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.

Pre-engraftment syndrome after double-unit cord blood transplantation: a distinct syndrome not associated with acute graft-versus-host disease.

Pre-engraftment syndrome (PES) occurring after cord blood transplantation (CBT) is poorly characterized. We reviewed 52 consecutive double-unit CBT recipients treated for high-risk hematologic malignancies. PES was defined as unexplained fever >38.3 degrees C (101 degrees F) not associated with infection and unresponsive to antimicrobials, and/or unexplained rash occurring before or at neutrophil recovery. CBT recipients (median age, 38 years; range, 3-66 years) received either myeloablative (MA; n=36) or nonmyeloablative (NMA; n=16) conditioning. Sixteen patients (31%) fulfilled PES criteria: 15 with fever (median at onset, 39 degrees C [102.2 degrees F]), 13 of whom also had rash, and 1 with rash alone. The median onset was 9 days (range, 5-12 days) posttransplantation (a median of 14 days before neutrophil recovery). Sixteen patients (14 with PES and 2 with infection and possible PES) received intravenous methylprednisolone (median dose, 1mg/kg; median duration, 3 days); 15 (94%) experienced resolution of fever within 24 hours. Recurrent PES (n=3) resolved with retreatment. There was no association between the development of PES and the likelihood of sustained donor engraftment, speed of neutrophil recovery, grade II-IV acute graft-versus-host disease (aGVHD), day-180 treatment-related mortality (TRM), or survival. PES is common after CBT, precedes neutrophil recovery, is distinct from and does not predict for aGVHD, and responds promptly to short-course corticosteroid 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.

Brachial artery fibromuscular dysplasia.

Fibromuscular dysplasia is a rare vascular disease that is characterized as nonatherosclerotic and noninflammatory in nature. This disease most commonly afflicts the renal and cerebrovascular beds but can rarely affect the upper extremity. We present the case of a 76-year-old woman who complained of a symptom complex, congruent with Raynaud's phenomenon on the right side. The patient had evidence of distal ischemia without the classic angiographic evidence of fibromuscular dysplasia on arteriography. The abnormal arterial section of the right brachial artery was resected and grafted with reversed saphenous vein. She has had no reoccurrence of her symptoms and no stenosis of her graft over a 3-year follow-up period.

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.

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.

A "no-wash" albumin-dextran dilution strategy for cord blood unit thaw: high rate of engraftment and a low incidence of serious infusion reactions.

Preparation of cord blood (CB) units for infusion by albumin-dextran dilution without centrifugation may be advantageous for adult patients to minimize cell loss and, unlike a bedside thaw, is still conducted in the controlled laboratory environment. Therefore, we studied CB transplantation (CBT) using this technique in 54 consecutive CBT recipients >20 kg. Patients (median age=42 years [range: 7-66 years]; median weight=71 kg [range: 24-109]) were transplanted for high-risk hematologic malignancies with myeloablative (n=35) or nonmyeloablative (n=19) conditioning and 4-6/6 human leukocyte antigen (HLA)-matched double-unit grafts. One hundred seven units were thawed with dilution, whereas 1 red blood cell (RBC)-replete unit was washed. A 5:1 dextran 40%/25% albumin solution was used. RBC-depleted units (n=104) were diluted >or=5.5-fold (median final volume 200 mL [range: 200-500]), whereas RBC-replete units (n=3) were diluted >or=4-fold (median final volume 400 mL [range: 400-535]). Total nucleated cell (TNC) recovery was 86%; the median infused TNC dose was 2.17x10(7)/kg/unit. Although 35 patients (65%) had a total of 45 infusion reactions (6 nausea, 31 hypertension, 3 pain, 1 rigors/fever, 2 transient hypoxia, 2 renal impairment) requiring additional therapy, there were no infusion-related serious adverse events, and reactions were not related to dimethyl sulfoxide (DMSO) dose/kg. Cumulative incidence of sustained donor engraftment was 94% (95% cumulative incidence [CI]: 87-100) with neutrophil recovery occurring at a median of 25 days (range: 13-43) in myeloablative and 10 days (range: 7-36) in nonmyeloablative recipients. CB thaw with albumin-dextran dilution reduces unit manipulation, and minimizes cell loss, speeds time to infusion, is associated with a tolerable infusion reaction profile, and a high rate of sustained engraftment in CBT recipients >or=20 kg.

Permacol (porcine dermal collagen) and Alloderm (acellular cadaveric dermis) as a vascular patch repair for common carotid arteriotomy in a rabbit model.

Occult injuries to arteries are common in trauma and evolution of their repair has been observed throughout military conflicts. Currently, autogenous vein and polytetrafluoroethylene (PTFE) are used as patch agents for arterial trauma. However, suitable vein is often lacking in multitrauma patients, and PTFE is prone to infection in the contaminated combat wound. The purpose of this study is to evaluate Permacol, porcine dermal collagen, and Alloderm, acellular cadaveric dermis, as suitable alternatives to PTFE with the potential benefit of being used in contaminated wounds. A New Zealand White rabbit common carotid arteriotomy model was used to compare Permacol (n = 12), Alloderm (n = 11), and PTFE (n = 13) for patch repair. Thrombin generation was examined using an enzyme-linked immunosorbent assay for thrombin-antithrombin complex. Histological samples were taken to analyze vessel lumen area, vessel diameter, intimal thickness, and medial thickness. Pathological examinations were made to compare rates of intimal hyperplasia, aneurysm, patency, and thrombus formation. The Permacol group showed equivalent rates of thrombus, aneurysm, and patency compared with PTFE. Increased lumen area was seen in the Permacol group, 0.344 mm2 (p = 0.02) compared with the PTFE group, 0.204 mm2. Permacol also had decreased incidence of intimal hyperplasia compared with PTFE, 50.0% versus 92% (p < 0.05). Alloderm had increased rates of aneurysm formation, 63.6% (p = 0.004) compared with PTFE, 0.0%, and Permacol groups, 8.3%. Alloderm also had increased intimal thickness through the patch, 0.076 mm (p = 0.18), compared with PTFE, 0.026 mm, and Permacol groups, 0.024 mm. Vessel diameter through the patch showed the Alloderm group, 1.87 mm (p = 0.004), was significantly larger than both the Permacol, 1.41 mm, and PTFE groups, 1.28 mm. Furthermore, Alloderm showed leukocyte migration around the patch. Enzyme-linked immunosorbent assay for thrombin-antithrombin complex was only elevated for PTFE in the 7-day postoperative measurement but was not statistically different from the other groups. Permacol has characteristics to be an effective alternative for PTFE for patch arteriotomy repair in our rabbit model. Futher studies need to be conducted to investigate the potential of Permacol in vascular trauma. Alloderm is not a suitable alternative to PTFE for patch arteriotomy repair.

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.

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.

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.

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.

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.