Mechanical versus manual cardiopulmonary resuscitation (CPR): an umbrella review of contemporary systematic reviews and more.

BACKGROUND: High-quality cardiopulmonary resuscitation (CPR) can restore spontaneous circulation (ROSC) and neurological function and save lives. We conducted an umbrella review, including previously published systematic reviews (SRs), that compared mechanical and manual CPR; after that, we performed a new SR of the original studies that were not included after the last published SR to provide a panoramic view of the existing evidence on the effectiveness of CPR methods. METHODS: PubMed, EMBASE, and Medline were searched, including English in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) SRs, and comparing mechanical versus manual CPR. A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) and GRADE were used to assess the quality of included SRs/studies. We included both IHCA and OHCA, which compared mechanical and manual CPR. We analyzed at least one of the outcomes of interest, including ROSC, survival to hospital admission, survival to hospital discharge, 30-day survival, and survival to hospital discharge with good neurological function. Furthermore, subgroup analyses were performed for age, gender, initial rhythm, arrest location, and type of CPR devices. RESULTS: We identified 249 potentially relevant records, of which 238 were excluded. Eleven SRs were analyzed in the Umbrella review (January 2014-March 2022). Furthermore, for a new, additional SR, we identified eight eligible studies (not included in any prior SR) for an in-depth analysis between April 1, 2021, and February 15, 2024. The higher chances of using mechanical CPR for male patients were significantly observed in three studies. Two studies showed that younger patients received more mechanical treatment than older patients. However, studies did not comment on the outcomes based on the patient's gender or age. Most SRs and studies were of low to moderate quality. The pooled findings did not show the superiority of mechanical compared to manual CPR except in a few selected subgroups. CONCLUSIONS: Given the significant heterogeneity and methodological limitations of the included studies and SRs, our findings do not provide definitive evidence to support the superiority of mechanical CPR over manual CPR. However, mechanical CPR can serve better where high-quality manual CPR cannot be performed in selected situations.

International Validation of the Canadian Syncope Risk Score : A Cohort Study.

BACKGROUND: The Canadian Syncope Risk Score (CSRS) was developed to predict 30-day serious outcomes not evident during emergency department (ED) evaluation. OBJECTIVE: To externally validate the CSRS and compare it with another validated score, the Osservatorio Epidemiologico della Sincope nel Lazio (OESIL) score. DESIGN: Prospective cohort study. SETTING: Large, international, multicenter study recruiting patients in EDs in 8 countries on 3 continents. PARTICIPANTS: Patients with syncope aged 40 years or older presenting to the ED within 12 hours of syncope. MEASUREMENTS: Composite outcome of serious clinical plus procedural events (primary outcome) and the primary composite outcome excluding procedural interventions (secondary outcome). RESULTS: Among 2283 patients with a mean age of 68 years, the primary composite outcome occurred in 7.2%, and the composite outcome excluding procedural interventions occurred in 3.1% at 30 days. Prognostic performance of the CSRS was good for both 30-day composite outcomes and better compared with the OESIL score (area under the receiver-operating characteristic curve [AUC], 0.85 [95% CI, 0.83 to 0.88] vs. 0.74 [CI, 0.71 to 0.78] and 0.80 [CI, 0.75 to 0.84] vs. 0.69 [CI, 0.64 to 0.75], respectively). Safety of triage, as measured by the frequency of the primary composite outcome in the low-risk group, was higher using the CSRS (19 of 1388 [0.6%]) versus the OESIL score (17 of 1104 [1.5%]). A simplified model including only the clinician classification of syncope (cardiac syncope, vasovagal syncope, or other) variable at ED discharge-a component of the CSRS-achieved similar discrimination as the CSRS (AUC, 0.83 [CI, 0.80 to 0.87] for the primary composite outcome). LIMITATION: Unable to disentangle the influence of other CSRS components on clinician classification of syncope at ED discharge. CONCLUSION: This international external validation of the CSRS showed good performance in identifying patients at low risk for serious outcomes outside of Canada and superior performance compared with the OESIL score. However, clinician classification of syncope at ED discharge seems to explain much of the performance of the CSRS in this study. The clinical utility of the CSRS remains uncertain. PRIMARY FUNDING SOURCE: Swiss National Science Foundation & Swiss Heart Foundation.

Utility of Combining High-Sensitive Cardiac Troponin I and PESI Score for Risk Management in Patients with Pulmonary Embolism in the Emergency Department.

BACKGROUND AND OBJECTIVES: Pulmonary embolism (PE) has a major burden of morbidity and mortality, consequently the need for a prompt risk stratification for these subjects is crucial. In order to evaluate the risk management and final disposition of patients with PE in the Emergency Department (ED), we conducted a study that was divided in two phases: Phase I retrospective study (RS), Phase II prospective study (PS). MATERIALS AND METHODS: In Phase I, 291 patients were enrolled while in Phase II, 83 subjects were evaluated. In both study phases, the enrolled subjects were analyzed for final disposition in ED using PESI score, right ventricle (RV) imaging, and high-sensitive cardiac troponin I (hs-cTnI) data. The RS patients were divided into low risk and high risk according to the sPESI score, while PS patients were grouped in low, intermediate, and high risk classes according to PESI score. In both study phases, all the studied patients were further divided into negative (hs-cTnI-) or positive (hs-cTnI+) groups according to hs-cTnI levels within normal or above cutoff values, respectively. For all enrolled subjects, CT pulmonary angiography was analyzed to assess the RV/LV diameter and volume ratio as an indicator of RV involvement. RESULTS: In both RS and PS phases, hs-cTnI+ group showed a higher PESI score. Nevertheless, a significant percentage of hs-cTnI+ patients resulted to be in the low-risk PESI class. Patients with a positive RV/LV ratio were more likely to have a hs-cTnI+ (p < 0.01), while among those with a negative ratio, 24 to 32% showed as hs-cTnI+. In the hs-cTnI+ group from both study phases, patients were more likely to be admitted in an ICU (RR 3.7, IC: 2.1-6.5). CONCLUSIONS: In conclusion, in patients with PE in the ED compared PESI score alone, the combination of hs-cTnI and PESI seems to be of greater utility in improving risk stratification and final disposition decision-making.

Advantage of Using of High-Sensitivity Troponin I Compared to Conventional Troponin I in Shortening Time to Rule out/in Acute Coronary Syndrome in Chest Pain Patients Presenting to the Emergency Department.

Background and Objectives: We aimed to compare the time to diagnosis for acute coronary syndromes using high-sensitivity troponin I (hsTnI) and conventional troponin I (TnI) in patients presenting to the emergency department (ED) with chest pain. Materials and Methods: This was an observational prospective study involving patients presenting to the ED of Sant'Andrea Hospital University la Sapienza in Rome (Italy) with chest pain from January to December 2014. Serum troponin was drawn at presentation, and at 3, 6, 9, and/or 12 h if clinically indicated. Depending on date of recruitment, patients had either hsTnI (Abbott Laboratories) or TnI (Abbott Laboratories) performed. The primary endpoint was the time to diagnosis at index visit. Results: A total of 1059 patients were recruited, (673 [63.6%] male, median age 60 years [interquartile range 49−73 years]), out of whom 898 (84.8%) patients were evaluated with hsTnI and 161 (15.2%) with TnI. A total of 393 (37.1%) patients had the diagnosis of acute coronary syndrome in ED. The median time to diagnosis for those evaluated with TnI was 400 min, IQR 120−720 min, while the use of hsTnI led to a significantly shorter time to diagnosis (median 200 min, IQR 100−200 min, p < 0.001). Conclusions: This study confirms that in patients presenting to the emergency department with chest pain, the use of hsTnI is associated with a reduced time to ruling in/out ACS, and, consequently, hsTnI should be routinely used over TnI for more rapid identification of ACS with benefits for patients and related costs.

30 Days Mortality Prognostic Value of POCT Bio-Adrenomedullin and Proenkephalin in Patients with Sepsis in the Emergency Department.

Background and Objective: Sepsis is a worldwide severe disease with a high incidence and mortality rate. Sepsis is a frequent cause of admission to the emergency department (ED). Although prognostic scores (Sequential Organ Failure Assessment, SOFA; New Early Warning Score, NEWS; Rapid Emergency Medicine Score, REMS) are commonly used for risk stratification in septic patients, many of these scores are of poor utility in the ED. In this setting, biomarkers are promising alternatives, easier to perform and potentially more specific. Bio-adrenomedullin (Bio-ADM) and Proenkephalin (PenKid) seem to have a key role in the development of organ dysfunctions induced by sepsis and, therefore, could help in the risk stratification of patients with sepsis at ED admission. The aim of this study was to evaluate the utility of Bio-ADM and PenKid, obtained through a point of care (POCT) device, in predicting 30 days mortality for patients presenting to the ED with sepsis. Methods and Results: In total, 177 consecutive adult patients with a diagnosis of sepsis presenting to the ED of San Giovanni Addolorata Hospital in Rome, Italy, between May 2021 and April 2022 were enrolled in this prospective observational study. For each patient, Bio-ADM and PenKid were obtained at ED admission together with SOFA, NEWS and REMS scores. Next, 30 days follow-up data were collected to evaluate patient mortality. Both biomarkers (Bio-ADM and PenKid) and clinical scores (SOFA, NEWS and REMS) were good predictors of mortality at 30 days, with Bio-ADM and REMS outperforming the others. Moreover, PenKid resulted in being linked with the worsening of kidney function. Conclusions: In patients presenting with sepsis in the ED, Bio-ADM and PenKid, evaluated with a POCT device, predicted 30-day mortality. These two biomarkers seem even more useful when integrated with clinical risk scores at ED admission.

Utility of Measuring Circulating Bio-Adrenomedullin and Proenkephalin for 30-Day Mortality Risk Prediction in Patients with COVID-19 and Non-COVID-19 Interstitial Pneumonia in the Emergency Department.

Background and Objectives: In order to accelerate the risk stratification of patients referred to the Emergency Department (ED) with interstitial pneumonia, it could be useful to provide new and effective laboratory tests for use. The aim of our study was to evaluate the prognostic role of two biomarkers, bio-adrenomedullin (Bio-ADM) and proenkephalin (penKid), in patients with interstitial pneumonia (IP) at ED admission. Materials and Methods: In 153 consecutive patients with IP, both from COVID-19 or non-COVID-19 etiology, we measured, in a prospective observational manner, penKid and Bio-ADM at ED admission and after 24 h. In order to evaluate patient outcomes, 30-day follow-ups were also performed. The endpoints were 24 h, 10-day, and 30-day mortality. Results: Both biomarkers were shown to be good predictors of adverse events at 30 days, with Bio-ADM outperforming penKid. Bio-ADM was linked with 24 h and 10-day patient mortality. Moreover, PenKid was related to parameters defining worsening kidney function. Conclusions: Both in patients with COVID-19 or non-COVID-19 interstitial pneumonia at ED admission, Bio-ADM and penKid were good predictors of patient mortality. To evaluate these two biomarkers could be considered to be useful during the first evaluation in the ED when integrated with clinical scores.

Usefulness of High-Sensitivity Troponin I in Risk Stratification and Final Disposition of Patients with Acute Heart Failure in the Emergency Department: Comparison between HFpEF vs. HFrEF.

Background and Objectives: In patients with acute heart failure (AHF), there is no definite evidence on the relationship between high-sensitivity cardiac troponin (hs-cTnI) and the left ventricular ejection fraction (LVEF) comparing the reduced and preserved EF conditions. Materials and Methods: Between January and April 2022, we retrospectively analyzed the data from 386 patients admitted to the emergency departments (ED) of five hospitals in Rome, Italy, for AHF. The criteria for inclusion were a final diagnosis of AHF; a cardiac ultrasound and hs-cTnI evaluations in the ED; and age > 18 yrs. We excluded patients with acute coronary syndrome (ACS). Based on echocardiography and hs-cTnI evaluations, the patients were grouped for (1) preserved (HFpEF) or (2) reduced LVEF (HFrEF) and a a) negative (within the normal range value) or b) positive (above the normal range value) of hs-cTnI, respectively. Results: There was a significant negative relationship between a positive test for hs-cTnI and LVEF. When compared to the group with a negative hs-cTnI test, the patients with a positive test, both from the HFpEF and HFrEF subgroups, were significantly more likely to have an adverse outcome, such as being admitted to the intensive care unit (ICU) or dying in the ED. Moreover, a reduced ejection fraction was linked with a final disposition to a higher level of care. Conclusions: In patients admitted to the ED for AHF without ACS, there is a negative relationship between hs-cTnI and a reduced LVEF, although a significant percentage of patients with a preserved LVEF also resulted to have high levels of hs-cTnI. In the absence of ACS, hs-cTnI seems to be a reliable biomarker of myocardial injury in AHF in the ED and should be considered as a risk stratification parameter for these subjects regardless of the left ventricular function. Further larger prospective studies are needed to confirm these preliminary data.

Is There a Risk of Misinterpretation of Potassium Concentration from Undetectable Hemolysis Using a POCT Blood Gas Analyzer in the Emergency Department?

Background and Objectives: Hemolysis is reported to be present in up to 10% of blood gas specimens in the central lab; however, few data on the incidence of hemolysis using a point-of-care testing (POCT) blood gas analysis are available in the setting of the emergency department. The aims of this study were: (1) to analyze the prevalence of hemolysis in blood gas samples collected in the ED using a POCT device; and (2) to evaluate the impact of hemolysis on blood sample results and its clinical consequences. Materials and Methods: We collected 525 consecutive POCT arterial blood gas samples using syringes with electrolyte-balanced heparin within 3 different EDs in the metropolitan area of Rome. Immediately after the collection, the blood samples were checked for the presence of hemolysis with a POCT instrument (i.e., HEMCHECK, H-10 ®). The samples were then subsequently processed for blood gasses, and an electrolytes analysis by a second operator blinded for the hemolysis results. A venous blood sample was simultaneously collected, analyzed for it's potassium value, and used as a reference. Results: Of the samples, 472 were considered for the statistics, while 53 were excluded due to the high percentage of hemolysis due to operator fault in carrying out the measurement. The final mean hemolysis per operator was 12% (±13% SD), and the total final hemolysis was 14.4%.Potassium (K+) was significantly higher in the hemolyzed group compared with the non-hemolyzed sample (4.60 ± 0.11 vs. 3.99 ± 0.03 mEq/L; p < 0.001), and there were differences between arterial potassium versus venous potassium (D(a-v) K+, 0.29 ± 0.06 vs.−0.19 ± 0.02 mEq/L, p < 0.01). A Bland−Altman analysis confirmed that hemolysis significantly overestimated blood potassium level. Conclusion: Almost 12% of POCT blood gas analysis samples performed in the ED could be hemolyzed, and the presence of this hemolysis is not routinely detected. This could cause an error in the interpretation of the results, leading to the consideration of potassium concentrations being below the lower limit within the normal limits and also leading to the diagnosis of false hyperkalemia, which would have potential clinical consequences in therapeutic decision-making in the ED. The routine use of a POCT hemolysis detector could help prevent any misdiagnoses.

Usefulness of Combining NT-proBNP Level and Right Atrial Diameter for Simple and Early Noninvasive Detection of Pulmonary Hypertension Among Adult Patients with Atrial Septal Defect.

BACKGROUND: Atrial septal defect developed pulmonary hypertension (ASD-PH) at first diagnosis due to late presentation are common in Indonesia. Transthoracic echocardiogram (TTE) is a common tool to detect ASD-PH, before proceeding to invasive procedure. The NT-proBNP measurement to screen ASD-PH is not yet considered the standard approach, especially in limited resource conditions. The objective of this study is to assess the value of NT-proBNP, along with simple TTE parameter, to screen PH among adults with ASD. METHODS: This was a cross-sectional study. The subjects were adult ASD-PH patients from the COHARD-PH  registry (n=357). Right heart catheterization (RHC) was performed to diagnose PH. Blood sample was withdrawn during RHC for NT-proBNP measurement. The TTE was performed as standard procedure and its regular parameters were assessed, along with NT-proBNP, to detect PH. RESULTS: Two parameters significantly predicted PH, namely NT-proBNP and right atrial (RA) diameter. The cut-off of NT-proBNP to detect PH was ≥140 pg/mL. The cut-off of RA diameter to detect PH was ≥46.0 mm. The combined values of NT-proBNP level ≥140 pg/mL and RA diameter ≥46.0 mm yielded 46.6% sensitivity, 91.8% specificity, 54.3% accuracy, 96.5% positive predictive value and 26.2% negative predictive value to detect PH, which were better than single value. CONCLUSION: NT-proBNP level ≥140 pg/mL represented PH in adult ASD patients. The NT-proBNP level ≥140 pg/mL and RA diameter ≥46.0 mm had a pre-test probability measures to triage patients needing more invasive procedure and also to determine when and if to start the PH-specific treatment.

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

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.

Study of loneliness and wisdom in 482 middle-aged and oldest-old adults: a comparison between people in Cilento, Italy and San Diego, 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 (N = 212 and 47, respectively) and San Diego, California, USA (N = 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.

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

BACKGROUND: The utility of BNP (B-type natriuretic peptide), NT-proBNP (N-terminal proBNP), and hs-cTn (high-sensitivity cardiac troponin) 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 those of clinical assessments, in patients >45-years old presenting with syncope to the emergency department 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 2 physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic end point. EGSYS (Evaluation of Guidelines in Syncope Study), a syncope-specific diagnostic score, served as the diagnostic comparator. Death and major adverse cardiac events at 30 and 720 days were the prognostic end points. Major adverse cardiac events 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. ROSE (Risk Stratification of Syncope in the Emergency Department), OESIL (Osservatorio Epidemiologico della Sincope nel Lazio), SFSR (San Fransisco Syncope Rule), and CSRS (Canadian Syncope Risk Score) 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 versus other causes (P<0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve, was 0.77 to 0.78 (95% CI, 0.74-0.81) for all 4 biomarkers, and superior to EGSYS (area under the curve, 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 area under the curve of 0.81 (P<0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving predefined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ≈30% of all patients. A total of 450 major adverse cardiac events occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for major adverse cardiac events was moderate-to-good (area under the curve, 0.75-0.79), superior to ROSE, OESIL, and SFSR, and inferior to CSRS. CONCLUSIONS: BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in emergency department patients with syncope. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT01548352.

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.

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.

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

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 (≥ 105 CFU/ml) with 97% accuracy, 92% sensitivity, 100% specificity, 99% PPV, and 96% NPV within a 5-h analytical time threshold.

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

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).

Circadian, weekly, seasonal, and temperature-dependent patterns of syncope aetiology in patients at increased risk of cardiac syncope.

AIMS: It is unknown whether cardiac syncope, and possibly also other syncope aetiologies exhibit circadian, weekly, seasonal, and temperature-dependent patterns. METHODS AND RESULTS: We prospectively recorded the exact time, date, and outside temperature of syncope of patients >40 years old presenting with syncope to the emergency department in a diagnostic multicentre study. Two independent cardiologists/emergency physicians adjudicated the final diagnosis based on all information becoming available during clinical work-up including 1-year follow-up. Among 1230 patients, the adjudicated aetiology was cardiac in 14.6%, reflex in 39.2%, orthostatic in 25.7%, other non-cardiac in 9.7%, and unknown in 10.8% of patients. All syncope aetiologies occurred much more frequently during the day when compared with the night (P < 0.01). While reflex and orthostatic syncope showed a broad peak of prevalence with 80.9% of these events occurring between 4 am and 4 pm, cardiac syncope showed a narrow peak of prevalence with 70.1% of all events occurring between 8 am and 2 pm. A weekly pattern was present for most syncope aetiologies, with events occurring mainly from Monday to Friday (P < 0.01). Reflex syncope displayed a seasonal rhythm and was more common in winter (P < 0.01), while cardiac syncope stayed constant over the year. Syncope occurred most often when the outside temperature was coldest. Overall the patterns observed for cardiac syncope were similar to the patterns observed for its differential diagnosis. CONCLUSION: Syncope aetiologies in patients >40 years old display circadian, weekly, seasonal, and temperature-dependent patterns. Unfortunately, these patterns do not allow to reliably differentiate cardiac syncope from other aetiologies.

Derivation and Validation of a Biomarker-Based Clinical Algorithm to Rule Out Sepsis From Noninfectious Systemic Inflammatory Response Syndrome at Emergency Department Admission: A Multicenter Prospective Study.

OBJECTIVES: To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. DESIGN: Multicenter prospective study. SETTING: At emergency department admission in five University hospitals. PATIENTS: Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholipase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholipase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. CONCLUSIONS: We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome.

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study.

BACKGROUND: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. METHODS: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. RESULTS: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). CONCLUSIONS: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02393781 . Registered on March 19, 2015.

Mixed-methods quantitative-qualitative study of 29 nonagenarians and centenarians in rural Southern Italy: focus on positive psychological traits.

OBJECTIVE: This was a study of positive psychological traits in a group of rural Italians aged 90 to 101 years, and their children or other family members. DESIGN: Mixed-methods quantitative (standardized rating scales) and qualitative (semi-structured interviews) study. SETTING: Study participants' homes in nine villages in the Cilento region of southern Italy. PARTICIPANTS: Twenty-nine nonagenarians and centenarians and 51 family members aged 51-75 years, selected by their general practitioners as a part of a larger study called CIAO (Cilento Initiative on Aging Outcomes). METHODS: We used published rating scales of mental and physical well-being, resilience, optimism, anxiety, depression, and perceived stress. Qualitative interviews gathered personal narratives of the oldest-old individuals, including migrations, traumatic events, and beliefs. Family members described their impressions about the personality traits of their older relative. RESULTS: Participants age ≥90 years had worse physical health but better mental well-being than their younger family members. Mental well-being correlated negatively with levels of depression and anxiety in both the groups. The main themes that emerged from qualitative interviews included positivity (resilience and optimism), working hard, and bond with family and religion, as described in previously published studies of the oldest old, but also a need for control and love of the land, which appeared to be unique features of this rural population. CONCLUSIONS: Exceptional longevity was characterized by a balance between acceptance of and grit to overcome adversities along with a positive attitude and close ties to family, religion, and land, providing purpose in life.

Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality.

BACKGROUND: Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. METHODS: The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. RESULTS: Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan. CONCLUSION: Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.