Worse Clinical Outcomes In Patients Research Articles

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<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<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

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 .

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.

Greater Disease Severity and Worse Clinical Outcomes in Patients Hospitalised with COVID-19 in Africa.

COVID-19 cardiovascular research from Africa is limited. This study describes cardiovascular risk factors, manifestations, and outcomes of patients hospitalised with COVID-19 in the African region, with an overarching goal to investigate whether important differences exist between African and other populations, which may inform health policies. A multinational prospective cohort study was conducted on adults hospitalised with confirmed COVID-19, consecutively admitted to 40 hospitals across 23 countries, 6 of which were African countries. Of the 5,313 participants enrolled globally, 948 were from African sites (n = 9). Data on demographics, pre-existing conditions, clinical outcomes in hospital (major adverse cardiovascular events (MACE), renal failure, neurological events, pulmonary outcomes, and death), 30-day vitality status and re-hospitalization were assessed, comparing African to non-African participants. Access to specialist care at African sites was significantly lower than the global average (71% vs. 95%), as were ICU admissions (19.4% vs. 34.0%) and COVID-19 vaccination rates (0.6% vs. 7.4%). The African cohort was slightly younger than the non-African cohort (55.0 vs. 57.5 years), with higher rates of hypertension (48.8% vs. 46.9%), HIV (5.9% vs. 0.3%), and Tuberculosis (3.6% vs. 0.3%). In African sites, a higher proportion of patients suffered cardiac arrest (7.5% vs. 5.1%) and acute kidney injury (12.7% vs. 7.2%), with acute kidney injury (AKI) appearing to be one of the strongest predictors of MACE and death in African populations compared to other populations. The overall mortality rate was significantly higher among African participants (18.2% vs. 14.2%). Overall, hospitalised African patients with COVID-19 had a higher mortality despite a lower mean age, contradicting literature that had previously reported a lower mortality attributed to COVID-19 in Africa. African sites had lower COVID-19 vaccination rates and higher AKI rates, which were positively associated with increased mortality. In conclusion, African patients were hospitalized with more severe COVID-19 cases and had poorer outcomes.

High Perceived Stress Predicts Worse Clinical Outcomes in Patients with Stable Coronary Heart Disease

Background. High stress is associated with coronary heart disease (CHD), but the impact of perceived stress on prognosis with stable CHD remains unclear. This study investigated the impact of high perceived stress (HPS) on cardiovascular events in stable CHD patients. Methods. From March 2015 and December 2020, 2215 stable CHD patients were recruited. The Chinese version of the Perceived Stress Scale-14 (CPSS) was used, with follow-up conducted every 6 months until the occurrence of a cardiovascular event or March 31, 2022. Cardiovascular-related events were used as outcomes, including myocardial infarction, unplanned revascularization, stroke, death, or rehospitalization from angina. Patients were divided into HPS (CPSS≥31) and nonhigh perceived stress (NHPS) groups. The Kaplan-Meier survival curves were plotted, and the log-rank test compared the incidence of adverse events after adjusting for sociodemographic, lifestyle, and clinical information. Results. The recruited CHD population was 59.6 years old on average, 79.6% male, 27.2 points average CPSS, and median follow-up of 47 months. There were 523 HPS patients, with 98 (18.7%) cardiovascular events, and 1692 NHPS patients with 239 (14.1%) cardiovascular events. The log-rank analysis showed that risk of cardiovascular events with HPS was higher than NHPS (P=0.012). After adjusting for demographic, lifestyle, and clinical information, the HPS group had significantly increased risk of events within 24 months (HR 1.369, 95% CI 1.037-1.807, P=0.027), but less impact after 24 months. Conclusions. HPS predicts subsequent cardiovascular events in patients with stable CHD within 24 months. Therefore, more attention should be given to CHD patients with HPS, which may improve clinical prognosis.

Association between mental health social worker staffing in psychiatric emergency wards and readmission outcomes: A nationwide survey in Japan

AbstractAimThe mental healthcare system in Japan is transitioning from institution‐based to community‐based treatment. To prevent prolonged hospitalization and community integration of psychiatric patients, mental health social workers (MHSWs) are pivotal in coordinating post‐discharge arrangements for psychiatric inpatients. This study aimed to propose a care model to improve clinical outcomes in psychiatric emergency wards in Japan.MethodsWe conducted a mail‐in questionnaire survey targeting medical facilities with psychiatric emergency wards. We collected data of the psychiatric care system, including facility profiles, staffing conditions and caseloads, and the provided psychiatric services and treatment options. Using multiple regression analyses, we explored associations between these data and clinical outcomes, focusing on the average number of days for hospitalization and the integration of patients into a community.ResultsData were collected from 82 facilities (response rate, 45.8%). The average number of days for hospitalization and community integration were 64.7 and 327.9 days, respectively. The caseloads for MHSWs were significantly associated with longer hospitalization (β = 0.31, p = 0.009) and shorter duration of community living (β = −0.28, p = 0.027).ConclusionThe clinical performance in psychiatric emergency wards surpassed the Japanese government's targets regarding these outcomes. We found that heavy caseloads on MHSWs were associated with worse clinical outcomes for patients in psychiatric emergency wards. These findings suggest that reducing MHSW caseloads (≤20 cases) may be a potential interventional strategy to prevent prolonged hospitalization and promote successful community integration of patients.

Prognostic impact and predictors of persistent renal dysfunction in acute kidney injury after percutaneous coronary intervention for acute myocardial infarction.

This study aimed to evaluate the prognostic impact and predictors of persistent renal dysfunction in acute kidney injury (AKI) after an emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). A total of 877 patients who underwent emergency PCI for AMI were examined. AKI was defined as serum creatinine (SCr) ≥ 0.3mg/dL or ≥ 50% from baseline within 48h after PCI. Persistent AKI was defined as residual impairment of SCr ≥ 0.3mg/dL or ≥ 50% from baseline 1month after the procedure. The primary outcome was the composite endpoints of death, myocardial infarction, hospitalization for heart failure, stroke, and dialysis. AKI and persistent AKI were observed in 82 (9.4%) and 25 (2.9%) patients, respectively. Multivariate Cox proportional hazards analysis demonstrated that persistent AKI, but not transient AKI, was an independent predictor of primary outcome (hazard ratio, 4.99; 95% confidence interval, 2.30-10.8; P < 0.001). Age > 75years, left ventricular ejection fraction < 40%, a high maximum creatinine phosphokinase MB level, and bleeding after PCI were independently associated with persistent AKI. Persistent AKI was independently associated with worse clinical outcomes in patients who underwent emergency PCI for AMI. Advanced age, poor cardiac function, large myocardial necrosis, and bleeding were predictors of persistent AKI.

Status Epilepticus after mechanical thrombectomy: The role of early EEG assessment in Stroke Unit, clinical and radiological prognostication

BackgroundConvulsive (CSE) and non-convulsive (NCSE) Status Epilepticus are a complication in 0.2–0.3% ischemic strokes. Large stroke and cortical involvement are the main risk factors for developing SE. This study evaluates the prevalence of SE in patients treated with endovascular thrombectomy (EVT) through EEG recording within 72- h from admission. Moreover, we compared clinical, radiological, and outcome measures in SE and no-SE patients. Materials and MethodsWe collected retrospectively demographical and clinical characteristics of acute ischemic stroke patients who underwent EVT, admitted in the Stroke Unit (SU) of the University Hospital of Trieste between January 2018 and March 2020 who underwent EEG recording within 72- h from the symptoms’ onset. ResultsOut of 247 EVT patients, 138 met the inclusion criteria, of whom 9 (6.5%) showed SE with median onset time of 1 day (IQR 1–2). No difference was found between the two groups as for age, sex, risk factors, grade of recanalization, etiology of stroke, and closed vessel. The no-SE group presented higher NIHSS improvement rate (p=0.025) compared to the SE group. The sum of the lobes involved in the ischemic lesion was significantly higher in SE group (p=0.048). ConclusionSE after EVT in large strokes is a non-rare complication, with most being NCSE. Performing a rapid EEG assessment in a Stroke Unit setting may allow for a prompt recognition and treatment of SE in the acute/hyper-acute phase. SE may be correlated with worse clinical outcomes in patients with large vessel occlusion.

Exacerbation of thromboinflammation by JAK2V617F mutation worsens the prognosis of cerebral venous sinus thrombosis

AbstractCerebral venous sinus thrombosis (CVST) is an uncommon venous thromboembolic event accounting for <1% of strokes resulting in brain parenchymal injuries. JAK2V617F mutation, the most frequent driving mutation of myeloproliferative neoplasms, has been reported to be associated with worse clinical outcomes in patients with CVST. We investigated whether hematopoietic JAK2V617F expression predisposes to specific pathophysiological processes and/or worse prognosis after CVST. Using an in vivo mouse model of CVST, we analyzed clinical, biological, and imaging outcomes in mice with hematopoietic-restricted Jak2V617F expression, compared with wild-type Jak2 mice. In parallel, we studied a human cohort of JAK2V617F-positive or -negative CVST. Early after CVST, mice with hematopoietic Jak2V617F expression had increased adhesion of platelets and neutrophils in cerebral veins located in the vicinity of CVST. On day 1, Jak2V617F mice had a worse outcome characterized by significantly more frequent and severe intracranial hemorrhages (ICHs) and higher mortality rates. Peripheral neutrophil activation was enhanced, as indicated by higher circulating platelet–neutrophil aggregates, upregulated CD11b expression, and higher myeloperoxydase plasma level. Concurrently, immunohistological and brain homogenate analysis showed higher neutrophil infiltration and increased blood-brain barrier disruption. Similarly, patients with JAK2V617F-positive CVST tended to present higher thrombotic burden and had significantly higher systemic immune-inflammation index, a systemic thromboinflammatory marker, than patients who were JAK2V617F-negative. In mice with CVST, our study corroborates that Jak2V617F mutation leads to a specific pattern including increased thrombotic burden, ICH, and mortality. The exacerbated thromboinflammatory response, observed both in mice and patients positive for JAK2V617F, could contribute to hemorrhagic complications.

Impact of hyperuricemia on 5-year clinical outcomes in patients with critical limb ischemia following percutaneous transluminal angioplasty.

A growing evidence on the correlation between hyperuricemia and cardiovascular disease (CVD) has been previously reported. However, there have been limited data on the impact of hyperuricemia on long-term clinical outcomes in patients with critical limb ischemia (CLI) who underwent percutaneous transluminal angioplasty (PTA). A total of 425 peripheral artery disease patients who underwent PTA for CLI were enrolled. The patients were divided into the hyperuricemia group (n = 101) and the normal group (n = 324). The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction, any coronary revascularization, and stroke, up to 5 years. The secondary endpoint was a major adverse limb event (MALE), including any repeated PTA, and target extremity surgery. Inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust for potential confounders. After IPTW matching analysis, compared to the normal group, the hyperuricemia group was associated with a higher incidence of MACCE (20.7% vs. 13.6%, hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.15-2.38, P = 0.006) including non-cardiac death (11.7% vs. 6.3%, HR: 1.95, 95% CI: 1.19-3.19, P = 0.006) and MALE (47.7% vs. 36.0%, HR: 1.62, 95% CI: 1.23-2.13, P = 0.001) including non-target extremity revascularization (15.0% vs. 6.8%, HR: 2.42, 95% CI: 1.52-3.84, P < 0.001). In the present study, hyperuricemia was associated with worse clinical outcomes in patients with CLI following PTA during 5-year clinical follow-up. Efficacy of controlling hyperuricemia in improving clinical outcomes should be evaluated in further studies.

Prognostic impact of combined non-severe aortic stenosis and mitral regurgitation on clinical outcomes: a single-centre retrospective study

ObjectivesThough the concomitant occurrence of non-severe aortic stenosis (AS) and mitral regurgitation (MR) is highly prevalent, there are limited data to guide clinical decision-making in this condition. Here, we attempt...

Effect of psychosocial factors on autonomic nervous system activity in patients with heart failure.

Autonomic imbalance predicts worse clinical outcomes in patients with heart failure (HF). Managing the variables affecting heart rate variability (HRV) might improve the clinical outcomes of patients with HF. This study aimed to investigate variables affecting HRV. We assessed autonomic nervous system activity (low-frequency [Lf], high-frequency [Hf], and Lf/Hf ratio) in 60 patients with HF, employing standard measures to capture short-term HRV. To estimate the independent effects of variables such as well-known cardiac risk factors and psychosocial conditions on HRV, multivariate analyses were conducted. For psychosocial variables, we assessed depression and quality of life in patients and their family caregivers. We also assessed the self-care behavior of patients and their caregivers' burden. Depression in family caregivers and self-care behavior of patients were independently associated with a decreased Hf (β-coefficient = 0.309, P = .039 and β-coefficient = -0.029, P = .047, respectively). Depression of family caregivers and self-care behavior of patients may affect HRV in patients with HF.

Evaluation of clinical and microbiological factors related to mortality in patients with Gram-negative bacterial infections treated with ceftazidime–avibactam: A prospective multicentric cohort study

ObjectivesThis study aimed to evaluate the clinical and microbiological risk factors associated with mortality in patients treated with ceftazidime–avibactam for carbapenem-resistant Gram-negative bacterial infections. MethodsThis multicentric prospective cohort study included hospitalized adult patients with a microbiologically confirmed infection treated with ceftazidime–avibactam for ≥48 hours. The clinical and microbiological risk factors for 30-day mortality were evaluated using a Cox regression model. ResultsOf the 193 patients evaluated from the five tertiary hospitals, 127 were included in the study. Thirty-five patients (27.6%) died within 30 days. Infections with AmpC beta-lactamase-carrying bacteria were independently related to 30-day mortality (adjusted hazard ratio [aHR] 2.49, 95% confidence interval [CI] 1.28–4.84, P < 0.01) after adjusting for time from infection to antimicrobial prescription (P = 0.04). Further, these bacterial infections were also related to higher in-hospital mortality (aHR 2.17, 95% CI 1.24–3.78, P < 0.01). Only one patient developed resistance to ceftazidime–avibactam during treatment. ConclusionsTreatment with ceftazidime–avibactam had worse clinical outcomes in patients with infections with bacteria with chromosomally encoded AmpC beta-lactamase. However, these findings should be confirmed in future studies.

Right Heart Remodeling and Outcomes in Patients With Tricuspid Regurgitation: A Literature Review and Meta-Analysis

BackgroundFunctional tricuspid regurgitation (TR) can develop either because of right ventricular (RV) remodeling (ventricular functional TR) and/or right atrial dilation (atrial functional TR). ObjectivesThis meta-analysis aimed to investigate the association between right heart remodeling and long-term (>1 year) all-cause mortality in patients with significant TR (at least moderate, ≥2+). MethodsMEDLINE, ISI Web of Science, and SCOPUS databases were searched. Studies reporting data on at least 1 RV functional parameter and long-term all-cause mortality in patients with significant TR were included. This study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements. ResultsOut of 8,902 studies, a total of 14 were included, enrolling 4,394 subjects. The duration of follow-up across the studies varied, ranging from a minimum of 15.5 months to a maximum of 73.2 months. Overall, long-term all-cause mortality was 31% (95% CI: 20%-41%; P ≤ 0.001). By means of meta-regression analyses, an inverse relation was found between tricuspid annular plane systolic excursion (11 studies enrolling 3,551 subjects, −6.3% [95% CI: −11.1% to −1.4%]; P = 0.011), RV fractional area change (9 studies, 2,975 subjects, −4.4% [95% CI: −5.9% to −2.9%]; P < 0.001), tricuspid annular dimension (7 studies, 2,986 subjects, −4.1% [95% CI: −7.6% to −0.5%]; P = 0.026), right atrial area (6 studies, 1,920 subjects, −1.9% [95% CI: −2.5% to −1.3%]; P < 0.001) and mortality. ConclusionsRV dysfunction parameters are associated to worse clinical outcomes in patients with TR, whereas right atrial dilatation is linked to a better prognostic outcome. Further studies are needed to unravel the pathophysiological differences within the functional TR spectrum. (Right heart remodeling and outcomes in patients with tricuspid regurgitation; CRD42023418667)

5-Hydroxymethylcytosine Profiling of Cell-Free DNA Identifies Bivalent Genes That Are Prognostic of Survival in High-Risk Neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in childhood. We previously showed that circulating cell-free DNA (cfDNA) and tumor biopsy derived 5-hydroxymethylcytosime (5-hmC) profiles identified patients with neuroblastoma who experienced subsequent relapse. Here, we hypothesized that 5-hmC modifications selectively enriched in cfDNA compared with tumor biopsy samples would identify epigenetic changes associated with aggressive tumor behavior and identify novel biomarkers of outcome in patients with high-risk neuroblastoma. 5-hmC profiles from cfDNA (n = 64) and tumor biopsies (n = 48) were compared. Two neuroblastoma cell lines underwent chromatin immunoprecipitation followed by sequencing (ChIP-Seq) for H3K27me3, H3K4me3, and H3K27ac; kethoxal-associated single-stranded DNA sequencing; hmC-Seal for 5-hmC; and RNA-sequencing (RNA-Seq). Genes enriched for both H3K27me3 and H3K4me3 in the included cell lines were defined as bivalent. Using bivalent genes defined in vitro, a bivalent signature was established in three publicly available cohorts of patients with neuroblastoma through gene set variation analysis. Differences between tumors with high or low bivalent signatures were assessed by the Kaplan-Meier method and Cox proportional hazards models. In cfDNA compared with tumor biopsy derived 5-hmC profiles, we found increased 5-hmC deposition on Polycomb Repressive Complex 2 target genes, a finding previously described in the context of bivalent genes. We identified 313 genes that bore bivalent chromatin marks, were enriched for mediators of neuronal differentiation, and were transcriptionally repressed across a panel of heterogeneous neuroblastoma cell lines. In three distinct clinical cohorts, low bivalent signature was significantly and independently associated with worse clinical outcome in patients with high-risk neuroblastoma. Low expression of bivalent genes is a biomarker of worse outcome in patients with high-risk neuroblastoma.

Lymphocyte subpopulations: a potential predictor of a response in patients with immune thrombocytopenia

ABSTRACT Objectives Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by increased platelet destruction and altered production. Despite the well-described pathophysiological background of immune dysregulation, current treatment guidelines consist of monotherapy with different drugs, with no tool to predict which patient is more suitable for each therapeutic modality. Methods In our study, we attempted to determine differences in the immune setting, comparing the patients’ responses to administered therapy. During 12-month follow-up, we assessed blood count, antiplatelet autoantibodies, and T lymphocyte subsets in peripheral blood in 35 patients with ITP (newly diagnosed or relapsed disease). Results Our data show that the value of antiplatelet autoantibodies, the percentage of cytotoxic T lymphocytes, and the immunoregulatory index (IRI, CD4+ / CD8+ T cell ratio) differ significantly by treatment response. Responders have a higher IRI (median 2.1 vs. 1.5 in non-responders, P = 0.04), higher antiplatelet autoantibodies (median 58 vs. 20% in non-responders, P = 0.01) and lower relative CD8+ T cells count (P = 0.02) before treatment. Discussion The results suggest that immunological parameters (antiplatelet autoantibodies, relative CD8+ T cell count and IRI) could be used as prognostic tools for a worse clinical outcome in patients with ITP. Conclusion These biomarkers could be utilized for stratification and eventually selection of treatment preferring combination therapy.

COVID-19 outcomes in patients with pre-existing cardiovascular disease and risk factors: perspectives from a hospital in Ireland

Background/Aims COVID-19 has led to substantial changes in the provision of emergency healthcare services. International data suggest that COVID-19 is associated with increased morbidity and mortality in patients with pre-existing cardiovascular disease and cardiovascular risk factors. This study aimed to explore the association between pre-existing cardiovascular disease and/or cardiovascular risk factors and COVID-19 disease severity and outcomes in an Irish hospital. Methods This retrospective study obtained data from a bioresource database of patients with confirmed COVID-19 infection (n=649) in a large hospital in Dublin. Data were collected on patients' demographic characteristics, cardiovascular diseases, cardiovascular disease risk factors and medications taken for cardiovascular conditions. The World Health Organization progression scale was used to assess the severity of COVID-19 infection in each patient. Cross-tabulation analysis was used to analyse associations between variables, with a P value of ≤0.05 indicating significance. Results Mortality rates were six times greater in patients with cardiovascular disease compared to those without cardiovascular disease (18.6% vs 3.1%). A higher percentage of patients with one or more cardiovascular risk factors had moderate (53.4%) or severe (19.1%) COVID-19 and higher mortality rates (10.7%) than those without cardiovascular risk factors. Of the patients who died from COVID-19 (n=40), 60.0% (n=24) had one or more cardiovascular diseases, while 80.0% (n=32) had one or more cardiovascular risk factors. Conclusions Existing cardiovascular disease and cardiovascular risk factors increase the risk of more severe disease and worse clinical outcomes in patients with COVID-19. Many cardiovascular risk factors are modifiable, so it is important to consider preventative education strategies designed to reduce modifiable risk factors to improve outcomes for patients with COVID-19.

COVID-19 outcomes in patients with pre-existing cardiovascular disease and risk factors: perspectives from a hospital in Ireland

Background/Aims COVID-19 has led to substantial changes in the provision of emergency healthcare services. International data suggest that COVID-19 is associated with increased morbidity and mortality in patients with pre-existing cardiovascular disease and cardiovascular risk factors. This study aimed to explore the association between pre-existing cardiovascular disease and/or cardiovascular risk factors and COVID-19 disease severity and outcomes in an Irish hospital. Methods This retrospective study obtained data from a bioresource database of patients with confirmed COVID-19 infection (n=649) in a large hospital in Dublin. Data were collected on patients' demographic characteristics, cardiovascular diseases, cardiovascular disease risk factors and medications taken for cardiovascular conditions. The World Health Organization progression scale was used to assess the severity of COVID-19 infection in each patient. Cross-tabulation analysis was used to analyse associations between variables, with a P value of ≤0.05 indicating significance. Results Mortality rates were six times greater in patients with cardiovascular disease compared to those without cardiovascular disease (18.6% vs 3.1%). A higher percentage of patients with one or more cardiovascular risk factors had moderate (53.4%) or severe (19.1%) COVID-19 and higher mortality rates (10.7%) than those without cardiovascular risk factors. Of the patients who died from COVID-19 (n=40), 60.0% (n=24) had one or more cardiovascular diseases, while 80.0% (n=32) had one or more cardiovascular risk factors. Conclusions Existing cardiovascular disease and cardiovascular risk factors increase the risk of more severe disease and worse clinical outcomes in patients with COVID-19. Many cardiovascular risk factors are modifiable, so it is important to consider preventative education strategies designed to reduce modifiable risk factors to improve outcomes for patients with COVID-19.