Impact of housing temperature on adipose tissue HDAC9 expression and adipogenic differentiation in high fat-fed mice.

OBJECTIVE: Impaired adipogenic differentiation exacerbates metabolic disease in obesity. This study reported that high-fat diet (HFD)-fed mice housed at thermoneutrality exhibited impaired adipogenic differentiation, attributed to increased expression of histone deacetylase 9 (HDAC9). However, the impact of HFD on adipogenic differentiation is reportedly variable, possibly reflecting divergent environmental conditions such as housing temperature. METHODS: C57BL/6J (wild-type [WT]) mice were housed at either thermoneutral (28-30°C) or ambient (20-22°C) temperature and fed HFD or chow diet (CD) for 12 weeks. For acute exposure experiments, WT or transient receptor potential cation channel subfamily M member 8 (TRPM8) knockout mice housed under thermoneutrality were acutely exposed to ambient temperature for 6 to 24 h. RESULTS: WT mice fed HFD and housed at thermoneutrality, compared with ambient temperature, gained more weight despite reduced food intake. They likewise exhibited increased inguinal adipose tissue HDAC9 expression and reduced adipogenic differentiation in vitro and in vivo compared with CD-fed mice. Conversely, HFD-fed mice housed at ambient temperature exhibited minimal change in adipose HDAC9 expression or adipogenic differentiation. Acute exposure of WT mice to ambient temperature reduced adipose HDAC9 expression independent of sympathetic ß-adrenergic signaling via a TRPM8-dependent mechanism. CONCLUSIONS: Adipose HDAC9 expression is temperature sensitive, regulating adipogenic differentiation in HFD-fed mice housed under thermoneutrality.

Integrative multiomics analysis of neointima proliferation in human saphenous vein: implications for bypass graft disease.

Introduction: Human saphenous veins (SV) are widely used as grafts in coronary artery bypass (CABG) surgery but often fail due to neointima proliferation (NP). NP involves complex interplay between vascular smooth muscle cells (VSMC) and fibroblasts. Little is known, however, regarding the transcriptomic and proteomic dynamics of NP. Here, we performed multi-omics analysis in an ex vivo tissue culture model of NP in human SV procured for CABG surgery. Methods and results: Histological examination demonstrated significant elastin degradation and NP (indicated by increased neointima area and neointima/media ratio) in SV subjected to tissue culture. Analysis of data from 73 patients suggest that the process of SV adaptation and NP may differ according to sex and body mass index. RNA sequencing confirmed upregulation of pro-inflammatory and proliferation-related genes during NP and identified novel processes, including increased cellular stress and DNA damage responses, which may reflect tissue trauma associated with SV harvesting. Proteomic analysis identified upregulated extracellular matrix-related and coagulation/thrombosis proteins and downregulated metabolic proteins. Spatial transcriptomics detected transdifferentiating VSMC in the intima on the day of harvesting and highlighted dynamic alterations in fibroblast and VSMC phenotype and behavior during NP. Specifically, we identified new cell subpopulations contributing to NP, including SPP1 + , LGALS3 + VSMC and MMP2 + , MMP14 + fibroblasts. Conclusion: Dynamic alterations of gene and protein expression occur during NP in human SV. Identification of the human-specific molecular and cellular mechanisms may provide novel insight into SV bypass graft disease.

Delayed Presentation of Cardiac Perforation After Modified Ravitch Pectus Excavatum Repair.

Pectus excavatum repair using a Nuss bar is a widely performed procedure and generally regarded to be quite safe. Rare catastrophic cardiovascular complications have been previously reported, by even the most experienced surgeons. These cases typically present with fulminant cardiogenic shock and have an associated high mortality rate. We present a delayed and atypical presentation for a patient with a cardiac perforation after repair of pectus excavatum who underwent successful repair.

Mediastinal esophageal leiomyosarcoma abutting a retroesophageal right subclavian artery: A case report.

INTRODUCTION: Esophageal leiomyosarcoma and arteria lusoria represent rare entities in thoracic disease. In the setting of arteria lusoria, careful surgical planning and preoperative imaging is essential. PRESENTATION OF CASE: A 53-year old male presented with a history of cough. Imaging demonstrated a 7-cm mediastinal mass at the level of the trachea and upper esophagus, abutting an incidentally found retroesophageal right subclavian artery. The right carotid artery originated from the aortic arch. Comprehensive evaluation demonstrated a mediastinal sarcoma. Given the tumor size and close association with vital structures, induction chemotherapy was given without response. He was therefore taken for resection, including possible esophagectomy. The mass was well-encapsulated, permitting mobilization off the surrounding structures, and was identified arising from the muscular layer of the esophagus. Postoperatively, he had a low-volume chyle leak, which resolved with conservative management. He was offered mediastinal adjuvant radiation due to close margins, but declined. The patient remained without evidence of disease for over two years, at which time a single pulmonary metastasis was noted and resected. DISCUSSION: Esophageal leiomyosarcoma are an uncommon intrathoracic malignancy and may present with symptoms of mass effect. While patients with arteria lusoria are typically asymptomatic, they may suffer surgical morbidity if this entity is not identified preoperatively. In this case, the aberrant artery was intimately involved with the leiomyosarcoma, increasing complexity and rendering complete oncologic resection challenging. CONCLUSION: Herein we present a challenging surgical resection of esophageal leiomyosarcoma in the setting of arteria lusoria, which was successfully treated tumor enucleation.

Management of Symptomatic Hepatic "Mega" Hemangioma.

The majority of giant hepatic cavernous hemangiomas are asymptomatic and can safely be observed. However, when a lesion becomes symptomatic, affecting quality of life or cannot be distinguished from a malignancy, then operative therapy should be considered. We herein present a case of a symptomatic 12cm × 14cm × 17cm "mega" hemangioma (>10cm) of the left hepatic lobe. This lesion was initially refractory to transarterial embolization of the left hepatic artery, but was subsequently treated successfully with a left lateral extended hepatic segmentectomy (resection). We thus advocate a rational treatment algorithm for management of hepatic "mega" hemangiomas.

The Future of the Academic Cardiothoracic Surgeon: Results of the TSRA/TSDA In-Training Examination Survey.

BACKGROUND: Traditionally cardiothoracic residents spent dedicated research time during general surgery equipping them for a potential academic career. Recent changes in training paradigms, including integrated programs that may not include research time, could affect the development of future academic cardiothoracic surgeons. METHODS: Responses to the 2015 Thoracic Surgery Directors' Association/Thoracic Surgery Residents' Association survey accompanying the in-training examination taken by current cardiothoracic surgery residents were analyzed. Three hundred fifty-four residents were surveyed with a response rate of 100%, although one was excluded from the analysis because of inconsistencies in responses. Statistical analysis included χ(2), Fisher's exact test, and multinomial logistic regression with significance set at a probability value of 0.05. RESULTS: Two hundred sixty-seven of 353 residents (76%) intended on performing research as part of their careers. Integrated residents as opposed to traditional residents (85% versus 69%; p = 0.003), males (78% versus 65%; p = 0.02), those pursuing additional training (85% versus 69%; p = 0.003), and those interested in academic careers (93% versus 33%; p < 0.001) were more likely to pursue research. Differences were also noted in specialty interest, with congenital and heart failure specialties most likely to pursue research careers (92% and 100%, respectively; p < 0.05). Residents intending on research careers were more likely to have had previous research experience, and the most common type of intended research was clinical outcomes (78%). On multinomial logistic regression, previous clinical outcomes research and academic practice were identified as predictors of a research career (odd ratios of 9.7 and 4.1, respectively; each p < 0.05). CONCLUSIONS: The majority of residents plan on pursuing research during their careers. Previous research experience appears to be a key determinant as well as specialty interest.

Gender and Cardiothoracic Surgery Training: Specialty Interests, Satisfaction, and Career Pathways.

BACKGROUND: The cardiothoracic surgical workforce is changing. Although 5% of practicing surgeons are women, 20% of current cardiothoracic surgery residents are women. The purpose of this study was to evaluate the influence of gender on specialty interest, satisfaction, and career pathways of current residents. METHODS: Responses to the mandatory 2015 Thoracic Surgery Residents Association/Thoracic Surgery Directors Association in-training examination survey taken by 354 residents (100% response rate) were evaluated. The influence of gender was assessed with the use of standard univariate analyses. RESULTS: Women accounted for 20% of residents, and the percentage did not vary with postgraduate year or program type (traditional versus integrated). Although no differences were found between the genders related to specialty interest, academic versus private practice career, or pursuit of additional training, women were more likely to pursue additional training in minimally invasive thoracic surgery (10% versus 2.5%, p = 0.001) and less likely to perform research in their careers (65% versus 88%, p = 0.043). Although women were equally satisfied with their career choice, had similar numbers of interviews and job offers, and felt equally prepared for their boards, graduating women felt less prepared technically (77% versus 90%, p = 0.01) and for practicing independently (71% versus 87%, p = 0.01). Women were less likely to be married (26% versus 62%, p < 0.001) and have children (19% versus 49%, p < 0.001). CONCLUSIONS: Although career satisfaction and specialty interest were similar between the genders, women were less likely to intend to perform research during their careers despite similar previous research experience. Women also demonstrated lower rates of marriage and childbearing compared with their male counterparts.

Characterizing the Operative Experience of Cardiac Surgical Trainees: What Are Residents Really Doing in the Operating Room?

BACKGROUND: The present study aimed to describe and compare the operative experience of cardiothoracic surgical residents for basic and advanced cardiac surgical procedures. METHODS: Data were obtained from the 2015 Thoracic Surgery Directors Association Survey administered to all thoracic surgical residents taking the yearly In-Service Training Examination (n = 356). Residents were asked whether they routinely served as the operative surgeon on various cardiac operations and operative tasks. Results were stratified by postgraduate year (PGY), residency type, and primary career interest. RESULTS: The survey response rate was 100%. Considering all training pathways, only 2 of 13 cardiac operations surveyed were routinely performed by graduating chief residents as the operative surgeon: coronary artery bypass grafting (CABG; 92%) and aortic valve replacement (AVR; 88%). Off-pump CABG, minimally invasive mitral valve operation, and transcatheter aortic interventions were infrequently (<30% of the time) performed by graduating residents as the operative surgeon. These results were similar when residents with a career interest in general thoracic surgery were excluded from the analysis. For the operative progression of integrated 6-year (I-6) residents, most began to routinely cannulate for cardiopulmonary bypass, perform proximal coronary anastomoses, and harvest the mammary artery during PGY3. The majority (>50%) of I-6 residents performed CABG as the operative surgeon by PGY4. CONCLUSIONS: There is pronounced heterogeneity in the cardiac operative experience of cardiothoracic surgical residents in the United States, with only CABG and AVR routinely performed by graduating residents as the operative surgeon. This heterogeneity may lead to insufficient training in certain procedures for many graduates.

Is Total Arch Replacement Associated With Worse Outcomes During Repair of Acute Type A Aortic Dissection?

BACKGROUND: As acute type A aortic dissection (ATAAD) remains a challenge, the extent of resection of the transverse arch remains debated during operative repair. The purpose of this study was to compare the outcomes of total arch repair versus ascending/proximal arch repair for ATAAD. METHODS: We retrospectively reviewed our aortic database of ATAAD between October 1999 and December 2014. Patients were divided into two groups: total arch repair versus proximal arch repair (hemiarch). Indications for arch replacement during ATAAD include aneurysm greater than 5 cm, complex arch tear, and arch rupture. Inhospital and long-term outcomes were compared between the two groups using univariate analysis and multiple logistic regression analysis. Survival was analyzed using Kaplan-Meier and log rank statistics, and assessment of risk factors for survival was conducted by Cox proportional hazards regression analysis. RESULTS: During the study period, we performed 489 repairs of ATAAD, 49 patients (10%) with total arch replacement and 440 patients (90%) with proximal arch replacement. Patients with total arch repair were older (62.4 ± 13.4 years versus 57.9 ± 14.8 years, p = 0.046) and had significantly increased retrograde aortic dissection, circulatory arrest, and retrograde cerebral perfusion times. The incidences of early mortality, stroke, and need for renal dialysis between the total arch and proximal arch group were not significantly different: 20.4% (10 of 49) versus 12.9% (57 of 440), 8.2% (4 of 49) versus 10.5% (46 of 440), and 27% (13 of 49) versus 17.6% (76 of 432), respectively. Late survival did not demonstrate a difference between groups. CONCLUSIONS: Acute type A aortic dissection remains a challenge associated with significant mortality and morbidity. When compared with a less aggressive resection, total arch replacement performed in an individualized fashion can be associated with acceptable early and late outcomes for ATAAD and was not associated with worse outcomes.

Endoscopic Ultrasound Estimates for Tumor Depth at the Gastroesophageal Junction Are Inaccurate: Implications for the Liberal Use of Endoscopic Resection.

BACKGROUND: Endoscopic resection is increasingly utilized for treating early stage esophageal cancer, and endoscopic ultrasound (EUS) frequently guides treatment selection. Studies report greater than 80% sensitivity and 90% specificity, but our experience suggests less accuracy at the gastroesophageal (GE) junction. The objective of this study is to determine the accuracy of EUS for depth of GE junction cancer and the potential treatment implications. METHODS: A retrospective review of a prospective database was performed for patients from 1995 to 2014 with GE junction esophageal cancer that underwent EUS staging and resection (surgical or endoscopic) without neo-adjuvant therapy. Patient, tumor, EUS, and pathologic characteristics were examined. RESULTS: For the 181 patients that met criteria, the median age was 66 years, 17% were female, 91% white, and 98% had adenocarcinoma. Concordance between EUS (u) T and pathologic (p) T was 48%, with 23% under-staged and 29% over-staged. The EUS was accurate in the following: uT0 6% (1 of 18); uT1a 56% (23 of 41); uT1b 58% (41 of 71); uT2 10% (2 of 21); and uT3 70% (21 of 30). Inaccurate EUS depth had potential to lead to over-treatment in 38% (27 of 71) of uT1b and 76% (16 of 21) of uT2. In 50% of pT1a tumors, EUS depth was T1b or greater. Logistic regression revealed tumor length (continuous variable) to be associated with inaccurate uT (p = 0.016). Accurately staged tumors were significantly longer than inaccurately staged tumors (2.7 vs 1.7 cm, p = 0.011). CONCLUSIONS: Early to intermediate GE junction tumors are frequently over-staged. This highlights the importance of diagnostic endoscopic resection for determining accurate tumor depth and selecting correct therapy.

Laparoscopic sleeve gastrectomy: outcomes at a military training center.

Laparoscopic sleeve gastrectomy (LSG) has gained support as a single-staged and stand-alone bariatric procedure. Reports of excess weight loss of 35 to 83 per cent, reduction in comorbidities, and decreased operative morbidity have garnered support for LSG. This study represents an initial outcome analysis of LSG performed solely at a military treatment center. This study is a retrospective analysis of all patients receiving LSG at Dwight D. Eisenhower Army Medical Center from September 2007 to December 2009. The patients were planned for a stand-alone procedure. One hundred and fifteen patients received LSG over this time period with a mean body mass index of 45.5 +/- 6.2 (range 35.1-58.3). The average age was 47.4 +/- 12.5 years. Diabetes mellitus was seen in 47 per cent and 68 per cent of patients had hypertension. The mean and median length of operation was 124 +/- 48 and 115.5 minutes. The mean percentage of excess weight loss was 16.6 +/- 6.40 per cent at 1 month, 31.5 +/- 7.6 per cent at 3 months, 41.2 +/- 13.9 per cent at 6 months, and 53.7 +/- 12.5 per cent at 1 year from surgery. One or more of patient's preoperative diabetic or hypertensive medications were improved postoperatively in 18.7 per cent and 16.3 per cent, respectively. Incidence of major complications occurred in 4.35 per cent of patients in this study to include four leaks (3.4%), one death (0.87%), and 10 readmissions. Midterm analysis of outcomes related to LSG as a single-stage bariatric procedure is promising as long-term outcome data is collected; the efficacy of this procedure as a sole bariatric procedure will continue to be borne out.

Comparison of Surgisis, AlloDerm, and Vicryl Woven Mesh grafts for abdominal wall defect repair in an animal model.

BACKGROUND: Surgisis and AlloDerm, two biosynthetic materials, have been previously used with success in abdominal wall repairs in the setting of contaminated fields. Historically, Vicryl Woven Mesh, a synthetic material, has also been used in such settings as a temporary bridge for abdominal wall reconstruction. This study compares Surgisis and AlloDerm with Vicryl Woven Mesh with respect to tensile strength, collagen remodeling, and neovascularization using a rat hernia model. METHODS: A prospective randomized trial of 54 Sprague-Dawley rats were assigned to the Surgisis, AlloDerm, or Vicryl Woven Mesh group with baseline, 30-day, and 60-day end points. A 1.5-cm x 5.0-cm defect was created in the right abdominis rectus muscle and repaired with an underlay bridge graft using the different treatment materials. Tensile strength was measured using an Instron tensiometer. Histologic specimens were evaluated for neovascularization, collagen deposition, and collagen organization at the 30- and 60-day time points. RESULTS: Surgisis had significantly greater tensile strength compared to Vicryl Woven Mesh at the baseline time point (0.142 vs. 0.091 MPa, p < 0.05). There were no differences between groups tensile strength at 30 or 60 days postoperatively. The Vicryl Woven Mesh and AlloDerm groups showed increases in tensile strength at 30 days postoperatively versus baseline (p < 0.05). Vicryl Woven Mesh, Surgisis, and AlloDerm all showed increases in tensile strength at 60 days postoperatively compared to 30 days postoperatively and at baseline (p < 0.05). Surgisis and AlloDerm had significantly greater (p < 0.05) amounts of collagen deposition and organization at 30 and 60 days compared to Vicryl Woven Mesh. There was no significant difference between AlloDerm and Surgisis with respect to collagen deposition and organization. Surgisis and AlloDerm showed a significantly greater amount (p < 0.05) of neovascularization than Vicryl Woven Mesh at both time points. In addition, Surgisis had a significantly greater amount (p < 0.05) of neovascularization than AlloDerm at both 30 and 60 days. CONCLUSION: Surgisis has increased baseline tensile strength compared to Vicryl Woven Mesh. Tensile strength in Vicryl Woven Mesh is equal to biosynthetic grafts after tissue incorporation. Biosynthetic grafts showed superior collagen deposition and organization. Surgisis mesh showed increased neovascularization over both AlloDerm and Vicryl Woven Mesh.