Deletion of Talin1 in Myeloid Cells Facilitates Atherosclerosis in Mice.

BACKGROUND: Integrin-regulated monocyte recruitment and cellular responses of monocyte-derived macrophages are critical for the pathogenesis of atherosclerosis. In the canonical model, talin1 controls ligand binding to integrins, a prerequisite for integrins to mediate leukocyte recruitment and induce immune responses. However, the role of talin1 in the development of atherosclerosis has not been studied. Our study investigated how talin1 in myeloid cells regulates the progression of atherosclerosis. METHODS: On an Apoe-/- background, myeloid talin1-deficient mice and the control mice were fed with a high-fat diet for 8 or 12 weeks to induce atherosclerosis. The atherosclerosis development in the aorta and monocyte recruitment into atherosclerotic lesions were analyzed. RESULTS: Myeloid talin1 deletion facilitated the formation of atherosclerotic lesions and macrophage deposition in lesions. Talin1 deletion abolished integrin ß2-mediated adhesion of monocytes but did not impair integrin α4ß1-dependent cell adhesion in a flow adhesion assay. Strikingly, talin1 deletion did not prevent Mn2+- or chemokine-induced activation of integrin α4ß1 to the high-affinity state for ligands. In an in vivo competitive homing assay, monocyte infiltration into inflamed tissues was prohibited by antibodies to integrin α4ß1 but was not affected by talin1 deletion or antibodies to integrin ß2. Furthermore, quantitative polymerase chain reaction and ELISA analysis showed that macrophages produced cytokines to promote inflammation and the proliferation of smooth muscle cells. Ligand binding to integrin ß3 inhibited cytokine generation in macrophages, although talin1 deletion abolished the negative effects of integrin ß3. CONCLUSIONS: Integrin α4ß1 controls monocyte recruitment during atherosclerosis. Talin1 is dispensable for integrin α4ß1 activation to the high-affinity state and integrin α4ß1-mediated monocyte recruitment. Yet, talin1 is required for integrin ß3 to inhibit the production of inflammatory cytokines in macrophages. Thus, intact monocyte recruitment and elevated inflammatory responses cause enhanced atherosclerosis in talin1-deficient mice. Our study provides novel insights into the roles of myeloid talin1 and integrins in the progression of atherosclerosis.

Heightened activation of embryonic megakaryocytes causes aneurysms in the developing brain of mice lacking podoplanin.

During early embryonic development in mammals, including humans and mice, megakaryocytes (Mks) first originate from primitive hematopoiesis in the yolk sac. These embryonic Mks (eMks) circulate in the vasculature with unclear function. Herein, we report that podoplanin (PDPN), the ligand of C-type lectin-like receptor (CLEC-2) on Mks/platelets, is temporarily expressed in neural tissue during midgestation in mice. Loss of PDPN or CLEC-2 resulted in aneurysms and spontaneous hemorrhage, specifically in the lower diencephalon during midgestation. Surprisingly, more eMks/platelets had enhanced granule release and localized to the lower diencephalon in mutant mouse embryos than in wild-type littermates before hemorrhage. We found that PDPN counteracted the collagen-1-induced secretion of angiopoietin-1 from fetal Mks, which coincided with enhanced TIE-2 activation in aneurysm-like sprouts of PDPN-deficient embryos. Blocking platelet activation prevented the PDPN-deficient embryo from developing vascular defects. Our data reveal a new role for PDPN in regulating eMk function during midgestation.

Mechanical thrombectomy versus catheter directed thrombolysis in patients with pulmonary embolism: A multicenter experience.

OBJECTIVES: Compare in-hospital outcomes of patients treated with either mechanical thrombectomy (MT) or catheter directed lysis (CDL) in treatment of acute pulmonary embolism (PE). METHODS: This is a multicenter, retrospective cohort study of patients undergoing MT or CDL for acute PE between 2014 and 2021. The primary outcome was the composite of in-hospital death, significant bleed, vascular complication, or need for mechanical support post-procedure. Secondary outcomes included the individual components of the composite outcome in addition to blood transfusions, invasive hemodynamics, echocardiographic data, and intensive care unit (ICU) utilization. RESULTS: 458 patients were treated for PE with 266 patients in the CDL arm and 192 patients in the MT arm. The primary composite endpoint was not significantly different between the two groups with CDL 12% versus MT 11% (p = 0.5). There was a significant difference in total length of ICU time required with more in the CDL group versus MT (3.8 ± 2.0 vs. 2.8 ± 3.0 days, p = 0.009). All other secondary end points showed no significant difference between the groups. CONCLUSIONS: In patients undergoing catheter directed treatment of PE, there was no difference between MT and CDL in terms of in-hospital mortality, bleeds, catheter-related complications, and hemodynamics.

A single healthcare experience with Impella RP.

OBJECTIVES: To understand the predictors of survival and indications for Impella RP in a single healthcare experience. BACKGROUND: The Impella RP can be used to temporarily support patients with right ventricular (RV) dysfunction after left ventricular assist device (LVAD) placement or myocardial infarction (MI). However, recent postmarket approval data have raised concerns of higher than expected mortality with this device. METHODS: A retrospective chart review and analysis of all patients that underwent Impella RP placement in the Emory Healthcare system between January 2016 and December 2018 were performed. Patients were classified according to the indication. RESULTS: A total of 39 patients underwent Impella RP placement. Six patients were post-LVAD, 9 were implanted for massive pulmonary embolism with persistent shock, 8 for postcardiac surgery RV failure (non-LVAD), 11 for RV failure post-MI, and 5 for new or worsening nonischemic cardiomyopathy. The worst survival was noted in MI-related cardiogenic shock group and in patients who presented with cardiac arrest (3/12). All observed deaths were due to persistent refractory shock. There was no device related death. Survival improved during the last year of experience compared to the first 2 years. CONCLUSION: This study supports the selective use of the Impella RP, with a higher than national reported survival rate (49% vs. 28.6%). Indication appears to be an important factor determining survival.

Functional coronary angiography in symptomatic patients with no obstructive coronary artery disease.

BACKGROUND: Patients without obstructive coronary artery disease (CAD) may have epicardial or microvascular dysfunction. The purpose of this study was to characterize patterns of epicardial and microvascular dysfunction in men and women with stable and unstable angina undergoing functional coronary angiography to inform medical therapy. METHODS: 163 symptomatic patients with ≤50% diameter stenosis and fractional flow reserve (FFR) > 0.8 underwent endothelium-dependent epicardial and microvascular function after intracoronary acetylcholine (10-4  M, 81 mcg over 3 minutes). Endothelium-independent function was assessed using coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) after intravenous adenosine (140 ug/kg/min). Coronary microvascular dysfunction (CMD) was defined as CFR < 2.5, HMR ≥2, or ≤50% change in coronary blood flow with acetylcholine (CBFACH ). RESULTS: Seventy-two percent had endothelial-dependent epicardial dysfunction (response to ACH: % ∆ in coronary artery diameter and ∆%CBFACH ) and 92% had CMD. Among CMD patients, 65% had CFR < 2.5, 35% had HMR ≥2, and 60% had CBFACH change ≤50%. CFR modestly correlated with HMR (r = -0.38, p < .0001). Among patients with normal CFR, 26% had abnormal epicardial and 20% had abnormal microvascular endothelial dysfunction. Women had a lower CFR (p = .02), higher FFR (p = .03) compared to men. There were no differences in epicardial and microvascular function between patients with stable and unstable angina. CONCLUSION: In patients with no obstructive CAD: CMD is prevalent, abnormal CFR does not correlate with epicardial or microvascular endothelial dysfunction, women have lower CFR, higher FFR but similar endothelial function compared to men.

Timing of peripubertal steroid exposure predicts visuospatial cognition in men: Evidence from three samples.

Experiments in male rodents demonstrate that sensitivity to the organizational effects of steroid hormones decreases across the pubertal window, with earlier androgen exposure leading to greater masculinization of the brain and behavior. Similarly, some research suggests the timing of peripubertal exposure to sex steroids influences aspects of human psychology, including visuospatial cognition. However, prior studies have been limited by small samples and/or imprecise measures of pubertal timing. We conducted 4 studies to clarify whether the timing of peripubertal hormone exposure predicts performance on male-typed tests of spatial cognition in adulthood. In Studies 1 (n = 1095) and 2 (n = 173), we investigated associations between recalled pubertal age and spatial cognition in typically developing men, controlling for current testosterone levels in Study 2. In Study 3 (n = 51), we examined the relationship between spatial performance and the age at which peripubertal hormone replacement therapy was initiated in a sample of men with Isolated GnRH Deficiency. Across Studies 1-3, effect size estimates for the relationship between spatial performance and pubertal timing ranged from. -0.04 and -0.27, and spatial performance was unrelated to salivary testosterone in Study 2. In Study 4, we conducted two meta-analyses of Studies 1-3 and four previously published studies. The first meta-analysis was conducted on correlations between spatial performance and measures of the absolute age of pubertal timing, and the second replaced those correlations with correlations between spatial performance and measures of relative pubertal timing where available. Point estimates for correlations between pubertal timing and spatial cognition were -0.15 and -0.12 (both p < 0.001) in the first and second meta-analyses, respectively. These associations were robust to the exclusion of any individual study. Our results suggest that, for some aspects of neural development, sensitivity to gonadal hormones declines across puberty, with earlier pubertal hormone exposure predicting greater sex-typicality in psychological phenotypes in adulthood. These results shed light on the processes of behavioral and brain organization and have implications for the treatment of IGD and other conditions wherein pubertal timing is pharmacologically manipulated.

Are there vocal cues to human developmental stability? Relationships between facial fluctuating asymmetry and voice attractiveness.

Fluctuating asymmetry (FA), deviation from perfect bilateral symmetry, is thought to reflect an organism's relative inability to maintain stable morphological development in the face of environmental and genetic stressors. Previous research has documented negative relationships between FA and attractiveness judgments in humans, but scant research has explored relationships between the human voice and this putative marker of genetic quality in either sex. Only one study (and in women only) has explored relationships between vocal attractiveness and asymmetry of the face, a feature-rich trait space central in prior work on human genetic quality and mate choice. We therefore examined this relationship in three studies comprising 231 men and 240 women from two Western samples as well as Hadza hunter-gatherers of Tanzania. Voice recordings were collected and rated for attractiveness, and FA was computed from two-dimensional facial images as well as, for a subset of men, three-dimensional facial scans. Through meta-analysis of our results and those of prior studies, we found a negative association between FA and vocal attractiveness that was highly robust and statistically significant whether we included effect sizes from previously published work, or only those from the present research, and regardless of the inclusion of any individual sample or method of assessing FA (e.g., facial or limb FA). Weighted mean correlations between FA and vocal attractiveness across studies were -.23 for men and -.29 for women. This research thus offers strong support for the hypothesis that voices provide cues to genetic quality in humans.

Safety of catheter-directed thrombolysis for massive and submassive pulmonary embolism: Results of a multicenter registry and meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) in the treatment of acute pulmonary embolism (PE). BACKGROUND: The use of CDT for the treatment of acute submassive and massive PE is increasing in frequency. However, its safety and efficacy have not been well elucidated. METHODS: This study is made of two parts: one is a two-center registry of acute PE patients treated with CDT. The safety outcome evaluated was any major complication including fatal, intracranial (ICH), intraocular, or retroperitoneal hemorrhage or any overt bleeding requiring transfusion or surgical repair. The efficacy outcome was acute change in invasive pulmonary artery systolic pressure (PASP). The second part is a meta-analysis of all contemporary studies that used CDT for PE. Reported outcomes are the same as in the registry, with the addition of right ventricular to left ventricular (RV/LV) ratio change. RESULTS: In the registry, 137 patients were included (age 59 ± 15, 50% male, 88% submassive PE). ICH occurred in two patients and major complications in 13 (9.4%). PASP decreased post procedure by 19 ± 15 mm Hg (95% CI 16-23). In the meta-analysis, 16 studies were included with 860 patients. Rate of ICH was 0.35% and the major complication rate was 4.65%, most requiring transfusion only. In-hospital mortality was 12.9% in the massive and 0.74% in the submassive group. All studies showed improvement in PASP and/or RV/LV ratio post CDT. CONCLUSIONS: CDT is associated with a low major complication rate. Randomized studies are needed to evaluate its efficacy relative to anticoagulation alone. © 2017 Wiley Periodicals, Inc.

Case Series of Patients With Intermediate-High Risk Pulmonary Embolism in the Setting of Trauma Undergoing Mechanical Thrombectomy.

In patients with pulmonary embolism (PE) in the setting of trauma, administration of fibrinolytic therapy is contraindicated due to high risk of hemorrhage. Several studies have demonstrated the safety and efficacy of mechanical thrombectomy among all-comers with PE as an alternative to catheter-directed thrombolytics. However, the risks and benefits of mechanical thrombectomy treatment for pulmonary embolism in a trauma population are not well established. A retrospective analysis was performed in all patients who presented to Level 1 Trauma Center with acute trauma who were found to have a pulmonary embolism (PE) treated with mechanical thrombectomy. From May 2019 to December 2020, six patients were identified. Average age was 54 years, and four patients were male. Four patients had a saddle PE on computed tomography. All patients had an intermediate-high risk PE with troponin I elevation >0.04 ng/mL (average 0.42 ng/mL). Pulmonary Embolism Severity Index (PESI) score in all six patients was class III or IV. In all patients, the mechanical thrombectomy was performed with mean-PA pressure changing from average 40.33 to 31.5 mmHg. Average Intensive Care Unit (ICU) length of stay post-procedure was five days with two patients not requiring ICU stay. No patient had post-operative bleeding during their index stay. Average hemoglobin drop after mechanical thrombectomy was 1.33 g/dL. One patient died <30 days post-procedure due to septic shock and another >90 days later (5 months) from cardiac arrest from recurrent PE. The other four patients were still living >90 days post-procedure. No immediate or delayed postoperative complications were identified. Mechanical thrombectomy appears to be a safe and effective treatment for patients with recent trauma who have an intermediate-high risk pulmonary embolism.

Barriers and facilitators to interhospital transfer of acute pulmonary embolism: An inductive qualitative analysis.

Background: Interhospital transfer (IHT) of patients with acute life-threatening pulmonary embolism (PE) is necessary to facilitate specialized care and access to advanced therapies. Our goal was to understand what barriers and facilitators may exist during this transfer process from the perspective of both receiving and referring physicians. Methods: This qualitative descriptive study explored physician experience taking care of patients with life threatening PE. Subject matter expert physicians across several different specialties from academic and community United States hospitals participated in qualitative semi-structured interviews. Interview transcripts were subsequently analyzed using inductive qualitative description approach. Results: Four major themes were identified as barriers that impede IHT among patients with life threatening PE. Inefficient communication which mainly pertained to difficulty when multiple points of contact were required to complete a transfer. Subjectivity in the indication for transfer which highlighted the importance of physicians understanding how to use standardized risk stratification tools and to properly triage these patients. Delays in data acquisition were identified in regards to both obtaining clinical information and imaging in a timely fashion. Operation barriers which included difficulty finding available beds for transfer and poor weather conditions inhibiting transportation. In contrast, two main facilitators to transfer were identified: good communication and reliance on colleagues and dedicated team for transferring and treating PE patients. Conclusion: The most prominent themes identified as barriers to IHT for patients with acute life-threatening PE were: (1) inefficient communication, (2) subjectivity in the indication for transfer, (3) delays in data acquisition (imaging or clinical), and (4) operational barriers. Themes identified as facilitators that enable the transfer of patients were: (1) good communication and (2) a dedicated transfer team. The themes presented in our study are useful in identifying opportunities to optimize the IHT of patients with acute PE and improve patient care. These opportunities include instituting educational programs, streamlining the transfer process, and formulating a consensus statement to serve as a guideline regarding IHT of patients with acute PE.

Changes in the care of acute cerebrovascular and cardiovascular conditions during the first year of the covid-19 pandemic in 746 hospitals in the USA: retrospective analysis.

Objective: To measure the impact of the covid-19 pandemic on admissions to hospital and interventions for acute ischemic stroke and acute myocardial infarction. Design: A retrospective analysis. Setting: 746 qualifying hospitals in the USA from the Premier Healthcare Database. Participants: Patients aged 18 years and older who were admitted to hospital with a primary diagnosis of acute ischemic stroke or acute myocardial infarction between 1 March 2019 and 28 February 2021. Main outcome measures: Relative changes in volumes were assessed for acute ischemic stroke and acute myocardial infarction hospital admissions as well as intravenous thrombolysis, mechanical thrombectomy, and percutaneous coronary intervention (overall and for acute myocardial infarction only) across the first year of the pandemic versus the prior year. Mortality in hospital and length of stay in hospital were also compared across the first year of the pandemic versus the corresponding period the year prior. These metrics were explored across the different pandemic waves. Results: Among 746 qualifying hospitals, admissions to hospital were significantly reduced after the covid-19 pandemic compared with before the pandemic for acute ischemic stroke (-13.59% (95% confidence interval-13.77% to -13.41%) and acute myocardial infarction (-17.20% (-17.39% to -17.01%)), as well as intravenous thrombolysis (-9.47% (-9.99% to -9.02%)), any percutaneous coronary intervention (-17.89% (-18.06% to -17.71%)), and percutaneous coronary intervention for acute myocardial infarction (-14.36% (-14.59% to -14.12%)). During the first year of the pandemic versus the previous year, the odds of mortality in hospital for acute ischemic stroke were 9.00% higher (3.51% v 3.16%; ratio of the means 1.09 (95% confidence interval (1.03 to 1.15); P=0.0013) and for acute myocardial infarction were 18.00% higher (4.81% v 4.29%; ratio of the means 1.18 (1.13 to 1.23); P<0.0001). Conclusions: We observed substantial decreases in admissions to hospital with acute ischemic stroke and acute myocardial infarction, but an increase in mortality in hospital throughout the first year of the pandemic. Public health interventions are needed to prevent these reductions in future pandemics.

Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease.

BACKGROUND: Experimental studies suggest that low wall shear stress (WSS) promotes plaque development and high WSS is associated with plaque destabilization. We hypothesized that low-WSS segments in patients with coronary artery disease develop plaque progression and high-WSS segments develop necrotic core progression with fibrous tissue regression. METHODS AND RESULTS: Twenty patients with coronary artery disease underwent baseline and 6-month radiofrequency intravascular ultrasound (virtual histology intravascular ultrasound) and computational fluid dynamics modeling for WSS calculation. For each virtual histology intravascular ultrasound segment (n=2249), changes in plaque area, virtual histology intravascular ultrasound-derived plaque composition, and remodeling were compared in low-, intermediate-, and high-WSS categories. Compared with intermediate-WSS segments, low-WSS segments developed progression of plaque area (P=0.027) and necrotic core (P<0.001), whereas high-WSS segments had progression of necrotic core (P<0.001) and dense calcium (P<0.001) and regression of fibrous (P<0.001) and fibrofatty (P<0.001) tissue. Compared with intermediate-WSS segments, low-WSS segments demonstrated greater reduction in vessel (P<0.001) and lumen area (P<0.001), and high-WSS segments demonstrated an increase in vessel (P<0.001) and lumen (P<0.001) area. These changes resulted in a trend toward more constrictive remodeling in low- compared with high-WSS segments (73% versus 30%; P=0.06) and more excessive expansive remodeling in high- compared with low-WSS segments (42% versus 15%; P=0.16). CONCLUSIONS: Compared with intermediate-WSS coronary segments, low-WSS segments develop greater plaque and necrotic core progression and constrictive remodeling, and high-WSS segments develop greater necrotic core and calcium progression, regression of fibrous and fibrofatty tissue, and excessive expansive remodeling, suggestive of transformation to a more vulnerable phenotype. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576576.

Coronary angiographic scoring systems: an evaluation of their equivalence and validity.

BACKGROUND: Multiple scoring systems have been devised to quantify angiographic coronary artery disease (CAD) burden, but it is unclear how these scores relate to each other and which scores are most accurate. The aim of this study was to compare coronary angiographic scoring systems (1) with each other and (2) with intravascular ultrasound (IVUS)-derived plaque burden in a population undergoing angiographic evaluation for CAD. METHODS: Coronary angiographic data from 3600 patients were scored using 10 commonly used angiographic scoring systems and interscore correlations were calculated. In a subset of 50 patients, plaque burden and plaque area in the left anterior descending coronary artery were quantified using IVUS and correlated with angiographic scores. RESULTS: All angiographic scores correlated with each other (range for Spearman coefficient [ρ] 0.79-0.98, P < .0001); the 2 most widely used scores, Gensini and CASS-70, had a ρ = 0.90 (P < .0001). All scores correlated significantly with average plaque burden and plaque area by IVUS (range ρ 0.56-0.78, P < .0001 and 0.43-0.62, P < .01, respectively). The CASS-50 score had the strongest correlation (ρ 0.78 and 0.62, P < .0001) and the Duke Jeopardy score the weakest correlation (ρ 0.56 and 0.43, P < .01) with plaque burden and area, respectively. CONCLUSIONS: Angiographic scoring systems are strongly correlated with each other and with atherosclerotic plaque burden. Scoring systems therefore appear to be a valid estimate of CAD plaque burden.

Nursing behaviors related to vancomycin and aminoglycoside administration.

The assessment of a program to promote appropriate knowledge and behaviors related to vancomycin and aminoglycoside administration by direct-care nurses working on the intensive care and a medical-surgical unit of one regional medical center is reported.

Hospital-Level Disparities in the Management and Outcomes of Cardiac Arrest Complicating Acute Myocardial Infarction.

There are limited contemporary data evaluating the relation between hospital characteristics and outcomes of patients with cardiac arrest complicating acute myocardial infarction (AMI-CA). As such, we used the National Inpatient Sample database (2000 to 2017), to identify adult admissions with primary diagnosis of AMI and concomitant CA. Interhospital transfers were excluded, and hospitals were classified based on location and teaching status (rural, urban nonteaching, and urban teaching) and bed size (small, medium, and large). Among 494,083 AMI-CA admissions, 9.3% received care at rural hospitals, 43.4% at urban nonteaching hospitals, and 47.3% at urban teaching hospitals. Compared with urban nonteaching and teaching hospitals, AMI-CA admissions at rural hospitals received lower rates of cardiac and noncardiac procedures. Admissions to urban teaching hospitals had higher rates of acute organ failure, concomitant cardiogenic shock, and cardiac and noncardiac procedures. When hospitals were stratified by bed size, 9.8% of AMI-CA admissions were admitted to small capacity hospitals, 26.0% to medium capacity, and 64.2% to large capacity hospitals. The use of cardiac and noncardiac procedures was lower in small hospitals with higher rates of use in medium and large hospitals. In-hospital mortality was higher in urban nonteaching (adjusted odds ratio [OR] 1.17; 95% confidence interval [CI]1.14 to 1.20; p <0.001) and urban teaching hospitals (adjusted OR 1.36; 95% CI 1.32 to 1.39; p <0.001) compared with rural hospitals. Compared with small hospitals, medium (adjusted OR 1.11; 95% CI 1.08 to 1.14; p <0.001) and large hospitals (adjusted OR 1.22; 95% CI 1.19 to 1.25; p <0.001) were associated with higher in-hospital mortality. In conclusion, AMI-CA admissions to large and urban hospitals had higher in-hospital mortality compared with small and rural hospitals potentially owing to greater acuity.

Localization of culprit lesions in coronary arteries of patients with ST-segment elevation myocardial infarctions: relation to bifurcations and curvatures.

BACKGROUND: Although culprit lesions in ST-segment elevation myocardial infarction (STEMI) cluster in the proximal coronary arteries, their relationship to bifurcations and curvatures, where blood flow is disturbed, is unknown. We hypothesized that (a) culprit lesions localize to disturbed flow distal to bifurcations and curvatures and (b) the distribution of culprit lesions in the left (LCA) and right coronary arteries (RCA) and resulting infarct size are related to the location of bifurcations and curvatures. METHODS: Emory University's contribution to the National Cardiovascular Data Registry was queried for STEMIs. Using quantitative coronary angiography, the distances from the vessel ostium, major bifurcations, and major curvatures to the culprit lesion were measured in 385 patients. RESULTS: Culprit lesions were located within 20 mm of a bifurcation in 79% of patients and closer to the bifurcation in the LCA compared with the RCA (7.4 ± 7.3 vs 17.7 ± 14.8 mm, P < .0001). Of RCA culprit lesions, 45% were located within 20 mm of a major curvature. Compared with those in the RCA, culprit lesions in the LCA were located more proximally (24.4 ± 16.5 vs 44.7 ± 28.8 mm, P = .0003) and were associated with larger myocardial infarctions as assessed by peak creatine kinase-MB (208 ± 222 vs 140 ± 153 ng/dL, P = .001) and troponin I (59 ± 62 vs 40 ± 35 ng/dL, P = .0006) and with higher in-hospital mortality (5.2% vs 1.1%, P = .04). CONCLUSIONS: In patients with STEMI, culprit lesions are frequently located immediately distal to bifurcations and in proximity to major curvatures where disturbed flow is known to occur. This supports the role of wall shear stress in the pathogenesis of STEMI.

Use of coronary physiology in the catheterization laboratory to guide treatment in patients with coronary artery disease.

OPINION STATEMENT: Fractional flow reserve (FFR) is an invasive pressure-derived index of epicardial stenosis severity used in the catheterization laboratory to assess the hemodynamic significance of coronary lesions when non-invasive functional assessment has either not been performed or is inconclusive. The rationale for the use of FFR is that coronary angiography cannot accurately predict the hemodynamic significance of lesions with diameter stenosis <90% and that there is a large body of literature supporting the use of FFR for directing coronary revascularization. Specifically, in patients with stable angina and low-risk acute coronary syndromes, revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery should be deferred for epicardial coronary stenoses with an FFR > 0.80. Use of FFR to direct coronary revascularization should continue to increase as it has been demonstrated to improve outcomes and reduce cost.

Religion and spirituality.

Many clients highly value religious and spiritual (R/S) commitments, and many psychotherapists have accommodated secular treatments to R/S perspectives. We meta-analyzed 51 samples from 46 studies (N = 3,290) that examined the outcomes of religious accommodative therapies and nonreligious spirituality therapies. Comparisons on psychological and spiritual outcomes were made to a control condition, an alternate treatment, or a subset of those studies that used a dismantling design (similar in theory and duration of treatment, but including religious contents). Patients in R/S psychotherapies showed greater improvement than those in alternate secular psychotherapies both on psychological (d =.26) and on spiritual (d = .41) outcomes. Religiously accommodated treatments outperformed dismantling-design alternative treatments on spiritual (d = .33) but not on psychological outcomes. Clinical examples are provided and therapeutic practices are recommended.