Treatment Strategies for Proximal Deep Vein Thrombosis: A Network Meta-analysis of Randomised Controlled Trials.

OBJECTIVE: To investigate the outcomes of treatment strategies for proximal and iliofemoral deep vein thrombosis (DVT). METHODS: Randomised controlled trials (RCTs) investigating outcomes of catheter directed thrombolysis (CDT), ultrasound assisted CDT (USCDT), percutaneous aspiration thrombectomy (PAT), and best medical therapy (BMT) for proximal DVT from 2000 onwards were considered. MEDLINE, EMBASE, and CINAHL were searched using the Healthcare Databases Advanced Search interface developed by the National Institute for Health and Care Excellence. The primary outcome was the rate of post-thrombotic syndrome (PTS), which was defined using the Villalta scoring system (score of ≥5). Secondary outcomes included vessel patency, recurrence, bleeding, and mortality. The network of evidence was summarised using network plots, and random effects network meta-analyses were performed. The certainty of evidence was assessed using the Certainty In Network Meta-Analysis (CINeMA) approach. RESULTS: Seven RCTs meeting the inclusion criteria were identified. There were direct comparisons between medical therapy, CDT, and USCDT across outcomes, except for patency. There were no direct comparisons between medical therapy and PAT (except for patency), and USCDT and PAT. There was no significant difference observed in PTS between the treatment modalities for proximal and iliofemoral DVT (low certainty). There was a significant difference in patency rates between medical therapy and USCDT (odds ratio [OR] 9.46, 95% confidence interval [CI] 3.05 - 29.35; low certainty) and CDT (OR 2.03, 95% CI 1.46 - 2.80; low certainty) in favour of USCDT and CDT, respectively, for proximal DVT. USCDT significantly improved patency rates compared with CDT (OR 4.67, 95% CI 1.58 - 13.81; very low certainty) for proximal DVT. There was no significant difference in DVT recurrence, bleeding, or mortality between treatment groups for proximal and iliofemoral DVT (low to moderate certainty for most comparisons). CONCLUSION: USCDT may improve patency rates compared with BMT and the other interventional treatment modalities used for the management of proximal DVT. However, no treatment modality showed superiority with regard to a reduction in PTS, and overall, the quality of available evidence is poor.

A microbiome and metabolomic signature of phases of cutaneous healing identified by profiling sequential acute wounds of human skin: An exploratory study.

Profiling skin microbiome and metabolome has been utilised to gain further insight into wound healing processes. The aims of this multi-part temporal study in 11 volunteers were to analytically profile the dynamic wound tissue and headspace metabolome and sequence microbial communities in acute wound healing at days 0, 7, 14, 21 and 28, and to investigate their relationship to wound healing, using non-invasive quantitative devices. Metabolites were obtained using tissue extraction, sorbent and polydimethylsiloxane patches and analysed using GCMS. PCA of wound tissue metabolome clearly separated time points with 10 metabolites of 346 being involved in separation. Analysis of variance-simultaneous component analysis identified a statistical difference between the wound headspace metabolome, sites (P = 0.0024) and time points (P<0.0001), with 10 out of the 129 metabolites measured involved with this separation between sites and time points. A reciprocal relationship between Staphylococcus spp. and Propionibacterium spp. was observed at day 21 (P<0.05) with a statistical correlation between collagen and Propionibacterium (r = 0.417; P = 0.038) and Staphylococcus (r = -0.434; P = 0.03). Procrustes analysis showed a statistically significant similarity between wound headspace and tissue metabolome with non-invasive wound devices. This exploratory study demonstrates the temporal and dynamic nature of acute wound metabolome and microbiome presenting a novel class of biomarkers that correspond to wound healing, with further confirmatory studies now necessary.

Electrical stimulation disrupts biofilms in a human wound model and reveals the potential for monitoring treatment response with volatile biomarkers.

Management of biofilm infections relies on time-consuming laboratory techniques and monitoring treatment by subjective clinical evaluations. Due to these limitations, there is a need to explore alternative strategies. The aims of this study were to assess the feasibility of using volatile organic compound (VOC) biomarkers to monitor treatment response and measure anti-biofilm efficacy of electrical stimulation (ES) in vitro and in human cutaneous wound biofilm models. Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa (PA) biofilms were exposed to ES, ciprofloxacin, or both, with efficacy assessed and quantified by fluorescence staining, enumeration, metabolic assays, and biomass quantification; VOCs were measured by gas chromatography-mass spectrometry. In vitro MSSA and PA and ex vivo PA biofilms exposed to ES showed significantly reduced bacterial viability, metabolic activity, and biomass compared to controls (p < 0.05). There was significant variation in the relative abundance of VOCs in in vitro MSSA and PA and in ex vivo PA biofilms exposed to ES and antibiotic (p < 0.05). 2-methyl-1-propanol was associated with MSSA viability (R = 0.93, p < 0.05), biomass (R = 0.97, p < 0.05), and metabolic activity (R = 0.93, p < 0.05) and 3-methyl-1-butanol was associated with PA biomass (R = 0.93, p < 0.05). We showed that ES and VOC biomarkers are possible options for alternative nonpharmacological antimicrobial management of biofilms and noninvasive monitoring of wound infection treatment responses, respectively.

Validation of biofilm formation on human skin wound models and demonstration of clinically translatable bacteria-specific volatile signatures.

Biofilms are major contributors to delayed wound healing and there is a need for clinically relevant experimental models to assess theranostics. Microorganisms release volatile organic compounds (VOCs) and the ability to identify these in infected cutaneous wounds could lead to efficient non-invasive diagnosis. The aims here were to develop and assess bacterial biofilm formation and identify their VOC profiles in an in vitro model and validate in human ex vivo incisional and excisional cutaneous wound models. Biofilm development was assessed using multiple microscopy techniques with biofilm-forming deficient controls and quantified using metabolic and biomass assays; and VOC production measured by gas chromatography-mass spectrometry. The production of most VOCs was affected by biofilm development and model used. Some VOCs were specific either for planktonic or biofilm growth. The relative abundance of some VOCs was significantly increased or decreased by biofilm growth phase (P < 0.05). Some Staphylococcus aureus and Pseudomonas aeruginosa VOCs correlated with biofilm metabolic activity and biomass (R ≤ -0.5; ≥0.5). We present for the first time bacterial biofilm formation in human ex vivo cutaneous wound models and their specific VOC profiles. These models provide a vehicle for human skin-relevant biofilm studies and VOC detection has potential clinical translatability in efficient non-invasive diagnosis of wound infection.

Volatile organic compound detection as a potential means of diagnosing cutaneous wound infections.

Chronic cutaneous wound infections and surgical site infections (SSIs) present a huge burden on the healthcare system and can lead to increased morbidity and mortality. Current diagnostic methods of identifying and confirming infection involve culture-based and molecular methods. Both techniques are time-consuming and delays commonly lead to untargeted empirical treatment. An ideal diagnostic method would be noninvasive and highly sensitive and detect pathogenic organisms with a high degree of accuracy to allow targeted treatment. Volatile organic compounds (VOCs) are a diverse group of carbon-based molecules produced and released by humans and microorganisms. VOC detection has the potential in aiding cutaneous wound infection diagnostics using noninvasive and time-efficient methods. This review provides a comprehensive update on VOCs produced and emitted by bacteria commonly associated with chronic wounds and SSIs. VOC sampling has the advantage of being painless, time-efficient, noninvasive, and reproducible. VOCs emitted by these organisms are diverse. In vitro studies have identified potential signature volatile profiles, which can be used in detecting these microorganisms. Combining these profiles with volatile profiles emitted from acute, chronic and surgical wounds in vivo could potentially allow identification of bacterial-specific VOCs. VOC detection has the potential for a relatively inexpensive, portable, noninvasive, and reliable clinical diagnostic tool, which could be used in detecting cutaneous wound infections and guiding their optimal management.

Pre-operative predictors of poor outcomes in patients undergoing surgical lower extremity revascularisation - Retrospective cohort study.

BACKGROUND: Surgical lower extremity revascularisation (LER) can lead to poor outcomes that include delayed hospital discharge, in-hospital mortality, major amputations and readmissions. The aim of this study was to identify pre-operative predictors associated with these poor clinical outcomes. MATERIALS AND METHODS: All patients (n = 635; mean age 69; male 67.4%) who underwent surgical LER over a 5 year period in a single tertiary vascular institution were identified. Patients considered to have suffered a poor outcome (Group A) included all in-hospital mortality and major amputations, delayed discharges with a length of stay (LOS) over one standard deviation above the mean or any readmission under any specialty within 12 months. Group A included 247 patients (38.9%) and the good outcome group included the remaining 388 patients (61.1%) from which a sample of 99 patients were selected as controls (Group B). RESULTS: Mean LOS for the entire study group was 14.4 ± 17.5 days, 12 month readmission rate was 29.1% and in-hospital mortality and major amputation rate was 2.7% and 1.4%, respectively. Pre-admission residence other than own home (OR 9.0; 95% CI 1.2-70.1; P = 0.036), atherosclerotic disease burden (OR 2.2; 95% CI 1.3-3.8; P = 0.003) and tissue loss (OR 3.0; 95% CI 1.6-5.3; P < 0.001) were identified as independent, statistically significant pre-operative predictors of poor outcome. Following discharge, group B patients had a significantly higher rate of amputation free survival and graft infection free survival (P < 0.001) compared to group A. CONCLUSION: Recognition of pre-operative predictors of poor outcome should inform case selection and identify high risk patients requiring intensive perioperative optimisation and post discharge follow up.

Cutaneous wound biofilm and the potential for electrical stimulation in management of the microbiome.

Infection contributes significantly to delayed cutaneous wound healing, which impacts patient care. External application of electrical stimulation (ES) has beneficial effects on wound repair and regeneration. The majority of studies to date have explored ES in relation to planktonic microorganisms, yet evidence indicates that bacteria in chronic wounds reside as antibiotic-resistant polymicrobial biofilms, which contribute to impairing wound healing. Culture-independent sequencing techniques have revolutionized our understanding of the skin microbiome and allowed a more accurate determination of microbial taxa and their relative abundance in wounds allowing a greater understanding of the host-microbial interface. Future studies combining the fields of ES, biofilm and microbiome research are necessary to fully elucidate the use of ES in the management of wound infection.

The efficacy of electrical stimulation in lower extremity cutaneous wound healing: A systematic review.

Current gold standard lower extremity cutaneous wound management is not always effective. Cutaneous wounds generate a "current of injury" which is directly involved in wound healing processes. Application of exogenous electrical stimulation has been hypothesised to imitate the natural electric current that occurs in cutaneous wounds. The aim of this extensive review was to provide a detailed update on the variety of electrical stimulation modalities used in the management of lower extremity wounds. Several different waveforms and delivery methods of electrical stimulation have been used. Pulsed current appears superior to other electrical modalities available. The majority of studies support the beneficial effects of pulsed current over conservative management of lower extremity cutaneous wounds. Although it appears to have no benefit over causal surgical intervention, it is a treatment option which could be utilised in those patients unsuitable for surgery. Other waveforms and modalities appear promising; however, they still lack large trial data to recommend a firm conclusion with regards to their use. Current studies also vary in quantity, quality and protocol across the different modalities. The ideal electrical stimulation device needs to be non-invasive, portable and cost-effective and provides minimal interference with patients' daily life. Further studies are necessary to establish the ideal electrical stimulation modality, parameters, method of delivery and duration of treatment. The development and implementation of newer devices in the management of acute and chronic wounds provides an exciting direction in the field of electrotherapy.

Single-Center Experience Following the Introduction of a Percutaneous Endovascular Aneurysm Repair First Approach.

We evaluated our experience following the introduction of a percutaneous endovascular aneurysm repair (pEVAR) first approach using Perclose Proglide assessing efficacy, complications, and identification of factors that could predict failure. A retrospective cohort study on patients over a 2-year period following the introduction of a pEVAR first approach was performed. The primary end point was defined as successful deployment and access site hemostasis. Percutaneous EVAR was technically successful in 41 (77.4%) of 53 patients and 83 (86.5%) of 96 access sites. Factors associated with failure were smaller common femoral artery (CFA) diameter ( P = .045) and CFA circumferential calcification of greater than 50% ( P = .0001). The incidence of access site infection was significantly higher in the failure group ( P = .008) as was procedure duration ( P = .026). Percutaneous EVAR first approach must be introduced with caution. Percutaneous EVAR failure occurs more often in patients with unfavorable access site anatomy. Success rate can be improved with careful patient selection.

Whole genome microarray data of chronic wound debridement prior to application of dermal skin substitutes.

Clinical consensus is that debridement is necessary for successful application of dermal skin substitutes (DSS) to chronic wounds. The aim here was to identify commonly expressed genes associated with wound healing in untreated acute wounds and chronic wounds treated with wound debridement followed by DSS. Cutaneous biopsies were taken at two time points from untreated acute and chronic wounds and from chronic wounds treated with DSS following debridement. Microarray analysis identified significant differences (p < 0.05) related to proliferation (HIPK2, LGR4, FGFR1, SRRT), migration (RHOC, PRPF40A, FGFR1), differentiation (TCF4, COL13A1, GNPTAB, HUWE1, FGFR1), angiogenesis (HIPK2, CASP8), extracellular matrix organization (VWA1), and apoptosis (BBC3, HIPK2, KLF11, PSME3, MSFD10, TOP2A, MLH1, CASP8, PDIA3, XAF1) when comparing untreated chronic wounds to chronic wounds treated with DSS, with similar expression levels compared to untreated acute wounds. Chronic wounds treated with debridement followed by DSS resemble untreated acute wounds at a genomic level. These novel findings, albeit with limited clinical specimen numbers, strengthen the recommendation to transform chronic into acute wounds prior to application of DSS.

The efficacy of electrical stimulation in experimentally induced cutaneous wounds in animals.

BACKGROUND: Complicated cutaneous wounds and their subsequent management can be a clinical challenge in veterinary medicine. There is still an unmet need for an ideal wound healing therapy that is able to stimulate efficiency and quality of repair. Skin wounds generate large and persistent endogenous electric currents and fields termed the "current of injury". The current of injury is involved in numerous processes of wound healing. These observations have led to the hypothesis that applied electrical stimulation (ES) may promote wound healing by imitating the natural electrical current that occurs in cutaneous wounds. OBJECTIVES: This review details the use, effect and mechanism of ES in different preclinical experimental cutaneous wound models and discusses the potential of how ES could be translated into veterinary practice. RESULTS: Studies have found a variable effect of ES on wound healing. Some have been positive with faster rates of wound re-epithelialization, increased wound collagen formation and angiogenesis noted. Other studies have shown no effect or detrimental results. The effects of ES are highly influenced by the ES modality, polarity and parameters. CONCLUSIONS AND CLINICAL IMPORTANCE: Electrical stimulation has the potential to play a significant role in enhancing cutaneous wound healing in veterinary practice. Clinical studies are necessary to corroborate the findings from experimental studies which have shown promise including the use of alternating pulsed and direct current and the use of bio-electric dressings. The ideal ES device would need to be safe, easy to use, portable, noninvasive and aid wound healing by having a beneficial effect on all wound healing stages.

Anatomic Variation of Rami Communicantes in the Upper Thoracic Sympathetic Chain: A Human Cadaveric Study.

BACKGROUND: Hyperhidrosis is secondary to over activation of the sympathetic nervous system and surgical sympathectomy is the treatment of choice when other modalities have failed. This study investigated anatomic variation in the upper thoracic sympathetic chain and associated rami communicantes among cadaveric specimens. It considers the implications of these findings on surgical techniques to treat hyperhidrosis. METHODS: The upper 4 thoracic sympathetic ganglia, intercostal nerves, and connecting rami were dissected, measured and mapped in 40 sides of 20 adult human cadavers. Ganglia location was recorded. The incidence, orientation, and distance travelled by rami communicantes was compared across different ganglionic levels and between sides. RESULTS: The percentage of ganglia located below their associated intercostal space was 6.25% with stellate ganglions present in 70% of specimens and Kuntz fibers noted in 40%. There was a stepwise reduction in incidence of rami from superior to inferior placed ganglia. The number of rami identified across all levels was significantly greater on the right (P = 0.03). The horizontal distance between the sympathetic chain and union of the rami on the intercostal nerves was significantly greater on the right across all levels (P = 0.04). CONCLUSIONS: There was substantial variation in the rami communicantes across the upper 4 ganglia and between right and left sides. Consideration of this variation should be given when planning surgical sympathectomy for hyperhidrosis particularly to avoid symptom recurrence.

Carotid endarterectomy for critical stenosis prior to cardiac surgery: Should it be done? A retrospective cohort study.

INTRODUCTION: Stroke remains a major cause of morbidity and mortality after cardiac surgery affecting 2% of patients. Extra-cranial carotid artery disease has been implicated in the aetiology of post cardiac surgery stroke. The aim of the study was to evaluate and compare the morbidity and mortality in patients undergoing cardiac surgery with or without staged carotid endarterectomy (CEA) in a tertiary referral centre. METHODS: A 5 year retrospective study was performed. The primary endpoints were defined as peri-operative stroke and myocardial infarction (MI) with secondary outcome defined as death within 30 days of surgery. RESULTS: In total 5924 cardiac procedures and 29 staged CEA's were performed. The rate of stroke and MI was significantly higher in patients undergoing staged CEA pre-cardiac surgery compared to patients undergoing cardiac surgery with confirmed or presumed normal carotid arteries (10.34% vs 1.43%; P = .008 and 13.79% vs 0.38%; P < .0001, respectively). There was no significant difference in the stroke and MI rate in those patients undergoing cardiac surgery with confirmed or presumed normal carotid arteries compared to those with significant carotid disease undergoing cardiac surgery with no prior carotid intervention (1.43% vs 3.16%; P > .05 and 0.38% vs 1.05%; P > .05, respectively). CONCLUSIONS: Carotid disease is associated with an increased risk of stroke post cardiac surgery. Staged carotid intervention cannot be justified based on these results. Increased risk of stroke post cardiac surgery in patients with significant carotid disease needs to be accepted, as the risk of stroke and MI during carotid intervention pre cardiac surgery is significantly higher.

The Role of Neuromediators and Innervation in Cutaneous Wound Healing.

The skin is densely innervated with an intricate network of cutaneous nerves, neuromediators and specific receptors which influence a variety of physiological and disease processes. There is emerging evidence that cutaneous innervation may play an important role in mediating wound healing. This review aims to comprehensively examine the evidence that signifies the role of innervation during the overlapping stages of cutaneous wound healing. Numerous neuropeptides that are secreted by the sensory and autonomic nerve fibres play an essential part during the distinct phases of wound healing. Delayed wound healing in diabetes and fetal cutaneous regeneration following wounding further highlights the pivotal role skin innervation and its associated neuromediators play in wound healing. Understanding the mechanisms via which cutaneous innervation modulates wound healing in both the adult and fetus will provide opportunities to develop therapeutic devices which could manipulate skin innervation to aid wound healing.

Resolution of carotid stenosis pre-carotid intervention: A case for selective preoperative duplex ultrasound.

INTRODUCTION: Spontaneous resolution of carotid stenosis is a phenomenon that has been described in literature in the past. At present it is not routine practise to scan patients prior to carotid endarterectomy surgery within the UK. PRESENTATION OF CASE: A 58 year old female presented to hospital with a history of sudden onset headache and left sided weakness. CT head showed findings in keeping with an acute right MCA territory infarct. A duplex ultrasound scan showed echolucent material in the right internal carotid artery forming a greater than 95% stenosis. The scan was unable to visualise the patency of the vessel distally due to the position of the mandible. The patient was provisionally listed for carotid endarterectomy. An MRA was requested prior to surgery to assess the patency of the distal internal carotid artery. The MRA of the carotids showed normal appearance of the common carotid, internal and vertebral arteries with no definite stenosis. A repeat duplex ultrasound confirmed there was no significant stenosis. DISCUSSION: The finding of complete resolution of stenosis on MRA was an unexpected event. Had the initial duplex imaging allowed visualisation of the distal vessel patency, our patient would have undergone unnecessary carotid surgery with the associated morbidity and mortality. CONCLUSION: This case report draws attention to the benefits of selective preoperative scanning, in sparing patients from unnecessary surgery as a result of finding occlusion or resolution of a previously diagnosed carotid stenosis.

Surgical management of a symptomatic extracranial internal carotid artery aneurysm and coexisting carotid body tumor.

Treatment of carotid body tumors and extracranial carotid artery aneurysms are well documented in the literature as separate entities. As distinct pathologies, they present technical difficulties with high complication rates. No patients with simultaneous carotid body tumors and extracranial internal carotid artery aneurysms have been reported. We report, to our knowledge, the first and subsequent surgical management of such a patient.

Amyand's hernia with a periappendicular abscess.

We present a rare case of a perforated vermiform appendix presenting as a strangulated inguinal hernia. An 89-year-old man presented to the surgical assessment unit with a 1-week history of progressively worsening abdominal pain, fever and a tender mass in the right iliac fossa. A diagnosis of strangulated inguinal hernia was made. Intraoperatively, a perforated appendix and a pus-filled sac were found. An appendicectomy and a Bassini repair of the hernia were performed with a satisfactory postoperative outcome. In the majority of cases Amyand's hernia is an intraoperative finding and its management depends on the extent of appediceal disease. In cases of perforated appendix with periappendiceal abscess within the hernial sac, an appedicectomy with Bassini's repair is recommended.

A rare case of a pure testicular seminoma presenting 7 years after a pineal germinoma.

Pure testicular seminomas occurring in patients with previous intracranial germ cell tumours are extremely rare. We present such a case. A 37-year-old gentleman presented to urology after previously being treated for a pineal germinoma with steroids and radiotherapy. On routine followup, he described symptoms of a testicular seminoma. This was managed surgically with radical orchidectomy. We discuss the possible causes of such an association with a review of the literature.