Modes of Failure in Venous Thromboembolism Prophylaxis.

Venous thromboembolism (VTE) is associated with potentially preventable in-hospital morbidity and mortality. Although evidence-based guidelines are widely available, their application in clinical practice varies markedly. VTE prophylaxis involves a multistep dynamic process that can fail at various points during hospital stay. Our aim was to identify defects in VTE prophylaxis. Upon admission, our patients undergo VTE risk stratification and orders for prophylaxis are entered. All patients that fulfill the criteria for the Patient Safety Indicator (PSI)-12, as defined by the Agency for Healthcare Research and Quality, are prospectively entered in a database. From a review of 138 PSI-12 patients, only 21 had correct risk stratification and appropriate chemoprophylaxis during their hospital stay; 70 had been incorrectly stratified, with 28 of these patients receiving incorrect prophylaxis due to incorrect stratification, thus delaying the correct administration of chemoprophylaxis for >24 h. Inadequate application of mechanical prophylaxis was noted in 114 patients. VTE prophylaxis relies on correct risk stratification, ordering appropriate pharmacomechanical measures and, finally, the delivery of this treatment throughout the hospital stay. A large percentage of patients who had a thromboembolic complication received inadequate prophylaxis. This study identifies potential areas for intervention to improve VTE prophylaxis.

Leveraging Electronic Health Record Implementation to Facilitate Clinical and Operational Quality Improvement in an Ambulatory Surgical Clinic.

The implementation of electronic health records is a challenging, complex process requiring significant resources. The temptation is to convert a paper process into electronic format. This strategy fosters a familiar product to the users but is fraught with pitfalls. We chose to utilize the opportunity of the implementation of an enterprise-wide ambulatory electronic health record to foster an overreaching clinical and operational improvement project in a multispecialty surgical ambulatory clinic practice. We interrogated every aspect of the practice: clinic design, scheduling, physical space, staffing, and clinical and operational workflows. We present here the results of a 3-year process improvement.

Thoracoabdominal aortic aneurysm repair: current endovascular perspectives.

Thoracoabdominal aneurysms account for roughly 3% of identified aneurysms annually in the United States. Advancements in endovascular techniques and devices have broadened their application to these complex surgical problems. This paper will focus on the current state of endovascular thoracoabdominal aneurysm repair, including specific considerations in patient selection, operative planning, and perioperative complications. Both total endovascular and hybrid options will be considered.

Mesenteric ischemia.

This article reviews the presentation, diagnosis, evaluation, and treatment of the various forms of mesenteric ischemia, including acute and chronic ischemia. In addition, nonocclusive mesenteric ischemia and median arcuate ligament compressive syndrome are covered. The goals are to provide a structured and evidence-based framework for the evaluation and management of patients with these intestinal ischemia syndromes. Special attention is given to avoiding typical pitfalls in the diagnostic and treatment pathways. Operative techniques are also briefly discussed, including an evidence-based review of newer endovascular techniques.

Low incidence of paraplegia after thoracic endovascular aneurysm repair with proactive spinal cord protective protocols.

OBJECTIVE: Paraparesis and paraplegia after thoracic endovascular aneurysm repair (TEVAR) is a greatly feared complication. Multiple case series report this risk up to 13% with no, or inconsistent, application of interventions to enhance and protect spinal cord perfusion. In this study, we report our single-institution experience of TEVAR, using the same proactive spinal cord ischemia protection protocol we use for open repair. METHODS: Endovascular thoracic aortic interventions were performed for both on-label (aneurysm) and off-label (trauma, other) indications. Aortic area covered was recorded as a fraction from the subclavian to celiac origins and reported as a percentage. If debranching was required, measurements were taken from the most distal arch vessel left intact. Intraoperative imaging and postoperative computed tomographic angiogram were used in calculating aortic percent coverage. Outcomes were recorded in a clinical database and analyzed retrospectively. The spinal cord ischemia protection included routine spinal drainage (spinal fluid pressure <10 mm Hg), endorphin receptor blockade (naloxone infusion), moderate intraoperative hypothermia (<35°C), hypotension avoidance (mean arterial pressure >90 mm Hg), and optimizing cardiac function. RESULTS: From 2005 to 2012, 94 consecutive TEVARs were studied. Indications were thoracic aneurysm (n = 48), plaque rupture with or without dissection (n = 23), trauma (n = 15), and other (n = 8). Forty-nine percent were acute, average age was 68.5 years, 60% (n = 56) were male, and the mean follow-up was 12 months. Mean length of aortic coverage was 161 mm, correlating to 59.4% aortic coverage. One patient had delayed paralysis (1.1%; observed/expected ratio, 0.12) and recovered enough to ambulate easily without assistance. Other complications included wound (7.5%), stroke (4.3%), myocardial infarct (4.3%), and renal failure (1.1%). CONCLUSIONS: Proactive spinal cord protective protocols appear to reduce the incidence of spinal ischemia after TEVAR compared with historical series. This study would suggest that active, as opposed to reactive, approaches to spinal ischemia portend a better long-term outcome. Multimodal protection is essential, especially if long segment coverage is planned.

From Ebers to EVARs: A Historical Perspective on Aortic Surgery.

Pathology of the aorta has been recognized for nearly three and a half millennia, dating back to the first recorded description in the scrolls of Ebers, circa 1550 BC. Since that time, treatment has evolved from magical medicinal remedies and incantations to nearly outpatient percutaneous interventions. From the first attempts at open surgical reconstruction in the 1700s and 1800s, to the latest generations of endovascular devices, innovative pioneers have pushed the envelope of surgical technique in developing unique and novel strategies to treat the ever complex pathology of the aorta. We are just now beginning to understand these pathologies at the molecular and genetic levels, and with that expansive extent of investigation enters a journal, dedicated solely to the aorta. With this article, we hope to illuminate the rich and deep history of aortic pathology, and the innovations leading to the technology of today. A firm understanding of our past provides a strong foundation for further growth into the future.

Screening for abdominal aortic aneurysms.

Ruptured AAA ranks as the 15th leading cause of death overall in the United States, and the 10th leading cause of death in men older than 55 years. Early identification of AAA can save livesand diminish cost. Screening programs havebeen implemented and studied in other countries and have shown a measurable and significant reduction in overall rate of aneurysm-related death. Currently, one-time screening of a small number of ever-smoking men when they turn 65 screening is not widely used in the United States and Medicare, at best, provides one-time screening of a small number of ever-smoking men when they turn 65 years old. Because more than 30,000 individuals in the United States die each year of ruptured AAA, a great deal of progress must be made to eradicate rupture from aneurysmal disease. A more comprehensive system of screening is required and this should be uniformly applied to the U.S. population. It is hoped that scoring systems such as the one outlined in this article, if widely adopted, can greatly enhance screening for aneurysmal disease and prevent the high mortality that stems from this serious vascular disease.

Interleukin-17-dependent autoimmunity to collagen type V in atherosclerosis.

RATIONALE: Considerable evidence shows atherosclerosis to be a chronic inflammatory disease in which immunity to self-antigens contributes to disease progression. We recently identified the collagen type V [col(V)] α1(V) chain as a key autoantigen driving the Th17-dependent cellular immunity underlying another chronic inflammatory disease, obliterative bronchiolitis. Because specific induction of α1(V) chains has previously been reported in human atheromas, we postulated involvement of col(V) autoimmunity in atherosclerosis. OBJECTIVE: To determine whether col(V) autoimmunity may be involved in the pathogenesis of atherosclerosis. METHODS AND RESULTS: Here, we demonstrate Th17-dependent anti-col(V) immunity to be characteristic of atherosclerosis in human coronary artery disease (CAD) patients and in apolipoprotein E-null (ApoE(-/-)) atherosclerotic mice. Responses were α1(V)-specific in CAD with variable Th1 pathway involvement. In early atherosclerosis in ApoE(-/-) mice, anti-col(V) immunity was tempered by an interleukin (IL)-10-dependent mechanism. In support of a causal role for col(V) autoimmunity in the pathogenesis of atherosclerosis, col(V) sensitization of ApoE(-/-) mice on a regular chow diet overcame IL-10-mediated inhibition of col(V) autoimmunity, leading to increased atherosclerotic burden in these mice and local accumulation of IL-17-producing cells, particularly in the col(V)-rich adventitia subjacent to the atheromas. CONCLUSIONS: These findings establish col(V) as an autoantigen in human CAD and show col(V) autoimmunity to be a consistent feature in atherosclerosis in humans and mice. Furthermore, data are consistent with a causative role for col(V) in the pathogenesis of atherosclerosis.

The effect of warfarin therapy on endoleak development after endovascular aneurysm repair (EVAR) of the abdominal aorta.

OBJECTIVES: The presence of an endoleak after endovascular abdominal aortic aneurysm (AAA) repair (EVAR) may predispose to sac expansion and potential sac rupture. The incidence of endoleak after AAA repair can be as high as 20% to 30%. We investigated whether warfarin anticoagulation was an independent risk factor for endoleak after EVAR for AAA. METHODS: All AAA patients who underwent elective EVAR were prospectively followed-up. Data for demographics, clinical comorbidities, outcomes, EVAR devices, and anticoagulation methods were recorded. All patients underwent routine follow-up at 1, 6, and 12 months and annually thereafter. Computed tomography angiography (CTA) with 3-dimensional (3D) volumetric analysis was also completed. RESULTS: During a 7-year period, 127 consecutive patients with infrarenal AAAs who underwent EVAR were monitored for a mean of 2.14 years. The average age at the time of EVAR was 73.8 years. Warfarin therapy alone was administered to 24 patients, and anticoagulation with antiplatelet therapy alone was administered to 103. During the study period, 38 (29.9%) endoleaks were documented. The overall endoleak rate was 13 of 24 in the warfarin group and 25 of 103 in the antiplatelet group (P = .004). CTA 3D volumetric aneurysm sac analysis showed an increase of 16.09% in the warfarin study group and a reduction of 9.71% in the antiplatelet group (P = .04). CONCLUSIONS: Anticoagulation with warfarin appears to be linked to an increased risk for the development of endoleak after EVAR, specifically type II. Volumetric analysis showed warfarin therapy also contributed to persistent aneurysm sac expansion. These data suggest that patients who require warfarin anticoagulation for other indications should be advised that they might be at an increased risk for the development of endoleaks, subsequent secondary interventions, persistent sac expansion, and possible delayed sac rupture.

Reflux-induced collagen type v sensitization: potential mediator of bronchiolitis obliterans syndrome.

BACKGROUND: Lung transplantation continues to have poor long-term survival partly because of the high incidence of bronchiolitis obliterans syndrome (BOS). Gastroesophageal reflux disease (GERD) has been implicated in BOS pathogenesis. We investigated the role of collagen type V [col(V)] sensitization in this process. METHODS: Only primary lung transplant recipients were included. Reflux status was assessed with pH monitoring, impedance plethysmography, and esophagogastroduodenoscopy. Sensitivity to col(V) was determined with trans vivo delayed-type hypersensitivity reaction (DTH). Kaplan-Meier analyses were performed. RESULTS: Of the 54 recipients, 26 had proven GERD. There were no significant between-group differences in diagnosis; donor and recipient age; sex; ischemic time; single vs bilateral; human leukocyte antigen A, B, and DR matching cytomegalovirus status; acute rejections; or mean follow-up period. The mean DTH response in the GERD group was 25.7 x 10(-4) inches vs 18.3 x 10(-4) inches in the non-GERD group (P = .023). There was a significant reduction in BOS-free survival in the GERD group for both BOS-I (GERD+, 28.3%; GERD-, 86.6%; P = .0001) and BOS-II/III (GERD+, 66.2%; GERD-, 91.7%; P = .0374). A second cohort of 53 patients awaiting lung transplantation also was assayed. The mean DTH response in the GERD group was 24.0 x 10(-4) inches vs 13.1 x 10(-4) inches in the non-GERD group (P = .003). There were no differences in age or sex. CONCLUSIONS: GERD is strongly associated with the development of BOS after primary lung transplantation. Col(V) sensitization is associated with reflux and BOS and may play an intermediary role in the pathogenesis of BOS. Trials using col(V) reactivity to assess the impact of antireflux procedures in patients with lung transplantation and idiopathic pulmonary fibrosis are warranted.

Microchimerism is strongly correlated with tolerance to noninherited maternal antigens in mice.

In mice and humans, the immunologic effects of developmental exposure to noninherited maternal antigens (NIMAs) are quite variable. This heterogeneity likely reflects differences in the relative levels of NIMA-specific T regulatory (T(R)) versus T effector (T(E)) cells. We hypothesized that maintenance of NIMA-specific T(R) cells in the adult requires continuous exposure to maternal cells and antigens (eg, maternal microchimerism [MMc]). To test this idea, we used 2 sensitive quantitative polymerase chain reaction (qPCR) tests to detect MMc in different organs of NIMA(d)-exposed H2(b) mice. MMc was detected in 100% of neonates and a majority (61%) of adults; nursing by a NIMA+ mother was essential for preserving MMc into adulthood. MMc was most prevalent in heart, lungs, liver, and blood, but was rarely detected in unfractionated lymphoid tissues. However, MMc was detectable in isolated CD4+, CD11b+, and CD11c+ cell subsets of spleen, and in lineage-positive cells in heart. Suppression of delayed type hypersensitivity (DTH) and in vivo lymphoproliferation correlated with MMc levels, suggesting a link between T(R) and maternal cell engraftment. In the absence of neonatal exposure to NIMA via breastfeeding, MMc was lost, which was accompanied by sensitization to NIMA in some offspring, indicating a role of oral exposure in maintaining a favorable T(R) > T(E) balance.

Multidisciplinary approach decreases length of stay and reduces cost for ventricular assist device therapy.

High implantation costs and long postoperative length of stay (LOS) in debilitated patients complicate ventricular assist device (VAD) therapy. Between July 2000 and February 2005, 30 patients received a VAD at our institution. Of those, 20 patients were successfully discharged from the hospital with VADs. In August 2003, a multidisciplinary team was formed consisting of all services for VAD patients to replace a single-discipline (cardiac surgery) system. This team evaluated potential VAD candidates and identified optimal timing for implantation. These 20 VAD patients were divided into two groups according to the initiation of multidisciplinary team; the traditional group (n=7, July 2000-July 2003) and the multidisciplinary group (n=13, August 2003-February 2005). Patient demographics were not different. The LOS decreased from 61 to 15 days (P<0.01), especially LOS on the floor decreased from 35 to 7 days (P=0.03). The floor cost was significantly reduced ($47,111 vs. $8742, P<0.01), leading to a decrease in total postoperative cost ($202,238 vs. $161,744, P<0.01). The 30-day readmission rate decreased (5/7 patients vs. 1/13 patients, P<0.01). A multidisciplinary approach significantly decreased LOS and cost after VAD therapy, mostly by decreasing the cost of routine non-ICU care, without increasing the readmission rate.

Th-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation.

RATIONALE: The pathogenesis of primary graft dysfunction (PGD), a serious complication of lung transplantation, is poorly understood. Human studies and rodent models have shown that collagen type V (col[V]), stimulates IL-17-dependent cellular immunity after lung transplantation. OBJECTIVES: To determine whether patients with end-stage lung disease develop pretransplant col(V)-specific cellular immunity, and if so, the impact of this response on PGD. METHODS: Trans-vivo delayed-type hypersensitivity (TV-DTH) assays were used to evaluate memory T-cell responses to col(V) in 55 patients awaiting lung transplantation. Pa(O(2))/Fi(O(2)) index data were used to assess PGD. Univariate risk factor analysis was performed to identify variables associated with PGD. Rats immunized with col(V) or irrelevant antigen underwent lung isografting to determine if prior anti-col(V) immunity triggers PGD in the absence of alloreactivity. MEASUREMENTS AND MAIN RESULTS: We found that 58.8% (10/17) of patients with idiopathic pulmonary fibrosis, and 15.8% (6/38) of patients without idiopathic pulmonary fibrosis tested while on the wait list for a lung transplant were col(V) DTH positive. Col(V) reactivity was CD4(+) T-cell and monocyte mediated, and dependent on IL-17, IL-1beta, and tumor necrosis factor (TNF)-alpha. Pa(O(2))/Fi(O(2)) indices were impaired significantly 6-72 hours after transplantation in col(V)-reactive versus nonreactive patients. Univariate risk factor analysis identified only preoperative TV-DTH to col(V) and ischemic time as predictors of PGD. Finally, in a rat lung isograft model, col(V) sensitization resulted in significantly lower Pa(O(2))/Fi(O(2)), increased local TNF-alpha and IL-1beta production, and a moderate-to-severe bronchiolitis/vasculitis when compared with control isografts. CONCLUSIONS: The data suggest that activation of innate immunity by col(V)-specific Th-17 memory cells represents a novel pathway to PGD after lung transplantation.

Developmental exposure to noninherited maternal antigens induces CD4+ T regulatory cells: relevance to mechanism of heart allograft tolerance.

We hypothesize that developmental exposure to noninherited maternal Ags (NIMA) results in alloantigen-specific natural and adaptive T regulatory (T(R)) cells. We compared offspring exposed to maternal H-2(d) (NIMA(d)) with nonexposed controls. In vitro assays did not reveal any differences in T cell responses pretransplant. Adoptive transfer assays revealed lower lymphoproliferation and greater cell surface TGF-beta expression on CD4(+) T cells of NIMA(d)-exposed vs control splenocytes. NIMA(d)-exposed splenocytes exhibited bystander suppression of tetanus-specific delayed-type hypersensitivity responses, which was reversed with Abs to TGF-beta and IL-10. Allospecific T effector cells were induced in all mice upon i.v. challenge with B6D2F1 splenocytes or a DBA/2 heart transplant, but were controlled in NIMA(d)-exposed mice by T(R) cells to varying degrees. Some (40%) NIMA(d)-exposed mice accepted a DBA/2 allograft while others (60%) rejected in delayed fashion. Rejector and acceptor NIMA(d)-exposed mice had reduced T effector responses and increased Foxp3(+) T(R) cells (CD4(+)CD25(+)Foxp3(+) T(R)) in spleen and lymph nodes compared with controls. The key features distinguishing NIMA(d)-exposed acceptors from all other mice were: 1) higher frequency of IL-10- and TGF-beta-producing cells primarily in the CD4(+)CD25(+) T cell subset within lymph nodes and allografts, 2) a suppressed delayed-type hypersensitivity response to B6D2F1 Ags, and 3) allografts enriched in LAP(+), Foxp3(+), and CD4(+) T cells, with few CD8(+) T cells. We conclude that the beneficial NIMA effect is due to induction of NIMA-specific T(R) cells during ontogeny. Their persistence in the adult, and the ability of the host to mobilize them to the graft, may determine whether NIMA-specific tolerance is achieved.

IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants.

Bronchiolitis obliterans syndrome (BOS), a process of fibro-obliterative occlusion of the small airways in the transplanted lung, is the most common cause of lung transplant failure. We tested the role of cell-mediated immunity to collagen type V [col(V)] in this process. PBMC responses to col(II) and col(V) were monitored prospectively over a 7-year period. PBMCs from lung transplant recipients, but not from healthy controls or col(IV)-reactive Goodpasture's syndrome patients after renal transplant, were frequently col(V) reactive. Col(V)-specific responses were dependent on both CD4+ T cells and monocytes and required both IL-17 and the monokines TNF-alpha and IL-1beta. Strong col(V)-specific responses were associated with substantially increased incidence and severity of BOS. Incidences of acute rejection, HLA-DR mismatched transplants, and induction of HLA-specific antibodies in the transplant recipient were not as strongly associated with a risk of BOS. These data suggest that while alloimmunity initiates lung transplant rejection, de novo autoimmunity mediated by col(V)-specific Th17 cells and monocyte/macrophage accessory cells ultimately causes progressive airway obliteration.

Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with incidence data and application to screening.

Although there have been numerous reports from around the world of mutations in the gene of chromosome 7 known as CFTR (cystic fibrosis transmembrane conductance regulator), little attention has been given to integrating these mutant alleles into a global understanding of the population molecular genetics associated with cystic fibrosis (CF). We determined the distribution of CFTR mutations in as many regions throughout the world as possible in an effort designed to: 1) increase our understanding of ancestry-genotype relationships, 2) compare mutational arrays with disease incidence, and 3) gain insight for decisions regarding screening program enhancement through CFTR multi-mutational analyses. Information on all mutations that have been published since the identification and cloning of the CFTR gene's most common allele, DeltaF508 (or F508del), was reviewed and integrated into a centralized database. The data were then sorted and regional CFTR arrays were determined using mutations that appeared in a given region with a frequency of 0.5% or greater. Final analyses were based on 72,431 CF chromosomes, using data compiled from over 100 original papers, and over 80 regions from around the world, including all nations where CF has been studied using analytical molecular genetics. Initial results confirmed wide mutational heterogeneity throughout the world; however, characterization of the most common mutations across most populations was possible. We also examined CF incidence, DeltaF508 frequency, and regional mutational heterogeneity in a subset of populations. Data for these analyses were filtered for reliability and methodological strength before being incorporated into the final analysis. Statistical assessment of these variables revealed that there is a significant positive correlation between DeltaF508 frequency and the CF incidence levels of regional populations. Regional analyses were also performed to search for trends in the distribution of CFTR mutations across migrant and related populations; this led to clarification of ancestry-genotype patterns that can be used to design CFTR multi-mutation panels for CF screening programs. From comprehensive assessment of these data, we offer recommendations that multiple CFTR alleles should eventually be included to increase the sensitivity of newborn screening programs employing two-tier testing with trypsinogen and DNA analysis.