Risk and clinical outcomes of acute myocardial infarction and acute ischemic stroke following gram-negative bloodstream infection.

OBJECTIVES: This retrospective cohort study examines incidence, risk factors, and clinical outcomes of acute myocardial infarction (AMI) and acute ischemic stroke (AIS) within one year of gram-negative bloodstream infection (GN-BSI) based on predefined clinical criteria. METHODS: Hospitalized adults with GN-BSI at Prisma Health-Midlands hospitals in South Carolina, USA from 2010 through 2015 were identified. Kaplan-Meier analysis was used to determine incidence of AMI and AIS within one year after GN-BSI. Multivariate Cox proportional hazards regression models were used to examine risk factors for AMI or AIS and impact on 1-year mortality. RESULTS: Among 1292 patients with GN-BSI, 263 and 17 developed AMI and AIS within 1-year with incidences of 23.4% and 1.9%, respectively. Majority of AMI were type 2 (164; 62%); 99 patients had type 1 AMI with incidence of 8.9%. Age >65 years (hazard ratio [HR] 1.52, 95% CI: 1.17-1.99), prior coronary artery disease or stroke (HR 1.74, 95% CI: 1.34-2.25), hypertension (HR 1.55, 95% CI: 1.13-2.15), end-stage renal disease (HR 1.52, 95% CI: 1.09-2.08), and quick Pitt bacteremia score (HR 1.55 per point, 95% CI: 1.40-1.72) were predictors of AMI/AIS. Development of type 1 AMI or AIS after GN-BSI was independently associated with increased 1-year mortality (HR 1.47, 95% CI: 1.03-2.07). CONCLUSIONS: AMI and AIS occur frequently within one year of GN-BSI and have negative impact on 1-year survival. Future randomized clinical trials are needed to determine the most effective clinical interventions for prevention of AMI/AIS following BSI in high risk patients and improve survival after these events.

Nonvariceal upper GI hemorrhage after percutaneous coronary intervention for acute myocardial infarction: a national analysis over 11 months.

BACKGROUND AND AIMS: Nonvariceal upper GI hemorrhage (NVUGIH) is a feared adverse event after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). We aimed to determine the incidence of NVUGIH after PCI for AMI and its impact on mortality, morbidity, and health care resource utilization over 11 months. METHODS: We used the Nationwide Readmission Database 2014. Inclusion criteria were (1) a principal diagnosis of ST or non-ST-elevation myocardial infarction, (2) in-hospital PCI, and (3) admission in January. Exclusion criteria were age less than 18 years and elective admission. The primary outcome was the 11-month incidence of NVUGIH. Secondary outcomes were 11-month mortality rate, prolonged mechanical ventilation, shock, upper endoscopy, length of stay, and total hospitalization costs and charges. Independent risk factors for NVUGIH were identified using multivariate logistic regression analysis. RESULTS: A total of 22,669 patients were included in the study. The mean age was 63.8 years (range, 63.4-64.1 years), and 31.7% of patients were female. The 11-month incidence of NVUGIH was 1.6%. The onset of NVUGIH was associated with an increase in the 11-month mortality rate (adjusted odds ratio, 1.94; 95% confidence interval, 1.01-3.72; P =.04). The upper endoscopy, shock, and prolonged mechanical ventilation rates were 72%, 6.2%, and 1.9%, respectively. In total, 26,532 days were associated with NVUGIH, with a total health care in-hospital economic burden of U.S.$17.6 million. Independent predictors of NVUGIH were female gender, Charlson comorbidity score, and length of stay. CONCLUSIONS: The 11-month incidence of NVUGIH among patients who undergo PCI for AMI is 1.6%. NVUGIH has a substantial impact on mortality, morbidity, and in-hospital health care resource utilization.

Poldip2 controls vascular smooth muscle cell migration by regulating focal adhesion turnover and force polarization.

Polymerase-δ-interacting protein 2 (Poldip2) interacts with NADPH oxidase 4 (Nox4) and regulates migration; however, the precise underlying mechanisms are unclear. Here, we investigated the role of Poldip2 in focal adhesion turnover, as well as traction force generation and polarization. Poldip2 overexpression (AdPoldip2) in vascular smooth muscle cells (VSMCs) impairs PDGF-induced migration and induces a characteristic phenotype of long cytoplasmic extensions. AdPoldip2 also prevents the decrease in spreading and increased aspect ratio observed in response to PDGF and slightly impairs cell contraction. Moreover, AdPoldip2 blocks focal adhesion dissolution and sustains H2O2 levels in focal adhesions, whereas Poldip2 knockdown (siPoldip2) significantly decreases the number of focal adhesions. RhoA activity is unchanged when focal adhesion dissolution is stimulated in control cells but increases in AdPoldip2-treated cells. Inhibition of RhoA blocks Poldip2-mediated attenuation of focal adhesion dissolution, and overexpression of RhoA or focal adhesion kinase (FAK) reverses the loss of focal adhesions induced by siPoldip2, indicating that RhoA and FAK mediate the effect of Poldip2 on focal adhesions. Nox4 silencing prevents focal adhesion stabilization by AdPoldip2 and induces a phenotype similar to siPoldip2, suggesting a role for Nox4 in Poldip2-induced focal adhesion stability. As a consequence of impaired focal adhesion turnover, PDGF-treated AdPoldip2 cells are unable to reduce and polarize traction forces, a necessary first step in migration. These results implicate Poldip2 in VSMC migration via regulation of focal adhesion turnover and traction force generation in a Nox4/RhoA/FAK-dependent manner.

Mortality rate in patients with diastolic dysfunction and normal systolic function.

BACKGROUND: Diastolic dysfunction (DD) is known to be associated with increased mortality rate in the presence of impaired systolic function. However, few prognostic data exist regarding the effect of DD in patients with normal systolic function. METHODS: We reviewed clinical records and echocardiographic findings of consecutive patients who underwent an outpatient echocardiogram that revealed normal systolic function (ejection fraction, ≥55%) from January 1, 1996, through December 31, 2005. Diastolic function was graded using echocardiographic Doppler variables designated as normal, mild (grade I, ie, impaired relaxation pattern), moderate (grade II, ie, pseudonormal pattern), or severe (grade III, ie, restrictive filling pattern) dysfunction. Propensity analysis was performed to compare outcomes among the groups. RESULTS: A total of 36 261 patients were identified (mean [SD] age, 58.3 [15.4] years; 54.4% female) with a mean (SD) follow-up time of 6.2 (2.3) years. In 65.2% of the cohort, DD was present, with mild DD being the most prevalent type of dysfunction. A total of 5789 deaths occurred during the follow-up period. The unadjusted survival rate was worse according to the presence and degree of DD (P <.001). However, after propensity matching, only moderate and severe DD were associated with an increased mortality risk (hazard ratio, 1.58; 95% confidence interval, 1.20-2.08; and hazard ratio, 1.84; 1.29-2.62, respectively; P <.001 for each). CONCLUSIONS: In this single-center study of patients with normal ejection fraction who presented for outpatient echocardiography, the presence of moderate or severe DD was an independent predictor of mortality. Mild DD, although prevalent, did not affect survival rate.

Exploitation of stem cell homing for gene delivery.

Stem cells have been the focus of numerous investigations to treat diseases as far ranging as diabetes, chronic heart failure and multiple sclerosis over the past decade. The process of stem-cell-based repair of acute injury involves homing and engrafting of the stem cell of interest to the site of injury followed by either differentiation of the stem cell to indigenous end-organ cells or liberation of paracrine factors that lead to preservation and/or optimization of organ function. Recognition of the ability of stem cells to home to sites of acute injury suggests that, if appropriately defined and harnessed, stem cell homing could serve as a means of local drug delivery through the infusion of genetically engineering stem cells that secrete gene products of interest. The authors have recently demonstrated the use of this approach in preclinical studies of acute myocardial function. In addition, the use of engineered cells that home to appropriate niches have been used to correct genetic deficiency states (i.e., severe combined immunodeficiency, diabetes mellitus) in patients with otherwise chronic debilitating diseases. This review focuses on exploiting stem cell homing for gene transfer and on the state of the art and the challenges that face the field.

Trends in epidemiology and management of breast cancer in developing Arab countries: a literature and registry analysis.

BACKGROUND: Registries and research on breast cancer in Arabic and developing countries are limited. METHODS: We searched PubMed, Medline, WHO and IAEA publications, national, regional, hospital tumor registries and abstracts. We reviewed and analyzed available data on epidemiological trends and management of breast cancer in Arab countries, and compared it to current international standards of early detection, surgery and radiation therapy. RESULTS: Breast cancer constitutes 13-35% of all female cancers. Almost half of patients are below 50 and median age is 49-52 years as compared to 63 in industrialized nations. A recent rise of Age-Standardized Incidence Rates (ASR) is noted. Advanced disease remains very common in Egypt, Tunisia, Saudi Arabia, Syria, Palestinians and others. Mastectomy is still performed in more than 80% of women with breast cancer. There are only 84 radiation therapy centers, 256 radiation oncologists and 473 radiation technologists in all Arab countries, as compared with 1875, 3068 and 5155, respectively, in the USA, which has an equivalent population of about 300 million. Population-based screening is rarely practiced. Results from recent campaigns and studies show a positive impact of clinical breast examination leading to more early diagnosis and breast-conserving surgery. CONCLUSIONS: Breast cancer is the most common cancer among women in Arab countries with a young age of around 50 years at presentation. Locally advanced disease is very common and total mastectomy is the most commonly performed surgery. Awareness campaigns and value of clinical breast examination were validated in the Cairo Breast Cancer Screening Trial. More radiation centers and early detection would optimize care and reduce the currently high rate of total mastectomies. Population-based screening in those countries with affluent resources and accessible care should be implemented.

Effects of young age at presentation on survival in breast cancer.

BACKGROUND: Young age remains a controversial issue as a prognostic factor in breast cancer. Debate includes patients from different parts of the world. Almost 50% of patients with breast cancer seen at the American University of Beirut Medical Center (AUBMC) are below age 50. METHODS: We reviewed 1320 patients seen at AUBMC between 1990 and 2001. We divided them in three age groups: Below 35, 35-50, and above 50. Data and survival were analyzed using Chi-square, Cox regression analysis, and Kaplan Meier. RESULTS: Mean age at presentation was 50.8 years. 107 patients were below age 35, 526 between 35-50 and 687 patients above age 50. Disease stages were as follows: stage I: 14.4%, stage II: 59.9%, stage III: 20% and stage IV: 5.7%. Hormone receptors were positive in 71.8% of patients below 35, in 67.6% of patients 35-50 and in 78.3% of patients above 50. Grade of tumor was higher as age at presentation was lower. More young patients received anthracycline-based adjuvant chemotherapy. Of hormone receptor-positive patients, 83.8% of those below age 35 years, 87.76% of those aged 35-50 years, and 91.2% of those aged above 50 years received adjuvant tamoxifen. The mean follow up time was 3.7 +/- 2.9 years. Time to death was the only variable analyzed for survival analysis. Excluding stage IV patients, tumor size, lymph node, tumor grade and negative hormone receptors were inversely proportional to survival. Higher percentage of young patients at presentation developed metastasis (32.4% of patients below 35, as compared to 22.9% of patients 35-50 and 22.8% of patients above 50) and had a worse survival. Young age had a negative impact on survival of patients with positive axillary lymph nodes, and survival of patients with positive hormonal receptors, but not on survival of patients with negative lymph nodes, or patients with negative hormonal receptors. CONCLUSION: Young age at presentation conferred a worse prognosis in spite of a higher than expected positive hormone receptor status, more anthracycline-based adjuvant chemotherapy and equivalent adjuvant tamoxifen hormonal therapy in younger patients. This negative impact on survival was seen in patients with positive lymph nodes and those with positive hormonal receptors.