Matthew Fok

Interleukin-1β mediates macrophage-induced impairment of insulin signaling in human primary adipocytes.

Adipose tissue expansion during obesity is associated with increased macrophage infiltration. Macrophage-derived factors significantly alter adipocyte function, inducing inflammatory responses and decreasing insulin sensitivity. Identification of the major factors that mediate detrimental effects of macrophages on adipocytes may offer potential therapeutic targets. IL-1β, a proinflammatory cytokine, is suggested to be involved in the development of insulin resistance. This study investigated the role of IL-1β in macrophage-adipocyte cross-talk, which affects insulin signaling in human adipocytes. Using macrophage-conditioned (MC) medium and human primary adipocytes, we examined the effect of IL-1β antagonism on the insulin signaling pathway. Gene expression profile and protein abundance of insulin signaling molecules were determined, as was the production of proinflammatory cytokine/chemokines. We also examined whether IL-1β mediates MC medium-induced alteration in adipocyte lipid storage. MC medium and IL-1β significantly reduced gene expression and protein abundance of insulin signaling molecules, including insulin receptor substrate-1, phosphoinositide 3-kinase p85α, and glucose transporter 4 and phosphorylation of Akt. In contrast, the expression and release of the proinflammatory markers, including IL-6, IL-8, monocyte chemotactic protein-1, and chemokine (C-C motif) ligand 5 by adipocytes were markedly increased. These changes were significantly reduced by blocking IL-1β activity, its receptor binding, or its production by macrophages. MC medium-inhibited expression of the adipogenic factors and -stimulated lipolysis was also blunted with IL-1β neutralization. We conclude that IL-1β mediates, at least in part, the effect of macrophages on insulin signaling and proinflammatory response in human adipocytes. Blocking IL-1β could be beneficial for preventing obesity-associated insulin resistance and inflammation in human adipose tissue.

Acute type A aortic dissection in the United Kingdom: Surgeon volume-outcome relation

Objectives Surgery for acute type A aortic dissection (ATAD) carries a high risk of operative mortality. We examined the surgeon volume‐outcome relation with respect to in‐hospital mortality for patients presenting with this pathology in the United Kingdom. Method Between April 2007 and March 2013, 1550 ATAD procedures were identified from the National Institute for Cardiovascular Outcomes Research database. A total of 249 responsible consultant cardiac surgeons from the United Kingdom recorded 1 or more of these procedures in their surgical activity over this period. We describe the patient population and mortality rates, focusing on the relationship between surgeon volume and in‐hospital mortality. Results The mean annual volume of procedures per surgeon during the 6‐year period ranged from 1 to 6.6. The overall in‐hospital mortality rate was 18.3% (283/1550). A mortality improvement at the 95% level was observed with a risk‐adjusted mean annual volume >4.5. Surgeons with a mean annual volume <4 over the study period had significantly higher in‐hospital mortality rates in comparison with surgeons with a mean annual volume ≥4 (19.3% vs 12.6%; P = .015). Conclusions Patients with ATAD who are operated on by lower‐volume surgeons experience higher levels of in‐hospital mortality. Directing these patients to higher‐volume surgeons may be a strategy to reduce in‐hospital mortality.

Long-term outcomes in thoracoabdominal aortic aneurysm repair for chronic type B dissection.

INTRODUCTION Open repair for chronic aortic dissection remains a challenging surgical option. Different centers report diverse experiences and outcomes pertaining to thoracoabdominal aortic aneurysm repair (TAAAR) for chronic type B dissection. We highlight our centers experience and results on a background of published literature and current evidence. METHODS We reviewed 214 open TAAAR performed between October 1998 and February 2014. Of these, chronic type B dissection was present in 62 (29.0%) patients. We reviewed these patients in terms of demographics, operative characteristics and outcomes. Thirteen (21.0%) patients had surgery on the descending thoracic aorta [Category A =2 (3.2%), B =0 (0%), C =11 (17.7%)] and 49 (79.0%) in the thoracoabdominal thoracic aorta [Crawford extent I =5 (8.1%), extent II =39 (62.9%), extent III =4 (6.5%), extent IV =1 (1.6%)]. Left heart bypass was used in 12 (19.4%) patients. RESULTS The composite in-hospital endpoint, adverse outcome-defined as operative death, renal failure necessitating dialysis at discharge, stroke, or permanent paraplegia or paraparesis-occurred after 28 (45.2%) procedures. There were 14 (22.6%) operative deaths. In-hospital mortality was seven (16.3%) out of 43 elective patients, and increased to seven (36.8%) of the 19 non-elective ones. Permanent paraplegia or paraparesis occurred after two (3.2%) cases, stroke occurred after seven (11.3%) and renal failure requiring dialysis occurred after 16 (25.8%). Mean follow-up time was 3.2 years and actuarial 5-year mortality was 27.4% [nine (14.5%) elective and eight (12.9%) non-elective patients]. CONCLUSIONS TAAAR in chronic type B dissection carries a substantial risk of early adverse outcomes. The results could be well alleviated with cases directed towards specialized regional and supra-regional centers. Although the endovascular approaches offer relatively low mortality and morbidity, there is a lack of long-term data and guidelines on their use. There is a need for a multidisciplinary international registry on the management of thoracoabdominal aortic aneurysms and dissection. This would provide a degree of guidance on relevant clinical and surgical judgments and outcomes.

Aortic Valve Repair: A Systematic Review and Meta-analysis of Published Literature.

UNLABELLED Background : It is widely accepted that aortic valve disease is surgically managed with aortic valve replacement (AVR) using different available prostheses. The long-term survival, durability of the valve, and freedom from reoperation after AVR are well established in published literature. Over the past two decades, aortic valve repair (AVr) has evolved into an accepted surgical option for patients with aortic valve disease. We review and analyze the published literature on AVr. Methods : A systematic review of the current literature was performed through three electronic databases from inception to August 2013 to identify all relevant studies relating to aortic valve repair. Articles selected were chosen by two reviewers. Articles were excluded if they contained a pediatric population or if the patient number was less than 50. RESULTS Twenty-four studies conformed to the inclusion criteria for inclusion in the systematic review. In total, 4986 patients underwent aortic valve repair. 7 studies represented bicuspid aortic valve (BAV) repair, 5 studies represented cusp prolapse, and 3 studies represented valve repair with root dilation or aneurysm. Overall weighted in-hospital mortality for all studies was low (1.46% ± 1.21). Preoperative aortic insufficiency (AI) ≥ 2+ did not correlate to reoperation for valve failure (Pearsons Rs 0.2705, P = 0.2585). AI at discharge was reported in 9 studies with a mean AI ≥ 2+ in 6.1% of patients. Weighted average percentage for valve reoperation following BAV repair was 10.23% ± 3.2. Weighted average reoperation following cusp prolapse repair was 3.83 ± 1.96. Weighted average reoperation in aortic valve sparing procedures with root replacement was 4.25% ± 2.46. Although there are limitations and complications of prosthetic valves, especially for younger individuals, there is ample published literature that confers strong evidence for AVR. On the contrary, aortic valve repair may be a useful option for selected patients, but there is lack of uniformity in data and absence of compelling supporting evidence. An international multi-center study comparing and assessing the results between AVR & AVr is the next step required. Currently, higher levels of evidence do not exist for aortic valve repair.

A Perspective on Natural History and Survival in Nonoperated Thoracic Aortic Aneurysm Patients.

There are many questions that remain unanswered in the understanding of the natural history of thoracic aortic aneurysm (TAA). This review will critically appraise the current published evidence on the natural history of TAA in nonoperated patients and their present rates of survival.

The History of Deep Hypothermic Circulatory Arrest in Thoracic Aortic Surgery.

Depending on the extent of aortic disease and surgical repair required, thoracic aortic surgery often involves periods of reduced cerebral perfusion. Historically, this resulted in detrimental neurological dysfunction, and high risk of mortality and morbidity. Over the last half century, rapid improvements have revolutionized aortic surgery. Among these, deep hypothermic circulatory arrest (DHCA) has drastically reduced the risk of mortality and morbidity following surgery on the thoracic aorta. This progress was facilitated by experimental pioneers such as Bigelow, who studied reduced oxygen expenditure consequent on induction of hypothermia in dogs. These encouraging findings led to trials in human cardiac surgery by Lewis in 1952 and further made possible the first successful aortic arch replacement by Denton Cooley and Michael De Bakey. Modern day surgery has come a long way from the use of immersion of the patient in ice baths and other primitive techniques previously described. This paper explores the development of deep hypothermic circulatory arrest from its origins to the present.

Brain protection in aortic arch aneurysm: antegrade or retrograde?

During open aortic arch repair, there is an interruption of cerebral perfusion and to prevent neurological sequelae, the hypothermic circulatory arrest has been established to provide sufficient brain protection coupled with adjuncts including retrograde and antegrade cerebral perfusion. To date, brain protection during open aortic arch repair is a contested topic as to which provides superior brain protection with little evidence existing to suggest supremacy of one modality over the other. This article reviews current literature reflecting on key and emerging studies in brain protection and their associated outcomes in patients undergoing open aortic arch surgery.

Video-Assisted Thoracoscopic Versus Robotic-Assisted Thoracoscopic Thymectomy: Systematic Review and Meta-analysis

Objective Minimally invasive thoracic surgical procedures, performed with or without the assistance of a robot, have gained popularity over the last decade. They have increasingly become the choice of intervention for a number of thoracic surgical operations. Minimally invasive surgery decreases postoperative pain, hospital stay and leads to a faster recovery in comparison with conventional open methods. Minimally invasive techniques to perform a thymectomy include video-assisted thoracoscopic surgery (VATS) or robotic-assisted thoracoscopic surgery (RATS). In this study, we aim to systematically review and interrogate the literature on minimally invasive thymectomy and draw a meta-analysis on the outcomes between the two approaches. Methods An extensive electronic health database search was performed on all articles published from inception to May 2015 for studies describing outcomes in VATS and RATS thymectomy. Results A total of 350 patients were included in this study, for which 182 and 168 patients underwent RATS and VATS thymectomy, respectively. There were no recorded in-hospital deaths for either procedure. There was no statistical difference in conversion to open, length of hospital stay, or postoperative pneumonia. Operational times for RATS thymectomy were longer. Conclusions The VATS and RATS thymectomy offer good and safe operative and perioperative outcomes. There is little difference between the two groups. However, there is poor evidence basis for the long-term outcomes in minimally invasive procedures for thymectomy. It is imperative that future studies evaluate oncological outcomes both short and long term as well as those related to safety.

Impact of cell purification technique of autologous human adult stem cells on inflammatory reaction.

Adult stem cells have shown fantastic regenerative potential as the cellular components of biomaterial mediated tissue engineering. Realising the biomedical potential of human adult stem cells (hASCs) however will require delivery in an ultra- purified format, without competing cells which may mediate inflammation, fibrosis or tumorigenesis. Purifying ASCs involves exhuming cells from primary tissue using immunoaffinity; which isolates pure populations with the complication of retained immunoglobulin (Ig); the clinical impact of which is currently not known. One of the negative outcomes of retained surface Ig is exacerbation of inflammation by leucocyte Fc receptor (FcR) activation, with consequences ranging from inflammatory cytokine and ROS release to chronic inflammation. The balance of ROS within a tissue will impact the efficacy of a stem cell therapy as ROS play an important role in stem cell self renewal and differentiation. In this study we utilised a chemiluminescent monitoring technique based on a ROS excitable photoprotein Pholasin, to quantify leucocyte ROS production in response to xenogeneic and recombinant human Ig of varying class and isotype with applications in stem cell selection. We were able to demonstrate inter-class differences in leucocyte ROS response to Ig which also varied between donors. This study highlighted the potential for utilising this technique for personalisation of autologous ASC therapies. This would allow clinicians to perform a rapid pre-operative screen to maximise the probability for success of an ASC intervention based on cell isolation using an Ig most appropriate for a specific patient.

Liverpool Aortic Surgery Symposium V: New Frontiers in Aortic Disease and Surgery

Aortic aneurysm disease is a complex condition that requires a multidisciplinary approach in management. The innovation and collaboration among vascular surgery, cardiothoracic surgery, interventional radiology, and other related specialties is essential for progress in the management of aortic aneurysms. The Fifth Liverpool Aortic Surgery Symposium that was held in May 2013 aimed at bringing national and international experts from across the United Kingdom and the globe to deliver their thoughts, applications, and advances in aortic and vascular surgery. In this report, we present a selected short synopsis of the key topics presented at this symposium.