Validation study of age-independent fibrosis score (Fibrosis-3 index) in patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Because the accuracy of the Fibrosis-4 (FIB-4) index for predicting liver fibrosis changes with age, the need for different cut-offs in various age groups has frequently been discussed. We developed the age-independent score, the Fibrosis-3 (FIB-3) index, and have shown its usefulness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB-3 index to predict fibrosis progression using a large new patient cohort. METHODS: The ability of the FIB-3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB-4 index using data from 1398 patients with MASLD enrolled in the Asia-based clinical outcome NAFLD study. RESULTS: The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB-3 and FIB-4 indices in the entire cohort. Using the single ideal cut-offs of the indices (3.41 for FIB-3 index and 2.01 for FIB-4 index), the predictive accuracy of the FIB-3 index was not significantly different from that of the FIB-4 index among patients aged <60 years; however, the accuracy of the FIB-3 index was significantly higher than that of the FIB-4 index in those aged ≥60 years (0.645 and 0.529, respectively; p < 0.0001). CONCLUSION: The high ability of the FIB-3 index with a single cut-off to predict liver fibrosis in patients with MASLD was confirmed. The FIB-3 index could serve as a useful tool for assessing liver fibrosis regardless of age.

Clinical impact of Academic Research Consortium for High Bleeding-Risk scores on clinical outcomes in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

High bleeding risk (HBR), as defined by the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria, has been recently reported to be associated with an increased risk of major bleeding events and cardiovascular events. We investigated the association between the ARC-HBR score and clinical outcomes in patients with stable coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). We assessed 328 consecutive patients with stable CAD who underwent PCI between January 2017 and December 2020. We scored the ARC-HBR criteria by assigning 1 point to each major criterion and 0.5 points to each minor criterion. Patients were stratified into low (ARC-HBR score < 1), intermediate (1 ≤ ARC-HBR score < 2), and high (ARC-HBR score ≥ 2) bleeding-risk groups. The primary outcome measure was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. We compared the discriminative abilities of the ARC-HBR score with the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS2°P) and ARC-HBR score with Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) thrombotic risk score. The mean patient age was 70.1 ± 10.2 years (males, 76.8%). During the median follow-up period of 983 (618-1338) days, 44 patients developed MACE. Kaplan-Meier curves showed that a stepwise significant increase in the cumulative incidence of MACE as the ARC-HBR score increased (log-rank p < 0.001). In the time-dependent receiver-operating characteristic curve analysis for predicting MACE within 2 years, the area under the curve (AUC) of the ARC-HBR score was significantly higher than that of the TRS2°P (AUC: 0.825 vs. 0.725, p value for the difference = 0.023) and similar to that of CREDO-Kyoto thrombotic risk score (AUC: 0.825 vs. 0.813, p value for the difference = 0.627). Conclusions: The ARC-HBR score adequately stratified future risk of MACE in patients with stable CAD who underwent PCI. The ARC-HBR score showed a higher discriminative ability for predicting mid-term MACE than the TRS2°P.

Benefits of Collaboration Between the Wound, Ostomy, and Continence Nurse and Orthopedic Surgeon When Treating Skin Defects After Soft Tissue Sarcoma Resection: A Retrospective Case-Control Study.

PURPOSE: The purpose of this study was to evaluate the benefits of collaborative management between orthopedic surgery and WOC nurses in patients undergoing resection of subcutaneous sarcomas. DESIGN: Retrospective case-control study. SUBJECTS AND SETTING: The sample comprised 25 patients who underwent wide resection for soft tissue sarcoma, followed by 2-stage split-thickness skin grafting. Data collection occurred between January 2015 and April 2021 in a university hospital based in Kagoshima, Japan. For comparison, we categorized these patients into 2 groups: intervention group participants were managed by an orthopedic surgeon and a WOC nurse; nonintervention group members were managed without WOC nurse participation. METHODS: Patient background and treatment-related information was retrospectively collected from medical records and compared between the WOC nurse intervention group and the nonintervention group, including maximum tumor diameter, surgical time, maximum skin defect diameter, length of hospital stay, and time from surgery to complete wound healing. RESULTS: The average length of hospital stay was significantly shorter in the WOC nurse intervention group compared with the nonintervention group (38.3 days, SD = 8.0 vs 47.1 days, SD = 10.2; P = .023). CONCLUSION: Collaborative wound management with a WOC nurse resulted in a shorter hospital length of stay when compared to traditional management with WOC nurse involvement. Based on these findings, we assert that WOC nurses provide an important bridge between postoperative wound management in patients undergoing resection of subcutaneous sarcomas.

Clinical Outcomes in Biopsy-Proven Nonalcoholic Fatty Liver Disease Patients: A Multicenter Registry-based Cohort Study.

BACKGROUND & AIMS: There are no detailed reports of clinical outcomes in Asian patients with nonalcoholic fatty liver disease (NAFLD) who undergo liver biopsy. We aimed to investigate the clinical outcomes of a large cohort of Asian patients with biopsy-proven NAFLD and evaluate the specific effects of nonalcoholic steatohepatitis and fibrosis stage. METHODS: This multicenter registry-based retrospective cohort study, called the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) in Asia, included 1398 patients. RESULTS: The median follow-up period was 4.6 years (range, 0.3-21.6 years), representing a total of 8874 person-years of follow-up. During that time, 47 patients died, and 1 patient underwent orthotopic liver transplantation. The leading cause of death was nonhepatic cancer (n = 10). The leading causes of liver-related death were liver failure (n = 9), hepatocellular carcinoma (HCC) (n = 8), and cholangiocellular carcinoma (n = 4). During follow-up, 37 patients developed HCC, 31 developed cardiovascular disease, and 68 developed nonhepatic cancer (mainly breast, stomach, and colon/rectum). Among our cohort of patients with NAFLD, liver-specific mortality was 2.34/1000 person-years (95% confidence interval [CI], 1.52-3.58), overall mortality was 5.34/1000 person-years (95% CI, 4.02-7.08), and HCC incidence was 4.17/1000 person-years (95% CI, 3.02-5.75). Liver fibrosis was independently associated with liver-related events but not overall mortality. CONCLUSIONS: Liver-related mortality was the leading cause of mortality in Asian patients with biopsy-confirmed NAFLD. Although fibrosis stage was independently associated with liver-related events, it was not associated with overall mortality after adjusting for confounders, such as histologic features of steatohepatitis.

Agile 3+ and Agile 4, noninvasive tests for liver fibrosis, are excellent formulae to predict liver-related events in nonalcoholic fatty liver disease.

AIM: The noninvasive tests (NITs) Agile 3+ and Agile 4 effectively identify patients with nonalcoholic fatty liver disease (NAFLD) complicated with advanced fibrosis (F3-4) and cirrhosis (F4), respectively. Little information is available on associations between Agile scores and intra-/extrahepatic events. The aim of this study was to determine the predictive performance of Agile scores for intra-/extrahepatic events in Asian patients with biopsy-proven NAFLD. METHODS: We undertook a retrospective multicenter cohort study to investigate associations between intra-/extrahepatic events and two Agile scores, Agile 3+ and Agile 4. The scores were obtained by combining clinical parameters and liver stiffness measurement using transient elastography. RESULTS: Among 403 enrolled patients, 11 had liver-related events (LREs), including seven with hepatocellular carcinoma (HCC). The incidence of LREs and HCC showed a stepwise increase in the advanced fibrosis group (F3-4), Agile 3+ rule-in (F3-4, highly suspected), and Agile 4 rule-in (F4, highly suspected) groups, compared to their counterparts. Hazard ratios for LREs in the advanced fibrosis group, Agile 3+ rule-in, and Agile 4 rule-in groups were 4.05 (p = 0.03), 23.5 (p = 0.003), and 45.5 (p < 0.001), respectively. The predictive performance results for Agile 3+ and Agile 4 were 0.780 and 0.866, respectively, which were higher than for fibrosis (0.595). Unlike for LREs, Agile scores failed to identify patients with extrahepatic events, including cardiovascular events and extrahepatic cancer. CONCLUSIONS: Agile 3+ and Agile 4 scores are excellent NITs for predicting LREs in patients with NAFLD, possibly without histological assessment.

Multicenter, retrospective, cohort study shows platelet counts predict hepatocellular carcinoma development in patients with nonalcoholic fatty liver disease.

AIM: Impacts of platelet counts at the time of liver biopsy on hepatocellular carcinoma (HCC) development in patients with nonalcoholic fatty liver disease (NAFLD) remain unknown. The aim of this study was to investigate the prognostic value of platelet counts in patients with biopsy-confirmed NAFLD using data from a multicenter study. METHODS: One thousand three hundred ninety-eight patients were included in this subanalysis of the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) in Asia study. Liver biopsy specimens were pathologically diagnosed, and histologically scored using the NASH Clinical Research Network system. Demographic, clinical, laboratory, and pathological data were collected. RESULTS: During a median follow-up period of 4.6 years (range, 0.3-21.6 years), which corresponds to 8874 person-years, 37 patients developed HCC. Using a cut-off baseline platelet count of 192 × 109/L, the lower platelet group had a higher HCC rate than the higher platelet group (6.7% vs. 0.4%; p < 0.001). This cut-off value significantly stratified the event-free rate for HCC. Lower platelet counts were associated with an increased risk of HCC development. Relative to patients with platelet counts of 192 × 109/L, patients with platelet counts of 100 × 109/L had an unadjusted hazard ratio (HR) for HCC development of 7.37 (95% confidence interval [CI], 3.81-14.2) and an adjusted HR of 11.2 (95% CI, 3.81-32.7; p < 0.001), adjusting for age, sex, NASH, and diabetes. CONCLUSIONS: Baseline platelet counts of 192 × 109/L and lower are associated with a higher risk of developing HCC in patients with biopsy-confirmed NAFLD and require active surveillance.

Noninvasive tests predict liver-related events and mortality in patients with nonalcoholic fatty liver disease: sub-analysis of the CLIONE-Asia study.

BACKGROUND AND AIMS: Noninvasive tests (NITs) have prognostic potential, but whether NITs are comparable with liver biopsy is unclear. This study aimed to examine the prognostic accuracy of NITs for liver-related mortality (LRM) and events (LREs) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). METHODS: We investigated 1313 patients with NAFLD. Patients were assigned to low-risk, indeterminate-risk, and high-risk groups using conventional cutoff values of each FIB-4 and NAFLD fibrosis score (NFS) and to stage 0-2 and stage 3-4 groups using the fibrosis stage. Survival and Cox regression analyses of the prognostic potential of NITs for LRM/LREs were conducted. RESULTS: During a median follow-up of 4.5 years, regarding to FIB-4, the incidence rate (/1000 person-years) in the low risk was zero for LRM and 0.5 for LREs. In contrast, the rate in stage 0-2 was 1.3 for LRM and 2.8 for LRE. The adjusted hazard ratios (aHRs) for LREs in the high risk compared with the low risk were 32.85 (P < 0.01). The aHRs in stage 3-4 compared with stage 0-2 were 2.68 (P = 0.02) for LREs and 2.26 (P = 0.582) for LRM. In the same fibrosis stage, the incidence of LRM/LREs was more frequent with a higher risk stratification. The same trend was observed for NFS. CONCLUSIONS: NITs accurately predict LRM and LREs as well as a liver biopsy in Japanese patients with NAFLD. Patients in the low risk may not require close follow-up for at least 5 years. The simple NITs could be an acceptable alternative method to performing a liver biopsy for the prognosis of NAFLD.

Identification of clinical phenotypes associated with poor prognosis in patients with nonalcoholic fatty liver disease via unsupervised machine learning.

BACKGROUND AND AIMS: Both fibrosis status and body weight are important for assessing prognosis in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify population clusters for specific clinical outcomes based on fibrosis-4 (FIB-4) index and body mass index (BMI) using an unsupervised machine learning method. METHODS: We conducted a multicenter study of 1335 biopsy-proven NAFLD patients from Japan. Using the Gaussian mixture model to divide the cohort into clusters based on FIB-4 index and BMI, we investigated prognosis for these clusters. RESULTS: The cohort consisted of 223 cases (16.0%) with advanced fibrosis (F3-4) as assessed from liver biopsy. Median values of BMI and FIB-4 index were 27.3 kg/m2 and 1.67. The patients were divided into four clusters by Bayesian information criterion, and all-cause mortality was highest in cluster d, followed by cluster b (P = 0.001). Regarding the characteristics of each cluster, clusters d and b presented a high FIB-4 index (median 5.23 and 2.23), cluster a presented the lowest FIB-4 index (median 0.78), and cluster c was associated with moderate FIB-4 level (median 1.30) and highest BMI (median 34.3 kg/m2 ). Clusters a and c had lower mortality rates than clusters b and d. However, all-cause of death in clusters a and c was unrelated to liver disease. CONCLUSIONS: Our clustering approach found that the FIB-4 index is an important predictor of mortality in NAFLD patients regardless of BMI. Additionally, non-liver-related diseases were identified as the causes of death in NAFLD patients with low FIB-4 index.

Different effects of medications for hypertension on renal function between patients with and without diabetes mellitus undergoing percutaneous coronary intervention: a retrospective single-center cohort study.

BACKGROUND: Diabetes mellitus (DM) and hypertension are well-known atherosclerosis risk factors. Furthermore, renal dysfunction is a crucial risk factor for patients with coronary artery disease (CAD), and managing renal function in these patients is complicated because of comorbid conditions and potential side effects during treatment. Therefore, this study aimed to investigate the effect of medications for hypertension on renal function after percutaneous coronary intervention (PCI) between patients with and without DM with statins. METHODS: In 297 consecutive patients undergoing PCI for stable angina pectoris, cystatin C (CysC) was evaluated at baseline and 9 months after PCI, and the percent change in CysC (%CysC) was calculated. The association of worsening renal function (WRF: %CysC ≥ 0) and baseline characteristics, including medications, was assessed. RESULTS: Among 297 hypertensive patients with statins, 196 and 101 were with and without DM, respectively. Angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker, and ß-blocker were prescribed in 56 (29%), 82 (42%), and 91 (46%) patients in the DM group, and 20 (20%), 52 (51%), and 52 (51%) in the non-DM group, respectively. The patients with WRF after PCI were 100 (51%) and 59 (58%) in the DM and non-DM groups (p = 0.261). Additionally, the %CysC had no significant differences between groups [median: 0%, interquartile range (IQR): -7.9% to 8.5% vs. median: 1.1%, IQR: -6.6% to 9.6%, p = 0.521]. Multivariate logistic analysis for WRF using relevant factors from univariate analysis showed that only ß-blocker [odds ratio (OR): 2.76, 95% confidence interval (CI): 1.03-7.90, p = 0.048] was independently associated with WRF in the DM group whereas ACEI (OR: 0.07, 95% CI: 0.01-0.47, p = 0.012) was negatively correlated with WRF in the non-DM group. CONCLUSION: The ß-blocker was the independent risk factor for WRF in patients with DM in the late phase after PCI for stable angina pectoris, while the use of ACEI had a renoprotective effect in patients without DM.

Association of preoperative clinical frailty and clinical outcomes in elderly patients with stable coronary artery disease after percutaneous coronary intervention.

There are few reports on the long-term clinical outcome after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) complicated with frailty. This novel study investigated the association between pre-PCI frailty and long-term clinical outcomes in elderly patients aged 65 years or older with stable CAD who underwent elective PCI. We assessed 239 consecutive patients aged 65 years or older with stable CAD who underwent successful elective PCI at Kagoshima City Hospital between January 1st, 2017 and December 31st, 2020. Frailty was retrospectively assessed using the Canadian Study and Aging Clinical Frailty Scale (CFS). Based on the pre-PCI CFS, patients were divided into two groups: the non-frail (CFS < 5) and the frail (CFS ≥ 5) group. We investigated the association between pre-PCI CFS and major adverse cardiovascular events (MACEs) defined as the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and heart failure requiring hospitalization. Additionally, we assessed the association between pre-PCI CFS and major bleeding events defined as Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The mean age was 74.8 ± 7.0 years, and 73.6% were men. According to the pre-PCI frailty assessment, 38 (15.9%) and 201 (84.1%) were classified as frail and non-frail groups, respectively. During a median follow-up of 962 (607-1284) days, 46 patients developed MACEs and 10 patients developed major bleeding events. Kaplan-Meier curves showed a significantly higher incidence of MACE in the frail group compared to those in the non-frail group (Log-rank p < 0.001). Even in multivariate analysis, pre-PCI frailty (CFS ≥ 5) was independently associated with MACE (HR 4.27, 95% CI 1.86-9.80, p-value: < 0.001). Additionally, the cumulative incidence of major bleeding events was significantly higher in the frail group than in the non-frail group (Log-rank p = 0.001). Pre-PCI frailty was an independent risk factor for MACE and bleeding events in elderly patients with stable CAD who underwent elective PCI.

Pre-Extubation Cuffed Tube Leak Test and Subsequent Post-Extubation Laryngeal Edema: Prospective, Single-Center Evaluation of PICU Patients.

OBJECTIVES: We performed our standard air leak, leak percentage, and cuff leak percentage tests in pediatric patients intubated with microcuff pediatric tracheal tubes (MPTTs) just before extubation. We examined the association between test findings and the subsequent occurrence of post-extubation laryngeal edema (PLE). DESIGN: Prospective, single-center, observational study. SETTING: PICU (June 1, 2020 to May 31, 2021). PATIENTS: Pediatric patients intubated and scheduled for extubation during the day shift in the PICU. INTERVENTIONS: Multiple pre-extubation leak tests were performed on each patient immediately before extubation. In our center, the standard leak test is positive if a leak is audible at 30 cm H 2 O applied pressure with the MPTT cuff deflated. Two other tests were calculated in the pressure control-assist control ventilator mode using the following formulas: leak percentage with deflated cuff = (inspiratory tidal volume [V t ]-expiratory V t ) × 100/inspiratory V t ; cuff leak percentage = (expiratory V t with inflated cuff-expiratory V t with deflated cuff) × 100/expiratory V t with inflated cuff. MEASUREMENTS AND MAIN RESULTS: The diagnostic criteria for PLE was made by at least two healthcare professionals and included upper airway stricture with stridor-requiring nebulized epinephrine. Eighty-five pediatric patients (< 15 yr) who had been intubated for at least 12 hours using the MPTT were included. Positive rates for the standard leak, leak percentage (cutoff 10%), and cuff leak percentage (cutoff 10%) tests were 0.27, 0.20, and 0.64, respectively. The standard leak, leak percentage, and cuff leak tests showed sensitivities of 0.36, 0.27, and 0.55, respectively; and specificities of 0.74, 0.81, and 0.35, respectively. PLE occurred in 11 of 85 patients (13%), and there were no instances of needing reintubation. CONCLUSIONS: The pre-extubation leak tests in current practice for intubated pediatric patients in the PICU all lack diagnostic accuracy for PLE.

Association of wound, ischemia, and foot infection clinical stage with frailty and malnutrition in chronic limb-threatening ischemia patients undergoing endovascular intervention.

OBJECTIVE: The Wound, Ischemia, and foot Infection (WIfI) clinical stage has been thought to have a prognostic value in Chronic limb-threatening ischemia (CLTI) patients, and frailty and nutritional status appear to represent pivotal factor affecting prognosis among CLTI patients. The purpose of this study was to examine clinical factors (including frailty and nutritional status) relevant to WIfI clinical stage. METHODS: This retrospective study investigated 200 consecutive CLTI patients. We individually assessed WIfI clinical stage, frailty according to the Clinical Frailty Scale (CFS) score, and malnutrition according to Geriatric Nutritional Risk Index (GNRI). We then compared mortality after endovascular intervention between a WIfI stage 1, 2 group and a stage 3, 4 group, and investigated associations between baseline characteristics (including CFS and GNRI) and WIfI clinical stage. RESULTS: Among 200 patients, 123 patients (62%) showed WIfI stage 1 or 2, and the remaining 77 patients (38%) had WIfI stage 3 or 4. CFS score was significantly higher in the WIfI stage 3, 4 group [median 6.0, interquartile range (IQR) 5.5-7.0] compared with the WIfI stage 1, 2 group (median 5.0, IQR 4.0-6.0, p < 0.001), and GNRI was significantly lower in the WIfI stage 3, 4 group (median 88, IQR 80-97) than in the WIfI stage 1, 2 (median 103, IQR 94-111, p < 0.001). Forty patients (20%) died after endovascular intervention. Incidences of all-cause and cardiac deaths were higher in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (27% vs. 15%, p = 0.047 and 12% vs. 3%, p = 0.040, respectively). Kaplan-Meier analysis showed a significantly lower survival rate in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (p = 0.002 by log-rank test). Multivariate logistic regression analysis using relevant factors from univariate analysis showed CFS score [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.41-3.13, p < 0.001), diabetes mellitus (OR 3.17, 95%CI 1.17-8.61, p = 0.023) and GNRI (OR 0.93, 95%CI 0.89-0.97, p = 0.002) significantly associated with WIfI stage 3 or 4. In addition, multivariate ordinal logistic regression analysis for WIfI clinical stage showed CFS score (OR 1.43, 95%CI 1.09-1.89, p = 0.011), diabetes mellitus (OR 1.77, 95%CI 1.26-2.54, p < 0.001), and high-sensitivity C-reactive protein (OR 1.14, 95%CI 1.02-1.28, p = 0.041) were positively associated with WIfI clinical stage, and GNRI correlated negatively with WIfI clinical stage (OR 0.95, 95%CI 0.91-0.97, p < 0.001). CONCLUSIONS: These results indicate that CLTI patients with high WIfI clinical stage may be more frail and malnourished, and be associated with poor prognosis after endovascular intervention.

Age-dependent effects of diabetes and obesity on liver-related events in non-alcoholic fatty liver disease: Subanalysis of CLIONE in Asia.

BACKGROUND AND AIM: Older age, type 2 diabetes mellitus (T2DM), and obesity are known risk factors for liver-related events (LREs). We investigated the impacts of T2DM and obesity on LRE according to age in Japanese patients with non-alcoholic fatty liver disease (NAFLD). METHODS: We performed a subanalysis of a retrospective cohort study (CLIONE in Asia), including 1395 patients with biopsy-proven NAFLD. The median follow-up was 4.6 years. RESULTS: The median age was 57 years, and 36.2% had T2DM. The median body mass index (BMI) was 27.4, and 28.5% were severely obese (BMI ≥ 30). During follow-up, 37 patients developed hepatocellular carcinoma (HCC), and 58 patients developed LRE. In patients younger than 65 years, advanced fibrosis (hazard ratio [HR] 7.69, P < 0.001) and T2DM (HR 3.37, P = 0.017) were HCC risk factors, and advanced fibrosis (HR 9.40, P < 0.001) and T2DM (HR 2.51, P = 0.016) were LRE risk factors. In patients 65 years and older, advanced fibrosis (HR 4.24, P = 0.010) and obesity (HR 4.60, P = 0.006) were HCC risk factors, and advanced fibrosis (HR 4.22, P = 0.002) and obesity (HR 4.22, P = 0.002) were LRE risk factors. CONCLUSION: Type 2 diabetes mellitus and obesity contributed to LRE in younger and older patients, respectively, along with advanced fibrosis. Therefore, controlling T2DM in patients younger than 65 years and controlling weight in patients 65 years and older could prevent LRE. The development of age-dependent screening and management strategies is necessary for patients with NAFLD.

Impact of nutritional status on prognosis in acute myocardial infarction patients undergoing percutaneous coronary intervention.

BACKGROUND: Malnutrition affects the prognosis of cardiovascular disease. Acute myocardial infarction (AMI) has been a major cause of death around the world. Thus, we investigated the impact of malnutrition as defined by Geriatric Nutritional Risk Index (GNRI) on mortality in AMI patients. METHODS: In 268 consecutive AMI patients who underwent percutaneous coronary intervention (PCI), associations between all-cause death and baseline characteristics including malnutrition (GNRI < 92.0) and Global Registry of Acute Coronary Events (GRACE) risk score were assessed. RESULTS: Thirty-three patients died after PCI. Mortality was higher in the 51 malnourished patients than in the 217 non-malnourished patients, both within 1 month after PCI (p < 0.001) and beyond 1 month after PCI (p = 0.017). Multivariate Cox proportional hazards regression modelling using age, left ventricular ejection fraction and GRACE risk score showed malnutrition correlated significantly with all-cause death within 1 month after PCI (hazard ratio [HR] 7.04; 95% confidence interval [CI] 2.30-21.51; p < 0.001) and beyond 1 month after PCI (HR 3.10; 95% CI 1.70-8.96; p = 0.037). There were no significant differences in area under the receiver-operating characteristic (ROC) curve between GRACE risk score and GNRI for predicting all-cause death within 1 month after PCI (0.90 vs. 0.81; p = 0.074) or beyond 1 month after PCI (0.69 vs. 0.71; p = 0.87). Calibration plots comparing actual and predicted mortality confirmed that GNRI (p = 0.006) was more predictive of outcome than GRACE risk score (p = 0.85) beyond 1 month after PCI. Furthermore, comparison of p-value for interaction of malnutrition and GRACE risk score for all-cause death within 1 month after PCI, beyond 1 month after PCI, and the full follow-up period after PCI were p = 0.62, p = 0.64 and p = 0.38, respectively. CONCLUSIONS: GNRI may have a potential for predicting the mortality in AMI patients especially in beyond 1 month after PCI, separate from GRACE risk score. Assessment of nutritional status may help stratify the risk of AMI mortality.

Prognostic impact of malnutrition on cardiovascular events in coronary artery disease patients with myocardial damage.

BACKGROUND: Stable coronary artery disease (CAD) patients with myocardial damage have a poor prognosis compared to those without myocardial damage. Recently, malnutrition has been reported to affect the prognosis of cardiovascular diseases. However, the effects of malnutrition on prognosis of CAD patients with myocardial damage remains uncertain. We investigated the effects of malnutrition on prognosis of CAD patients with myocardial damage who received percutaneous coronary intervention (PCI). METHODS: Subjects comprised 241 stable CAD patients with myocardial damage due to myocardial ischemia or infraction. Patients underwent successful revascularization for the culprit lesion by PCI using second-generation drug-eluting stents and intravascular ultrasound. The geriatric nutritional risk index (GNRI), which is widely used as a simple method for screening nutritional status using body mass index and serum albumin, was used to assess nutritional status. Associations between major cardiovascular and cerebrovascular events (MACCE) and patient characteristics were assessed. RESULTS: Mean GNRI was 100 ± 13, and there were 55 malnourished patients (23%; GNRI < 92) and 186 non-malnourished patients (77%). MACCE occurred within 3 years after PCI in 42 cases (17%), including 34 deaths (14%), and the malnourished group showed a higher rate of MACCE (38%) compared with the non-malnourished group (11%, p < 0.001). Univariate Cox proportional hazards analyses showed that MACCE was associated with age [hazard ratio (HR), 1.04; 95% confidence interval (CI), 1.04-1.07; p = 0.004], prior heart failure (HR 2.35; 95% CI 1.10-5.01; p = 0.027), high-sensitivity C-reactive protein (HR 1.08; 95% CI 1.03-1.11; p < 0.001), hemodialysis (HR 2.63; 95% CI 1.51-4.58; p < 0.001) and malnutrition (HR 3.69; 95% CI 2.11-6.42; p < 0.001). Multivariate Cox proportional hazards analysis revealed hemodialysis (HR 2.17; 95% CI 1.19-3.93; p = 0.011) and malnutrition (HR 2.30; 95% CI 1.13-4.67; p = 0.020) as significantly associated with MACCE. Furthermore, Cox proportional hazards models using malnutrition and hemodialysis revealed that patients with malnutrition and hemodialysis were at greater risk of MACCE after PCI than patients with neither malnutrition nor hemodialysis (HR 6.91; 95% CI 3.29-14.54; p < 0.001). CONCLUSIONS: In CAD patients with myocardial damage, malnutrition (GNRI < 92) represents an independent risk factor for MACCE. Assessment of nutritional status may help stratify the risk of cardiovascular events and encourage improvements in nutritional status.

Sex-specific relationship between abdominal obesity and new-onset atrial fibrillation in the general Japanese population.

The incidence of atrial fibrillation (AF) is expected to increase with increasing obesity and number of geriatric patients in Japan. Although higher body mass index and abdominal obesity are associated with an increased risk of AF, the sex-specific relationship between abdominal obesity and new-onset AF is unclear. This study aimed to investigate the sex-specific relationship between abdominal obesity and new-onset AF. This retrospective study evaluated the annual health checkup data of 67,379 adults (33,562 males; age, 54 ± 10 years) without baseline AF from April 2008 to March 2016. Participants were grouped according to waist circumference (WC): large-WC group (males, ≥ 85 cm; females, ≥ 90 cm) and normal-WC group. Logistic regression analyses were performed to determine the strength of the association between abdominal obesity and new-onset AF, overall and separately for males and females. During a median follow-up of 5 years, 280 (0.4%) new cases of AF were recorded. Univariate analysis revealed a significant increase in new-onset AF in males (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.49-2.60; p < 0.001) but not in females (OR, 1.69; 95% CI, 0.96-2.97; p = 0.068) in the large-WC group. After adjusting for clinical variables, multivariate analysis revealed that a large WC was significantly associated with new-onset AF in males (OR, 1.76; 95% CI, 1.31-2.36; p < 0.001) but not in females (OR, 1.22; 95% CI, 0.68-2.18; p = 0.514). Abdominal obesity is associated with an increased risk of new-onset AF in men.

Effects of Perioperative Administration of Acetaminophen on Postoperative Shivering: A Randomized, Triple-Blind, Placebo-Controlled Trial.

BACKGROUND: In this randomized, triple-blind, placebo-controlled trial, we tested the hypothesis that perioperative acetaminophen administration has a prophylactic effect on postoperative shivering. METHODS: Forty-five women scheduled for gynecological laparotomy were randomized to either the acetaminophen or the placebo groups. After induction of general anesthesia, the test drug (acetaminophen 15 mg/kg) or placebo (0.9% saline) was intravenously administered over 15 minutes. The primary outcome measure was the incidence of severe postoperative shivering (ie, shivering score >2) in the postanesthesia care unit, where patients stayed for 30 minutes after their emergence from anesthesia. For the secondary outcomes, core body temperature (BT) was recorded at the forehead just before anesthesia induction (time 0 [T0]), at the start of surgery (time 1 [T1]), at the end of surgery (time 2 [T2]), at the initiation of postoperative observation in the postanesthesia care unit (time 3 [T3]), and 30 minutes after T3 (time 4 [T4]). At 1 hour after T4 (ie, time 5 [T5]), the BT was recorded from the axilla (BTA). Primary outcome was analyzed using a χ test. BT recorded at the forehead (BTF) and BTA were analyzed using a 2-way repeated-measures analysis of variance (ANOVA) and a 2-sample t test, respectively. For all comparisons, a P value <.05 was considered statistically significant. RESULTS: The study duration was 2 years. Of the 45 patients initially enrolled, 8 patients were excluded. The acetaminophen and placebo groups included 18 and 19 patients, respectively. The incidence of severe postoperative shivering in the postanesthesia care unit was significantly lower in the acetaminophen group (22.2%) than in the placebo group (73.7%) (relative risk, 0.302; 95% confidence interval, 0.122-0.746; P = .005). Two-way repeated-measures ANOVA showed a significant effect of time (F4,140 = 54.8; P < .001) and a significant time by treatment interaction (F4,140 = 9.61; P < .001) but did not show a main effect of the treatment (F1,35 = 1.83; P = .185) in BTF. Moreover, BTA at T5 was significantly lower in the acetaminophen group (mean [standard deviation {SD}], 37.2°C [0.48°C]) than in the placebo group (37.9°C [0.63°C]; P < .001). CONCLUSIONS: Our findings in patients undergoing gynecological laparotomy suggest that perioperative acetaminophen administration can prevent postoperative severe shivering. This prophylactic effect might be due to suppressing the postoperative increase in the BT set point, rather than lowering the threshold for shivering, as observed with clonidine.

Reintroducing testosterone in the db/db mouse partially restores normal glucose metabolism and insulin resistance in a leptin-independent manner.

BACKGROUND: Testosterone signals through the androgen receptor (AR) and AR knockout mice develop obesity, suggesting a functional association between AR and leptin signaling. Furthermore, physiological blood concentrations of testosterone have been found to inhibit the development of arteriosclerosis, obesity and diabetes. However, these findings have not been verified by testosterone replacement in animal models and whether or not testosterone acts directly by activating AR to enhance leptin signaling, or indirectly by its conversion into estrogen remains unclear. Therefore, we investigated the effect of exogenously supplemented testosterone on glucose and lipid metabolism. METHODS: Four-week-old male leptin receptor-knockout db/db mice were used as controls for a model of obesity retaining low testosterone. Mice were divided into sham-operated, castrated, or castrated and testosterone-supplemented groups and fed a high-fat diet (HFD) for 2 weeks from 5 weeks of age. Testosterone concentrations, blood glucose, plasma insulin levels, and intraperitoneal glucose tolerance and insulin tolerance were measured. At 7 weeks, triglyceride and glycogen content were measured in the liver and muscle. Lipid accumulation in the liver and soleus muscle was determined by immunohistochemistry with Oil Red O. Statistical analyses were performed using the Student's t-test or ANOVA where applicable. RESULTS: Lower testosterone levels in db/db mice compared with wild type (WT) db/+ mice were associated with glucose intolerance and fatty liver. Furthermore, castrated male db/db mice at 4 weeks of age progressively developed glucose intolerance accompanying a 15% increase in liver fat. Male mice fed a HFD had lower levels of testosterone compared with those fed a normal diet. We found that exogenous testosterone replacement injected subcutaneously into castrated male db/db mice alleviated the exacerbation of fatty liver and glucose intolerance, suggesting a leptin-independent mechanism. This mechanism is most likely mediated through gonadal axis suppression in this mouse model. CONCLUSIONS: In summary, testosterone may use a novel pathway to complement leptin signaling to regulate glucose and lipid metabolism, and thus offers a new therapeutic target to treat metabolic disorders.

Association Between Waist-to-Height Ratio and Endothelial Dysfunction in Patients With Morbidity　- A Report From the FMD-J Study.

BACKGROUND: Waist circumference (WC), waist-to-height ratio (WHtR) and body mass index (BMI) are known as easy anthropometric markers of abnormal obesity and screening tools for predicting cardiovascular outcomes, but which indices are best is unclear. We therefore investigated the superiority and association between each index and low flow-mediated dilatation (FMD) as a surrogate marker for cardiovascular outcomes in patients with morbidity in a large Japanese prospective cohort.Methods and Results:A total of 1,645 Japanese patients who had coronary artery disease and hypertension or diabetes mellitus were enrolled, and 1,087 of them were analyzed. The high-WHtR group (≥0.5) showed greater morbidity and increased inflammation in association with atherosclerosis compared with the low-WHtR group. High WHtR and advanced age were identified as predictors of low FMD (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.02-1.88, P=0.037 and OR 1.55, 95% CI 1.19-2.01, P=0.001, respectively). However, WC was not associated with that risk in either sex (male: OR 1.37, 95% CI 0.97-1.93, P=0.076; female: OR 1.08, 95% CI 0.68-1.73, P=0.74), and no association was evident between high BMI and low FMD (OR 0.92, 95% CI 0.71-1.19, P=0.54). CONCLUSIONS: WHtR offers a superior predictor of decreased FMD than other anthropometric indices, and progression of arteriosclerosis might be detected more sensitively. Further study is needed to investigate the relationship between cardiovascular mortality and WHtR.