BackgroundConventional proteomic approaches have thus far been unable to identify novel serum biomarkers for ovarian cancer that are more sensitive and specific than the current clinically used marker, CA-125. Because endogenous peptides are smaller and may enter the circulation more easily than proteins, a focus on the low-molecular-weight region may reveal novel biomarkers with enhanced sensitivity and specificity. In this study, we deciphered the peptidome of ascites fluid from 3 ovarian cancer patients and 3 benign individuals (ascites fluid from patients with liver cirrhosis).ResultsFollowing ultrafiltration of the ascites fluids to remove larger proteins, each filtrate was subjected to solid phase extraction and fractionated using strong cation exchange chromatography. The resultant fractions were analyzed using an Orbitrap mass spectrometer. We identified over 2000 unique endogenous peptides derived from 259 proteins. We then catalogued over 777 peptides that were found only in ovarian cancer ascites. Our list of peptides found in ovarian cancer specimens includes fragments derived from the proteins vitronectin, transketolase and haptoglobin.ConclusionsPeptidomics may uncover previously undiscovered disease-specific endogenous peptides that warrant further investigation as biomarkers for ovarian cancer.
Objectives
Isolated dizziness is a challenging stroke presentation in the emergency department, but little is known about this problem in other clinical settings. We sought to compare stroke hospitalizations after treat-and-release clinic visits for purportedly “benign dizziness” between general and specialty care settings.
Methods
This was a population-based retrospective cohort study from a national database. We included clinic patients with a first incident treat-and-release visit diagnosis of non-specific dizziness/vertigo or a peripheral vestibular disorder (ICD-9-CM 780.4 or 386.x [not 386.2]). We compared general care (internal medicine, family medicine) vs. specialty care (neurology, otolaryngology) providers. We used propensity scores to control for baseline stroke risk differences unrelated to dizziness diagnosis. We measured excess (observed>expected) stroke hospitalizations in the first 30 d (i.e., missed strokes associated with an adverse event).
Results
We analyzed 144,355 patients discharged with “benign dizziness” (n=117,117 diagnosed in general care; n=27,238 in specialty care). After propensity score matching, patients in both groups were at higher risk of stroke in the first 30 d (rate difference per 10,000 treat-and-release visits for “benign dizziness” 24.9 [95% CI 18.6–31.2] in general care and 10.6 [95% CI 6.3–14.9] in specialty care). Short-term stroke risk was higher in general care than specialty care (relative risk, RR 2.2, 95% CI 1.5–3.2) while the long-term risk was not significantly different (RR 1.3, 95% CI 0.9–1.9), indicating higher misdiagnosis-related harms among dizzy patients who initially presented to generalists after adequate propensity matching.
Conclusions
Missed stroke-related harms in general care were roughly twice that in specialty care. Solutions are needed to address this care gap.
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