Worse Clinical Outcomes In Patients Research Articles

Prognostic value of peak heart rate on cardiopulmonary exercise testing in patients with chronic heart failure

Abstract Backgrounds Many factors are known to be related to impaired exercise capacity or worse clinical outcomes in patients with chronic heart failure (CHF). Peak heart rate achievement by cardiopulmonary exercise testing (CPET) can be easily obtained on CPET. However, less data is available regarding the impact of peak heart rate on exercise capacity or long-term clinical outcomes in patients with CHF. Purpose We sought to investigate whether lower heart rate during peak exercise displayed poorer exercise capacity and worse clinical outcomes in patients with CHF. Methods We examined consecutive 435 patients with CHF referred for CPET in our university hospital between 2013 and 2018. The primary outcome was a composite of all-cause death or hospitalization due to worsening heart failure. Patients were divided into two groups according to the optimal cut-off value of peak heart rate based on receiver operating characteristic curve analysis. Results Patients with lower peak heart rate (≤112/min, n=164) were older and, higher brain natriuretic peptide level compared to those with higher peak heart rate (>112/min, n=271). Heart rate during peak exercise was significantly correlated with peak oxygen consumption (peak V̇O2) (Figure 1A), peak workload achievement (Figure 1B), and ventilatory efficiency (V̇E/V̇CO2 slope) (Figure 1C). There were 80 patients with events over a median follow-up period of 3.4 (Interquartile range 0.7–5.6) years. Patients with lower peak heart rate had about 3.0-fold higher risk of events compared to those with high peak heart rate (hazard ratio [HR] 3.17; 95% confidence interval [CI], 2.01–4.98) (Figure 2). In a multivariable Cox regression, 10 bpm-decreased in peak heart rate was associated with 12% increased adverse events (HR 0.88; 95%CI, 0.78–0.98). Conclusions Peak heart rate achievement on CPET was associated with reduced exercise capacity and worse clinical outcomes, suggesting that peak heart rate is useful for risk stratification in patients with CHF. Further study is required to identify therapies targeting peak heart rate to improve the exercise capacity or clinical outcomes in patients with CHF.Figure1Figure2

Prognostic value of albumin-bilirubin score in patients with chronic heart failure

Abstract Background Liver dysfunction is one of the common comorbidities, and associated with worse clinical outcomes in patients with chronic heart failure (CHF). Recently, the albumin-bilirubin (ALBI) score has been developed as an effective and convenient scoring system for assessing liver function. However, the prognostic significance of the ALBI score in patients with CHF remained to be clarified. Purpose We sought to investigate the clinical significance of ALBI score on outcome prediction in patients with CHF. Methods We prospectively examined 1567 symptomatic CHF patients (median age 74, inter quartile range [IQR] 64-82 years, mean left ventricular ejection fraction [LVEF] 49 ± 15.9 %, median N-terminal pro-brain natriuretic peptide [NT-pro BNP] 801 [IQR 372-1820] pg/ml) in a multicentre registry with 27 Japanese sites between January 2020 and December 2023. The ALBI score was calculated according to the following formula: log10 total bilirubin (mg/dl) × 0.06 + albumin (g/dL) × 10 × (-0.085). Studied patients were divided into three groups according to the ALBI grade; ALBI score ≤ -2.60 (Grade1, n = 691), -2.60 < ALBI score ≤ -1.39 (Grade 2, n = 864), ALBI score > -1.39 (Grade3, n = 12). Primary outcome of interest was a composite of all-cause death and hospitalisation due to worsening heart failure. Results Patient with higher ALBI grade had higher age, New York Heart Association functional class, NT-pro BNP level, prevalence of atrial fibrillation and chronic obstructive pulmonary disease, and lower body mass index, systolic blood pressure, haemoglobin level, serum albumin level and estimated glomerular filtration rate compared to those with lower ALBI grade. LVEF was comparable between the groups. During a median follow-up period of 537 (IQR 285-701) days, the primary outcome occurred in 267 patients (17%). Higher ALBI grade were significantly related to increased incidence of the primary outcome (P for trend < 0.001) (Figure 1). Multivariable Cox regressions showed that a higher ALBI score was independently associated with higher risk of the primary outcome (hazard ratio 2.8, 95% confidential interval (CI) 2.08-3.77, P < 0.001), even after adjustment for the MAGGIC score as an established risk prediction model, NT-pro BNP, aspartate aminotransferase, and platelet counts. Furthermore, addition of the ALBI score to the MAGGIC score significantly increased c-index from 0.70 (95% CI 0.66-0.74) to 0.73 (95% CI 0.69-0.76) (P < 0.001) (Figure 2). The net reclassification improvement afforded by the ALBI score was 26% for the primary outcome (P<0.001). Conclusions Liver dysfunction assessed by the ALBI score was independently associated with worse clinical outcomes in patients with CHF. Moreover, addition of the score to the existing risk prediction model significantly increased the ability of outcome prediction, suggesting beneficial clinical application of the ALBI score in patients with CHF.

Association of gut microbiota imbalance with risk of postoperative infections in patients with left ventricular assist device

Abstract Background Infections are the most common complications following left ventricular assist device (LVAD) implantation and associated with adverse events. Gut microbial imbalance may predispose to mucosal colonization with pathogens, resulting in a risk of subsequent serious infections. However, it remains unclear whether gut microbiota imbalance is associated with postoperative infections in patients with LVAD. Purpose The aim of this study was to investigate whether gut microbiota imbalance was associated with postoperative infections in patients with LVAD. Methods We prospectively examined 22 consecutive LVAD patients who were admitted to a university hospital for routine check-ups and had stool cultures taken between March 2022 and December 2023. All patients had no signs of infection. The patients were divided into two groups according to positive (normal bacterial flora and other bacteria including Streptococcus viridans, Klebsiella, or Extended-spectrum β-lactamase Escherichia coli; n = 7) and negative (normal bacterial flora only; n = 15) for stool culture. The primary outcome was serious infection requiring hospitalisation treated with intravenous antimicrobial agents. Results Patients were predominantly male (68%) and the median age was 49 (interquartile range [IQR] 29-58) years. There were no significant differences in age, sex, primary aetiology of heart failure, type of LVAD devices, time on LVAD support, the history of infection, or antibiotics use within six months between the groups. During a median follow-up period of 316 days (IQR 242-559), the primary outcome occurred in seven patients (32%), including four hospitalisation for driveline infections, two pneumoniae and bacterial bloodstream infections, and one lung abscess and bacterial bloodstream infection. Kaplan–Meier analysis showed that the adverse events more frequently occurred in LVAD patients with positive for stool culture (P = 0.010) (Figure). A multivariable Cox regression analysis showed that positive for stool culture was independently associated with an increased subsequent risk of the primary outcome (hazard ratio 6.99, 95% confidence interval 1.17-41.7, P = 0.033), even after adjustments for age, male, body mass index, diabetes, INTERMACS profile, mechanical circulatory support, serum creatinine, serum albumin, and white blood cell count, which are known to be strong determinants of worse clinical outcomes in patients with LVAD. Conclusions In patients with LVAD, gut microbial imbalance was associated with subsequent serious infections. These findings suggest that the screening of stool culture might be useful for early identification of high-risk patients for infectious complication after LVAD implantation.

Clinical outcomes in ventilator-associated pneumonia patients with and without chronic obstructive pulmonary disease: A retrospective observational study.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Critically ill patients with COPD exacerbations may require invasive mechanical ventilation (IMV). Ventilator-associated pneumonia (VAP) commonly occurs in the intensive care unit (ICU) and is usually associated with high mortality. Current studies on the relationship between COPD and VAP are limited. This work compares the etiology and clinical outcomes of VAP between patients with and without COPD in Taiwan. This retrospective observational study was conducted at the Chiayi Chang Gung Memorial Hospital. Patients with VAP were enrolled between January 2015 and December 2019. The COPD diagnosis was based on post-bronchodilator pulmonary function tests. We compared the bacterial etiology, ICU and hospital stay length, IMV duration, and mortality. A total of 175 patients with VAP were enrolled, 44% of whom presented pre-existing COPD. The disease severity on the day of admission was similar in both groups. Microorganisms were identified in 83 (47%) patients, with Pseudomonas aeruginosa, Acinetobacter spp., and Klebsiella pneumoniae being the most common pathogens. The proportion of multi-drug resistant isolates showed no significant differences between groups. Most patients underwent antibiotic treatment before VAP onset. The length of ICU and hospital stays and IMV duration after VAP onset were similar between groups, as well as ICU mortality, in-hospital mortality and 14-day mortality. Our study revealed that COPD was not associated with worse clinical outcomes in patients with VAP. No significant differences in bacterial etiology were observed between the two groups.

Obesity hypoventilation syndrome is associated with worse in-hospital outcomes in patients with acute myocardial infarction: A nationwide study

BackgroundObesity hypoventilation syndrome (OHS) is a condition characterized by obesity, daytime hypercapnia, and sleep-disordered breathing. The impact of OHS on outcomes in patients with acute myocardial infarction (AMI) remains poorly understood. MethodsWe conducted a retrospective analysis using data from the National Inpatient Sample (2016–2020) to evaluate the outcomes of patients with OHS admitted for ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). ResultsAmong STEMI and NSTEMI patients, 0.15 % and 0.37 % had OHS, respectively. After adjusting for confounders, OHS was associated with higher odds of in-hospital mortality, cardiac arrest, acute kidney injury, renal replacement therapy, and respiratory failure requiring intubation in NSTEMI patients. In STEMI patients, OHS was associated with higher odds of cardiac arrest, acute kidney injury, and respiratory failure. ConclusionOHS is associated with worse clinical outcomes in patients admitted with AMI, particularly in those with NSTEMI.

Abstract C007: Quemliclustat (CD73 Inhibitor) reduces adenosine-regulated NR4A gene expression and increases mPDAC inflammation in patients from the ARC-8 trial

Abstract Background: Metastatic pancreatic ductal adenocarcinomas (mPDACs) express high levels of the adenosine-generating enzyme CD73 and therapeutically represent a significant unmet medical need, with median patient overall survival (OS) of <1 year. The small-molecule quemliclustat (quemli; AB680) was designed to inhibit soluble and cell-bound CD73 enzymatic activity, thereby providing the capability of reversing adenosine-mediated anti-tumor immune suppression. Quemli, in combination with gemcitabine/nab-paclitaxel (G/nP) ± anti-PD-1 antibody zimberelimab (zim), demonstrated encouraging clinical activity in the first line (1L) mPDAC study ARC-8 (NCT04104672), with median OS ranging from 14.6-19.4 months. Methods and Results: We began by identifying surrogates for tumor adenosine levels, given that it is not possible to measure adenosine levels directly in clinical samples. Cell culture experiments indicated that the stable adenosine analogue NECA can drive upregulation of the NR4A family of transcription factors (NR4A1, NR4A2, and NR4A3) in cancer cells as well as cancer-associated stromal cells (fibroblasts). Treatment with quemli reversed NR4A gene family upregulation, supporting a model in which high baseline levels of NR4A expression in tumors may be reflective of tumors with higher levels of adenosine. Next, we investigated quemli’s mechanism of action (MoA) by transcriptomic assessment of 37 matched pairs of pre- compared to post-treated mPDACs from ARC-8 patients dosed with 100mg of quemli. Treatment with quemli-containing regimens led to a significant reduction in tumor expression levels of the NR4A gene family. Decreased NR4A family tumor expression after treatment was accompanied by a significant increase in tumor inflammation, as measured by a T-cell activation gene signature. Analysis of a published transcriptional dataset from the nivolumab + G/nP control arm of the PRINCE trial in front-line mPDAC (NCT03214250) indicated that high levels of tumor NR4A1, 2, and 3 expression portend significantly worse clinical outcomes in patients treated with this IO/chemotherapy regimen, highlighting a potential opportunity for quemli to provide clinical benefit by reversing adenosine-mediated immunosuppression in mPDAC. Conclusion:Quemli + G/nP treatment was associated with a reduction in tumor expression levels of adenosine-regulated NR4A gene family and was accompanied by an increase in tumor inflammation. Given the adenosine-modulating MoA, patients with mPDACs expressing high levels of NR4A in baseline tumor tissue, which portended poor prognosis in 1L mPDACs treated with G/np-containing regimen from the PRINCE study, may benefit from treatment with quemli. A phase 3 trial (PRISM-1) of G/nP +/- quemli in the 1L mPDAC setting is being planned. Citation Format: Ji Yun Kim, Ning Wang, Ben Weeder, Enzo Stagnaro, Karim Mrouj, Jose Aquino, Xian He, Eileen M O’Reilly, Shubham Pant, Gulam A Manji, Zev A Wainberg, Joon Rhee, Brandon Beagle, Daniel DiRenzo, Matthew J Walters, Angelo Kaplan, Sean Cho, Omar Kabbarah. Quemliclustat (CD73 Inhibitor) reduces adenosine-regulated NR4A gene expression and increases mPDAC inflammation in patients from the ARC-8 trial [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C007.

Cigarette Smoking Is Associated With Lower Chance of Hepatitis B Surface Antigen Seroclearance and Altered Host Immunity.

Cigarette smoking is associated with worse clinical outcomes in patients with chronic hepatitis B (CHB) infection, but the effects on hepatitis B surface antigen (HBsAg) seroclearance are unclear. This study aimed to investigate the effect of active smoking on HBsAg seroclearance (SC) and its impact on peripheral blood lymphocytes in patients with CHB infection. Longitudinal follow-up data was retrieved in 7833 antiviral-treated CHB subjects identified from a centralised electronic patient record database (Part 1). Phenotypic analysis of peripheral blood mononuclear cells (PBMCs) from 27 CHB-infected patients (6 active smokers; 13 with SC) was performed by flow cytometry to assess programmed death-1 (PD-1) expression and proportion of regulatory T cells (CD4+CD25+CD127lo). Effector function of HBV-specific T cells was examined by comparing granzyme B (GZMB) and transforming growth factor beta (TGFβ) production in undepleted PBMCs and Treg-depleted PBMCs after 7 days invitro stimulation with HBV envelope protein overlapping peptides (Part 2). Over a median follow-up of 5 years, smoking was associated with lower probability of SC (aHR 0.70, 95% CI 0.57-0.87). PD-1 expression was increased in CD4+T cells, CD8+T cells and CD20+B cells among smokers compared to non-smokers and positively correlated with pack years (all p < 0.05). Treg depletion led to partial functional recovery of HBV-specific T cells, with significantly bigger magnitude in smokers (p = 0.0451, mean difference = 4.68%) than non-smokers (p = 0.012, mean difference = 4.2%). Cigarette smoking is associated with lower chance of HBsAg seroclearance, higher PD-1 expression on lymphocytes, and impairment of effector functions of HBV-specific T cells in CHB.

Secondary Conduits in Coronary Artery Bypass Grafting Surgery

BackgroundRecent evidence has suggested use of the right internal mammary artery (RIMA) is associated with worse clinical outcomes in patients undergoing coronary artery bypass grafting (CABG) surgery. Therefore, we compared the clinical consequences of secondary conduit selection (RIMA vs radial artery vs saphenous vein) after CABG. MethodsA post-hoc analysis of the CABG Off or On Pump Revascularization Study, involving 3913 patients from 79 centers in 19 countries who underwent CABG surgery and received arterial grafting with at least 2 grafts. Outcomes of interest were all-cause mortality, myocardial infarction, stroke, and revascularization. ResultsA total of 3913 patients received veins (3210; 68%), radial arteries (549; 12%), or RIMAs (154; 3%) to supplement left internal mammary artery to left anterior descending artery grafts. The risk of all-cause mortality was reduced in patients who received secondary radial arteries compared with veins (weighted hazard ratio [HR], 0.79; 95% CI, 0.64-0.98) and increased in patients who received RIMA compared with veins (weighted HR, 1.37; 95% CI, 1.13-1.68) after 4.8 years of follow-up. Multiple and single arterial grafting had a similar mortality risk (weighted HR, 0.87; 95% CI, 0.73-1.03). ConclusionsSupplementing left internal mammary artery to left anterior descending artery grafting using radial arteries led to better clinical outcomes than veins, and too few RIMA were available to draw definitive conclusions. A randomized trial is needed to clarify the role of the RIMA in multiple arterial grafting CABG surgery.

Initial non-adherence to lipid-lowering medication: a systematic literature review

BackgroundThe impact on cardiovascular health is lost when a patient does not obtain a newly prescribed lipid-lowering medication, a situation termed “initial medication nonadherence” (IMN). This research summarizes the published evidence on the prevalence, associated factors, consequences, and solutions for IMN to prescribed lipid-lowering medication in the United States.MethodsA systematic literature search using PubMed and Google Scholar, along with screening citations of systematic reviews, identified articles published from 2010 to 2021. Studies reporting results of IMN to lipid-lowering medications were included. Studies that evaluated non-adult or non-US populations, used weaker study designs (e.g., case series), or were not written in English were excluded.ResultsThere were 19 articles/18 studies that met inclusion and exclusion criteria. Estimates of the prevalence of IMN to newly prescribed lipid-lowering medications ranged from 10 to 18.2% of patients and 1.4–43.8% of prescriptions (n = 9 studies). Three studies reported prescriber and patient characteristics associated with IMN. Hispanic ethnicity, Black race, lower Charlson Comorbidity Index score and no ED visits or hospitalization were associated with IMN. Lipid lowering prescriptions from primary care providers were also associated with IMN. Four studies described patient-reported reasons for IMN, including preference for lifestyle modifications, lack of perceived need, and side effect concerns. Four intervention studies reported mixed results with automated calls, live calls, or letters. One study reported worse clinical outcomes in patients with IMN: higher levels of low-density lipoprotein and greater risk of emergency department visits.ConclusionsUp to one-fifth of patients fail to obtain a newly prescribed lipid-lowering medication but there is limited information about the clinical consequences. Future research should assess outcomes and determine cost-effective approaches to address IMN to lipid-lowering therapy.

Early Anuria in Incident Peritoneal Dialysis Patients: Incidence, Risk Factors, and Associated Clinical Outcomes

Rationale & ObjectiveThe development of anuria was linked to worse clinical outcomes in patients undergoing peritoneal dialysis (PD). Our objective was to investigate the incidence, risk factors, and associated clinical outcomes of anuria within the first year after PD. Study DesignRetrospective Cohort Study. Setting & ParticipantsPatients who started continuous ambulatory peritoneal dialysis (CAPD) at our center between 2006 and 2020 were included and followed up until January 31, 2023. ExposureAge, gender, diabetes, temporary hemodialysis, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs), diuretics, baseline urine volume, serum albumin, daily glucose exposure, peritonitis, and incremental PD. OutcomesThe primary outcome was early anuria, defined as 24-hour urine volume ≤ 100mL within the first year of PD initiation. Secondary outcomes included all-cause mortality, cardiovascular disease (CVD) mortality, technique failure, and peritonitis. Analytical ApproachCox proportional hazards model. ResultsA total of 2592 CAPD patients aged 46.7 ± 14.9 years were recruited. Among them, 58.9% were male, 24.0 % had diabetes. Within the first year of PD therapy, 159 (6.13%) patients developed anuria, with a median duration of 7.53 (interquartile range [IQR] 3.93-10.0) months. Higher baseline urine volume (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.90-0.97), higher serum albumin (HR 0.92, 95% CI 0.88-0.95), with diabetes before PD (HR 0.57, 95% CI 0.35-0.92), and prescribed incremental PD (HR 0.27, 95% CI 0.14-0.51) were associated with a reduced risk for early anuria, while a higher level of daily glucose exposure (HR 1.01, 95% CI 1.00-1.01) was identified as a risk factor for early anuria. Subgroup analyses showed that using ACEI/ARBs was linked to a lower risk of early anuria (HR 0.25, 95% CI 0.09-0.69) in diabetic patients. Treating early anuria as a time-dependent covariate, early anuria was associated with a higher risk for all-cause mortality (HR 1.69, 95% CI 1.23-2.32) and technique failure (HR 1.43, 95% CI 1.00-2.04) after adjusting for confounding factors. LimitationsSingle-center and observational study. ConclusionsThe incidence of early anuria in our center was 6.13%. Higher baseline urine volume, higher serum albumin, a history of diabetes, incremental PD start, and lower daily glucose exposure were associated with lower risks of early anuria. In patients with diabetes mellitus, non-use of ACEI/ARBs was associated with early anuria. Early anuria was related to a higher risk for all-cause mortality and technique failure.

Shock cardiogénico en el infarto agudo de miocardio con enfermedad multivaso: estrategia de revascularización según el territorio isquémico

Introduction and objectivesThe association of revascularization strategy with clinical outcomes according to the ischemic territory of nonculprit lesion has not been documented in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS). This study aimed to compare outcomes between culprit-only and immediate multivessel percutaneous coronary intervention (PCI) according to ischemic territory in patients with AMI-CS. MethodsA total of 536 patients with AMI-CS and multivessel disease from the SMART-RESCUE registry were categorized according to ischemic territory (nonculprit left main/proximal left anterior descending artery [LM/pLAD] vs culprit LM/pLAD vs no LM/pLAD). The primary outcome was a patient-oriented composite endpoint (POCE) consisting of all-cause death, myocardial infarction, rehospitalization due to heart failure, or repeat revascularization at 1 year. ResultsAmong the total population, 108 patients had nonculprit LM/pLAD, 228 patients had culprit LM/pLAD, and 200 patients had no LM/pLAD, with the risk of POCE being higher in patients with large ischemic territory lesions (53.6% vs 53.4% vs 39.6%; P = .02). Multivessel PCI was associated with a significantly lower risk of POCE compared with culprit-only PCI in patients with nonculprit LM/pLAD (40.7% vs 66.9%; HR, 0.52; 95%CI, 0.29-0.91; P=.02), but not in those with culprit LM/pLAD (P=.46) or no LM/pLAD (P=.47). A significant interaction existed between revascularization strategy and large nonculprit ischemic territory (P=.03). ConclusionsLarge ischemic territory involvement was associated with worse clinical outcomes in patients with AMI-CS and multivessel disease. Immediate multivessel PCI might improve clinical outcomes in patients with a large nonculprit ischemic burden.

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH. The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10). Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56). This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care. ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013). This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

Malnutrition risk and associated factors in hospitalized older adult patients with neurological diseases: a retrospective cohort study

ABSTRACT Introduction Malnutrition risk (MR) in older adults with neurological disorders is high, but there is little evidence for validated screening tools in this group, as well as for the clinical and socioeconomic factors associated with a high MR. Objectives To determine the association of MR using the Malnutrition Universal Screening Tool (MUST) with mortality and length of stay (LOS) in older adults with neurological diseases. Secondarily, the association of clinical, and socioeconomic factors with MR and clinical outcomes was sought. Methods A retrospective cohort study was carried out at a third-level neurological disease referral center in Mexico. All patients older than 60 years admitted from January 2017 to December 2018 were considered. MUST, clinical and socioeconomic factors were assessed at hospital admission. Outcomes were followed up to hospital discharge or a maximum of 6 months. Results A total of 765 patients were included, of whom 24.7% (n = 189) were at high risk. A high MR was independently associated with mortality (OR 3.09; 95% CI 1.60-5.98, p = .001) and LOS >14 days (OR 4.38; 95% CI 2.79-6.89, p = <.001). The only factors independently associated with high MR was economic dependence and unemployment. Patients with high MR and economic dependence (OR 4.0; 95% CI 1.34-11.99, p = .013) or unemployment (OR 3.43; 95% CI 1.17-10.06, p = .025) had the highest mortality. Conclusions In hospitalized older adults with neurological diseases, high MR is independently associated with increased mortality and LOS. Economic dependence or unemployment are associated with worse clinical outcomes in patients with high MR.

Early relevant alerts from remote monitoring in heart failure patients with a cardiac implanted electronic device: what implications for long term outcome?

Abstract Background Alarms generated by remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) have been associated with worse clinical outcomes in patients with heart failure (HF). However, whether the timing of RM alerts impact on the clinical trajectories of HF patients is still debated. Purpose To examine the impact of alerts occurring in the first 180 days after CIED implant on clinical outcomes, as well as potential predictors. Methods we retrospectively enrolled all patients with a history of HF implanted with a CRT-D or an ICD at our tertiary. We collected data regarding ATP, shock and HF score above threshold (defined as multiparametric scores provided and validated by all CIED manufacturers). We defined early relevant alerts (Early-RA) as alarms received during the first 180 days after implant. The primary clinical outcome of the study was a composite of death or HF hospitalization. Logistic and Cox regression analyses were used to determine associations. The occurrence of early-RA was used as a time dependent covariate. Results A total of 272 patients were included in the analysis (median age 67.4 years, IQR 58.6-74.6, 19.9% female). Twenty patients had an early-RA (7.3% of the overall study population) and were found to be older, more severely symptomatic for HF, with a higher prevalence of atrial fibrillation (AF) and chronic kidney disease (CKD) (all p values&amp;lt;0.05). On the other hand, HF etiology and prevalence of CRT-D did not differ between the two groups. At univariate logistic regression analysis, we found the following factors as significantly associated with early-RA: age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.00-1.10), NYHA class (OR 2.44, 95% CI 1.01-5.82) and CKD (OR 3.41, 95% CI 1.21-8.98), but these results were not confirmed at the multivariable logistic regression. After a median follow-up of 959 days (IQR 432-1484), patients reporting an early-RA had more primary outcome events (45.0% vs 12.3% p&amp;lt;0.001). At time-dependent multivariable Cox regression analysis adjusted for age, sex, left ventricular ejection fraction and type of CIED, we found that early-RA were independently associated with a higher risk of the primary outcome (hazard ratio [HR] 3.61, 95%CI 1.42-9.18) (Figure). Early-RA were also associated with a higher risk of death (HR 5.58, 95% CI 1.68-18.50) while no significant association was found for HF hospitalization (HR 2.46, 95% CI 0.80-7.57, p=0.116). Conclusions The occurrence of alerts detected by RM of CIEDs in a relatively early phase (within 180 days from implant), is associated with a higher risk of a composite of death and HF hospitalization in HF patients.Study Outcome according to Early RATime dependent Cox regression

Closing the Gap: Approaches to Improving Colorectal Surgery Care for the Uninsured and Underinsured

AbstractHealth insurance plays a critical role in access to and delivery of health care in the United States. As the only industrialized nation without universal health coverage, Americans without adequate insurance (i.e., uninsured or underinsured individuals) face numerous obstacles to obtaining necessary health care. In this article, we review the mechanisms by which inadequate insurance leads to worse clinical outcomes in patients with common benign and malignant colorectal pathologies. We then discuss several evidence-based solutions for improving access to optimal colorectal care for these patients. These include increasing access to and affordability of health insurance, mitigating disparities between differently insured populations, strengthening the health care safety net, and tailoring outreach and clinical decision-making for the uninsured and underinsured. By exploring the nuance and impact of inadequate insurance coverage, we ultimately seek to highlight critical opportunities for future research and advocacy within the realm of insurance design and policy.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979.

Cardiogenic shock complicating acute myocardial infarction and multivessel disease: revascularization strategy according to ischemic territory

Introduction and objectivesThe association of revascularization strategy with clinical outcomes according to the ischemic territory of nonculprit lesion has not been documented in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS). This study aimed to compare outcomes between culprit-only and immediate multivessel percutaneous coronary intervention (PCI) according to ischemic territory in patients with AMI-CS. MethodsA total of 536 patients with AMI-CS and multivessel disease from the SMART-RESCUE registry were categorized according to ischemic territory (nonculprit left main/proximal left anterior descending artery [LM/pLAD] vs culprit LM/pLAD vs no LM/pLAD). The primary outcome was a patient-oriented composite endpoint (POCE) consisting of all-cause death, myocardial infarction, rehospitalization due to heart failure, or repeat revascularization at 1 year. ResultsAmong the total population, 108 patients had nonculprit LM/pLAD, 228 patients had culprit LM/pLAD, and 200 patients had no LM/pLAD, with the risk of POCE being higher in patients with large ischemic territory lesions (53.6% vs 53.4% vs 39.6%; P = .02). Multivessel PCI was associated with a significantly lower risk of POCE compared with culprit-only PCI in patients with nonculprit LM/pLAD (40.7% vs 66.9%; HR, 0.52; 95%CI, 0.29-0.91; P=.02), but not in those with culprit LM/pLAD (P=.46) or no LM/pLAD (P=.47). A significant interaction existed between revascularization strategy and large nonculprit ischemic territory (P=.03). ConclusionsLarge ischemic territory involvement was associated with worse clinical outcomes in patients with AMI-CS and multivessel disease. Immediate multivessel PCI might improve clinical outcomes in patients with a large nonculprit ischemic burden.

A simple angio-based coronary flow assessment of culprit vessels in primary percutaneous coronary intervention is associated with long-term prognosis after ST-segment-elevation myocardial infarction

BackgroundDespite prompt reperfusion, the risk of adverse clinical outcomes following ST-segment-elevation myocardial infarction (STEMI) remains pronounced, owing partly to suboptimal reperfusion. However, coronary functional evaluation is seldom feasible during primary percutaneous coronary intervention (PPCI). We aimed to examine the clinical implication of a simple coronary assessment based on single-angiographic view (μQFR) during PPCI in discriminating impaired coronary flow and adverse outcomes for STEMI. MethodsSTEMI Patients undergoing successful PPCI were enrolled and followed up prospectively from 4 medical centers in China. Post-PPCI μQFR of culprit vessels were analyzed. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal MI, ischemia-driven target-vessel revascularization and readmission for heart failure. ResultsA total of 570 patients with STEMI were enrolled, and post-PCI μQFR was analyzable in 557 (97.7%) patients, with a median of 0.94. Patients with low post-PCI μQFR showed higher incidence of adverse outcomes than those with high μQFR, showing a 2.5-fold increase in the risk for MACE (hazard ratio: 2.51, 95% confidence intervals: 1.33 to 4.72; P = 0.004). Moreover, post-PCI μQFR significantly increased discriminant ability for the occurrence of MACE when added to traditional GRACE risk score for STEMI (integrated discrimination improvement: 0.029; net reclassification index: 0.229; P < 0.05). ConclusionsA low μQFR of culprit vessel in PPCI is independently associated with worse clinical outcomes in patients with STEMI. The single-angiographic-view-based coronary evaluation is a feasible tool for discriminating poor prognosis and could serve as a valuable complement in risk stratification for STEMI.

Clinical Outcomes and Resource Utilization in Patients With Peripheral Arterial Disease Hospitalized for Acute Coronary Syndrome

Previous studies have shown an association between acute limb ischemia and higher mortality in patients with Acute Myocardial Infarction. Although Peripheral Artery Disease is a well-known risk factor for development of macrovascular pathology, the effect of its severity is not well investigated in patients hospitalized for Acute Coronary Syndrome (ACS). Using a national cohort of patients with various degrees of Peripheral Arterial Disease, we investigated in-hospital outcomes in patients who were admitted for ACS. Using the 2016-2020 Nationwide Readmissions Database, we queried all patients who were hospitalized for ACS (Unstable Angina, Non ST-Elevation Myocardial Infarction, and ST-Elevation Myocardial Infarction). Patients were further divided into three groups, either No Peripheral Arterial Disease (Non-PAD), Peripheral Arterial Disease (PAD) or Critical Limb Ischemia (CLI). Multivariable models were designed to adjust for patient and hospital factors and examine the association between ACS and PAD severity. Of an approximately 3,834,181 hospitalizations for ACS, 6.4% had PAD, 0.2% had CLI and all other were Non-PAD. Following risk adjustment, in hospital mortality was higher by 24% in PAD (AOR 1.24, 95%CI 1.21-1.28) and 86% in CLI (AOR 1.86, 95%CI 1.62-2.09) compared to Non-PAD. Furthermore, PAD and CLI were linked to 1.23-fold (95%CI 1.20-1.26) and 1.67-fold (95%CI 1.45-1.86) greater odds of cardiogenic shock compared to Non-PAD. Additionally, PAD and CLI were linked with higher odds of mechanical circulatory support usage, cardiac arrest and acute kidney injury compared to Non-PAD. Lastly, duration of hospital stay, hospitalization costs and odds of non-home discharge and 30-day readmissions were greater in patients with PAD and CLI compared to Non-PAD. PAD severity was associated with worse clinical outcomes in patients with ACS, including in hospital mortality and resource utilization.

Ticagrelor downregulates the expression of proatherogenic and proinflammatory miR125-b compared to clopidogrel: A randomized, controlled trial

BackgroundPlatelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatory microRNAs, including miR-125a, miR-125b and miR-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel. ObjectivesWe compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel. MethodsAfter percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors. ResultsExpression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor. ConclusionsTicagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.