Prehospital Predictors of Atypical STEMI Symptoms.

Introduction: Rapid prehospital identification of patients with ST-elevation myocardial infarction (STEMI) is a critical step to reduce time to treatment. Broad screening with field 12-lead ECGs can lead to a high rate of false positive STEMI activations due to low prevalence. One strategy to reduce false positive STEMI interpretations is to limit acquisition of 12-lead ECGs to patients who have symptoms strongly suggestive of STEMI, but this may delay care in patients who present atypically and lead to disparities in populations with more atypical presentations. We sought to assess patient factors associated with atypical STEMI presentation.Methods: We retrospectively analyzed consecutive adult patients for whom Los Angeles Fire Department paramedics obtained a field 12-lead ECG from July 2011 through June 2012. The regional STEMI receiving center registry was used to identify patients with STEMI. Patients were designated as having typical symptoms if paramedics documented provider impressions of chest pain/discomfort, cardiac arrest, or cardiac symptoms, otherwise they were designated as having atypical symptoms. We utilized logistic regression to determine patient factors (age, sex, race) associated with atypical STEMI presentation.Results: Of the 586 patients who had STEMI, 70% were male, 43% White, 16% Black, 20% Hispanic, 5% Asian and 16% were other or unspecified race. Twenty percent of STEMI patients (n = 117) had atypical symptoms. Women who had STEMI were older than men (74 years [IQR 62-83] vs. 60 years [IQR 53-70], p < 0.001). Univariate predictors of atypical symptoms were older age and female sex (p < 0.0001), while in multivariable analysis older age [odd ratio (OR) 1.05 per year, [95%CI 1.04-1.07, p < 0.0001] and black race (OR vs White 2.18, [95%CI 1.20-3.97], p = 0.011) were associated with atypical presentation.Conclusion: Limiting prehospital acquisition of 12-lead ECGs to patients with typical STEMI symptoms would result in one in five patients with STEMI having delayed recognition, disproportionally impacting patients of older age, women, and Black patients. Age, not sex, may be a better predictor of atypical STEMI presentation.

Genetic profile, PTEN mutation and therapeutic role of PTEN in glioblastomas.

New therapeutic strategies are needed to improve survival in glioblastoma (GBM) the most malignant astrocytic tumor. We evaluated: a) the genetic status of 22 GBMs by comparative genomic hybridization (CGH); b) the specific role of mutation and/or homozygous deletion of PTEN in the genesis of GBM; and c) the possible therapeutic role of PTEN against GBM, in vitro. CGH demonstrated that the most frequent region of gain was at chromosome 7p, whereas the most frequent losses occurred at chromosomes 10q and 13q. Losses at chromosome 10 were found in 36% of patients, and PTEN was mutated in 27% of the 22 GBMs, including 4 point mutations and 2 homozygous deletions. The possible therapeutic role of PTEN in GBM was also studied in a system based on retroviral infection of the GBM cell line A172, homozygously deleted at the PTEN locus. A172 growth and proliferation rate were reduced by 50% after PTEN transduction. Moreover, we showed that inhibition of cell growth occurred through the PI3K/Akt/p27 pathway. Our findings suggest that PTEN participates in the genesis of GBM, and might be further studied as a candidate therapeutic agent in other testing systems.

PTEN, DMBT1, and p16 alterations in diffusely infiltrating astrocytomas.

Losses at chromosomes 10q and 9p are genetic events implicated in the genesis of diffusely infiltrating astrocytomas. We studied the role of PTEN (10q23.3), DMBT1 (10q25.3-26.1) and p16 (9p21) tumor suppressor genes in a series of 50 low- and high-grade astrocytomas. A genetic screening for point mutations, homozygous deletions and promoter hypermethylation was done by PCR-SSCP, direct sequencing, differential PCR, and methylation specific PCR. PTEN was mutated in 23% and homozygously deleted in 9% GBMs, but not in grade II and III astrocytomas. Homozygous deletions of DMBT1 were found in 5% GBMs and 13% low-grade astrocytomas, but not in anaplastic astrocytomas. p16 suffered homozygous deletion in 27% GBMs and 13% low-grade astrocytomas, though no p16 point mutations were found in any of the 50 astrocytomas. p16 promoter hypermethylation was found in 9% GBMs and 6% low-grade astrocytomas. Our results might indicate that PTEN alterations are late genetic events in the progression of low to high-grade astrocytomas, versus DMBT1 and p16 alterations that also occur in low-grade astrocytomas, and might be considered as early genetic events. The majority of samples did not present more than one alteration. Taken together, these data suggest that there are multiple independent mechanisms to control cell growth and prevent GBM tumorigenesis, and that aberrations in several distinct pathways or at several sites within a pathway are needed to overcome these control mechanisms.