Systematic review of the venous thromboembolism risk assessment models used in aesthetic plastic surgery

BACKGROUND: A reliable venous thromboembolism (VTE) risk assessment model (RAM) can assist surgeons in identifying patients who would benefit from VTE prophylaxis. This systematic review was aimed at summarising the current available evidence on VTE RAMs used in aesthetic plastic surgery. METHODS: A comprehensive search was performed in the PubMed, EMBASE and Cochrane databases to include primary studies describing VTE RAMs in aesthetic plastic surgery from 1946 to February 2019. The objective was to compare the different VTE RAMs described for aesthetic plastic surgery to recommend a reliable model to stratify patients. RESULTS: Of the 557 articles identified in the PubMed, EMBASE and Cochrane databases, six articles were included in the final review. Five different RAMs were used in the included studies: Caprini 2005 RAM, Caprini 2010 RAM, Davison-Caprini 2004 RAM, the American Society of Anaesthesiologist's (ASA) physical status grading system and a tool developed by Wes et al. The difference in risk weightage amongst the tools along with the VTE incidences for different categories was compared. The Caprini 2005 RAM was the most widely reported tool and validated in plastic surgery patients. CONCLUSION: Amongst the five different tools currently used, the Caprini 2005 RAM was the most widely reported. This tool was validated in plastic surgery patients and reported to be a sensitive and reliable tool for VTE risk stratification; therefore, current data support its use until further higher quality evidence becomes available. Because of the heterogeneity of the data and low quality of the current evidence, a definitive recommendation cannot be made on the best VTE RAM for patients undergoing aesthetic plastic surgery. This paper highlights the need for randomised controlled trials evaluating the various RAMs which are essential to support future recommendations and guidelines

Hypoxia upregulates angiogenesis and synovial cell migration in rheumatoid arthritis

INTRODUCTION: Rheumatoid arthritis (RA) is characterised by invasion of cartilage, bone and tendon by inflamed synovium. Previous studies in our laboratory have shown that hypoxia is a feature of RA synovitis. In the present study, we investigated the consequences of hypoxia on angiogenesis and synovial fibroblast migration in RA. METHODS: Synovial tissue was harvested from RA patients, and synovial membrane cells were cultured under conditions either of hypoxia (1% oxygen) or normoxia (21% oxygen). Protein levels of matrix metalloproteinases (MMPs) and angiogenic factors were measured, while RNA was extracted for PCR quantification of MMPs/tissue inhibitors of MMP (TIMPs) and angiogenic factors. Migration of RA synovial fibroblasts through collagen, and the effect of RA synovial cell supernatants in an in vitro angiogenesis assay, were utilised to determine the functional relevance of changes in mRNA/protein. RESULTS: We observed upregulation under hypoxic conditions of MMPs responsible for collagen breakdown, specifically collagenase MMP-8, and the gelatinases MMP-2 and MMP-9, at both mRNA and protein levels. Increased MT1-MMP mRNA was also observed, but no effect on TIMP-1 or TIMP-2 was detected. RA fibroblast migration across collagen was significantly increased under hypoxic conditions, and was dependent on MMP activity. Furthermore, expression of angiogenic stimuli, such as vascular endothelial growth factor (VEGF), and VEGF/placental growth factor heterodimer, was also increased. Crucially, we show for the first time that hypoxia increased the angiogenic drive of RA cells, as demonstrated by enhanced blood vessel formation in an in vitro angiogenesis assay. CONCLUSIONS: Hypoxia may be responsible for rendering RA synovial lining proangiogenic and proinvasive, thus leading to the debilitating features characteristic of RA

The interplay between Angiogenesis, Hypoxia and inflammation in rheumatoid hand disease

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory condition affecting 1- 3% of the world population. Half of all patients with RA have tendon involvement. This often leads to multiple tendon ruptures. Tendon rupture is a strong indicator of poor, longterm, hand function. When tendons rupture, painful reconstructive surgery is currently the only way of restoring useful hand function. Patients with RA also develop characteristic deformities which often interfere with hand function. These include swan-neck, boutonniere and ulnar drift deformities. In particular, the development of ulnar drift in RA hands has always been very difficult to explain and is equally difficult to correct surgically. Local hypoxia and angiogenesis are recognised as key events which may initiate and perpetuate joint destruction in RA. More recently, they have also been shown to be important in tendon rupture. Previous studies carried out by our group used a microelectrode technique to demonstrate that invasive tenosynovium in RA patients is markedly hypoxic compared to tenosynovium in patients without RA. The results of these studies led us to conclude that hypoxia plays a key role in initiating and perpetuating tendon destruction in the same way that hypoxia affects RA joints. Therefore, my research set out to investigate the role of tissue hypoxia in tendon rupture in more detail. To further investigate the effects of hypoxia in RA, synovial tissue was harvested and cultured under either hypoxic (1% O2) or normoxic (21% O2) conditions. Under hypoxic conditions, I observed a significant upregulation of the matrix metalloproteinases (MMP) responsible for collagen breakdown. This upregulation was inhibited in the presence of a universal blocker for MMP. The expression of angiogenic stimuli such as vascular endothelial growth factor was also increased and crucially, my data showed that hypoxia increases the angiogenic drive of RA cells, as demonstrated by enhanced blood vessel formation in an in-vitro angiogenesis functional assay. In this way, I was able to show that hypoxia creates a stimulus for RA tenosynovium which is proangiogenic and proinvasive facilitating the tendon ruptures observed in RA. This has not previously been demonstrated. Intrinsic muscle dysfunction has been suggested as one of the mechanisms for the development of ulnar drift in RA hands. To investigate the possible link between hypoxia and ulnar drift, I speculated that the weakness and dysfunction of the intrinsic muscles observed in RA hands may also be due to hypoxia. Direct measurement of tissue oxygen in the intrinsic muscles of the RA hand has never been performed. Using our microelectrode technique, I found that the intrinsic muscles of RA patients undergoing elective surgery (n=30) are significantly more hypoxic than the intrinsic muscles of patients without RA (n=30). Within the RA group, I also observed a spatial trend for increasing hypoxia in the intrinsic muscles going from radial to ulnar. There was a further trend for increasing hypoxia moving from proximal to distal in the upper limb. My data confirmed that the intrinsic muscles are the most hypoxic. Therefore, it seems possible that hypoxia may at the very least contribute to the intrinsic muscle contracture and atrophy which are commonly observed in the RA hand. In so doing, intrinsic muscle hypoxia may contribute to the development of ulnar drift and the other deformities in the hand of RA patients. These findings have also never been demonstrated before. Many of the drugs currently used to treat RA (including anti-TNFα drugs) fail to prevent inflammation of the tenosynovium in the hand in a significant proportion of patients. We are also unaware of any treatments to block, reverse or ameliorate the effects of chronic muscle hypoxia. These findings may explain why many of the disabling effects of RA often continue despite otherwise adequate control of pain and other symptoms, especially in the hand. This study represents a further step forward on the path to understanding the debilitating effects of RA in the hand and may lead to the development of new treatments to prevent them

The interplay between angiogenesis, hypoxia and inflammation in rheumatoid hand disease

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory condition affecting 1- 3% of the world population. Half of all patients with RA have tendon involvement. This often leads to multiple tendon ruptures. Tendon rupture is a strong indicator of poor, longterm, hand function. When tendons rupture, painful reconstructive surgery is currently the only way of restoring useful hand function. Patients with RA also develop characteristic deformities which often interfere with hand function. These include swan-neck, boutonniere and ulnar drift deformities. In particular, the development of ulnar drift in RA hands has always been very difficult to explain and is equally difficult to correct surgically. Local hypoxia and angiogenesis are recognised as key events which may initiate and perpetuate joint destruction in RA. More recently, they have also been shown to be important in tendon rupture. Previous studies carried out by our group used a microelectrode technique to demonstrate that invasive tenosynovium in RA patients is markedly hypoxic compared to tenosynovium in patients without RA. The results of these studies led us to conclude that hypoxia plays a key role in initiating and perpetuating tendon destruction in the same way that hypoxia affects RA joints. Therefore, my research set out to investigate the role of tissue hypoxia in tendon rupture in more detail. To further investigate the effects of hypoxia in RA, synovial tissue was harvested and cultured under either hypoxic (1% O2) or normoxic (21% O2) conditions. Under hypoxic conditions, I observed a significant upregulation of the matrix metalloproteinases (MMP) responsible for collagen breakdown. This upregulation was inhibited in the presence of a universal blocker for MMP. The expression of angiogenic stimuli such as vascular endothelial growth factor was also increased and crucially, my data showed that hypoxia increases the angiogenic drive of RA cells, as demonstrated by enhanced blood vessel formation in an in-vitro angiogenesis functional assay. In this way, I was able to show that hypoxia creates a stimulus for RA tenosynovium which is proangiogenic and proinvasive facilitating the tendon ruptures observed in RA. This has not previously been demonstrated. Intrinsic muscle dysfunction has been suggested as one of the mechanisms for the development of ulnar drift in RA hands. To investigate the possible link between hypoxia and ulnar drift, I speculated that the weakness and dysfunction of the intrinsic muscles observed in RA hands may also be due to hypoxia. Direct measurement of tissue oxygen in the intrinsic muscles of the RA hand has never been performed. Using our microelectrode technique, I found that the intrinsic muscles of RA patients undergoing elective surgery (n=30) are significantly more hypoxic than the intrinsic muscles of patients without RA (n=30). Within the RA group, I also observed a spatial trend for increasing hypoxia in the intrinsic muscles going from radial to ulnar. There was a further trend for increasing hypoxia moving from proximal to distal in the upper limb. My data confirmed that the intrinsic muscles are the most hypoxic. Therefore, it seems possible that hypoxia may at the very least contribute to the intrinsic muscle contracture and atrophy which are commonly observed in the RA hand. In so doing, intrinsic muscle hypoxia may contribute to the development of ulnar drift and the other deformities in the hand of RA patients. These findings have also never been demonstrated before. Many of the drugs currently used to treat RA (including anti-TNFα drugs) fail to prevent inflammation of the tenosynovium in the hand in a significant proportion of patients. We are also unaware of any treatments to block, reverse or ameliorate the effects of chronic muscle hypoxia. These findings may explain why many of the disabling effects of RA often continue despite otherwise adequate control of pain and other symptoms, especially in the hand. This study represents a further step forward on the path to understanding the debilitating effects of RA in the hand and may lead to the development of new treatments to prevent them.EThOS - Electronic Theses Online ServiceRAFT, Royal College of Surgeons, Dunhill Medical TrustGBUnited Kingdo

Muscle hypoxia in rheumatoid hands: does it play a role in ulnar drift?

PURPOSE: The cause of ulnar drift in patients with rheumatoid arthritis (RA) is unknown. It may occur because of external forces applied to the fingers during normal use. Alternatively, it may arise after changes in the internal forces on the anatomy of the digits owing to alterations in the supporting structures of the joints or their control mechanisms, or both. Intrinsic muscle tightness, which is commonly seen in RA hands, may be the result of adaptive shortening or a direct consequence of RA. Previous studies carried out by our group have shown that joints, tendons, and associated synovium in RA hands are consistently hypoxic. Therefore, we formed the hypothesis that there is a difference in hand/forearm muscle oxygen tension in RA versus non-RA. METHODS: We measured tissue oxygen levels in the intrinsic muscles of the hands and forearm muscles of 29 patients with a diagnosis of RA, who were undergoing elective surgery. We measured oxygen levels using a microelectrode technique. A total of 31 patients without RA undergoing elective surgery served as matched controls. RESULTS: Our results show that the intrinsic muscles of RA patients are significantly more hypoxic than in non-RA controls. Moreover, there is a trend in the RA group for increasing hypoxia in a radial-to-ulnar direction when comparing the different intrinsic muscle groups. We also demonstrate that forearm and thenar and hypothenar muscles are significantly more hypoxic in RA versus non-RA patients. CONCLUSIONS: The intrinsic muscle weakness, intrinsic tightness, and muscle wasting observed in RA may not be due to disuse atrophy resulting from joint disease. From our data, we speculate that these changes may be the result of direct muscular involvement in RA leading to muscle hypoxia

Gene expression studies to investigate disease mechanisms in rheumatoid arthritis: Does angiogenesis play a role?

Gene expression studies represent a new and challenging approach that allows molecular dissection of complex diseases such as rheumatoid arthritis (RA). Optimally, gene analysis should be conducted in isolated populations of cells so that the differential gene expression may be directly correlated with transcription of genes. RA fibroblasts constitute the majority of the expanding synovial cell mass in the RA joint, and alterations in their phenotype are likely to be important in the pathogenic process. However, RA involves many cell types from tissues adjacent to the synovium and the important cell types are not known. Analysis of gene expression profiles by processing a complex tissue such as whole paws can provide useful information about dysregulated genes, not only in the synoviocytes but also in other, neighbouring cells (monocytes, osteocytes and chondrocytes) that may contribute to disease pathology. This review will focus on the use of gene expression studies, both in isolated cells and in whole tissue, as a means of studying the molecular mechanisms involved particularly in the angiogenic process in RA. In particular, we will focus on synovial angiogenesis, since the synovial vascular density is altered in RA. This will provide an increased surface area for inflammatory cell trafficking, as well as delivering nutrients and oxygen to the proliferating synovial cells. Therapeutic approaches targeting angiogenic factors such as vascular endothelial growth factor (VEGF), which is increased in RA, have already shown some clinical success in oncology, and in mouse models of arthritis. © 2007 Bentham Science Publishers Ltd

Angiogenesis and plastic surgery.

SUMMARY: Angiogenesis, the formation of new blood vessels from an existing vascular bed, is a normal physiological process which also underpins many--apparently unrelated--pathological states. It is an integral factor in determining the success or failure of many procedures in plastic and reconstructive surgery. As a result, the ability to control the process would be of great therapeutic benefit. To appreciate the potential benefits and limitations of recent advances in our understanding of angiogenesis, it is important to comprehend the basic physiology of blood vessel formation. This review aims to summarise current knowledge of the way in which angiogenesis is controlled and to look at how disordered vessel development results in pathology relevant to plastic surgery. Through this we hope to provide a comprehensive overview of the recent advances in angiogenesis as they relate to plastic surgery, particularly the promotion of flap survival, tendon healing, nerve regeneration, fracture healing and ulcer treatments