Efficacy and Tolerability of Ivabradine for Cardiomyopathy in Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is an intractable X-linked myopathy caused by dystrophin gene mutations. Patients with DMD suffer from progressive muscle weakness, inevitable cardiomyopathy, increased heart rate (HR), and decreased blood pressure (BP). The aim of this study was to clarify the efficacy and tolerability of ivabradine treatment for DMD cardiomyopathy.A retrospective analysis was performed in 11 patients with DMD, who received ivabradine treatment for more than 1 year. Clinical results were analyzed before (baseline), 6 months after, and 12 months after the ivabradine administration.The initial ivabradine dose was 2.0 ± 1.2 mg/day and the final dose was 5.6 ± 4.0 mg/day. The baseline BP was 95/64 mmHg. A non-significant BP decrease to 90/57 mmHg was observed at 1 month but it recovered to 97/62 mmHg at 12 months after ivabradine administration. The baseline HR was 93 ± 6 bpm and it decreased to 74 ± 12 bpm at 6 months (P = 0.011), and to 77 ± 10 bpm at 12 months (P = 0.008). A linear correlation (y = 2.2x + 5.1) was also observed between the ivabradine dose (x mg/day) and HR decrease (y bpm). The baseline LVEF was 38 ± 12% and it significantly increased to 42 ± 9% at 6 months (P = 0.011) and to 41 ± 11% at 12 months (P = 0.038). Only 1 patient with the lowest BMI of 11.0 kg/m2 and BP of 79/58 mmHg discontinued ivabradine treatment at 6 months, while 1-year administration was well-tolerated in the other 10 patients.Ivabradine decreased HR and increased LVEF without lowering BP, suggesting it can be a treatment option for DMD cardiomyopathy.

Ligation of left gastric vein may cause delayed gastric emptying after pancreatoduodenectomy: a retrospective study.

BACKGROUND: This study aimed to determine which running pattern of the left gastric vein (LGV) is most frequently ligated in subtotal stomach-preserving pancreatoduodenectomy (SSPPD) and how LGV ligation affects delayed gastric emptying (DGE) after SSPPD. METHODS: We retrospectively analysed 105 patients who underwent SSPPD between January 2016 and September 2021. We classified the running pattern of LGV as follows: type 1 runs dorsal to the common hepatic artery (CHA) or splenic artery (SpA) to join the portal vein (PV), type 2 runs dorsal to the CHA or SpA and joins the splenic vein, type 3 runs ventral to the CHA or SpA and joins the PV, and type 4 runs ventral to the CHA or SpA and joins the SpV. Univariate and multivariate analyses were used to identify differences between patients with and without DGE after SSPPD. RESULTS: Type 1 LGV running pattern was observed in 47 cases (44.8%), type 2 in 23 (21.9%), type 3 in 12 (11.4%), and type 4 in 23 (21.9%). The ligation rate was significantly higher in type 3 (75.0%) LGVs (p < 0.0001). Preoperative obstructive jaundice (p = 0.0306), LGV ligation (p < 0.0001), grade B or C pancreatic fistula (p = 0.0116), and sepsis (p = 0.0123) were risk factors for DGE in the univariate analysis. Multivariate analysis showed that LGV ligation was an independent risk factor for DGE (odds ratio: 13.60, 95% confidence interval: 3.80-48.68, p < 0.0001). CONCLUSION: Type 3 LGVs are often ligated because they impede lymph node dissection; however, LGV preservation may reduce the occurrence of DGE after SSPPD.

Identification of microRNA-96-5p as a postoperative, prognostic microRNA predictor in nonviral hepatocellular carcinoma.

AIM: The microRNA (miR) clusters miR-183/96/182 and miR-217/216a/216b are significantly upregulated in nonviral hepatocellular carcinoma (NBNC-HCC). Here, we investigate the impact of each member of these clusters on the clinical outcome of NBNC-HCC and analyze the antitumor effects of miR-96-5p. METHODS: The association between recurrence-free survival of 111 NBNC-HCC patients and the levels of miR-183-5p, miR-96-5p, miR-182-5p, miR-217-5p, miR-216a-5p, and miR-216b-5p in tumor and adjacent tissues was investigated. The impact of miR-96-5p on apoptosis and invasion of a hepatoma cell line, HepG2, was investigated by cell counting, Transwell assay, and flow cytometry, respectively. RESULTS: MicroRNA-183-5p, miR-96-5p, miR-182-5p, miR-217-5p, and miR-216b-5p were significantly upregulated in tumor tissues compared to the adjacent tissues (p = 0.0005, p = 0.0030, p = 0.0002, p = 0.0011, and p = 0.0288, respectively). By multivariate Cox regression analysis, high tumor/adjacent ratios of miR-182-5p (p = 0.007) and miR-217-5p (p = 0.008) were associated with poor recurrence-free survival. In contrast, a low tumor/adjacent ratio of miR-96-5p (p < 0.001) was associated with poor recurrence-free survival. It suggested that further upregulation of miR-96-5p in tumors might have an inhibitory effect on recurrence. Transfection of miR-96-5p mimic significantly induced apoptosis of HepG2 cells, in association with downregulation of Nucleophosmin 1 (NPM1) and a decrease of phosphorylated AKT protein. Interestingly, simultaneous knockdown of the NPM1 and AKT genes induced apoptosis. MicroRNA-96-5p also suppressed proliferation and invasion, which inhibited epithelial-to-mesenchymal transition of HCC cells. CONCLUSION: MicroRNA-96-5p as a tumor suppressor would be valuable to stratify NBNC-HCC patients at high risk of recurrence.

Automated Design of Li+ -Conducting Polymer by Quantum-Inspired Annealing.

Automated molecule design by computers is an essential topic in materials informatics. Still, generating practical structures is not easy because of the difficulty in treating material stability, synthetic difficulty, mechanical properties, and other miscellaneous parameters, often leading to the generation of junk molecules. The problem is tackled by introducing supervised/unsupervised machine learning and quantum-inspired annealing. This autonomous molecular design system can help experimental researchers discover practical materials more efficiently. Like the human design process, new molecules are explored based on knowledge of existing compounds. A new solid-state polymer electrolyte for lithium-ion batteries is designed and synthesized, giving a promising room temperature conductivity of 10-5 S cm-1 with reasonable thermal, chemical, and mechanical properties.

The influence of the interval between percutaneous transhepatic gallbladder drainage and cholecystectomy on perioperative outcomes: a retrospective study.

BACKGROUND: Percutaneous transhepatic gallbladder drainage (PTGBD) is recommended for acute cholecystitis patients at high risk for surgical treatment. However, there is no evidence about the best timing of surgery after PTGBD. Here, we retrospectively investigated the influence of the interval between PTGBD and surgery on perioperative outcomes and examined the optimal timing of surgery after PTGBD. METHODS: We performed a retrospective analysis of 22 patients who underwent cholecystectomy after PTGBD from January 2008 to August 2019. We examined perioperative factors between patients with an interval of ≤ 7 days between PTGBD and cholecystectomy (≤ 7-day group; n = 12) and those with an interval of ≥ 8 days (≥ 8-day group; n = 10). Moreover, we also examined perioperative factors between patients with an interval of ≤ 14 days from PTGBD to cholecystectomy (≤ 14-day group; n = 10) and those with an interval of ≥ 15 days (≥ 15-day group; n = 12). RESULTS: Of the 22 patients, 9 had Grade I cholecystitis, 12 had Grade II cholecystitis, and 2 had Grade III cholecystitis. Nine patients had high-grade cholecystitis before PTGBD and 13 had a poor general condition. We examined perioperative factors between patients with an interval of ≤ 7 days between PTGBD and cholecystectomy (≤ 7-day group; n = 12) and those with an interval of ≥ 8 days (≥ 8-day group; n = 10). The C-reactive protein (CRP) level before surgery was significantly higher (12.70 ± 1.95 mg/dL vs. 1.13 ± 2.13 mg/dL, p = 0.0007) and the total hospitalization was shorter (17.6 ± 8.0 days vs. 54.1 ± 8.8 days, p = 0.0060) in the ≤ 7-day group than in the ≥ 8-day group. We also examined perioperative factors between patients with an interval of ≤ 14 days from PTGBD to cholecystectomy (≤ 14-day group; n = 14) and those with an interval of ≥ 15 days (≥ 15-day group; n = 8). The CRP level before surgery was significantly higher (11.13 ± 2.00 mg/dL vs. 0.99 ± 2.64 mg/dL, p = 0.0062) and the total hospitalization was shorter (19.5 ± 7.2 days vs. 59.9 ± 9.5 days, p = 0.0029) in the ≤ 14-day group than in the ≥ 15-day group. However, there were no significant differences between the ≤ 14-day group and the ≥ 15-day group in the levels of hepatic enzymes before surgery, adhesion grade, amount of bleeding during surgery, operative duration, frequency of surgical complications, or length of hospitalization after surgery. CONCLUSIONS: The interval between PTGBD and surgery has little influence on perioperative outcomes.

Relationship Between Mitral Leaflet Size and Coaptation and Their Associated Factors in Patients with Normal Left Ventricular Size and Systolic Function.

Enlargement of the mitral valve (MV) has gained attention as a compensatory mechanism for functional mitral regurgitation (FMR). We aimed to determine if MV leaflet area is associated with MV coaptation-zone area and identify the clinical factors associated with MV leaflet size and coaptation-zone area in patients with normal left ventricle (LV) systolic function and size using real-time 3D echocardiography (RT3DE).We performed RT3DE in 135 patients with normal LV size and ejection fraction. MV leaflet and coaptation-zone areas were measured using custom 3D software. The clinical factors associated with MV leaflet and coaptation-zone areas were evaluated using univariate and multivariate linear regression analyses.There was a significant relationship between MV leaflet and coaptation-zone areas (r = 0.499, P < 0.001). MV leaflet area was strongly associated with body surface area (BSA) (r = 0.905, P < 0.001) rather than LV size and age. MV leaflet area/BSA was independently associated with male gender (P = 0.002), lower diastolic blood pressure (P = 0.042), and LV end-diastolic volume (LVEDV) index (P = 0.048); MV coaptation-zone area/BSA was independently associated with lower LVEDV index (P = 0.01).In patients with normal LV systolic function and size, MV leaflet size has a significant impact on competent MV coaptation. MV leaflet area might be intrinsically determined by body size rather than age and LV size, and the MV leaflet area/BSA is relatively constant. On the other hand, some clinical factors might also influence MV leaflet and coaptation-zone area.

Mitral Valvular Coaptation-Zone Area Is Associated with the Severity of Atherosclerosis Assessed by Cardio-Ankle Vascular Index.

Preservation of the mitral valve (MV) size is essential for valve function, and a reduced MV coaptation-zone area increases the risk of developing functional mitral regurgitation (FMR). We aimed to determine if the MV leaflet and coaptation-zone areas were associated with the severity of atherosclerosis assessed by cardio-ankle vascular index (CAVI) in patients with normal left ventricle (LV) systolic function and size by real-time 3D echocardiography (RT3DE).We performed RT3DE analysis in 66 patients with normal LV size and ejection fraction who underwent 2D echocardiography and CAVI. MV coaptation-zone areas were measured by custom 3D software and indexed by body surface area (BSA). The associations of clinical factors and mean CAVI with MV leaflet and coaptation-zone areas were evaluated by univariable and multivariable linear regression analyses.On univariable analysis, MV leaflet area/BSA was significantly associated with age (r = -0.335, P = 0.0069) and mean CAVI (r = -0.464, P < 0.001), and MV coaptation-zone area was significantly associated with age (r = -0.626, P < 0.001), hypertension (r = -0.626, P < 0.001), dyslipidemia (r = -0.626, P < 0.001), E/e' (r = -0.626, P < 0.001), and CAVI (r = -0.740, P < 0.001). On multivariable analysis, mean CAVI was independently associated only with MV leaflet area/BSA (standardized coefficient = -0.611, P < 0.001) and MV coaptation-zone area/BSA (standardized coefficient = -0.74, P < 0.001).In patients with normal LV systolic function and size, MV leaflet and coaptation-zone areas might be reduced according to advancing atherosclerosis. Patients with atherosclerosis might be at increased risk of developing FMR.

High Prevalence of Left Ventricular Non-Compaction and Its Effect on Chemotherapy-Related Cardiac Dysfunction in Patients With Hematological Diseases.

BACKGROUND: Recent progress in chemotherapy has prolonged the survival of patients with hematological diseases, but has also increased the number of patients with chemotherapy-related cardiac dysfunction (CTRCD). However, the causes of individual variations and risk factors for CTRCD have yet to be fully elucidated.Methods and Results:Consecutive echocardiograms of 371 patients were retrospectively evaluated for the presence of left ventricular (LV) non-compaction (LVNC). Individual LV ejection fraction (LVEF) outcome estimates were made using bivariate linear regression with log-transformed duration Akaike information criterion (AIC) model fitting. The prevalence of LVNC was 6-fold higher in patients with hematological diseases than in those with non-hematological diseases (12% vs. 2%; risk ratio 6.1; 95% confidence interval [CI] 2.0, 18.2). Among patients with hematological diseases, the ratio of myeloid diseases was significantly higher in the group with LVNC (P=0.031). Deterioration of LVEF was more severe in patients with than without LVNC (-14.4 percentage points/year [95% CI -21.0, -7.9] vs. -4.6 percentage points/year [95% CI -6.8, -2.4], respectively), even after multivariate adjustment for baseline LVEF, background disease distributions, cumulative anthracycline dose, and other baseline factors. CONCLUSIONS: LVNC is relatively prevalent in patients with hematological diseases (particularly myeloid diseases) and can be one of the major risk factors for CTRCD. Detailed cardiac evaluations including LVNC are recommended for patients undergoing chemotherapy.

Frequency of Clinical Monitoring of Serum Concentrations of Digoxin, Potassium, and Creatinine, and Recording of Electrocardiograms in Digoxin-Treated Patients: A Japanese Claims Database Analysis.

Guidelines for cardiovascular drug therapy recommend monitoring serum digoxin concentration (SDC) in patients receiving digoxin treatment, especially those with renal dysfunction and hypokalemia. However, only a few studies have reported the prevalence of SDC monitoring and laboratory testing in clinical practice. Therefore, the aim of this study was to describe the frequency of SDC monitoring and laboratory testing in digoxin users and to assess the association between SDC monitoring and patient characteristics. We used the Japanese insurance claims data covering approximately 1.7 million patients aged 20-74 years between January 1, 2005 and March 31, 2014. All patients who had at least one prescription for digoxin were included. The frequency of SDC and laboratory tests was calculated and the association between patient characteristics and SDC monitoring was assessed using logistic regression analysis. A total of 98867 prescriptions of digoxin were issued to 3458 patients between 2005 and 2014. The annual mean frequencies of monitoring SDC, serum potassium level and serum creatinine level and of recording electrocardiograms was 16.8, 34.8, 38.7, and 24.1%, respectively. Atrial fibrillation, chronic heart failure, renal diseases, and use of oral anticoagulants were associated with SDC monitoring. We found the frequency of SDC monitoring to be relatively low in Japanese clinical practice.

Are there gender differences in the association between body mass index and left ventricular diastolic function? A clinical observational study in the Japanese general population.

BACKGROUND: Increased body mass index (BMI) is a major risk factor for heart failure with preserved ejection fraction (HFpEF), and HFpEF is more prevalent in elderly females than males. We hypothesized that there may be gender differences in the association between BMI and echocardiographic left ventricular (LV) diastolic parameters. METHODS: We enrolled 456 subjects (243 males) without overt cardiac diseases, all of whom underwent a health checkup. Early (E) and late (A) diastolic transmitral flow velocity, early diastolic mitral annular velocity (e'), and left atrial (LA) volume index were measured by echocardiography to assess LV diastolic function. To examine gender differences in the association between BMI and LV diastolic function, we analyzed the interaction effects of gender on the association between BMI and echocardiographic LV diastolic parameters. RESULTS: Although there were significant gender differences in the association between BMI and E/A and e' in the crude model (interaction effect 0.037 and 0.173, respectively; P = .006 and .022, respectively), these differences were not statistically significant after adjustment for factors related to LV diastolic function. On the other hand, there were significant associations between BMI and LV diastolic parameters in each gender, even after adjustment. CONCLUSIONS: Our findings suggest there is no gender difference in the association between BMI and echocardiographic LV diastolic parameters. However, the association between BMI and LV diastolic parameters was significant in both genders. Controlling body weight might be beneficial for both women and men to prevent progression of LV diastolic dysfunction and development of HFpEF.

Age-Dependent Echocardiographic and Pathologic Findings in a Rat Model with Duchenne Muscular Dystrophy Generated by CRISPR/Cas9 Genome Editing.

Duchenne muscular dystrophy (DMD) is X-linked recessive myopathy caused by mutations in the dystrophin gene. Although conventional treatments have improved their prognosis, inevitable progressive cardiomyopathy is still the leading cause of death in patients with DMD. To explore novel therapeutic options, a suitable animal model with heart involvement has been warranted.We have generated a rat model with an out-of-frame mutation in the dystrophin gene using CRISPR/Cas9 genome editing (DMD rats). The aim of this study was to evaluate their cardiac functions and pathologies to provide baseline data for future experiments developing treatment options for DMD.In comparison with age-matched wild rats, 6-month-old DMD rats showed no significant differences by echocardiographic evaluations. However, 10-month-old DMD rats showed significant deterioration in left ventricular (LV) fractional shortening (P = 0.024), and in tissue Doppler peak systolic velocity (Sa) at the LV lateral wall (P = 0.041) as well as at the right ventricular (RV) free-wall (P = 0.004). These functional findings were consistent with the fibrotic distributions by histological analysis.Although the cardiac phenotype was milder than anticipated, DMD rats showed similar distributions and progression of heart involvement to those of patients with DMD. This animal may be a useful model with which to develop effective drugs and to understand the underlying mechanisms of progressive heart failure in patients with DMD.

Heart Transplantation Ameliorates Ambulation Capacity in Patients With Muscular Dystrophy　- An Analysis of 9 Cases.

BACKGROUND: Heart transplantation (HTx) is reported to have a comparable effect on the prognosis of heart failure patients without muscular disease and for those with muscular dystrophy (MD). However, little is known about the changes in muscular diseases in patients with MD after HTx. Methods and Results: We assessed the ambulatory capacity of 9 patients with MD who underwent HTx. All patients demonstrated improvement in ambulation to varying degrees and 1 patient successfully climbed Mount Fuji 3.8 years after HTx. CONCLUSIONS: HTx potentially improves not only the prognosis but also the ambulatory capacity of patients with MD.

C-reactive protein/albumin ratio is a poor prognostic factor of esophagogastric junction and upper gastric cancer.

BACKGROUND AND AIM: The C-reactive protein (CRP)/albumin (Alb) ratio has been reported as a novel prognostic marker in several cancers. The objective of this study was to investigate the prognostic value of the CRP/Alb ratio in patients who underwent surgery for adenocarcinoma of the esophagogastric junction (AEG) and upper gastric cancer (UGC). METHODS: Data for 144 patients who underwent surgery for AEG and UGC were reviewed. The CRP/Alb ratio, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, Glasgow Prognostic Score, and controlling nutritional status score were calculated, and the relationship between these biomarkers and postoperative prognosis was analyzed. RESULTS: The optimal cutoff value of the CRP/Alb ratio was determined to be 0.1. According to the cutoff value of CRP/Alb ratio, patients were divided into two groups (CRP/Alb < 0.1, n = 124; CRP/Alb ≥ 0.1, n = 20). The 5-year recurrence-free survival and overall survival (OS) rates were significantly lower in the patients with the CRP/Alb ratio ≥ 0.1 than in those with the CRP/Alb ratio < 0.1 (recurrence-free survival: 44.9% vs 77.9%, P = 0.0011; OS: 43.4% vs 82.0%, P < 0.0001). In the multivariate analyses, the N-stage, and CRP/Alb ratio ≥ 0.1 were identified as independent predictive factors for OS in patients with AEG and UGC (P = 0.0061 and P = 0.0439, respectively). CONCLUSIONS: The CRP/Alb ratio was strongly associated with poor prognosis in patients who underwent surgery for AEG and UGC.

Postoperative Skeletal Muscle Loss Predicts Poor Prognosis of Adenocarcinoma of Upper Stomach and Esophagogastric Junction.

BACKGROUND: The relationship between postoperative changes in muscle mass and the prognosis of malignancies remains controversial. We aimed to determine whether a decrease in skeletal muscle mass after surgical resection can predict long-term outcomes in patients with adenocarcinoma of upper stomach (AUS) and esophagogastric junction (AEGJ). METHODS: We reviewed 146 patients who underwent curative surgery for AUS and AEGJ. We assessed the skeletal muscle index pre- and post-surgery and 6 months postoperatively. The rate of decrease in skeletal muscle index (SMI) was calculated and its relationship with clinicopathological factors and prognosis was analyzed. RESULTS: Among the 146 patients studied, 115 underwent re-assessment of SMI 6 months postoperatively. The mean decrease in SMI was more prominent in patients with recurrence than in those without recurrence (19.0 ± 2.3 vs. 7.4 ± 0.9%, respectively, P < 0.0001). AUS and AEGJ patients with a >19% decrease in SMI showed significantly lower 5-year overall survival and recurrence-free rates than those with a <19% decrease in SMI (recurrence-free survival: 33.4 vs. 89.2%, respectively, P < 0.0001; overall survival: 40.6 vs. 90.0%, respectively, P < 0.0001). Multivariate analyses indicated that a ≥19% decrease in SMI could predict poor overall survival independently in patients with AUS and AEGJ (P = 0.0070). CONCLUSIONS: A ≥19% postoperative decrease in SMI was substantially associated with poor survival in patients with AUS and AEGJ.

Detection of Pulmonary Hypertension with Systolic Pressure Estimated by Doppler Echocardiography.

Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (PAP) ≥ 25 mmHg at rest as assessed by right heart catheterization (RHC), and Doppler-derived systolic PAP (sPAPECHO) or tricuspid regurgitation pressure gradient (TRPG) is widely used to screen for PH. However, the cutoff value of sPAPECHO or TRPG for detecting a mean PAP ≥ 25 mmHg that was determined invasively has not been well defined.We studied 189 patients who underwent RHC. Echocardiography was performed within 24 hours of invasive evaluation, and sPAPECHO was defined as the TRPG with right atrial pressure estimated on the basis of the current guideline.From the receiver operating characteristic (ROC) curve analysis, the optimal sPAPECHO, and TRPG cutoffs for detecting PH were 41 mmHg (sensitivity, 92%; specificity, 91%; area under the curve = 0.95) and 36 mmHg (sensitivity, 90%; specificity, 93%; area under the curve = 0.95), respectively. The area under the TRPG ROC curve was similar to the area under the sPAPECHO ROC curve.Given that Doppler echocardiography is required to accurately detect PH rather than to accurately estimate systolic PAP, our results provide useful information with regard to screening patients for PH and recommending further investigations on PH.

Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma: A Multi-institutional Study.

BACKGROUND: The Controlling Nutritional Status (CONUT) score is an objective tool that is widely used to assess the nutritional status in patients, including those with cancer. The relationship between the CONUT score and prognosis in patients who have undergone hepatic resection has not been evaluated in a multi-institutional study. METHODS: Data were retrospectively collected for 2461 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent at 13 institutions between January 2004 and December 2015. Patients were assigned to two groups: preoperative CONUT scores ≤ 3 (low CONUT score) and ≥ 4 (high CONUT score). Clinicopathological characteristics, surgical outcomes, and long-term survival were compared using propensity score matching analysis. RESULTS: Of the 2461 patients, 540 (21.9%) had high (≥ 4) and 1921 (78.1%) had low (≤ 3) preoperative CONUT scores. Overall, a high CONUT score was significantly associated with older age, female sex, low body mass index, low serum albumin, high serum total bilirubin, low lymphocyte count, low serum cholesterol, shorter prothrombin time, higher indocyanine green retention test at 15 min, Child-Pugh B (vs. A), liver cirrhosis, minor resection, shorter operation time, massive blood loss, blood transfusion, and postoperative complications. After propensity score matching, a higher CONUT score was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS) using multivariate analysis. CONCLUSIONS: This retrospective, multi-institutional analysis showed that, in patients who undergo curative hepatectomy for HCC, the preoperative CONUT score is predictive of worse OS and RFS, even after propensity score matching analysis.

Potential effect of recombinant thrombomodulin on ischemia-reperfusion liver injury in rats.

AIM: Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High-mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage-associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury. METHODS: Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1. RESULTS: In rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(-) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(-) group after surgery (P < 0.001). The levels of tumor necrosis factor-α and interleukin-6 in the liver tissue 24 h after surgery were significantly lower in the rTM(+) group than the rTM(-) group (P < 0.001). The plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(-) group (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(-) group (P < 0.001). CONCLUSIONS: Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1.

Positive predictive value of ICD-10 codes for acute myocardial infarction in Japan: a validation study at a single center.

BACKGROUND: In Japan, several large healthcare databases have become available for research since the early 2000's. However, validation studies to examine the accuracy of these databases remain scarce. We conducted a validation study in order to estimate the positive predictive value (PPV) of local or ICD-10 codes for acute myocardial infarction (AMI) in Japanese claims. In particular, we examined whether the PPV differs between claims in the Diagnosis Procedure Combination case mix scheme (DPC claims) and in non-DPC claims. METHODS: We selected a random sample of 200 patients from all patients hospitalized at a large tertiary-care university hospital between January 1, 2009 and December 31, 2011 who had an inpatient claim assigned a local or ICD-10 code for AMI. We used a standardized data abstraction form to collect the relevant information from an electronic medical records system. Abstracted information was then categorized by a single cardiologist as being either definite or not having AMI. RESULTS: In a random sample of 200 patients, the average age was 67.7 years and the proportion of males was 78.0%. The PPV of the local or ICD-10 code for AMI was 82.5% in this sample of 200 patients. Further, of 178 patients who had an ICD-10 code for AMI based on any of the 7 types of condition codes in the DPC claims, the PPV was 89.3%, whereas of the 161 patients who had an ICD-10 code for AMI based on any of 3 major types of condition codes in the DPC claims, the PPV was 93.8%. CONCLUSION: The PPV of the local or ICD-10 code for AMI was high for inpatient claims in Japan. The PPV was even higher for the ICD-10 code for AMI for those patients who received AMI care through the DPC case mix scheme. The current study was conducted in a single center, suggesting that a multi-center study involving different types of hospitals is needed in the future. The accuracy of condition codes for DPC claims in Japan may also be worth examining for conditions other than AMI such as stroke.

Prognostic Value of a Simple Echocardiographic Parameter, the Right Ventricular Systolic to Diastolic Duration Ratio, in Patients with Advanced Heart Failure with Non-Ischemic Dilated Cardiomyopathy.

The prognostic value of the right ventricular (RV) systolic to diastolic duration ratio (S/D ratio) in patients with advanced heart failure is not clear.We enrolled 45 patients with DCM (40 ± 13 years, 33 male) who were admitted to our hospital for evaluation or treatment of heart failure. The RV systolic and diastolic durations were measured using continuous Doppler imaging of tricuspid regurgitation, and the RV S/D ratio was calculated. Cardiac events were defined as cardiac death or left ventricular assist device implantation within the first year. Twenty-eight cardiac events occurred. The RV S/D ratio was significantly higher in the event group than in the event-free group (1.8 ± 0.8 versus 1.2 ± 0.5, P = 0.008). Univariate analysis showed that the RV S/D ratio, plasma brain natriuretic peptide concentration, left atrial volume index, and mitral deceleration time were associated with these events. Receiver operating characteristic curve analysis revealed that the optimal RV S/D cutoff value to predict events was 1.2 (sensitivity 79%, specificity 65%, area under the curve 0.745). Kaplan-Meier analysis indicated a significantly higher event rate in patients with an RV S/D ratio > 1.2 (log-rank test, P = 0.003). The addition of an RV S/D ratio > 1.2 improved the prognostic utility of a model that included conventional variables (P = 0.014).In patients with advanced heart failure with DCM, the RV S/D ratio was higher in patients with events than in those without events. The addition of the RV S/D ratio to conventional parameters may provide better prognostic information.

Reconsideration of Inferior Vena Cava Parameters for Estimating Right Atrial Pressure in an East Asian Population　- Comparative Simultaneous Ultrasound-Catheterization Study.

BACKGROUND: Ultrasound measurements of the inferior vena cava (IVC) diameter (IVCD), together with its respiratory variation, provide a noninvasive estimate of right atrial pressure (RAP). However, there is a paucity of studies that have compared this technique with simultaneous catheterization. We explored the best cut-off values of IVC parameters for elevated RAP in comparison with RAP measured by catheterization.Methods and Results:We prospectively enrolled 120 East Asian patients who were scheduled for catheterization. The IVCD and IVC collapsibility index (IVCCI) were measured according to the current guidelines. The optimal maximum IVCD (IVCDmax) and IVCCI cut-offs for detecting elevated RAP (RAP ≥10 mmHg) were 17 mm and 40%, respectively. When we combined both in proportion to the guidelines, the sensitivity and specificity for detecting elevated RAP were 75% and 94%, respectively. When the cut-off values from the current guidelines (>21 mm and <50%) were applied, the respective sensitivity and specificity were 42% and 99%. Interestingly, the cut-off value of the optimal IVCDmax indexed by body surface area (11 mm/m2) was similar to previous Western population data. When we combined both cut-off values (11 mm/m2and 40%), the sensitivity and specificity were 75% and 95%, respectively. CONCLUSIONS: The optimal absolute IVCDmax and IVCCI cut-offs to detect elevated RAP were smaller than those in the current guidelines. Indexed IVCDmax may be an IVC parameter that can be used internationally.