Rapid chromatin repression by Aire provides precise control of immune tolerance.

Aire mediates the expression of tissue-specific antigens in thymic epithelial cells to promote tolerance against self-reactive T lymphocytes. However, the mechanism that allows expression of tissue-specific genes at levels that prevent harm is unknown. Here we show that Brg1 generates accessibility at tissue-specific loci to impose central tolerance.

Epigenomics of human CD8 T cell differentiation and aging.

The efficacy of the adaptive immune response declines dramatically with age, but the cell-intrinsic mechanisms driving immune aging in humans remain poorly understood. Immune aging is characterized by a loss of self-renewing naïve cells and the accumulation of differentiated but dysfunctional cells within the CD8 T cell compartment. Using ATAC-seq, we inferred the transcription factor binding activities correlated with naive and central and effector memory CD8 T cell states in young adults.

Therapeutic Interchange of Clevidipine For Sodium Nitroprusside in Cardiac Surgery.

Background: Generic price inflation has resulted in rising acquisition costs for sodium nitroprusside (SNP), an agent historically described as the drug of choice for the treatment of perioperative hypertension in cardiac surgery.

Purpose: To describe the implementation and cost avoidance achieved by utilizing clevidipine as an alternative to SNP in cardiac surgery patients at a 520-bed community teaching hospital that performs more than 300 cardiac surgeries each year.

Methods: A multidisciplinary team inclusive of anesthesiologists, intensivists, pharmacists, and surgeons collaborated to develop a therapeutic interchange for SNP in cardiac surgery patients.

Discovery of novel non-synonymous SNP variants in 988 candidate genes from 6 centenarians by target capture and next-generation sequencing.

Despite evidence of a substantial genetic component, the genetic factors that underlie longevity in humans remain to be identified. Previous genome-wide linkage and association studies have not found strong evidence for the contribution of common variants besides the APOE gene, suggesting the role of rare variants in human longevity. To discover rare variants that might contribute to longevity, we selected 988 candidate genes and performed a pilot study to identify novel non-synonymous variants in 6 Ashkenazi Jewish centenarians older than 105.

The impact of blood conservation on outcomes in cardiac surgery: is it safe and effective?

Background: Increasing evidence shows that perioperative blood transfusion in cardiac surgery is associated with increased postoperative morbidity and mortality and decreased long-term survival. Tolerance of "permissive anemia" is an important element of perioperative blood conservation strategy. The safety of tolerating perioperative anemia has been a significant deterrent for widespread application of blood conservation.

Blood conservation in practice: an overview.

Allogeneic blood transfusions are associated with risks and unfavourable outcomes. Blood conservation provides an alternative, with potential to improve patient care with limited or no blood transfusion. Many approaches are available, but the most essential ones are simple and cost free.

Postoperative blood loss and transfusion associated with use of Hextend in cardiac surgery patients at a blood conservation center.

Background: Hydroxyethyl starch (HES) solutions are readily available colloids, but their widespread use is shadowed by controversies surrounding their effects on bleeding. This retrospective study was conducted to evaluate the relationship between Hextend (HEX; Hospira, Inc.) doses of 1 to 20 mL/kg and allogeneic transfusion and 24-hour chest tube drainage (CTD) in cardiac surgeries at a blood conservation center.

Anesthetic consideration for descending thoracic aortic aneurysm repair.

Anesthesia for surgery of the aorta poses some of the most difficult challenges for anesthesiologists. Major hemodynamic and physiologic stresses and sophisticated techniques of extracorporeal support are superimposed on patients with complex medical disease states. In this review, etiologies, natural history, and surgical techniques of thoracic aortic aneurysm are presented.

Use of the Hemobag for modified ultrafiltration in a Jehovah's Witness patient undergoing cardiac surgery.

Modified ultrafiltration is an important technique to concentrate the patient's circulating blood volume and the residual whole blood in the extracorporeal circuit post-cardiopulmonary bypass. The Hemobag system is a device cleared by the US Food and Drug Administration and represents a novel and safe modification of traditional modified ultrafiltration systems. It is quick and easy to operate by the perfusionist during the hemoconcentration process.

Geographic regional differences in rocuronium bromide dose-response relation and time course of action: an overlooked factor in determining recommended dosage.

Background: Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China.

Methods: Neuromuscular block of six consecutive 50-microg/kg rocuronium incremental doses followed by 300 microg/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland).

Predictors of transfusion requirements for cardiac surgical procedures at a blood conservation center.

Background: Previous studies defining perioperative risk factors for allogeneic transfusion requirements in cardiac surgery were limited to highly selected cardiac surgery populations or were associated with high transfusion rates. The purpose of this study was to determine perioperative risk factors and create a formula to predict transfusion requirements for major cardiac surgical procedures in a center that practices a multimodality approach to blood conservation.

Methods: We performed an observational study on 307 consecutive patients undergoing coronary artery bypass grafting, valve, and combined (coronary artery bypass grafting and valve) procedures.

Multidisciplinary management of a Jehovah's Witness patient for the removal of a renal cell carcinoma extending into the right atrium.

Purpose: To highlight the management of a Jehovah's witness surgical patient presenting for cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest.

Clinical Features: A 47-yr-old male, Jehovah's Witness, with renal cell carcinoma was admitted for left radical nephrectomy and excision of tumour thrombus extending into the junction of the inferior vena cava (IVC) and right atrium (RA). The preoperative goals were to maximize red blood cell mass, delineate the extent of tumour extension and develop a surgical plan incorporating blood conservation strategies to minimize blood loss.

Comparison of arterial systolic pressure variation with other clinical parameters to predict the response to fluid challenges during cardiac surgery.

Prophylactic optimization of stroke volume during surgery has been thought by some to reduce complications following surgery. Mechanical ventilation has been shown to induce variations in systolic systemic arterial blood pressure. Measuring such variations in systolic pressure (SPV) might serve as an attractive method for guiding fluid therapy intraoperatively.

Anesthetic considerations for endovascular aortic repair.

Endovascular aortic repair is a new alternative to conventional surgical techniques. A variety of devices available for endovascular aortic repair are discussed and the outcomes after repair are reviewed. Anesthetic considerations during endovascular repair are dictated by the device being used, as well as the site of device deployment.