Systematic review of inframalleolar endovascular interventions and rates of limb salvage, wound healing, restenosis, rest pain, reintervention and complications.

OBJECTIVES: Peripheral artery disease is estimated to affect 237 million individuals worldwide. Critical limb ischaemia, also known as chronic limb threatening ischaemia is a consequence of the progression of peripheral artery disease which occurs in ∼21% of patients over a five-year period. The aim of this systematic review is to assess the use of additional below-the-ankle angioplasty in comparison to the use of above-the-ankle angioplasty alone, and the subsequent rates of amputation, wound healing, restenosis, rest pain, reintervention and complications. METHODS: This systematic review was undertaken in accordance with PRISMA guidelines following a registered protocol (CRD42019154893). Online databases were searched using a search strategy of 20 keywords. Included articles reported the outcome for inframalleolar (pedal artery, pedal arch, plantar arteries) angioplasty with additional proximal angioplasty in comparison to proximal angioplasty alone. GRADE assessment was applied to assess the quality of the evidence. RESULTS: After screening 1089 articles, 10 articles met the inclusion criteria. Comparative performance assessment of below-the-ankle with above-the-ankle versus above-the-ankle angioplasty alone was undertaken in 3 articles, with the remaining 7 articles reporting outcomes of below-the-ankle with above-the-ankle angioplasty with no distinct comparator group. Significant decrease in major lower limb amputation at the last follow-up in the below-the-ankle group when compared with the above-the-ankle angioplasty alone group was observed in a single study (3.45% vs. 14.9%, p < 0.05). Improved wound healing rate at follow-up in the below-the-ankle group versus above-the-ankle angioplasty alone group was also reported in a single study (59.3% vs. 38.1%, p < 0.05). Subsequent rate of amputation after below-the-ankle angioplasty has been estimated as 23.5%. CONCLUSION: To date, there is a lack of studies assessing inframalleolar interventions and their use in improving limb salvage, wound healing and symptomatology. Prospective RCTs should be undertaken with adequate participant numbers to be sufficiently powered and report clinically important end-points.

Systematic review on the management of ileoanal pouch-vaginal fistulas after restorative proctocolectomy in the treatment of ulcerative colitis.

AIM: Ileoanal pouch-vaginal fistula (PVF) is a relatively common complication of restorative proctocolectomy with ileal pouch-anal anastomosis. There are several operative approaches in the management of PVF. There is currently no consensus as to which approach is the most effective or which should be attempted first. METHOD: A systematic review was undertaken following a publicly available protocol registered with PROSPERO (CRD42019133750) in accordance with PRISMA guidelines. Online searches of databases MEDLINE and Embase, Cochrane Library, ClinicalTrials.gov, EU Clinical Trials and ISRCTN registry were performed. RESULTS: Twenty-seven articles met the criteria for inclusion in the study: 13 retrospective cohort studies, two prospective cohort studies, eight case series, three case reports and a case-control study. A narrative synthesis was performed due to heterogeneity between included articles. Our study included 577 PVFs, and the incidence rate was 2.1%-17.1%. Both local and abdominal approaches were used in the management of PVF. The overall success of local and abdominal procedures was 44.9% and 60.2% respectively. ROBINS-I assessment revealed a critical risk of bias. GRADE assessment indicated a very low certainty in effect size and evidence quality. CONCLUSION: Local interventions and abdominal approaches have a high failure rate. The results of this review will aid the counselling of patients with this condition. Furthermore, we provide an algorithm for discussion on the management of PVF based on experience at our local centre. The studies available on the management of PVF are low quality; a large prospective registry and Delphi consensus are required to further this area of research.

Distinctive clinical and histological characteristics of atrophic and hypertrophic facial photoageing.

BACKGROUND: Photoageing describes complex cutaneous changes which occur following chronic exposure to solar ultraviolet radiation (UVR). Amongst White Northern Europeans, facial photoageing appears as distinct clinical phenotypes: 'hypertrophic' photoageing (HP) and 'atrophic' photoageing (AP). Deep, coarse wrinkles predominate in individuals with HP, whereas those with AP have relatively smooth, unwrinkled skin with pronounced telangiectasia. AP individuals have an increased propensity for developing keratinocyte cancers. OBJECTIVES: To investigate whether histological differences underlie these distinct phenotypes of facial photoageing. METHODS: Facial skin biopsies were obtained from participants with AP (10 M, 10 F; mean age: 78.7 years) or HP (10 M, 10 F; mean age: 74.5 years) and were assessed histologically and by immunohistochemistry. RESULTS: Demographic characterization revealed 95% of AP subjects, as compared to 35% with HP, were Fitzpatrick skin type I/II; of these, 50% had a history of one or more keratinocyte cancers. There was no history of keratinocyte cancers in the HP cohort. Analysis of UVR-induced mitochondrial DNA damage confirmed that all volunteers had received similar lifetime cumulative doses of sun exposure. Histologically, male AP had a significantly thicker epidermis than did AP females or those of either sex with HP. HP facial skin exhibited severe solar elastosis, whereas in AP facial skin, solar elastosis was apparent only in females. Loss of papillary dermal fibrillin-rich microfibrils occurred in all HP and AP female subjects, but not in AP males. Furthermore, male AP had a significant reduction in collagen VII at the dermal-epidermal junction than did AP females or those of either sex with HP. CONCLUSIONS: This study provides further evidence that AP and HP represent distinct clinical and histological entities. Knowledge of these two phenotypes is clinically relevant due to the increased prevalence of keratinocyte cancers in those - particularly males - with the AP phenotype.

A systematic review of the management of synthetic mesh erosion of the rectum following urogynaecological surgery.

AIM: Synthetic rectal mesh erosion is a challenging complication following urogynaecological surgery. The aim of this study was to determine the optimal management of rectal mesh erosion following urogynaecological surgery. METHOD: A systematic review was undertaken following a pre-defined protocol registered with PROSPERO (CRD42018112425) in accordance with PRISMA guidelines. Searches of MEDLINE online database, Cochrane Library and clinical trial registries (ClinicalTrials.gov, EU Clinical Trials, ISRCTN registry) were performed. The included articles were heterogeneous - therefore a narrative synthesis was performed. RESULTS: Fourteen studies were included in the review: 11 case reports, one case series, one retrospective cohort and one prospective multicentre trial. Fourteen rectal mesh erosions were identified. Eight (57%) of the rectal erosions underwent major abdominal surgery. In two of these cases, the abdominal approach was used only after failure of the transanal route. Five (36%) of the mesh erosions were managed using a transanal approach. In one case, the mesh passed without intervention. CONCLUSION: Synthetic rectal mesh erosion can be managed successfully via either a transanal or a transabdominal approach with a partial or complete excision of the mesh. An examination under anaesthetic with an attempted transanal removal of mesh should be considered the first step in the management of this condition before consideration of more invasive surgery.

The marriage of psychology and law: testamentary capacity.

Banks v. Goodfellow [1870. LR 5 QB 549 (Eng.)] is almost 150 years old, yet still stands as authority for the principle that unsoundness of the mind will not rebut testamentary capacity where it does not affect the will itself. Readers of this journal would know that psychology has advanced greatly during this sesquicentenary, and yet the law relating to testamentary capacity has remained relatively stagnant. We review the present laws relating to decision-making for adults with impaired capacity, particularly in Queensland, and also review various models of gauging decision-making capacity in other jurisdictions. We argue that qualified experts should be enlisted to make determinations about testamentary capacity when questions of capacity arise. We also argue the case for the development of scientifically validated protocols to assess decision-making capacity in the testamentary context.

In vitro protective effects of an aqueous extract of Clitoria ternatea L. flower against hydrogen peroxide-induced cytotoxicity and UV-induced mtDNA damage in human keratinocytes.

The traditional practice of eating the flowers of Clitoria ternatea L. or drinking their infusion as herbal tea in some of the Asian countries is believed to promote a younger skin complexion and defend against skin aging. This study was conducted to investigate the protective effect of C. ternatea flower water extract (CTW) against hydrogen peroxide-induced cytotoxicity and ultraviolet (UV)-induced mitochondrial DNA (mtDNA) damage in human keratinocytes. The protective effect against hydrogen peroxide-induced cytotoxicity was determined by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, and mtDNA damage induced by UV was determined by polymerase chain reaction. Preincubation of HaCaT with 100, 250, and 500 µg/ml CTW reduced cytotoxicity effects of H2 O2 compared with control (H2 O2 alone). CTW also significantly reduced mtDNA damage in UV-exposed HaCaT (p < .05). CTW was chemically-characterized using high resolution liquid chromatography-mass spectrometry. The main compounds detected were assigned as anthocyanins derived from delphinidin, including polyacylated ternatins, and flavonol glycosides derived from quercetin and kaempferol. These results demonstrated the protective effects of C. ternatea flower extracts that contain polyacylated anthocyanins and flavonol glycosides as major constituents, against H2 O2 and UV-induced oxidative stress on skin cells, and may provide some explanation for the putative traditional and cosmetic uses of C. ternatea flower against skin aging.

Oxidative stress and ageing.

Oxidative stress is the resultant damage due to redox imbalances (increase in destructive free radicals [reactive oxygen species (ROS)] and reduction in antioxidant protection/pathways) and is linked to ageing in many tissues including skin. In ageing skin there are bioenergetic differences between keratinocytes and fibroblasts which provide a potential ageing biomarker. The differences in skin bioenergy are part of the mitochondrial theory of ageing which remains one of the most widely accepted ageing theories describing subsequent increasing free radical generation. Mitochondria are the major source of cellular oxidative stress and form part of the vicious cycle theory of ageing. External and internal sources of oxidative stress include UVR/IR, pollution (environment), lifestyle (exercise and diet), alcohol and smoking all of which may potentially impact on skin although many exogenous actives and endogenous antioxidant defence systems have been described to help abrogate the increased stress. This also links to differences in skin cell types in terms of the UVR action spectrum for nuclear and mitochondrial DNA damage (the latter a previously described UVR biomarker in skin). Recent work associates bioenergy production and oxidative stress with pigment production thereby providing another additional potential avenue for targeted anti-ageing intervention in skin. This new data supporting the detrimental effects of the numerous wavelengths of UVR may aid in the development of cosmetic/sunscreen design to reduce the effects of photoageing. Recently, complex II of the mitochondrial electron transport chain appears to be more important than previously thought in the generation of free radicals (suggested predominantly by non-human studies). We investigated the relationship between complex II and ageing using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering a wide age range. Complex II activity significantly decreased with age in fibroblasts (P = 0·015), but not in keratinocytes. This was associated with a significant decline in transcript expression (P = 0·008 and P = 0·001) and protein levels (P = 0·0006 and P = 0·005) of the SDHA and SDHB catalytic subunits of complex II respectively. In addition there was a significant decrease in complex II activity with age (P = 0·029) that was specific to senescent skin cells, our study being the first to investigate these differences with senescence and skin age. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II. Our study provides a future potential biomarker for monitoring the progression of skin ageing.

Oxidative stress--a key emerging impact factor in health, ageing, lifestyle and aesthetics.

Oxidative stress is the resultant damage that arises due to redox imbalances, more specifically an increase in destructive free radicals and reduction in protection from antioxidants and the antioxidant defence pathways. Oxidation of lipids by reactive oxygen species (ROS) can damage cellular structures and result in premature cell death. At low levels, ROS-induced oxidative stress can be prevented through the action of antioxidants, however, when ROS are present in excess, inflammation and cytotoxicity eventually results leading to cellular oxidative stress damage. Increasing evidence for the role of oxidative stress in various diseases including neurological, dermatological, and cardiovascular diseases is now emerging. Mitochondria are the principal source (90%) of ROS in the cell, with superoxide radicals being generated when molecular oxygen is combined with free electrons. Given the key role of mitochondria in the generation of cellular oxidative stress it is worth considering this organelle and the process in more detail and to provide methods of intervention.

Mitochondrial DNA damage as a biomarker for ultraviolet radiation exposure and oxidative stress.

The skin is regularly exposed to the harmful effects of sunlight, such as ultraviolet radiation (UVR), which leads to ageing effects as well as clinical precancerous lesions and skin cancer. The accumulation of mitochondrial DNA (mtDNA) damage has been strongly associated as an underlying cause of the general ageing process in tissues and mtDNA damage has been associated with cancer development in many tissues including human skin. This scenario is linked to the key roles of mitochondrial function and mtDNA both in terms of energy production and also oxidative stress production as well as a mediator of apoptosis. We and others have pioneered the use of mtDNA damage as a highly sensitive biomarker of UVR exposure and oxidative stress in human skin; furthermore, ageing-dependent mtDNA mutations can be accelerated by exposure to sunlight. In addition, this review will also highlight useful applications of mtDNA as a biomarker of UVR-induced oxidative stress including effects of antioxidants.

Increasing the therapeutic efficacy of docetaxel for cutaneous squamous cell carcinoma through the combined inhibition of phosphatidylinositol 3-kinase/AKT signalling and autophagy.

Early-stage cutaneous squamous cell carcinoma (cSCC) has a favourable prognosis. Metastatic disease is probably associated with chemoresistance mediated through the activation of pro-survival phosphatidylinositol 3-kinase/AKT signalling. Inhibition of activated AKT partially increases chemosensitivity but induces autophagy, the principal lysosomal mechanism for the bulk degradation and recycling of proteins and damaged organelles. The aim of the current study was to test the hypothesis that combined inhibition of AKT signalling and autophagy by the lysosomal inhibitor chloroquine increases the susceptibility to docetaxel-induced apoptosis of cSCC cells isolated from a lymph-node metastasis. Combined AKT inhibition and chloroquine treatment of MET 4 cSCC cells resulted in significantly enhanced inhibition of cell viability and apoptosis induced by clinically achievable concentrations of docetaxel (P < 0.001). Inhibition of both autophagy and AKT thus represents an effective and viable therapeutic strategy to increase the cytotoxicity of docetaxel for the treatment of advanced cSCC.

Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency.

We now report a mutation in the nuclear-encoded flavoprotein (Fp) subunit gene of the succinate dehydrogenase (SDH) in two siblings with complex II deficiency presenting as Leigh syndrome. Both patients were homozygous for an Arg554Trp substitution in the Fp subunit. Their parents (first cousins) were heterozygous for the mutation that occurred in a conserved domain of the protein and was absent from 120 controls. The deleterious effect of the Arg to Trp substitution on the catalytic activity of SDH was observed in a SDH- yeast strain transformed with mutant Fp cDNA. The Fp subunit gene is duplicated in the human genome (3q29; 5p15), with only the gene on chromosome 5 expressed in human-hamster somatic cell hybrids. This is the first report of a nuclear gene mutation causing a mitochondrial respiratory chain deficiency in humans.

Students managing work and study role boundaries: a person-centred approach.

To cope with demands of working while studying, students must structure the boundaries between these roles (e.g., integrate or segment them) to suit their preferences and circumstances. However, students differ on how well they do this, and we do not yet understand the factors that contribute to managing work and study well. We sought to determine if different student groups existed and if the groups reported different work, study, and wellbeing outcomes. Using latent profile analysis and assessing work-study boundary congruence and flexibility (N = 808; 76% female; MAge 19.6 years), we identified four groups of (a) "balanced" (65.4%; with moderate boundary congruence and flexibility); (b) "high work congruence and flexibility" (17.5%; working arrangements supportive of study role); (c) "low work congruence and flexibility" (9.7%; unsupportive workplace arrangements); and (d) "low study congruence" (7.3%; study arrangements unsupportive of work role). These groups reported different work/study demands, role conflict, study burnout, and perceived employability, with "balanced" and "high work congruence and flexibility" groups scoring more positively and "low work congruence and flexibility" and "low study congruence" groups scoring more negatively. Results supported that different student groups existed, and these will need different supports to manage their multiple role responsibilities.

A Systematic Review of Multilevel Influenced Risk-Taking in Helicopter and Small Airplane Normal Operations.

The violation of aviation rules, particularly meteorological flight rules, can have fatal outcomes. Violation can sometimes be explained by intentional risk-taking, alternatively it can be the manifestation of a strategy to enhance performance and influence outcomes, such as saving time or fulfilling customer expectations. The aim of this study was to determine the types of risk-taking behavior within extant empirical research and identify multilevel antecedents related to risk-taking in the context of aviation operations, via a systematic literature review. 4,742 records were identified, which after screening resulted in the detailed consideration of 10 studies, three qualitative and seven quantitative studies, which met the eligibility criteria. Only published works were included in the review, thus the results may have been subject to publication bias, however, the types of risk taking within the research were consistent with that observed in Australian and New Zealand accident reports. The predominate risk-taking behavior was that of continuing Visual Flight Rules (VFR) flight into deteriorating conditions / Instrument Meteorological Conditions (IMC). Multilevel influences could be categorized under two overarching themes, being "continuation influence" and "acceptance of risk / normalization of deviance." One or both themes was consistently observed across the finding in all studies, although precaution should be given to the relative frequency of the reported associations. This review indicates the value of considering the social and organizational influences on risk-taking, and suggests avenues for future research, in particular exploring the influences through a Self-Determination Theory (SDT) lens.

Mitochondrial DNA mutations in head and neck cancer are infrequent and lack prognostic utility.

BACKGROUND: Mitochondrial DNA (mtDNA) mutations occur in head and neck squamous cell carcinoma (HNSCC) and are most frequently detected in the displacement-loop (D-loop) region. The D-loop is considered to be important because it controls mitochondrial gene expression and mtDNA replication. There is currently no evidence that mtDNA mutations can be used as prognostic or predictive biomarkers in HNSCC. METHODS: We used denaturing high performance liquid chromatography to screen the entire mitochondrial genome of six oral squamous cell carcinoma-derived cell lines and then focused on detecting D-loop abnormalities in 34 HNSCC tissue samples. RESULTS: Mitochondrial DNA mutations are not ubiquitous in HNSCC because only half of the cell lines had detectable mtDNA abnormalities following screening of the entire mitochondrial genome and only 18% (6 of 34) of tissue samples had D-loop mutations. There was no correlation between D-loop mutations and determinates of clinical outcome; specifically, tumour stage and the expression of hypoxia-inducible genes included in a highly prognostic hypoxia metagene. CONCLUSIONS: Taken together, these data suggest that mtDNA D-loop mutations are stochastic events that may not significantly influence the biology of HNSCC and supports the hypothesis that mtDNA mutations in cancer represent bystander genotoxic damage as a consequence of tumour development and progression.

Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: a randomized controlled trial.

BACKGROUND: Previous epidemiological, animal and human data report that lycopene has a protective effect against ultraviolet radiation (UVR)-induced erythema. OBJECTIVES: We examined whether tomato paste--rich in lycopene, a powerful antioxidant--can protect human skin against UVR-induced effects partially mediated by oxidative stress, i.e. erythema, matrix changes and mitochondrial DNA (mtDNA) damage. METHODS: In a randomized controlled study, 20 healthy women (median age 33 years, range 21-47; phototype I/II) ingested 55 g tomato paste (16 mg lycopene) in olive oil, or olive oil alone, daily for 12 weeks. Pre- and postsupplementation, UVR erythemal sensitivity was assessed visually as the minimal erythema dose (MED) and quantified with a reflectance instrument. Biopsies were taken from unexposed and UVR-exposed (3 × MED 24 h earlier) buttock skin pre- and postsupplementation, and analysed immunohistochemically for procollagen (pC) I, fibrillin-1 and matrix metalloproteinase (MMP)-1, and by quantitative polymerase chain reaction for mtDNA 3895-bp deletion. RESULTS: Mean ± SD erythemal D(30) was significantly higher following tomato paste vs. control (baseline, 26·5 ± 7·5 mJ cm(-2); control, 23 ± 6·6 mJ cm(-2); tomato paste, 36·6 ± 14·7 mJ cm(-2); P = 0·03), while the MED was not significantly different between groups (baseline, 35·1 ± 9·9 mJ cm(-2); control, 32·6 ± 9·6 mJ cm(-2); tomato paste, 42·2 ± 11·3 mJ cm(-2)). Presupplementation, UVR induced an increase in MMP-1 (P = 0·01) and a reduction in fibrillin-1 (P = 0·03). Postsupplementation, UVR-induced MMP-1 was reduced in the tomato paste vs. control group (P = 0·04), while the UVR-induced reduction in fibrillin-1 was similarly abrogated in both groups, and an increase in pCI deposition was seen following tomato paste (P = 0·05). mtDNA 3895-bp deletion following 3 × MED UVR was significantly reduced postsupplementation with tomato paste (P = 0·01). CONCLUSIONS: Tomato paste containing lycopene provides protection against acute and potentially longer-term aspects of photodamage.

A quality assurance programme for cell salvage in cardiac surgery.

At the same time as cell salvage was introduced into our institution for all patients undergoing cardiac surgery with cardiopulmonary bypass, we established a supporting programme of quality assurance to reassure clinicians regarding safety and efficacy. Data collected in patients operated on between 2001 and 2007 included pre- and post-wash heparin concentration, haemoglobin concentration and free haemoglobin concentration. Cell salvage was used in 6826 out of a total of 7243 patients (94%). Post-wash heparin concentration was consistently low (always < 0.4 IU.ml(-1)). There was a significant decrease in post-wash haemoglobin concentration in 2003 compared to 2001, from a median (IQR [range]) of 19.6 (16.7-22.2 [12.9-25.5]) g.dl(-1) to 17.5 (13.6-20.8 [12.6-23.7]) g.dl(-1) (p < 0.015). In addition, there was a significant increase in free plasma haemoglobin in 2006 compared to 2001, from 0.5 (0.3-0.8 [0.1-2.6]) g.l(-1) to 0.8 (0.3-1.4 [0.3-5.2]) g.l(-1) (p < 0.001). This programme led to the detection of a change in operator behaviour in 2003 and progressive machine deterioration resulting in appropriate fleet replacement in 2006. You can respond to this article at http://www.anaesthesiacorrespondence.com.

Systematic review on the benefit of graduated compression stockings in the prevention of venous thromboembolism in low-risk surgical patients.

OBJECTIVES: The aim of this systematic review is to assess the performance of graduated compression stockings (GCS) in comparison to no venous thromboembolism (VTE) prophylaxis in the prevention of hospital-acquired thrombosis in low-risk surgical patients undergoing short-stay procedures. METHODS: Aligning with PRISMA guidelines, online databases MEDLINE and EMBASE, Cochrane Library® and trial registries were searched. Eligible articles reported the VTE rate in low-risk surgical patients either receiving GCS or no VTE prophylaxis. RESULTS: Narrative synthesis was performed on a single eligible article. The included study arm consisted of participants undergoing knee arthroscopy with the use of GCS alone reporting a total of 29 VTE events (4.4%), 16 of which were asymptomatic DVTs (2.4%). CONCLUSION: There is a complete lack of evidence to support the use of GCS in the prevention of HAT for low-risk surgical patients. An adequately powered trial is required to provide level-IA evidence to support this practice.

Are venous thromboembolism risk assessment tools reliable in the stratification of microvascular risk following lower extremity reconstruction?

INTRODUCTION: The incidence of flap failure is significantly higher in the lower extremity compared to free tissue transfer in the head, neck and breast. The most common cause of flap failure is venous thrombosis. The aim of this study was to assess the reliability of venous thromboembolism (VTE) risk assessment tools in this high-risk cohort and to assess the ability of such tools to identify patients at risk of developing microvascular venous thrombosis and venous thromboembolism following lower extremity free flap reconstruction. METHODS: A single centre retrospective cohort study was conducted between August 2012-August 2019. Adult patients who had undergone free tissue transfer following open lower extremity fractures were eligible for inclusion. All patients were retrospectively risk assessed using the Department of Health (DoH), Modified Caprini and Padua VTE risk assessment tools. RESULTS: Fifty-eight patients were included; all were at high risk of DVT according to the DoH (mean score ± SD, 3.7 ± 0.93), Caprini (10.2 ± 1.64) and Padua (5.4 ± 0.86) risk assessment tools. All patients received appropriate thromboprophylaxis; the incidence of symptomatic hospital acquired VTE was 3.5%. Micro-anastomotic venous thrombosis occurred in 4 patients resulting in one amputation. Partial flap necrosis occurred in 7 patients. There were no significant differences in scaled Caprini (median score, 10 vs 9, z = 1.289, p = 0.09), DoH (3 vs 3, z = 0.344, p = 0.36), and Padua (5 vs 5.5, z= -0.944, p = 0.17) scores between those with and without microvascular venous thrombosis. CONCLUSION: This data suggests that current VTE risk assessment tools do not predict risk of microvascular venous thrombosis following lower extremity reconstruction. Further prospective studies are required to optimise risk prediction models and thromboprophylaxis use in this cohort.

Surgical and non-surgical approaches in the management of lower limb post-thrombotic syndrome.

Introduction: Post-thrombotic syndrome (PTS) is a common lifelong condition affecting up to 50% of those suffering from deep vein thrombosis (DVT). PTS compromises function and quality of life with subsequent venous ulceration in up to 29% of those affected.Areas covered: A literature review of surgical and non-surgical approaches in the prevention and treatment of PTS was undertaken. Notable areas include the use of percutaneous endovenous interventions and the use of graduated compression stockings (GCS) after acute proximal DVT.Expert opinion: In patients with acute iliofemoral DVT, we think it is important to have a frank conversation with the patient about catheter-directed thrombolysis, aiming to reduce the severity of PTS experienced. We advocate ultrasound-accelerated thrombolysis with adjunctive procedures, such as deep venous stenting for proximal iliofemoral DVT. For patients with isolated femoral DVT, we believe that anticoagulation and GCS should be recommended. In patients with established PTS, we recommend GCS for symptomatic relief. We recommend that patients engage in regular exercise where possible with the prospect of gaining symptomatic relief. For those with severe PTS that has a significant effect on quality of life, we discuss the patient's case at a multi-disciplinary team meeting to plan for endovenous intervention.

Real-time polymerase chain reaction analysis of a 3895-bp mitochondrial DNA deletion in epithelial swabs and its use as a quantitative marker for sunlight exposure in human skin.

BACKGROUND: The use of mitochondrial DNA (mtDNA) damage as a reliable and highly sensitive biomarker of ultraviolet (UV) radiation exposure in both the dermis and epidermis has now been well developed by our group and others. We have previously identified a 3895-bp mtDNA deletion which occurred more frequently and to a higher level in usually sun-exposed skin as opposed to occasionally sun-exposed skin. This work focused on older-aged individuals and, in particular, perilesional, histologically normal skin biopsies taken from patients with skin cancer. OBJECTIVES: To develop novel, less-invasive methods of obtaining skin samples (i.e. epidermis) from volunteers covering a much wider age range and larger number of individuals (n = 239). METHODS: The 3895-bp deletion was quantified by a specific real-time polymerase chain reaction assay in normal human epidermis samples taken from three body sites with differing sun exposure. RESULTS: The results show a statistical increase of the level of the 3895-bp deletion with increasing sun exposure in the epidermal swabs of human skin (P < 0·001) and with increasing age of the donor in the needle biopsy samples. CONCLUSIONS: These data suggest that the upper layers of the epidermis are an accessible and reliable site for assessing mtDNA damage caused by UV exposure.