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Abstract Aim The coronavirus disease 2019 (COVID‐19) pandemic greatly impacted medical resources such as cancer screening, diagnosis, and treatment given to people for various diseases. We surveyed the impacts of the pandemic on the incidence of complications and mortality following pancreaticoduodenectomy for pancreatic cancer in Japan. Methods Data on patients who underwent pancreaticoduodenectomy for pancreatic cancer were extracted from the Japanese National Clinical Database (NCD) between 2018 and 2021. The number of the pancreaticoduodenectomy for pancreatic cancer were obtained and then the morbidity and mortality rates were evaluated using a standardized morbidity/mortality ratio (SMR), which is the ratio of the observed number of incidences to the expected number of incidences calculated by the risk calculator previously developed by the NCD. Results This study included 22 255 cases. The number of pancreaticoduodenectomies exhibited an increasing trend even during the COVID‐19 pandemic. The mean observed incidence rates of Grade C pancreatic fistula and Clavien–Dindo grade ≥4 complications, and the 30‐day mortality and surgical mortality rates were 0.8%, 1.8%, 0.8% and 0.9%, respectively. The standardized morbidity ratios did not increase during the COVID‐19 pandemic. The standardized mortality ratios remained within the range of variations observed before the COVID‐19 pandemic. Conclusion The increasing trend in the number of pancreaticoduodenectomies and favorable short‐term outcomes even in the COVID‐19 pandemic suggest the medical care for pancreatic cancer in Japan functioned well during the pandemic.

Abstract Aim To examine the potential negative effects of the COVID‐19 pandemic on short‐term postoperative outcomes of emergency surgery for gastroduodenal perforation in Japan. Methods A total of 7973 cases of gastroduodenal perforation from 2019 to 2021 were retrieved from the National Clinical Database (NCD), which includes >95% of surgical cases in Japan. Data were analyzed nationally and in subgroups for subjects in areas with high infection levels (HILs). Postoperative 30‐d mortality, surgical mortality, and complications (Clavien–Dindo (CD) grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Results Nationally, data from 2019 vs 2020 and 2021 showed 30‐d mortality of 175 (6.7%) vs 398 (7.4%), surgical mortality of 250 (9.5%) vs 537 (10.1%), and complications (CD ≥3) of 558 (21.2%) vs 1163 (21.8%). Among these data, the only significantly high SMR was found for complications in July 2020 (1.36 [95% CI: 1.001–1.80]). In areas with HILs, data from 2019 vs 2020 and 2021 indicated 30‐d mortality of 91 (6.3%) vs 215 (7.3%), surgical mortality of 135 (9.4%) vs 294 (10.0%), and complications (CD ≥3) of 304 (21.1%) vs (23.1%). In these data, no month had a significantly high SMR. Conclusion The COVID‐19 pandemic had few negative effects on outcomes after surgery for gastroduodenal perforation. These findings suggest that the emergency system for gastroduodenal perforation in Japan was generally maintained during the pandemic.

The mechanism by which the skin, a non-visual tissue, responds to light remains unknown. To date, opsin expression has been demonstrated in keratinocytes, melanocytes, and fibroblasts, all of which are skin-derived cells. In this study, we examined whether the visual cycle, by which opsin activity is maintained, is present in skin keratinocytes. We also identified the wavelengths of light to which opsin in keratinocytes responds and explored their effects on skin keratinocytes. The fetal rat skin keratinocytes used in this study expressed OPN2, 3, and 5 in addition to enzymes involved in the visual cycle, and all-trans-retinal, which is produced by exposure to light, was reconverted to 11-cis-retinal, resulting in opsin activation. Using the production of all-trans-retinal after light exposure as an indicator, we discovered that keratinocytes responded to light at 450 nm. Furthermore, actin alpha cardiac muscle 1 expression in keratinocytes was enhanced and cell migration was suppressed by exposure to light at these wavelengths. These results indicate that keratinocytes express various opsins and have a visual cycle that keeps opsin active. Moreover, keratinocytes were shown to respond to the blue/UV region of the light spectrum, suggesting that opsin plays a role in the light response of the skin.

Abstract Aim Possible negative effects of the COVID‐19 pandemic on short‐term postoperative outcomes for colorectal perforation in Japan were examined in this study. Methods The National Clinical Database (NCD) is a large‐scale database including more than 95% of surgical cases in Japan. We analyzed 13 107 cases of colorectal perforation from 2019 to 2021. National data were analyzed, and subgroup analyses were conducted for subjects in prefectures with high infection levels (HILs) and metropolitan areas (Tokyo Met. and Osaka Pref.). Postoperative 30‐day mortality, surgical mortality, and postoperative complications (Clavien–Dindo grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Results In the NCD, postoperative 30‐day mortality occurred in 1371 subjects (10.5%), surgical mortality in 1805 (13.8%), and postoperative complications in 3950 (30.1%). Significantly higher SMRs were found for 30‐day mortality in November 2020 (14.6%, 1.39 [95% CI: 1.04–1.83]) and February 2021 (14.6%, 1.48 [95% CI: 1.10–1.96]), and for postoperative complications in June 2020 (37.3%, 1.28 [95% CI: 1.08–1.52]) and November 2020 (36.4%, 1.21 [95% CI: 1.01–1.44]). The SMRs for surgical mortality were not significantly high in any month. In prefectures with HILs and large metropolitan areas, there were few months with significantly higher SMRs. Conclusions The COVID‐19 pandemic had limited negative effects on postoperative outcomes in patients with colorectal perforation. These findings suggest that the emergency system for colorectal perforation in Japan was generally maintained during the pandemic.

Abstract Background Anemia has negative effects on long‐term outcomes of rectal cancer patients; however, its status as a risk factor for severe complications is disputed. Perioperative risks may differ based on the severity of pre‐surgical anemia; nonetheless, no previous study has investigated these differences. This study identified risks of severe postoperative complications in rectal cancer patients based on severity of their pre‐surgical anemia. Materials and Methods This study enrolled patients who underwent low anterior resection for rectal cancer and were registered in the Japanese National Clinical Database (NCD) between 2017 and 2019. Anemia severity was categorized into three levels: mild, moderate, and severe. A logistic regression model was applied to calculate the risk‐adjusted odds ratio (OR) of severe complications after surgery. Results This study analyzed a cohort of 51 765 rectal cancer patients who underwent low anterior resection. Results showed that severe complications occurred in 10.9% of patients and were significantly more frequent in patients with anemia (13.6%) than those with normal hemoglobin levels (9.2%). Risk‐adjusted ORs of severe complications in the severe, moderate, and mild anemia groups versus the normal group for males were 1.19 (95% confidence interval [CI]: 0.89–1.58), 1.47 (1.34–1.62), and 1.21 (1.12–1.31), respectively. Those for females were 1.39 (0.90–2.15), 1.64 (1.37–1.97), and 1.36 (1.16–1.58), respectively. Conclusions According to this large cohort study, pre‐surgical anemia significantly increases the risk of severe postoperative complications in rectal cancer patients. Even mild anemia presents a significant risk.

Abstract Background The COVID‐19 outbreak made conventional medical care impossible, forcing changes in both healthcare providers and patients. In Japan, COVID‐19 infection began spreading in earnest in 2020 and exploded in 2021. There was concern that the medical impact of COVID‐19 in 2021 would differ from that in 2020. We aimed to clarify the impact of COVID‐19 on mortality and anastomotic leakage in laparoscopic surgery for gastric cancer and rectal cancer in Japan using the National Clinical Database (NCD). Methods We collected data from patients who underwent laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR) from January 2018 to December 2021 from the NCD, a web‐based surgical registration system in Japan. The number of surgical cases, monthly incidence of mortality and morbidity (anastomotic leakage), standardized mortality ratio (SMR), and standardized morbidity‐leakage ratio (SMLR [ratio of observed patients to expected patients calculated using the risk calculator established in the NCD]) were evaluated. Results The numbers of LDG and LLAR cases continued to decline in the first year of the pandemic in 2020 and were as low in 2021 as in 2020. Although the numbers of robot‐assisted LDG and LLAR cases increased, the growth rate was lower than the rate of increase prior to the pandemic. Mortality and anastomotic leakage, two of the most important complications, as assessed by SMR and SMLR, did not worsen during the pandemic in comparison to the pre‐pandemic period. Conclusions Laparoscopic surgeries were performed safely in Japan and were not affected by the COVID‐19 pandemic.

Abstract For endemic benthos inhabiting hydrothermal vent fields, larval recruitment is critical for population maintenance and colonization via migration among separated sites. The vent‐endemic limpet, Lepetodrilus nux, is abundant at deep‐sea hydrothermal vents in the Okinawa Trough, a back‐arc basin in the northwestern Pacific; nonetheless, it is endangered due to deep‐sea mining. This species is associated with many other vent species and is an important successor in these vent ecosystems. However, limpet genetic diversity and connectivity among local populations have not yet been examined. We conducted a population genetics study of L. nux at five hydrothermal vent fields (maximum geographic distance, ~545 km; depths ~700 m to ~1650 m) using 14 polymorphic microsatellite loci previously developed. Genetic diversity has been maintained among these populations. Meanwhile, fine population genetic structure was detected between distant populations, even within this back‐arc basin, reflecting geographic distances between vent fields. There was a significant, positive correlation between genetic differentiation and geographic distance, but no correlation with depth. Contrary to dispersal patterns predicted by an ocean circulation model, genetic migration is not necessarily unidirectional, based on relative migration rates. While ocean circulation contributes to dispersal of L. nux among vent fields in the Okinawa Trough, genetic connectivity may be maintained by complex, bidirectional dispersal processes over multiple generations.

Background: Myocardial infarction-related left ventricular pseudoaneurysm (LVP), covered by the adjacent pericardial or scar tissue, is a fatal sequela of left ventricular rupture. Whereas hypertrophic cardiomyopathy (HCM) may cause left ventricular true aneurysm. Differentiating LVP from left ventricular true aneurysm is crucial because their natural histories and treatment strategies are distinct. However, the incidence and management of HCM-related LVP remain unknown. Case presentation: An 88-year-old man was admitted to our hospital with sudden-onset chest pain. Upon initial examination, vital signs were stable, and a grade 4/6 systolic murmur was noted. An electrocardiogram revealed atrial fibrillation and poor R-wave progression without ST-T changes or negative T-waves. An echocardiography showed mild left ventricular hypertrophy, mid-ventricular obstruction with a significant intraventricular pressure gradient, left ventricular outflow tract obstruction, and a small left ventricular apical outpouching. Cardiac computed tomography angiography (CCTA) assisted in the diagnosis of LVP, and an accompanying pericardial effusion suggested impending cardiac rupture. Because the patient initially refused our proposed urgent surgery, medication was initiated with continuous hemodynamic monitoring in the intensive care unit; however, the patient's condition did not improve. During a semi-urgent surgical repair of the aneurysmal wall, LVP was observed and confirmed by pathology. Myocardial tissue adjacent to the pseudoaneurysm was consistent with that of HCM. Subsequently, a final diagnosis of HCM-related LVP was made. The postoperative course was notable for transient profound hypotension. Thereafter, the patient died of non-occlusive mesenteric ischemia on day 6. Conclusions: To our knowledge, this is the first reported case of HCM-related LVP mimicking impending cardiac rupture. Our case highlights the importance of considering HCM-related LVP in patients with left ventricular outpouching and CCTA in the LVP diagnosis. In further research, data on the appropriate management of HCM-related LVP should be accumulated.

Background: Patterns of analgesic use before and after total joint replacement (TJR) in patients with knee/hip osteoarthritis (OA) is not well reported. Methods: This retrospective longitudinal analysis used JMDC claims data of patients who underwent knee/hip replacement surgery from 2010 to 2019. Primary outcome was proportion of patients using analgesics pre-surgery, immediately post-surgery, and in post-surgery period. Factors affecting post-surgery analgesic withdrawal and opioid prescriptions were assessed using logistic regression. Results: Of all (N = 3168) patients, those with knee OA (91.1 %) and hip OA (82.5 %) used analgesics pre-surgery, and 96.1 % with knee OA and 84.9 % with hip OA required analgesics even 3 months post-surgery. NSAIDs were most commonly used pre- and post-surgery in both OA groups. Before surgery, 15.6 % (knee OA) and 13.7 % of patients (hip OA) used weak opioids, and 23.1 % (knee OA) and 10.5 % (hip OA) of patients continued them post-surgery. Strong opioid use was noted in 2.2 % and 1.2 % of patients pre-surgery, and 5.8 % and 3.4 % of patients post-surgery in the knee and hip OA groups, respectively. Using pre-operative oral NSAIDs (odds ratio [OR]:0.56; 95 % confidence interval [CI]:0.44–0.72) and weak opioids (OR:0.58; 95 % CI:0.38–0.87) associated with withdrawal of post-surgery analgesics in patients with hip OA, and using intra-articular hyaluronic acid pre-surgery (OR:0.45; 95 % CI:0.21–0.97) was significant in patients with knee OA. Using weak (OR:4.59; 95 % CI:3.44–6.13) and strong opioids (OR:2.48; 95 % CI:1.01–6.07) pre-surgery associated with post-operative opioid use in patients with hip OA, and weak opioid use was significant in patients with knee OA (OR:7.00; 95 % CI:4.65–10.54). Conclusion: This study reported difference in analgesic use before and after TJR, and that many patients required analgesics even 3 months after TJR surgery in Japan. Pre-operative analgesic use associated with continued use after surgery. Optimal pain management before and immediately after TJR is important to reduce post-operative analgesic use, especially opioids.

Abstract Aim The Coronavirus Disease 2019 (COVID‐19) pandemic affected the allocation of various medical resources to several areas, including intensive care units (ICUs). However, currently, its impact on the short‐term postoperative outcomes of gastrointestinal cancer surgeries remains unclear. We aimed to evaluate the impact of the pandemic on the incidence of complications occurring after low anterior resection in patients with rectal cancer in Japan. Methods Data from the Japanese National Clinical Database between 2018 and 2021 were retrospectively examined. The primary outcome of the study was the postoperative morbidity and mortality rates before and after COVID‐19 pandemic. Moreover, the postoperative ICU admission rate was assessed. Morbidity and mortality rates were also assessed using a standardized morbidity/mortality ratio (SMR, the ratio of the actual number of incidences to the expected number of incidences calculated by the risk calculator). Results This study included 74 181 patients, including 43 663 (58.9%) from COVID‐19 epidemic areas. The mean actual incidences of anastomotic leakage (AL) and pneumonia during the study period were 9.2% and 0.9%, respectively. The SMRs of these complications did not increase during the pandemic but those of AL declined gradually. The mean 30‐day mortality and operative mortality rates were 0.3% and 0.5%, respectively. Moreover, SMRs did not change significantly in the pandemic or regional epidemic status. The ICU admission rate temporarily decreased, especially in the epidemic areas. Conclusion Although the pandemic temporarily decreased the ICU admission rate, its impact on short‐term outcomes following low anterior resection in patients with rectal cancer was insignificant in Japan.

Abstract Background The coronavirus disease 2019 (COVID‐19) pandemic had resulted in either failure to provide required medical resources or delayed treatment for gastric cancer patients. This study aimed to investigate the impact of COVID‐19 on the incidence of postoperative complications using a nationwide Japanese database of patients undergoing distal gastrectomy for gastric cancer. Methods We collected the data of patients who underwent distal gastrectomy from January 2018 to December 2021 from the National Clinical Database (NCD), a web‐based surgical registration system in Japan. The number of surgical cases, the use of intensive care units, and the incidence of morbidity per month were analyzed. We also calculated the standardized mortality ratio (SMR), defined as the ratio of the number of observed patients to the expected number of patients calculated using the risk calculator established in the NCD, for several morbidities, including pneumonia, sepsis, 30‐day mortality, and surgical mortality. Results A decrease of 568 gastrectomies was observed from April 2020 to May 2020. Although the absolute number of patients admitted to intensive care units had declined since 2020, the proportion of patients admitted to the ICU did not change before and after the pandemic. Mortality and critical morbidity (such as pneumonia and sepsis) rates were not worse during the pandemic compared to pre‐pandemic periods per the SMR. Conclusions Surgical management was conducted adequately through the organized efforts of the entire surgery department in our country even in a pandemic during which medical resources and staff may have been limited.

O resíduo florestal é todo e qualquer material que resulta da colheita ou do processamento da madeira que possa permanecer sem utilização definida no processo. As cinzas advindas da queima de carvão têm sido amplamente utilizadas em pesquisas; trabalhos com o uso de cinzas de biomassa, no entanto, ainda são recentes. O objetivo desta pesquisa consistiu em verificar a viabilidade da inserção de cinzas no traço de um compósito cimento-madeira. Foram realizados testes físicos para a determinação das propriedades físicas, densidade, inchamento e absorção de água, sendo também avaliadas a inibição do cimento com os materiais adicionais e a temperatura de hidratação da mistura. Para as cinzas, foram realizados testes para a obtenção do seu teor, avaliação da composição química, análise da distribuição granulométrica e espectroscopia de infravermelho com a transformada de Fourier (FTIR). A mistura com a cinza apresentou resultado superior em relação à mistura sem a cinza, nas propriedades de densidade e inchamento, dando indícios de que a utilização da cinza de biomassa é recomendada na fabricação de materiais cimentícios compósitos com resíduo de madeira, pois pode contribuir com menor degradação do material, que será avaliado em testes de durabilidade na sequência deste estudo.

Abstract Aim This study aimed to evaluate the impact of the coronavirus disease (COVID‐19) pandemic on elective endoscopic surgeries in Japan using the National Clinical Database. Methods We retrospectively analyzed the clinicopathological factors and surgical outcomes of laparoscopic cholecystectomy (LC), laparoscopic distal gastrectomy (LDG), and laparoscopic low anterior resection (LLAR) and compared the monthly numbers of each procedure performed in 2020 with those in 2018 and 2019. The degree of infection in prefectures was classified into low and high groups. Results In 2020, the number of LCs (except for acute cholecystitis) was 76 079 (93.0% of that in 2019), the number of LDGs was 14 271 (85.9% of that in 2019), and the number of LLARs was 19 570 (88.1% of that in 2019). Although the number of robot‐assisted LDG and LLAR cases increased in 2020, the growth rate was mild compared with that in 2019. There was little difference in the number of cases in the degree of infection in the prefectures. The numbers of LC, LDG, and LLAR cases decreased from May to June and recovered gradually. In late 2020, the proportion of T4 and N2 cases of gastric cancer and the number of T4 cases of rectal cancer increased compared with those in 2019. There was little difference between the proportions of postoperative complications and mortality in the three procedures between 2019 and 2020. Conclusion The number of endoscopic surgeries decreased in 2020 as a result of the COVID‐19 pandemic. However, the procedures were performed safely in Japan.

Abstract This work aimed to investigate the involvement of the thalamic nuclei in mesial temporal lobe epilepsy (MTLE) and identify the influence of interictal epileptic discharges on the neural basis of memory processing by evaluating the functional connectivity (FC) between the thalamic nuclei and default mode network-related area (DMNRA) using magnetoencephalography. Preoperative datasets of nine patients with MTLE with seizure-free status after surgery and those of nine healthy controls were analyzed. The FC between the thalamic nuclei (anterior nucleus [ANT], mediodorsal nucleus [MD], intralaminar nuclei [IL]), hippocampus, and DMNRA was examined for each of the resting, pre-spike, spike, and post-spike periods in the delta to ripple bands using magnetoencephalography. The FC between the ANT, MD, hippocampus, and medial prefrontal cortex increased in the gamma to ripple bands, whereas the FC between the ANT, IL, and DMNRA decreased in the delta to beta bands, compared with that of the healthy controls at rest. Compared with the rest period, the pre-spike period had significantly decreased FC between the ANT, MD, and DMNRA in the ripple band. Different FC changes between the thalamic nuclei, hippocampus, and DMNRA of specific connections in a particular band may reflect impairment or compensation in the memory processes.

BackgroundCoronavirus disease (COVID-19)-associated acute pericarditis has recently received much attention owing to its high frequency associated with pericardial tamponade (PT), showing unfavorable prognosis. However, early diagnosis and treatment remain challenging in cases of non-specific signs and symptoms.Case presentationA 64-year-old man was admitted to our hospital for acute osteomyelitis of the toes and was properly treated with antimicrobial agents. Three days after admission, the patient developed mild COVID-19 without pneumonia, for which early anti-COVID-19 agents were initiated. Nevertheless, the patient developed hemorrhagic PT due to acute pericarditis 2 weeks later, which was confirmed by cardiac magnetic resonance, requiring an urgent pericardiocentesis. Although cytological analysis of the hemorrhagic pericardial fluid strongly suggested adenocarcinoma, the atypical cells were eventually proven to be mesothelial cells with reactive atypia. Furthermore, lymph nodes swelling with abnormal 2-[18F]-fluoro-2-deoxy-D-glucose accumulation on imaging were suggestive of malignancy. However, biopsy examination revealed multiple non-caseating granulomas in the lymph node, unlikely due to malignancy. Eventually, the temporal association of the preceding COVID-19 with the occurrence of subacute PT without other identifiable cause led to a final diagnosis of COVID-19-associated acute pericarditis. With anti-inflammatory and corticosteroids treatment, the patient's symptoms involving the pericardial structure and function were completely resolved along with improvements in size of the affected lymphadenopathies.ConclusionsWe encountered a unique case of COVID-19-associated acute pericarditis exhibiting hemorrhagic PT. This case underscores the residual risk of delayed pericardial involvement even in patients with mild COVID-19 who receive early treatment, and the recognition that COVID-19 may cause various cytomorphological and histological features. Additionally, the importance of considering this rare entity as a cause of hemorrhagic pericardial effusions should be highlighted.

Abstract Aim This study aimed to investigate the effect of the coronavirus disease pandemic on the number of surgeries for gastroenterological cancer cases in Japan. Methods The data recorded in the National Clinical Database of Japan between 2018 and 2020 were utilized for this study. Five specific surgeries for primary cancers and surgery for acute diffuse peritonitis were considered the primary endpoints. We divided the study period into the prepandemic and postpandemic (after April 2020) periods and examined the number of surgeries in relation to clinical factors. Results Overall, 228 860 surgeries were analyzed. Among the five primary cancer surgeries, the number of distal gastrectomies for gastric cancer decreased the most (to 81.0% of the monthly number in the prepandemic period), followed by that of low anterior resections for rectal cancer (91.4%). In contrast, the number of pancreaticoduodenectomies for pancreatic cancer increased by 7.1%, while that of surgeries for peritonitis remained stable. This trend was observed nationwide. We also noted a marked reduction in the number of distal gastrectomy (to 72.5%), low anterior resection (84.0%), and esophagectomy (88.8%) procedures for T1 tumors. The noncurative resection rate and mortalities were low despite the increased proportion of T4 tumors and older patients. Conclusion A marked reduction in surgeries for gastric and rectal cancers with early T factors may reflect prioritization of surgeries and reduction in cancer screenings. Although the quality of the surgery was maintained in terms of reduced mortalities and morbidities, the long‐term effects of this pandemic should be monitored.

Abstract Aim The National Clinical Database (NCD) of Japan is a nationwide data entry system for surgery, and it marked its 10th anniversary in 2020. The aim was to present the 2020 annual report of gastroenterological surgery of the NCD. Methods The data of the surgical procedures stipulated by the training curriculum for board‐certified surgeons of the Japanese Society of Gastroenterological Surgery in the NCD from 2011 to 2020 were summarized. Results In total, 5 622 845 cases, including 593 088 cases in 2020, were extracted from the NCD. The total number of gastroenterological surgeries increased gradually in these 10 years, except for the year 2020 due to the COVID‐19 pandemic. The annual number of surgeries of each organ, except the pancreas and liver, decreased by 0.4%–13.1% in 2020 compared to 2019. The surgical patients were consistently aging, with more than 20% of all gastroenterological surgeries in 2020 involving patients aged 80 years or older. The participation of board‐certified surgeons increased for each organ (75.9%–95.7% in 2020). The rates of endoscopic surgery also increased constantly. Although the incidences of postoperative complications of each organ increased by 0.7%–7.9% in these 10 years, postoperative mortality rates decreased by 0.2%–1.5%. Conclusions We present here the short‐term outcomes of each gastroenterological operative procedure in 2020. This review of the 10‐years of NCD data of gastroenterological surgery revealed a consistent increase of the number of surgeries (except for in 2020), especially endoscopic procedures, and aging of the Japanese population. The good safety of Japanese gastroenterological surgeries was also indicated.

Abstract Large-diameter keyaki (Zelkova serrata Makino) logs have long been used in Japan as high-quality material especially for traditional construction and furniture. However, unlike other major wood species in Japan, keyaki has been practically considered as a wood species of high difficulty when processing. Keyaki frequently shows processing defects due to sawing, such as warping, cracking, and so forth, which often reduces the production yield of logs. Furthermore, there are drastic differences in those behaviors between individual logs, so causing unexpected processing defects. A scientific approach is required to improve this situation, but data on the material characteristics of keyaki were scarce. This study aimed to characterize the radial pattern of the residual stress as one of the processing-related characteristics. The measurement method was also examined. This study used diametral planks obtained from large-diameter keyaki logs to measure released strain of residual stress from pith to the bark sides. The results showed the distribution of released strain often showed peculiar zig-zag patterns characterized with localized residual stress, unlike the smooth bell curve pattern seen in typical logs of other species. Because of the unique characteristics, some practical points related to the measuring methodology were investigated. The extent of influence of this residual stress in the longitudinal direction was limited to within 30 cm from the site of measurement of the strain. In addition, the length of log necessary to measure the released strain without being affected by crosscutting was more than four times the log diameter—greater than the diameter ratio theorized by previous studies.

Objectives: Human Leukocyte Antigen HLA-B*57:01 and B*58:01 are considered anti-HIV-1 protective alleles. HLA-B*57:01/58:01-restricted HIV-1 Gag TW10 (TSTLQEQIGW, Gag residues 240-249) epitope-specific CD8+ T cell responses that frequently select for a Gag escape mutation, T242N, with viral fitness cost are crucial for HIV-1 control. Although this finding has been observed in cohorts where HIV-1 subtype B or C predominates, the protective impact of HLA-B*57:01/58:01 has not been reported in Southeast Asian countries where HIV-1 CRF01_AE is the major circulating strain. Here, the effect of HLA-B*57:01/58:01 on CRF01_AE infection was investigated. Methods: The correlation of HLA-B*57:01/58:01 with viral load and CD4 counts were analyzed in the CRF01_AE-infected Vietnamese cohort (N = 280). The impact of the T242N mutation on CRF01_AE replication capacity was assessed. Results: HLA-B*57:01/58:01-positive individuals mostly had HIV-1 with T242N (62/63) but showed neither a significant reduction in viral load nor increased CD4 counts relative to B*57:01/58:01-negative participants. In vitro and in vivo analyses revealed a significant reduction in viral fitness of CRF01_AE with T242N. In silico analysis indicated reduced presentation of epitopes in the context of CRF01_AE compared to subtype B or C in 10/16 HLA-B*57:01/58:01-restricted HIV-1 epitopes. Conclusion: The protective impact of HLA-B*57:01/58:01 on CRF01_AE infection is impaired despite strong suppressive pressure by TW10-specific CD8+ T cells.

Background: Transient constrictive pericarditis (TCP) is a distinct constrictive pericarditis (CP) subtype characterized by acute pericardial inflammation and transient constrictive physiology. If left untreated, it may progress to irreversible CP requiring pericardiectomy. However, making an early diagnosis of TCP remains difficult. Case presentation: A 51-year-old man presented with fever, chest pain, and dyspnea following preceding flu symptoms. An initial investigation suggested right-sided heart failure. Laboratory results revealed elevated inflammatory markers and hepatic enzyme levels. Echocardiography revealed pericardial effusion with a normal ejection fraction and diastolic ventricular septal bounce suggestive of pericardial constriction. Computed tomography suggested acute descending mediastinitis with pericarditis and pleuritis; however, detailed examinations ruled out this possibility. The constellation of increased serological inflammation, pericardial thickness/effusion, and constrictive physiology suggested TCP, confirmed by cardiac magnetic resonance (CMR) and hemodynamic studies. CMR also revealed coexistent myocarditis. After a thorough assessment for the cause of TCP, a viral etiology was suspected. Paired serology for virus antibody titers revealed a significant increase only in coxsackievirus A4 (CVA4) titers. With prompt anti-inflammatory treatment, the patient’s pericardial structure and function and concomitant inflammation of the surrounding tissues were nearly completely recovered, leading to a final diagnosis of TCP caused by CVA4. The subsequent clinical course was uneventful without recurrence at the 1-year follow-up. Conclusions: Here we described the first case of TCP caused by CVA4 concurrent with mediastinitis, myocarditis, and pleuritis, all of which were successfully resolved with anti-inflammatory treatment. Acute mediastinitis secondary to TCP is rare. This case highlights the clinical importance of assessing pericardial diseases as a source of acute mediastinitis and considering CVA4 as an etiology of TCP. An evaluation including multimodal cardiac imaging and serology for virus antibody titers may be useful for an exploratory diagnosis of TCP in right-sided heart failure patients with pericardial effusion.

Abstract Background Chronic constipation is prevalent and involves both colon sensitivity and various changes in intestinal bacteria, particularly mucosa-associated microflora. Here we examined regulatory mechanisms of TRPV4 expression by co-culturing colon epithelial cell lines with intestinal bacteria and their derivatives. We also investigated TRPV4 expression in colon epithelium from patients with constipation. Methods Colon epithelial cell lines were co-cultured with various enterobacteria (bacterial components and supernatant), folate, LPS, or short chain fatty acids. TRPV4 expression levels and promoter DNA methylation were assessed using pyrosequencing, and microarray network analysis. For human samples, correlation coefficients were calculated and multiple regression analyses were used to examine the association between clinical background, rectal TRPV4 expression level and mucosa-associated microbiota. Results Co-culture of CCD841 cells with P. acnes, C. perfringens, or S. aureus transiently decreased TRPV4 expression but did not induce methylation. Co-culture with clinical isolates and standard strains of K. oxytoca, E. faecalis, or E. coli increased TRPV4 expression in CCD841 cells, and TRPV4 and TNF-alpha expression were increased by E. coli culture supernatants but not bacterial components. Although folate, LPS, IL-6, TNF-alpha, or SCFAs alone did not alter TRPV4 expression, TRPV4 expression following exposure to E. coli culture supernatants was inhibited by butyrate or TNF-alphaR1 inhibitor and increased by p38 inhibitor. Microarray network analysis showed activation of TNF-alpha, cytokines, and NOD signaling. TRPV4 expression was higher in constipated patients from the terminal ileum to the colorectum, and multiple regression analyses showed that low stool frequency, frequency of defecation aids, and duration were associated with TRPV4 expression. Meanwhile, incomplete defecation, time required to defecate, and number of defecation failures per 24 h were associated with increased E. faecalis frequency. Conclusions Colon epithelium cells had increased TRPV4 expression upon co-culture with K. oxytoca, E. faecalis, or E. coli supernatants, as well as TNFα-stimulated TNFαR1 expression via a pathway other than p38. Butyrate treatment suppressed this increase. Epithelial TRPV4 expression was increased in constipated patients, suggesting that TRPV4 together with increased frequency of E. faecalis may be involved in the pathogenesis of various constipation symptoms.

Abstract Background Comprehensive metabolomic analyses have been conducted in various institutes and a large amount of metabolomic data are now publicly available. To help fully exploit such data and facilitate their interpretation, metabolomic data obtained from different facilities and different samples should be integrated and compared. However, large-scale integration of such data for biological discovery is challenging given that they are obtained from various types of sample at different facilities and by different measurement techniques, and the target metabolites and sensitivities to detect them also differ from study to study. Results We developed iDMET, a network-based approach to integrate metabolomic data from different studies based on the differential metabolomic profiles between two groups, instead of the metabolite profiles themselves. As an application, we collected cancer metabolomic data from 27 previously published studies and integrated them using iDMET. A pair of metabolomic changes observed in the same disease from two studies were successfully connected in the network, and a new association between two drugs that may have similar effects on the metabolic reactions was discovered. Conclusions We believe that iDMET is an efficient tool for integrating heterogeneous metabolomic data and discovering novel relationships between biological phenomena.

Abstract Body mass index (BMI) distribution and its impact on cardiovascular disease (CVD) vary between Asian and western populations. The study aimed to reveal time-related trends in the prevalence of obesity and underweight and safe ranges of BMI in Japanese patients with CVD. We analyzed 5,020,464 records from the national Japanese Registry of All Cardiac and Vascular Diseases—Diagnosis Procedure Combination dataset over time (2012–2019) and evaluated BMI trends and the impact on in-hospital mortality for six acute CVDs: acute heart failure (AHF), acute myocardial infarction (AMI), acute aortic dissection (AAD), ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Patients were categorized into five groups using the WHO Asian-BMI criteria: underweight (

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) induces chronic asymptomatic latent infection with a substantial proviral load but without significant viral replication in vivo. Cumulative studies have indicated involvement of CD8-positive (CD8+) cells, including virus-specific CD8+ T cells in the control of HTLV-1 replication. However, whether HTLV-1 expression from latently infected cells in vivo occurs in the absence of CD8+ cells remains unclear. Here, we examined the impact of CD8+ cell depletion by monoclonal anti-CD8 antibody administration on proviral load in HTLV-1-infected cynomolgus macaques. Five cynomolgus macaques were infected with HTLV-1 by inoculation with HTLV-1-producing cells. Administration of monoclonal anti-CD8 antibody in the chronic phase resulted in complete depletion of peripheral CD8+ T cells for approximately 2 months. All five macaques showed an increase in proviral load following CD8+ cell depletion, which peaked just before the reappearance of peripheral CD8+ T cells. Tax-specific CD8+ T-cell responses were detected in these recovered CD8+ T cells. Importantly, anti-HTLV-1 antibodies also increased after CD8+ cell depletion, indicating HTLV-1 antigen expression. These results provide evidence indicating that HTLV-1 can proliferate from the latent phase in the absence of CD8+ cells and suggest that CD8+ cells are responsible for the control of HTLV-1 replication. IMPORTANCE HTLV-1 can cause serious diseases such as adult T-cell leukemia (ATL) in humans after chronic asymptomatic latent infection with substantial proviral load. Proviruses are detectable in peripheral lymphocytes in HTLV-1 carriers, and the association of a higher proviral load with a higher risk of disease progression has been observed. However, neither substantial viral structural protein expression nor viral replication was detectable in vivo. Cumulative studies have indicated involvement of CD8+ cells, including virus-specific CD8+ T cells in the control of HTLV-1 replication. In the present study, we showed that CD8+ cell depletion by monoclonal anti-CD8 antibody administration results in HTLV-1 expression and an increase in proviral load in HTLV-1-infected cynomolgus macaques. Our results indicate that HTLV-1 can proliferate in the absence of CD8+ cells, suggesting that CD8+ cells are responsible for the control of HTLV-1 replication. This study provides insights into the mechanism of virus-host immune interaction in latent HTLV-1 infection.

Background: Takotsubo cardiomyopathy (TTC) is a non-ischaemic cardiomyopathy, characterized by transient wall motion abnormalities of the left ventricle. Although biventricular involvements are common with a poor prognosis, isolated right ventricular (RV) involvement of TTC is a rare, and its diagnosis remains challenging. Case presentation: We encountered a case of isolated RV-TTC presenting as acute RV failure, with progression to cardiogenic shock requiring intensive treatment. Conflicting echocardiographic findings of RV asynergy with RV enlargement despite normal left ventricular wall motion and mild tricuspid regurgitation led to the correct diagnosis. Finally, the patient showed complete recovery with normalization of cardiac structure and function. Conclusions: This case underscores the clinical significance of considering isolated RV-TTC as a new distinct variant form of TTC in terms of presentation, diagnostic findings, differential diagnosis, treatment strategy, and prognosis.

Abstract Background The risk of choking increases with aging, and the number of cases of choking-induced cardiac arrest is increasing. However, few studies have examined the prognosis of choking-induced cardiac arrest. The aim of this study was to reveal the rates of survival and dependence on devices in the long term after choking-induced cardiac arrest. Methods We analyzed data from the Shizuoka Kokuho Database, which consists of claims data of approximately 2.2 million people, from April 2012 to September 2018. We selected patients with choking-induced cardiac arrest who received cardiopulmonary resuscitation in the hospital. Patients were excluded if they were less than 20 years old, had an upper airway tumor, received ventilation assistance, or received enteral nutrition in the month prior to cardiac arrest. The primary outcome was death, and the secondary outcomes were the rates of survival at 3-months and independence on devices. Descriptive statistics are presented and compared among age groups (20–64 years, 65–74 years, 75–84 years, 85 years and older), and survival time analysis (Kaplan-Meier method) was performed. Results In total, 268 patients were analyzed, including 26 patients in the 20–64 age group, 33 patients in the 65–74 age group, 70 patients in the 75–84 age group, and 139 patients in the ≥85 age group. The overall 3-month survival rate was 5.6% (15/268). The 3-month survival rates were 3.8% (1/26) in the 20–64 age group, 15.2% (5/33) in the 65–74 age group, 8.6% (6/70) in the 75–84 age group, and 2.2% (3/139) in the ≥85 age group. The overall 12-month survival rate was 2.6% (7/268). Of the 7 patients who survived for 12 months, 3 received ventilation management and 5 received tube or intravenous feedings at 3 months. These survivors were still receiving ventilation assistance and tube feedings in the hospital and had not been discharged at 12 months. Conclusions The prognosis of choking-induced cardiac arrest was extremely poor when patients were not resuscitated before hospital arrival. Those who survived were mostly dependent on assistive devices. Additionally, none of the survivors dependent on assistive devices had discontinued the use of the devices at the long-term follow-up.

Abstract Vaccine‐associated myocarditis (VAM) is a rare entity but can result in potentially serious sequelae if left untreated. However, the mechanisms of the complications of VAM and its treatment remain unclear. Herein, we report the first case of VAM related to pneumococcal immunization, presenting as a local and systemic inflammatory reaction, in which the patient developed significant secondary mitral regurgitation, resulting in acute heart failure. Finally, the patient recovered completely following corticosteroid treatment. This case highlights the value of cardiac magnetic resonance and the pitfall of endomyocardial biopsy in establishing the definitive diagnosis of VAM and emphasizes the importance of optimal management in understanding the mechanism and instituting the treatment for secondary mitral regurgitation caused by VAM.

Abstract Background Osteoarthritis (OA) is one of the costliest and most disabling forms of arthritis, and it poses a major public health burden; however, its detailed etiology, pathophysiology, and metabolism remain unclear. Therefore, the purpose of this study was to investigate the key plasma metabolites and metabolic pathways, especially focusing on radiographic OA severity and synovitis, from a large sample cohort study. Methods We recruited 596 female volunteers who participated in the Iwaki Health Promotion Project in 2017. Standing anterior-posterior radiographs of the knee were classified by the Kellgren-Lawrence (KL) grade. Radiographic OA was defined as a KL grade of ≥ 2. Individual effusion-synovitis was scored according to the Whole-Organ Magnetic Resonance Imaging Scoring System. Blood samples were collected, and metabolites were extracted from the plasma. Metabolome analysis was performed using capillary electrophoresis time-of-flight mass spectrometry. To investigate the relationships among metabolites, the KL grade, and effusion-synovitis scores, partial least squares with rank order of groups (PLS-ROG) analyses were performed. Results Among the 82 metabolites examined in this assay, PLS-ROG analysis identified 42 metabolites that correlated with OA severity. A subsequent metabolite set enrichment analysis using the significant metabolites showed the urea cycle and tricarboxylic acid cycle as key metabolic pathways. Moreover, further PLS-ROG analysis identified cystine (p = 0.009), uric acid (p = 0.024), and tyrosine (p = 0.048) as common metabolites associated with both OA severity and effusion-synovitis. Receiver operating characteristic analyses showed that cystine levels were moderately associated with radiographic OA (p < 0.001, area under the curve 0.714, odds ratio 3.7). Conclusion Large sample metabolome analyses revealed that cystine, an amino acid associated with antioxidant activity and glutamate homeostasis, might be a potential metabolic biomarker for radiographic osteoarthritis and early phase synovitis.

Abstract Sarcopenia comprises a low skeletal muscle index (SMI) and low muscle strength (MS) or low physical function. Many sarcopenia biomarkers have been reported. With Crohn’s disease (CD), a low SMI is predictive of intestinal complications. Therefore, many CD studies have reported that sarcopenia is defined by SMI alone. This study investigated the sarcopenia frequency by assessing the SMI and MS of Japanese patients with CD and biomarkers predicting a low SMI. We evaluated the SMI using a bioelectrical impedance analysis, handgrip strength, and C-reactive protein, albumin, interleukin-6, tumor necrosis factor-α, growth differentiation factor (GDF)-8, and GDF-15 levels as biomarker candidates for 78 CD patients at our hospital. Sarcopenia and a low SMI were observed in 7.7% and 42.3% of the patients, respectively. There was a significant difference in the GDF-15 levels of the low SMI group and normal group according to the multivariate analysis (P = 0.028; odds ratio [OR], 1.001; 95% confidence interval [CI] 1.000–1.002). When evaluated by sex, males exhibited a negative correlation between the GDF-15 level and SMI (Pearson’s r = − 0.414; P = 0.0031), and the multivariate analysis indicated a significant difference in the GDF-15 levels (P = 0.011; OR, 1.001; 95% CI 1.000–1.002). GDF-15 levels may indicate a low SMI with CD.

The abnormal lipid metabolism in the liver that occurs after high caloric intake is the main cause of nonalcoholic fatty liver disease (NAFLD). Differences between samples from healthy livers and livers from individuals with NAFLD indicate that changes in liver function occur during disease progression. Here, we examined changes in protein expression in a fatty liver model in the early stages of obesity to identify potential alterations in function. The proteins expressed in the liver tissue of pre‐obese rats were separated via SDS/PAGE and stained with Coomassie brilliant blue‐G250. Peptide mass fingerprinting indicated an increase in the expression of carbonic anhydrase 3 (CA3) relative to controls. Western blotting analysis confirmed the increase in CA3 expression, even in an early fat‐accumulation state in which excessive weight gain had not yet occurred. In human hepatoma HepG2 cells, fat accumulation induced with oleic acid also resulted in increased CA3 expression. When the cells were in a state of fat accumulation, treating them with the CA3 inhibitors acetazolamide (ACTZ) or 6‐ethoxyzolamide (ETZ) suppressed fat accumulation, but only ETZ somewhat reduced the fat‐induced upregulation of CA3 expression. Expression of CA3 was therefore upregulated in response to the consumption of a high‐fat diet, even in the absence of an increase in body weight. The suppression of CA3 activity by ACTZ or ETZ reduced fat accumulation in hepatocytes, suggesting that CA3 is involved in the development of fatty liver.

Abstract Background and Aim In Japan, the actual number of stoma constructions and stoma closures is not known. The aim of this study was to conduct a survey to determine the number of gastrointestinal stoma constructions and closures in Japan. Methods Enrolled participants comprised patients undergoing selected gastrointestinal surgeries who were recorded in the National Clinical Database. This database uses the “Common Items for Gastrointestinal Surgeons.” These procedures were formulated by the Japanese Society of Gastroenterological Surgery during 2013–2018. Results According to the National Clinical Database, a total of 154,323 gastrointestinal stomas were constructed between January 1, 2013 and December 31, 2018. By procedure, there were 78,723 cases of stoma construction, 39,653 of abdominoperineal resection, 2470 total pelvic exenteration procedures, and 33,572 Hartmann's procedures. The ratio of stoma closures to stoma constructions increased annually in patients under 70 y of age but not in older patients. Approximately 35% of total colectomies, 60% of proctocolectomies, and 20% of low anterior resections were accompanied by stoma construction. The number of patients with rectal cancer who underwent colostomy increased gradually during the study period and the number who underwent stoma construction increased among older patients. Conclusion The number of cases of gastrointestinal stoma construction has increased gradually in Japan, and the proportion of older patients is increasing each year. The purposes and surgical techniques for stoma construction are diverse and are expected to increase in Japan, a super‐aged society.

Skin exposed to ultraviolet light produces hydrogen peroxide (H2O2) and reactive oxygen species (ROS) that cause protein denaturation and other disorders. We investigated whether electrolyticreduction ion water (ERI), which has reducing properties and has been reported to protect skin, exhibits antioxidant activity in skin keratinocytes. The antioxidant activity of ERI was first examined using DPPH assay and Electron Spin Resonance to test for radicals, and using the Amplex Red method to test for H2O2. Concentration-dependent scavenging of hydroxyl radical but no H2O2 depletion were detected. An investigation of the expression of heme oxygenase-1, which is upregulated by oxidative response in cells, showed an increase through H2O2 oxidation, which was inhibited by ERI in a concentration-dependent manner. This suggests that ERI directly removes ROS. Quantitative real-time polymerase chain reaction analysis was performed to determine whether ERI regulates the expression of aquaporin 3 (AQP3), a known H2O2 transporter. This analysis revealed that ERI enhances AQP3 expression in a concentration-dependent manner and is involved in the transport of intracellular H2O2 to the extracellular space. In addition, ERI inhibited H2O2-induced cytotoxicity in a concentration-dependent manner. These results suggest that ERI protects keratinocytes from ROS by directly scavenging them and indirectly by eliminating them through the promotion of the efflux of intracellular H2O2. [ABSTRACT FROM AUTHOR]

Abstract Background Esophagectomy followed by gastric conduit reconstruction is a standard surgical procedure for esophageal cancer. However, there is no evidence of the superiority or inferiority of the posterior mediastinal (PM) versus the retrosternal (RS) reconstruction route with regard to short‐term outcomes after esophagectomy. We aimed to elucidate whether the reconstruction route can affect the short‐term outcomes after esophagectomy followed by gastric conduit reconstruction. Methods We reviewed the clinical data of patients who underwent esophagectomy between 2016 and 2018 from the Japanese National Clinical Database. This study included 9786 patients who underwent gastric conduit reconstruction through the PM or RS route with cervical anastomosis. Results Of the 9786 patients analyzed, 3478 and 6308 underwent gastric conduit reconstruction thorough the PM and RS routes, respectively. The incidence of anastomotic leak and surgical site infection (SSI) was significantly lower in the PM group than in the RS group (11.7% vs 13.8%, P = .005 and 8.4% vs 14.9%, P

Foramen magnum dural arteriovenous fistula (FM-DAVF) is a subset of craniocervical junction arteriovenous fistulas. We report a rare case of FM-DAVF with early rebleeding and review the literature. A 50-year-old man experienced 3 episodes of intracranial bleeding from a vessel malformation in the acute stage. We identified an FM-DAVF, supplied by multiple feeding arteries (eg, left ascending pharyngeal artery) that drained into the straight sinus and left superior petrosal sinus. The draining vein had venous varices. We performed transarterial feeder embolization and surgical disconnection of the DAVF. Early rebleeding of FM-DAVF is rare. High-risk patients require risk assessment and appropriate treatment as soon as possible in the acute stage.

Abstract Background Hemoglobin A1c (HbA1c) levels are routinely measured during health check-ups and are used as an indicator of glycemic control in Japan. However, only a few studies have followed up individuals to assess the risk of diabetes development and worsening based on HbA1c screening results. This study evaluated the relationship between HbA1c screening results and the risk of diabetes development and worsening. Methods Data were collected from the Shizuoka Kokuho Database, a Japanese administrative claims database of insured individuals aged > 40 years. We included individuals available for follow-up from April 2012 to March 2018 who had not received any diabetes treatment before March 2014. HbA1c screening results were categorized into 4 groups based on the HbA1c levels at the 2012 and 2013 health check-ups: group A, those whose HbA1c levels were 6.5% in 2012 but 6.5% in 2012 and 2013; and group D, those whose HbA1c levels were 6.5% in 2013. Logistic regression models were used to analyze diabetes development and worsening, defined as the initiation of diabetes treatment by March 2018 and the use of injection drugs by participants who initiated diabetes treatment by March 2018. Results Overall, 137,852 individuals were analyzed. After adjusting for covariates, compared with group A, group B was more likely to initiate treatment within 4 years (odds ratio: 22.64; 95% confidence interval: 14.66–34.99). In patients who initiated diabetes treatment by March 2018, injection drugs were less likely used by group D than by group A (odds ratio: 0.28; 95% confidence interval: 0.12–0.61). Conclusions Our study suggests that although HbA1c levels measured during health check-ups were correlated with the risk of diabetes development and worsening, HbA1c levels in a single year may not necessarily provide sufficient information to consider these future risks.

Abstract Background We aimed to present the 2019 annual report of the gastroenterological section of the National Clinical Database (NCD). Methods We reviewed 609,589 cases recorded in 2019 and 5,029,764 cases registered from 2011 to 2019 for the 115 selected gastroenterological surgical procedures. Results The main features of gastroenterological surgery in Japan were similar to those described in the 2018 annual report, namely, that 1) operative numbers gradually increased in all procedures, except gastrectomy and hepatectomy, which decreased in these years; 2) in all eight major gastroenterological surgeries, the age distribution tended toward older patients; 3) the morbidity of esophagectomy, hepatectomy, and pancreaticoduodenectomy increased, but mortality was minimized in all procedures; 4) all eight major gastroenterological procedures have increasingly been performed under laparoscopy; and 5) board‐certified surgeons were increasingly involved. These trends in recent years were more prominent in 2019. Conclusions Thanks to the continuous cooperation and dedication of the surgeons, medical staff, and surgical clinical reviewers who registered the clinical data into the NCD, it is possible to understand the comprehensive landscape of surgery in Japan and to disclose new evidence in this field. The Japanese Society of Gastroenterological Surgery will continue to promote the value of this database and encourage the use of feedback and clinical studies using the NCD, now and in the future. Generating further approaches to surgical quality improvement are important directions for future research.

Abstract To determine whether temporal subtraction (TS) CT obtained with non-rigid image registration improves detection of various bone metastases during serial clinical follow-up examinations by numerous radiologists. Six board-certified radiologists retrospectively scrutinized CT images for patients with history of malignancy sequentially. These radiologists selected 50 positive and 50 negative subjects with and without bone metastases, respectively. Furthermore, for each subject, they selected a pair of previous and current CT images satisfying predefined criteria by consensus. Previous images were non-rigidly transformed to match current images and subtracted from current images to automatically generate TS images. Subsequently, 18 radiologists independently interpreted the 100 CT image pairs to identify bone metastases, both without and with TS images, with each interpretation separated from the other by an interval of at least 30 days. Jackknife free-response receiver operating characteristics (JAFROC) analysis was conducted to assess observer performance. Compared with interpretation without TS images, interpretation with TS images was associated with a significantly higher mean figure of merit (0.710 vs. 0.658; JAFROC analysis, P = 0.0027). Mean sensitivity at lesion-based was significantly higher for interpretation with TS compared with that without TS (46.1% vs. 33.9%; P = 0.003). Mean false positive count per subject was also significantly higher for interpretation with TS than for that without TS (0.28 vs. 0.15; P

Infectious aortic aneurysm (IAA) can be a rare but potentially fatal sequela of infectious inflammatory disease of the aortic wall with a high incidence of rupture. The definitive diagnosis is based on vascular imaging of the aneurysm using contrast-enhanced computed tomography (CE-CT) and identification of the causative microorganism from positive blood cultures (BCs). However, IAA remains extremely difficult to diagnose and treat in patients with prior antimicrobial treatment or with renal dysfunction. Here we describe a case of an 85-year-old woman with IAA caused by Arthrobacter russicus presenting with abdominal pain and fever that was initially diagnosed as a presumptive urinary tract infection and treated with empiric antimicrobial therapy. However, persistent abdominal pain with increased serological inflammation necessitated further evaluation. Unenhanced multimodality imaging considering the renal dysfunction revealed infectious aortitis of the infrarenal abdominal aorta, together with the initial culture results, leading to the tentative diagnosis of Klebsiella pneumoniae aortitis. Thereafter, serial monitoring with unenhanced magnetic resonance angiography (MRA) using thin-slab maximum intensity projection (TS-MIP) revealed acute aortic expansion strongly suggestive of a pseudoaneurysm that was successfully treated with early surgical repair under adequate infection control. Despite negative Gram staining and tissue culture results for the excised aortic wall, a definitive diagnosis of IAA secondary to A. russicus rather than K. pneumoniae was finally made by confirming the histologic findings consistent with IAA and the identification of A. russicus 16S rRNA on the resected aortic wall. The patient also developed a vascular graft infection during the postoperative course that required long-term systemic antimicrobial therapy. This case highlights the value of unenhanced MRA in the early detection of IAA in patients with renal dysfunction and the importance of a molecular diagnosis for identifying the causative microorganism in cases of culture- or tissue-negative IAA.

The minimum sample volume for capillary electrophoresis-Fourier transform mass spectrometry (CE-FTMS) useful for analyzing hydrophilic metabolites was investigated using samples obtained from colorectal cancer patients. One, two, five, and ten biopsies were collected from tumor and nontumor parts of the surgically removed specimens from each of the five patients who had undergone colorectal cancer surgery. Metabolomics was performed on the collected samples using CE-FTMS. To determine the minimum number of specimens based on data volume and biological interpretability, we compared the number of annotated metabolites in each sample with different numbers of biopsies and conducted principal component analysis (PCA), hierarchical cluster analysis (HCA), quantitative enrichment analysis (QEA), and random forest analysis (RFA). The number of metabolites detected in one biopsy was significantly lower than those in 2, 5, and 10 biopsies, whereas those detected among 2, 5, and 10 pieces were not significantly different. Moreover, a binary classification model developed by RFA based on 2-biopsy data perfectly distinguished tumor and nontumor samples with 5- and 10-biopsy data. Taken together, two biopsies would be sufficient for CE-FTMS-based metabolomics from a data content and biological interpretability viewpoint, which opens the gate of biopsy metabolomics for practical clinical applications.

Abstract Aims/Introduction Increased incidence of hospitalization for heart failure (HHF) among patients with diabetes is increasingly being reported. We investigated the incidence of adverse cardiovascular events including HHF among patients with type 2 diabetes mellitus, and the potential clinical improvement with sodium–glucose cotransporter 2 inhibitors (SGLT2i) using a contemporary administrative claims database from a large governmental district of Japan. Materials and Methods We included initiators of any oral glucose‐lowering drugs between 2013 and 2018. We estimated the 5‐year cumulative incidence of hospitalization for HF, myocardial infarction and stroke, treating death as a competing risk. We evaluated the possible impact of introducing SGLT2i to the potential recipients of the drug, using the inclusion criteria from Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA‐REG OUTCOME) and Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 (DECLARE‐TIMI 58) trials, assuming the same risk reduction as theirs. Results Among 23,340 drug initiators (54.0% men, and 6.4% aged >85 years), the 5‐year cumulative incidence was 5.4% (95% confidence interval 4.9–5.9%) for HHF, 1.9% (95% confidence interval 1.7–2.2%) for myocardial infarction admission and 6.1% (95% confidence interval 5.7–6.6%) for stroke admission. Among 6,192 patients with laboratory test data, 651 (10.5%) and 2,680 (43.3%) patients met the EMPA‐REG‐like and DECLARE‐like criteria, respectively. The 5‐year cumulative incidence among the 2,849 patients meeting either of the criteria was estimated to decrease from 97.1 to 75.6 events through 75% adoption of SGLT2i. Conclusions The incidence of HHF was similar to that of stroke. A significant portion of our cohort met the inclusion criteria for major randomized clinical trials for SGLT2i, and estimated reduction in the HHF events was substantial.

Abstract Aims/Introduction Glucose fluctuation (GF) is a residual risk factor for coronary artery disease (CAD). We investigated whether GF influenced clinical outcomes and progression of coronary stenosis in stable CAD patients. Materials and Methods In this prospective study, 101 consecutive lipid‐controlled stable CAD patients underwent percutaneous coronary intervention were enrolled, and GF was expressed as the mean amplitude of glycemic excursion (MAGE) obtained by continuous glucose monitoring before the procedure was evaluated. At 9 months after enrollment, culprit and non‐culprit (mild‐to‐moderate stenosis without ischemia) lesions were serially assessed by angiography. Cardiovascular events (CVE) consisting of cardiovascular death, non‐fatal myocardial infarction or ischemia‐driven revascularization during 2‐year follow up, rapid progression in non‐culprit lesions (defined as ≥10% luminal narrowing progression in lesions with stenosis ≥50%, ≥30% luminal narrowing progression in non‐culprit lesions with stenosis

The novel coronavirus disease (COVID-19) has resulted in a global pandemic. Recently, COVID-19-related pneumothorax has gained attention because of the associated prolonged hospital stay and high mortality. While most cases of pneumothorax respond well to conservative and supportive care, some cases of refractory pneumothorax with persistent air leaks (PALs) do not respond to conventional therapies. There is a lack of evidence-based management strategies to this regard. We describe the case of a 73-year-old man with COVID-19-related acute respiratory distress syndrome (ARDS) who developed delayed tension pneumothorax with PALs caused by alveolopleural fistulas. Despite chest tube drainage, autologous blood pleurodesis, and endoscopic procedures, the PALs could not be closed, and were complicated by thoracic empyema. Subsequent minimally invasive open-window thoracostomy (OWT) with vacuum-assisted closure (VAC) therapy helped successfully control the refractory PALs. Serial chest computed tomography monitoring was useful for the early detection of the pneumothorax and understanding of its temporal relationship with air-filled lung cysts. Our case provides a new perspective to the underlying cause of refractory pneumothorax with PALs, secondary to COVID-19-related ARDS, and underscores the potential of OWT with VAC therapy as a therapeutic alternative in such cases.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis involving small-to-medium-sized vessels characterized by asthma, vasculitis, and peripheral eosinophilia. EGPA-associated eosinophilic myocarditis (EM) occurs rarely, yet can be fatal if left untreated. Moreover, the accurate diagnosis of EGPA-associated EM without vasculitis is exceptionally difficult because of the overlapping features with EM of other causes. We report a case of probable EGPA with subclinical neurological involvement that presented with acute EM. The constellation of peripheral eosinophilia, left ventricular dysfunction, and normal epicardial coronary arteries raised suspicion of acute EM, which was confirmed by cardiac magnetic resonance (CMR) investigation and endomyocardial biopsy (EMB). Prompt systemic administration of corticosteroids completely restored and normalized myocardial structure and function. Although the patient's history suggested the presumed hypersensitivity myocarditis, EMB revealed EM without vasculitis, not hypersensitivity, leading to a tentative diagnosis of idiopathic hypereosinophilic syndrome. Interestingly, the characteristic findings of vasculitis on CMR imaging strongly suggested EGPA-associated EM. Although the patient had no clinical neurological manifestations, a nerve conduction study confirmed mononeuritis multiplex, leading to the final diagnosis of probable EGPA. Therefore, this case highlights the diagnostic challenge associated with EGPA and the diagnostic synergy of CMR and EMB for an exploratory diagnosis of EGPA-associated EM.

Abstract Takotsubo cardiomyopathy (TCM) causes QT interval prolongation, potentially leading to a fatal arrhythmia. We report the first case of TCM associated with licorice‐induced pseudoaldosteronism causing fatal arrhythmia in an older patient on polypharmacy including yokukansan (TJ‐54) and galantamine. Polypharmacy should be resolved to prevent unexpected adverse events in older patients.

Objectives: This study aimed to examine the clinical characteristics of colonic diverticular bleeding (CDB) in elderly individuals. Methods: This retrospective case-control study was conducted at a single tertiary center. A total of 519 patients (356 men and 163 women; mean age of 73.1 ± 12.5 years) with CDB and hospitalized between January 2004 and May 2019 were analyzed. The subjects were divided into two groups: the elderly (274 individuals aged 75 years; mean age, 82.1 ± 5.3 years) and non-elderly (245 individuals aged

Abstract Background Thyroid storm (TS) is a rare but potentially life-threatening sequelae of untreated or undertreated hyperthyroidism. While TS frequently causes high-output heart failure, low-output heart failure related to dilated cardiomyopathy (DCM) is extremely rare. Tachycardia is a common clinical presentation of TS, and β1-selective blockers are the first-line agents for treating TS-associated tachycardia. However, given that β-blockers have negative chronotropic and negative inotropic effects, amiodarone may be safe and effective for the treatment of TS-induced tachyarrhythmia in patients with moderate to severe heart failure. While long-term amiodarone administration causes hypothyroidism, or less frequently, hyperthyroidism, little is known about the effects of short-term amiodarone administration on thyroid function. Case presentation A 31-year-old healthy woman presented with worsening dyspnoea. She was tachycardic with multifocal atrial tachycardia (MAT) of 184 beats/min, confirmed by electrocardiogram. Echocardiographic findings were consistent with DCM, with an ejection fraction of 20%. Thus, she was initially diagnosed with acute heart failure due to DCM with coexistent MAT. Tachycardia persisted despite cardioversion attempts and treatment with multiple anti-arrhythmic drugs. Consequently, she rapidly progressed to cardiogenic shock and respiratory decompensation, which required intubation and an intra-aortic balloon pump support. Moreover, the undiagnosed Graves' disease, lack of suspicion, and postponed analysis of thyroid function tests led to a delayed diagnosis of TS. Amiodarone, which was initiated for MAT, unexpectedly ameliorated thyrotoxicosis, resulting in a euthyroid state and the patient’s significantly improved condition and cardiac function. She was discharged on day 40. Finally, she underwent total thyroidectomy; thyroid pathology was consisting with Graves' disease. Her postoperative course was uneventful. Conclusions Herein, we describe a case of delayed diagnosis of dilated thyrotoxic cardiomyopathy with coexistent MAT. The patient required intensive care due to the catastrophic sequelae and was successfully treated with amiodarone. This is the first case report of TS-associated MAT and highlights the clinical importance of high suspicion of TS in de novo heart failure with any tachyarrhythmia or DCM of unknown etiology and the potential effects of short-term amiodarone administration in the treatment of TS.

Abstract A 69‐year‐old female diagnosed with ostial left anterior descending artery acute myocardial infarction underwent percutaneous coronary intervention using combined directional coronary atherectomy followed by drug‐coated balloon angioplasty. This report highlights a novel management strategy with no permanent scaffold left in the coronary artery.

Abstract Background Pneumothorax is an extrapulmonary air accumulation within the pleural space between the lung and chest wall. Once pneumothorax acquires tension physiology, it turns into a potentially lethal condition requiring prompt surgical intervention. Common symptoms are chest pain and dyspnea; hence an electrocardiogram (ECG) is often performed in emergent settings. However, early diagnosis of pneumothorax remains challenging since chest pain and dyspnea are common symptomatology in various life-threatening emergencies, often leading to overlooked or delayed diagnosis. While the majority of left-sided pneumothorax-related ECG abnormalities have been reported, right-sided pneumothorax-related ECG abnormalities remain elucidated. Case presentation A 51-year-old man presented to the emergency department with acute-onset chest pain and dyspnea. Upon initial examination, the patient had a blood pressure of 98/68 mmHg, tachycardia of 100 beats/min, tachypnea of 28 breaths/min, and oxygen saturation of 94% on ambient air. Chest auscultation revealed decreased breath sounds on the right side. ECG revealed sinus tachycardia, phasic voltage variation of QRS complexes in V4–6, P-pulmonale, and vertical P-wave axis. Chest radiographs and computed tomography (CT) scans confirmed a large right-sided pneumothorax. The patient’s symptoms, all the ECG abnormalities, and increased heart rate on the initial presentation resolved following an emergent tube thoracostomy. Moreover, we found that these ECG abnormalities consisted of two independent factors: respiratory components and the diaphragm level. Besides, CT scans demonstrated the large bullae with a maximum diameter of 46 × 49 mm in the right lung apex. Finally, the patient showed complete recovery with a thoracoscopic bullectomy. Conclusions Herein, we describe a case of a large right-sided primary spontaneous pneumothorax with characteristic ECG findings that resolved following re-expansion of the lung. Our case may shed new light on the mechanisms underlying ECG abnormalities associated with a large right-sided pneumothorax. Moreover, ECG manifestations may provide useful information to suspect a large pneumothorax or tension pneumothorax in emergent settings where ECGs are performed on patients with acute chest pain and dyspnea.

Abstract Background and Aim Colonic diverticular bleeding (CDB) stops spontaneously, but sometimes, excessive bleeding does not allow hemostasis and requires interventional radiology (IR)/surgery. We examined risk factors in patients who required IR/surgery for CDB and late recurrent bleeding rate after IR/surgery. Methods This retrospective case–control study was conducted at a tertiary center. We included 608 patients who required hospitalization for CDB. Patients were investigated for risk factors using logistic regression analysis. We also investigated early and late recurrent bleeding rates following IR/surgery. Results In 261 patients (42.9%), the bleeding source was identified, and endoscopic hemostasis was performed; 23 (3.8%) required IR/surgery. In multivariate analysis, shock state with a blood pressure of ≤90 mmHg (P