Prevalence of cardiac amyloidosis in atrial fibrillation: a CMR study prior to catheter ablation.

The frequency of cardiac amyloidosis potentially present in patients with atrial fibrillation (AF) remains unclear. The purpose of this study is to determine the frequency and clinical characteristics of cardiac amyloidosis latent in AF by performing cardiac magnetic resonance imaging (MRI) in patients scheduled for AF ablation. We retrospectively analyzed 193 consecutive patients who underwent CA and cardiac MRI for atrial fibrillation. The primary endpoint of the study was the frequency of histologically confirmed cardiac amyloidosis or suspected cardiac amyloidosis [positive imaging findings on cardiac MRI strongly suspecting cardiac amyloidosis (diffuse subendocardial late gadolinium enhancement or MRI-derived extracellular volume of > 0.40)]. Among the 193 patients, 8 were confirmed or suspected cases of cardiac amyloidosis, representing a frequency of 4% (8/193 patients). Multivariate analysis identified interventricular septal thickness at end-diastole (LVSd) as an independent and significant predictor of cardiac amyloidosis (OR: 1.72, 95% CI 1.12-2.87, p = 0.020).The optimal cut-off value for IVSd was determined to be > 12.9 mm based on the Youden index. At this cut-off, the sensitivity was 75.0% (95% CI 34.9-96.8%) and the specificity was 92.3% (95% CI 87.4-95.7%), allowing for the identification of patients with definite or suspected cardiac amyloidosis. The frequency of confirmed and suspected cases of cardiac amyloidosis among patients with an IVSd > 12.9 mm was 30% (6/20 patients). In addition, prevalence of biopsy-proven cardiac amyloidosis was 10% (2/20). The prevalence of cardiac amyloidosis in atrial fibrillation patients scheduled for ablation with cardiac hypertrophy is not negligible.

Integrator complex subunit 6 promotes hepatocellular steatosis via ß-catenin-PPARγ axis.

Hepatic adipogenesis has common mechanisms with adipocyte differentiation such as PPARγ involvement and the induction of adipose tissue-specific molecules. A previous report demonstrated that integrator complex subunit 6 (INTS6) is required for adipocyte differentiation. This study aimed to investigate INTS6 expression and its role in hepatic steatosis progression. The expression of INTS6 and PPARγ was examined in the liver of a mouse model of steatohepatitis and in paired liver biopsy samples from 11 patients with severe obesity and histologically proven metabolic dysfunction associated steatohepatitis (MASH) before and one year after bariatric surgery. To induce hepatocellular steatosis in vitro, an immortalized human hepatocyte cell line Hc3716 was treated with free fatty acids. In the steatohepatitis mouse model, we observed hepatic induction of INTS6, PPARγ, and adipocyte-specific genes. In contrast, ß-catenin which negatively regulates PPARγ was reduced. Biopsied human livers demonstrated a strong positive correlation (r2 = 0.8755) between INTS6 and PPARγ mRNA levels. After bariatric surgery, gene expressions of PPARγ, FABP4, and CD36 were mostly downregulated. In our in vitro experiments, we observed a concentration-dependent increase in Oil Red O staining in Hc3716 cells after treatment with the free fatty acids. Alongside this change, the expression of INTS6, PPARγ, and adipocyte-specific genes was induced. INTS6 knockdown using siRNA significantly suppressed cellular lipid accumulation together with induction of ß-catenin and PPARγ downregulation. Collectively, INTS6 expression closely correlates with PPARγ. INTS6 suppression significantly reduced hepatocyte steatosis via ß-catenin-PPARγ axis, indicating that INTS6 could be a novel therapeutic target for treating MASH.

Effects of the Coronavirus disease 2019 pandemic on mortality in patients with lung cancer: A multiple mediation analysis in Japan.

COVID-19 pandemic has had a substantial effect on healthcare systems worldwide, including the care of patients with lung cancer. The impact of healthcare disruptions and behavioral changes on lung cancer mortality is unclear. Patients newly diagnosed with lung cancer during the pandemic period 2020-2021 were compared with those diagnosed in the pre-pandemic 2018-2019. The primary outcome was all-cause mortality within 1 year. Cox proportional hazards regression analyses were conducted to estimate the changes in mortality between pandemic and pre-pandemic. Multiple mediation analyses were performed to determine the factors that accounted for the changes in mortality. In total, 5785 patients with lung cancer were included in this study. The overall mortality rate was significantly higher during the pandemic compared with the pre-pandemic (crude hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05, 1.29). Mediation analyses showed that not receiving tumor-directed treatment, diagnosis at an older age, and decreased diagnosis through cancer screening significantly accounted for 17.5% (95%CI: 4.2, 30.7), 13.9% (95%CI: 0.8, 27.0), and 12.4% (95%CI: 3.0, 21.8) of the increased mortality, respectively. This study revealed a significant increase in mortality risk in patients with lung cancer who have not received tumor-directed treatment or cancer screening, despite potential selection bias for follow-up status. Efforts should be focused on ensuring timely access to healthcare services, optimizing treatment delivery, and addressing the unique challenges faced by patients with lung cancer during the pandemic to mitigate the impact of the pandemic on lung cancer outcomes and provide clinical care to vulnerable populations.

Delayed onset septic pelvic thrombophlebitis treated by tissue-plasminogen activator following initial treatment for massive right ovarian vein thrombosis and methicillin-resistant Staphylococcus aureus bacteremia: A case report.

Septic pelvic thrombophlebitis (SPT) is a rare condition that forms thrombosis in the pelvic veins, typically the ovarian veins, with subsequent infection and inflammation. We present a case of right ovarian vein thrombosis (ROVT), methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, and delayed onset of SPT symptoms, requiring tissue-plasminogen activator. A 40-year-old woman, G3P2, at 38 weeks' gestation, was admitted with a fever of 39°C. She had cervical insufficiency and had been often on bed rest. Blood culture revealed MRSA and computed tomography revealed a large ROVT. She received vancomycin and direct oral anticoagulant, and her fever resolved by day 3. On day 16, fever recurred with severe pain over the ROVT. Second computed tomography showed thickening of venous wall with enhancement around ROVT, consistent with SPT. Since pain and fever gradually exacerbated despite treatment with DOAC and antimicrobials, she was started on heparin and tissue plasminogen activator on days 23 and 25, respectively. Along with recanalization on the thrombosis by day 29, fever and abdominal pain resolved. We experienced a case of delayed onset SPT associated with MRSA bacteremia and a large ROVT. MRSA bacteremia might cause the originally existing ROVT to become an infection source, resulting in SPT with recurrent symptoms and long-term treatment. Early and strict anticoagulation is crucial in cases with a large thrombosis and bacteremia, due to the high risk of progression to SPT. This case highlights the importance of recanalization for the treatment of SPT and usefulness of administration of tissue-plasminogen activator for the massive thrombosis.

Idiopathic thoracic spinal cord herniation into the vertebra progressing for 3 years.

A 43-year-old, previously healthy man experienced a decreased sensation in the left lower extremity without preceding spinal trauma. At presentation, the patient exhibited slight motor weakness in the left lower extremity, in addition to decreased pain sensation below the ipsilateral T7. Spinal magnetic resonance imaging (MRI) revealed abnormal findings consistent with idiopathic thoracic spinal cord herniation (ITSCH) at the T5/6 level. Computed tomography (CT) revealed a small vertebral erosion at the lower T5. The patient's symptoms gradually progressed over the next 3 years. MRI revealed marked lateral elongation of the cord at the T5/6 and apparent intravertebral cord herniation. The patient underwent ITSCH reduction through T5-6 laminectomies. The herniated cord was vertically long with a bulbous rostral part. Successful ITSCH reduction was achieved and the patient's postoperative course was uneventful. ITSCH is a progressive pathology that requires prompt surgical reduction. Certain ITSCHs may be complicated by intravertebral cord herniation.

Multicenter study of invasive gastric cancer detected after 10 years of Helicobacter pylori eradication in Japan: Clinical, endoscopic, and histopathologic characteristics.

Objectives: Gastric cancer can be diagnosed even in patients long after Helicobacter pylori eradication. Most cases involve intramucosal lesions; however, some are invasive and require surgery. To clarify appropriate long-term surveillance methods, this study compared invasive gastric cancer diagnosed ≥10 and <10 years after eradication. Methods: This retrospective multicenter study included 14 institutions. We included 377 patients with gastric cancer with submucosal or deep invasion after surgical or endoscopic resection. Ordered logistic regression analysis was used to explore the factors contributing to the pathological stage and histological type. Results: Invasive gastric cancer was detected in 84 patients (Group L) and 293 patients (Group S) ≥10 and <10 years after H. pylori eradication, respectively. Endoscopic mucosal atrophy at the time of cancer detection was similar in both groups; 50% of the patients had severe atrophy. Annual endoscopy correlated with early pathological stage (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.14-0.54, p < 0.001). Group L exhibited an independent correlation with the advanced pathological stage (OR 2.27, 95% CI 1.06-4.88, p = 0.035) and the undifferentiated type (OR 2.12, 95% CI 1.16-3.90, p = 0.015). The pure differentiated type and early pathological stage significantly (p = 0.001) correlated with severe mucosal atrophy in Group S but not in Group L. Conclusions: Invasive cancers diagnosed ≥10 years after H. pylori eradication were likely to be more malignant in histological type and pathological stage. Gastric cancer surveillance should continue regardless of endoscopic atrophy, particularly ≥10 years after eradication.

Assessing the Influence of the COVID-19 Pandemic on Gastric Cancer Mortality Risk.

BACKGROUND: The global impact of the coronavirus disease 2019 (COVID-19) pandemic on public health has been significant. Upper gastrointestinal endoscopy for screening and diagnosis decreased along with new gastric cancer (GC) diagnoses. METHODS: This study assesses how the pandemic affected GC mortality using data from Hiroshima Prefecture, comparing mortality rates between patients diagnosed during the pandemic (2020 and 2021) and pre-pandemic (2018 and 2019) periods. The crude hazard ratios (HRs) and HRs adjusted for age, sex, clinical stage, treatment status, and travel distance to the nearest GC screening facility were estimated using Cox regression models. Subgroup and sensitivity analyses were also performed. RESULTS: A total of 9571 patients were diagnosed, with 4877 eligible for follow-up. The median age was 74 years, and 69% were male. The median follow-up period was 157 days, with events per 1000 person-years at 278 and 374 in the pre-pandemic and pandemic periods, respectively (crude HR, 1.37; adjusted HR, 1.17). The sensitivity and subgroup analyses yielded consistent results. CONCLUSIONS: The COVID-19 pandemic increased mortality risk in patients with GC. Further studies are required to observe long-term outcomes and identify the disparities contributing to the increased mortality risk.

Sterile versus non-sterile gloves during cystoscopy: A randomized prospective single-blind study.

Objective: The objective of this study is to evaluate the need for sterile gloves during cystoscopy by comparing the incidence of UTI symptoms between patients in whom the procedure is performed with non-sterile gloves with those performed with non-sterile gloves. Patients and Methods: This study had a randomized, prospective, single-blind design and included patients aged >20 years who underwent cystoscopy in either of two outpatient clinics between September 2015 and November 2021. The patients were allocated to a sterile group or a non-sterile group. Only the urologists were aware of whether or not the gloves were sterile. The patients were instructed to report any symptoms suggestive of UTI after cystoscopy. Results: A total of 1258 patients were enrolled in the sterile group and 1376 in the non-sterile group. Symptoms of UTI were reported by six patients (0.48%) in the sterile group and six (0.44%) in the non-sterile group. The between-group difference was not statistically significant (p = 0.88). Conclusion: It is not necessary to use sterile gloves during routine cystoscopy.

In vitro anti-severe acute respiratory syndrome coronavirus 2 effect of Ephedra przewalskii Stapf extract.

ETHNOPHARMACOLOGICAL RELEVANCE: The terrestrial stems of Ephedra (Ephedra spp.; including Ephedra sinica Stapf and Ephedra przewalskii Stapf) extracts are used in traditional medicines in East Asia. In Japan, the Kampo formula containing E. sinica extract is prescribed for the treatment of the common cold, influenza virus infections, and mild symptoms of coronavirus disease 2019 (COVID-19). Although ephedrine alkaloids in E. sinica exert antitussive effects, they may have side effects associated with the sympathetic nervous system. E. przewalskii extract, a drug used in traditional Uyghur and Mongolian medicine, is considered to be free of ephedrine alkaloids and is a promising candidate for the treatment of infectious diseases. However, its use is currently limited because evidence of its antiviral efficacy remains inconclusive. AIM OF THE STUDY: We compared the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects of E. przewalskii and E. sinica extracts in vitro. Additionally, we examined the differences in their antiviral effects against different SARS-CoV-2 strains. MATERIALS AND METHODS: VeroE6/TMPRSS2 cells were infected with SARS-CoV-2 (Conventional, Delta, and Omicron strains-BA.1, BA.2, BA.4, and BA.5), and lysates prepared from each herbal extract were added. The infectious titer was determined using the 50% tissue culture infectious dose (TCID50) method; in turn, the half-maximal inhibitory concentration (IC50) was calculated for each extract to compare the antiviral efficacy of E. sinica and E. przewalskii extracts. Further, the extracts were compared with remdesivir for their antiviral efficacy against the conventional viral strain. To verify the effect of the inactivation of virus particles, these extracts were added to each SARS-CoV-2 strain, and the infectious titers were determined using the TCID50 method. RESULTS: The antiviral efficacy (i.e., IC50) of the E. przewalskii extract against each SARS-CoV-2 strain was 2.7-10.8-fold greater than that of the E. sinica extract. The antiviral efficacy of the E. przewalskii extract against conventional viral strains was compared with that of remdesivir, which was 1/27.6 of remdesivir's efficacy. The E. sinica extract showed minimal inactivation of virus particles of each strain, whereas the E. przewalskii extract resulted in substantial viral inactivation. CONCLUSIONS: The E. przewalskii extract showed higher antiviral activity against SARS-CoV-2 than the E. sinica extract. Overall, our study suggests that E. przewalskii extract can be used for the treatment of viral infections, including COVID-19.

Gender difference of geographic distribution of physicians in Japan: three-point analysis of 1994, 2004 and 2014.

BACKGROUND: Japan's medical education system produces 9,000 graduates annually. Despite the government's implementation of several strategies, including increasing the number of doctors trained, the country still struggles with a shortage of physicians in rural areas. This study examined this issue, focusing on gender and considering years of physician experience, demographic and geographic factors. METHODS: We analyzed the Physician Census from 1994, 2004, and 2014, examining data on physicians' gender and the number of years since licensure. To correct the impact of municipal mergers, the analysis was aligned with the number of municipalities in 2014 (1741). We examined data from each physician (gender and years of medical experience) and analyzed the demographic and geographic distribution trend using Spearman correlation coefficients. We then used the Gini coefficient to evaluate the distribution change of physicians based on gender and years of experience. RESULTS: The number of physicians increased 1.29-fold over the 20-year observation period (1.23-fold for male physicians and 2.17-fold for female physicians), and the percentage of female physicians increased from 13.4% to 20.4%. We found that 87.7% of physicians were concentrated in the top 1/3 municipalities in terms of population. The number of female physicians was higher at 91.8% compared to 86.8% for male physicians. The Gini coefficients were lower for veteran physicians of both sexes than for younger physicians. The Gini coefficient for all physicians was 0.315-0.298-0.298 (male physicians: 0.311-0.289-0.283, female physicians: 0.394-0.385-0.395) The Gini coefficients for female compared to male physicians were higher in all age groups, showing that The distribution of female physicians is skewed toward urban areas. CONCLUSION: Female physicians are less distributed in rural areas than male physicians. In addition, despite the fact that the number of female physicians has increased more than male physicians over the past 20 years, the geographic ubiquity of female physicians has not improved. Since the trend of increasing the number of female physicians is expected to continue in the future, it is necessary to take some measures, such as providing a work-life balance suitable for female physicians.

No significant association between non-Helicobacter pylori Helicobacter infection with gastritis-related indices and gastric cancer.

BACKGROUND: Non-Helicobacter pylori Helicobacter (NHPH) has recently been linked to various gastric diseases. However, the relationship between NHPH infection and gastric cancer remains controversial. This study aimed to identify the effect of NHPH infection on gastritis and gastric cancer development. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissues were obtained from 73 patients with gastric cancer, of whom 21 cases were Helicobacter pylori (Hp) current infection, 37 cases were Hp previous infection, and 15 cases were Hp naïve infection, and were screened for NPHPs using polymerase chain reaction. The results were compared with NHPH infection rates in the patients with gastritis-related diseases reported in the previous study. We evaluated the association of NHPH infection with gastritis and clinicopathological features of gastric cancer. RESULTS: NHPH infection rates were 4/21 (19%) in "Hp current" patients, 4/37 (11%) in "Hp previous" infection patients, and 1/15 (7%) in "Hp naïve" patients, showing no significant difference in infection rates based on Hp infection status. NHPH infection rates in gastric cancer patients were similar to those in the patients with gastritis-related diseases reported in the previous study. A comparison of NHPH-positive and negative patients showed no significant differences in atrophic gastritis status, serum gastritis markers, or clinicopathological characteristics of gastric cancer, such as localization, size, gross type, differentiation, or depth. CONCLUSIONS: The association between gastric cancer and NHPH infection would have important implications for gastric cancer prevention, diagnostics, and treatment, however, no significant association was found in this particular population.

Diagnostic accuracy of whole heart coronary magnetic resonance angiography: a systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to comprehensively investigate the diagnostic ability of 1.5 T and 3.0 T whole heart coronary angiography (WHCA) to detect significant coronary artery disease (CAD) on X-ray coronary angiography. METHODS: A literature search of electronic databases, including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE, was performed to retrieve and integrate articles showing significant CAD detectability of 1.5 and 3.0 T WHCA. RESULTS: Data from 1899 patients from 34 studies were included in the meta-analysis. 1.5 T WHCA had a summary area under ROC of 0.88 in the patient-based analysis, 0.90 in the vessel-based analysis, and 0.92 in the segment-based analysis. These values for 3.0 T WHCA were 0.94, 0.95, 0.96, respectively. Contrast-enhanced 3.0 T WHCA had significantly higher specificity than non-contrast-enhanced 1.5 T WHCA on a patient-based analysis (0.87, 95% CI 0.80-0.92 vs. 0.74, 95% CI 0.64-0.82, P = 0.02). There were no differences in diagnostic performance on a patient-based analysis by use of vasodilators, beta-blockers or between Asian and Western countries. CONCLUSIONS: The diagnostic performance of WHCA was deemed satisfactory, with contrast-enhanced 3.0 T WHCA exhibiting higher specificity compared to non-contrast-enhanced 1.5 T WHCA in a patient-based analysis. There were no significant differences in diagnostic performance on a patient-based analysis in terms of vasodilator or beta-blocker use, nor between Asian and Western countries. However, further large-scale multicentre studies are crucial for the widespread global adoption of WHCA.

Light and heavy chain deposition disease with focal amyloid deposition diagnosed with mass spectrometry: a case report.

BACKGROUND: Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry. CASE PRESENTATION: We report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain. CONCLUSIONS: This is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.

Diagnostic performance of the normal range of gastrin calculated using strict criteria based on a combination of serum markers and pathological evaluation for detecting gastritis: a retrospective study.

BACKGROUND: The ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate "patients without gastritis" (defined as true A patients) from those "with gastritis." A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis. METHODS: Patients who underwent endoscopy and blood tests at Hiroshima University Hospital were enrolled in the study and categorized into the "pathologically-evaluated group" and "endoscopically-evaluated group," according to the evaluation method of atrophic gastritis. Initially, we measured serum gastrin concentrations in the normal stomach cases in the pathologically-evaluated group and calculated the normal range of serum gastrin concentrations. We used the upper limit of this normal range of serum gastrin concentrations and performed a validation study to determine its usefulness as a diagnostic marker for distinguishing between cases of gastritis and true A in the endoscopically-evaluated group. RESULTS: The 95th percentile of serum gastrin concentrations in pathologically-evaluated normal stomach cases was 34.12-126.03 pg/mL. Using the upper limit of this normal range of serum gastrin concentrations, the sensitivity, specificity, positive predictive value, and negative predictive value for gastritis were 52.8%, 92.6%, 97.0%, and 31.0%, respectively. Additionally, the receiver operating characteristic (ROC) curve for the endoscopically-evaluated group showed an area under the ROC curve of 0.80. CONCLUSION: The gastrin cut-off value of 126 pg/mL has a good positive predictive value (97.0%) for detecting gastritis positing its use as a marker for cases requiring endoscopy. However, the identification of patients with gastritis having normal serum gastrin concentrations due to insufficient sensitivity remains a challenge for the future.

Increased care-need in older long-term care insurance users after the 2018 Japan Floods: a retrospective cohort study based on the Japanese long-term care insurance claims.

BACKGROUND: Level of care-need (LOC) is an indicator of elderly person's disability level and is officially used to determine the care services provided in Japan's long-term care insurance (LTCI) system. The 2018 Japan Floods, which struck western Japan in July 2018, were the country's second largest water disaster. This study determined the extent to which the disaster affected the LOC of victims and compared it with that of non-victims. METHODS: This is a retrospective cohort study, based on the Japanese long-term care insurance claims from two months before (May 2018) to five months after the disaster (December 2018) in Hiroshima, Okayama, and Ehime prefectures, which were the most severely damaged areas in the country. A code indicating victim status, certified by a residential municipality, was used to distinguish between victims and non-victims. Those aged 64 years or younger, those who had the most severe LOC before the disaster, and those whose LOC increased even before the disaster were excluded. The primary endpoint was the augmentation of pre-disaster LOC after the disaster, which was evaluated using the survival time analysis. Age, gender, and type of care service were used as covariates. RESULTS: Of the total 193,723 participants, 1,407 (0.7%) were certified disaster victims. Five months after the disaster, 135 (9.6%) of victims and 14,817 (7.7%) of non-victims experienced the rise of LOC. The victim group was significantly more likely to experience an augmentation of LOC than the non-victim group (adjusted hazard ratio 1.24; 95% confidence interval 1.06-1.45). CONCLUSIONS: Older people who were affected by the disaster needed more care than before and the degree of care-need increase was substantially more than non-victims. The result suggests that natural disasters generate more demand for care services among the older people, and incur more resources and cost for society than before.

Clinical characteristics and long-term prognosis of type 1 gastric neuroendocrine tumors in a large Japanese national cohort.

OBJECTIVES: Optimal management of type 1 gastric neuroendocrine tumors (T1-GNETs) remains unknown, with few reports on their long-term prognosis. This study investigated the clinical characteristics and long-term prognosis of T1-GNETs. METHODS: We reviewed the medical records of patients diagnosed with T1-GNET during 1991-2019 at 40 institutions in Japan. RESULTS: Among 172 patients, endoscopic resection (ER), endoscopic surveillance, and surgery were performed in 84, 61, and 27, respectively, including 27, 77, and 2 patients with pT1a-M, pT1b-SM, and pT2 tumors, respectively. The median tumor diameter was 5 (range 0.8-55) mm. Four (2.9%) patients had lymph node metastasis (LNM); none had liver metastasis. LNM rates were significantly higher in tumors with lymphovascular invasion (LVI) (15.8%; 3/19) than in those without (1.1%; 1/92) (P = 0.016). For tumors <10 mm, LVI and LNM rates were 18.4% (14/76) and 2.2% (2/90), respectively, which were not significantly different from those of tumors 10-20 mm (LVI 13.3%; 2/15, P = 0.211; and LNM 0%; 0/17, P = 1.0). However, these rates were significantly lower than those of tumors >20 mm (LVI 60%; 3/5, P = 0.021; and LNM 40%; 2/5, P = 0.039). No tumor recurrence or cause-specific death occurred during the median follow-up of 10.1 (1-25) years. The 10-year overall survival rate was 97%. CONCLUSIONS: Type 1 gastric neuroendocrine tumors showed indolent nature and favorable long-term prognoses. LVI could be useful in indicating the need for additional treatments. ER for risk prediction of LNM should be considered for tumors <10 mm and may be feasible for tumors 10-20 mm. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network (UMIN) under the identifier UMIN000029927.

Omentin Modulates Chronic Cardiac Remodeling After Myocardial Infarction.

Background: Omentin, a circulating adipokine, is downregulated in complications of obesity, including heart disease. Here, we investigated whether omentin modulates adverse cardiac remodeling in mice after myocardial infarction (MI). Methods and Results: Transgenic mice expressing the human omentin gene in fat tissue (OMT-Tg) and wild-type (WT) mice were subjected to permanent ligation of the left anterior descending coronary artery (LAD) to induce MI. OMT-Tg mice had a higher survival rate after permanent LAD ligation than WT mice. Moreover, OMT-Tg mice had lower heart weight/body weight (HW/BW) and lung weight/body weight (LW/BW) ratios at 4 weeks after coronary artery ligation compared with WT mice. OMT-Tg mice also showed decreased left ventricular diastolic diameter (LVDd) and increased fractional shortening (%FS) following MI. Moreover, an increase in capillary density in the infarct border zone and a decrease in myocardial apoptosis, myocyte hypertrophy, and interstitial fibrosis in the remote zone following MI, were more prevalent in OMT-Tg than WT mice. Finally, intravenous administration of adenoviral vectors expressing human omentin to WT mice after MI resulted in decreases in HW/BW, LW/BW, and LVDd, and an increase in %FS. Conclusions: Our findings document that human omentin prevents pathological cardiac remodeling after chronic ischemia, suggesting that omentin represents a potential therapeutic molecule for the treatment of ischemic heart disease.

First Measurements on Triple Oxygen Isotopes of Dissolved Inorganic Phosphate in the Hydrosphere.

Although dissolved inorganic phosphate (DIP) is an important nutrient in the hydrosphere, it is difficult to quantitatively clarify the dynamics of DIP in the hydrosphere using the δ18O value of DIP as a tracer. In this study, we quantified the triple oxygen isotopic compositions (Δ'17O) of DIP relative to VSMOW with the reference line with a slope of 0.528 as an additional tracer to clarify the sources and dynamics of DIP in the hydrosphere. We found significant variation in the Δ'17O values of riverine DIP in urban areas, ranging from -107 × 10-6 to +3 × 10-6, while those of DIP in the effluents from wastewater treatment plants (WWTP) and DIP extracted from the chemical fertilizers showed -56 ± 5 × 10-6 (1SD) and -98 ± 5 × 10-6, respectively. We conclude that both the DIP supplied directly from the artificial loads (the WWTP effluent and chemical fertilizers) showing 17O-depleted Δ'17O values and the DIP turned over via the aquatic biosphere showing 17O-enriched Δ'17O values similar to ambient H2O were the major sources of riverine DIP. High-precision determination of the Δ'17O value of DIP can contribute to quantitative clarification of the dynamics of DIP in the hydrosphere.

Coronary flow reserve evaluated by phase-contrast cine cardiovascular magnetic resonance imaging of coronary sinus: a meta-analysis.

BACKGROUND: Phase-contrast cine cardiovascular magnetic resonance (CMR) of the coronary sinus has emerged as a non-invasive method for measuring coronary sinus blood flow and coronary flow reserve (CFR). However, its clinical utility has not yet been established. Here we performed a meta-analysis to clarify the clinical value of CMR-derived CFR in various cardiovascular diseases. METHODS: An electronic database search was performed of PubMed, Web of Science Core Collection, Cochrane Advanced Search, and EMBASE. We compared the CMR-derived CFR of various cardiovascular diseases (stable coronary artery disease [CAD], hypertrophic cardiomyopathy [HCM], dilated cardiomyopathy [DCM]) and control subjects. We assessed the prognostic value of CMR-derived CFR for predicting major adverse cardiac events (MACE) in patients with stable CAD. RESULTS: A total of 47 eligible studies were identified. The pooled CFR from our meta-analysis was 3.48 (95% confidence interval [CI], 2.98-3.98) in control subjects, 2.50 (95% CI, 2.38-2.61) in stable CAD, 2.01 (95% CI, 1.70-2.32) in cardiomyopathies (HCM and DCM). The meta-analysis showed that CFR was significantly reduced in stable CAD (mean difference [MD] = -1.48; 95% CI, -1.78 to -1.17; p < 0.001; I2 = 0%; p for heterogeneity = 0.33), HCM (MD = -1.20; 95% CI, -1.63 to -0.77; p < 0.001; I2 = 0%; p for heterogeneity = 0.49), and DCM (MD = -1.53; 95% CI, -1.93 to -1.13; p < 0.001; I2 = 0%; p for heterogeneity = 0.45). CMR-derived CFR was an independent predictor of MACE for patients with stable CAD (hazard ratio = 0.52 per unit increase; 95% CI, 0.37-0.73; p < 0.001; I2 = 84%, p for heterogeneity < 0.001). CONCLUSIONS: CMR-derived CFR was significantly decreased in cardiovascular diseases, and a decreased CFR was associated with a higher occurrence of MACE in patients with stable CAD. These results suggest that CMR-derived CFR has potential for the pathological evaluation of stable CAD, cardiomyopathy, and risk stratification in CAD.

The impact of early-stage COVID-19 pandemic on the diagnosis and treatment of gastric cancer: A cross-sectional study using a large-scale cancer registry in Hiroshima, Japan.

Background: After the confirmation of coronavirus infection in Japan, a behavioral change caused people and physicians to refrain from visiting hospitals or undergoing examinations. This study aimed to assess how the trend of diagnosis in gastric cancers changed, and how it affected the therapeutic strategies and the interval from diagnosis to treatment during the COVID-19 pandemic. Methods: We use 15 cancer-designated hospitals' registries in Hiroshima, Japan. The target period was March to December 2020, and the same period in 2019 was set as the control period. The monthly mean of diagnoses and the interval from diagnosis to treatment were compared overall and separately by age, treatment procedure, diagnostic process, and clinical stage. Result: In 2020, the monthly mean (standard deviation [SD]) of patients was 192.2 (29.9), a significant 20.1% decrease from 240.7 (20.7) in 2019 due to older age and curative treatment groups. By reason for performing endoscopy, the change rate in cancer screening, endoscopic follow-up, and symptomatic status were -27.0%, -18.0%, and -17.3%, respectively. Meanwhile, the interval (days) from diagnosis to treatment (SD) was 37.8 (26.5) in 2020, significantly shorter than 46 (31.5) in 2019. Conclusion: From 2019 to 2020, we observed a significant decrease in the diagnosis of curable early-stage gastric cancer and treatments, although the interval from diagnosis to treatment decreased. This study suggests that cancer screening played a significant role in the decline in cancer diagnosis that occurred during the COVID-19 pandemic. Even under COVID-19 pandemic conditions, there should be an awareness of cancer screening and endoscopic follow-up.