Oral enteral nutrition in the emergency department for children with bronchiolitis hospitalized on high flow nasal cannula.

OBJECTIVES: We assessed whether initiation of oral enteral nutrition in the emergency department (ED) for patients with bronchiolitis hospitalized on humidified high flow nasal cannula (HHFNC) was associated with a shorter hospital length of stay (LOS) without an increase in return ED visits or hospital readmissions. PATIENTS AND METHODS: This retrospective cohort study included children ≤24 months of age with bronchiolitis hospitalized to the general pediatric floor on HHFNC in two time periods: October 1, 2018 - April 30, 2019, and following implementation of a revised institutional bronchiolitis pathway that encouraged enteral nutrition initiation in the ED, October 1, 2021 - April 30, 2022. The primary outcome of interest was hospital LOS where the exposure was enteral feeding in the ED. RESULTS: We included 391 'fed', 114 'not fed' and 304 'unknown' patients. HHFNC treatment time (25 h for 'fed' vs. 43 h for 'not fed' vs. 35 h for'unknown', p = 0.0001) and hospital LOS (39 h for 'fed' vs. 56 h for 'not fed' vs. 48 h for 'unknown', p = 0.0001) was shorter in the 'fed' group. There were no significant differences in return ED visits or hospital readmissions. Using our median LOS (45.1 h, inter-quartile range 30.2, 64.4 h) while controlling for age, sex, initial HHFNC flow rate, the respiratory oxygenation (ROX) index, viral etiology, and time period, an adjusted logistic regression analysis demonstrated that patients fed in the ED were 1.8 times more likely to have a hospital LOS of <45 h (aOR 1.88, 95% CI 1.11-3.18, p = 0.019). CONCLUSIONS: Initiation of oral enteral nutrition in the ED for patients with bronchiolitis on HHFNC is associated with a shorter hospital LOS without an increase in return ED visits or hospital readmissions. Future prospective studies are needed to develop feeding recommendations for children with bronchiolitis receiving HHFNC support.

Collagenase treatment reduces the anisotropy of ultrasonic backscatter in rat myocardium by reducing collagen crosslinks.

Dysregulation of collagen deposition, degradation, and crosslinking in the heart occur in response to increased physiological stress. Collagen content has been associated with ultrasonic backscatter (brightness), and we have shown that the anisotropy of backscatter can be used to measure myofiber alignment, that is, variation in the brightness of a left ventricular short-axis ultrasound. This study investigated collagen's role in anisotropy of ultrasonic backscatter; female Sprague-Dawley rat hearts were treated with a collagenase-containing solution, for either 10 or 30 min, or control solution for 30 min. Serial ultrasound images were acquired at 2.5-min intervals throughout collagenase treatment. Ultrasonic backscatter was assessed from anterior and posterior walls, where collagen fibrils are predominately aligned perpendicular to the angle of insonification, and the lateral and septal walls, where collagen is predominately aligned parallel to the angle of insonification. Collagenase digestion reduced backscatter anisotropy within the myocardium. Collagen remains present in the myocardium throughout collagenase treatment, but crosslinking is altered within 10 min. These data suggest that crosslinking of collagen modulates the anisotropy of ultrasonic backscatter. An Anisotropy Index, derived from differences in backscatter from parallel and perpendicularly aligned fibers, may provide a noninvasive index to monitor the progression and state of myocardial fibrosis.

Acute pyelonephritis in pregnancy and plasma syndecan-1: evidence of glycocalyx involvement.

BACKGROUND: Acute pyelonephritis, a risk factor for maternal sepsis, adult respiratory distress syndrome, and preterm labor, is a frequent cause of hospitalization. This condition is characterized by excessive intravascular inflammation and endothelial cell activation and dysfunction. Syndecan-1, a major component of the glycocalyx, is a gel-like layer that covers the luminal surface of healthy endothelial cells, preserving and mediating many endothelial functions. During pregnancy, there is an additional potential source of syndecan-1, the "syncytiotrophoblast glycocalyx," which lines the intervillous space. Insults that damage the glycocalyx lead to a shedding of syndecan-1 into the circulation. Hence, syndecan-1 has been proposed as a marker of endothelial injury in conditions such as sepsis, trauma, cardiovascular disease, and diabetes mellitus. OBJECTIVE: The objective of this study was to determine whether the plasma syndecan-1 concentration changes in women with acute pyelonephritis in the presence or absence of bacteremia. STUDY DESIGN: This cross-sectional study included three groups: (1) non-pregnant women (n = 25); (2) women with an uncomplicated pregnancy from whom samples were collected preterm (n = 61) or at term (n = 69); and (3) pregnant women diagnosed with acute pyelonephritis from whom samples were collected at the time of diagnosis during the second and third trimesters (n = 33). The diagnosis of acute pyelonephritis was based on clinical findings and a positive urine culture for bacteria. Blood culture results were available in 85% (28/33) of women with acute pyelonephritis. Plasma concentrations of syndecan-1 were determined by a validated immunoassay. RESULTS: (1) Women with an uncomplicated pregnancy had a higher plasma concentration of syndecan-1 than non-pregnant women. The geometric mean (95% confidence interval [CI]) of syndecan-1 concentration was 51.0 (12.1-216.1) ng/mL in non-pregnant controls; 1280 (365-4487) ng/mL in normal preterm gestations; and 1786 (546-5834) ng/mL in normal term gestations (adjusted p < .005 for all three between group comparisons); (2) plasma syndecan-1 concentrations increased with gestational age among women with a normal pregnancy (p < .001, R2 = 0.27); (3) syndecan-1 multiple of the mean (MoM) values in pregnant patients with acute pyelonephritis were higher than those in normal pregnant women based on second- and third-trimester samples (p = .048, 1.26-fold change). The increase was driven primarily by cases with a positive blood culture (p = .009, 1.74-fold change); (4) when data from third-trimester samples were compared, overall differences in syndecan-1 MoM values between cases and controls were slightly larger (p = .03, 1.36- fold change), which were especially contributed to by cases with a positive blood culture (p = .023, fold change 1.79-fold change). CONCLUSIONS: Plasma syndecan-1 concentration is higher in pregnant women and increases as a function of gestational age. Patients with acute pyelonephritis have a higher plasma concentration of syndecan-1, and this is particularly the case in the presence of bacteremia.

Association between respiratory rate oxygenation index and need for positive pressure ventilation in children on high flow nasal cannula for bronchiolitis.

Our objective was to evaluate the association of respiratory rate oxygenation index (ROX) with the need for positive pressure ventilation in children < 2 years of age with bronchiolitis on high flow nasal cannula (HFNC) therapy. We performed a single-center prospective observational study of a convenience sample of children < 2 years of age with bronchiolitis who had HFNC initiated in the pediatric emergency department between November and March, 2018-2020. ROX was calculated as pulse oximetry/FiO2/respiratory rate at HFNC initiation. Demographics, need for positive pressure ventilation (PPV), disposition, and hospital length of stay were collected. Logistic regression model was used to determine the odds ratio for PPV need relative to the highest ROX quartile. Of the 373 patients included, 49 (13.1%) required PPV. ROX was lower in patients who required PPV compared with those who did not (5.86 [4.71-7.42] vs. 6.74 [5.46-8.25]; p = 0.01). Logistic regression revealed that those patients whose ROX was in the lowest quartile (< 5.39) were three times more likely to require PPV compared to those in the highest quartile (> 8.21). These results held true after adjusting for confounders (odds ratio 3.1; 95% CI [1.3 to 7.5]; p = 0.02). The model's AUROC (0.701) indicated acceptable discrimination between cases and controls. CONCLUSION: Low ROX index was associated with the need for PPV in children with bronchiolitis on HFNC. The risk stratification provided and ROX threshold for risk stratification require confirmation in other populations with a larger sample size. WHAT IS KNOWN: • Demographic and clinical factors associated with high flow nasal cannula (HFNC) therapy in children with bronchiolitis has been studied. WHAT IS NEW: • This is the first study to  report the utility of association of Respiratory Rate Oxygenation (ROX) index for need for positive pressure ventilation (PPV) in children < 2 years of age with bronchiolitis on HFNC therapy. • ROX was lower in children who required PPV and children whose ROX was in the lowest quartile (< 5.39) were three times more likely to require PPV compared to those in the highest quartile (> 8.21).

Pain Management Program in Cardiology: A Template for Application of Normalization Process Theory and Social Marketing to Implement a Change in Practice Quality Improvement.

Quality improvement plays a major role in healthcare, and numerous approaches have been developed to implement changes. However, the reasons for success or failure of the methods applied often remains obscure. Normalization process theory, recently developed in sociology, provides a flexible framework upon which to construct quality improvement. We sought to determine if examination of a successful quality improvement project, using normalization process theory and social marketing, provided insight into implementation. We performed a retrospective analysis of the steps taken to implement a pain management program in an electrophysiology clinic. We mapped these steps, and the corresponding social marketing tools used, to elements of normalization process theory. The combination of mapping implementation steps and marketing approaches to the theory provided insight into the quality-improvement process. Specifically, examination of the steps in the context of normalization process theory highlighted barriers to implementation at individual, group, and organizational levels. Importantly, the mapping also highlighted how facilitators were able to overcome the barriers with marketing techniques. Furthermore, integration with social marketing revealed how promotion of tangibility of benefits aided communication and how process co-creation between stakeholders enhanced value. Our implementation of a pain-management program was successful in a challenging environment composed of several stakeholder groups with entrenched initial positions. Therefore, we propose that the behavior change elements of normalization process theory combined with social marketing provide a flexible framework to initiate quality improvement.

Gender-specific associations between coronary heart disease and other chronic diseases: cross-sectional evaluation of national survey data from adult residents of Germany.

BACKGROUND: Combinations of coronary heart disease (CHD) and other chronic conditions complicate clinical management and increase healthcare costs. The aim of this study was to evaluate gender-specific relationships between CHD and other comorbidities. METHODS: We analyzed data from the German Health Interview and Examination Survey (DEGS1), a national survey of 8152 adults aged 18-79 years. Female and male participants with self-reported CHD were compared for 23 chronic medical conditions. Regression models were applied to determine potential associations between CHD and these 23 conditions. RESULTS: The prevalence of CHD was 9% (547 participants): 34% (185) were female CHD participants and 66% (362) male. In women, CHD was associated with hypertension (OR = 3.28 (1.81-5.9)), lipid disorders (OR = 2.40 (1.50-3.83)), diabetes mellitus (OR = 2.08 (1.24-3.50)), kidney disease (OR = 2.66 (1.101-6.99)), thyroid disease (OR = 1.81 (1.18-2.79)), gout/high uric acid levels (OR = 2.08 (1.22-3.56)) and osteoporosis (OR = 1.69 (1.01-2.84)). In men, CHD patients were more likely to have hypertension (OR = 2.80 (1.94-4.04)), diabetes mellitus (OR = 1.87 (1.29-2.71)), lipid disorder (OR = 1.82 (1.34-2.47)), and chronic kidney disease (OR = 3.28 (1.81-5.9)). CONCLUSION: Our analysis revealed two sets of chronic conditions associated with CHD. The first set occurred in both women and men, and comprised known risk factors: hypertension, lipid disorders, kidney disease, and diabetes mellitus. The second set appeared unique to women: thyroid disease, osteoporosis, and gout/high uric acid. Identification of shared and unique gender-related associations between CHD and other conditions provides potential to tailor screening, preventive, and therapeutic options.

Deep sedation for transvenous lead extraction: a large single-centre experience.

AIMS: Transvenous lead extraction for cardiac implantable electronic devices (CIED) is of growing importance. Nevertheless, the optimal anaesthetic approach, general anaesthesia vs. deep sedation (DS), remains unresolved. We describe our tertiary centre experience of the feasibility and safety of DS. METHODS AND RESULTS: Extraction procedures were performed in the electrophysiology (EP) laboratory by two experienced electrophysiologists. We used intravenous Fentanyl, Midazolam, and Propofol for DS. A stepwise approach with locking stylets, dilator sheaths, and mechanical sheaths via subclavian, femoral, or internal jugular venous access was utilized. Patient characteristics and procedural data were collected. Logistic regression models were used to identify parameters associated with sedation-related complications. Extraction of 476 leads (dwelling time/patient 88 ± 49 months, 30% ICD leads) was performed in 220 patients (64 ± 17 years, 80% male). Deep sedation was initiated with bolus administration of Fentanyl, Midazolam, and Propofol; mean doses 0.34 ± 0.12 µg/kg, 24.3 ± 6.8 µg/kg, and 0.26 ± 0.13 mg/kg, respectively. Deep sedation was maintained with continuous Propofol infusion (initial dose 3.7 ± 1.1 mg/kg/h; subsequently increased to 4.7 ± 1.2 mg/kg/h with 3.9 ± 2.6 adjustments) and boluses of Midazolam and Fentanyl as indicated. Sedation-related episodes of hypotension, requiring vasopressors, and hypoxia, requiring additional airway management, occurred in 25 (11.4%) and 5 (2.3%) patients, respectively. These were managed without adverse consequences. Five patients (2.3%) experienced major intraprocedural complications; there were no procedure-related deaths. All of our logistic regression models indicated intraprocedural support was associated with administration higher Fentanyl doses. CONCLUSION: Transvenous lead extraction under DS in the EP laboratory is a safe procedure with high success rates when performed by experienced staff.

Sodium Nitrite-Mediated Cardioprotection in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Cost-Effectiveness Analysis.

OBJECTIVES: In the follow-up of patients in a trial of intracoronary sodium nitrite given during primary percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI), we found a reduction in the incidence of major adverse cardiac events (MACEs). Specifically, MACE rates were 5.2% versus 25.0% with placebo at 3 years ( P = .013). Such MACE reductions should also be associated with economic benefit. Thus, we assessed the cost utility of sodium nitrite therapy versus standard primary PCI only. METHODS AND RESULTS: We developed a model to simulate costs and quality-adjusted life years (QALYs) over the first 36 months after ST-Segment Elevation Myocardial Infarction (STEMI). Decision tree analysis was used to assess different potential cardiovascular outcomes after STEMI for patients in both treatment groups. Model inputs were derived from the NITRITE-AMI study. Cost of comparative treatments and follow-up in relation to cardiovascular events was calculated from the United Kingdom National Health Service perspective. Higher procedural costs for nitrite treatment were offset by lower costs for repeat revascularization, myocardial infarction, and hospitalization for heart failure compared to primary PCI plus placebo. Nitrite treatment was associated with higher utility values (0.91 ± 0.19 vs 0.82 ± 0.30, P = .041). The calculated incremental cost-effectiveness ratio of £2177 per QALY indicates a cost-effective strategy. Furthermore, positive results were maintained when input parameters varied, indicating the robustness of our model. In fact, based on the difference in utility values, the cost of nitrite could increase by 4-fold (£2006 per vial) and remain cost-effective. CONCLUSION: This first analysis of sodium nitrite as a cardioprotective treatment demonstrates cost-effectiveness. Although more comparative analysis and assessment of longer follow-up times are required, our data indicate the considerable potential of nitrite-mediated cardioprotection.

Remote ischemic preconditioning fails to reduce infarct size in the Zucker fatty rat model of type-2 diabetes: role of defective humoral communication.

Remote ischemic preconditioning (RIPC), the phenomenon whereby brief ischemic episodes in distant tissues or organs render the heart resistant to infarction, has been exhaustively demonstrated in preclinical models. Moreover, emerging evidence suggests that exosomes play a requisite role in conveying the cardioprotective signal from remote tissue to the myocardium. However, in cohorts displaying clinically common comorbidities-in particular, type-2 diabetes-the infarct-sparing effect of RIPC may be confounded for as-yet unknown reasons. To investigate this issue, we used an integrated in vivo and in vitro approach to establish whether: (1) the efficacy of RIPC is maintained in the Zucker fatty rat model of type-2 diabetes, (2) the humoral transfer of cardioprotective triggers initiated by RIPC are transported via exosomes, and (3) diabetes is associated with alterations in exosome-mediated communication. We report that a standard RIPC stimulus (four 5-min episodes of hindlimb ischemia) reduced infarct size in normoglycemic Zucker lean rats, but failed to confer protection in diabetic Zucker fatty animals. Moreover, we provide novel evidence, via transfer of serum and serum fractions obtained following RIPC and applied to HL-1 cardiomyocytes subjected to hypoxia-reoxygenation, that diabetes was accompanied by impaired humoral communication of cardioprotective signals. Specifically, our data revealed that serum and exosome-rich serum fractions collected from normoglycemic rats attenuated hypoxia-reoxygenation-induced HL-1 cell death, while, in contrast, exosome-rich samples from Zucker fatty rats did not evoke protection in the HL-1 cell model. Finally, and unexpectedly, we found that exosome-depleted serum from Zucker fatty rats was cytotoxic and exacerbated hypoxia-reoxygenation-induced cardiomyocyte death.

Colchicine for primary prevention of atrial fibrillation after open-heart surgery: Systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation occurs frequently after open-heart surgery. It is associated with increased morbidity and mortality, longer hospital stays, and increased healthcare costs. Prophylactic administration of colchicine may mitigate post-operative atrial fibrillation (POAF). METHODS: We searched PubMed, ClinicalTrials.gov and CENTRAL databases to identify randomized controlled trials (RCTs) that; (1) compared prophylactic use of colchicine to placebo, or usual care, in patients with sinus rhythm who underwent elective open-heart surgery and (2) reported POAF-incidence. We excluded trials focused on incidence of atrial fibrillation after percutaneous interventions or colchicine treatment of diagnosed pericarditis or post-pericardiotomy-syndrome. A random-effects model was used to pool data for POAF-incidence as the primary outcome and for drug-related adverse effects, major adverse events (death and stroke), and hospital length-of-stay as secondary outcomes. RESULTS: We included five RCTs (1412 patients). Colchicine treatment reduced POAF-events by 30% versus placebo or usual care (18% vs. 27%, risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.84, p=0.0002). Adverse drug-related effects, especially gastrointestinal intolerance, increased with colchicine; (21% vs. 8.2%, RR 2.52, 95% CI 1.62 to 3.93, p<0.0001). However, major adverse events were unchanged (3.2% vs. 3.2%, RR 0.96, 95% CI 0.48 to 1.95, p=0.92). Length-of-stay decreased by 1.2days with colchicine (95% CI -1.89 to -0.44, p=0.002). CONCLUSION: Colchicine demonstrated superior efficacy versus usual care for prevention of atrial fibrillation after cardiac surgery. Moreover, colchicine treatment was associated with shorter hospital stays. These benefits outweigh increased risk of adverse drug-related effects; although further work is needed to minimize gastrointestinal effects.

Ischemic Conditioning Attenuates Platelet-Mediated Thrombosis: A Tale of Reverse Translation.

Data obtained in both preclinical models and humans have revealed that the favorable cardiac consequences of ischemic conditioning extend beyond a direct effect on the cardiomyocyte. In the current review, we summarize our as-yet limited understanding of the complex relationships between ischemic conditioning, platelet activation-aggregation, and cardioprotection.

Biomarker-based diagnosis of pacemaker and implantable cardioverter defibrillator pocket infections: A prospective, multicentre, case-control evaluation.

BACKGROUND: The use of cardiac implantable electronic devices (CIED) has risen steadily, yet the rate of cardiac device infections (CDI) has disproportionately increased. Amongst all cardiac device infections, the pocket infection is the most challenging diagnosis. Therefore, we aimed to improve diagnosis of such pocket infection by identifying relevant biomarkers. METHODS: We enrolled 25 consecutive patients with invasively and microbiologically confirmed pocket infection. None of the patients had any confounding conditions. Pre-operative levels of 14 biomarkers were compared in infected and control (n = 50) patients. Our selected biomarkers included white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), lipopolysaccharide binding protein, high-sensitivity C-reactive protein (HS-CRP), polymorphonuclear-elastase, presepsin, various interleukins, tumor necrosis factor α (TNF-α), and granulocyte macrophage colony-stimulating factor (GM-CSF). RESULTS: Of the 25 patients with isolated pocket infection (70±13years, 76% male, 40% ICDs), none presented with leukocytosis. In contrast, they had higher serum levels of HS-CRP (p = 0.019) and PCT (p = 0.010) than control patients. Median PCT-level was 0.06 ng/mL (IQR 0.03-0.07 ng/mL) in the study group versus 0.03 ng/mL (IQR 0.02-0.04 ng/mL) in controls. An optimized PCT cut-off value of 0.05 ng/mL suggests pocket infection with a sensitivity of 60% and specificity of 82%. In addition TNF-α- and GM-CSF-levels were lower in the study group. Other biomarkers did not differ between groups. CONCLUSION: Diagnosis of isolated pocket infections requires clinical awareness, physical examination, evaluation of blood cultures and echocardiography assessment. Nevertheless, measurement of PCT- and HS-CRP-levels can aid diagnosis. However, no conclusion can be drawn from normal WBC-values. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01619267.

Calcium Administration Is Associated with Adverse Outcomes in Critically Ill Patients Receiving Parenteral Nutrition: Results from a Natural Experiment Created by a Calcium Gluconate Shortage.

STUDY OBJECTIVE: Parenteral calcium is frequently administered to critically ill patients. However, animal studies demonstrate that calcium administration during critical illness heightens inflammation and leads to shock, organ dysfunction, and mortality. We sought to evaluate the association between calcium administration and adverse outcomes in critically ill patients receiving parenteral nutrition (PN). DESIGN: Retrospective cohort examined before and during a calcium gluconate shortage. During the shortage, calcium was absent from PN, but calcium supplementation outside of PN was allowed. The shortage resulted in a natural experiment that included a group of patients who did not receive calcium. SETTING: Intensive care units (ICUs) in three teaching hospitals. PATIENTS: A total of 259 adults who received PN in the ICU for 48 hours or longer. MEASUREMENTS AND MAIN RESULTS: Patients were divided into quartiles based on amount of parenteral calcium received; the lowest quartile received no calcium. End points were in-hospital mortality, acute respiratory failure, new-onset shock, and a composite of any one of these end points. For patients not on mechanical ventilation or vasoactive support when PN started, logistic regression revealed that calcium administration was associated with mortality (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.08-5.69), acute respiratory failure (OR 2.43, 95% CI 1.28-4.60), new-onset shock (OR 2.81, 95% CI 1.22-6.44), and the combined end point (OR 2.33, 95% CI 1.31-4.16). The odds of adverse outcomes increased as the calcium dose increased. CONCLUSION: Calcium administration correlated with adverse outcomes in critically ill patients receiving PN. The data suggest that administration of parenteral calcium to critically ill patients may be harmful.

Remote ischemic conditioning and renal function after contrast-enhanced CT scan: A randomized trial.

PURPOSE: Remote ischemic conditioning has been shown to protect against kidney injury in animal and human studies of ischemia-reperfusion. Recent evidence suggests that conditioning may also provide protection against kidney injury caused by contrast medium. The purpose of this study was to determine if conditioning protected against increases in serum creatinine (SCr) after contrast-enhanced computed tomography (CECT). METHODS: A randomised controlled trial (NCT 01741896) was performed with institutional review board approval and informed patient consent. Adult in-patients undergoing abdomino-pelvic CECT were allocated to conditioned or control groups. Conditioning consisted of four cycles of five minutes of cuff-induced arm ischemia with three minutes of reperfusion applied ~40 minutes before CECT. The primary outcome was SCr change after CECT. RESULTS: Baseline characteristics were similar in both groups. For all patients, conditioning reduced the risk ratio (RR) of increased SCr; RR 0.65 (95% confidence intervals 0.41 to 1.04). The protective effect was greater and the evidence for protection stronger when analysis was restricted to patients with pre-scan reduced renal function (eGFR.

Point-of-care assessment of platelet reactivity in the emergency department may facilitate rapid rule-out of acute coronary syndromes: a prospective cohort pilot feasibility study.

OBJECTIVE: Accurate, efficient and cost-effective disposition of patients presenting to emergency departments (EDs) with symptoms suggestive of acute coronary syndromes (ACS) is a growing priority. Platelet activation is an early feature in the pathogenesis of ACS; thus, we sought to obtain an insight into whether point-of-care testing of platelet function: (1) may assist in the rule-out of ACS; (2) may provide additional predictive value in identifying patients with non-cardiac symptoms versus ACS-positive patients and (3) is logistically feasible in the ED. DESIGN: Prospective cohort feasibility study. SETTING: Two urban tertiary care sites, one located in the USA and the second in Argentina. PARTICIPANTS: 509 adult patients presenting with symptoms of ACS. MAIN OUTCOME MEASURES: Platelet reactivity was quantified using the Platelet Function Analyzer-100, with closure time (seconds required for blood, aspirated under high shear, to occlude a 150 µm aperture) serving as the primary endpoint. Closure times were categorised as 'normal' or 'prolonged', defined objectively as the 90th centile of the distribution for all participants enrolled in the study. Diagnosis of ACS was made using the standard criteria. The use of antiplatelet agents was not an exclusion criterion. RESULTS: Closure times for the study population ranged from 47 to 300 s, with a 90th centile value of 138 s. The proportion of patients with closure times ≥138 s was significantly higher in patients with non-cardiac symptoms (41/330; 12.4%) versus the ACS-positive cohort (2/105 (1.9%); p=0.0006). The specificity of 'prolonged' closure times (≥138 s) for a diagnosis of non-cardiac symptoms was 98.1%, with a positive predictive value of 95.4%. Multivariate analysis revealed that the closure time provided incremental, independent predictive value in the rule-out of ACS. CONCLUSIONS: Point-of-care assessment of platelet reactivity is feasible in the ED and may facilitate the rapid rule-out of ACS in patients with prolonged closure times.

From ischemic conditioning to 'hyperconditioning': clinical phenomenon and basic science opportunity.

Thousands of articles have been published on the topic of ischemic conditioning. Nevertheless, relatively little attention has been given to assessment of conditioning's dose-response characteristics. Specifically, the consequences of multiple conditioning episodes, what we will term "hyperconditioning", have seldom been examined. We propose that hyperconditioning warrants investigation because it; (1) may be of clinical importance, (2) could provide insight into conditioning mechanisms, and (3) might result in development of novel models of human disease. The prevalence of angina pectoris and intermittent claudication is sufficiently high and the potential for daily ischemia-reperfusion episodes sufficiently large that hyperconditioning is a clinically relevant phenomenon. In basic science, attenuation of conditioning-mediated infarct size reduction found in some studies after hyperconditioning offers a possible means to facilitate further discernment of cardioprotective signaling pathways. Moreover, hyperconditioning's impact extends beyond cytoprotection to tissue structural elements. Several studies demonstrate that hyperconditioning produces collagen injury (primarily fiber breakage). Such structural impairment could have adverse clinical consequences; however, in laboratory studies, selective collagen damage could provide the basis for models of cardiac rupture and dilated cardiomyopathy. Accordingly, we propose that hyperconditioning represents the dark, but potentially illuminating, side of ischemic conditioning - a paradigm that merits attention and prospective evaluation.

Venous thromboembolism in an industrial north american city: temporal distribution and association with particulate matter air pollution.

BACKGROUND: Emerging evidence, mainly from Europe and Asia, indicates that venous thromboembolism (VTE) occurs most often in winter. Factors implicated in such seasonality are low temperature-mediated exacerbation of coagulation and high levels of particulate matter (PM) air pollution. However, in contrast to most European and Asian cities, particulate matter pollution peaks in the summer in many North American cities. OBJECTIVES: We aimed to exploit this geographical difference and examine the temporal distribution of VTE in a cold-weather, North American city, Detroit, with a summer PM peak. Our goal was thereby to resolve the influence of temperature and PM levels on VTE. METHODS: Our retrospective, analytical semi-ecological study used chart review to confirm 1,907 acute, ambulatory VTE cases, divided them by location (Detroit versus suburban), and plotted monthly VTE frequency distributions. We used Environmental Protection Agency data to determine the temporal distribution of PM pollution components in Detroit. Suburban PM air pollution is presumed negligible and therefore not monitored. RESULTS: Acute VTE cases in Detroit (1,490) exhibited a summer peak (June 24(th)) and differed from both a uniform distribution (P<0.01) and also that of 1,123 no-VTE cases (P<0.02). Levels of 10 µm diameter PM and coarse particle (2.5 to 10 µm) PM also exhibited summer peaks versus a winter peak for 2.5 µm diameter PM. Contrary to their urban counterparts, suburban cases of acute VTE (417) showed no monthly variation. CONCLUSIONS: The summer peak of acute VTE in Detroit indicates that low temperature is not a major factor in VTE pathogenesis. In contrast, concordance of the 10 µm diameter PM, coarse particle, and the Detroit VTE monthly distributions, combined with no monthly suburban VTE variation, is consistent with a role for PM pollution. Furthermore, divergence of the VTE and 2.5 µm PM distributions suggests that particle size may play a role.