Publications by authors named "Salvatore Di Somma"

131 Publications

Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study.

Crit Care 2021 02 15;25(1):61. Epub 2021 Feb 15.

Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP-HP Nord, University of Paris, Paris, France.

Background: Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality in cardiogenic shock patients.

Methods: The aim was to assess relationships between cDPP3 during the initial intensive care unit (ICU) stay and short-term outcome in the AdrenOSS-1, a prospective observational multinational study in twenty-four ICU centers in five countries. AdrenOSS-1 included 585 patients admitted to the ICU with severe sepsis or septic shock. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by the Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use and need for renal replacement therapy. cDPP3 levels were measured upon admission and 24 h later.

Results: Median [IQR] cDPP3 concentration upon admission was 26.5 [16.2-40.4] ng/mL. Initial SOFA score was 7 [5-10], and 28-day mortality was 22%. We found marked associations between cDPP3 upon ICU admission and 28-day mortality (unadjusted standardized HR 1.8 [CI 1.6-2.1]; adjusted HR 1.5 [CI 1.3-1.8]) and between cDPP3 levels and change in renal and liver SOFA score (p = 0.0077 and 0.0009, respectively). The higher the initial cDPP3 was, the greater the need for organ support and vasopressors upon admission; the longer the need for vasopressor(s), mechanical ventilation or RRT and the higher the need for fluid load (all p < 0.005). In patients with cDPP3 > 40.4 ng/mL upon admission, a decrease in cDPP3 below 40.4 ng/mL after 24 h was associated with an improvement of organ function at 48 h and better 28-day outcome. By contrast, persistently elevated cDPP3 at 24 h was associated with worsening organ function and high 28-day mortality.

Conclusions: Admission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.
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http://dx.doi.org/10.1186/s13054-021-03471-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885215PMC
February 2021

Mortality risk prediction in elderly patients with cardiogenic shock: results from the CardShock study.

ESC Heart Fail 2021 Apr 31;8(2):1398-1407. Epub 2021 Jan 31.

Division of Emergency Medicine, Department of Emergency Medicine and Services, Helsinki University Hospital, PO Box 900, Helsinki, 00029 HUS, Finland.

Aims: This study aimed to assess the utility of contemporary clinical risk scores and explore the ability of two biomarkers [growth differentiation factor-15 (GDF-15) and soluble ST2 (sST2)] to improve risk prediction in elderly patients with cardiogenic shock.

Methods And Results: Patients (n = 219) from the multicentre CardShock study were grouped according to age (elderly ≥75 years and younger). Characteristics, management, and outcome between the groups were compared. The ability of the CardShock risk score and the IABP-SHOCK II score to predict in-hospital mortality and the additional value of GDF-15 and sST2 to improve risk prediction in the elderly was evaluated. The elderly constituted 26% of the patients (n = 56), with a higher proportion of women (41% vs. 21%, P < 0.05) and more co-morbidities compared with the younger. The primary aetiology of shock in the elderly was acute coronary syndrome (84%), with high rates of percutaneous coronary intervention (87%). Compared with the younger, the elderly had higher in-hospital mortality (46% vs. 33%; P = 0.08), but 1 year post-discharge survival was excellent in both age groups (90% in the elderly vs. 88% in the younger). In the elderly, the risk prediction models demonstrated an area under the curve of 0.75 for the CardShock risk score and 0.71 for the IABP-SHOCK II score. Incorporating GDF-15 and sST2 improved discrimination for both risk scores with areas under the curve ranging from 0.78 to 0.84.

Conclusions: Elderly patients with cardiogenic shock have higher in-hospital mortality compared with the younger, but post-discharge outcomes are similar. Contemporary risk scores proved useful for early mortality risk prediction also in the elderly, and risk stratification could be further improved with biomarkers such as GDF-15 or sST2.
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http://dx.doi.org/10.1002/ehf2.13224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006692PMC
April 2021

Comparison of cardiovascular disease and cancer prevalence between Mediterranean and north European middle-aged populations (The Cilento on Ageing Outcomes Study and The Malmö Offspring Study).

Intern Emerg Med 2021 Jan 30. Epub 2021 Jan 30.

Department of Medical-Surgery Sciences and Translational Medicine, University of Rome Sapienza, Rome, Italy.

Mediterranean diet protects from both cardiovascular disease (CVD) and cancer. In the 1960s, Ancel Keys defined the concept of Mediterranean diet in the South Italian region of Cilento and proposed it as a key factor for healthy ageing in the region. The aim of the current study was to compare the prevalence of CVD and cancer between a middle-aged population from Cilento and those of a Northern European population from Malmö, Sweden. We clinically characterized two middle-aged (50-67 years of age) population-based samples from Cilento (n = 809) and Malmö (n = 1025), Sweden, respectively. Logistic regression was used to calculate odds ratios (95% confidence interval) for disease prevalence in Malmö versus Cilento inhabitants adjusted for age and sex (model 1) and adjusted for all cardiometabolic risk factors (model 2). The prevalence of hypertension, current smoking, diabetes mellitus and levels of body mass index and triglycerides were lower, whereas HDL-cholesterol was higher in Malmö than in Cilento. LDL-cholesterol was higher and estimated glomerular filtration rate was lower in Malmö than in Cilento. The odds ratio for cardiovascular disease in Malmö versus Cilento inhabitants was 1.13 (0.69-1.87) (P = 0.62) in model 1, whereas it was significantly elevated in model 2 [2.03 (1.14-3.60) (P = 0.016)]. Moreover, the odds ratio for cancer in Malmö versus Cilento was 2.78 (1.81-4.27) (P < 0.001) in model 1 and 3.11 (1.97-4.92) (P < 0.001) in model 2. The higher odds of CVD and cancer in Malmö versus Cilento, when risk factors were accounted for, suggests the existence of unknown protective factors in Cilento.
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http://dx.doi.org/10.1007/s11739-020-02625-4DOI Listing
January 2021

Development of an electrocardiogram-based risk calculator for a cardiac cause of syncope.

Heart 2021 Jan 27. Epub 2021 Jan 27.

Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland

Objective: To develop an ECG-based tool for rapid risk assessment of a cardiac cause of syncope in patients ≥40 years.

Methods: In a prospective international multicentre study, 2007 patients ≥40 years presenting with syncope were recruited in the emergency department (ED) of participating centres ranging from large university hospitals to smaller rural hospitals in eight countries from May 2010 to July 2017. 12-Lead ECG recordings were obtained at ED presentation following the syncopal event. The primary diagnostic outcome, a cardiac cause of syncope, was centrally adjudicated by two independent cardiologists using all available clinical information including 12-month follow-up. ECG predictors for a cardiac cause of syncope were identified using penalised backward selection and a continuous-scale likelihood was calculated based on regression analysis coefficients. Findings were validated in an independent US multicentre cohort including 2269 patients.

Results: In the derivation cohort, a cardiac cause of syncope was adjudicated in 267 patients (16%). Seven ECG criteria were identified as predictors for this outcome: heart rate and QTc-interval (continuous predictors), rhythm, atrioventricular block, ST-segment depression, bundle branch block and ventricular extrasystole/non-sustained ventricular tachycardia (categorical predictors). Diagnostic accuracy of these combined predictors for a cardiac cause of syncope was high (area under the curve 0.80, 95% CI 0.77 to 0.83). Overall, 138 patients (8%) were rapidly triaged towards rule-out and 181 patients (11%) towards rule-in of a cardiac cause of syncope. External validation showed similar performance.

Conclusion: In patients ≥40 years with a syncopal event, a combination of seven ECG criteria enabled rapid assessment of the likelihood that syncope was due to a cardiac cause.

Trial Registration Number: NCT01548352 (BASEL IX), NCT01802398 (SRS study).
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http://dx.doi.org/10.1136/heartjnl-2020-318430DOI Listing
January 2021

Hypernatremia and moderate-to-severe hyponatremia are independent predictors of mortality in septic patients at emergency department presentation: A sub-group analysis of the need-speed trial.

Eur J Intern Med 2021 Jan 5;83:21-27. Epub 2020 Nov 5.

Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy; Emergency Medicine Department AOU Maggiore della Carità, Novara, Italy.

Study Objective: Early risk stratification of septic patients presenting to the emergency department (ED) is challenging. The aim of the study was to evaluate the prognostic role of plasmatic sodium level (Na) derangements at ED presentation in septic patients.

Methods: According to Na at ED presentation patients were divided in eunatremic (136-145 mEq/L), hypernatremic (>145 mEq/L) and hyponatremic (<136 mEq/L). Hyponatremic patients were subsequently divided in mild (130-135 mEq/L), moderate (125-129 mEq/L) and severe (<125 mEq/L). 7 and 30-day mortality was evaluated according to Na derangements and the degree of hyponatremia. The same analysis was then performed only in respiratory tract infection-related (RTI-r) sepsis patients.

Results: 879 septic patients were included in this analysis, 40.3% had hyponatremia, 5.7% hypernatremia. Hypernatremia showed higher mortality rates at both endpoints compared to eunatremia and hyponatremia (p<0.0001 for both). Eunatremia and mild hyponatremia were compared vs. moderate-to-severe hyponatremia showing a significant difference in terms of 7 and 30-day survival (p = 0.004 and p = 0.007, respectively). The Cox proportional model identified as independent predictors of 7 and 30-day mortality moderate-to-severe hyponatremia (HR 4.89[2.38-10.03] and 1.79[1.07-3.01], respectively) and hypernatremia (HR 3.52[1.58-7.82] and 2.14[1.17-3.92], respectively). The same analysis was performed in patients with respiratory tract infection-related sepsis (n = 549), with similar results.

Conclusion: Both hypernatremia and moderate-to-severe hyponatremia at ED presentation independently predict mortality in septic patients, allowing early risk stratification and suggesting more aggressive therapeutic strategies.
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http://dx.doi.org/10.1016/j.ejim.2020.10.003DOI Listing
January 2021

Short Term Home Oxygen Therapy for COVID-19 patients: The COVID-HOT algorithm.

J Family Med Prim Care 2020 Jul 30;9(7):3209-3219. Epub 2020 Jul 30.

Department of Research and Innovation, St. Luke's University Health Network, Bethlehem, Pennsylvania, USA.

Innovative solutions are required to effectively address the unprecedented surge of demand on our healthcare systems created by the COVID-19 pandemic. Home treatment and monitoring of patients who are asymptomatic or mildly symptomatic can be readily implemented to ameliorate the health system burden while maintaining safety and effectiveness of care. Such endeavor requires careful triage and coordination, telemedicine and technology support, workforce and education, as well as robust infrastructure. In the understandable paucity of evidence-based, protocolized approaches toward HOT for COVID-19 patients, our group has created the current document based on the cumulative experience of members of the Joint ACAIM-WACEM COVID-19 Clinical Management Taskforce. Utilizing available evidence-based resources and extensive front-line experience, the authors have suggested a pragmatic pathway for providing safe and effective home oxygen therapy in the community setting.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1044_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567238PMC
July 2020

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines.

Cardiol J 2020 19;27(6):661-676. Epub 2020 Oct 19.

Pavia, Italy.

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.
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http://dx.doi.org/10.5603/CJ.a2020.0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079117PMC
October 2020

Incidence, characteristics, determinants, and prognostic impact of recurrent syncope.

Europace 2020 12;22(12):1885-1895

Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland.

Aims: The aim of this study is to characterize recurrent syncope, including sex-specific aspects, and its impact on death and major adverse cardiovascular events (MACE).

Methods And Results: We characterized recurrent syncope in a large international multicentre study, enrolling patients ≥40 years presenting to the emergency department (ED) with a syncopal event within the last 12 h. Syncope aetiology was centrally adjudicated by two independent cardiologists using all information becoming available during syncope work-up and long-term follow-up. Overall, 1790 patients were eligible for this analysis. Incidence of recurrent syncope was 20% [95% confidence interval (CI) 18-22%] within the first 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95% CI 1.11-2.01) or syncope with an unknown aetiology even after central adjudication (HR 2.11, 95% CI 1.54-2.89) had an increased risk for syncope recurrence. Least Absolute Shrinkage and Selection Operator regression fit on all patient information available early in the ED identified >3 previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95% CI 1.64-2.75). Recurrent syncope carried an increased risk for death (HR 1.87, 95% CI 1.26-2.77) and MACE (HR 2.69, 95% CI 2.02-3.59) over 24 months of follow-up, however, with a time-dependent effect. These findings were confirmed in a sensitivity analysis excluding patients with syncope recurrence or MACE before or during ED evaluation.

Conclusion: Recurrence rates of syncope are substantial and vary depending on syncope aetiology. Importantly, recurrent syncope carries a time-dependent increased risk for death and MACE.

Trial Registration: BAsel Syncope EvaLuation (BASEL IX, ClinicalTrials.gov registry number NCT01548352).
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http://dx.doi.org/10.1093/europace/euaa227DOI Listing
December 2020

Management Algorithm for Subclinical Hypoxemia in Coronavirus Disease-2019 Patients: Intercepting the "Silent Killer".

J Emerg Trauma Shock 2020 Apr-Jun;13(2):110-113. Epub 2020 Jun 10.

Department of Research and Innovation, St. Luke's University Health Network, Bethlehem, Pennsylvania, USA.

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http://dx.doi.org/10.4103/JETS.JETS_72_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472808PMC
June 2020

Study of loneliness and wisdom in 482 middle-aged and oldest-old adults: a comparison between people in Cilento, Italy and San Diego, USA.

Aging Ment Health 2020 Oct 1:1-11. Epub 2020 Oct 1.

School of Medicine, University of California San Diego, San Diego, CA, USA.

Objectives: There has been growing research interest in loneliness and wisdom in recent decades, but no cross-cultural comparisons of these constructs using standardized rating measures in older adults, especially the oldest-old. This was a cross-sectional study of loneliness and wisdom comparing middle-aged and oldest-old adults in Cilento, Italy and San Diego, United States.

Method: We examined loneliness and wisdom, using the UCLA Loneliness Scale Version 3 (UCLA-3) and San Diego Wisdom Scale (SD-WISE), respectively, in four subject groups: adults aged 50-65 and those ≥90 years from Cilento, Italy ( = 212 and 47, respectively) and San Diego, California, USA ( = 138 and 85, respectively).

Results: After controlling for education, there were no significant group differences in levels of loneliness, while on SD-WISE the Cilento ≥90 group had lower scores compared to the other three groups. There was a strong inverse correlation between loneliness and wisdom in each of the four subject groups. Loneliness was negatively associated while wisdom was positively associated with general health, sleep quality, and happiness in most groups, with varying levels of significance.

Conclusion: These results largely support cross-cultural validity of the constructs of loneliness and wisdom, and extend previous findings of strong inverse correlations between these two entities. Loneliness has become a growing public health problem, and the results of our study suggest that wisdom could be a protective factor against loneliness, although alternative explanations are also possible. Research on interventions to reduce loneliness by enhancing wisdom in older adults is needed.
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http://dx.doi.org/10.1080/13607863.2020.1821170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012404PMC
October 2020

The 2019-2020 Novel Coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2) Pandemic: A Joint American College of Academic International Medicine-World Academic Council of Emergency Medicine Multidisciplinary COVID-19 Working Group Consensus Paper.

J Glob Infect Dis 2020 Apr-Jun;12(2):47-93. Epub 2020 May 22.

Working Group on International Health Security, The American College of Academic International Academic Medicine, USA.

What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined to be coronavirus disease 2019 (COVID-19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel , was subsequently isolated as the causative agent. SARS-CoV-2 is transmitted by respiratory droplets and fomites and presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea, vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway inflammatory cytokine response and multiorgan failure. As of this article's publication date, COVID-19 has spread to approximately 200 countries and territories, with over 4.3 million infections and more than 290,000 deaths as it has escalated into a global pandemic. Public health concerns mount as the situation evolves with an increasing number of infection hotspots around the globe. New information about the virus is emerging just as rapidly. This has led to the prompt development of clinical patient risk stratification tools to aid in determining the need for testing, isolation, monitoring, ventilator support, and disposition. COVID-19 spread is rapid, including imported cases in travelers, cases among close contacts of known infected individuals, and community-acquired cases without a readily identifiable source of infection. Critical shortages of personal protective equipment and ventilators are compounding the stress on overburdened healthcare systems. The continued challenges of social distancing, containment, isolation, and surge capacity in already stressed hospitals, clinics, and emergency departments have led to a swell in technologically-assisted care delivery strategies, such as telemedicine and web-based triage. As the race to develop an effective vaccine intensifies, several clinical trials of antivirals and immune modulators are underway, though no reliable COVID-19-specific therapeutics (inclusive of some potentially effective single and multi-drug regimens) have been identified as of yet. With many nations and regions declaring a state of emergency, unprecedented quarantine, social distancing, and border closing efforts are underway. Implementation of social and physical isolation measures has caused sudden and profound economic hardship, with marked decreases in global trade and local small business activity alike, and full ramifications likely yet to be felt. Current state-of-science, mitigation strategies, possible therapies, ethical considerations for healthcare workers and policymakers, as well as lessons learned for this evolving global threat and the eventual return to a "new normal" are discussed in this article.
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http://dx.doi.org/10.4103/jgid.jgid_86_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384689PMC
May 2020

Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

Am J Kidney Dis 2020 12 15;76(6):826-841.e1. Epub 2020 Jul 15.

Columbia University Vagelos College of Physicians and Surgeons, New York, NY.

Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.

Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.

Setting & Study Populations: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.

Selection Criteria For Studies: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.

Data Extraction: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.

Analytical Approach: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.

Results: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively.

Limitations: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies.

Conclusions: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.
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http://dx.doi.org/10.1053/j.ajkd.2020.05.015DOI Listing
December 2020

Potential Immunotherapeutic Targets for Hypoxia Due to COVI-Flu.

Shock 2020 10;54(4):438-450

Department of Surgery, The University of Alabama at Birmingham, Birmingham, Alabama.

The world is currently embroiled in a pandemic of coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of COVID-19 disease ranges from asymptomatic to fatal acute respiratory distress syndrome. In few patients, the disease undergoes phenotypic differentiation between 7 and 14 days of acute illness, either resulting in full recovery or symptom escalation. However, the mechanism of such variation is not clear, but the facts suggest that patient's immune status, comorbidities, and the systemic effects of the viral infection (potentially depending on the SARS-CoV-2 strain involved) play a key role. Subsequently, patients with the most severe symptoms tend to have poor outcomes, manifest severe hypoxia, and possess elevated levels of pro-inflammatory cytokines (including IL-1β, IL-6, IFN-γ, and TNF-α) along with elevated levels of the anti-inflammatory cytokine IL-10, marked lymphopenia, and elevated neutrophil-to-lymphocyte ratios. Based on the available evidence, we propose a mechanism wherein SARS-CoV-2 infection induces direct organ damage while also fueling an IL-6-mediated cytokine release syndrome (CRS) and hypoxia, resulting in escalating systemic inflammation, multi-organ damage, and end-organ failure. Elevated IL-6 and hypoxia together predisposes patients to pulmonary hypertension, and the presence of asymptomatic hypoxia in COVID-19 further compounds this problem. Due to the similar downstream mediators, we discuss the potential synergistic effects and systemic ramifications of SARS-CoV-2 and influenza virus during co-infection, a phenomenon we have termed "COVI-Flu." Additionally, the differences between CRS and cytokine storm are highlighted. Finally, novel management approaches, clinical trials, and therapeutic strategies toward both SARS-CoV-2 and COVI-Flu infection are discussed, highlighting host response optimization and systemic inflammation reduction.
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http://dx.doi.org/10.1097/SHK.0000000000001627DOI Listing
October 2020

Proenkephalin Predicts Organ Failure, Renal Replacement Therapy, and Mortality in Patients With Sepsis.

Ann Lab Med 2020 11 17;40(6):466-473. Epub 2020 Jun 17.

Department of Medical-Surgery Sciences and Translational Medicine, School of Medicine and Psychology, Sapienza-University, Sant' Andrea Hospital, Rome, Italy.

Background: Kidney failure occurs frequently and is associated with high mortality during sepsis. Proenkephalin (PENK) is an emerging biomarker of kidney function. We explored whether PENK levels could predict severity, organ failure, and mortality in septic patients.

Methods: We measured the PENK level in the plasma of 215 septic patients using the sphingotest penKid assay (Sphingotec GmbH, Hennigsdorf, Germany). This was analyzed in terms of sepsis severity, vasopressor use, 30-day mortality, sequential organ failure assessment (SOFA) renal subscore, the Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (CKD-EPI eGFR) categories, and renal replacement therapy (RRT) requirement.

Results: The PENK levels were significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (P=0.02, P=0.007, P<0.001, respectively). The PENK levels were significantly associated with SOFA renal subscore and CKD-EPI eGFR categories (both P<0.001). The distribution of lower eGFR (<60 mL/min/1.73 m), RRT requirement, SOFA renal subscore, and the number of organ failures differed significantly according to the PENK quartile (P for trend<0.001 or 0.017). The 30-day mortality rate also differed significantly according to the PENK quartile (P for trend<0.001).

Conclusions: PENK could be an objective and reliable marker to predict severity, organ failure, and 30-day mortality in septic patients.
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http://dx.doi.org/10.3343/alm.2020.40.6.466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295958PMC
November 2020

Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?

Intern Emerg Med 2020 Aug 26;15(5):801-812. Epub 2020 May 26.

Department of Medical-Surgery Sciences and Translational Medicine, University of Rome Sapienza, Rome, Italy.

Of huge importance now is to provide a fast, cost-effective, safe, and immediately available pharmaceutical solution to curb the rapid global spread of SARS-CoV-2. Recent publications on SARS-CoV-2 have brought attention to the possible benefit of chloroquine in the treatment of patients infected by SARS-CoV-2. Whether chloroquine can treat SARS-CoV-2 alone and also work as a prophylactic is doubtful. An effective prophylactic medication to prevent viral entry has to contain, at least, either a protease inhibitor or a competitive virus ACE2-binding inhibitor. Using bromhexine at a dosage that selectively inhibits TMPRSS2 and, in so doing, inhibits TMPRSS2-specific viral entry is likely to be effective against SARS-CoV-2. We propose the use of bromhexine as a prophylactic and treatment. We encourage the scientific community to assess bromhexine clinically as a prophylactic and curative treatment. If proven to be effective, this would allow a rapid, accessible, and cost-effective application worldwide.
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http://dx.doi.org/10.1007/s11739-020-02383-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249615PMC
August 2020

Cognitive Health of Nonagenarians in Southern Italy: A Descriptive Analysis from a Cross-Sectional, Home-Based Pilot Study of Exceptional Longevity (Cilento Initiative on Aging Outcomes Or CIAO).

Medicina (Kaunas) 2020 May 5;56(5). Epub 2020 May 5.

Great Network, 00191 Rome, Italy.

Nonagenarians and centenarians (NCs) are an extremely fragile population, particularly in regard to their physical and cognitive function. The aim of this study was to define the neurocognitive profiles among 29 NCs and their 49 younger cohabitants aged 50-75 years from The Cilento Initiative on Aging Outcomes (CIAO) Pilot study in the South of Italy that had provided initial hypotheses regarding positive psychological traits related to exceptional longevity. : During the home visits, lifestyle information with specific questionnaires, functional autonomy and the neuropsychological Mini Mental Scale Examination (MMSE), and the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) scale were obtained by qualified study personnel. The total blood oxidative capacity was also determined by testing the reactive derivative of oxygen metabolites (d-ROM) and by the Biological Antioxidant Potential (BAP). In all individuals, the APOE genotype determination was also performed. : All the subjects in both groups showed high adherence to the Mediterranean Diet. None of the NCs had severe cognitive impairment, and a very low incidence of dementia was found. The data obtained on the Activities ed Instrumental Activities of Daily Living (ADL-IADL) scale showed that the majority of NCs (16/29) were autonomous in daily life activities. The comparative assessment of NCs and cohabitants showed no significant differences in the laboratory assessment of oxidative stress and APOE genotype. In the Cilento Region of Southern Italy, NCs seemed to have good cognitive status when compared to younger cohabitants aging 50-65 years without significant differences in oxidative stress markers or APOE genotype. These results might be related to optimal adherence to the Mediterranean diet, although other lifestyle factors and positive personality traits may also contribute to their healthy aging. Further studies on a larger population should be performed to confirm the results of this pilot study.
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http://dx.doi.org/10.3390/medicina56050218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279440PMC
May 2020

An Italian registry of chest pain patients in the emergency department: clinical predictors of acute coronary syndrome.

Minerva Med 2020 Apr;111(2):120-132

Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.

Background: The aim of this study was to describe the population of patients arriving in several Italian Emergency Departments (EDs) complaining of chest pain suggestive of acute coronary syndrome (ACS) in order to evaluate the incidence of ACS in this cohort and the association between ACS and different clinical parameters and risk factors.

Methods: This is an observational prospective study, conducted from the 1st January to the 31st December 2014 in 11 EDs in Italy. Patients presenting to ED with chest pain, suggestive of ACS, were consecutively enrolled.

Results: Patients with a diagnosis of ACS (N.=1800) resulted to be statistically significant older than those without ACS (NO ACS; N.=4630) (median age: 70 vs. 59, P<0.001), and with a higher prevalence of males (66.1% in ACS vs. 57.5% in NO ACS, P<0.001). ECG evaluation, obtained at ED admission, showed new onset alterations in 6.2% of NO ACS and 67.4% of ACS patients. Multiple logistic regression analysis showed that the following parameters were predictive for ACS: age, gender, to be on therapy for cardio-vascular disease (CVD), current smoke, hypertension, hypercholesterolemia, heart rate, ECG alterations, increased BMI, reduced SaO2.

Conclusions: Results from this observational study strengthen the importance of the role of the EDs in ruling in and out chest pain patients for the diagnosis of ACS. The analysis put in light important clinical and risk factors that, if promptly recognized, can help Emergency Physicians to identify patients who are more likely to be suffering from ACS.
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http://dx.doi.org/10.23736/S0026-4806.20.06472-1DOI Listing
April 2020

The Integration of qSOFA with Clinical Variables and Serum Biomarkers Improves the Prognostic Value of qSOFA Alone in Patients with Suspected or Confirmed Sepsis at ED Admission.

J Clin Med 2020 Apr 22;9(4). Epub 2020 Apr 22.

Unit of Internal Medicine, Clinica Medica, Department of Medical Surgical and Health Sciences-University of Trieste, Strada di Fiume 447, 34100 Trieste, Italy.

Background: The prognostic value of quick sepsis-related organ failure assessment (qSOFA) outside intensive care units has been criticized. Therefore, we aimed to improve its ability in predicting 30-day all-cause mortality, and in ruling out the cases at high risk of death among patients with suspected or confirmed sepsis at emergency department (ED) admission.

Methods: This study is a secondary analysis of a prospective multicenter study. We built three predictive models combining qSOFA with the clinical variables and serum biomarkers that resulted in an independent association with 30-day mortality, in both 848 undifferentiated patients (Group 1) and in 545 patients definitively diagnosed with sepsis (Group 2). The models reaching the highest negative predictive value (NPV) with the minimum expenditure of biomarkers in Group 1 and in Group 2 were validated in two cohorts of patients initially held out due to missing data.

Results: In terms of the area under the receiver-operating characteristic curve, all six models significantly exceeded qSOFA in predicting prognosis. An "extended" qSOFA (eqSOFA1) in Group 1 and an eqSOFA2 integrated with C-reactive protein and mid-regional proadrenomedullin (eqSOFA2+CRP+MR-proADM) in Group 2 reached the best NPV (0.94 and 0.93, respectively) and ease of use. eqSOFA1 and eqSOFA2+CRP+MR-proADM performed equally well in both the inception and validation cohorts.

Conclusions: We have derived and validated two prognostic models that outweigh qSOFA in predicting mortality and in identifying the low risk of death among patients with suspected or confirmed sepsis at ED admission.
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http://dx.doi.org/10.3390/jcm9041205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230329PMC
April 2020

Biomarkers for prediction of mortality in left-sided infective endocarditis.

Int J Infect Dis 2020 Jul 10;96:25-30. Epub 2020 Mar 10.

Heart Institute (InCor), University of São Paulo Medical School, Brazil.

Background: Evidence regarding biomarkers for risk prediction in patients with infective endocarditis (IE) is limited. We aimed to investigate the value of a panel of biomarkers for the prediction of in-hospital mortality in patients with IE.

Methods: Between 2016 and 2018, consecutive IE patients admitted to the emergency department were prospectively included. Blood concentrations of nine biomarkers were measured at admission (D0) and on the seventh day (D7) of antibiotic therapy: C-reactive protein (CRP), sensitive troponin I (s-cTnI), procalcitonin, B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL6), tumor necrosis factor α (TNF-α), proadrenomedullin, alpha-1-acid glycoprotein, and galectin 3. The primary endpoint was in-hospital mortality.

Results: Among 97 patients, 56% underwent cardiac surgery, and in-hospital mortality was 27%. At admission, six biomarkers were independent predictors of in-hospital mortality: s-cTnI (OR 3.4; 95%CI 1.8-6.4; P<0.001), BNP (OR 2.7; 95%CI 1.4-5.1; P=0.002), IL-6 (OR 2.06; 95%CI 1.3-3.7; P=0.019), procalcitonin (OR 1.9; 95%CI 1.1-3.2; P=0.018), TNF-α (OR 1.8; 95%CI 1.1-2.9; P=0.019), and CRP (OR 1.8; 95%CI 1.0-3.3; P=0.037). At admission, S-cTnI provided the highest accuracy for predicting mortality (area under the ROC curve: s-cTnI 0.812, BNP 0.727, IL-6 0.734, procalcitonin 0.684, TNF-α 0.675, CRP 0.670). After 7 days of antibiotic therapy, BNP and inflammatory biomarkers improved their performance (s-cTnI 0.814, BNP 0.823, IL-6 0.695, procalcitonin 0.802, TNF-α 0.554, CRP 0.759).

Conclusion: S-cTnI concentration measured at admission had the highest accuracy for mortality prediction in patients with IE.
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http://dx.doi.org/10.1016/j.ijid.2020.03.009DOI Listing
July 2020

HDL Subclass Analysis in Predicting Metabolic Syndrome in Koreans With High HDL Cholesterol Levels.

Ann Lab Med 2020 Jul;40(4):297-305

Department of Medical-Surgery Sciences and Translational Medicine, University La Sapienza Rome, Sant'Andrea Hospital, Rome, Italy.

Background: High-density lipoprotein cholesterol (HDL-C) is a complex mixture of subclasses with heterogeneous atheroprotective activities. We analyzed HDL-C subclass in relation to cardiovascular risk and metabolic syndrome (MetS) in a population with high HDL-C levels.

Methods: A total of 300 Korean individuals with high HDL-C levels (≥2.331 mmol/L) were enrolled following a comprehensive general medical examination including body composition analysis. HDL3-C levels were measured using the HDL3-EX SEIKEN kit (Randox Ltd., Crumlin, UK) and non-HDL3-C levels were calculated by subtracting HDL3-C levels from total HDL-C levels.

Results: HDL3-C levels and HDL3-C proportion had a weak positive correlation with low-density lipoprotein cholesterol (LDL-C) and triglycerides (r=0.21, r=0.25; r=0.26, r=0.34, respectively, all <0.001); in contrast, non-HDL3-C levels had a weak negative correlation with these parameters (r=-0.17 and r=-0.25, respectively, both <0.005). HDL3-C levels and HDL3-C proportion were significantly higher in the MetS group (N=8) than in the non-MetS group (0.71 vs 0.63 mmol/L, =0.001; 29.7 vs 25.8%, =0.001, respectively); these were the only predictors of MetS among the lipid variables (areas under the curves [AUC]=0.84 and 0.83, respectively, both =0.001).

Conclusions: In populations with high HDL-C levels, HDL-C subclass may provide a greater amount of information on cardiovascular risk and MetS than HDL-C levels alone.
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http://dx.doi.org/10.3343/alm.2020.40.4.297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054694PMC
July 2020

Cardiovascular health of nonagenarians in southern Italy: a cross-sectional, home-based pilot study of longevity.

J Cardiovasc Med (Hagerstown) 2020 Feb;21(2):89-98

Great Network.

Background: The Cilento region of southern Italy has a high prevalence of nonagenarians and centenarians. Few studies of the oldest old have included echocardiographic and/or electrocardiographic data, in a home-based setting.

Objectives: The objective of this pilot study was to delineate the key lifestyle, medical, echocardiographic, and electrocardiographic features of a sample of nonagenarians and centenarians and their younger cohabitants from Cilento, via a comprehensive, home-based cardiovascular assessment. The ultimate aim is to identify the cardiovascular profile and lifestyle factors associated with longevity.

Methods: Twenty-six nonagenarians and centenarians (mean age 94 ± 3 years) and 48 younger cohabitants aged 50-75 years (mean 62 ± 5) underwent a comprehensive cardiovascular evaluation in their homes.

Results: In contrast to their younger cohabitants, nonagenarians and centenarians did not smoke, had lower fasting glucose levels, and lower LDL cholesterol despite being half as likely to be taking statins, and showing similar adherence to a Mediterranean diet. Over half of nonagenarians and centenarians (15/26) remained autonomous with their activities of daily living. Prevalence of self-reported coronary artery disease and stroke among nonagenarians and centenarians was low (11.5%), though a significant number had atrial fibrillation (31%) or congestive heart failure (27%). Although 62% of nonagenarians and centenarians had at least moderate valvular disease on echocardiography, less than 25% of those affected reported dyspnea.

Conclusion: Nonagenarians and centenarians in the Cilento region had a healthy metabolic profile and a low prevalence of clinical cardiovascular disease. Even among nonagenarians and centenarians with structural heart abnormalities, report of symptoms is low. Larger studies in the Cilento population may help elucidate the mechanisms underlying cardiovascular health in the oldest old.
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http://dx.doi.org/10.2459/JCM.0000000000000910DOI Listing
February 2020

Comparative analysis for the implication of serum cardiac troponin measurements by conventional versus high-sensitivity assays in patients with traumatic brain injury.

Minerva Cardioangiol 2020 Feb 28;68(1):27-33. Epub 2019 Nov 28.

Section of Trauma and Vascular Surgery, Department of Surgery, Hamad General Hospital, Doha, Qatar.

Background: Stress-induced myocardial injury is not well-studied in patients with head injury. We aimed to assess the prognostic implication of positive (+ve) Troponins (Tn) measurements by conventional (cTnT) versus High-Sensitivity (HsTnT) assay in patients with traumatic brain injury (TBI).

Methods: A retrospective analysis was conducted for patients who were admitted with TBI. Patient demographics, clinical presentation, troponin assay results, TBI lesions, and hospital outcomes were analyzed and compared based on troponin assay (cTnT versus HsTnT).

Results: Across the study period, 654 patients with TBI had troponin levels measured within 24 h postinjury (cTnT=252 and HsTnT=402). The mean age was 31 years and 46% had positive troponins. There were 147 deaths (22.5%); of them 54% had +ve HsTnT, 23% had +ve cTnT, 16% had -ve cTnT and 7% had -ve HsTnT). When the troponins were tested ≤4 h postinjury, the mortality was 10.2% in patients with -ve cTnT and 4% in patients with -ve HsTnT. There was no documented obvious direct trauma to the heart. Overall, patients with positive troponins had lower Glasgow Coma Scale (GCS), higher Injury Severity Scores and higher rates of brain edema (P=0.001), pneumonia and sepsis (P=0.001) than those with negative troponin results. In two different models, multivariate regression analysis showed that +ve cTnT and +ve HsTnT were independent predictors of mortality (OR 4.02, 95% CI: 1.72-9.39) and (OR 4.31; 95% CI: 1.76-10.57); respectively, after adjusting for age, injury severity scores, GCS at ED, head AIS, pneumonia, ARDS, surgical interventions, and chest injury.

Conclusions: Although the positivity of any troponin assay is associated with high mortality post-TBI, the use of HsTnT relatively outperforms the conventional troponin assay for early risk stratification and detection of stress-induced myocyte injury in patients with TBI.
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http://dx.doi.org/10.23736/S0026-4725.19.05084-9DOI Listing
February 2020

A new point-of-care test for the rapid detection of urinary tract infections.

Eur J Clin Microbiol Infect Dis 2020 Feb 9;39(2):325-332. Epub 2019 Nov 9.

Science Department, Università degli Studi Roma Tre, Rome, Italy.

Urinary tract infections (UTIs) are among the most common infections in all age groups. Fast and accurate diagnosis is essential to ensure a timely and effective therapy. Alongside with reference culture-based methods, several point-of-care tests (POCTs) for early detection of UTIs have been developed, but they have not been significantly implemented in current clinical practice. The Micro Biological Survey (MBS) POCT is a simple test developed by MBS Diagnostics Ltd. (London, UK) for the detection and management of UTIs. The present study has been undertaken to investigate the potentials and limits of the MBS POCT. A total of 349 patients were enrolled in two open-label, monocentric, non-interventional clinical trials in collaboration with an Emergency Medicine department and the outpatient clinic of two hospitals in Rome. Results of urine analysis using the MBS POCT were compared with those of the routine culture-based tests for UTI diagnosis performed by the hospital laboratory. The MBS POCT provided fast results revealing high bacterial count UTIs (≥ 10 CFU/ml) with 97% accuracy, 92% sensitivity, 100% specificity, 99% PPV, and 96% NPV within a 5-h analytical time threshold.
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http://dx.doi.org/10.1007/s10096-019-03728-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010689PMC
February 2020

Prevalence of Pulmonary Embolism in Patients With Syncope.

J Am Coll Cardiol 2019 08;74(6):744-754

Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland.

Background: The prevalence of pulmonary embolism (PE) in patients presenting with syncope to the emergency department (ED) is largely unknown. This information, however, is necessary to balance the potential medical benefit or harm of systematic PE screening in patients presenting with syncope to the ED.

Objectives: This study sought to determine the prevalence of PE in patients with syncope.

Methods: Unselected patients presenting with syncope to the ED were prospectively enrolled in a diagnostic multicenter study. Pre-test clinical probability for PE was assessed using the 2-level Wells score and the results of D-dimer testing using age-adapted cutoffs. Presence of PE was evaluated by imaging modalities, when ordered as part of the clinical assessment by the treating ED physician or by long-term follow-up data.

Results: Long-term follow-up was complete in 1,380 patients (99%) at 360 days and 1,156 patients (83%) at 720 days. Among 1,397 patients presenting with syncope to the ED, PE was detected at presentation in 19 patients (1.4%; 95% confidence interval [CI]: 0.87% to 2.11%). The incidence of new PEs or cardiovascular death during 2-year follow-up was 0.9% (95% CI: 0.5% to 1.5%). In the subgroup of patients hospitalized (47%), PE was detected at presentation in 15 patients (2.3%; 95% CI: 1.4% to 3.7%). The incidence of new PEs or cardiovascular death during 2-year follow-up was 0.9% (95% CI: 0.4% to 2.0%).

Conclusions: PE seems to be a rather uncommon cause of syncope among patients presenting to the ED. Therefore, systematic PE-screening in all patients with syncope does not seem warranted. (BAsel Syncope EvaLuation Study [BASEL IX]; NCT01548352).
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http://dx.doi.org/10.1016/j.jacc.2019.06.020DOI Listing
August 2019

Bioactive adrenomedullin, proenkephalin A and clinical outcomes in an acute heart failure setting.

Open Heart 2019;6(2):e001048. Epub 2019 Jul 3.

Department of Cardiology, Skånes universitetssjukhus Malmö, Malmoe, Sweden.

Objectives: In an acute heart failure (AHF) setting, proenkephalin A 119-159 (penKid) has emerged as a promising prognostic marker for predicting worsening renal function (WRF), while bioactive adrenomedullin (bio-ADM) has been proposed as a potential marker for congestion. We examined the diagnostic value of bio-ADM in congestion and penKid in WRF and investigated the prognostic value of bio-ADM and penKid regarding mortality, rehospitalisation and length of hospital stay in two separate European AHF cohorts.

Methods: Bio-ADM and penKid were measured in 530 subjects hospitalised for AHF in two cohorts: Swedish HeArt and bRain failure inVESTigation trial (HARVEST-Malmö) (n=322, 30.1% female; mean age 75.1+11.1 years; 12 months follow-up) and Italian GREAT Network Rome study (n=208, 54.8% female; mean age 78.5+9.9 years; no follow-up available).

Results: PenKid was associated with WRF (area under the curve (AUC) 0.65, p<0.001). In multivariable logistic regression analysis of the pooled cohort, penKid showed an independent association with WRF (adjusted OR (aOR) 1.74, p=0.004). Bio-ADM was associated with peripheral oedema (AUC 0.71, p<0.001), which proved to be independent after adjustment (aOR 2.30, p<0.001). PenKid was predictive of in-hospital mortality (OR 2.24, p<0.001). In HARVEST-Malmö, both penKid and bio-ADM were predictive of 1-year mortality (aOR 1.34, p=0.038 and aOR 1.39, p=0.030). Furthermore, bio-ADM was associated with rehospitalisation (aOR 1.25, p=0.007) and length of hospital stay (β=0.702, p=0.005).

Conclusion: In two different European AHF cohorts, bio-ADM and penKid perform as suitable biomarkers for early detection of congestion severity and WRF occurrence, respectively, and are associated with pertinent clinical outcomes.
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http://dx.doi.org/10.1136/openhrt-2019-001048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615850PMC
February 2021

Circulating Biologically Active Adrenomedullin Predicts Organ Failure and Mortality in Sepsis.

Ann Lab Med 2019 Sep;39(5):454-463

Departments of Medical-Surgery Sciences and Translational Medicine, School of Medicine and Psychology, Sapienza - University, Sant' Andrea Hospital, Rome, Italy.

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Biologically active adrenomedullin (bio-ADM) is an emerging biomarker for sepsis. We explored whether bio-ADM concentration could predict severity, organ failure, and 30-day mortality in septic patients.

Methods: In 215 septic patients (109 patients with sepsis; 106 patients with septic shock), bio-ADM concentration was measured at diagnosis of sepsis, using sphingotest bio-ADM (Sphingotec GmbH, Hennigsdorf, Germany) and analyzed in terms of sepsis severity, vasopressor use, and 30-day mortality. The number of organ failures, sequential (sepsis-related) organ failure assessment (SOFA) score, and 30-day mortality were compared according to bio-ADM quartiles.

Results: Bio-ADM concentration was significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (all <0.0001). Bio-ADM quartiles were associated with the number of organ failures (<0.0001), as well as SOFA cardiovascular, renal, coagulation, and liver subscores (all <0.05). The 30-day mortality rate showed a stepwise increase in each bio-ADM quartile (all <0.0001). Bio-ADM concentration and SOFA score equally predicted the 30-day mortality (area under the curve: 0.827 vs 0.830).

Conclusions: Bio-ADM could serve as a useful and objective biomarker to predict severity, organ failure, and 30-day mortality in septic patients.
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http://dx.doi.org/10.3343/alm.2019.39.5.454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502946PMC
September 2019

B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope.

Circulation 2019 Feb 25. Epub 2019 Feb 25.

Cardiovascular Research Institue Basel (CRIB), University Hospital Basel, Switzerland.

Background: The utility of B-type Natriuretic Peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin (hs-cTn) concentrations for diagnosis and risk-stratification of syncope is incompletely understood.

Methods: We evaluated the diagnostic and prognostic accuracy of BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations, alone and against the ones of clinical assessments, in patients >45years presenting with syncope to the emergency department (ED) in a prospective diagnostic multicenter study. BNP, NT-proBNP, hs-cTnT and hs-cTnI concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by two physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic endpoint. The EGSYS, a syncope-specific diagnostic score, served as the diagnostic comparator. Death and MACE at 30 and 720 days were the prognostic endpoints. MACE were defined as death, cardiopulmonary resuscitation, life-threatening arrhythmia, implantation of pacemaker/implantable cardioverter defibrillator, acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack, intracranial bleeding or valvular surgery. The ROSE, OESIL, San Fransisco Syncope Rule (SFSR) and Canadian Syncope Risk Score (CSRS) served as the prognostic comparators.

Results: Among 1538 patients eligible for diagnostic assessment, cardiac syncope was the adjudicated diagnosis in 234 patients (15.2%). BNP, NT-proBNP, hs-cTnT, and hs-cTnI were significantly higher in cardiac syncope vs. other causes (p<0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve (AUC), was 0.77-0.78 (95% confidence interval (CI) 0.74-0.81) for all four biomarkers, and superior to the one of EGSYS (AUC 0.68 [95%-CI 0.65-0.71], p<0.001). Combining BNP/NT-proBNP with hs-cTnT/hs-cTnI further improved diagnostic accuracy to an AUC of 0.81 (p<0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving pre-defined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ~30% of all patients. A total of 450 MACE occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for MACE was moderate-to-good (AUC 0.75-0.79), superior to ROSE, OESIL and SFSR, and inferior to the CSRS.

Conclusions: BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in ED patients with syncope.

Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01548352.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038358DOI Listing
February 2019