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Abstract Background Extracorporeal membrane oxygenation (ECMO) might be required as a treatment option in patients with critical pulmonary embolism (PE). However, the clinical features and outcomes of the use of ECMO for critical acute PE are still limited. The present study aimed to clarify the clinical characteristics, management strategies and outcomes of patients with acute PE requiring ECMO in the current era using data from a large-scale observational database. Methods We analyzed the data of the COMMAND VTE Registry-2: a physician-initiated, multicenter, retrospective cohort study enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). Among 2035 patients with acute symptomatic PE, there were 76 patients (3.7%) requiring ECMO. Results Overall, the mean age was 58.4 years, and 34 patients (44.7%) were men. Cardiac arrest or circulatory collapse at diagnosis was reported in 67 patients (88.2%). The 30-day incidence of all-cause death was 30.3%, which were all PE-related deaths. The 30-day incidence of major bleeding was 54.0%, and the vast majority of bleedings were procedure site-related bleeding events and surgery-related bleeding (22.4%). The 30-day incidence of all-cause death was 6.3% in 16 patients with surgical intervention, 43.8% in 16 patients with catheter intervention, 25.0% in 16 patients with thrombolytic therapy, and 39.3% in 28 patients with anticoagulation only. Conclusions The current large real-world VTE registry in Japan revealed clinical features and outcomes of critical acute PE requiring ECMO in the current era, which suggested several unmet needs for future clinical trials.

Background: Ischemic stroke is a serious complication in patients with cancer-associated venous thromboembolism (CAVTE), although data remain scarce in the direct oral anticoagulant era. Objectives: This study aimed to investigate the incidence and identify predictive risk factors of ischemic stroke in patients with CAVTE. Methods: From the Contemporary Management and Outcomes in Patients With Venous Thromboembolism Registry-2 enrolling 5197 venous thromboembolism (VTE) patients across 31 centers in Japan between January 2015 and August 2020, we selected 1507 patients with active cancer. We calculated the cumulative incidence function of ischemic stroke accounting for the competing risk of death and investigated risk factors for ischemic stroke in a subdistribution hazard model of multivariable analysis. Results: During a median follow-up period of 1020 days, 71 patients (4.7%) developed ischemic stroke, and the cumulative incidence of ischemic stroke was 4.0% at 1 year and 4.7% at 3 years. Independent risk factors of ischemic stroke included pancreatic cancer (hazard ratio [HR], 4.24; 95% CI, 2.13-8.43), ovarian cancer (HR, 2.82; 95% CI, 1.31-6.08), lung cancer (HR, 2.35; 95% CI, 1.20-4.57), dyslipidemia (HR, 1.76; 95% CI, 1.01-3.09), metastasis (HR, 1.70; 95% CI, 1.02-2.82), higher D-dimer at VTE diagnosis (HR, 1.09; 95% CI, 1.04-1.14), and younger age (HR, 0.84; 95% CI, 0.71-0.999). Conclusion: In this large VTE registry in the direct oral anticoagulant era, the cumulative incidence of ischemic stroke was 4.0% at 1 year and 4.7% at 3 years in patients with CAVTE, and several independent risk factors of ischemic stroke were identified, including pancreatic cancer, ovarian cancer, lung cancer, dyslipidemia, metastasis, higher D-dimer at VTE diagnosis, and younger age.

Background: Cholecystolithiasis and choledocholithiasis are common biliary disorders that can lead to significant complications if left untreated. Among these complications, the formation of impacted CBD stones, particularly at the Ampulla of Vater, poses a unique clinical challenge. The Ampulla of Vater is the anatomical site where the common bile duct (CBD) and pancreatic duct converge, and its obstruction can lead to biliary colic, cholangitis, or pancreatitis. Urgent stone removal is critical for improving the patient’s condition. Case: A 48-year-old male patient presents to the emergency department with right upper abdominal pain since 10 days ago accompanied with icteric sclera since 10 days ago. There was nausea and vomiting when eating high-fat foods. The stools were brownish in color, the urine color was similar to tea color. The patient regularly takes UDCA 3 x 250 mg IO, simvastatin 1 x 20mg IO, curcuma 3 x1 tab IO, lansoprazole 2 x 30mg IO. Physical examination showed icteric eyes, jaundice, liver enlargement 2 fingers below costae arch with positive Murphy's sign. Complete blood examination showed leukocytosis, decreased hemoglobin, hypokalemia, as well as increased direct bilirubin, total bilirubin, and indirect bilirubin. BOF result showed sentinel loop on the right umbilical region suspected inflammatory process. MRI impression of choledocholithiasis causing dilatation of EHBD and IHBD proximal aspect without signs of cholangitis, hepatomegaly, simple cyst of left kidney (Bosniak I). Abdominal ultrasound with the conclusion of cholecystitis with dilatation and thickening of the ductus cysticus wall suspicious of inflammation, dilatation of the right and left IHBD, common hepatic duct, to the proximal common biliary duct, the presence of distal obstruction cannot be evaluated because it is covered by intestinal shadows, mild prostatic hypertrophy accompanied by prostate calcification. After Cholecystectomy and Explore CBD transduodenal, the patient was placed with thoracic drain with good outcome. Conclusion: The transduodenal approach to evacuating impacted CBD stones at the Ampulla of Vater is a valuable technique that can yield excellent outcomes in select cases. This case report underscores the importance of a tailored approach based on individual patient anatomy and stone characteristics.

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a life‐threatening complication post‐acute pulmonary embolism (PE). The assessment of CTEPH incidence and risk factors post‐acute PE in the era of direct oral anticoagulants remains insufficient. Methods and Results The COMMAND VTE Registry‐2 (contemporary management and outcomes in patients with venous thromboembolism registry‐2) is a multicenter registry that recruited consecutive patients with acute symptomatic venous thromboembolism from 31 centers across Japan. The primary outcome was to demonstrate the detection rate of CTEPH after acute PE in routine clinical practice. Out of the 5197 patients with venous thromboembolism included in the COMMAND VTE Registry‐2, 2787 were diagnosed with acute PE. Following a median follow‐up duration of 747 days, 48 cases of CTEPH were detected, and the cumulative diagnosis of CTEPH in routine clinical practice was 2.3% at 3 years. Independent risk factors for the detection of CTEPH by multivariable Cox regression analysis included women (hazard ratio [HR] 2.09 [95% CI, 1.05–4.14]), longer interval from symptom onset to diagnosis of PE (each 1 day, HR 1.04 [95% CI, 1.01–1.07]), hypoxemia at diagnosis (HR 2.52 [95% CI, 1.26–5.04]), right heart load (HR 9.28 [95% CI, 3.19–27.00]), lower D‐dimer value (each 1 μg/mL, HR 0.96 [95% CI, 0.92–0.99]), and unprovoked PE (HR 2.77 [95% CI, 1.22–6.30]). Conclusions In the direct oral anticoagulant era, the cumulative diagnosis of CTEPH after acute PE was 2.3% at 3 years, and several independent risk factors for CTEPH were identified, which could be useful for screening a high‐risk population after acute PE.

Background: Hirschsprung is a disease that occurs in the intestine, and cases most often appear in the colon (colon). Symptoms that usually arise are chronic constipation, failure to grow, and malnutrition. The surgical procedure approach that can be performed in this case is by carrying out an exploration laparatomy and placed a colostomy on the patient. Case: A 22-year-old male patient presents to the emergency department with abdominal pain, His pain began suddenly then dissappear gradually, accompanied by flatulence and nausea since a week ago. Other complaints such as fever and vomiting are denied. Patients with a history of defecation patterns every 2-3 days. Patients complain of difficulty defecating since last week before admitted, the stool form was a small amount of liquid, frequency is 2-3x/day. Stool with blood (-), black or tarry stool (-). Patients with a history of circumcision surgery. The results of the examination showed an increase in WBC 15.11. Based on the BOF results, the results described as a leading to paralytic ileus, Fecal material prominent as high as the pelvic cavum. In addition, based on the results of abdominal ultrasound, it is said that most of the scanning areas are covered by prominent intestinal gas, mild fatty liver. After the exploratory laparatomy, no signs of malignancy were found in the patient, but there was suspicion towards Hirschsprung where the patient did not have the flexura hepatica ligament and the lienalis flexura ligament. Conclusion: Hirschsprung requires surgical procedures that must be explained throughly to patient and families. The surgical procedure approach that can be performed in this case is by carrying out an exploratory laparatomy and the placed a colostomy on the patient. And colon in loop will be used to determine and evaluate the intestine height with aganglionic.

Background The simplified Pulmonary Embolism Severity Index (sPESI) score could help identify low‐risk patients with pulmonary embolism for home treatment. However, the application of the sPESI score and selection for home treatment have not been fully evaluated in the direct oral anticoagulants era. Methods and Results The COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) Registry‐2 is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism. The current study population consists of 2496 patients with hemodynamically stable pulmonary embolism (2100 patients [84%] treated with direct oral anticoagulants), who were divided into 2 groups: sPESI scores of 0 and ≥1. We investigated the 30‐day mortality, home treatment prevalence, and factors predisposing to home treatment using the Kaplan‐Meier method and logistic regression model. Patients with an sPESI score of 0 accounted for 612 (25%) patients, and only 17% among 532 patients with out‐of‐hospital pulmonary embolism were treated at home. The cumulative 30‐day mortality was lower in patients with an sPESI score of 0 than the score of ≥1 (0% and 4.8%, log‐rank P

Abstract Aims There are minimal data on the prognostic impact of right atrial strain during the reservoir phase (RASr) in patients with immunoglobulin light‐chain (AL) cardiac amyloidosis. Methods and results Among 78 patients who were diagnosed with AL cardiac amyloidosis at Kumamoto University Hospital from 2007 to 2022, 72 patients with sufficient two‐dimensional speckle tracking imaging data without chemotherapy before the diagnosis were retrospectively analysed. During a median follow‐up of 403 days, 31 deaths occurred. Age and the rate of male sex were not significantly different between the all‐cause death group and the survival group (age, 70.4 ± 8.8 years vs. 67.0 ± 10.0 years, P = 0.14, male sex, 65% vs. 66%, P = 0.91). The estimated glomerular filtration rate (eGFR) was significantly lower, and B‐type natriuretic peptide (BNP) and high sensitivity cardiac troponin T (hs‐cTnT) were significantly higher, in the all‐cause death group versus the survival group (eGFR, 48.2 ± 21.0 mL/min/1.73 m2 vs. 59.4 ± 24.4 mL/min/1.73 m2, P 311.2 pg/mL) had a significantly high probability of all‐cause death (both, P

Background There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long‐term outcomes from the warfarin era to the DOAC era. Methods and Results We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010–2014) and Registry 2: 5197 patients in the DOAC era (2015–2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P

Background: Although the prevalence rate of valvular heart disease (VHD) is high in patients with systemic lupus erythematosus (SLE), the predictive factors of concomitant VHD have not been fully evaluated. Methods and results: Among 288 patients with SLE who underwent transthoracic echocardiography at Kumamoto University Hospital from 2016 to 2021, 241 patients with sufficient echocardiographic data were retrospectively analysed. Among them, 22 (9 %) had VHD (10 had mitral regurgitation, 3 had aortic regurgitation, 6 had tricuspid regurgitation, 1 had mitral regurgitation and tricuspid regurgitation, and 2 had a prosthetic cardiac valve). After excluding the two patients with a prosthetic cardiac valve, we divided the remaining patients into two groups: the VHD group and non-VHD group. Multivariate logistic regression analysis revealed that age and the platelet count were significantly and independently associated with having VHD (age: odds ratio, 1.06; 95 % confidence interval, 1.02–1.10; p

Background Although the close relationship between cancer and venous thromboembolism (VTE) has been identified, risk stratification for VTE in Japanese patients with cancer remains unclear.

Abstract Cavotricuspid isthmus (CTI) ablation is an important treatment strategy for CTI-dependent atrial flutter (AFL). The location of the catheter contact area is confirmed by the contact vector direction (CVD) through three-dimensional mapping during the procedure. However, the relationship between CVD during radiofrequency ablation and its efficacy in achieving CTI block has not been clarified. This study aimed to investigate the relationship between CVD and efficacy in achieving CTI block. CVDs during radiofrequency ablation were divided into proximal vectors against the distal tip (P-vector) and other vectors (normal-vector). In 39 patients who underwent CTI linear ablation, the CTIs were divided into two segments: the tricuspid valve area (anterior) and inferior vena cava area (posterior). The frequency of the residual conduction gap was compared between segments in which the P- and normal-vectors were observed. P-vectors were observed in 13 of the 78 segments. The median ablation index was not significantly different between segments in which the P-vector and normal-vector were observed (398.2 [384.2–402.2] vs. 393.3 [378.3–400.1], p = 0.15). However, residual conduction gaps were significantly more frequently observed in the segment in which the P-vector was observed than those in which only the normal-vector was observed (6/13, 46.2% vs. 3/65, 4.6%; p

Abstract Aims Understanding cardiac function after anthracycline administration is very important from the perspective of preventing the onset of heart failure. Although cardiac magnetic resonance and echocardiography are recognized as the ‘gold standard’ for detecting cardiotoxicity, they have many shortcomings. We aimed to investigate whether cardiac computed tomography (CCT) could replace these techniques, assessing serial changes in cardiac tissue characteristics as determined by CCT after anthracycline administration. Methods and results We prospectively investigated 15 consecutive breast cancer patients who were scheduled to receive anthracycline therapy. We performed echocardiography and CCT before and 3, 6, and 12 months after anthracycline treatment. The mean cumulative administered anthracycline dose was 269.9 ± 14.6 mg/m2 (doxorubicin‐converted dose). Of the 15 enrolled patients who received anthracycline treatment for breast cancer, none met the definition of cardiotoxicity. The CCT‐derived extracellular volume fraction tended to continue to increase after anthracycline treatment and had relatively similar dynamics to the left ventricular ejection fraction and global longitudinal strain as determined by echocardiography. Conclusions Our findings indicated that CCT could provide adequate information about the characteristics of myocardial tissue after anthracycline administration. CCT may improve the understanding of cardiotoxicity by compensating for the weaknesses of echocardiography. This technique could be useful for understanding cardiac tissue characterization as a ‘one‐stop shop’ evaluation, providing new insight into cardiooncology.

Background: Left ventricular (LV) apical sparing by transthoracic echocardiography (TTE) has not been widely accepted to diagnose transthyretin amyloid cardiomyopathy (ATTR-CM), because it is time consuming and requires a level of expertise. We hypothesized that automatic assessment may be the solution for these problems. Methods-and-Results: We enrolled 63 patients aged ≥70 years who underwent 99mTc-labeled pyrophosphate (99mTc-PYP) scintigraphy on suspicion of ATTR-CM and performed TTE by EPIQ7G, and had enough information for two-dimensional speckle tracking echocardiography at Kumamoto University Hospital from January 2016 to December 2019. LV apical sparing was described as a high relative apical longitudinal strain (LS) index (RapLSI). Measurement of LS was repeated using the same apical images with three different measurement packages as follows: (1) full-automatic assessment, (2) semi-automatic assessment, and (3) manual assessment. The calculation time for full-automatic assessment (14.7 ± 1.4 sec/patient) and semi-automatic assessment (66.7 ± 14.4 sec/patient) were significantly shorter than that for manual assessment (171.2 ± 59.7 sec/patient) (p

Abstract Background Cowden syndrome is a rare autosomal-dominant disease with a high risk of malignant tumors of the breast, commonly caused by germline mutations in the PTEN gene. Most breast cancers related to Cowden syndrome showed typically a slow-growing and favorable clinical course. Here, we report a progressive case of triple-negative breast cancer in a patient who was diagnosed with Cowden syndrome. Case presentation A 35-year-old female with breast cancer was referred to our hospital. Histopathological examination of the tumor showed that it was triple-negative breast cancer with high proliferation marker. Preoperative positron emission tomography-computed tomography showed abnormal uptake in the left cerebellar hemisphere in addition to the right breast and axillary lymph node. Brain T2-weighted magnetic resonance imaging revealed hyperintense bands in the left cerebellar hemisphere lesion, which demonstrated a “tiger-stripe” appearance. The patient’s mother had died of endometrial cancer. Subsequently, she underwent genetic testing, leading to a diagnosis of Cowden syndrome with a pathogenic variant c.823_840del.18 at exon 8 in PTEN. She was treated with neoadjuvant chemotherapy of eribulin and cyclophosphamide followed by adriamycin and cyclophosphamide. However, her tumors increased after these treatments. She was immediately surgically treated and received adjuvant chemotherapy of capecitabine. Unfortunately, the cancer recurred in the lung nine months after surgery. We then administered paclitaxel and bevacizumab therapy, but the disease rapidly progressed. Consequently, the patient died due to breast cancer about three months after recurrence. Conclusion We report an aggressive case of cancer with Cowden syndrome which was resistant to standard chemotherapy. Alteration of the phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin pathway due to inactivating PTEN protein may be associated with chemoresistance and serves as a candidate for therapeutic intervention in PTEN-related cancers.

Abstract Aims To clarify the usefulness of left atrial (LA) function and left ventricular (LV) function obtained by two‐dimensional (2D) speckle tracking echocardiography to diagnose concomitant transthyretin amyloid cardiomyopathy (ATTR‐CM) in patients with aortic stenosis (AS). Methods and results We analysed 72 consecutive patients with moderate to severe AS who underwent 99mTc‐pyrophosphate (PYP) scintigraphy at Kumamoto University Hospital from January 2012 to September 2020. We divided these 72 patients into 2 groups based on their 99mTc‐PYP scintigraphy positivity or negativity. Among 72 patients, 16 patients (22%) were positive, and 56 patients (78%) were negative for 99mTc‐PYP scintigraphy. In clinical baseline characteristics, natural logarithm troponin T was significantly higher in the 99mTc‐PYP scintigraphy‐positive than scintigraphy‐negative group (−2.9 ± 0.5 vs. −3.5 ± 0.8 ng/mL, P 0.47 s−1 was 96.6% (28/29). Conclusions Left atrial and LV strain analysis were significantly associated with 99mTc‐PYP scintigraphy positivity in ATTR‐CM patients with moderate to severe AS. The combination of the peak LSR in LA and RapLSI might be a useful predictor of the presence of ATTR‐CM in patients with moderate to severe AS.

Abstract Aims It has been reported that a staging system combining N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity troponin T (hs‐cTnT) or estimated glomerular filtration rate (eGFR) is useful in patients with wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM). However, these studies were mainly conducted in Western countries, and their usefulness for the Japanese population is unclear. We examined and validated the staging system using hs‐cTnT, eGFR, and B‐type natriuretic peptide (BNP) in Japanese patients with ATTRwt‐CM. Methods and results We retrospectively evaluated 176 patients with ATTRwt‐CM. The cut‐off values of hs‐cTnT and eGFR were selected as 0.05 ng/mL and 45 mL/min/1.73 m2, respectively, based on a previous report. The optimal cut‐off value of BNP was 255.6 pg/mL to predict all‐cause mortality (sensitivity, 75%; specificity, 58%; area under the curve, 0.69; 95% confidence interval [CI], 0.61–0.78; P 0.05 ng/mL) and BNP (>250 pg/mL) and decreased eGFR (

Abstract Background It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years. Methods This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged

Background/Aims The Heart Failure Association (HFA)-PEFF score is recognized as a simple method to diagnose heart failure (HF) with preserved ejection fraction (HFpEF). This study aimed to evaluate the relationship between HFA-PEFF scores and cardiovascular outcomes in HFpEF patients. Methods A total of 502 consecutive HFpEF patients were prospectively observed for up to 1,500 days. Cardiovascular outcomes were compared between two groups of patients, defined by their HFA-PEFF scores: those who scored 2–4 (the intermediate-score group) and those who scored 5–6 group (the high-score group). Overall, 236 cardiovascular events were observed during the follow-up period (median, 1,159 days). Results Kaplan-Meier analysis showed that there were significant differences in composite cardiovascular events and HF-related events between the intermediate-score group and the high-score group (p = 0.003 and p < 0.001, respectively). Multivariate Cox proportional hazards analysis showed that the HFA-PEFF scores significantly predicted future HF-related events (hazard ratio, 1.66; 95% confidence interval [CI], 1.11 to 2.50; p = 0.014); receiver operating characteristic analysis confirmed this relationship (area under the curve, 0.633; 95% CI, 0.574 to 0.692; p < 0.001). The cutoff HFA-PEFF score for the identification of HF-related events was 4.5. Decision curve analysis revealed that combining the HFA-PEFF score with conventional prognostic factors improved the prediction of HF-related events. Conclusions HFA-PEFF scores may be useful for predicting HF-related events in HFpEF patients.