Impact of Cancer History on Temporal Changes in the Cardiopulmonary Exercise Test of Patients with Cardiovascular Disease.

The elevated risk of cardiovascular disease (CVD) in cancer patients and survivors is likely the result of normal age-related pathologies coupled with the direct and indirect effects of cancer therapy that extend across multiple systems. The purpose of this study was to investigate the impact of cardiac rehabilitation (CR) on CVD patients with a history of cancer.In this study, patients who had participated in the outpatient CR program were enrolled and were divided into 2 groups (cancer survivor group and no-cancer group) based on their history of cancer. The cardiopulmonary exercise test (CPET) was performed at the beginning (baseline) and at the end of the CR program (follow-up). The results of CPET at baseline and those at follow-up were analyzed retrospectively.A total of 105 patients were analyzed in this study. The cancer survivor group had 25 patients, and the non-cancer group 80. At baseline, peak oxygen uptake (peak VO2) (14.7 [11.9 to 17.6] mL/kg/minute versus 11.3 [9.7 to 14.7] mL/kg/minute; P = 0.003) was significantly lower in cancer survivors. The percent changes in peak VO2 between baseline and follow-up were not significantly different between the 2 groups (7.9 % [-11.5 to 24.5] versus 9.4 % [-7.5 to 27.3] P = 0.520).The percent changes in peak VO2 of CR participants were not significantly different despite their cancer history.

Long-Term Maintenance of Normal Serum Vitamin B1 Levels Is Associated with Better Outcomes in Patients with Heart Failure.

Deficiency of vitamin B1 (VB1), an essential micronutrient, causes heart failure (HF). A recent randomized controlled trial failed to show any improvement in HF prognosis after short-term VB1 supplementation. In the current study, we investigated the efficacy of long-term maintenance of normal blood VB1 levels in preventing adverse outcomes in patients with HF.This study included 88 consecutive patients with HF who received guideline-directed medical therapy at Arida Municipal Hospital. The patients were divided into 3 groups: a control group with normal VB1 levels and no VB1 supplementation (normal group, n = 25), and those presenting with VB1 deficiency, who either required short-term VB1 supplementation (short-term supplementation group, n = 25), or long-term maintenance of normal blood VB1 levels (long-term maintenance group, n = 38). The time to the first appearance of composite outcomes, including cardiovascular death and hospitalization for HF, was compared between the 3 groups.VB1 deficiency was observed in 63 (72%) patients. The Kaplan-Meier curve showed that the long-term maintenance group had better outcomes than the other 2 groups. In the multivariate analysis, long-term maintenance of normal blood VB1 levels and age were independent predictors of composite outcomes.VB1 deficiency is frequently observed, and the long-term maintenance of normal blood VB1 levels may result in better outcomes in patients with HF. Our results suggest that the detection of VB1 deficiency and long-term restoration of VB1 levels may be part of the overall therapeutic strategy for HF.

Protein expression of the amino acid transporter SLC7A5 in tumor tissue is prognostic in early-stage colorectal cancer.

Proteins overexpressed in early-stage cancers may serve as early diagnosis and prognosis markers as well as targets for cancer therapies. In this study, we examined the expression of an essential amino acid carrier SLC7A5 (LAT1, CD98, or 4F2 light chain) in cancer tissue from two well-annotated cohorts of 575 cases of early-stage and 106 cases of late-stage colorectal cancer patients. Immunohistochemistry showed SLC7A5 overexpression in 72.0% of early-stage and 56.6% of late-stage cases. SLC7A5 expression was not influenced by patient gender, age, location, or mismatch repair status, although it appeared to be slightly less prevalent in tumors of mucinous differentiation or with lymphovascular invasion. Statistical analyses revealed a positive correlation between SLC7A5 overexpression and both overall survival and disease-free survival in early-stage but not late-stage cancers. Co-expression analyses of the TCGA and CPTAC colorectal cancer cohorts identified a network of gene transcripts positively related to SLC7A5, with its heterodimer partner SLC3A2 having the highest co-expression score. Network analysis uncovered the SLC7A network to be significantly associated with ncRNA such as tRNA processing and the mitotic cell cycle. Since SLC7A5 is also a marker of activated lymphocytes such as NK, T, and B lymphocytes, SLC7A5 overexpression in early colorectal cancers might trigger a strong anti-tumor immune response which could results in better clinical outcome. Overall, our study provides clear evidence of differential SLC7A5 expression and its prognostic value for early-stage colorectal cancer, although the understanding of its functions in colorectal tumorigenesis and cancer immunity is currently rather limited and awaits further characterization.

Propensity score matching as an effective strategy for biomarker cohort design and omics data analysis.

BACKGROUND: Analysis of omics data that contain multidimensional biological and clinical information can be complex and make it difficult to deduce significance of specific biomarker factors. METHODS: We explored the utility of propensity score matching (PSM), a statistical technique for minimizing confounding factors and simplifying the examination of specific factors. We tested two datasets generated from cohorts of colorectal cancer (CRC) patients, one comprised of immunohistochemical analysis of 12 protein markers in 544 CRC tissues and another consisting of RNA-seq profiles of 163 CRC cases. We examined the efficiency of PSM by comparing pre- and post-PSM analytical results. RESULTS: Unlike conventional analysis which typically compares randomized cohorts of cancer and normal tissues, PSM enabled direct comparison between patient characteristics uncovering new prognostic biomarkers. By creating optimally matched groups to minimize confounding effects, our study demonstrates that PSM enables robust extraction of significant biomarkers while requiring fewer cancer cases and smaller overall patient cohorts. CONCLUSION: PSM may emerge as an efficient and cost-effective strategy for multiomic data analysis and clinical trial design for biomarker discovery.

Blood pressure reduction with empagliflozin in Japanese patients with type 2 diabetes and cardiovascular diseases: a post-hoc sub-analysis of the placebo-controlled randomized EMBLEM trial.

Detailed effect of sodium-glucose cotransporter 2 inhibitors on blood pressure (BP) in Japanese patients with type 2 diabetes (T2D) at a high risk of cardiovascular disease (CVD) is not fully understood. In this post-hoc sub-analysis of placebo-controlled randomized EMBLEM trial for Japanese patients with T2D and CVD, 105 participants (empagliflozin N = 52, placebo N = 53) were included, and office systolic/diastolic BPs and mean arterial pressure (MAP) over 24 weeks were estimated using mixed-effects models for repeated measures. Empagliflozin therapy, compared to placebo, reduced systolic/diastolic BPs (mean group difference in change from baseline to week 24; -5.9 [95% confidence interval (CI), -10.4 to -1.4] mmHg/-2.9 [95% CI, -6.2 to 0.4] mmHg) and MAP ( - 3.8 [95% CI, -7.0 to -0.7] mmHg). The systolic BP reduction was almost consistent across differing background clinical characteristics and usage status of anti-hypertensive medications.

Impact of Periprocedural Myocardial Injury on Long-Term Outcomes After Percutaneous Coronary Intervention Requiring Atherectomy.

The prognostic implications of cardiac troponin elevation after percutaneous coronary intervention (PCI) with atherectomy have not been established. The aim of this study was to investigate the incidence of periprocedural myocardial injury (PMI) and its association with cardiovascular events in patients with severely calcified lesions who underwent PCI with atherectomy. The study analyzed 346 patients (377 lesions) who underwent PCI with atherectomy between January 2018 and December 2021. Peak post-PCI high-sensitivity cardiac troponin (hs-cTn) was measured. The primary outcome was target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction, and clinically driven target lesion revascularization. A lesion-based analysis was conducted to assess the association of PMI with TLF up to 5 years after PCI. Increase of hs-cTn was seen with 362 lesions (96%), and significant PMI, defined as hs-cTn increase ≥70 × upper reference limit, was seen with 83 lesions (22%). Significant PMI was associated with a significantly greater risk of TLF (adjusted hazard ratio 1.93, 95% confidence interval 1.12 to 3.30, p = 0.017), primarily driven by an increased risk of cardiovascular death (adjusted hazard ratio 5.29, 95% confidence interval 1.46 to 19.16, p = 0.011). In conclusion, hs-cTn increase was frequently observed in patients who underwent PCI with atherectomy, and significant PMI was associated with an increased risk of TLF and cardiovascular death.

PPAR agonists in PBC: Where do we go from here? Or how to choose between the new and the old.

The recent phase 3 trials of peroxisome proliferator-activated receptor (PPAR) agonists in primary biliary cholangitis (PBC) patients with incomplete response to ursodeoxycholic acid (UDCA) demonstrated very promising short-term biochemical responses. However, long-term outcomes, crucial in chronic diseases like PBC, remain uncertain. While real-world data (RWD) support surrogate endpoints, there's a need to validate long-term efficacy especially with combination therapies. Bezafibrate, an off-label option with extensive RWD, demonstrated short-term response, reduced patients' pruritus, and improved long-term outcomes. Therefore, the therapeutic choice between new selective PPAR agonists and old bezafibrate poses a challenge. Undoubtedly further investigations into new PPAR agonists in terms of long-term efficacy are warranted, but prospective, randomized trials in post-approval settings are very unlikely to be successfully conducted, necessitating alternative approaches using RWD rather than traditional trial design. Finally, it will be essential to identify patients who may be intolerant and/or unresponsive to PPAR agonists.

Impact of Climate on the Incidence of Acute Coronary Syndrome　- Differences Between Japan and Thailand.

Background: Although there are many reports of temperature being associated with the onset of acute coronary syndrome (ACS), few studies have examined differences in ACS due to climatic differences between Japan and Thailand. The aim of this joint Japan-Thailand study was to compare patients with myocardial infarction in Japanese and Thai hospitals in different climates. Methods and Results: We estimated the climate data in 2021 for the Wakayama Prefecture and Chonburi Province, two medium-sized cities in Japan and Thailand, respectively, and ACS patients who were treated at the Wakayama Medical University (WMU) and Burapha University Hospital (BUH), the two main hospitals in these provinces (ACS patient numbers: WMU, n=177; BUH, n=93), respectively. In the Chonburi Province, although the average temperature was above 25℃, the number of ACS cases in BUH varied up to threefold between months (minimum: July, 4 cases; maximum: October, 14 cases). In Japan and Thailand, there was a mild to moderate negative correlation between temperature-atmospheric pressure at the onset of ACS, but different patterns for temperature-humidity (temperature-atmospheric pressure, temperature-humidity, and atmospheric pressure-humidity: correlation index; r=-0.561, 0.196, and -0.296 in WMU vs. r=-0.356, -0.606, and -0.502 in BUH). Conclusions: The present study suggests that other climatic conditions and factors, not just temperature, might be involved in the mechanism of ACS.

Importance of reassessment to identify trajectories of chronic transition of clinical indicators in post-myocardial infarction management.

Despite advances in multidisciplinary acute care for myocardial infarction (MI), the clinical need to manage heart failure and elevated mortality risks in the remote phase of MI remains unmet. Various prognostic models have been established using clinical indicators obtained during the acute phase of MI; however, most of these indicators also show chronic changes in the post-MI phase. Although relevant guidelines recommend follow-up assessments of some clinical indicators in the chronic phase, systematic reassessment has not yet been fully established and implemented in a real-world clinical setting. Therefore, clinical evidence of the impact of such chronic transitions on the post-MI prognosis is lacking. We speculate that post-MI reassessment of key clinical indicators and the impact of their chronic transition patterns on long-term prognoses can improve the quality of post-MI risk stratification and help identify residual risk factors. Several recent studies have investigated the impact of the chronic transition of some clinical indicators, such as serum albumin level, mitral regurgitation, and left-ventricular dysfunction, on post-MI prognosis. Interestingly, even in MI survivors with these indicators within their respective normal ranges in the acute phase of MI, chronic transition to an abnormal range was associated with worsening cardiovascular outcomes. On the basis of these recent insights, we discuss the clinical significance of post-MI reassessment to identify the trajectories of several clinical indicators and elucidate the potential residual risk factors affecting adverse outcomes in MI survivors.

RECAM-J 2023-Validation and development of the Japanese version of RECAM for the diagnosis of drug-induced liver injury.

AIM: The diagnosis of drug-induced liver injury (DILI) is challenging. We modified the revised electronic version of the Roussel Uclaf Causality Assessment Method (RUCAM) for the diagnosis of DILI (RECAM), the scoring system developed in US and Spanish cohorts in 2022, and developed RECAM-J 2023 to align with the clinical practice in Japan. In the current study, we introduce RECAM-J 2023 and verify its performance in the context of Japanese patients with DILI. METHODS: After translation of RECAM into Japanese, modifications were made to develop RECAM-J 2023 without any alteration to the scores. To examine the validity and performance of RECAM-J 2023, clinical information on DILI and non-DILI cases in Japan were retrospectively collected. The diagnosis of DILI was made by expert's decision. Then we scored each case using RECAM-J 2023, and calculated area under curve (AUC) values for identification for DILI. RESULTS: We collected data from 538 DILI and 128 non-DILI cases. The sum of highly probable (HP) and probable (PR) cases categorized by RECAM-J 2023 were only 206 (38%) in DILI cases. As the primary cause of low scores was the deduction with missing hepatitis virus markers, which is unlikely to be an issue in prospective applications, we rescored without these deductions. At this time, the sum of HP and PR was raised to 421 (78%). The AUCs of RECAM-J 2023 without deductions were 0.70 and 0.88 for identifying at least HP, and at least PR, respectively. CONCLUSION: RECAM-J 2023, when prospectively used without any missing hepatitis virus markers, provides acceptable performance for identifying at least PR DILI cases in Japanese daily clinical practice.

Design of biodegradable cellulose filtration material with high efficiency and breathability.

Using respiratory protective equipment is one of the relevant preventive measures for infectious diseases, including COVID-19, and for various occupational respiratory hazards. Because experienced discomfort may result in a decrease in the utilization of respirators, it is important to enhance the material properties to resolve suboptimal usage. We combined several technologies to produce a filtration material that met requirements set by a cross-disciplinary interview study on the usability of protective equipment. Improved breathability, environmental sustainability, and comfort of the material were achieved by electrospinning poly(ethylene oxide) (PEO) nanofibers on a thin foam-formed fabric from regenerated cellulose fibers. The high filtration efficiency of sub-micron-sized diethylhexyl sebacate (DEHS) aerosol particles resulted from the small mean segment length of 0.35 µm of the nanofiber network. For a particle diameter of 0.6 µm, the filtration efficiency of a single PEO layer varied in the range of 80-97 % depending on the coat weight. The corresponding pressure drop had the level of 20-90 Pa for the airflow velocity of 5.3 cm/s. Using a multilayer structure, a very high filtration efficiency of 99.5 % was obtained with only a slightly higher pressure drop. This opens a route toward designing sustainable personal protective media with improved user experience.

Vibrio fluvialis Bacteremia in an Immunocompetent Patient with Acute Cholangitis.

Vibrio fluvialis is a bacterium that can be found in both seawater and freshwater, and it is responsible for causing gastroenteritis and cholangitis. V. fluvialis bacteremia has rarely been reported. We report a case of V. fluvialis bacteremia due to cholangitis in an immunocompetent adult who was exposed to seawater regularly as a sushi chef. The increased risk of V. fluvialis entry into the body resulting from frequent consumption of raw fish and regular exposure to seawater, bile outflow impairment caused by transient inflammation of the bile duct, and the presence of multiple bile acid resistance-related genes in V. fluvialis may lead to the development of acute cholangitis and subsequent bacteremia in immunocompetent patients.

Intracoronary Near-Infrared Spectroscopy to Predict No-Reflow Phenomenon During Percutaneous Coronary Intervention in Acute Coronary Syndrome.

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) can identify the lipid-rich lesions, described as high lipid-core burden index (LCBI). The aim of this study was to investigate the relation between lipid-core plaque (LCP) in the infarct-related lesion detected using NIRS-IVUS and no-reflow phenomenon during percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). We investigated 371 patients with ACS who underwent NIRS-IVUS in the infarct-related lesions before PCI. The extent of LCP in the infarct-related lesion was calculated as the maximum LCBI for each of the 4-mm longitudinal segments (maxLCBI4mm) measured by NIRS-IVUS. The patients were divided into 2 groups using a maxLCBI4mm cut-off value of 400. The overall incidence of no-reflow phenomenon was 53 of 371 (14.3%). No-reflow phenomenon more frequently occurred in patients with maxLCBI4mm ≥400 compared with those with maxLCBI4mm<400 (17.5% vs 2.5%, p <0.001). After propensity score matching, multivariable logistic regression analysis demonstrated that maxLCBI4mm (odds ratio: 1.008; 95% confidence interval: 1.005 to 1.012, p <0.001) was independently associated with the no-reflow phenomenon. The maxLCBI4mm of 719 in the infarct-related lesion had the highest combined sensitivity (69.8%) and specificity (72.1%) for the identification of no-reflow phenomenon. In conclusion, in patients with ACS, maxLCBI4mm in the infarct-related lesion assessed by NIRS-IVUS was independently associated with the no-reflow phenomenon during PCI.

Primary biliary cholangitis drug evaluation and regulatory approval: Where do we go from here?

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The management landscape was transformed 20 years ago with the advent of Ursodeoxycholic Acid (UDCA). Up to 40% of patients do not, however, respond adequately to UDCA and therefore still remain at risk of disease progression to cirrhosis. The introduction of Obeticholic acid (OCA) as second-line therapy for patients failing UDCA has improved outcomes for PBC patients. There remains, however, a need for better treatments for higher risk patients. The greatest threat facing our efforts to improve treatment in PBC is, paradoxically, the regulatory approval model providing conditional marketing authorisation for new drugs based on biochemical markers on the condition that long-term, randomized placebo-controlled outcomes trials are performed to confirm efficacy. As demonstrated by the COBALT confirmatory study with OCA, it is difficult to retain patients in the required follow-on confirmatory placebo-controlled PBC outcomes trials when a licensed drug is commercially available. New PBC therapies in development such as the PPAR agonists, face even greater challenges in demonstrating outcomes benefit through randomized placebo-controlled studies once following conditional marketing authorisation, as there will be even more treatment options available. A recently published EMA Reflection Paper provides some guidance on the regulatory pathway to full approval but fails to recognise the importance of Real-World Data in providing evidence of outcomes benefit in rare diseases. Here we explore the impact of the EMA reflection paper on PBC therapy and offer pragmatic solutions for generating evidence of long-term outcomes through Real World data collection.

Risk factors for placenta accreta spectrum in pregnancies conceived after frozen-thawed embryo transfer in a hormone replacement cycle.

OBJECTIVE: Assisted reproductive technology (ART), especially frozen-thawed embryo transfer (FET) in a hormone replacement cycle (HRC), is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies achieved after FET in an HRC. STUDY DESIGN: We performed a case-control study in two tertiary perinatal centres in Japan. Among 14,028 patients who delivered at ≥24 weeks of gestation or were transferred after delivery to two tertiary perinatal centres between 2010 and 2021, 972 conceived with ART and 13,056 conceived without ART. PAS was diagnosed on the basis of the FIGO classification for the clinical diagnosis of PAS or retained products of conception after delivery at ≥24 weeks of gestation. We excluded women with fresh embryo transfer, FET with a spontaneous ovulatory cycle, a donor oocyte cycle, and missing details of the ART treatment. Finally, among women who conceived after FET in an HRC, 62 with PAS and 340 without PAS were included in this study. Multivariate logistic regression models were used for case-control comparisons, with adjustment for maternal age at delivery, parity, endometriosis or adenomyosis, the number of previous uterine surgeries of caesarean section, myomectomy, endometrial polypectomy or endometrial curettage, placenta previa, the stage of transferred embryos, and endometrial thickness at the initiation of progestin administration. RESULTS: PAS was associated with ≥2 previous uterine surgeries (adjusted odds ratio, 3.57; 95 % confidence interval, 1.60-7.97) and the stage of embryo transfer (blastocysts: adjusted odds ratio, 2.89; 95 % confidence interval, 1.15-7.26). In patients with <2 previous uterine surgeries, PAS was associated with an endometrial thickness of <7.0 mm (adjusted odds ratio, 5.18; 95 % confidence interval, 1.10-24.44). CONCLUSION: Multiple uterine surgeries and the transfer of blastocysts are risk factors for PAS in pregnancies conceived after FET in an HRC. In women with <2 previous uterine surgeries, a thin endometrium before FET is also a risk factor for PAS in these pregnancies.

Epidemiology of Fontan-associated liver disease in Japan: Results from a nationwide survey in 2021.

AIM: Although the Fontan procedure has improved the survival of patients with single-ventricle heart disease, the long-term consequences of the procedure have been a concern. This study aimed to explore the patients' postoperative clinical characteristics, including a diagnosis of Fontan-associated liver disease (FALD). METHODS: A nationwide Japanese epidemiological survey of post-Fontan patients was undertaken in 2021. The survey targets were selected from all departments of pediatrics, pediatric surgery, cardiology, cardiovascular surgery, and gastroenterology using stratified random sampling by the number of beds. Each department was asked to complete a mail-back questionnaire on the numbers of patients and their clinical characteristics. The diagnosis of FALD was made by each attending physician. RESULTS: The estimated number of post-Fontan patients was 7810 (95% confidence interval, 5430-10 200) in 2020, with a period prevalence of 61.9 per million. During the follow-up of 13.8 years after the Fontan procedure, 40% of patients were diagnosed with FALD. An elevated γ-glutamyl transpeptidase level was the most common finding leading to the FALD diagnosis (41%), and 45% of the patients also showed liver fibrosis. Compared with non-FALD patients, FALD patients were older, had longer duration since the Fontan procedure, and had more severe cardiac or liver conditions. However, more than half of the non-FALD patients had elevated liver enzyme levels, suggesting underestimation of the number of FALD patients. CONCLUSIONS: In 2020, approximately 40% of post-Fontan patients underwent follow-up with a diagnosis of FALD, although the lack of established diagnostic criteria for FALD could affect the reported prevalence of FALD.

Bone-Regeneration Therapy Using Biodegradable Scaffolds: Calcium Phosphate Bioceramics and Biodegradable Polymers.

Calcium phosphate-based synthetic bone is broadly used for the clinical treatment of bone defects caused by trauma and bone tumors. Synthetic bone is easy to use; however, its effects depend on the size and location of the bone defect. Many alternative treatment options are available, such as joint arthroplasty, autologous bone grafting, and allogeneic bone grafting. Although various biodegradable polymers are also being developed as synthetic bone material in scaffolds for regenerative medicine, the clinical application of commercial synthetic bone products with comparable performance to that of calcium phosphate bioceramics have yet to be realized. This review discusses the status quo of bone-regeneration therapy using artificial bone composed of calcium phosphate bioceramics such as ß-tricalcium phosphate (ßTCP), carbonate apatite, and hydroxyapatite (HA), in addition to the recent use of calcium phosphate bioceramics, biodegradable polymers, and their composites. New research has introduced potential materials such as octacalcium phosphate (OCP), biologically derived polymers, and synthetic biodegradable polymers. The performance of artificial bone is intricately related to conditions such as the intrinsic material, degradability, composite materials, manufacturing method, structure, and signaling molecules such as growth factors and cells. The development of new scaffold materials may offer more efficient bone regeneration.

Safety and effectiveness of SARS-CoV-2 vaccines for patients with intractable hepatobiliary diseases: A multicenter, questionnaire-based, cross-sectional study.

AIM: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease. METHODS: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected. RESULTS: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination. CONCLUSION: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

Effects of ipragliflozin on left ventricular diastolic function in patients with type 2 diabetes: A sub-analysis of the PROTECT trial.

BACKGROUND: We hypothesized that the beneficial effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on diastolic function might depend on baseline left ventricular (LV) systolic function. METHODS: To investigate the effects of SGLT2 inhibitors on LV diastolic function in patients with type 2 diabetes mellitus (T2DM), we conducted a post-hoc sub-study of the PROTECT trial, stratifying the data according to LV ejection fraction (LVEF) at baseline. After excluding patients without echocardiographic data at baseline or 24 months into the PROTECT trial, 31 and 38 patients with T2DM from the full analysis dataset of the PROTECT trial who received ipragliflozin or no SGLT2 inhibitor (control), respectively, were included. The primary endpoint was a comparison of the changes in echocardiographic parameters and N-terminal pro-brain natriuretic peptide levels from baseline to 24 months between the two groups stratified according to baseline LVEF. RESULTS: Differences in diastolic functional parameters (e' and E/e') were noted between the two groups. Among the subgroups defined according to median LVEF values, those with higher LVEF (≥60 %) who received ipragliflozin appeared to have a higher e' and lower E/e' than did those who received the standard of care with no SGLT2 inhibitor, indicating longitudinal improvements between baseline and follow up (p = 0.001 and 0.016, respectively). CONCLUSIONS: Ipragliflozin generally improved LV diastolic function in patients with type 2 diabetes, the extent of this improvement might appear to vary with LV systolic function.