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Rationale and Objectives: Post-TAVR persistent pulmonary hypertension (PH) is a better predictor of poor outcome than pre-TAVR PH. In this longitudinal study we sought to evaluate whether pulmonary artery (distensibility (D PA ) measured on preprocedural ECG-gated CTA is associated with persistent-PH and 2-year mortality after TAVR., Materials and Methods: Three hundred and thirty-six patients undergoing TAVR between July 2012 and March 2016 were retrospectively included and followed for all-cause mortality until November 2017. All patients underwent retrospectively ECG-gated CTA prior to TAVR. Main pulmonary artery (MPA) area was measured in systole and in diastole. D PA was calculated as: [(area-MPA max -area-MPA min )/area-MPA max ]%. ROC analysis was performed to assess the AUC for persistent-PH. Youden Index was used to determine the optimal threshold of D PA for persistent-PH. Two groups were compared based on a D PA threshold of 8% (specificity of 70% for persistent-PH). Kaplan-Meier, Cox proportional-hazard, and logistic regression analyses were performed. The primary clinical endpoint was defined as persistent-PH post-TAVR. The secondary endpoint was defined as all-cause mortality 2 years after TAVR., Results: Median follow-up time was 413 (interquartiles 339-757) days. A total of 183 (54%) had persistent-PH and 68 (20%) patients died within 2-years after TAVR. Patients with D PA <8% had significantly more persistent-PH (67% vs 47%, p<0.001) and 2-year deaths (28% vs 15%, p=0.006), compared to patients with D PA >8%. Adjusted multivariable regression analyses showed that D PA <8% was independently associated with persistent-PH (OR 2.10 [95%-CI 1.3-4.5], p=0.007) and 2-year mortality (HR 2.91 [95%-CI 1.5-5.8], p=0.002). Kaplan-Meier analysis showed that 2-year mortality of patients with D PA <8% was significantly higher compared to patients with D PA ≥8% (mortality 28% vs 15%; log-rank p=0.003)., Conclusion: D PA on preprocedural CTA is independently associated with persistent-PH and two-year mortality in patients who undergo TAVR., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: The objective of this work was to delineate career progression and research productivity of women practicing cardiothoracic surgery in the academic setting., Methods: Cardiothoracic surgeons at the 79 accredited US cardiothoracic surgery training programs in 2020 were included in this cross-sectional analysis. Data regarding subspecialization, training, practice history, and publications were gathered from public sources including department websites, CTSNet, and Scopus., Results: A total of 1065 surgeons (51.3% cardiac, 32.1% thoracic, 16.6% congenital) were identified. Women accounted for 10.6% (113) of the population (7.9% of cardiac, 15.5% of thoracic, 9.6% of congenital surgeons). The median number of cardiothoracic surgeons per institution was 12 (interquartile range [IQR], 10-17), with a median of 1 woman (IQR, 0-2). Fifteen of 79 programs (19%) had no women. Among women faculty 5.3% were clinical instructors, 51.3% were assistant professors, 23.0% were associate professors, 16.8% were full professors, and 3.5% had unspecified titles (vs 2.0%, 32.9%, 23.0%, 37.5%, and 4.6% among men, respectively; P < .001). Women and men authored a comparable number of first-author (0.4 [IQR, 0.0-1.3] vs 0.5 [IQR, 0.0-1.1], P = .56) publications per year but fewer last-author (0.1 [IQR, 0.0-0.7] vs 0.4 [IQR, 0.0-1.3], P < .0001) and total publications per year (2.7 [IQR, 1.0-6.2] vs 3.7 [IQR, 1.3-7.8], P = .05) than men. The H-index was lower for women than for men overall (8.0 [IQR, 3.0-15.0] vs 15.0 [IQR, 7.0-28.0], P < .001) but was similar between men and women who had been practicing for 10 to 20 years., Conclusions: Gender disparities persist in academic cardiothoracic surgery. Efforts should be made to support women in achieving senior roles and academic productivity., (Copyright © 2023 The Society of Thoracic Surgeons. All rights reserved.)

Objective: Retrograde false lumen perfusion has limited the utility of aortic stent grafting for chronic aortic dissection. It is unknown whether balloon septal rupture can improve the outcomes for endovascular management of chronic aortic dissection., Methods: Included patients underwent false lumen obliteration and creation of a single-lumen aortic landing zone using balloon aortoplasty during thoracic endovascular aortic repair. The distal thoracic stent graft was sized to the total aortic lumen diameter, and septal rupture was performed within the stent graft with a compliant balloon in the region 5 cm proximal to the distal fabric edge. Clinical and radiographic outcomes are reported., Results: Forty patients, with an average age 56 years, underwent thoracic endovascular aortic repair with septal rupture. Seventeen patients (43%) had chronic type B dissections, 17 of 40 patients (43%) had residual type A dissections, and 6 of 40 patients (15%) had acute type B dissections. Nine cases were emergency, complicated by rupture or malperfusion. Perioperative complications included 1 death (2.5%) due to rupture of the descending thoracic aorta and 2 (5%) instances each of stroke (neither permanent) and spinal cord ischemia (1 permanent). Two (5%) stent graft-induced new injuries were seen. Average postoperative computed tomography follow-up was 1.4 years. Thirteen patients (33%) had a decrease in aortic size, 25 of 39 patients (64%) were stable, and 1 of 39 patients (2.6%) had an increased aortic size. Partial and complete false lumen thrombosis were achieved in 10 of 39 patients (26%) and 29 of 39 patients (74%), respectively. Midterm aortic-related survival was 97.5% at an average of 1.6 years., Conclusions: Controlled balloon septal rupture offers an effective endovascular method to treat aortic dissection in the distal thoracic aorta., (© 2023 The Author(s).)

Aortic dissection is a chronic disease that requires lifelong clinical and imaging surveillance, long after the acute event. Imaging has an important role in prognosis, timing of repair, device sizing, and monitoring for complications, especially in the endovascular therapy era. Important anatomic features at preprocedural imaging include the location of the primary intimal tear and aortic zonal and branch vessel involvement, which influence the treatment strategy. Challenges of repair in the chronic phase include a small true lumen in conjunction with a stiff intimal flap, complex anatomy, and retrograde perfusion from distal reentry tears. The role of thoracic endovascular aortic repair (TEVAR) remains controversial for treatment of chronic aortic dissection. Standard TEVAR is aimed at excluding the primary intimal tear to decrease false lumen perfusion, induce false lumen thrombosis, promote aortic remodeling, and prevent aortic growth. In addition to covering the primary intimal tear with an endograft, several adjunctive techniques have been developed to mitigate retrograde false lumen perfusion. These techniques are broadly categorized into false lumen obliteration and landing zone optimization strategies, such as the provisional extension to induce complete attachment (PETTICOAT), false lumen embolization, cheese-wire fenestration, and knickerbocker techniques. Familiarity with these techniques is important to recognize expected changes and complications at postintervention imaging. The authors detail imaging options, provide examples of simple and complex endovascular repairs of aortic dissections, and highlight complications that can be associated with various techniques. Online supplemental material is available for this article. © RSNA, 2022.

Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays., Methods: At our institution, 2 strategies for providing DAA therapy to HCV - recipients of HCV + transplants have been used. For thoracic organ recipients, an institution-subsidized course of initial therapy was provided to ensure an early treatment initiation date. For abdominal organ recipients, insurance approval for DAA coverage was sought once viremia developed, and treatment was initiated only once the insurance-authorized supply of drug was received. To evaluate the clinical impact of these 2 strategies, we retrospectively collected data pertaining to the timing of DAA initiation, duration of recipient viremia, and monetary costs incurred by patients and the institution for patients managed under these 2 DAA coverage strategies., Results: One hundred fifty-two transplants were performed using HCV viremic donor organs. Eighty-nine patients received DAA treatment without subsidy, and 62 received DAA treatment with subsidy. One patient who never developed viremia posttransplant received no treatment. Subsidizing the initial course enabled earlier treatment initiation (median, 4 d [interquartile range (IQR), 2-7] vs 10 [IQR, 8-13]; P  < 0.001) and shorter duration of viremia (median, 16 d [IQR, 12-29] vs 36 [IQR, 30-47]; P  < 0.001). Institutional costs averaged $9173 per subsidized patient and $168 per nonsubsidized patient. Three needlestick exposures occurred in caregivers of viremic patients., Conclusions: Recipients and their caregivers stand to benefit from earlier DAA treatment initiation; however, institutional costs to subsidize DAA therapy before insurance authorization are substantial. Insurance authorization processes for DAAs should be revised to accommodate this unique patient group., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

In 1960, Dr Nina Starr Braunwald became the first woman to perform open heart surgery. Sixty years later, despite the fact that women outnumbered men in American medical school in 2017, men still dominate the field of cardiac surgery. Women surgeons remain underrepresented in cardiac surgery; 11% of practicing cardiac surgeons in Canada were women in 2015, and 6% of practicing adult cardiac surgeons in the US were women in 2019. Although women remain a minority in other surgical specialties also, cardiothoracic surgery remains one of the most unevenly-gender distributed specialties. Why are there so few women cardiac surgeons, and why does it matter? Evidence is emerging regarding the benefits of diversity for a variety of industries, including healthcare. In order to attract and retain the best talent, we must make the cardiac surgery environment more diverse, equitable, and inclusive. Some causes of perpetuation of the gender gap have been documented in the literature-these include uneven compensation and career advancement opportunities, outdated views on family dynamics, and disproportionate scrutiny of women surgeons, causing additional workplace frictions for women. Diversity is an organizational strength, and gender-diverse institutions are more likely to outperform their non-gender-diverse counterparts. Modifiable issues perpetuate the gender gap, and mentorship is key in helping attract, develop, and retain the best and brightest within cardiac surgery. Facilitating mentorship opportunities is key to reducing barriers and bridging the gap., (© 2021 The Authors.)

Background: Thoracic endovascular aortic repair (TEVAR) has become first-line treatment for descending thoracic aortic rupture (DTAR), but its midterm and long-term outcomes remain undescribed. This study evaluated whether TEVAR would improve midterm outcomes of nontraumatic DTAR relative to open surgical repair (OSR)., Methods: Between December 1999 and October 2018, 118 patients with DTAR were treated with either OSR (n = 39) or TEVAR (n = 79) at a single center. Primary end points were 30-day and long-term all-cause mortalities. Secondary end points included stroke, permanent spinal cord ischemia (SCI), prolonged ventilation support or tracheostomy, permanent hemodialysis, and aortic reintervention., Results: Thirty-day mortality was significantly lower with TEVAR (OSR, 38.5%; TEVAR, 16.5%; P = .01). Stroke (15.6% vs 3.8%; P = .03), permanent SCI (15.6% vs 2.5%; P = .02), prolonged ventilation (30.8% vs 8.9%; P = .002), and tracheostomy (12.8% vs 2.5%; P = .04) were significantly lower after TEVAR than OSR. Need for hemodialysis trended higher after OSR (12.8% vs 5.1%; P = .2). Mean follow ups were 1048 ± 1591 days for OSR group and 828 ± 1258 days for TEVAR. All-cause mortality at last follow-up was significantly lower after TEVAR than OSR (35.4% vs 66.7%; P = .001). Aortic reintervention was required more frequently within 30 days after TEVAR (15.2% vs 2.6%; P = .06). By multivariate analysis, TAAA was an independent predictor for mortality., Conclusions: TEVAR improves both early and midterm outcomes of DTAR relative to OSR. TAAA was a predictor of mortality. Endovascular approach to DTAR may provide the greatest chance at survival., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Burnout among surgeons has been attributed to increased workload and decreased autonomy. Although prior studies have examined burnout among transplant surgeons, no studies have evaluated burnout in abdominal transplant surgery fellows. The objective of our study was to identify predictors of burnout and understand its impact on personal and patient care during fellowship. A survey was sent to all abdominal transplant surgery fellows in an American Society of Transplant Surgeons-accredited fellowship. The response rate was 59.2% (n = 77) and 22.7% (n = 17) of fellows met criteria for burnout. Fellows with lower grit scores were more likely to exhibit burnout compared with fellows with higher scores (3.6 vs 4.0, P = .026). Those with burnout were more likely to work >100 hours per week (58.8% vs 27.6%, P = .023), have severe work-related stress (58.8% vs 22.4%, P = .010), consider quitting fellowship (94.1% vs 20.7%, P < .001), or make a medical error (35.3% vs 5.2%, P = .003). This national analysis of abdominal transplant fellows found that burnout rates are relatively low, but few fellows engage in self-care. Personal and program-related factors attribute to burnout and it has unacceptable effects on patient care. Transplant societies and fellowship programs should develop interventions to give fellows tools to prevent and combat burnout., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

A 59-year-old man with a history of coarctation repair, mechanical aortic valve, and warfarin therapy presented with right flank pain. Computed tomography showed a large hematoma encircling an intact descending thoracic aorta. Computed tomography angiography demonstrated multiple areas of intercostal artery extravasation. An interventional radiologist performed angiography and embolization. The patient's course was complicated by an effusion and hypoxia, but no further bleeding was noted. We hypothesize that coarctation associated aneurysms and potential vessel wall weakness are the causes of hematoma in our case. We present this case with history of repaired coarctation with multiple spontaneous intercostal artery aneurysmal rupture., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Any quantitative assessment of blood flow using conventional angiography remains impossible with current technology. Physicians decide the clinical end point of a procedure by subjective interpretation. Color-coded digital subtraction angiography has been invented to meet this demand and is used primarily in neuroradiology. This report presents the endovascular treatment of a rare complex combination of peripheral artery disease and arteriovenous fistula using guidance of blood flow parameters, such as area under the curve.

The frozen elephant technique has simplified aortic arch surgery. As with thoracic endovascular aortic repair, frozen elephant technique reconstructions often require reintervention. Skilled endovascular management of frozen elephant technique complications is imperative as novel devices emerge. We describe 2 patients who required early intervention for severe foreshortening and incomplete expansion of the Thoraflex (Vascutek, Inchinnan, United Kingdom) stent graft., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac surgery for structural heart disease has poor outcomes in the presence of cardiogenic shock or advanced heart failure. We applied venoarterial extracorporeal membrane oxygenation (ECMO) to restore end-organ function and resuscitate patients before high-risk cardiac operation., Methods: Twelve patients with cardiogenic shock and end-organ failure were evaluated for cardiac surgery. The average Society of Thoracic Surgeons mortality risk was 24% ± 13%. Patients were peripherally cannulated on ECMO for 7 ± 4 days, before undergoing operation for prosthetic mitral stenosis (n = 4), ruptured papillary muscle (n = 4), ischemic ventricular septal defect (n = 3), or severe aortic stenosis (n = 1)., Results: Mean age was 61 ± 8 years. Comorbidities included acute renal failure (n = 11), inotrope requirement (n = 10), intraaortic balloon pump (n = 8), severe acidosis (n = 6), high-dose vasopressor requirement (n = 8), and cardiac arrest (n = 1). With ECMO support, vasopressor requirement, central venous pressure, creatinine, lactate, pH, pulmonary hypertension, and The Society of Thoracic Surgeons mortality risk and EuroSCORE (European System for Cardiac Operative Risk Evaluation) II all improved significantly. Care was withdrawn in 1 patient on ECMO with initially unknown anoxic brain injury. No patients required dialysis at discharge. Complications included 1 permanent stroke. All operative patients survived to hospital discharge. Average length of follow-up was 420 days, with 2 patient deaths at 76 and 230 days and 6 patients surviving over 1 year., Conclusions: ECMO can be used as a bridge to heart valve or septal defect surgery in severely decompensated patients. Through recovery of end-organ function, ECMO may allow surgical correction of structural heart disease in patients considered inoperable or convert a salvage situation to an elective operation., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Throughout surgery, specialization in a procedure has been shown to improve outcomes. Currently, there is no evidence for or against subspecialization in coronary surgery. Tasked with the goal of improving outcomes after isolated coronary artery bypass grafting (CABG), our institution sought to determine whether the development of a subspecialized coronary surgery program would improve morbidity and mortality., Methods: All isolated CABG operations at a single institution were retrospectively examined in two distinct periods, 2002 to 2013 and 2013 to 2016, before and after the implementation of a subspecialized coronary surgery program. Improved policies included leadership and subspecialization of a program director, standardization of surgical technique and postoperative care, and monthly multidisciplinary quality review. Outcomes were collected and compared., Results: Between 2002 and 2013, 3,256 CABG operations were done by 16 surgeons, the most frequent surgeon doing 33%. Between 2013 and 2016, 1,283 operations were done by 10 surgeons, 70% by the coronary program director. CABGs done in the specialized era had shorter bypass and clamps times and increased use of bilateral internal mammary arteries. Blood transfusion and complication rates, including permanent stroke and prolonged ventilation, were significantly decreased after implementation of the coronary program. Likewise, overall operative mortality (2.67% vs 1.48%, p = 0.02) was significantly reduced., Conclusions: Subspecialization in CABG and dedicated coronary surgery programs may lead to faster operations, increased use of bilateral internal mammary arteries, fewer complications, and improved survival after isolated CABG., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We report a patient with refractory electrical storm after coronary artery bypass grafting who was successfully treated with thoracoscopic sympathectomy. Cardiac arrest with ventricular tachycardia occurred on postoperative day 2, and the patient required emergency support with venoarterial extracorporeal membrane oxygenation. Frequent episodes of ventricular tachycardia prevented cardiac recovery and weaning from mechanical circulatory support. A percutaneous left stellate ganglion block initially demonstrated successful prevention of ventricular tachycardia, and definitive sympathetic denervation was achieved by a left thoracoscopic sympathectomy. The patient remained in normal sinus rhythm and gained recovery of baseline ventricular function, permitting successful decannulation and weaning of inotropic support., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: To determine if preoperative embolic stroke is associated with an increased risk of postoperative stroke among patients undergoing early operation for mitral valve (MV) infective endocarditis (IE), we compared outcomes among patients presenting with and without acute stroke., Methods: From 2003 to 2015, 243 consecutive patients underwent surgery for active MV IE. Patients were categorized into 2 groups: 72% (174 of 243 patients) with no preoperative acute stroke (clinical, radiographic or both) and 28% (69 of 243 patients) with stroke. Both preoperative and postoperative strokes were confirmed in all patients with brain computed tomography or magnetic resonance imaging and comprehensive examination by a neurologist., Results: Among patients presenting with stroke, 33% (23 of 69 patients) were asymptomatic and had only positive imaging findings. The median time from admission to operation was 5 days. The overall rate of new postoperative stroke was 4% (10 of 243 patients). The rate of postoperative stroke was not different between the 2 groups: 4% (7 of 174 patients) among patients with no preoperative stroke and 4% (3 of 69 patients) with stroke (p = 0.9). One patient developed a hemorrhagic conversion of an acute infarct. Operative mortality was 7% (13 of 174 patients) among patients with no preoperative stroke and 7% (5 of 69 patients) among patients with stroke (p = 0.9)., Conclusions: MV surgery for IE and acute stroke can be performed early with a low risk of postoperative neurologic complications. When indicated, surgical intervention for MV IE complicated by acute stroke should not be delayed., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A 64-year-old male with end-stage lung disease underwent right orthotopic lung transplantation. After doing well initially, he developed acute hypoxemic respiratory failure with allograft pneumonia. Donor operative cultures demonstrated mold of the Mucor species, which were corroborated by donor endobronchial cultures obtained near the right mainstem bronchial anastomosis. The patient was treated with reoperative bilateral orthotopic lung transplantation in combination with antifungal agents. The operation was performed successfully, using lungs donated after cardiac death and treated with ex vivo lung perfusion. The patient has recovered well, remaining on room air with good allograft function, without evidence of fungal disease., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Only 40% of patients with atrial fibrillation (AF) undergoing cardiac surgery are treated with surgical AF correction. We prospectively studied endocardial cryoablation of the Cox-maze III lesion set following prespecified rhythm assessment with outpatient telemetry., Methods: Between 2007 and 2011, 136 patients underwent surgical AF correction using an argon-powered cryoablation device. Patients wore continuous electrocardiogram monitoring prior to and at 6, 12, and 24 months after surgery. The average length of monitoring was 6.5±1 days prior to surgery and 11±4 days at each time point after surgery. Patients were assessed for cardiac rhythm, interval cardioversion or ablation procedures, pacemaker placement, and the use of warfarin or antiarrhythmic medications. The primary endpoint of this study was freedom from AF at 1 year., Results: Mean patient age was 66±12 years, 50% (69 of 138) were male and 41% (55 of 134) had persistent AF. CryoMaze was done in conjunction with mitral valve operation in 95% (131 of 138) and other procedures in 41% (56 of 138). Follow-up was 96% complete at 1 year and 90% at 2 years. Freedom from AF was 76% at 1 year. Perioperative mortality and stroke rates were both 1.5% (2 of 138). Perioperative pacemaker implantation was required in 7% (9 of 136). In univariate analysis, younger age, female gender, decreased height and weight, smaller preoperative and postoperative left atrial diameter, intermittent AF, and freedom from AF at discharge were associated with freedom from AF at 1 year. Actuarial 2- and 4-year (Kaplan-Meier) survival were 93% and 80%, respectively., Conclusions: The CryoMaze procedure is safe and is associated with 76% freedom from AF at 1 year., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Acute lung injury (ALI) and the development of the multiple organ dysfunction syndrome (MODS) are major causes of death in trauma patients. Gut inflammation and loss of gut barrier function as a consequence of splanchnic ischemia-reperfusion (I/R) have been implicated as the initial triggering events that contribute to the development of the systemic inflammatory response, ALI, and MODS. Since hypoxia-inducible factor (HIF-1) is a key regulator of the physiological and pathophysiological response to hypoxia, we asked whether HIF-1 plays a proximal role in the induction of gut injury and subsequent lung injury. Utilizing partially HIF-1α-deficient mice in a global trauma hemorrhagic shock (T/HS) model, we found that HIF-1 activation was necessary for the development of gut injury and that the prevention of gut injury was associated with an abrogation of lung injury. Specifically, in vivo studies demonstrated that partial HIF-1α deficiency ameliorated T/HS-induced increases in intestinal permeability, bacterial translocation, and caspase-3 activation. Lastly, partial HIF-1α deficiency reduced TNF-α, IL-1β, cyclooxygenase-2, and inducible nitric oxide synthase levels in the ileal mucosa after T/HS whereas IL-1β mRNA levels were reduced in the lung after T/HS. This study indicates that prolonged intestinal HIF-1 activation is a proximal regulator of I/R-induced gut mucosal injury and gut-induced lung injury. Consequently, these results provide unique information on the initiating events in trauma-hemorrhagic shock-induced ALI and MODS as well as potential therapeutic insights.

Intestinal ischemia after trauma-hemorrhagic shock (T/HS) results in gut barrier dysfunction and the production/release of biologically active and tissue injurious factors in the mesenteric lymph, which, in turn, causes acute lung injury and a systemic inflammatory state. Since T/HS-induced lung injury is associated with pulmonary endothelial and epithelial cell programmed cell death (PCD) and was abrogated by mesenteric lymph duct ligation, we sought to investigate the cellular pathways involved. Compared with trauma-sham shock (T/SS) rats, a significant increase in caspase-3 and M30 expression was detected in the pulmonary epithelial cells undergoing PCD, whereas apoptosis-inducing factor (AIF), but not caspase-3, was detected in endothelial cells undergoing PCD. This AIF-mediated pulmonary endothelial PCD response was validated in an in situ femoral vein assay where endothelial cells were found to express AIF but not caspase-3. To complement these studies, human umbilical vein endothelial cell (HUVEC), human lung microvascular endothelial cell (HLMEC), and human alveolar type II epithelial cell (A549) lines were used as in vitro models. T/HS lymph induced the nuclear translocation of AIF in HUVEC and HLMEC, and caspase inhibition in these cells did not afford any cytoprotection. For proof of principle, AIF silencing in HUVEC reversed the cytotoxic effects of T/HS on cell viability and DNA fragmentation. In A549 cells, T/HS lymph activated caspase-3-mediated apoptosis, which was partially abrogated by N-benzyloxycarbonyl-Val-Ala-Asp (zVAD). Additionally, T/HS lymph did not cause the nuclear translocation of AIF in A549 cells. Collectively, T/HS-induced pulmonary endothelial PCD occurs via an AIF-dependent caspase-independent pathway, whereas epithelial cells undergo apoptosis by a caspase-dependent pathway.

The studies of the mechanisms by which trauma-hemorrhagic shock leads to gut injury and dysfunction have largely ignored the nonbacterial factors contained within the lumen of the intestine. Yet, there is increasing evidence suggesting that intraluminal pancreatic proteases may be involved in this process. Thus, we tested the hypothesis that pancreatic proteases are necessary for the trauma-hemorrhagic shock-induced gut injury and the production of biologically active mesenteric lymph by determining the extent to which pancreatic duct ligation (PDL) would limit gut injury and mesenteric lymph bioactivity. To assess the effect of PDL on gut injury and dysfunction gut morphology, the mucus layer structure and the gut permeability were measured in the following four groups of male rats subjected to laparotomy (trauma) and hemorrhagic shock (pressure, 30 mmHg for 90 min): (1) rats subjected to trauma plus sham-shock (T/SS), (2) T/SS rats undergoing PDL (T/SS + PDL), (3) rats subjected to trauma and hemorrhagic shock (T/HS), and (4) rats subjected to T/HS + PDL. The ability of mesenteric lymph from these four rat groups to kill endothelial cells and activate neutrophils was tested in vitro. The PDL did not affect any of the parameters studied because there were no differences between the T/SS and the T/SS + PDL groups. However, PDL protected the gut from injury and dysfunction because PDL significantly abrogated T/HS-induced mucosal villous injury, loss of the intestinal mucus layer, and gut permeability. Likewise, PDL totally reversed the endothelial cell cytotoxic activity of T/HS lymph and reduced the ability of T/HS lymph to prime naive neutrophils for an augmented respiratory burst. Thus, it seems that intraluminal pancreatic proteases are necessary for the T/HS-induced gut injury and the production of bioactive mesenteric lymph.

Antibodies to pneumococcus are thought to represent the primary mechanism of naturally acquired resistance to colonization. Here, however, we show that, in patients with chronic obstructive pulmonary disease (COPD), resistance to pneumococcal colonization is not associated with higher concentrations of serum anti-capsular or -noncapsular antibodies. We compared preacquisition serum antibody concentrations to capsular antigens 6B, 7F, 14, 19F, and 23F from patients with COPD who did and did not acquire pneumococcal respiratory tree colonization over the course of 2 years. Colonized patients did not have lower anti-capsular antibody concentrations than control subjects who did not acquire pneumococcus. We found no difference in functional antibody concentrations between colonized patients and control subjects. Furthermore, colonized patients had significantly higher preacquisition concentration of antibody directed against the whole cell and pneumococcal surface protein A than control subjects. We thus conclude that, in adult patients with COPD, resistance to pneumococcal colonization is unlikely to be determined by higher serum antibody concentrations to pneumococcal antigens.

California Healthy Cities and Communities is the longest running statewide program of its kind in the nation. After providing a brief history the authors give an overview of the supporting activities and resources the Program provides to Healthy Cities and Communities initiatives throughout California.