Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: A multi-institutional retrospective study

BackgroundThe aim of this study was to investigate the clinical value of nutritional and immunological prognostic scores as predictors of outcomes and to identify the most promising scoring system for patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-institutional study.MethodsData were retrospectively collected for 589 patients who underwent surgical resection for PDAC. Prognostic analyses were performed for overall (OS) and recurrence-free survival (RFS) using tumor and patient-related factors, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), modified GPS, C-reactive protein-to-albumin ratio, Controlling Nutritional Status score, and the Geriatric Nutritional Risk Index.ResultsCompared with PDAC patients with high PNI values (≥46), low PNI (<46) patients showed significantly worse overall survival (OS) (multivariate hazard ratio (HR), 1.432; 95% CI, 1.069–1.918; p = 0.0161) and RFS (multivariate HR, 1.339; 95% CI, 1.032–1.736; p = 0.0277). High carbohydrate antigen 19–9 (CA19-9) values (≥450) were significantly correlated with shorter OS (multivariate HR, 1.520; 95% CI, 1.261–2.080; p = 0.0002) and RFS (multivariate HR, 1.533; 95% CI, 1.199–1.961; p = 0.0007). Stratification according to PNI and CA19-9 was also significantly associated with OS and RFS (log rank, P < 0.0001).ConclusionsOur large cohort study showed that PNI and CA19-9 were associated with poor clinical outcomes in PDAC patients following surgical resection. Additionally, combining PNI with CA19-9 enabled further classification of patients according to their clinical outcomes.     

Impacts of frailty on health care costs among community-dwelling older adults: A meta-analysis of cohort studies

BackgroundThe demands for health care services from the frail elderly individuals in the community continue to increase, which will exert a tremendous burden on health care costs. However, little is known regarding the magnitude of these impacts. In this study, we performed a systematic review and meta-analysis of the evidence to explore the impact of frailty on health care costs among community-dwelling older adults.Materials and methodsRelevant published articles were searched from PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Full-text Database (VIP), Wanfang Database, Chinese Biomedical Literature Database (CBM), and the reference lists of articles. Publishedcohort or cross-sectional studies assessing the impacts of frailty on health care costs among community-dwelling older adults were identified (to June 2020). The outcomes on health care costs before and after baseline were stratified by frailty status.ResultsA total of 7 cohort studies comprised of a total of 3,750,611 participants were included in our study. Our analyses showed that: (1) compared with the robust group, health care costs increased by $79–13,423.83 (standardized mean difference, SMD = 0.22, 95% Confidence interval, 95% CI, 0.22–0.22; P < 0.00001) in the pre-frail elderly and by $616–32,549.96 (SMD = 0.55, 95% CI, 0.44–0.67; P < 0.00001) in the frail elderly in the community. A significantly higher in the increase of health care costs was observed in the frail group compared with the pre-frail group(SMD = 0.35, 95% CI, 0.19–0.51; P < 0.0001); (2) the frailty phenotype components increased the health care costs of the elderly in community (weight loss: $1,630–6,209, SMD = 0.43, 95% CI, 0.17–0.69; P = 0.001; weakness: $275–7,586, SMD = 0.24, 95% CI, 0.08–0.40; P = 0.001; exhaustion: $1,545–10,559, SMD = 0.31, 95% CI, 0.13–0.49; P = 0.0006; slowness: $352–1,1891, SMD = 0.40, 95% CI = 0.14–0.65; P = 0.003; low physical activity: $512–3,459, SMD = 0.26, 95% CI, 0.16–0.36; P < 0.00001); (3) the increase in the frailty index was parallel with the increase in health care costs by $12,363–21,066 (SMD = 0.41, 95% CI, 0.29–0.53; P < 0.00001).Conclusions and ImplicationsThis study revealed the adverse economic impacts of frailty status, frailty phenotype components, and frailty index on health care costs in community-dwelling older adults. Future research is warranted to investigate costs incurred by interventions to improve frailty, which will provide further insights into additional health care costs due to frailty.     

Long-term effects of non-retrieved inferior vena cava filters on recurrences of venous thromboembolism in cancer and non-cancer patients: From the COMMAND VTE registry

BackgroundThere is a paucity of data comparing the long-term outcomes after inferior vena cava (IVC) filters placement for patients with acute venous thromboembolism (VTE) between those with and without active cancer.MethodsIn the COMMAND VTE Registry, we evaluated the effects of IVC filter use on the long-term clinical outcomes stratified by the presence and absence of active cancer.ResultsAmong 2,626 patients with acute symptomatic VTE, there were 604 patients with active cancer, and 2022 patients without active cancer. IVC filters were placed and not retrieved in 455 patients (17%) in the entire cohort, in 150 patients (24.8%) in the active cancer stratum, and in 305 patients (15.1%) in the non-cancer stratum. In the entire cohort, non-retrieved IVC filter placement was not associated with a lower adjusted risk for PE recurrence (HR 0.59, 95% CI 0.30–1.15, P = 0.122), but with an increased adjusted risk for DVT recurrence (HR 2.27, 95% CI 1.43–3.60, P<0.001). In the non-cancer stratum, the non-retrieved IVC filter placement was associated with a decreased risk for PE (HR 0.29, 95% CI 0.09–0.93, P = 0.037), but not with an increased risk for DVT (HR 1.73, 95% CI 0.89–3.38, P = 0.108), while in the active cancer stratum, it was associated with an increased risk for DVT (HR 2.47, 95% CI 1.24–4.91, P = 0.010), but not with a decreased risk for PE (HR 0.82, 95% CI 0.34-–1.96, P = 0.650).ConclusionsThere were some differences in the risk-benefit balance between VTE patients with and without active cancer.     

Sirolimus improves the prognosis of liver recipients with hepatocellular carcinoma: A single-center experience

BackgroundTumor recurrence after liver transplantation (LT) for selective patients diagnosed with hepatocellular carcinoma (HCC) in the setting of cirrhosis is the greatest challenge effecting the prognosis of these patients. The aim of this study was to evaluate the efficacy of sirolimus on the prognosis for these recipients.MethodsThe data from 193 consecutive HCC patients who had undergone LT from January 2015 to December 2019 were retrospectively analyzed. These patients were divided into the sirolimus group [patients took sirolimus combined with calcineurin inhibitors (CNIs) (n = 125)] and non-sirolimus group [patients took CNI-based therapy without sirolimus (n = 68)]. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups. The prognostic factors and independent risk factors for RFS and OS were further evaluated.ResultsNon-sirolimus was an independent risk factor for RFS (HR = 2.990; 95% CI: 1.050-8.470; P = 0.040) and OS (HR = 3.100; 95% CI: 1.190-8.000; P = 0.020). A higher proportion of patients beyond Hangzhou criteria was divided into the sirolimus group (69.6% vs. 80.9%, P = 0.030). Compared with the non-sirolimus group, the sirolimus group had significantly better RFS (P < 0.001) and OS (P < 0.001). Further subgroup analysis showed similar results.ConclusionsThis study demonstrated that sirolimus significantly decreased HCC recurrence and prolonged RFS and OS in LT patients with different stage of HCC.     

Prior statin use and the incidence of in-hospital arrhythmia in acute coronary syndrome: A systematic review and meta-analysis

BackgroundThe benefit of prior statin use to reduce the incidence of arrhythmia in acute coronary syndrome (ACS) is still a matter of debate. Statins have multiple pleiotropic effects, which may reduce the incidence of in-hospital arrhythmia. A systematic review and meta-analysis were performed to evaluate prior statin use and the incidence of in-hospital arrhythmia in ACS.MethodsThis systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We performed a literature search through Pubmed, Proquest, EBSCOhost, and Clinicaltrial.gov. A random-effect model was used due to moderate heterogeneity. Quality assessment was performed using Newcastle Ottawa Scale. Sensitivity analysis was performed by using leave one or two out method. PROSPERO registration number: CRD42022336402.ResultsNine eligible studies consisting of 86,795 patients were included. A total of 22,130 (25.5%) patients were in statin use before the index ACS event. The prevalence of old myocardial infarction, heart failure, hypertension, diabetes mellitus, and chronic renal failure and concomitant treatment with aspirin, clopidogrel, and beta blocker was higher in the prior statin group compared to no previous statin. Overall, prior statin use was associated with a significantly lower incidence of in-hospital arrhythmia during ACS compared to no previous statin (OR 0.60; 95% CI 0.49–0.72; P < 0.00001; I² = 54%, P-heterogeneity = 0.03). In subgroup analysis, previous statin use reduced the incidence of atrial fibrillation or atrial flutter (OR 0.64; 95% CI 0.43–0.95; P = 0.03; I² = 73%, P-heterogeneity = 0.01) and ventricular tachycardia or ventricular fibrillation (OR 0.57; 95% CI 0.49–0.65; P < 0.00001; I² = 8%, P-heterogeneity = 0.35).ConclusionsBased on aggregate patient data, prior statin use may reduce the incidence of in-hospital arrhythmia during ACS, particularly atrial fibrillation or atrial flutter and ventricular tachycardia or ventricular fibrillation.     

Inotrope Use and Outcomes Among Patients Hospitalized for Heart Failure: Impact of Systolic Blood Pressure,Cardiac Index,and Etiology

BackgroundInotropes are widely used in hospitalized systolic heart failure (HF) patients, especially those with low systolic blood pressure (SBP) or cardiac index. In addition, inotropes are considered to be harmful in nonischemic HF.Methods and ResultsWe examined the association of in-hospital inotrope use with (1) major events (death, ventricular assist device, or heart transplant) and (2) study days alive and out of hospital during the first 6 months in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness, which excluded patients with immediate need for inotropic therapy. Predefined subgroups of interest were baseline SBP <100 versus ≥100 mm Hg, cardiac index <1.8 vs ≥1.8 L min⁻¹ m⁻², and ischemic versus nonischemic HF etiology. Inotropes were frequently used in both the <100 mm Hg (88/165 [53.3%]) and the ≥100 mm Hg (106/262 [40.5%]) SBP subgroups and were associated with higher risk for major events in both subgroups (adjusted hazard ratio [HR] 2.85, 95% confidence interval [CI] 1.59–5.12 [P < .001]; and HR 1.86, 95% CI 1.02–3.37 [P = .042]; respectively). Risk with inotropes was more pronounced among those with cardiac index ≥1.8 L min⁻¹ m⁻² (n = 114; HR 4.65, 95% CI 1.98–10.9; P < .001) vs <1.8 L min⁻¹ m⁻² (n = 82; HR 1.48, 95% CI 0.61–3.58; P = .39). Event rates were higher with inotropes in both ischemic (n = 215; HR 2.64, 95% CI 1.49–4.68; P = .001) and nonischemic (n = 216; HR 2.19, 95% CI 1.18–4.07; P = .012) patients. Across all subgroups, patients who received inotropes spent fewer study days alive and out of hospital.ConclusionsIn the absence of cardiogenic shock or end-organ hypoperfusion, inotrope use during hospitalization for HF was associated with unfavorable 6-month outcomes, regardless of admission SBP, cardiac index, or HF etiology.     

Flow-Mediated Dilation Normalization Predicts Outcome in Chronic Heart Failure Patients

BackgroundReduced flow-mediated dilation (FMD) is a known prognostic marker in heart failure (HF), but may be influenced by the brachial artery (BA) diameter. Aiming to adjust for this influence, we normalized FMD (nFMD) by the peak shear rate (PSR) and tested its prognostic power in HF patients.Methods and ResultsBA diameter, FMD, difference in hyperemic versus rest brachial flow velocity (FVD), PSR (FVD/BA), and nFMD (FMD/PSR × 1000) were assessed in 71 HF patients. At follow-up (mean 512 days), 19 HF (27%) reached the combined endpoint (4 heart transplantations [HTs], 1 left ventricle assist device implantation [LVAD], and 14 cardiac deaths [CDs]). With multivariate Cox regression analysis, New York Heart Association functional class ≥III (hazard ratio [HR] 9.36, 95% confidence interval [CI] 2.11–41.4; P = .003), digoxin use (HR 6.36, 95% CI 2.18–18.6; P = .0010), FMD (HR 0.703, 95% CI 0.547–0.904; P = .006), PSR (HR 1.01, 95% CI 1.005–1.022; P = .001), FVD (HR 1.04, 95% CI 1.00–1.06; P = .02), and nFMD (HR 0.535, 95% CI 0.39–0.74; P = .0001) were predictors of unfavorable outcome. Receiver operating characteristic curve for nFMD showed that patients with nFMD >5 seconds had significantly better event-free survival than patients with nFMD ≤5 seconds (log-rank test: P < .0001).ConclusionsnFMD is a strong independent predictor of CD, HT, and LVAD in HF with left ventricular ejection fraction <40%. Patients with nFMD >5 seconds have a better prognosis than those with lower values.     

Right ventricular systolic pressure – Non-invasive bedside predictor of mortality and readmission in heart failure with reduced and preserved ejection fraction hospitalization

ObjectiveTo study the prognostic role of right ventricular systolic pressure (RVSP) in patients with heart failure (HF).BackgroundAlthough RVSP is a readily available echocardiographic parameter, it is often underused. Its prognostic role in patients with heart failure is not well established compared with pulmonary artery pressure measured by right heart catheterization.MethodsThis single-center retrospective cohort study included patients with acute heart failure hospitalization admitted to the hospital from January 2005 to December 2018. The primary predictor was right ventricular systolic pressure (RVSP) obtained from bedside transthoracic echocardiography at admission. We divided RVSP into two groups, RVSP <40 mm Hg (reference group) and RVSP ≥40 mm Hg. Primary outcome was all-cause mortality. Secondary outcomes were all-cause readmission and cardiac readmission. We conducted propensity-score matching and applied cox-proportional hazard model to compute hazard ratio (HR) with 95% confidence interval (CI).ResultsOut of 972 HF patients, 534 patients had RVSP <40 mm Hg and 438 patients had RVSP ≥40 mm Hg. Patients with RVSP ≥40 mm Hg compared with RVSP <40 mm Hg were associated with higher rates of death [HR: 1.60, 95% CI: 1.22–2.09, P-value = 0.001], all-cause readmissions [HR: 1.37, 95% CI: 1.09–1.73, P-value = 0.008] and cardiac readmissions [HR: 1.41, 95% CI: 1.07–1.85, P-value = 0.014].ConclusionHigher RVSP (≥40 mm Hg) in HF patients was associated with higher rates of death, all-cause readmissions, and cardiac readmissions. RVSP can be considered as a prognostic marker for mortality and readmission.     

Effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood: A systematic review and meta-analysis

ObjectiveThe risk of metabolic disease in adulthood is not only attributed to an unhealthy lifestyle after birth but also to famine exposure during the foetal period. This systematic review and meta-analysis aimed to evaluate the effects of foetal exposure to famine as a risk factor for developing nonalcoholic fatty liver disease (NAFLD) in adulthood.MethodsStudies were retrieved from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to evaluate the effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood.ResultsSix studies involving 90,582 subjects were included in this meta-analysis. Foetal exposure to famine was associated with an increased risk of NAFLD(RR = 1.17, 95% CI: 1.08–1.27, P < 0.0001). Exposure to famine during the foetal period significantly increased the incidence of NAFLD in women (RR = 1.27, 95% CI: 1.16–1.40, P <0.00001), while similar results were not observed in the male subgroup (RR =0.99, 95% CI: 0.89–1.11, P = 0.88). Foetal exposure to famine was associated with the risk of mild NAFLD (RR = 1.17, 95% CI: 1.02–1.33, P = 0.02) and moderate to severe NAFLD (RR = 1.51, 95% CI: 1.16–1.98, P = 0.002).ConclusionsFoetal exposure to famine is associated with an increased risk of NAFLD in adulthood. Women with NAFLD and moderate to severe NAFLD have a more robust association with foetal exposure to famine.     

Intraoperative autologous transfusion and oncologic outcomes in liver transplantation for hepatocellular carcinoma: a propensity matched analysis

BackgroundIntraoperative autologous transfusion (IAT) of salvaged blood is a common method of resuscitation during liver transplantation (LT), however concern for recurrence in recipients with hepatocellular carcinoma (HCC) has limited widespread adoption.MethodsA review of patients undergoing LT for HCC between 2008 and 2018 was performed. Clinicopathologic and intraoperative characteristics associated with inferior recurrence-free (RFS) and overall survival (OS) were identified using Kaplan–Meier analysis and uni-/multi-variable Cox proportional hazards modeling. Propensity matching was utilized to derive clinicopathologically similar groups for subgroup analysis.ResultsOne-hundred-eighty-six patients were identified with a median follow up of 65 months. Transplant recipients receiving IAT (n = 131, 70%) also had higher allogenic transfusions (median 5 versus 0 units, P < 0.001). There were 14 recurrences and 46 deaths, yielding an estimated 10-year RFS and OS of 89% and 67%, respectively. IAT was not associated with RFS (HR 0.89/liter, P = 0.60), or OS (HR 0.98/liter, P = 0.83) pre-matching, or with RFS (HR 0.97/liter, P = 0.92) or OS (HR 1.04/liter, P = 0.77) in the matched cohort (n = 49 per group).ConclusionIAT during LT for HCC is not associated with adverse oncologic outcomes. Use of IAT should be encouraged to minimize the volume of allogenic transfusion in patients undergoing LT for HCC.     

Safety and efficacy of anticoagulant monotherapy in atrial fibrillation and stable coronary artery disease: A systematic review and meta-analysis

BackgroundAdjunctive use of oral anticoagulant (OAC) and antiplatelet therapy (APT) in patients with stable coronary artery disease (CAD) and nonvalvular atrial fibrillation (AF) is a challenge of daily practice.MethodsA comprehensive literature search of databases was performed to identify studies comparing the safety and efficacy of OAC monotherapy and combined therapy (OAC plus single (S) APT). Events including major adverse cardiovascular events (MACE), all-cause mortality, stroke and major bleeding were analyzed.ResultsSeven articles comprising 11,070 subjects were identified. Combined therapy was associated with a significantly higher risk of major bleeding (pooled hazard ratio (HR) of 1.62, 95% CI 1.40–1.86, p=<0.0001) compared to the OAC monotherapy. There was no significant difference between the two comparison arms in terms of MACE (HR 1.14; 95% CI 0.97–1.34, p = 0.11), stroke (HR 1.05; 95% CI 0.77–1.43, p = 0.78) and all-cause mortality (HR 1.15; 95% CI 0.94–1.40, p = 0.16). Stratified analysis by inclusion of only patients with coronary stents attenuated the safety effect of monotherapy. Subgroup analysis based on the study design, type of OAC, major bleeding criteria and APT revealed findings consistent with the pooled HR. The combined therapy group had a 19% and 38% higher risk of MACE in studies with a history of MI (p = 0.03) and with the use of rivaroxaban (p = 0.02), respectively.ConclusionOAC monotherapy might have a lower incidence of major bleeding events with no higher overall risk of MACE, ischemic stroke and all-cause mortality compared to the combined therapy group.     

Prognostic impact of tumor vascularity on CT in resectable intrahepatic cholangiocarcinoma

BackgroundWe investigated the vascularity of intrahepatic cholangiocarcinoma (ICC) on computed tomography (CT) images and its association with ICC recurrence after surgery and prognosis after recurrence.MethodsIn this retrospective study, the data of patients who underwent resection with curative intent for ICC between March 2001 and July 2017 were reviewed. Clinicopathologic factors including tumor vascularity (hypovascular, rim-enhancement, and hypervascular) on CT that could affect recurrence-free survival (RFS) were assessed. The association between the vascularity of recurrent ICC and survival after recurrence was also analyzed.ResultsOverall, 147 patients were enrolled and followed up for a median of 36.1 months of which, 101 (68.7%) experienced ICC recurrence. Hypervascularity of ICC showed better RFS than other vascularities [rim-enhanced image hazard ratio (HR), 3.893; 95% confidence interval (CI), 1.700–8.915, p = 0.001; hypovascular image HR, 6.241; 95% CI, 2.670–14.586, p < 0.001]. The hypervascular recurrent ICC was also significantly associated with better survival after recurrence (log-rank test, p < 0.001).ConclusionHypervascular ICC was associated with a longer RFS and better prognosis after recurrence. The vascularity of ICC on CT may be a noninvasive, accessible, and useful prognostic index, and should be considered while planning treatment.     

Tailored adjuvant gemcitabine versus 5-fluorouracil/folinic acid based on hENT1 immunohistochemical staining in resected pancreatic ductal adenocarcinoma: A biomarker stratified prospective trial

BackgroundThe study aimed to evaluate the clinical outcomes of tailored adjuvant chemotherapy according to human equilibrative nucleoside transporter 1 (hENT1) expression in resected pancreatic ductal adenocarcinoma (PDA).MethodsPatients who underwent pancreatectomy for PDA were enrolled prospectively. According to intra-tumoral hENT1 expression, the high hENT1 (≥50%) group received gemcitabine and the low hENT1 (<50%) group received 5-fluorouracil plus folinic acid (5-FU/FA). The propensity score-matched control consisted of patients who received hENT1-independent adjuvant chemotherapy. The primary outcome was recurrence free survival (RFS) and the secondary outcomes were overall survival (OS) and toxicities.ResultsBetween May 2015 and June 2017, we enrolled 44 patients with resected PDA. During a median follow-up period of 28.5 months, the intention-to-treat population showed much longer median RFS [22.9 (95% CI, 11.3–34.5) vs. 10.9 (95% CI, 6.9–14.9) months, P = 0.043] and median OS [36.2 (95% CI, 26.5–45.9) vs. 22.1 (95% CI, 17.7–26.6) months, P = 0.001] compared to the controls. Among 5 patients in the low hENT1 group who discontinued treatment, 2 patients receiving 5-FU/FA discontinued treatment due to drug toxicities (febrile neutropenia and toxic epidermal necrolysis).ConclusionTailored adjuvant chemotherapy based on hENT1 staining provides excellent clinical outcomes among patients with resected PDA.Clinical trial registrationclinicaltrials.gov identifier: NCT02486497.     

Polychemotherapy or gemcitabine in advanced pancreatic cancer: A meta-analysis

BackgroundGemcitabine monotherapy is the cornerstone of treatment for advanced pancreatic cancer. To date, no clear survival benefit has been found when combination chemotherapy has been compared with gemcitabine alone, except in a few studies. This meta-analysis compared the efficacy of polychemotherapy with gemcitabine alone in advanced pancreatic cancer.MethodsRandomised trials comparing combination chemotherapy with gemcitabine alone were identified through electronic searches of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials. Overall survival, reported as the hazard ratio at the 95% confidence interval, was the primary outcome measure.Results29 trials (19 phase III and 10 small randomised trials) that included 8421 patients were identified. Overall, polychemotherapy significantly improved overall survival (hazard ratio = 0.87; 95% CI, 0.81–0.93; P < 0.0001), progression-free survival (hazard ratio = 0.77; 95% CI, 0.70–0.84; P < 0.00001), and response rate (risk ratio = 1.71; 95% CI, 1.42–2.07; P < 0.00001) compared with gemcitabine alone.ConclusionsCompared with gemcitabine monotherapy, combinations of two or more drugs (particularly those with novel agents or associated with >20% response rates and triplets) improved outcomes and response rate in advanced pancreatic cancer, and they could be considered a new standard of care in advanced settings.     

Association between the visceral adiposity index and risks of all-cause and cause-specific mortalities in a large cohort: Findings from the UK biobank

Background and aimsThe visceral adiposity index (VAI) has been recently established as a measure of visceral fat distribution and is shown to be associated with a wide range of adverse health events. However, the precise associations between the VAI score and all-cause and cause-specific mortalities in the general population remain undetermined.Methods and resultsIn this large-scale prospective epidemiological study, 357,457 participants (aged 38–73 years) were selected from the UK Biobank. We used Cox competing risk regression models to estimate the association between the VAI score and all-cause, cardiovascular disease (CVD), cancer, and other mortalities. The VAI score was significantly correlated with an increased risk of all-cause mortality (hazard ratio [HR], 1.200; 95% confidence interval [CI], 1.148–1.255; P < 0.0001), cancer mortality (HR, 1.224; 95% CI, 1.150–1.303; P < 0.0001), CVD mortality (HR, 1.459; 95% CI, 1.148–1.255; P < 0.0001), and other mortalities (HR, 1.200; 95% CI, 1.148–1.255; P < 0.0001) after adjusting for a series of confounders. In addition, the subgroup analyses showed that HRs were significantly higher in participants who were male, aged below 65 years, and body mass index less than 25.ConclusionIn summary, VAI was positively associated with an increased risk of all-cause and cause-specific mortalities in a nationwide, well-characterised population identified in a UK Biobank. The VAI score might be a complementary traditional predictive indicator for evaluating the risk of adverse health events in the population of Western adults aged 38 years and older.     

Outcomes after curative therapy for hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: a meta-analysis and review of current literature

BackgroundThis systematic review and meta-analysis aimed to compare the outcomes of curative therapy (resection, transplantation, ablation) for hepatocellular carcinoma (HCC) arising from non-alcoholic fatty liver disease (NAFLD) and non-NAFLD etiologies.MethodsA systematic search of PubMed, EMBASE and Cochrane Library was conducted for studies comparing survival, peri- and post-operative outcomes. Quality assessment was performed using the Newcastle–Ottawa scale.ResultsFindings for 5579 patients were pooled across 9 studies and examined. Analysis demonstrated improved disease-free survival (DFS; HR 0.85, 95% CI 0.74–0.98, p = 0.03) and overall survival (OS; HR 0.87; 95% CI 0.81–0.93; p < 0.0001) in NAFLD-HCC patients undergoing liver resection as compared to non-NAFLD HCC patients. NAFLD-HCC patients undergoing all forms of curative therapy were similarly associated with improved OS (HR 0.96; 95% CI 0.86–1.06; p = 0.40) and DFS (HR 0.85; 95% CI 0.74–0.98; p = 0.03), albeit results being significant only for DFS. Only 2 studies reported higher rates of peri- and post-operative complications in patients with NAFLD-HCC. Significant inter-study heterogeneity precluded further analysis.ConclusionNAFLD-HCC patients can enjoy long-term survival benefit with aggressive curative therapy. Peri- and post-operative morbidity should be mitigated with pre-operative optimization of comorbidities, and deliberately close post-operative monitoring.     

A systematic review and meta-analysis of adjuvant transarterial chemoembolization after curative resection for patients with hepatocellular carcinoma

BackgroundThe aim of this study was to systematically evaluate and determine those patients with hepatocellular carcinoma (HCC) that would benefit from the administration of postoperative adjuvant transarterial chemoembolization (PA-TACE).MethodsPubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) and observational studies up to July 30, 2019. The outcome of Overall survival (OS) and disease-free survival (DFS) were extracted and converted to hazard ratios (HRs) with 95% confidence intervals (95%CIs).ResultsA total of 40 studies (10 RCTs and 30 non-RCTs) involving 11,165 patients were included. Overall, PA-TACE was associated with an increased OS [HR, 0.71 (95% CI, 0.65–0.77); P < 0.001] and DFS [HR, 0.73 (95% CI, 0.66–0.80); P < 0.001]. Subgroup analysis in patients with microvascular invasion (MVI), tumor diameter >5 cm or multinodular tumors demonstrated that PA-TACE improved OS and DFS. In patients without MVI, PA-TACE showed no improvement in OS [HR, 1.14 (95% CI, 0.85–1.53); P = 0.370], and resulted in worse DFS than curative resection alone [HR, 1.20 (95% CI, 1.03–1.39); P = 0.002].ConclusionThis meta-analysis indicated that PA-TACE was beneficial in patients with HCC who were at high risk of postoperative recurrence including tumor diameter >5 cm, multinodular tumors and MVI-positive. In patients with tumor diameter ≤5 cm, single tumor or MVI-negative. PA-TACE does not appear to improve outcomes and may potentially promote postoperative recurrence in certain patients.     

A Common NOS1AP Genetic Polymorphism,rs12567209 G>A,Is Associated With Sudden Cardiac Death in Patients With Chronic Heart Failure in the Chinese Han Population

BackgroundVariants in NOS1AP associated with cardiac repolarization and sudden cardiac death (SCD) in coronary artery disease have been reported. Whether they are related to mortality and QTc interval in chronic heart failure (CHF) has not been investigated.Methods and ResultsA total of 1,428 patients with CHF and 480 control subjects were genotyped for 6 SNPs of NOS1AP, and the genetic associations with mortality as well as QTc interval were analyzed. During a median follow-up period of 52 months, 467 patients (32.70%) died, of which deaths 169 (36.19%) were SCD. The A allele of rs12567209 was associated with greater risk of all-cause death and SCD (hazard ratio [HR] 1.381, 95% confidence interval [CI] 1.124–1.698 [P = .002], and HR 1.645, 95% CI 1.184–2.287 [P = .003], respectively). After adjusting for other risk factors, significant differences remained (HR 1.309, 95% CI 1.054–1.624 [P = .015], and HR 1.601, 95% CI 1.129–2.271 [P = .008]). The A allele was also associated with prolongation of QTc interval by 4.04 ms in the entire population (P = .026).ConclusionsThe A allele of rs12567209 in NOS1AP may serve as an independent predictor of all-cause death and SCD in patients with CHF, it is also associated with prolonged QTc interval in the Chinese Han population.     

Sex Differences in the Clinical Outcomes After Left Atrial Appendage Closure: A Systematic Review and Meta-Analysis

IntroductionLeft atrial appendage occlusion (LAAO) has emerged as a reasonable alternative to oral anticoagulation in a selective group of patients with atrial fibrillation (AF). While women are known to have higher risk of AF-related stroke, the impact of sex differences on the clinical outcomes of LAAO has not been well-studied.ObjectiveWe sought to perform a meta-analysis evaluating sex differences on the outcomes of patients undergoing LAAO.MethodsWe searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases (from inception to October 2021) for studies evaluating the impact of sex difference on LAAO procedural outcomes. We used a random-effects model to calculate risk ratio (RR) with 95% confidence intervals (CI). In-hospital all-cause mortality and ischemic stroke were the primary endpoints. In-hospital pericardial effusion/cardiac tamponade, major bleeding, technical success, device-related thrombus, and hospital length of stay were secondary outcomes.ResultsA total of 5 studies with 54,754 patients were included, of whom 22,461 (41%) were females. Female sex was associated with higher rates of in-hospital all-cause mortality (RR 2.18; 95% CI 1.46–3.26; P = 0.0001) and in-hospital ischemic stroke (RR 1.67; 95% CI 1.06–2.61; P = 0.03) when compared with males. Females had higher rates of in-hospital major bleeding (RR 1.93; 95% CI 1.40–2.67; P < 0.0001) and hospital length of stay >1 day (RR 1.38; 95% CI 1.33–1.45; P < 0.00001). There were no differences between females and males in terms of technical success (RR 1.00; 95% CI 1.00–1.00; P = 1.00) and device-related thrombus and (RR 0.94, 95% CI 0.31–2.82; P = 0.91).ConclusionWomen are more likely to experience worse periprocedural outcomes with longer hospital stay after LAA closure. Further efforts are needed to increase the participation of women in clinical studies and to assess these differences to properly address the discrepancy in outcomes between men and women.     

Differential associations between body mass index and outcome in different age groups in patients with myocardial infarction

ObjectiveTo investigate the association between age and body mass index (BMI) and mortality in patients with myocardial infarction (MI). Methods We divided 6453 patients into three age groups (<60, 60–75, >75 years) and five BMI categories. Thirty-day and long-term all-cause mortality were assessed.ResultsNo association was found between the BMI category and 30-day mortality in any age group. The association between BMI and long-term multivariable-adjusted mortality risk was age-dependent. Overweight patients had a lower risk than patients with BMI <25 kg/m² in all age groups (HR 0.62; 95%CI 0.45–0.85; p = 0.003, HR 0.78; 95%CI 0.65–0.93; p = 0.005, HR 0.82; 95%CI 0.70–0.95; p = 0.011 for ages <60, 60–75, >75 years, respectively). The lower risk of death as a function of BMI shifted upward with age, and the risk was also lower in patients with obesity grade I (HR 0.81; 95% CI 0.66–0.98; p = 0.035 and HR 0.78; 95% CI 0.63–0.97; p = 0.023 for ages 60–75, >75 years, respectively). Excessive obesity was harmful only in the oldest group. Patients with obesity grade III had more than a 2.5 times higher mortality risk than patients with BMI <25 kg/m² only in this group (HR 2.58; 95%CI 1.27–5.24; p = 0.009). An obesity paradox was found in all age groups.ConclusionOur results suggest that moderate weight gain with age improves long-term survival after MI and that the magnitude of this “protective” weight gain is greater in older compared to younger patients. However, excessive weight gain (obesity grade III) is particularly harmful in the oldest age group. The exact relationship between BMI, age, and mortality remains unclear.