The Diagnostic Role of Uric Acid to Creatinine Ratio for the Identification of Patients with Adverse Pulmonary Embolism Outcomes

Background: Uric acid (UA) is the final product of purine metabolism and a marker of oxidative stress that may be involved in the pathophysiology of cardiovascular and thromboembolic disease. The aim of the current study is to investigate the potential value of UA to creatinine ratio (UA/Cr) as a diagnostic tool for the outcome of patients admitted with acute pulmonary embolism (PE) and the correlations with other parameters. Methods: We evaluated 116 patients who were admitted for PE in a respiratory medicine department. PE was confirmed with computed tomography pulmonary angiography. Outcomes evaluated were hospitalization duration, mortality or thrombolysis and a composite endpoint (defined as mortality or thrombolysis). Patients were assessed for PE severity with the PE Severity Index (PESI) and the European Society of Cardiology (ESC) 2019 risk stratification. Results: The median (interquartile range) UA/Cr level was 7.59 (6.3–9.3). UA/Cr was significantly associated with PESI (p < 0.001), simplified PESI (p = 0.019), and ESC 2019 risk stratification (p < 0.001). The area under the curve (AUC) for prediction of 30-day mortality by UA/Cr was 0.793 (95% CI: 0.667–0.918). UA/Cr levels ≥7.64 showed 87% specificity and 94% negative predictive value for mortality. In multivariable analysis UA/Cr was an independent predictor of mortality (HR (95% CI): 1.620 (1.245–2.108), p < 0.001) and composite outcome (HR (95% CI): 1.521 (1.211–1.908), p < 0.001). Patients with elevated UA/Cr levels (≥7.64) had longer hospitalization (median (IQR) 7 (5–11) vs. 6 (5–8) days, p = 0.006)), higher mortality (27.3% vs. 3.2%, p = 0.001) and worse composite endpoint (32.7% vs. 3.4%, p < 0.001). Conclusion: Serum UA/Cr ratio levels at the time of PE diagnosis are associated with disease severity and risk stratification, and may be a useful biomarker for the identification of patients at risk of adverse outcomes.

Genetic Determinants of Serum Calcification Propensity and Cardiovascular Outcomes in the General Population

Background:Serum calciprotein particle maturation time (T50), a measure of vascular calcification propensity, is associated with cardiovascular morbidity and mortality. We aimed to identify genetic loci associated with serum T50 and study their association with cardiovascular disease and mortality.Methods:We performed a genome-wide association study of serum T50 in 2,739 individuals of European descent participating in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, followed by a two-sample Mendelian randomization (MR) study to examine causal effects of T50 on cardiovascular outcomes. Finally, we examined associations between T50 loci and cardiovascular outcomes in 8,566 community-dwelling participants in the Rotterdam study.Results:We identified three independent genome-wide significant single nucleotide polymorphism (SNPs) in the AHSG gene encoding fetuin-A: rs4917 (p = 1.72 × 10−101), rs2077119 (p = 3.34 × 10−18), and rs9870756 (p = 3.10 × 10−8), together explaining 18.3% of variation in serum T50. MR did not demonstrate a causal effect of T50 on cardiovascular outcomes in the general population. Patient-level analyses revealed that the minor allele of rs9870756, which explained 9.1% of variation in T50, was associated with a primary composite endpoint of all-cause mortality or cardiovascular disease [odds ratio (95% CI) 1.14 (1.01–1.28)] and all-cause mortality alone [1.14 (1.00–1.31)]. The other variants were not associated with clinical outcomes. In patients with type 2 diabetes or chronic kidney disease, the association between rs9870756 and the primary composite endpoint was stronger [OR 1.40 (1.06–1.84), relative excess risk due to interaction 0.54 (0.01–1.08)].Conclusions:We identified three SNPs in the AHSG gene that explained 18.3% of variability in serum T50 levels. Only one SNP was associated with cardiovascular outcomes, particularly in individuals with type 2 diabetes or chronic kidney disease.

Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis

Background: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. Methods: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Results: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65–1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03–1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71–0.96) but may have little or no effect on mortality (RR: 1.08, 0.51–2.31). Conclusions: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.

Oncological Outcomes After Hippocampus-Sparing Whole-Brain Radiotherapy in Cancer Patients With Newly Diagnosed Brain Oligometastases: A Single-Arm Prospective Observational Cohort Study in Taiwan

BackgroundPromisingly, the technique of hippocampus sparing during WBRT (HS-WBRT) might preserve NCFs. In this research, we examined oncological outcomes, with emphasis on neurologic/non-neurologic causes of death, CNS progression, and leptomeningeal disease (LMD) recurrence in cancer patients who underwent HS-WBRT.MethodsOne hundred and fourteen cancer patients with newly diagnosed brain oligometastases underwent HS-WBRT were consecutively enrolled. The cumulative incidence of cancer-specific deaths (neurologic or non-neurologic), LMD recurrence, and the composite endpoint of CNS progression (CNS-CE) as the first event were computed with a competing-risks approach to characterize the oncological outcomes after HS-WBRT.ResultsPatients with intact brain metastases had a significantly increased likelihood of dying from non-neurologic causes of death associated with early manifestation of progressive systemic disease (hazard ratio for non-neurologic death, 1.78; 95% CI, 1.08–2.95; p = 0.025; competing-risks Fine–Gray regression), which reciprocally rendered them unlikely to encounter LMD recurrence or any pattern of CNS progression (HR for CNS-CE as the first event, 0.13; 95% CI, 0.02–0.97; p = 0.047; competing-risks Fine–Gray regression). By contrast, patients with resection cavities post-craniotomy had reciprocally increased likelihood of CNS progression which might be associated with neurologic death eventually.ConclusionsPatterns of oncological endpoints including neurologic/non-neurologic death and cumulative incidence of CNS progression manifesting as LMD recurrence are clearly clarified and contrasted between patients with intact BMs and those with resection cavities, indicating they are clinically distinct subgroups.Trial RegistrationClinicalTrials.gov, Identifier: NCT02504788, NCT03223675.

Efficiency of Nicotinamide-based Supportive Therapy in Lymphopenia for Patients With COVID-19: A Randomized Controlled Trial

Background: The purpose of this study was to investigate the efficiency of nicotinamide-based supportive therapy in lymphopenia for patients with coronavirus disease-2019 (COVID-19). Methods: 24 patients diagnosed with the COVID-19 were randomly divided into two groups (n=12) during hospitalization in the ratio of 1:1. Based on the conventional treatment, the treatment group was given 100mg nicotinamide, five times a day. The control group only received routine treatments. The primary endpoint was the change in absolute lymphocyte counts. The secondary endpoints included both the in-hospital death and the composite endpoint of aggravation, according to upgraded oxygen therapy, improvement of nursing level, and ward rounds of superior physicians for changes of conditions. Results: The full blood counts before and after receiving the nicotinamide were comparable in each group (all P>0.05). Before and after receiving the nicotinamide, mean absolute lymphocyte counts were similar between the two groups ([0.94±0.26]*109/L versus [0.89±0.19]*109/L, P=0.565; [1.15±0.48]*109/L versus [1.02±0.28]*109/L, P=0.445, respectively). Therefore, there was no statistically significant difference in the lymphocyte improvement rate between the two groups (23.08±46.10 versus 16.52±24.10, P=0.67). There was also no statistically significant difference for the secondary endpoints between the two groups.Conclusion: Among patients with COVID-19, there was no statistically significant difference in change of full blood counts and the absolute lymphocyte counts before and after intervention in both groups. Therefore, no new evidence was found for the effect of niacinamide on lymphopenia in patients with COVID-19.Trial registration: ClinicalTrials.gov, NCT04910230. Registered 1 June 2021-retrospectively registered.

A multi-center, international, randomized, 2-year, parallel-group study to assess the superiority of IVUS-guided PCI versus qualitative angio-guided PCI in unprotected left main coronary artery (ULMCA) disease: Study protocol for OPTIMAL trial

Background Percutaneous coronary intervention (PCI) is used increasingly for revascularization of unprotected left main coronary artery (LMCA) disease. Observational studies and subgroup analyses from clinical trials, have suggested a possible benefit from the use of intravascular ultrasound (IVUS) guidance when performing unprotected LMCA PCI. However, the value of imaging with IVUS has never been proven in an appropriately powered randomized clinical trial. The OPtimizaTIon of Left MAin PCI With IntravascuLar Ultrasound (OPTIMAL) trial has been designed to establish whether IVUS-guided PCI optimization on LMCA is associated with superior clinical outcomes when compared with standard qualitative angiography-guided PCI. Methods The OPTIMAL trial is a randomized, multicenter, international study designed to enroll a total of 800 patients undergoing PCI for unprotected LMCA disease. Patients will be randomized in a 1:1 fashion to IVUS-guided PCI versus angiogram-guided PCI. In patients allocated to the angiogram-guided arm, use of IVUS is discouraged, unless there are safety concerns. In patients allocated to the IVUS guidance arm, pre-procedural IVUS assessment is highly recommended, whilst post-procedural IVUS assessment is mandatory to confirm appropriate stenting result and/or to guide stent result optimization, according to predefined criteria. Patients will be followed up to 2 years after the index procedure. The primary outcome measure is the Academic Research Consortium (ARC) patient-oriented composite endpoint (PoCE) which includes all-cause death, any stroke, any myocardial infarction and any repeat revascularization at 2 years follow-up. Discussion The OPTIMAL trial aims to provide definitive evidence about the clinical impact of IVUS-guidance during PCI to an unprotected LMCA. It is anticipated by the investigators, that an IVUS-guided strategy will be associated with less clinical events compared to a strategy guided by angiogram alone. Trial registration ClinicalTrials.gov: NCT04111770. Registered on October 1, 2019.

Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab

BackgroundSequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour necrosis factor (anti-TNF)-α therapy following the α4β7 integrin blocker vedolizumab (VDZ) or VDZ after an anti-TNF has more favourable clinical outcomes in UC in a real-world outpatient setting.MethodsPatients with UC who were exposed to first-line anti-TNF (adalimumab or infliximab) or VDZ who subsequently switched to the alternate class between May 2013 and August 2020 were identified by reviewing patient databases at 10 hospitals. Data were collected retrospectively using patient records. Baseline demographics, disease activity indices, biochemical markers, endoscopic Mayo score, colectomy rates, treatment persistence and urgent hospital utilisation composite endpoint (UHUC) rates were examined over a 52-week period.ResultsSecond-line week 52 treatment persistence was higher in the VDZ group (71/81, 89%) versus the anti-TNF group (15/34, 44%; p=0.0001), as were week 52 colectomy-free survival (VDZ: 77/80, 96%, vs anti-TNF: 26/32, 81%; p=0.009), week 52 UHUC survival (VDZ: 68/84, 81%, vs anti-TNF: 20/34, 59%; p=0.002) and week 52 corticosteroid-free clinical remission (CFCR) rates (VDZ: 22/34, 65%, vs anti-TNF: 4/20, 20%; p=0.001).ConclusionCompared with second-line anti TNF usage, the VDZ second-line cohort had significantly higher 52-week treatment persistence, UHUC survival, higher colectomy-free survival rates and higher week 52 CFCR. These data suggest that VDZ is an effective biologic in UC as a second-line therapy after anti-TNF exposure. It highlights the effect of biological order on clinically important outcomes.

Introduction of a new scoring tool to identify clinically stable heart failure patients

Introduction Heart failure (HF) poses a burden on specialist care, making referral of clinically stable HF patients to primary care a desirable goal. However, a structured approach to guide patient referral is lacking. Methods The Maastricht Instability Score—Heart Failure (MIS-HF) questionnaire was developed to objectively stratify the clinical status of HF patients: patients with a low MIS-HF (0–2 points, indicating a stable clinical condition) were considered for treatment in primary care, whereas high scores (> 2 points) indicated the need for specialised care. The MIS-HF was evaluated in 637 consecutive HF patients presenting between 2015 and 2018 at Maastricht University Medical Centre. Results Of the 637 patients, 329 (52%) had a low score and 205 of these 329 (62%) patients were referred to primary care. The remaining 124 (38%) patients remained in secondary care. Of the 308 (48%) patients with a high score (> 2 points), 265 (86%) remained in secondary care and 41 (14%) were referred to primary care. The primary composite endpoint (mortality, cardiac hospital admissions) occurred more frequently in patients with a high compared to those with a low MIS-HF after 1 year of follow-up (29.2% vs 10.9%; odds ratio (OR) 3.36, 95% confidence interval (CI) 2.20–5.14). No significant difference in the composite endpoint (9.8% vs 12.9%; OR 0.73, 95% CI 0.36–1.47) was found between patients with a low MIS-HF treated in primary versus secondary care. Conclusion The MIS-HF questionnaire may improve referral policies, as it helps to identify HF patients that can safely be referred to primary care.

Clinical Utility and Cost Effectiveness of Long-Acting Lipoglycopeptides Used in Deep-Seated Infections among Patients with Social and Economic Barriers to Care

The use of long-acting lipoglycopeptides (LaLGPs) in serious, deep-seated infections is of increasing interest. The purpose of this study is to evaluate the economic and clinical utility of LaLGPs in patients requiring protracted antibiotic courses who are not ideal candidates for oral transition or outpatient parenteral antibiotic therapy (OPAT). This is a retrospective, observational, matched cohort study of adult patients who received a LaLGP. Patients were matched 1:1 to those who received standard of care (SOC). Cost effectiveness was evaluated as total healthcare-related costs between groups. Clinical failure was a composite endpoint of mortality, recurrence, or need for extended antibiotics beyond planned course within 90 days of initial infection. There was no difference in clinical failure between the two cohorts (22% vs. 30%; p = 0.491). Six patients in the SOC cohort left against medical advice (AMA) prior to completing therapy. Among those who did not leave AMA, receipt of LaLGPs resulted in a decreased hospital length of stay by an average of 13.6 days. The average total healthcare-related cost of care was USD 295,589 in the LaLGP cohort compared to USD 326,089 in the SOC cohort (p = 0.282). Receipt of LaLGPs may be a beneficial treatment option for patients with deep-seated infections and socioeconomic factors who are not candidates for oral transition or OPAT.

The Diagnostic and Prognostic Value of Plasma Galectin 3 in HFrEF Related to the Etiology of Heart Failure

Aim: The aim of present study is to evaluate the diagnostic and prognostic value of plasma galectin 3 (Gal-3) for HF originating from different causes.Methods: We investigated the plasma levels and expression of Gal-3 in cardiac tissues in two transgenic (TG) strains of mice with cardiomyocyte-restricted overexpression of either β2- adrenergic receptor (β2- AR TG) or Mammalian sterile 20-like kinase 1 (Mst1-TG) in the present study. Additionally, 166 patients suffering from heart failure with reduced ejection fraction (HFrEF) in two hospitals within the Shaanxi province were examined in this study. All these patients were treated according to the Chinese HF guidelines of 2014; subsequently, they were followed up for 50 months, and we analyzed the prediction value of baseline Gal-3 to endpoints in these patients.Results: Gal-3 was localized in the cytoplasm and nucleus of cardiomyocytes, often formed aggregates in Mst1-TG mice. Extracellular Gal-3 staining was uncommon in Mst1-TG hearts. However, in β2-AR TG mice, although Gal-3 was also expressed in myocardial cells, it was more highly expressed in interstitial cells (e.g., fibroblasts and macrophages). Plasma Gal-3 was comparable between nTG and Mst1-TG mice. However, plasma Gal-3 was higher in β2-AR TG mice than in nTG mice. In the cohort of HFrEF patients, the median plasma Gal-3 concentration was 158.42 pg/mL. All participants were divided into two groups according to Gal-3 levels. Patients with Gal-3 concentrations above the median were older, and had lower plasma hemoglobin, but higher plasma creatinine, tissue inhibitor of metalloproteinases 1 (TIMP-1), left ventricular end systolic diameter (LVESD), left ventricular end-systolic volumes (LVESV) and end-diastolic, as well as left ventricular end-diastolic volumes (LVEDV). Spearman correlation analysis revealed that Gal-3 was positively correlated with TIMP-1 (r = 0.396, P &lt; 0.001), LVESV (r = 0.181, P = 0.020) and LVEDV (r = 0.190, P = 0.015). The 50-month clinical follow-up revealed 43 deaths, 97 unplanned re-hospitalizations, and 111 composite endpoint events. Cox analysis demonstrated that although Gal-3 did not provide any prognostic value in either total-HF subjects or coronary-heart-disease (CHD) patients, it did provide prognostic value in non-CHD patients.Conclusion: Although plasma Gal-3 is associated with TIMP-1 and echocardiographic parameters, the diagnostic and prognostic value of Gal-3 in HFrEF is determined by the etiology of HF.