A bioassay using intestinal organoids to measure CFTR modulators in human plasma.

Treatment efficacies of drugs depend on patient-specific pharmacokinetic and pharmacodynamic properties. Here, we developed an assay to measure functional levels of the CFTR potentiator VX-770 in human plasma and observed that VX-770 in plasma from different donors induced variable CFTR function in intestinal organoids. This assay can help to understand variability in treatment response to CFTR potentiators by functionally modeling individual pharmacokinetics.

Five-year clinical experience with Abiomed BVS 5000 as a ventricular assist device for cardiac failure.

Mechanical support for the failing heart has interested and challenged cardiac specialists for decades. In the United States alone, there are close to 375,000 cardiac surgical procedures performed each year, and, despite the recent advances in myocardial protection, surgical techniques, intra-aortic balloon therapy and maximal pharmacological support, postoperative ventricular dysfunction continues to occur in 0.5-1.0% of all patients undergoing cardiac surgery. This retrospective review describes our 5-year clinical experience at the Brigham and Women's Hospital with the Abiomed BVS 5000 as a means of ventricular support. During the period of 1994 to present, 7,428 cardiac surgical operations were performed at our institution. The Abiomed BVS 5000 has been implanted in 47 patients exhibiting ventricular failure. There were 38 patients in the bridge-to-recovery group and nine patients in the bridge-to-transplantation group. Twenty-five patients (66%) in the bridge-to-recovery group were weaned and 16 patients (42%) went on to discharge. In the bridge-to-transplantation group, one patient actually recovered myocardial function and one expired on the device. The remaining seven patients (77%) underwent cardiac transplantation with post-transplant survival at 66%. Overall, patients were supported in the isolated left ventricular mode (28%), in the biventricular mode (45%) and in the isolated right ventricular mode (28%). The Abiomed BVS 5000 has been shown to be a safe and simple cardiac support system with no mechanical failure. Our experience shows that a substantial number of patients suffering from ventricular failure will benefit from the use of this device. The results also justify the use of this device in groups of patients other that of postcardiotomy ventricular failure.

The logistics and cost-effectiveness of circulatory support: advantages of the ABIOMED BVS 5000.

BACKGROUND: In 1994, the ABIOMED BVS 5000 was incorporated into our acute cardiac assist armamentarium. This report is a general overview of our experience. A hypothetical cost analysis focusing on specific devices and device-related personnel contrasted the BVS 5000 with our prior model of centrifugal pump use. METHODS: In 3 years, 22 patients were supported with the BVS 5000, as a biventricular assist device in 40%, right ventricular assist device in 27%, and left ventricular assist device in 32%. Indications were postcardiotomy support in 12, acute myocarditis in 2, bridge to transplant in 4, and failed heart transplant in 4. The cost analysis was performed retrospectively. The actual cost of disposable blood pumps, including replacement pumps, and cannulae constituted the BVS cost. The hypothetical centrifugal costs included the disposables, replacement cones, as well as the labor costs of the continuous perfusionist coverage. RESULTS: Of the 22 patients, 10 (45%) were weaned and 13 (59%) were successfully discharged. Five patients were transplanted while on BVS 5000 support, accounting for a higher rate of discharge. Comparison of "actual" BVS costs with "projected" centrifugal costs revealed differences based upon the intended application of the BVS. In bridge-to-transplant patients with long duration of support, the daily cost of support was dramatically lower with the BVS 5000. For short-term postcardiotomy support, acute myocarditis, or failed transplant, the differences were small. CONCLUSIONS: Because the BVS 5000 was readily managed by the intensive care unit nursing staff, this system displaced centrifugal systems in our program. Outcome measures of weaning and successful discharge were improved relative to our prior experience with centrifugal pumps. Even without taking indirect costs into account, the hypothetical cost analysis supported continued use of the BVS system for acute cardiac assistance.

QEEG changes during cardiopulmonary bypass: relationship to postoperative neuropsychological function.

The relationship of changes in intraoperative QEEG and postoperative cognitive function was studied in 32 patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass (CPB). All patients were anesthetized with a high dose narcotic technique in which CPB was carried out using moderate hypothermia. EEG recorded continuously throughout each procedure was analyzed using the neurometric technique. Neuropsychological (NP) evaluations were administered to all patients before, 1 week and 2-3 months postoperatively. A decrement in postoperative performance of 2 standard deviations in two or more tests from preoperative testing was defined as a new cognitive deficit. Of the patients studied, 40.6% demonstrated a new postoperative cognitive deficit at 1 week. At 2-3 months postoperatively, 28.1% continued to show a cognitive deficit. Discriminant analysis of the QEEG as a function of NP performance was calculated at select times during the surgical procedure. QEEG prediction of NP performance was just above chance at the 1 week comparison but excellent for the 2-3 month comparisons. This study suggests that with appropriate monitoring protocols, intraoperative QEEG may predict cognitive dysfunction experienced by patients 2-3 months postoperatively.

A modified collection and rapid infusion system for shed whole blood autotransfusion during aortic aneurysm surgery.

We describe our experience in 10 patients (5 males) undergoing resection of a descending thoracic aortic aneurysm or a thoracoabdominal aortic aneurysm in which a modified shed whole blood collection and autotransfusion system was used. This modification allows several options for the processing and autotransfusion of shed blood: use of the cell saving device or the ultrafiltration of collected blood, and the autotransfusion of unprocessed shed whole blood. Either low dose heparin or sodium citrate was used for anticoagulation. All 10 patients underwent autotransfusion and volume resuscitation with the modified rapid infusion device. Total autotransfusion ranged from 1400 ml to 7843 ml. Ultrafiltration volumes ranged from 600 ml to 1100 ml. There were no intraoperative deaths and no patient reoperations for bleeding. Arterial blood gases, potassium, and platelet counts were all within the normal laboratory ranges. This modification enables the clinician to process poor quality shed blood and reinfuse whole blood, in an attempt to decrease the need for homologous blood products.

Shed whole blood autotransfusion during aortic aneurysm operation with a modified collection infusion system.

We describe a modified shed whole blood collection and autotransfusion system that allows several options for the processing and autotransfusion of shed blood: use of the Cell Saver (Haemonetics, Braintree, MA) or the ultrafiltration of collected blood, and the autotransfusion of unprocessed shed whole blood. The system has proved useful for transfusion in the setting of thoracic aortic operations, and we describe here our experience in 5 patients undergoing resection of a descending thoracic aortic aneurysm in whom this system was used.