Systematic hybrid laparoscopic and endovascular treatment of median arcuate ligament syndrome: A single-center experience.

Background: Median arcuate ligament syndrome (MALS) is caused by celiac trunk (CT) compression by the median arcuate ligament. Clinically, this pathology varies from postprandial pain (Dunbar syndrome) to a life-threatening hemorrhage because of a rupture of a gastroduodenal artery aneurysm (GAA). Due to the low prevalence of this disease, there is no standard management for MALS. Material and method: This was a single-center, retrospective study of 13 patients. Two groups were identified on the basis of the initial clinical presentation: those operated for a GAA rupture (bleeding group-BG) and those operated electively for Dunbar syndrome (Dunbar syndrome group-DG). The primary endpoint was 30-day postoperative complications of a systematic laparoscopic release of the median arcuate ligament and stenting during the same procedure. Results: Seven patients (54%) underwent elective surgery. Six patients (46%) underwent semiurgent repair under elective conditions post-embolization for GAA bleeding. The total operative time was longer in the BG (p = 0.06). Two patients in the BG suffered early major complications and needed reintervention, and those in the DG had a lower comprehensive complication index. No mortality was reported at 30 days. Overall median length of stay was 5 days (IQR: 3.5-15.3). Patients in the DG had a significantly shorter length of stay (p = 0.02). At 6 months, the primary and secondary CT stent patencies were 82% and 100%, respectively. There were no high-flow GAA recurrences. Conclusions: A combined approach of laparoscopic release of the median arcuate ligament and stenting during the same procedure is feasible and safe, and this approach must be systematically discussed in symptomatic patients.

Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging.

The ideal preservation temperature for donation after circulatory death kidney grafts is unknown. We investigated whether subnormothermic (22 °C) ex vivo kidney machine perfusion could improve kidney metabolism and reduce ischemia-reperfusion injury. Methods: To mimic donation after circulatory death procurement, kidneys from 45-kg pigs underwent 60 min of warm ischemia. Kidneys were then perfused ex vivo for 4 h with Belzer machine perfusion solution UW at 22 °C or at 4 °C before transplantation. Magnetic resonance spectroscopic imaging coupled with LCModel fitting was used to assess energy metabolites. Kidney perfusion was evaluated with dynamic-contrast enhanced MRI. Renal biopsies were collected at various time points for histopathologic analysis. Results: Total adenosine triphosphate content was 4 times higher during ex vivo perfusion at 22 °C than at 4 °C perfusion. At 22 °C, adenosine triphosphate levels increased during the first hours of perfusion but declined afterward. Similarly, phosphomonoesters, containing adenosine monophosphate, were increased at 22 °C and then slowly consumed over time. Compared with 4 °C, ex vivo perfusion at 22 °C improved cortical and medullary perfusion. Finally, kidney perfusion at 22 °C reduced histological lesions after transplantation (injury score: 22 °C: 10.5 ± 3.5; 4 °C: 18 ± 2.25 over 30). Conclusions: Ex vivo kidney perfusion at 22°C improved graft metabolism and protected from ischemia-reperfusion injuries upon transplantation. Future clinical studies will need to define the benefits of subnormothermic perfusion in improving kidney graft function and patient's survival.

Hydrogen Sulphide Release via the Angiotensin Converting Enzyme Inhibitor Zofenopril Prevents Intimal Hyperplasia in Human Vein Segments and in a Mouse Model of Carotid Artery Stenosis.

OBJECTIVE: Hypertension is a major risk factor for intimal hyperplasia (IH) and re-stenosis following vascular and endovascular interventions. Preclinical studies suggest that hydrogen sulphide (H2S), an endogenous gasotransmitter, limits re-stenosis. While there is no clinically available pure H2S releasing compound, the sulfhydryl containing angiotensin converting enzyme inhibitor zofenopril is a source of H2S. Here, it was hypothesised that zofenopril, due to H2S release, would be superior to other non-sulfhydryl containing angiotensin converting enzyme inhibitors (ACEi) in reducing intimal hyperplasia. METHODS: Spontaneously hypertensive male Cx40 deleted mice (Cx40-/-) or wild type (WT) littermates were randomly treated with enalapril 20 mg or zofenopril 30 mg. Discarded human vein segments and primary human smooth muscle cells (SMCs) were treated with the active compound enalaprilat or zofenoprilat. IH was evaluated in mice 28 days after focal carotid artery stenosis surgery and in human vein segments cultured for seven days ex vivo. Human primary smooth muscle cell (SMC) proliferation and migration were studied in vitro. RESULTS: Compared with control animals (intima/media thickness 2.3 ± 0.33 µm), enalapril reduced IH in Cx40-/- hypertensive mice by 30% (1.7 ± 0.35 µm; p = .037), while zofenopril abrogated IH (0.4 ± 0.16 µm; p < .002 vs. control and p > .99 vs. sham operated Cx40-/- mice). In WT normotensive mice, enalapril had no effect (0.9665 ± 0.2 µm in control vs. 1.140 ± 0.27 µm; p > .99), while zofenopril also abrogated IH (0.1623 ± 0.07 µm; p < .008 vs. control and p > .99 vs. sham operated WT mice). Zofenoprilat, but not enalaprilat, also prevented IH in human vein segments ex vivo. The effect of zofenopril on carotid and SMCs correlated with reduced SMC proliferation and migration. Zofenoprilat inhibited the mitogen activated protein kinase and mammalian target of rapamycin pathways in SMCs and human vein segments. CONCLUSION: Zofenopril provides extra beneficial effects compared with non-sulfhydryl ACEi in reducing SMC proliferation and re-stenosis, even in normotensive animals. These findings may hold broad clinical implications for patients suffering from vascular occlusive diseases and hypertension.

Predictive Factors of Surgical Complications in the First Year Following Kidney Transplantation.

BACKGROUND: In the recent years, an increased use of marginal donors and grafts and a growing prevalence of peripheral arterial disease in the recipients have been observed. Meanwhile, the open surgical technique for kidney transplantation has not changed. The aim of this study is to analyze all surgical complications occurring in the first year after kidney transplant and to determine potential predictive risk factors. METHODS: Data of the 399 patients who underwent kidney transplant in our University Hospital between January 2006 and December 2015 were retrospectively reviewed. The primary endpoint was the overall rate of vascular, parietal and urological complications at 1 year following kidney transplantation. The secondary outcomes were graft and patient' survival rates, and the identification of predictive factors of the surgical complications. RESULTS: 24% of patients developed 134 complications. Vascular complication represented 39% of all complications and resulted in 9 graft losses. Parietal and urological complications represented 46-15% of all complications, respectively, No parietal or urological complications were associated with graft loss. 5 patients died during the 1st year, none of these cases was associated with graft loss. The graft survival rate reached 96% at 1 year, including patients still alive. The occurrence of surgical complication was associated with reduced graft survival at 1 year. Using a multivariate analysis, 4 predictive factors were identified: age, deceased donor, operative time and dyslipidemia. CONCLUSION: Surgical complications after kidney transplantation remained frequent and age, deceased kidney donors, and operative time were identified as risk factors. As vascular complications were a major cause of early graft loss, efforts should aim to reduce their occurrence to increase graft survival.

The effects of COVID-19 pandemic on patients with lower extremity peripheral arterial disease: A near miss disaster.

BACKGROUND: The COVID-19 pandemic has led to widespread postponement and cancelation of elective vascular surgeries in Switzerland. The consequences of these decisions are poorly understood. PATIENTS AND METHODS: In this observational, retrospective, single-center cohort study, we describe the impact of COVID-19 pandemic containment strategies on patients with lower extremity peripheral arterial disease (PAD) referred during the period March 11, to May 11, 2020, compared to the same time frames in 2018 to 2019. Patients admitted for acute limb ischemia (ALI) or chronic PAD and undergoing urgent or elective vascular surgery or primary amputation were included. Patients' characteristics, indications for admission, and surgical features were analyzed. The occurrence of 30 day outcomes was assessed, including length of stay, rates of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), and procedural and hemodynamic success. RESULTS: Overall, 166 patients were included. Fewer subjects per 10 day period were operated in 2020 compared to, 2018 to 2019 (6.7 vs. 10.5, respectively; P < 0.001). The former had higher rates of chronic obstructive pulmonary disease (COPD) (25% vs. 11.1%; P = 0.029), and ASA score (3.13 vs. 2.90; P = 0.015). The percentage of patients with ALI in 2020 was about double that of the same period in 2018 to 2019 (47.5% vs. 24.6%; P = 0.006). Overall, the types of surgery were similar between 2020 and 2018 to 2019, while palliative care and primary amputations occurred only in 2020 (5 out 40 cases). The rate of post-operative MACE was significantly higher in 2020 (10% vs. 2.4%; P = 0.037). CONCLUSIONS: During the first state of emergency for COVID-19 pandemic in 2020, less regular medical follow-up and hindered hospital access could have resulted in more acute and advanced clinical presentations of patients with PAD undergoing surgery. Guidelines are needed to provide appropriate care to this vulnerable population and avoid a large-scale disaster.

Ex Vivo Analysis of Kidney Graft Viability Using 31P Magnetic Resonance Imaging Spectroscopy.

BACKGROUND: The lack of organs for kidney transplantation is a growing concern. Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]). However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable measure of kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. Thus, pMRI could predict kidney energy state, and its viability before transplantation. METHODS: To mimic DCD, pig kidneys underwent 0, 30, or 60 min of warm ischemia, before hypothermic machine perfusion. During the ex vivo perfusion, we assessed energy metabolites using pMRI. In addition, we performed Gadolinium perfusion sequences. Each sample underwent histopathological analyzing and scoring. Energy status and kidney perfusion were correlated with kidney injury. RESULTS: Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (30 and 60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. CONCLUSIONS: ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft and patient's survival.

Impact of an intra-abdominal cooling device during open kidney transplantation in pigs.

BACKGROUND: Transplantation of kidneys from deceased donors is still associated with a high rate of postoperative renal dysfunction. During implantation into the recipient, the kidney rewarms. This second warm ischaemia time, which is not monitored, is harmful especially if prolonged. We recently developed an intra-abdominal cooling device that efficiently prevents kidney rewarming during robotic transplantation, and prevents ischaemia-reperfusion injuries. We tested the benefits of this cooling device during open kidney transplantation in pigs. METHODS: Kidneys were procured from large pigs by open bilateral nephrectomy. Following procurement, kidneys were flushed with 4°C Institut Georges Lopez-1 preservation solution, and placed on ice. Animals then underwent double sequential autologous open renal transplantation with (n = 7) and without (n = 6) intra-abdominal cooling. RESULTS: Mean anastomosis time was similar between groups (43.9 ± 13 minutes). At reperfusion, the renal cortex temperature was lower in the group with cooling (4.3 ± 1.1°C vs 26.5 ± 5.5°C, p <0.001). The cooled kidneys tended to be protected from injury, including some histopathological ischaemia-reperfusion lesions. With the device, kidneys had a better immediate postoperative urine output (p = 0.05). CONCLUSION: Our results indicate that the intra-abdominal cooling device significantly reduced second warm ischaemic time during transplantation, is technically safe and does not prolong anastomotic time.

Hydrogen sulfide-releasing peptide hydrogel limits the development of intimal hyperplasia in human vein segments.

Currently available interventions for vascular occlusive diseases suffer from high failure rates due to re-occlusive vascular wall adaptations, a process called intimal hyperplasia (IH). Naturally occurring hydrogen sulfide (H2S) works as a vasculoprotective gasotransmitter in vivo. However, given its reactive and hazardous nature, H2S is difficult to administer systemically. Here, we developed a hydrogel capable of localized slow release of precise amounts of H2S and tested its benefits on IH. The H2S-releasing hydrogel was prepared from a short peptide attached to an S-aroylthiooxime H2S donor. Upon dissolution in aqueous buffer, the peptide self-assembled into nanofibers, which formed a gel in the presence of calcium. This new hydrogel delivered H2S over the course of several hours, in contrast with fast-releasing NaHS. The H2S-releasing peptide/gel inhibited proliferation and migration of primary human vascular smooth muscle cells (VSMCs), while promoting proliferation and migration of human umbilical endothelial cells (ECs). Both NaHS and the H2S-releasing gel limited IH in human great saphenous vein segments obtained from vascular patients undergoing bypass surgery, with the H2S-releasing gel showing efficacy at a 5x lower dose than NaHS. These results suggest local perivascular H2S release as a new strategy to limit VSMC proliferation and IH while promoting EC proliferation, hence re-endothelialization. STATEMENT OF SIGNIFICANCE: Arterial occlusive disease is the leading cause of death in Western countries, yet current therapies suffer from high failure rates due to intimal hyperplasia (IH), a thickening of the vascular wall leading to secondary vessel occlusion. Hydrogen sulfide (H2S) is a gasotransmitter with vasculoprotective properties. Here we designed and synthesized a peptide-based H2S-releasing hydrogel and found that local application of the gel reduced IH in human vein segments obtained from patients undergoing bypass surgery. This work provides the first evidence of H2S efficacy against IH in human tissue, and the results show that the gel is more effective than NaHS, a common instantaneous H2S donor.

Ten Year Experience of Using Cryopreserved Arterial Allografts for Distal Bypass in Critical Limb Ischaemia.

OBJECTIVE/BACKGROUND: In critical limb ischaemia (CLI), current guidelines recommend revascularisation whenever possible, preferentially through endovascular means. However, in the case of long occlusions or failed endovascular attempts, distal bypasses still have a place. Single segment great saphenous vein (GSV), which provides the best conduit, is often not available and currently there is no consensus about the best alternative graft. METHODS: From January 2006 to December 2015, 42 cryopreserved arterial allografts were used for a distal bypass. Autologous GSVs or alternative autologous conduits were unavailable for all patients. The patients were observed for survival, limb salvage, and allograft patency. The results were analysed with Kaplan-Meier graphs. RESULTS: Estimates of secondary patency at one, two and five years were 81%, 73%, and 57%, respectively. Estimates of primary patency rates at one, two and five years were 60%, 56%, and 26%, respectively. Estimates of limb salvage rates at one, two and five years were 89%, 89%, and 82%, respectively. Estimates of survival rates at one, two and five years were 92%, 76% and 34%, respectively. At 30 days, major amputations and major adverse cardiac events were one and zero, respectively. Six major amputations occurred during the long-term follow up. CONCLUSION: Despite a low primary patency rate at two years, the secondary patency of arterial allografts is acceptable for distal bypasses. This suggests that cryopreserved arterial allografts are a suitable alternative for limb saving distal bypasses in the absence of venous conduits, improving limb salvage rates and, possibly, quality of life.

Evaluating intimal hyperplasia under clinical conditions.

OBJECTIVES: Open arterial revascularization using venous segments is frequently associated with the development of intimal hyperplasia (IH), leading to severe restenosis and graft failure. The lack of treatment to prevent this pathology is a major problem. Therefore, we generated a new porcine model, which closely mimics the clinical development of human IH, to test the therapeutic potential of candidate drugs. METHODS: A patch of jugular vein was sutured to the right common carotid artery of pigs, to expose the vein to haemodynamic conditions of the arterial bed. Four weeks after surgery, the operated vessels which received no further treatment (the control group) were compared with (i) contralateral, non-operated vessels (the healthy group); (ii) vessels of pigs that received a perivascular application of a drug-free microparticle gel (the placebo group) and (iii) vessels of pigs that perioperatively received the same gel loaded with 10-mg atorvastatin (the atorvastatin group). RESULTS: When compared with non-operated vessels, all operated segments displayed a sizable IH which was thicker in the venous patch than in the host artery. These alterations were associated with a thickening of the intima layer of both vessels in the absence of inflammation. The intima/media ratio has been significantly increased by 2000-fold in the vein patches. Perivascular application of atorvastatin did not prevent IH formation. However, the drug increased the adventitial neovascularization in the operated vessels. CONCLUSIONS: The novel porcine model allows for monitoring IH formation under haemodynamic conditions which mimic clinical situations. It should facilitate the screening of innovative treatments to prevent restenosis.

Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production.

Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1α. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in ECs in vitro, and increased capillary density in mouse skeletal muscle in vivo via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1α. We also identified a requirement for cystathionine-γ-lyase in VEGF-dependent angiogenesis via increased hydrogen sulfide (H2S) production. H2S mediated its proangiogenic effects in part by inhibiting mitochondrial electron transport and oxidative phosphorylation, resulting in increased glucose uptake and glycolytic ATP production.

Who Should Be Operated When Presenting with a Ruptured Abdominal Aortic Aneurysm? A Monocentric Study in a Tertiary Hospital.

BACKGROUND: Mortality with ruptured abdominal aortic aneurysms (rAAAs) is 80% overall, 50% when operated, and 100% when not operated. Distinguishing in emergency patients who should be operated versus being offered palliative treatment is difficult. We sought to identify key factors to consider in this decision-making. METHODS: Between 2001 and 2014, we selected all consecutive patients with rAAA treated by open or endovascular procedures in a tertiary hospital for inclusion in this retrospective, single-center study. Symptomatic aneurysms and isolated ruptured iliac aneurysms were excluded. The primary outcome was in-hospital mortality, and secondary outcomes were institutionalization rate and long-term mortality. Associations between predictive factors and in-hospital mortality were evaluated using univariate logistic regression. The local ethics committee approved this study. RESULTS: The mean age (±standard deviation) of the 72 included patients was 73 years (±9.0) and 88% were men. Among the 65 open (90%) and 7 endovascular procedures (10%), overall in-hospital mortality was 21%, 1- and 2-year mortalities were both 26%, and the institutionalization rate was 5%. Mean follow-up was 43 months (Kaplan-Meier estimate). Univariate analysis identified age as associated with a 20% per year increased risk of in-hospital mortality (correlation, P < 0.0001). Female sex was the other main preoperative risk factor correlated with in-hospital mortality (P = 0.006). Significant perioperative risk factors were suprarenal clamping (P = 0.038), amount of fresh frozen plasma transfused (P = 0.018), and number of blood transfusions (P < 0.0001). CONCLUSIONS: The most significant preoperative mortality-related factors were age and female sex. Our study also showed that institutionalization and long-term mortality are not factors to consider in the decision-making process.

[Thromboangiitis obliterans: notions for practice]. / Thromboangéite oblitérante :notions pour la pratique.

Thromboangiitis obliterans is an occlusive vasculopathy affecting small- and medium-size arteries. It can result in severe ischemic status. Thrombophlebitis can be associated. The exact etiology has still to be elucidated. Smoking is the main contributing factor. Diagnosis is based on clinic and paraclinic context, as well as exclusion of other vascular pathologies. Its management consists in complete smoking cessation and instauration of vasodilator treatment. Revascularization is an option that has to be evaluated on a case by case basis. New promising therapeutic approaches are emerging.

La thromboangéite oblitérante se caractérise principalement par une atteinte occlusive des artères de petit et moyen calibres, pouvant mener à un tableau clinique ischémique grave. Une thrombophlébite peut y être associée. L'étiologie exacte n'est pas encore connue. Le tabagisme est le facteur de risque prépondérant. Le diagnostic se base sur les contextes clinique et paraclinique, ainsi que l'exclusion d'autres pathologies vasculaires. La prise en charge consiste en l'arrêt définitif du tabagisme et l'introduction de traitements vasodilatateurs. Les options de revascularisation sont à discuter de cas en cas. De nouvelles modalités thérapeutiques semblent prometteuses.

Connexin37 reduces smooth muscle cell proliferation and intimal hyperplasia in a mouse model of carotid artery ligation.

AIMS: Intimal hyperplasia (IH) is an abnormal response to vessel injury characterized by the dedifferentiation, migration, and proliferation of quiescent vascular smooth muscle cells (VSMC) to form a neointima layer. Vascular connexins (Cx) are involved in the pathophysiology of various vascular diseases, and Cx43, the main Cx expressed in VSMC, has been shown to promote VSMC proliferation and IH. The aim of this study was to investigate the participation of another Cx, namely Cx37, in the formation of the neointima layer. METHODS AND RESULTS: Wild-type (WT) and Cx37-deficient (Cx37-/-) C57BL/6J mice were subjected to carotid artery ligation (CAL), a model of vessel injury and IH. The neointima developed linearly in WT until 28 days post surgery. In contrast, the neointima layer was almost absent 14 days after surgery in Cx37-/- mice, and twice as more developed after 28 days compared to WT mice. This large neointima formation correlated with a two-fold increase in cell proliferation in the media and neointima regions between 14 and 28 days in Cx37-/- mice compared to WT mice. The CAL triggered Cx43 overexpression in the media and neointima layers of ligated carotids in WT mice, and selectively up-regulated Cx37 expression in the media layer, but not in the neointima layer. The de novo expression of Cx37 in human primary VSMC reduced cell proliferation and P-Akt levels, in association with lower Cx43 levels, whereas Cx43 overexpression increased P-Akt levels. CONCLUSION: The presence of Cx37 in the media layer of injured arteries restrains VSMC proliferation and limits the development of IH, presumably by interfering with the pro-proliferative effect of Cx43 and the Akt pathway.

Zenith Bifurcated Iliac Side Branch Device: Mid-term Results and Assessment of Risk Factors for Intraoperative Thrombosis.

BACKGROUND: The aim of this study is to evaluate the short- and mid-term results of the Zenith bifurcated iliac side branch device (ZBIS) in the treatment of common iliac artery (CIA) aneurysms, and to assess risk factors for intraoperative internal iliac artery (IIA) thrombosis. METHODS: All patients who underwent endovascular treatment of either an isolated CIA aneurysm or an aortoiliac aneurysm using the ZBIS device in the departments of vascular surgery of Strasbourg (France) and Lausanne (Switzerland) between January 2010 and December 2014 were retrospectively collected. RESULTS: Thirty-one implantations were performed: 30 patients underwent 31 endovascular CIA aneurysm treatments with the ZBIS device. Mean operative time was 188 min. Technical success was obtained in 26 implantations (84%). In 5 implantations (16%), the final angiogram revealed an IIA thrombosis. Thirty-day mortality was 3.2%. Thirty-day morbidity was 13.3%. Mean follow-up was 15 months. Overall survival was 96% at 1 year and 89% at 2 years. In intention-to-treat analysis, primary patency of the internal iliac side branch was 84% at 1 year and 76% at 2 years (5 peroperative IIA occlusions and 1 late occlusion). Freedom from reintervention was 89% at 1 and 2 years. One case of type III endoleak and 2 cases of type II endoleaks were identified. Only type III endoleak required an additional intervention with a covered stent. Aneurysm diameter decreased in 15 implantations (48%) and remained stable in 16 implantations (52%). Clinical, radiological, and peroperative parameters were analyzed to identify risk factor for intraoperative thrombosis of the internal iliac side branch. Notion of intraoperative difficulties (any additional procedure that was not initially planned and increasing the operating time) appeared as a risk factor in multivariate analysis (P < 0.01, standard deviation 1.27, odds ratio 30.6). CONCLUSIONS: The main findings of our study is that the procedure can be difficult to perform in particular conditions and can lead to peroperative failure in these cases, highlighting the need for adequate patients screening. When technical success is obtained, outcomes can be considered as satisfactory.

Is Overnight Fasting before Surgery Too Much or Not Enough? How Basic Aging Research Can Guide Preoperative Nutritional Recommendations to Improve Surgical Outcomes: A Mini-Review.

Dietary restriction (DR) is best known for extending lifespan in experimental model organisms, but also increases resistance to a variety of clinically relevant stressors, including those associated with surgery. Extended periods of DR, lasting months to years, are required for optimal longevity benefits in rodents, but short-term dietary preconditioning (less than 1 week) remarkably protects from acute injury. Here, we discuss recent advances in our understanding of the mechanistic basis of short-term DR and fasting in the context of surgical stress resistance, including upstream amino acid sensing by the GCN2 and mTORC1 pathways, and downstream effector mechanisms including increased insulin-dependent prosurvival signaling and elevated endogenous hydrogen sulfide production. We also review the current trend in preoperative nutrition away from preoperative fasting and towards carbohydrate loading. Finally, we discuss the rationale for the nonmutually exclusive use of brief DR or pharmacological DR mimetics to precondition against the stress and potential complications of surgery.

Surgical injury induces local and distant adipose tissue browning.

The adipose organ, which comprises brown, white and beige adipocytes, possesses remarkable plasticity in response to feeding and cold exposure. The development of beige adipocytes in white adipose tissue (WAT), a process called browning, represents a promising route to treat metabolic disorders. While surgical procedures constantly traumatize adipose tissue, its impact on adipocyte phenotype remains to be established. Herein, we studied the effect of trauma on adipocyte phenotype one day after sham, incision control, or surgical injury to the left inguinal adipose compartment. Caloric restriction was used to control for surgery-associated body temperature changes and weight loss. We characterized the trauma-induced cellular and molecular changes in subcutaneous, visceral, interscapular, and perivascular adipose tissue using histology, immunohistochemistry, gene expression, and flow cytometry analysis. After one day, surgical trauma stimulated adipose tissue browning at the site of injury and, importantly, in the contralateral inguinal depot. Browning was not present after incision only, and was largely independent of surgery-associated body temperature and weight loss. Adipose trauma rapidly recruited monocytes to the injured site and promoted alternatively activated macrophages. Conversely, PDGF receptor-positive beige progenitors were reduced. In this study, we identify adipose trauma as an unexpected driver of selected local and remote adipose tissue browning, holding important implications for the biologic response to surgical injury.

PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals.

The mechanisms responsible for the persistence of HIV-1 after many years of suppressive antiretroviral therapy (ART) have been only partially elucidated. Most of the studies investigating HIV-1 persistence have been performed with blood, although it is well known that germinal centers (GCs) within lymph nodes (LNs) serve as primary sites for HIV-1 replication. We sought to identify the memory CD4 T cell populations in blood and LNs that are responsible for the production of replication-competent and infectious HIV-1, as well as for active and persistent virus transcription in ART-treated (for 1.5-14.0 years), aviremic (<50 HIV RNA copies/ml) HIV-infected individuals. We demonstrate that LN CD4 T cells that express programmed cell death 1 (PDCD1; also known as PD-1), which are composed of about 65% T follicular helper cells as defined by the expression of the cell surface receptors CXCR5 and PD-1, are the major source of replication-competent HIV-1 and of infectious virus, as compared to any other (CXCR5(-)PD-1(-) and CXCR5(+)PD-1(-)) blood or LN memory CD4 T cell populations. LN PD-1(+) cells accounted for 46% and 96% of the total pools of memory CD4 T cells containing inducible replication-competent or infectious virus, respectively. Notably, higher levels of cell-associated HIV-1 RNA were present in LN PD-1(+) cells after long-term (up to 12 years) ART than in other memory CD4 T cell subpopulations. These results indicate that LN PD-1(+) cells are the major CD4 T cell compartment in the blood and LNs for the production of replication-competent and infectious HIV-1, and for active and persistent virus transcription in long-term-ART-treated aviremic individuals. Thus, these cells may represent a major obstacle to finding a functional cure for HIV-1 infection.

Endovascular Versus Open Abdominal Aortic Aneurysm: Best Decision.

Since the first implantation of an endograft in 1991, endovascular aneurysm repair (EVAR) rapidly gained recognition. Historical trials showed lower early mortality rates but these results were not maintained beyond 4 years. Despite newer-generation devices, higher rates of reintervention are associated with EVAR during follow-up. Therefore, the best therapeutic decision relies on many parameters that the physician has to take in consideration. Patient's preferences and characteristics are important, especially age and life expectancy besides health status. Aneurysmal anatomical conditions remain probably the most predictive factor that should be carefully evaluated to offer the best treatment. Unfavorable anatomy has been observed to be associated with more complications especially endoleak, leading to more re-interventions and higher risk of late mortality. Nevertheless, technological advances have made surgeons move forward beyond the set barriers. Thus, more endografts are implanted outside the instructions for use despite excellent results after open repair especially in low-risk patients. When debating about AAA repair, some other crucial points should be analysed. It has been shown that strict surveillance is mandatory after EVAR to offer durable results and prevent late rupture. Such program is associated with additional costs and with increased risk of radiation. Moreover, a risk of loss of renal function exists when repetitive imaging and secondary procedures are required. The aim of this article is to review the data associated with abdominal aortic aneurysm and its treatment in order to establish selection criteria to decide between open or endovascular repair.

Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia.

Venous bypass grafts often fail following arterial implantation due to excessive smooth muscle cells (VSMC) proliferation and consequent intimal hyperplasia (IH). Intercellular communication mediated by Connexins (Cx) regulates differentiation, growth and proliferation in various cell types. Microarray analysis of vein grafts in a model of bilateral rabbit jugular vein graft revealed Cx43 as an early upregulated gene. Additional experiments conducted using an ex-vivo human saphenous veins perfusion system (EVPS) confirmed that Cx43 was rapidly increased in human veins subjected ex-vivo to arterial hemodynamics. Cx43 knock-down by RNA interference, or adenoviral-mediated overexpression, respectively inhibited or stimulated the proliferation of primary human VSMC in vitro. Furthermore, Cx blockade with carbenoxolone or the specific Cx43 inhibitory peptide 43gap26 prevented the burst in myointimal proliferation and IH formation in human saphenous veins. Our data demonstrated that Cx43 controls proliferation and the formation of IH after arterial engraftment.