrated that chemical modification of the existing aptamers enhanced the binding and targeting affinity to targets of interest without additional SELEX procedures. [ABSTRACT FROM AUTHOR]

Background: Computerized cognitive training (CCT) has been proposed as a potential therapy for cognitive decline. One of the benefits of CCT is a transfer effect, but its mechanism on the memory domain is unclear. This study aimed to investigate the transfer effect of non-memory multidomain CCT on the memory domain and its neural basis in patients with mild cognitive impairment (MCI) through a randomized controlled trial., Methods: Patients with MCI recruited from memory clinics were randomly assigned to either the CCT or the control group. The CCT group received multidomain CCT training excluding memory training, while the control group read educational books with learning-based quizzes twice a week for 8 weeks. Participants underwent memory tests yielding a composite score, other cognitive domain tests, non-cognitive scales, and resting-state functional magnetic resonance imaging (rsfMRI), at baseline and after intervention. Within- and between-group comparisons, group × time interactions, and seed-to-voxel analyses in memory-involving brain networks were performed., Results: The CCT group showed improvement over the control group in memory domain (Group × time, F = 5.87, P = 0.03, η 2  = 0.31), which was related with the increased connectivity in the hippocampal-frontal and fusiform-occipital network. No other cognitive and non-cognitive symptoms differed between groups after adjusting for covariates., Conclusion: Eight weeks of multidomain CCT without memory training improved memory function and restored functional network in the hippocampal and medial temporal region in MCI patients. These results can provide evidence for the transferring ability of CCT on memory functioning with its neural basis., (© 2024 The Author(s). Psychogeriatrics published by John Wiley & Sons Australia, Ltd on behalf of Japanese Psychogeriatric Society.)

In Alzheimer's disease, chronic neuroinflammation is accompanied by amyloid and tau pathologies. Especially, aberrant microglial activation is known to precede the regional tau pathology development, but the mechanisms how microglia affect tau spread remain largely unknown. Here, we found that toll-like receptor 2 (TLR2) in microglia recognizes oligomeric tau as a pathogenic ligand and induces inflammatory responses. Knockout of TLR2 reduced tau pathology and microglial activation in rTg4510 tau transgenic mice. Treatment of oligomeric tau induced TLR2 activation and increased inflammatory responses in microglial cells. TLR2 further mediated the tau-induced microglial activation and promoted tau uptake into neurons in neuron-microglia co-culture system and in mouse hippocampus after intracranial tau injection. Importantly, treatment with anti-TLR2 monoclonal antibody Tomaralimab blocked TLR2 activation and inflammatory responses in a dose-dependent manner, and significantly reduced tau spread and memory loss in rTg4510 mice. These results suggest that TLR2 plays a crucial role in tau spread by causing aberrant microglial activation in response to pathological tau, and blocking TLR2 with immunotherapy may ameliorate tau pathogenesis in Alzheimer's disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Waxy maize is mainly cultivated in South Korea for the production of food and snacks, and colored maize with increased anthocyanin content is used in the production of functional foods and medicinal products. Association mapping analysis (AMA) is supported as the preferred method for identifying genetic markers associated with complex traits. Our study aimed to identify molecular markers associated with two anthocyanin content and six seed coat color traits in near-isogenic lines (NILs) of colored waxy maize assessed through AMA. We performed AMA for 285 SSR loci and two anthocyanin content and six seed coat color traits in 10 NILs of colored waxy maize. In the analysis of population structure and cluster formation, the two parental lines (HW3, HW9) of "Mibaek 2ho" variety waxy maize and the 10 NILs were clearly divided into two groups, with each group containing one of the two parental inbred lines. In the AMA, 62 SSR markers were associated with two seed anthocyanin content and six seed coat color traits in the 10 NILs. All the anthocyanin content and seed coat color traits were associated with SSR markers, ranging from 2 to 12 SSR markers per characteristic. The 12 SSR markers were together associated with both of the two anthocyanin content (kuromanin and peonidin) traits. Our current results demonstrate the effectiveness of SSR analysis for the examination of genetic diversity, relationships, and population structure and AMA in 10 NILs of colored waxy maize and the two parental lines of the "Mibaek 2ho" variety waxy maize.