Human Neutrophil α-Defensins 1-3 Are Upregulated in the Microenvironment of Fibrotic Liver.

Background and Objectives: Neutrophil infiltration is an established signature of Non-Alcoholic Fatty Liver Disease (NAFLD) and Steatohepatitis (NASH). The most abundant neutrophilic peptide, alpha-defensin, is considered a new evolving risk factor in the inflammatory milieu, intimately involved in lipid mobilization. Our objective is to assess for potential association between alpha-defensin immunostains and NAFLD severity. Materials and Methods: We retrospectively investigated the liver biopsies of NAFLD/NASH patients, obtained at Hillel Yaffe Medical center between the years 2012 and 2016. Patients' characteristics were recorded, including relevant blood tests at the time of biopsy. Each biopsy was semi-quantitatively scored using NAFLD Activity Score (NAS) and NASH fibrosis stage. The biopsies were immunostained for alpha-defensin. The precipitation of alpha-defensin was correlated to NAS and fibrosis. Results: A total of 80 biopsies were evaluated: male ratio 53.2%, mean age 44.9 ± 13.2 years, 54 had fibrosis grades 0-2, and 26 were grade 3-4. Conventional metabolic risk factors were more frequent in the high-grade fibrosis group. Immunostaining for alpha-defensin disclosed higher intensity (a.u.) in grade 3-4 fibrosis relative to grades 0-2, 25% vs. 6.5%, p < 0.05, respectively. Moreover, alpha-defensin staining was nicely co-localized with fibrosis. Conclusions: In our group of NASH/NAFLD patients, higher metabolic risk profile was associated with higher fibrosis grade. Immunostaining for alpha-defensin showed patchy intense staining concordant with high fibrosis, nicely co-localized with histological fibrosis. Whether alpha-defensin is a profibrotic risk factor or merely risk marker for fibrosis must be clarified in future studies.

[DIRECT ADMISSION OF STEMI PATIENTS TO THE CARDIAC CARE UNIT VERSUS ADMISSION VIA THE EMERGENCY DEPARTMENT FOR PRIMARY CORONARY INTERVENTION IMPROVES SHORT AND LONG-TERM SURVIVAL].

INTRODUCTION: Shortening door-to-balloon time intervals in ST-elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI) is necessary in order to limit myocardial damage. Direct admission to the cardiac care unit (CCU) facilitates this goal. We compared characteristics and short- and long-term mortality of PPCI-treated STEMI patients admitted directly to the CCU with those admitted via the emergency department (ED). METHODS: To compare 303 patients admitted directly to the CCU (42%) with 427 admitted via the ED (58%) included in the current registry comprising 730 consecutive PPCI-treated STEMI patients. RESULTS: Groups were similar regarding demographics, medical history and risk factors. Pain-to-CCU time was 151±164 minutes (median-94) for patients admitted directly and 242±226 minutes (160) for those admitted via the ED, while door-to-balloon intervals were 69±42 minutes (61) and 133±102 minutes (111), respectively. LVEF evaluated during admission (48.3±13% [47.5%] vs. 47.7±13.7% [47.5%]) and mean CK level (893±1157 [527] vs. 891±1255 [507], p=0.45) were similar between groups. Mortality was 4.2% vs. 10.3% at 30-days (p<0.002), 7.6% and 14.3% at one-year (p<0.01), reaching 12.2% and 21.9% at 3.9±2.3 years (median-3.5, p<0.004) among directly-admitted patients vs. those admitted via the ED, respectively. Long-term mortality was 4.1%, 9.4%, 21.4%, and 16% for pain-to-balloon quartiles of <140 min, 141-207 min, 208-330 min, and >330 mins, respectively (p=0.026). CONCLUSIONS: Direct admission of STEMI patients to the CCU for PPCI facilitated the attainment of guidelines-dictated door-to-balloon time intervals and yielded improved short- and long-term mortality. Longer pain-to-balloon time was associated with higher long-term mortality.

Repeat Coronary Angiography in Patients Aged over 50 Years with Previously Normal/Non-Obstructive Coronary Angiogram-Insights from a Retrospective Study.

(1) Introduction: A significant proportion of patients undergoing coronary angiography (CAG) have normal (NCA) or non-obstructive coronary artery disease (NOCAD). This study retrospectively tested the incidence of re-catheterization, and long-term outcomes of this population in patients aged over 50 years. (2) Methods: We identified all patients above 50 years of age with NOCAD who underwent their first CAG at our center between January 2008 and December 2019. Patients were evaluated for their baseline characteristics, risk factors profile, and indication for CAG. Patients undergoing repeat CAG after the index procedure were assessed for the above, including the primary preventive pharmacotherapy prescribed. (3) Results: A total of 1939 patients were reported to have NOCAD. Of these, 1756 (90%) patients (62% males, median age 66 (56-75) years) had no repeat angiography (group 1). Repeat angiography was performed in 10%: 136 (7%) proved futile (median time for repeat angiography 5 (3-8) years) (group 3), and 47 (3%) ended with angioplasty (median time for repeat angiography 4 (3-6) years) (group 2). Male gender, BMI above 30 (23% vs. 13%), hypertension (68% vs. 57%), diabetes (28% vs. 17%) and smoking (36% vs. 19%) were significantly higher in the interventional group. Regression analysis showed both paroxysmal atrial fibrillation and hyperlipidemia were significantly associated with repeat CAG. The indication for the first CAG was mainly symptoms related. In the interventional repeat angiography (n = 47) the incidence of troponin positive cases increased from 8.2% before intervention to 57.5%, 50% being ST elevation cases. The symptoms-related cases went from 36.7% to 18.4%. Intriguingly, 85% of the interventional group were not prescribed statin and/or aspirin on a regular basis, and/or did not adhere to treatment. (4) Conclusions: NOCAD is a frequent occurrence. The threshold for repeat angiography must be higher, better reserved to troponin positive cases. Moreover, patients must be handled according to their risk profile, not being mistakenly reassured by a snapshot benign coronary angiography.

The Diagnostic Value of Human Neutrophilic Peptides 1-3 in Acute Pediatric Febrile Illness.

Background: It is prudent to develop biomarkers that enhance the differentiation between viral and bacterial infection in order to support expeditious and judicious antimicrobial implementation in emergency department admissions. Human neutrophilic peptides 1-3 (HNP1-3) are the major neutrophilic peptides with potent antimicrobial activity. Methods: We tested the performance of the plasma HNP1-3 test in a prospective observational cohort of children admitted to the emergency department for fever. We validated this test with traditionally used biomarkers and final diagnoses. An expert panel reviewed the patient's data and gave a final diagnosis. The final diagnosis was classified as definite, probable, or possible. Results: A total of 111 children (98 with fever and 13 control) were recruited: 55% male, mean age 6.3 years. Plasma HNP1-3 levels were higher with bacterial infections: 10,428 (5789-14,866) vs. 7352 (3762-10,672) pg/mL, p = 0.007. HNP1-3 were negatively correlated with age: r = -0.207, p = 0.029. Of the different categorical variables tested, only c-reactive protein (CRP) (≥42.3 mg/dL), neutrophil count (≥10.2), and age (odds ratio = 1.185, p = 0.013 and 95%CI = 1.037-1.354) had significant diagnostic capability for bacterial disease prediction. Conclusions: Due to its low diagnostic value in febrile patients, the HNP1-3 value is not currently recommended to support pathogen differentiation in children in an emergency setting. Further studies are needed to support its clinical use.

Remote Surgical Discussion of Multivessel Coronary Artery Disease Patients without Surgery on Site-Retrospective Insights.

OBJECTIVE: The heart team approach is highly advocated for in treatment decision making in patients with multivessel disease (MVD). Nevertheless, many centers lack on-site cardiac surgical services (CSS)/formal heart team. Our local alternative is of remote surgical consultation without a structured image sharing platform. In our understanding, the incidence of anatomical complete revascularization (ACR) under this daily practice, and its clinical impact, has not been discussed before. METHODS: We analyzed 477 consecutive patients who were surgically revascularized between January 2009 and March 2018 for MVD, after remote surgical consultation. Unstable, late arrival, and ST elevation patients were excluded (n = 163). ACR was considered grafting all anatomic lesions > 50%. Syntax score (SS) calculation and ACR categorization were determined by an independent interventionalist using diagnostic angiograms and available operative reports (n = 267). Patients' outcomes were assessed in relation to multiple clinical variables including troponin result and the revascularization status. RESULTS: Three hundred and fourteen patients were included. Mean age was 64 years, and mean SS-II was 27.3 ± 11. At the 4-year follow-up, the observed mortality (11.8% and 12.9%, with troponin-positive and -negative groups, respectively), myocardial infarction (11.8%), and repeat revascularization (9.8%) were higher than those predicted using a nomogram depicting the predicted 4-year mortality as a function of the SYNTAX II Score (5.3%, 8.8%, and 3.5%, respectively, p = 0.02). ACR was reported in 33% of 267 available patients' reports. After multivariate adjustment ACR was the only variable associated with a significant increase in 4-year mortality (12.3% vs. 6.7%, p < 0.05). CONCLUSIONS: Partial revascularization in the absence of on-site CSS and a structured heart team platform is a frequent occurrence. Not surprisingly, this occurrence was associated with a higher risk for mid-term mortality. An upfront, structured, virtual, heart team interface is mandatory to particularly prioritize the completeness of revascularization when considering the optimal revascularization mode.

Morphine Use in ST-Elevation Myocardial Infarction With Downstream P2Y12 Receptor Blockers-Insight From Observational Study.

BACKGROUND AND AIMS: Morphine use for patients presenting with NSTE-ACS is associated with excess mortality. However, the role of morphine in STE-ACS is ill characterized. We have recently confirmed direct prothrombotic effect of morphine using murine models. We sought to explore whether morphine use in STE-ACS patients, used to be scheduled for downstream P2Y12 blockers, is negatively associated with procedural and clinical outcomes. METHODS: A single-center, observational retrospective analysis enrolling 130 non-randomized stable patients sustaining STE-ACS as their first manifestation of coronary disease, who presented between December 2010 and June 2013. All were managed by early invasive approach. Of study patients, 55 were treated by morphine, and 75 were not. All were administered downstream P2Y12 blockers according to an already abandoned local policy. Outcomes evaluated included TIMI grade flow, thrombus burden, ST-segment resolution, myocardial function by echocardiography, and cardiovascular death. RESULTS: Morphine administration was associated with a significantly higher incidence of impaired final TIMI grade flow (TIMI < 3, 40% vs 4%, P < .05), lower incidence of ST-segment resolution >70% (40.7% vs 76.5%, P < .05), and a higher incidence of moderate or severe systolic dysfunction (48.1% vs 29.1%, P < .05) compared with morphine naive patients. Interestingly, the overall mortality rate was higher in the morphine-treated group (18% vs 5.3%, P < .05). CONCLUSIONS AND RELEVANCE: Morphine administration combined with the downstream P2Y12 blockers practice signify a group with a higher occurrence of impaired myocardial reperfusion and cardiovascular death despite established on-time primary angioplasty.

Impact of the Admission Pathway on the Gender-Related Mortality of Patients With ST-Elevation Myocardial Infarction.

The mortality of women with ST-elevation myocardial infarction (STEMI) exceeds that of men, supposedly the result of older age and co-morbidities. Patients with STEMI can be transported directly to the catherization lab by the emergency medical service (EMS) or to the emergency department (ED) by the EMS, a regular ambulance, or independently. This raises the question whether gender disparity in the transport of patients with STEMI may affect time to therapy and consequently explain the disparate outcome in men and women with STEMI. We analyzed a large nationwide registry of prospectively-recorded patients with acute coronary syndromes in order to determine if there is a survival gap between men and women with STEMI, and to assess the gender-related effect of admission pathway on time intervals and 5-year mortality. Study population included 2,740 patients with STEMI who underwent primary percutaneous coronary interventions, comprising 464 women (17%, median-70 years) and 2,276 men (83%, median-58 years). The unadjusted 5-year mortality of women was higher compared with men (26.4% vs 15.6%, p = 0.001) but adjustment abrogated this survival difference. Regardless of adjustment, the 5-year mortality of patients with STEMI admitted directly to the catherization lab or to the ED by EMS was similar for men and women but significantly lower in the directly admitted patients (p <0.028). In contrast, admission to the ED by non-EMS was associated with markedly worse survival among women. These results indicate that women suspected of STEMI benefit from transportation by the EMS and should use this pathway exclusively to reach the hospital.

Prognosis of Patients With Left Circumflex Artery Acute Myocardial Infarction in Relation to ST-Segment on Admission Electrocardiogram.

BACKGROUND: Total thrombotic occlusion of the left circumflex (LCX) artery may present without ST-segment elevations; the clinical outcomes of such patients remain unclear. OBJECTIVE: To examine the difference in clinical outcomes between patients with acute myocardial infarction (MI) due to LCX occlusion or stenosis with and without ST-segment elevation. METHODS: The present study is based on an observational, retrospective cohort comprising all patients admitted to 2 centers between 2009 and 2019 with MI due to LCX disease. Clinical outcomes included recurrent percutaneous coronary intervention (PCI), hospitalization due to acute coronary syndrome (ACS), and mortality. Risk factors for mortality were assessed using logistic regression analysis. RESULTS: During the study period, a total of 897 patients with LCX-related MI were treated. Most (56.6%) presented with non-ST segment elevation MI (NSTEMI), which was associated with higher rates of 1-year hospitalization for ACS (15.8% vs 11.1%; P=.05) and PCI (20.9% vs 14.4%; P=.05) compared with ST-segment elevation MI (STEMI) patients. STEMI was associated with higher 30-day mortality compared with NSTEMI (3.9% vs 1.7%, respectively; P=.05), with no difference in mortality after 1 year (6.7% vs 5.6%, respectively; P=.55). Multivariate analysis found left dominant circulation (odds ratio [OR], 2.62; 95% confidence interval [CI], 1.4-4.7) and diabetes mellitus (OR, 2.13; 95% CI, 1.2-3.6) to be independent predictors for 1-year mortality. CONCLUSION: Patients suffering from NSTEMI and STEMI related to LCX occlusion or stenosis have similar 1-year mortality. Left dominant circulation was associated with higher short- and long-term mortality. These results suggest that a substantial population of patients who present as NSTEMI should be treated as promptly and aggressively as STEMI patients.

Differentiation between myopericarditis and acute myocardial infarction on presentation in the emergency department using the admission C-reactive protein to troponin ratio.

BACKGROUND: The treatment of myopericarditis is different than that of acute myocardial infarction (AMI). However, since their clinical presentation is frequently similar it may be difficult to distinguish between these entities despite a disparate underlying pathogenesis. Myopericarditis is primarily an inflammatory disease associated with high C-reactive protein (CRP) and relatively low elevated troponin concentrations, while AMI is characterized by the opposite. We hypothesized that evaluation of the CRP/troponin ratio on presentation to the emergency department could improve the differentiation between these two related clinical entities whose therapy is different. Such differentiation should facilitate triage to appropriate and expeditious therapy. METHODS: We evaluated the CRP/troponin ratio on presentation among patients consecutively included in a large single center registry that included 1898 consecutive patients comprising 1025 ST-elevation myocardial infarction (STEMI) patients, 518 Non-STEMI (NSTEMI) patients, and 355 patients diagnosed on discharge as myopericarditis. CRP and troponin were sampled on admission in all patients and their ratio was assessed against discharge diagnosis. ROC analysis of the CRP/troponin ratios evaluated the diagnostic accuracy of myopericarditis against all AMI, STEMI, and NSTEMI patients. RESULTS: Median admission CRP/troponin ratios were 84, 65, and 436 mg×ml/liter×ng in STEMI, NSTEMI and myopericarditis groups, respectively (p<0.001) demonstrating good differentiating capability. The Receiver-operator-curve of admission CRP/troponin ratio for diagnosis of myopericarditis against all AMI, STEMI, and NSTEMI patients yielded an area-under-the curve of 0.74, 0.73, and 0.765, respectively. CRP/troponin ratio>500 resulted in specificity exceeding 85%, and for a ratio>1000, specificity>92%. CONCLUSION: The CRP/troponin ratio can serve as an effective tool to differentiate between myopericarditis and AMI. In the appropriate clinical context, the CRP/troponin ratio may preclude further evaluation.

Acute diagonal-induced ST-elevation myocardial infarction and electrocardiogram-guidance in the era of primary coronary intervention: New insights into an old tool.

BACKGROUND: Previous studies, published before the advent of primary reperfusion, described the electrocardiographic features of ST-segment elevation myocardial infarction (STEMI) caused by total diagonal artery occlusion, as demonstrated at pre-discharge coronary angiography. We aimed to assess the electrocardiographic and echocardiographic features in STEMI unequivocally attributed to a diagonal lesion in the era of primary coronary intervention. METHODS: The electrocardiograms and echocardiograms of patients sustaining STEMI caused by diagonal artery involvement were compared with those of patients with STEMI attributed to proximal or mid left anterior descending artery (LAD) lesions. ST-segment deviations were measured at four different points in each lead and analyzed against TIMI flow and SNuH score. The electrocardiographic and echocardiographic features of each group were mapped. RESULTS: In contrast to previous studies claiming an ever-present incidence of at least 1-mm ST-segment elevation in leads I and aVL with diagonal STEMI, we report 86% of any ST-elevation in leads I, aVL and V2 (64-71% for ST-elevation >1 mm). Both higher SNuH score and pre-intervention TIMI flow were associated with larger lateral ST-elevations (85.7% and 86.4-95.5%, respectively). Higher prevalence of ST-depression in the inferior leads reflecting reciprocal changes was observed in patients with diagonal-induced STEMI (57-76% vs. 24-51% in LAD obstructions, p <0.05). CONCLUSION: The most sensitive and predictive sign for acute ischemia was any degree of ST-deviation measured 1 mm beyond the J point. ST-elevations in I, aVL and V2, sparing V3-V5, strongly favor isolated diagonal lesion. Proximal LAD lesion lacking ST-segment elevations in leads I and aVL is primarily due to wraparound LAD anatomy.

Optimal Timing for Coronary Intervention in Patients With Transient ST-Elevation Myocardial Infarction.

STEMI patients admitted urgently to the hospital but experience early complete resolution of both ischemic symptoms and ST-elevations on the electrocardiogram are diagnosed as transient STEMI (TSTEMI). Current evidence indicates that primary intervention is plausible but in certain circumstances intervention can be delayed. We sought to examine whether there is a time limit to such a delay that may affect long-term outcome. Study population included prospectively admitted TSTEMI patients whose demographics, pertinent medical history, and clinical and angiographic features were recorded. Study patients were divided by the median time interval from admission to intervention and their characteristics and long-term survival were compared. Study population comprised 260 consecutive patients (age: 57±10 years, men: 84%) diagnosed as TSTEMI who were included from January 2000 to June 2019, which represent 6% of all STEMI patients. Coronary angiography was performed in 254 patients. The median time interval from admission to angiography was 17 hours (IQR: 7.2 to 38.7 hours). Early (<17 hours from admission) and late (>17 hours from admission) study groups were comparable. One patient died during admission and 41 throughout the long follow-up period of 8.5 ± 5.2 years (median: 8.2 years, IQR: 3.4 to 13.1). Mortality of early-treated TSTEMI patients (11.2%) was significantly lower than of the late-treated patients (21.6%, p <0.04). The Kaplan-Meier curve demonstrated a clear tendency toward improved survival in early-treated TSTEMI patients (p <0.09). In conclusion, the present data suggest that TSTEMI patients should be treated, if not by primary coronary intervention, then at least within 17 hours from admission to achieve better long-term outcome.

Characteristics, Management, and Outcome of Transient ST-elevation Versus Persistent ST-elevation and Non-ST-elevation Myocardial Infarction.

Patients with acute myocardial infarctions (AMIs) present as persistent ST-elevation myocardial infarction (STEMI) or as non-ST-segment elevation myocardial infarction (NSTEMI). In some patients with STEMI, ST elevations are transient and resolve before coronary intervention (transient ST-elevation myocardial infarction [TSTEMI]). We analyzed our registry comprising all consecutive patients with AMI admitted during 2009 to 2014, and compared the characteristics, management, and outcome of patients with TSTEMI with those of patients with STEMI and NSTEMI. Of 1,847 patients with AMI included in the registry, 1,073 patients sustained a STEMI (58%), 649 had a NSTEMI (35%), and 126 presented with TSTEMI (6.9%). Patients with TSTEMI were younger than patients with NSTEMI and STEMI (56.5 vs 62.8, p <0.001, and 59.5 years, p <0.02, respectively), smoked more (77.8 vs 54.0, p <0.001, and 62.1%, p <0.0005), and fewer were hypertensive (52.4 vs 74.2% and 58.8%, both p <0.001) and diabetic (26.2% vs 47.7%, p <0.0001, and 36.9%, p <0.02). The extent of coronary artery disease in patients with TSTEMI was similar to that of patients with STEMI except for less involvement of the left anterior descending artery (p <0.001), but less extensive than in NSTEMI patients. TSTEMI involved less myocardial damage by troponin-T level (p <0.005) with better cardiac function (LVEF 61% vs 55% and 49%, both p <0.0001). Mortality was lower among TSTEMI both in-hospital (0 vs 2.3% [p = NS] and 4.2% [p <0.01]) and long-term (4.8% vs 14.7% and 14.2%, both p <0.003) at a median of 36 months. In conclusion, TSTEMI is an acute coronary syndrome distinct from NSTEMI and STEMI, characterized by fewer risk factors, a similar extent of coronary artery disease to STEMI, but is associated with less myocardial damage and portends a better outcome.