Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas: A Strobe-Compliant Study

Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973–2011), and Linköping Cancer (LC, 1972–2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; LC, P = 0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057–1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493–10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CI, 0.106–1.192; P = 0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.     

Comparison of Modified Blumgart pancreaticojejunostomy and pancreaticogastrostomy after pancreaticoduodenectomy

Background

The aim of this study was to compare perioperative outcomes after Blumgart pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG) for pancreatic-enteric reconstruction following pancreaticoduodenectomy.

Methods

Data of patients undergoing Blumgart PJ and PG were retrieved from prospectively-collected database. Matched patients in each surgical groups were included based on the Callery risk scoring system for clinically relevant postoperative pancreatic fistula (CR-POPF) (grades B and C). Surgical parameters and risks were compared between these two groups.

Results

A total of 206 patients undergoing PD were included. Blumgart PJ was associated with shorter postoperative hospital stay (median (range) 25 (10–99) vs. 27 (10–97) days, P = 0.022). There was no surgical mortality in the Blumgart PJ group, but a 4.9% perioperative mortality in the PG, P = 0.030. The CR-POPF by Blumgrt PG is significantly lower than that by PG for overall patients (7% vs. 20%, P = 0.007), especially for those in intermediate fistula risk zone (6% vs. 21%, P = 0.048) and high fistula risk zone (14% vs. 47%, P = 0.038).

Conclusions

Blumgart PJ is superior to PG in terms of pancreatic leakage and surgical mortality. Blumgart PJ can be recommended for pancreatic reconstruction after PD for all pancreatic remnant subtypes.     

Prognostic relevance of Wilms tumor 1 (WT1) gene Exon 7 mutations in-patient with cytogenetically normal acute myeloid leukemia

This study aimed to assess the prognostic influences of Wilms tumor 1 (WT1) gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML) among Egyptian patients. Exon 7 of WT1 was screened for mutations in samples from 82 CN-AML patients out of 203 newly diagnosed AML patients, using a high-resolution capillary electrophoresis. Seven out of 82 AML patients (8.3 %) harbored WT1 mutations. There was no significant difference between the mutant WT1 and wild type AML patients as regard age, sex, French–American–British subtypes and the prevalence of success of induction remission therapy (P < 0.5). AML patients with mutant WT1 had shorter overall survival as compared to those patients with wild WT1 (HR = 1.38; 95 % CI 4.79–6.86; P = 0.004). In conclusion, CN-AML patients with WT1 gene mutation have poor clinical outcome. We recommend testing the WT1 mutations as part of molecularly based risk assessment and risk-adapted treatment stratification of patients with CN-AML.     

Prediction of loss of correction after hemiepiphysiodesis for the alignment of lower limb angular deformities

Guided growth by temporary hemiepiphysiodesis (HEPD) is established for the alignment of lower limb angular deformities. This retrospective cohort study was designed to assess the effect of HEPD in idiopathic coronal plane deformities around the knee and on the frontal knee joint line orientation, and to test the frontal knee joint line as predictive means for recurrence.Fourty-four patients (78 deformities: valgus n = 64, varus n = 14) were enrolled in the retrospective observational study. Mechanical axis deviation, mechanical lateral distal femoral angle, and mechanical medial proximal tibial angle were assessed prior to surgery and during follow-up. The facultative frontal knee joint line angle (FKJLA) was used as predictive tool. Cases of remaining growth potential (n = 45/78) after implant removal were followed to assess rebound deformity.Pre-operative angles of the mechanical axis were corrected average 9.0 months after HEPD. Pre-operative assessment of the frontal knee joint line revealed a mean of 3.9° in valgus, and –1.0° in varus deformities. At time of complete deformity correction, mean FKJLA was –0.2° in valgus, and –0.8° in varus deformities. Mean shift of FKJLA was significantly higher after singleHEPD compared to combiHEPD (P < .001). Patients having an unphysiological FKJLA (>/<0°–3°) after correction of mechanical axis had a significantly higher risk of rebound deformity (P = .01). Regression analysis showed a 60.5% higher risk of rebound deformity per each degree deviating from the FKJLA physiological range. Age, gender, or body mass index had no impact.Temporary HEPD offers great potential for the correction of the mechanical axis and the frontal knee joint line. An unphysiological change of the frontal knee joint line is associated with a high risk of recurrent angular deformities. CombiHEPD instead of singleHEPD seems to be safer to prevent detrimental frontal knee joint line shift.Level of Evidence: Retrospective comparative therapeutic study, Level III.     

Percutaneous coronary intervention in insulin‐treated diabetic patients: A meta‐analysis

BackgroundThis meta‐analysis of randomized controlled trials (RCTs) compared long‐term adverse clinical outcomes of percutaneous coronary intervention (PCI) in insulin‐treated diabetes mellitus (ITDM) and non‐ITDM patients.MethodsThis is a meta‐analysis study. The PubMed and Embase databases were searched for articles on long‐term adverse clinical outcomes of PCI in ITDM and non‐ITDM patients. The risk ratios (RR) and 95% confidence intervals (CI) were calculated.ResultsA total of 11 related RCTs involving 8853 DM patients were included. Compared with non‐ITDM patients, ITDM patients had significantly higher all‐cause mortality (ACM) (RR = 1.52, 95% CI: 1.25–1.85, p _{heterogeneity} = .689, I ² = 0%), major adverse cardiac and cerebrovascular events (MACCE) (RR = 1.35, 95% CI: 1.18–1.55, p _{heterogeneity} = .57, I ² = 0%), myocardial infarction (MI) (RR = 1.41, 95% CI: 1.16–1.72, p _{heterogeneity} = .962, I ² = 0%), and stent thrombosis (ST) (RR = 1.75, 95% CI: 1.23–2.48, p _{heterogeneity} = .159, I ² = 32.4%). No significant difference was found in the target lesion revascularization (TLR) and target vessel revascularization (TVR) between the ITDM and non‐ITDM groups.ConclusionsThe results showed that ITDM patients had significantly higher ACM, MACCE, MI, and ST, compared with non‐ITDM patients.     

Comparison of the efficiency between electrocardiogram and echocardiogram for left ventricular hypertrophy evaluation in patients with hypertension: Insight from the Korean Hypertension Cohort Study

In patients with hypertension, left ventricular hypertrophy (LVH) represents a risk factor for cardiovascular disease and asymptomatic organ damage. Currently, electrocardiography (ECG) and two‐dimensional echocardiography (Echo) are the most widely used methods for LVH evaluation. This study aimed to compare the long‐term outcomes of LVH, as evaluated by ECG and Echo, in patients with hypertension. Patients diagnosed with hypertension as a primary disease between 2006 and 2011 were enrolled in the Korean Hypertension Cohort study. The study finally included 1743 patients who underwent both ECG and Echo. The primary endpoint was defined as the composite of major adverse cardiovascular events (MACEs) or death. Overall, LVH was identified in 747 patients. The patients were categorized into four groups according to the detection of LVH by ECG or Echo: No LVH (n = 996), LVH diagnosed by ECG alone (n = 181), LVH diagnosed by Echo alone (n = 415), LVH diagnosed by both ECG and Echo (n = 151). After adjusting for variables, the incidence of MACEs or death was significantly greater in patients with LVH diagnosed by ECG alone (hazards ratio [HR]: 1.69; 95% confidence interval [CI]: 1.22–2.35; P = .001), LVH diagnosed by Echo alone (HR: 1.54; 95% CI: 1.16–2.05; P = .002), and LVH diagnosed by both ECG and Echo (HR: 1.87; 95% CI: 1.18–2.94; P = .002) than in those with no LVH. Both ECG and Echo are efficient diagnostic tools for LVH and useful for long‐term risk stratification. Additional Echo evaluation for LVH is helpful for predicting long‐term outcomes only in patients without LVH diagnosis by ECG.     

The Prognostic Relevance of BAALC and ERG Expression Levels in Cytogenetically Normal Pediatric Acute Myeloid Leukemia

Cytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). About 45 % of de novo adult AML and 20 % of pediatric AML lack cytogenetic abnormalities, so identification of predictive molecular markers might improve therapy. Mutation status of FLT3, NPM1 genes and gene expression levels of ERG, BAALC have been postulated as possible prognostic markers in pediatric AML with normal karyotype. Pretreatment blood samples from 47 cytogenetically normal AML patients were analysed for BAALC and ERG expression using real time RT-PCR. The patients were dichotomized at BAALC and ERG mean expression into low and high expression based on the median expression as cutoff. BAALC showed high expression in (24/47; 51.1 %) of patients and ERG high expression was detected in (22/47; 46.6 %). With follow-up for 1 year, patients with high BAALC and high ERG had inferior EFS (P = 0.001, P = 0.017 respectively), overall survival (P = 0.001, 0.08 respectively), and low rates of induction remission (P = 0.001, P = 0.0017 respectively) as compared to those with low expression. Also there was significant positive association between high expression of BAALC; ERG and FLT-ITD mutations (P = 0.016; P = 0.007 respectively). Multivariable analysis confirmed that high BAALC expression is an independent risk factor for EFS [HR for EFS 1.9(1.04–3.46) P = 0.037]; and OS [HR OS 1.55(1.7–3.36) P = 0.03]. In conclusion: Over expression of BAALC could predict adverse clinical outcome and may define important risk factor in cytogenetically normal pediatric AML.     

Outcomes of Dissection Angles as Predictor of Restenosis after Drug-Coated Balloon Treatment

Aim: The predictors of restenosis after endovascular therapy (EVT) with paclitaxel drug-coated balloons (DCBs) have not been clearly established. The present study aimed to investigate the association of post-procedural dissection, as evaluated using intravascular ultrasound (IVUS), with the risk of restenosis following femoropopliteal EVT with paclitaxel DCBs. Methods: In the present single-center retrospective study, 60 de novo femoropopliteal lesions (44 patients) that underwent EVT with DCBs, without bail-out stenting, were enrolled. The primary outcome was 1-year primary patency. Risk factors for restenosis were evaluated using a Cox proportional hazards regression model and random survival forest analysis. Results: The 1-year primary patency rate was 57.2% [95% confidence interval, 45%–72%]. IVUS-evaluated post-procedural dissection was significantly associated with the risk of restenosis ( P =0.002), with the best cutoff point of 64º [range, 39º–83º]. The random survival forest analysis showed that the variable importance measure of IVUS-evaluated dissection was significantly lower than that of the reference vessel diameter ( P ＜0.001), not different from that of the lesion length ( P =0.41), and significantly higher than that of any other clinical feature (all P ＜0.05). Conclusion: IVUS-evaluated post-procedural dissection was associated with 1-year restenosis following femoropopliteal EVT with DCB.     

Efficacy and safety of early initiation of Sacubitril/Valsartan in patients after acute myocardial infarction: A meta‐analysis

Some randomized controlled trials have compared the effectiveness and safety outcomes between early initiation of Sacubitril/Valsartan and angiotensin‐converting enzyme inhibitors (ACEIs) in patients after acute myocardial infarction. Therefore, our current meta‐analysis aimed to clarify the confusion. Four Databases and relevant grey literature were searched for studies from inception to July 2, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias. Four studies involving 6154 patients were included to perform meta‐analysis. The results of meta‐analysis showed that the left ventricular ejection fraction in the Sacubitril/Valsartan group was higher than the ACEI group (SMD: 0.37, 95% CI: 0.19–0.55, P = .000), the incidence of major adverse cardiac events in the Sacubitril/Valsartan group was lower than the ACEI group (RR: 0.61, 95% CI: 0.46–0.82, P = .001), while the incidences of cardiac death (RR: 1.00, 95% CI: 0.81–1.24, P = 1.000) and the heart failure hospitalization (RR: 0.62, 95% CI: 0.37–1.03, P = .065) showed no difference. For the incidences of myocardial infarction and the adverse side effects, there was no obvious advantage of the Sacubitril/Valsartan group over the ACEI group, because the meta‐analysis was not performed due to the limited trials. This study indicated that early initiation of Sacubitril/Valsartan in patients after acute myocardial infarction was superior to ACEI in reducing the risks of major adverse cardiac events and left ventricular ejection fraction increasing. As for the other outcomes (the incidences of cardiac death, the heart failure hospitalization, the myocardial infarction and the adverse side effects), Sacubitril/Valsartan showed no obvious advantage than ACEI.     

Association between aspirin use and cardiovascular outcomes in ALLHAT participants with and without chronic kidney disease: A post hoc analysis

It is unclear whether aspirin is beneficial for prevention of CVD in patients with CKD. We performed a secondary analysis of the ALLHAT trial to assess the effect of baseline aspirin use on nonfatal myocardial infarction (MI) or fatal coronary heart disease (CHD), all‐cause mortality, and stroke. Baseline characteristics of aspirin users and nonusers were used to generate propensity‐matched cohorts. Using conditional Cox proportional hazard regression models, we examined the effect of aspirin on the outcomes in the cohort at large and across 3 levels of kidney function (eGFR ≥90, 60–89, and <60). 11 250 ALLHAT participants reported using aspirin at baseline. The propensity‐matched dataset included 6894 nonusers matched with replacement to achieve a balanced analysis population (n = 22 500). Risk of fatal CHD or nonfatal MI (HR = 0.94, 95% CI 0.86–1.02) and stroke (HR = 1.01, 95% CI 0.89–1.15) was not significantly different between groups. Aspirin users were at significantly lower risk of all‐cause mortality compared to nonusers (HR = 0.82, 95% CI 0.76–0.88). Aspirin use was not associated with incidence of fatal CAD or nonfatal MI in patients with CVD (HR = 0.93, CI 0.84–1.04) or without CVD at baseline (HR = 1.04, CI 0.82–1.32). Results were consistent across strata of GFR (interaction p value NS). In hypertensive patients at high cardiovascular risk, aspirin use is not associated with risk of nonfatal MI, fatal CHD, or stroke; however, aspirin use is associated with lower risk of all‐cause mortality. These results are consistent across baseline eGFR.     

Optimal blood pressure for patients with end‐stage renal disease following coronary interventions

Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end‐stage renal disease (ESRD) (eGFR < 15 ml/min/1.73m²) still unclear. The authors aimed to investigate the ideal achieved BP in ESRD patients with CAD after coronary intervention. Five hundred and seventy‐five ESRD patients who had undergone percutaneous coronary interventions (PCIs) were enrolled and their clinical outcomes were analyzed according to the category of systolic BP (SBP) and diastolic BP (DBP) achieved. The clinical outcomes included major cardiovascular events (MACE) and MACE plus hospitalization for congestive heart failure (total cardiovascular (CV) event).The mean systolic BP was 135.0 ± 24.7 mm Hg and the mean diastolic BP was 70.7 ± 13.1 mm Hg. Systolic BP 140–149 mm Hg and diastolic BP 80–89 mm Hg had the lowest MACE (11.0%; 13.2%) and total CV event (23.3%; 21.1%). Patients with systolic BP < 120 mm Hg had a higher risk of MACE (HR: 2.01; 95% CI: 1.17–3.46, p = .008) than those with systolic BP 140–149 mm Hg. Patients with systolic BP ≥ 160 mm Hg (HR: 1.84; 95% CI, 3.27–1.04, p = .04) and diastolic blood BP ≥ 90 mm Hg (HR: 2.19; 95% CI: 1.15–4.16, p = .02) had a higher risk of total CV event rate when compared to those with systolic BP 140–149 mm Hg and diastolic BP 80–89 mm Hg. A J‐shaped association between systolic (140–149 mm Hg) and diastolic (80–89 mm Hg) BP and decreased cardiovascular events for CAD was found in patients with ESRD after undergoing PCI in non‐Western population.     

Automatically assessed P‐wave predicts cardiac events independently of left atrial enlargement in patients with cardiovascular risks: The Japan Morning Surge‐Home Blood Pressure Study

A prolonged P‐wave in electrocardiography (ECG) reflects atrial remodeling and predicts the development of atrial fibrillation (AF). The authors enrolled 810 subjects in the Japan Morning Surge Home Blood Pressure (J‐HOP) study who had ≥1 cardiovascular (CV) risk factor. The duration of P‐wave was automatically analyzed by standard 12‐lead electrocardiogram. Left atrial (LA) enlargement and left ventricular hypertrophy (LVH) were measured on echocardiography. The primary end points were fatal/nonfatal cardiac events: myocardial infarction, sudden death, and hospitalization for heart failure. The maximum P‐wave duration (Pmax) from the 12 leads was selected for analysis. The authors compared four prolonged P‐wave cutoffs (Pmax = 120, 130, 140, 150 ms) and cardiac events. LA diameter and left ventricular mass index (LVMI) were significantly associated with Pmax (r = 0.08, P = .02 and r = 0.17, P < .001, respectively). When the cutoff level was Pmax 120 or 130 ms, prolonged P‐wave was not associated with cardiac events (P = .45 and P = .10), but when a prolonged P‐wave was defined as Pmax ≥ 140 ms (n = 50) or Pmax ≥ 150 ms (n = 19), the patients in those groups had significantly higher incidence of cardiac events than others (P < .001 and P = .03). A Cox proportional hazards model including age, gender, body mass index, smoking, regular drinker, hypertension, dyslipidemia, diabetes, office systolic blood pressure, heart rate, LA enlargement, and LVH revealed that prolonged P‐wave defined as Pmax ≥ 140 ms was independently associated with cardiac events (hazard ratio: 4.23; 95% confidence interval: 1.30–13.77; P = .02). In conclusion, the automatically assessed prolonged P‐wave was associated with cardiac events independently of LA enlargement and LVH in Japanese patients with CV risks.     

Preventive effect of aspirin on preeclampsia in high‐risk pregnant women with stage 1 hypertension

Studies reported that women in a low‐risk cohort with stage 1 hypertension defined as 130–139 mmHg/80–89 mmHg, according to the American College of Cardiology/American Heart Association, are more likely to develop into preeclampsia than women with normotensive in the early gestation. In this study, the authors investigated whether preeclampsia was more likely to occur in stage 1 hypertensive women compared to the normotensive pregnant women in a high‐risk cohort, which was based on the randomized controlled trial of "Low‐dose Aspirin in the Prevention of Preeclampsia in China." Meanwhile, the authors further evaluated the preventive effect of aspirin for preeclampsia in stage 1 hypertension subset. In women enrolled at or before 16 weeks of gestation, in the control group, the preeclampsia occurrence was significantly higher in stage 1 hypertensive woman than in the normotensive women (20.4% vs. 6.2%, aOR 3.960, 95% CI 1.299–12.074, p = .016), while no difference was observed in the aspirin group (4.5% vs. 4.2%, aOR 0.921, 95% CI 0.140–6.070, p = .932). In stage 1 hypertension, the incidences of preeclampsia and preterm birth were significantly lower in the aspirin group as compared to the control group (4.5% vs. 20.4%, aOR 0.139, 95% CI 0.027–0.716, p = .018; 4.5% vs. 18.4%, aOR 0.141, 95% CI 0.025–0.782, p = .025). Compared with the control group, the aspirin group displayed significantly prolonged gestational age at delivery (38.6 ± 1.2 vs. 37.4 ± 3.4, p = .042). This study indicates that the newly classified stage 1 hypertension might be an additional risk factor for preeclampsia in Chinese high‐risk pregnant women, and aspirin intervention might be useful.     

Risk of bleeding and use of platelet transfusions in patients with hematologic malignancies: recurrent event analysis

A recent randomized trial (TOPPS) compared prophylactic platelet transfusions (for counts <10×10⁹/L) with a strategy of no-prophylaxis in adults with hematologic malignancies. Seventy percent of enrolled patients received an autologous hematopoietic stem cell transplant. Statistical models were developed to explore which patient factors or clinical characteristics are important prognostic factors for bleeding. These models were presented for baseline characteristics and for recurrent analysis of bleeding to assess the risks of World Health Organization grade 2–4 bleeding on any given day. Additional analyses explored the importance of fever. Treatment plan (chemotherapy/allogeneic hematopoietic stem cell transplant), female sex, and treatment arm (no-prophylaxis) were significantly associated with an increased number of days of bleeding. The number of days with a platelet count <10×109/L was significantly associated with a grade 2–4 bleed (P<0.0001). Patients with a temperature of at least 38°C had the highest hazard of a grade 2–4 bleed (hazard ratio: 1.7, 95% confidence interval: 1.3 to 2.4, compared with the risk in patients with a temperature <37.5°C). There was no evidence that minor bleeding predicted a grade 2–4 bleed. The results highlighted the limited role of correction of thrombocytopenia by platelet transfusion in reducing the risk of bleeding. Clinically stable patients undergoing autologous hematopoietic stem cell transplantation had the lowest risk of bleeding and benefited least from prophylactic platelet transfusions. Prospective studies are required to address the usefulness of risk factors to support better targeted platelet transfusions. TOPPS Controlled-Trials.com number ISRCTN08758735.     

Impact of revascularization in patients with post‐infarction left ventricular aneurysm and ventricular tachyarrhythmia

BackgroundVentricular arrhythmia is a leading cause of cardiac death among patients with post‐infarction left ventricular aneurysm (PI‐LVA). The effect of coronary revascularization in PI‐LVA patients with ventricular tachyarrhythmia remains unknown. This study aims to investigate the impact of revascularization therapy on clinical outcomes in these patients.MethodsA total of 238 PI‐LVA patients were enrolled, and 59 patients were presented with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Patients were classified into 4 groups by treatment strategies (medical or revascularization) and the presence of VT/VF: group 1 (n = 57): VT/VF− and revascularization−; group 2 (n = 122): VT/VF− and revascularization+; group 3 (n = 34): VT/VF+ and revascularization+; and group 4 (n = 25): VT/VF+ and revascularization‐. The clinical outcomes were compared, and the primary endpoint was cardiac death or heart transplantation.ResultsPatients were followed up for 45 ± 16 months, and 41 patients (17.2%) reached the primary endpoint. Kaplan–Meier analysis showed that in VT/VF− patients, revascularization associated with higher cardiac survival compared with medical therapy (log‐rank p = .002), but in VT/VF+ patients, revascularization did not predict better cardiac outcome (log‐rank p = .901). Cox regression analysis revealed PET‐EF (HR 4.41, 95% CI: 1.72–11.36, p = .002) and moderate/severe mitral regurgitation (HR 2.32, 95% CI: 1.02–5.30, p = .046) as independent predictors of adverse cardiac outcome in patients with VT/VF.ConclusionPI‐LVA patients with VT/VF are at high risk of adverse cardiac outcome, and coronary revascularization does not mitigate this risk, although revascularization was associated with higher cardiac survival in PI‐LVA patients without VT/VF.     

Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open‐label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40–160 mg/day or febuxostat 10–60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio‐ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (–2.9 and –2.5 mg/dl; both p < 0.001) and morning home systolic BP (–3.6 and –5.1 mm Hg; both p < 0.01) after 24 weeks'' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin‐creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (–20.8%; p = 0.021), but not febuxostat (–8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks'' treatment.     

Functional measures,inflammatory markers and endothelin-1 as predictors of 360-day survival in centenarians

Centenarians represent a rapidly growing population. To better characterize this specific age group, we have performed a cross-sectional study to observe associations between functional measures and a range of biochemical markers, including inflammatory markers and their significance as predictors of 360-day survival. Medical history and physical and functional assessment (Mini-Mental State Examination (MMSE), Katz Index (activities of daily living, ADL) and Barthel Index (Barthel Index) of Activities of Daily Living, and Lawton Instrumental Activities of Daily Living Scale (Lawton IADL)) were conducted on 86 101.9 ± 1.2-year-old (mean ± SD) subjects (70 women, 16 men). Blood tests were performed on 84 subjects of whom 43 also had extended biomarker assessment. As a reference group 30 51.8 ± 5.0-year old healthy subjects (20 women, 10 men) were recruited. The centenarians received follow-up phone calls. Fifty-two centenarians (60 %) survived ≥360 days. Longer survival was associated with higher MMSE (hazard ratio, HR = 0.934, 95 % confidence interval (CI) 0.896–0.975, P = .002), ADL (HR = 0.840, 95 % CI 0.716–0.985, P = .032), Barthel Index (HR = 0.988, 95 % CI 0.977–0.999, P = .026), and albumin level (HR .926, 95 % CI 0.870–0.986, P .016) and with lower white blood cell (WBC) (HR = 1.161, 95 % CI 1.059–1.273, P = .001), C-reactive protein (CRP) (HR = 1.032, 95 % CI 1.014–1.050, P < .001), IL-6 (HR = 1.182, 95 % CI 1.047–1.335, P = .007), and endothelin-1 (ET-1) level (HR = 3.711, 95 % CI 1.233–11.169, P = .020). Centenarians had higher 360-day survival probability with MMSE ≥13 (P < .001), ADL ≥1 (P < .001), Barthel Index ≥15 (P < .001), Lawton IADL ≥10 points (P = .009), WBC <8.3 G/L (P = .039), CRP <10 mg/L (P < .001), IL-6 <6 pg/mL (P .002), and ET-1 <1.1 pg/mL (P .007). Our results indicate that functional measures, inflammatory markers, and endothelin-1 are predictors of 360-day survival in centenarians.     

Nocturnal heart rate rising is a risk factor for poor renal outcomes in patients with chronic kidney disease and hypertension

The association of heart rate (HR) dipping pattern with renal outcomes in chronic kidney disease (CKD) patients with hypertension has never been investigated. In order to demonstrate if HR dipping pattern is a risk factor for renal outcomes, cardiovascular (CV) diseases, and mortality in hypertensive patients with CKD, we conducted the prospective longitudinal observational study. Patients were divided into three groups according to their nocturnal HR: HR dippers (night–day HR ratio ≤ 0.9), HR non‐dippers (0.9 < night–day HR ratio ≤ 1.0), and HR risers (night–day HR ratio > 1.0). The primary outcome was renal endpoint, a composite outcome of progression to end‐stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥ 50%; the secondary outcomes included poor renal outcomes, CV events, and death. A total of 34 (11.3%) patients reached renal endpoint after a follow‐up of 34 ± 17 months. Both HR non‐dippers and HR risers were predictive to renal endpoint (hazard ratio 2.58, 95% confidence interval (CI) 1.04‐ 6.4, P = .04; hazard ratio 3.95, 95% CI 1.33‐ 11.79, P = .01, respectively), while only HR risers was shown to be correlated with a decline in eGFR≥ 50% (hazard ratio 5.28, 95% CI 1.45–19.16, P < .05), and decline in eGFR (β ‐0.17, 95% CI ‐0.33‐ ‐0.01, P = .04). No predictive value was found for HR dipping pattern to mortality and CV events. In conclusion, our study provided the first evidence that HR non‐dippers, especially risers were a risk factor for poor renal outcomes in hypertensive patients with CKD.     

Independent and combined effects of hypertension and diabetes on clinical outcomes in patients with COVID‐19: A retrospective cohort study of Huoshen Mountain Hospital and Guanggu Fangcang Shelter Hospital

It is widely recognized that hypertension is one of the major risk factor for disease severity and mortality in patients with coronavirus disease 2019 (COVID‐19). However, type 2 diabetes mellitus (T2DM) and hypertension are frequent comorbid conditions, complicating the assessment of hypertension''s individual contribution to the risk. The aims of this study were to evaluate the contributions of hypertension alone, T2DM alone, or their combination to the risk of death, acute respiratory distress syndrome (ARDS)/respiratory failure, and severe COVID‐19 infection. Additionally, we assessed risks associated with elevated blood pressure and fasting blood glucose on the same three clinical outcomes. Multivariate logistic models were used for these analyses. Among the 3400 patients, 3327(97.9%) survived and 73(2.1%) died. Compared to patients having neither hypertension nor T2DM (n = 1392), the risk of mortality was significantly higher in patients with T2DM alone (n = 226, OR 5.26 [95% CI: 2.39–11.58]) or with T2DM in combination with hypertension (n = 507, OR 3.02, [95% CI: 1.48–6.15]). Similarly, T2DM was a risk factor for development of ARDS/respiratory failure and severe infection. Hypertension alone (n = 1275) only conferred additional risk for the development of severe infection (OR 1.22 [95% CI: 1.00–1.51]). In conclusion, neither hypertension nor elevated blood pressure was independent risk factors for death or ARDS/respiratory failure but hypertension marginally increased the risk of severe COVID‐19 infection. The risk associated with hypertension is accentuated through its confounding effect on T2DM.     

Circulating choline is associated with coronary artery stenosis in patients with hypertension: A cross‐sectional study of Chinese adults

Choline is an important nutrient involved in multiple biosynthesis pathways. However, whether circulating choline levels are associated with the risk of hypertension (HTN) and artery stenosis in HTN remains unknown. We investigated the correlations of plasma choline with HTN and coronary artery injury and explored the utility of plasma choline as a diagnostic biomarker for HTN and artery stenosis. 193 HTN patients and 154 age‐ and sex‐matched healthy controls (CON) were recruited in this study. Fasting plasma choline was detected using liquid chromatography tandem mass spectrometry. Choline levels were significantly higher in HTN without artery stenosis (HTN‐AS) than CON (8.07 [7.19‐9.24] μM vs 7.03 [6.21‐8.13] μM, P < .01) group and were further upregulated in HTN with artery stenosis (HTN + AS) (8.63 [7.09‐10.59] μM, P < .01) group. Patients with multivessel disease (MVD) also exhibited higher choline levels than those with single vessel disease (SVD) (8.64 [7.16‐10.55] μM vs 8.04(6.74‐9.38) μM, P < .01). Increased choline levels were independently associated with the risk of HTN (OR = 1.2, 95% CI: 1‐1.45, P = .05), HTN + AS (OR = 1.27, 95% CI: 1.09‐1.48, P < .01), and MVD (OR = 1.16, 95% CI: 1.02‐1.31, P = .02) after adjustment for multiple risk factors. Receiver operating characteristic (ROC) analysis showed that choline had an area under curve (AUC) score of 0.69, 0.67, and 0.63 in determining HTN, HTN + AS, and MVD. In conclusion, higher choline levels were associated with increased risk of HTN and artery stenosis in hypertensive patients.