Low value of inherited thrombophilia testing among patients with stroke or transient ischemic attack: A three-year retrospective study.

BACKGROUND/PURPOSE: Inherited thrombophilia testing in the acute inpatient setting is controversial and expensive, and rarely changes clinical management. We evaluated ordering patterns and results of inpatient inherited thrombophilia testing for patients who presented with an isolated acute ischemic stroke or transient ischemic attack (TIA) without concurrent venous thromboembolism. METHODS: We retrospectively analyzed patients admitted for acute ischemic stroke or TIA between January 1st, 2019 and December 31st, 2021 at Thomas Jefferson University Hospitals in Philadelphia, PA and who underwent inherited thrombophilia testing during the hospital admission. Charts were reviewed to determine stroke risk factors, test results, and clinical management. RESULTS: Among 2108 patients admitted for acute ischemic stroke or TIA (including branch and central retinal artery occlusions) during the study period, the study included 249 patients (median age 49.0 years, 50.2% female) who underwent inpatient testing for factor V Leiden, prothrombin G20210A variant, hyperhomocysteinemia, PAI-1 elevation, and deficiencies of protein C and S and antithrombin. 42.2% of patients had at least one abnormal test, and among the 1035 tests ordered, 14.3% resulted abnormal. However, 28% of abnormal tests were borderline positive antigen or activity assays that likely represented false positives. There was no significant difference in the likelihood of a positive test among patients without stroke risk factors vs those with risk factors (47.1% vs 40.9%, P = .428), nor any significant difference between those under vs over age 50 years (45.7% vs 38.3%, P = .237). No patients with an abnormal result had their clinical management changed as a result. Charges for the tests totaled $468,588 USD. CONCLUSIONS: Inherited thrombophilia testing in the hospital immediately following isolated acute arterial ischemic stroke or TIA was associated with high rates of likely false positive results and was expensive. Positive results did not change clinical management in a single case.

Diabetes mellitus associated neurovascular lesions in the retina and brain: A review.

Diabetes mellitus (DM) is now recognized as a system-wide, autoimmune, inflammatory, microvascular disorder, which, in the retina and brain results in severe multifocal injury now recognized as a leading cause, world-wide, of progressive vision loss and dementia. To address this problem, resulting primarily from variations in glycemia in the prediabetic and overt diabetic states, it must be realized that, although some of the injury processes associated with diabetes may be system wide, there are varying responses, effector, and repair mechanisms that differ from organ to organ or within varying cell structures. Specifically, within the retina, and similarly within the brain cortex, lesions occur of the "neurovascular unit", comprised of focal microvascular occlusions, inflammatory endothelial and pericyte injury, with small vessel leakage resulting in injury to astrocytes, Müller cells, and microglia, all of which occur with progressive neuronal apoptosis. Such lesions are now recognized to occur before the first microaneurysms are visible to imaging by fundus cameras or before they result in detectable symptoms or signs recognizable to the patient or clinician. Treatments, therefore, which currently are not initiated within the retina until edema develops or there is progression of vascular lesions that define the current staging of retinopathy, and in the brain only after severe signs of cognitive failure. Treatments, therefore are applied relatively late with some reduction in progressive cellular injury but with resultant minimal vision or cognitive improvement. This review article will summarize the multiple inflammatory and remediation processes currently understood to occur in patients with diabetes as well as pre-diabetes and summarize as well the current limitations of methods for assessing the structural and functional alterations within the retina and brain. The goal is to attempt to define future screening, monitoring, and treatment directions that hopefully will prevent progressive injury as well as enable improved repair and attendant function.

Mechanics and hemodynamics of esophageal varices during peristaltic contraction.

Our hypothesis states that variceal pressure and wall tension increase dramatically during esophageal peristaltic contractions. This increase in pressure and wall tension is a natural consequence of the anatomy and physiology of the esophagus and of the esophageal venous plexus. The purpose of this study was to evaluate variceal hemodynamics during peristaltic contraction. A simultaneous ultrasound probe and manometry catheter was placed in the distal esophagus in nine patients with esophageal varices. Simultaneous esophageal luminal pressure and ultrasound images of varices were recorded during peristaltic contraction. Maximum variceal cross-sectional area and esophageal luminal pressures at which the varix flattened, closed, and opened were measured. The esophageal lumen pressure equals the intravariceal pressure at variceal flattening due to force balance laws. The mean flattening pressures (40.11 +/- 16.77 mmHg) were significantly higher than the mean opening pressures (11.56 +/- 25.56 mmHg) (P < or = 0.0001). Flattening pressures >80 mmHg were generated during peristaltic contractions in 15.5% of the swallows. Variceal cross-sectional area increased a mean of 41% above baseline (range 7-89%, P < 0.0001) during swallowing. The peak closing pressures in patients that experience future variceal bleeding were significantly higher than the peak closing pressures in patients that did not experience variceal bleeding (P < 0.04). Patients with a mean peak closing pressure >61 mmHg were more likely to bleed. In this study, accuracy of predicting future variceal bleeding, based on these criteria, was 100%. Variceal models were developed, and it was demonstrated that during peristaltic contraction there was a significant increase in intravariceal pressure over baseline intravariceal pressure and that the peak intravariceal pressures were directly proportional to the resistance at the gastroesophageal junction. In conclusion, esophageal peristalsis in combination with high resistance to blood flow through the gastroesophageal junction leads to distension of the esophageal varices and an increase in intravariceal pressure and wall tension.

A new ultrasound-guided esophageal variceal pressure-measuring device.

OBJECTIVE: To develop a noninvasive method and device to determine intravariceal pressure and variceal wall tension by measuring the variables of the Laplace equation and test this device in a model of esophageal varices. METHODS: Two variceal pressure measurement devices were constructed. The first device consists of an Olympus 20 MHz ultrasound transducer placed next to a latex balloon catheter attached to a pressure transducer. The second device was constructed by placing the same ultrasound transducer inside a latex condom balloon attached to a pressure transducer. These pressure measurement devices were tested blindly in varix models with different intravariceal pressures, by inflating the balloon to flatten the varix models. Each variceal pressure was measured 10 times by two separate investigators blinded to the actual pressures. The mean intravariceal pressures were calculated. The variceal models were made of a latex balloon filled with water and coffeemate. RESULTS: The correlation coefficient between the actual and measured varix pressures for both devices was 0.99. The percent error ranged from 0 to 10%. The correlation coefficient between the investigators making the blinded measurements for both devices was 0.98. CONCLUSION: Two pressure-measuring devices were developed to determine intravariceal pressure in a model varix system. These devices demonstrate a low percent error and a high correlation to the actual variceal pressures with low intra- and interobserver variability. These devices have the potential to measure all the variables of the Laplace equation for wall tension. We plan to test these devices in human subjects.

A new device for measuring esophageal variceal pressure.

BACKGROUND: Esophageal varices are a frequent source of bleeding in patients with cirrhosis. Elevated intravariceal pressure is associated with variceal bleeding. There is no simple, easy-to-use device for noninvasive measurement of intravariceal pressure. The purposes of this study were to develop a noninvasive method for measuring intravariceal pressure, and to develop a model of esophageal varices that can be used to test this pressure measurement device. METHODS: A variceal pressure measurement device was constructed by placing a 20 MHz US transducer in a latex balloon catheter sheath and attaching the catheter to a pressure transducer. The pressure measurement device was passed though the accessory channel of a large-channel endoscope and tested in blinded fashion by using tip deflection to compress each of 4 variceal models with the device. The pressure within each model was measured 10 times by 2 separate investigators blinded to the actual pressures. The mean (SD) pressure was calculated for each model. The variceal models were made of nitrocellulose dialysis tubing filled with water. Each "varix" had the same diameter but a different intraluminal pressure (5.5, 10, 15, 21.5 mm Hg). OBSERVATIONS: The correlation coefficient between the actual and measured "varix" pressures for the first investigator (L.S.M.) was r = 0.96: 99% CI [0.93, 0.98]. For the varix models with pressures of 21.5, 15, 10, and 5.5 the percent errors were, respectively, 9.5, 3.9, 5.1, and 0.7. The correlation coefficient between the actual and measured varix pressures for the second investigator (Q.D.) was r = 0.97: 99% CI [0.94, 0.98]. For the varix models with pressures of 21.5, 15, 10, and 5.5 the percent errors were, respectively, 10.3, 3.4, 9.8, and 1.1. The correlation coefficient between the 2 investigators (L.S.M., Q.D.) for the varix model pressures was r = 0.97: 99% CI [0.95, 0.99]. CONCLUSION: The variceal pressure measuring device developed for this study measured intravariceal pressure in a model varix with a low percent error and high correlation to the actual pressures. Intraobserver and interobserver variability was low.