Biomarkers Correspond with Echocardiographic Phenotypes in Heart Failure with Preserved Ejection Fraction: A Secondary Analysis of the RELAX Trial.

Background: Little is known about the relationship between structural phenotypes in in heart failure with preserved ejection fraction (HFpEF) and cardiac biomarkers. We used cluster analysis to identify cardiac structural phenotypes and their relationships to biomarkers in HFpEF. Methods and results: Latent class analysis (LCA) was applied to echocardiographic data including left atrial enlargement (LAE), diastolic dysfunction (DD), E/e', EF≤55%, and right ventricular dysfunction from 216 patients enrolled in the RELAX trial. Three structural phenotypes were identified. Phenotype A had the most grade II DD. Phenotype B had the most grade III DD, worst LAE, elevated E/e' and right ventricular dysfunction. Phenotype C had the least DD and moderate LAE. Phenotypes B and C had prevalent atrial fibrillation (AF). Phenotype B patients had increased carboxy-terminal telopeptide of collagen type I (CITP), cystatin-c (CYSTC), endothelin-1 (ET1), NT-proBNP, and high-sensitivity troponin I (TNI). Type A had the next highest CITP and CYSTC levels while Type C had next highest NT-proBNP. Conclusions: Structural HFpEF phenotypes demonstrated different characteristics including cardiac biomarkers. These findings may help explain phenotype-specific differences in natural history and prognosis, and they may represent phenotype-specific pathophysiology that could be amenable to targeted therapy.

Clinical outcomes of cemented vs. uncemented reverse total shoulder arthroplasty for proximal humerus fractures: a systematic review.

BACKGROUND: Reverse total shoulder arthroplasty is an established treatment method for comminuted proximal humerus fractures. Both cemented and uncemented techniques exist, with uncemented reverse total shoulder offering many theoretical advantages, including improved biologic fixation, absence of cement related complications, and ease of revision if necessary. There are few studies comparing the outcomes of the two techniques. METHODS: The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search for studies assessing clinical outcomes of reverse total shoulder arthroplasty for proximal humerus fractures was performed of PubMed, Embase, Web of Science, and Cochrane Library. Main outcomes included Constant Score (CS), American Shoulder and Elbow Surgeons (ASES) score, and complication rate. Inclusion criteria were as follows: indication for arthroplasty was fracture; minimum one year follow up; article in English. Exclusion criteria were as follows: review articles; biomechanical or cadaver studies. Quality analysis was performed using the Cochrane Risk of Bias tool (RoB 2) and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool. RESULTS: A total of 682 studies were identified through the initial search, with 36 studies meeting all inclusion criteria. There were 24 studies investigating cemented technique, 10 studies examining uncemented technique, and two studies involving both techniques. There was no difference in mean follow up between patients receiving a cemented vs. uncemented rTSA (32.3 months vs. 30.6 months, p = 0.06). Patients who received a cemented rTSA had a significantly higher Constant-Murley score than those who received an uncemented rTSA (59.4 vs 55.9, p < .001). There was no difference between the two groups when comparing ASES Scores (77.5 vs 78.6, p = 0.54) and overall complication rates (11.1% vs 11.8%, p = 0.23). CONCLUSION: Both cemented and uncemented rTSA are both valid options for treating acute proximal humerus fractures. Cemented rTSA may portend slightly improved clinical outcomes with similar overall complication rates compared to uncemented rTSA for proximal humerus fractures.

Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis.

The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA's globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique "fingerprint" or "biomarker" vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

Surgery Resident Perceptions of the Clicker Evaluation System: A Novel Approach to Collecting and Utilizing Clinical Faculty Performance Data.

OBJECTIVE: Medical trainees often have a process in place to receive feedback from clinical faculty regarding overall performance. While there is guidance on effective methodologies for faculty to provide feedback for learners, there is a dearth of literature analyzing trainees' evaluation of faculty performance. We sought to identify an effective and anonymous method for surgery residents to evaluate clinical faculty. DESIGN: The Department of Orthopedic Surgery at Virginia Commonwealth University (VCU) Health implemented a novel process to gather annual clinical faculty performance data from residents for the purpose of program improvement starting in 2012. Specifically, residents used a web-based audience response system, also known as a "clicker" system, to evaluate faculty performance over the academic year. During the June 2018 evaluation session, residents also completed an anonymous, 9 question survey to assess the residents' perceptions regarding this clicker evaluation process. SETTING: VCU Health System, a tertiary care hospital in Richmond, Virginia. PARTICIPANTS: All 24 orthopaedic surgery residents at VCU Health participated in the evaluation process and completed the perception survey in 2018. RESULTS: Ninety-six percent (n = 23) of the residents agreed that they are able to accurately rate their attendings' performance, felt confident that their responses remained anonymous, and that their departmental chair values their opinion when evaluating their attendings' performance through the clicker process. Qualitative responses identified anonymity as a strength of the clicker process, while opportunities for improvement included refinement of questions. CONCLUSIONS: The clicker evaluation system is an effective and anonymous method for resident evaluation of clinical faculty performance in academic settings. Future steps include refinement of questions based on departmental goals for education, adoption of the clicker evaluation system by other specialties, as well as research into ways to optimize the clicker evaluation process. Additional research should be done to see if and how the clicker evaluation feedback translates into change in clinical faculty behavior.

Dynamic Regulation of SARS-Cov-2 Binding and Cell Entry Mechanisms in Remodeled Human Ventricular Myocardium.

Using serial analysis of myocardial gene expression employing endomyocardial biopsy starting material in a dilated cardiomyopathy cohort, we show that mRNA expression of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) cardiac myocyte receptor ACE2 is up-regulated with remodeling and with reverse remodeling down-regulates into the normal range. The proteases responsible for virus-cell membrane fusion were expressed but not regulated with remodeling. In addition, a new candidate for SARS-CoV-2 cell binding and entry was identified, the integrin encoded by ITGA5. Up-regulation in ACE2 in remodeled left ventricles may explain worse outcomes in patients with coronavirus disease 2019 who have underlying myocardial disorders, and counteracting ACE2 up-regulation is a possible therapeutic approach to minimizing cardiac damage.

Analysis of Outcomes in 8304 Patients Undergoing Lead Extraction for Infection.

Background Patients undergoing lead extraction for infected devices have worse outcomes compared with those with noninfected devices. We assessed predictors of in-hospital mortality and procedure-related major adverse events (MAEs) in a large cohort undergoing lead extraction. Methods and Results Deidentified hospital records procedure from 7 states between 1994 and 2013 were aggregated and International Classification of Disease, Ninth Revision (ICD-9) procedure codes were used to identify hospital records reporting lead extraction. MAEs included death, cardiac tamponade, hemothorax, and need for emergent cardiac surgery. Predictors of in-hospital MAEs for infected compared with noninfected leads were identified using multivariate regression. Associations between outcomes and specific microbe were also assessed. In total, 57 220 discharges specified lead extraction. Infected leads accounted for the minority of total lead extractions compared with fractured leads (16.1 versus 59.8%, 25.7% not reported). There were 3298 MAEs (5.8%) including 980 deaths (1.7%). Multivariate predictors of MAE included black race, atrial fibrillation, anemia, heart failure, and admission via either hospital transfer or emergency department versus home (all P<0.001). Infected leads were associated with an increased risk of death (4.6% versus 0.9%, P<0.001) compared with leads with fracture only. Among patients with microbial data, staphylococcal infection was most common, whereas streptococcal infection was associated with the worst outcomes. Conclusions Patients undergoing extraction of infected leads have higher in-hospital mortality and adverse events compared with noninfected leads. Streptococcus, anemia, and heart failure are predictors of adverse outcomes.

Sex Differences in Outcomes and Responses to Spironolactone in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of TOPCAT Trial.

OBJECTIVES: This study sought to investigate sex differences in outcomes and responses to spironolactone in patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND: HFpEF affects women more frequently than men. Sex differences in responses to effects of mineralocorticoid antagonists have not been reported. METHODS: This was an exploratory, post hoc, non-pre-specified analysis of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. Subjects with symptomatic HF and a left ventricular ejection fraction ≥45% were randomized to spironolactone or placebo therapy. Subjects enrolled from the Americas were analyzed. The primary outcome was a composite of cardiovascular (CV) death, cardiac arrest, or HF hospitalization. Secondary outcomes included all-cause mortality, CV, and non-CV mortality and CV, HF, and non-CV hospitalization. Sex differences in outcomes and treatment effects were determined using time-to-event analysis. RESULTS: In total, 882 of 1,767 subjects (49.9%) were women. Women were older with fewer comorbidities but worse patient-reported outcomes. There were no sex differences in outcomes in the placebo arm or in response to spironolactone for the primary outcome or its components. Spironolactone therapy was associated with reduced all-cause mortality in women (hazard ratio: 0.66; p = 0.01) but not in men (pinteraction = 0.02). CONCLUSIONS: In TOPCAT, women and men presented with different clinical profiles and similar clinical outcomes. The interaction between spironolactone and sex in TOPCAT overall and in the present analysis was nonsignificant for the primary outcome, but there was a reduction in all-cause mortality associated with spironolactone therapy in women, with a significant interaction between sex and treatment arm. Prospective evaluation is needed to determine whether spironolactone therapy may be effective for treatment of HFpEF in women. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302).

Myocardial microRNAs associated with reverse remodeling in human heart failure.

BACKGROUND: In dilated cardiomyopathies (DCMs) changes in expression of protein-coding genes are associated with reverse remodeling, and these changes can be regulated by microRNAs (miRs). We tested the general hypothesis that dynamic changes in myocardial miR expression are predictive of ß-blocker-associated reverse remodeling. METHODS: Forty-three idiopathic DCM patients (mean left ventricular ejection fraction 0.24 ± 0.09) were treated with ß-blockers. Serial ventriculography and endomyocardial biopsies were performed at baseline, and after 3 and 12 months of treatment. Changes in RT-PCR (candidate miRs) or array-measured miRs were compared based on the presence (R) or absence (NR) of a reverse-remodeling response, and a miR-mRNA-function pathway analysis (PA) was performed. RESULTS: At 3 months, 2 candidate miRs were selectively changed in Rs, decreases in miR-208a-3p and miR-591. PA revealed changes in miR-mRNA interactions predictive of decreased apoptosis and myocardial cell death. At 12 months, 5 miRs exhibited selective changes in Rs (decreases in miR-208a-3p, -208b-3p, 21-5p, and 199a-5p; increase in miR-1-3p). PA predicted decreases in apoptosis, cardiac myocyte cell death, hypertrophy, and heart failure, with increases in contractile and overall cardiac functions. CONCLUSIONS: In DCMs, myocardial miRs predict the time-dependent reverse-remodeling response to ß-blocker treatment, and likely regulate the expression of remodeling-associated miRs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01798992. FUNDING: NIH 2R01 HL48013, 1R01 HL71118 (Bristow, PI); sponsored research agreements from Glaxo-SmithKline and AstraZeneca (Bristow, PI); NIH P20 HL101435 (Lowes, Port multi-PD/PI); sponsored research agreement from Miragen Therapeutics (Port, PI).

Sex differences and in-hospital outcomes in patients undergoing mechanical circulatory support implantation.

BACKGROUND: Mechanical circulatory support (MCS) is a widely available management strategy. No studies have described sex differences in both extracorporeal and durable MCS. We analyzed sex-related differences of in-hospital outcomes for extracorporeal and durable MCS using administrative hospital data. METHODS: In total, 134.5 million hospital records between 1994 and 2012 were screened for placement of MCS using procedure codes of the International Classification of Diseases-9, Clinical Modification. Major adverse events (MAEs) were defined as death, major bleeding, stroke, device infection or mechanical complication. Participation in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry was determined on an annual basis using quarterly reports of the INTERMACS. Associations between characteristics and outcomes were determined using multivariable logistic regression. RESULTS: Sex was reported in 3,523 of 4,337 patients undergoing MCS placement from 45 INTERMACS sites (n = 1,383) and 246 non-INTERMACS sites (n = 2,954). Twenty-two percent were female. Baseline characteristics were significantly different with women being slightly younger (33.5% vs 27.4% age <50 years, p < 0.001; mean 55.7 ± 17.3 vs 56.1 ± 14.6 years) with fewer comorbidities. Women had higher rates of in-hospital mortality (52.3% vs 40.8%, p < 0.001) and MAEs (64.8% vs 52.5%, p < 0.001). Women had an 89% higher likelihood of MAEs when corrected for multivariate predictors (p < 0.001). In-hospital mortality decreased over time for both men and women (10% relative risk reduction/year, p < 0.001), but mortality in women was higher than in men throughout the study period. CONCLUSION: There are significant sex differences in characteristics and outcomes of patients receiving MCS. Women had higher in-hospital mortality and were at increased risk of MAEs, which could not be explained by age or comorbid conditions. Further research on the causes of these disproportionate outcomes is needed.

Characteristics and In-Hospital Outcomes of Peripartum Cardiomyopathy Diagnosed During Delivery in the United States From the Nationwide Inpatient Sample (NIS) Database.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is associated with advanced maternal age, African-American race, hypertensive disorders of pregnancy, and multiple-gestation pregnancies. Less is known regarding racial differences in risk factors and predictors of adverse in-hospital outcomes. METHODS AND RESULTS: A total of 1,337 women with PPCM were identified with the use of the Nationwide Inpatient Sample (2004-2011). Clinical profiles and maternal outcomes in delivering mothers with and without PPCM were compared and stratified by race. In multivariate analysis, established risk factors for PPCM were confirmed. Anemia (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.6-2.5; P < .0001), asthma (OR 2.2, 95% CI 1.5-3.2; P = .0002), smoking (OR 33.6, 95% CI 9.3-159.4; P < .0001), and thyroid disease (OR 5.9; 95% CI 1.5-21.3; P = .01) were associated with PPCM. Risk factors significant in whites, African Americans, and Hispanics were hypertension during pregnancy and anemia. Patients with PPCM had higher rates of in-hospital adverse outcomes (P < .0001), but no differences in race or comorbidities predicted adverse events. CONCLUSIONS: Hypertensive disorders during pregnancy and anemia were associated with PPCM in whites, African Americans, and Hispanics, providing further evidence that vascular stress may play a role in the pathogenesis of PPCM. Thyroid disorders may represent a novel risk factor for PPCM.

QTc interval screening in an opioid treatment program.

Methadone is highly effective for opioid dependency, but it is associated with Torsade de pointes. Although electrocardiography (ECG) has been proposed, its utility is uncertain, because an ECG-based intervention has not been described. An ECG-based cardiac safety program in methadone maintenance patients was evaluated in a single opioid treatment program from September 1, 2009, to August 31, 2011, in the United States. Time from pretreatment to repeat ECG in new entrants was assessed. The proportion with marked rate-corrected QT (QTc) interval prolongation (>500 ms) and the effect of the intervention on the QTc interval in this group were evaluated. Multivariate predictors of QTc interval change were assessed using a mixed-effects model. Of 531 new entrants, 436 (82%) underwent ≥1 electrocardiographic assessment, and 186 (35%) underwent pretreatment ECG. Median time to follow-up ECG was 43 days but decreased over time (p <0.0001). In 21 patients with QTc intervals >500 ms, the mean QTc interval from peak to final ECG decreased significantly (-55.5 ms, 95% confidence interval -77.0 to -33.9, p = 0.001), and 12 of 21 (57.1%) decreased to lower than the 500-ms threshold. In new entrants with serial ECG, only methadone dose (p = 0.009) and pretreatment QTc interval (p <0.0001) were associated with the magnitude of QTc interval change. In conclusion, this study suggests that the implementation of an ECG-based intervention in methadone maintenance can decrease the QTc interval in high-risk patients; clinical characteristics alone were inadequate to identify patients in need of electrocardiographic screening.

Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy.

BACKGROUND: Retinal vasculopathies, including diabetic retinopathy (DR), threaten the vision of over 100 million people. Retinal pericytes are critical for microvascular control, supporting retinal endothelial cells via direct contact and paracrine mechanisms. With pericyte death or loss, endothelial dysfunction ensues, resulting in hypoxic insult, pathologic angiogenesis, and ultimately blindness. Adipose-derived stem cells (ASCs) differentiate into pericytes, suggesting they may be useful as a protective and regenerative cellular therapy for retinal vascular disease. In this study, we examine the ability of ASCs to differentiate into pericytes that can stabilize retinal vessels in multiple pre-clinical models of retinal vasculopathy. METHODOLOGY/PRINCIPAL FINDINGS: We found that ASCs express pericyte-specific markers in vitro. When injected intravitreally into the murine eye subjected to oxygen-induced retinopathy (OIR), ASCs were capable of migrating to and integrating with the retinal vasculature. Integrated ASCs maintained marker expression and pericyte-like morphology in vivo for at least 2 months. ASCs injected after OIR vessel destabilization and ablation enhanced vessel regrowth (16% reduction in avascular area). ASCs injected intravitreally before OIR vessel destabilization prevented retinal capillary dropout (53% reduction). Treatment of ASCs with transforming growth factor beta (TGF-ß1) enhanced hASC pericyte function, in a manner similar to native retinal pericytes, with increased marker expression of smooth muscle actin, cellular contractility, endothelial stabilization, and microvascular protection in OIR. Finally, injected ASCs prevented capillary loss in the diabetic retinopathic Akimba mouse (79% reduction 2 months after injection). CONCLUSIONS/SIGNIFICANCE: ASC-derived pericytes can integrate with retinal vasculature, adopting both pericyte morphology and marker expression, and provide functional vascular protection in multiple murine models of retinal vasculopathy. The pericyte phenotype demonstrated by ASCs is enhanced with TGF-ß1 treatment, as seen with native retinal pericytes. ASCs may represent an innovative cellular therapy for protection against and repair of DR and other retinal vascular diseases.

Left ventricular dysfunction in patients receiving cardiotoxic cancer therapies are clinicians responding optimally?

OBJECTIVES: The purpose of this study was to examine treatment practices for cancer therapy-associated decreased left ventricular ejection fraction (LVEF) detected on echocardiography and whether management was consistent with American College of Cardiology/American Heart Association guidelines. BACKGROUND: Patients treated with anthracyclines or trastuzumab are at risk of cardiotoxicity. Decreased LVEF represents a Class I indication for drug intervention according to American College of Cardiology/American Heart Association guidelines. METHODS: Patients receiving anthracycline or trastuzumab at Stanford University from October 2005 to October 2007 and who had undergone echocardiography before and after receiving an anthracycline or trastuzumab were identified. Chart review examined chemotherapy regimens, cardiac risk factors, imaging results, concomitant medications, and cardiology consultations. RESULTS: Eighty-eight patients received therapy with an anthracycline or trastuzumab and had a pre-treatment and follow-up echocardiogram. Ninety-two percent were treated with anthracyclines, 17% with trastuzumab after an anthracycline, and 8% with trastuzumab without previous treatment with anthracycline. Mean baseline LVEF was 60%, with 14% having a baseline <55%. Forty percent had decreased LVEF (<55%) after anthracycline and/or trastuzumab treatment. Of these patients, 40% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 51% beta-blocker therapy, and 54% cardiology consultation. Of patients with asymptomatic decreased LVEF, 31% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 35% beta-blocker therapy, and 42% cardiology consultation. Of those with symptomatic decreased LVEF, 67% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 100% beta-blocker therapy, and 89% cardiology consultation. CONCLUSIONS: Many cancer survivors are not receiving treatment consistent with heart failure guidelines. There is substantial opportunity for collaboration between oncologists and cardiologists to improve the care of oncology patients receiving cardiotoxic therapy.

Elevated serum interleukin-6 (IL-6) in solid-organ transplant recipients is positively associated with tissue destruction and IL-6 gene expression in the periodontium.

BACKGROUND: The number of transplanted solid organs and life expectancy after transplantation are steadily rising worldwide. Inflammation is widely recognized as playing a pivotal role in transplant rejection, and several studies have shown that serum interleukin-6 (IL-6) levels can identify individuals who are at greater risk for rejection. Given the known association between IL-6 and chronic periodontitis, the aim of our study was to assess the periodontal status of solid-organ transplant subjects compared to systemically healthy controls, to quantify the IL-6 levels in the serum and periodontal tissues, and to explore their association. METHODS: Forty-seven heart and kidney transplant and 18 systemically healthy age-matched individuals were recruited. Subjects received a complete periodontal examination, and blood and periodontal tissue samples were collected for quantification of IL-6 protein and mRNA levels, respectively. RESULTS: Transplant subjects had significantly higher serum IL-6 levels and slightly but statistically significantly increased mean probing depths than healthy controls. Multivariable linear regression analysis adjusting for gender, diabetes, smoking, and immunosuppressant dose showed that the mean probing depth, number of missing teeth, and mean percentage of sites with > or =4 mm attachment loss were independent predictors for elevated serum IL-6 levels. Transplant subjects with chronic periodontitis had higher mean serum IL-6 levels than those without chronic periodontitis, and there was a positive correlation between periodontal IL-6 gene expression levels and serum IL-6 protein levels. CONCLUSIONS: Periodontal tissue destruction and local IL-6 synthesis are associated with elevated serum IL-6 levels in transplant recipients. This may have serious implications in solid-organ transplant deterioration and chronic rejection.

Can doctors and nurses recognize depression in patients hospitalized with an acute myocardial infarction in the absence of formal screening?

OBJECTIVE: The objective of this study was to determine the ability of cardiovascular healthcare workers to assess the presence or absence of symptoms of depression in patients hospitalized with acute myocardial infarction (AMI) in the absence of formal screening. METHODS: Patients admitted with AMI underwent screening using the Beck Depression Inventory (BDI) administered by a research assistant. The cardiovascular nurse, medicine resident or intern, and attending cardiologist caring for the patient were then approached (blinded to the BDI results) and asked to assess, using a visual analog scale, whether the patient had symptoms that would warrant further evaluation for depression. RESULTS: BDI screening and at least one provider assessment were completed for 60 patients with AMI. A total of 18 of 60 patients (30.0%) had a BDI score of > or =10. Symptoms of depression were considered not present in 24 of 32 patient assessments when the BDI was > or =10 (75% false-negatives). The mean BDI score of patients assessed as depressed by at least one provider (6.7 +/- 6.3) was no different from the mean BDI score of patients assessed as not depressed (7.5 +/- 7.2, p = .67). Overall, there was little correlation between BDI scores and provider assessments, and this was not influenced by provider type or provider gender. CONCLUSIONS: Cardiovascular nurses and medicine residents and interns underrecognize depression in patients with AMI in the absence of formal screening. Formal screening for symptoms of depression should be considered part of routine AMI care.

Carcinoembryonic antigen family receptor recognition by gonococcal Opa proteins requires distinct combinations of hypervariable Opa protein domains.

Neisserial Opa proteins function as a family of adhesins that bind heparan sulfate proteoglycan (HSPG) or carcinoembryonic antigen family (CEACAM) receptors on human host cells. In order to define the CEACAM binding domain on Opa proteins, we tested the binding properties of a series of gonococcal (strain MS11) recombinants producing mutant and chimeric Opa proteins with alterations in one or more of the four surface-exposed loops. Mutagenesis demonstrated that the semivariable domain, present in the first loop, was completely dispensable for CEACAM binding. In contrast, the two hypervariable (HV) regions present in the second and third loops were essential for binding; deletion of either domain resulted in loss of receptor recognition. Deletion of the fourth loop resulted in a severe decrease in Opa expression at the cell surface and could therefore not be tested for CEACAM binding. Chimeric Opa variants, containing combinations of HV regions derived from different CEACAM binding Opa proteins, lost most of their receptor binding activity. Some chimeric variants gained HSPG binding activity. Together, our results indicate that full recognition of CEACAM receptors by Opa proteins requires a highly coordinate interplay between both HV regions. Furthermore, shuffling of HV regions may result in novel HSPG receptor binding activity.