The angiogenic properties of mesenchymal stem/stromal cells and their therapeutic potential.

BACKGROUND: Blood vessel formation is fundamental to development, while its dysregulation can contribute to serious disease. Expectations are that hundreds of millions of individuals will benefit from therapeutic developments in vascular biology. MSCs are central to the three main vascular repair mechanisms. SOURCES OF DATA: Key recent published literature and ClinicalTrials.gov. AREAS OF AGREEMENT: MSCs are heterogeneous, containing multi-lineage stem and partly differentiated progenitor cells, and are easily expandable ex vivo. There is no single marker defining native MSCs in vivo. Their phenotype is strongly determined by their specific microenvironment. Bone marrow MSCs have skeletal stem cell properties. Having a perivascular/vascular location, they contribute to vascular formation and function and might be harnessed to regenerate a blood supply to injured tissues. AREAS OF CONTROVERSY: These include MSC origin, phenotype and location in vivo and their ability to differentiate into functional cardiomyocytes and endothelial cells or act as vascular stem cells. In addition their efficacy, safety and potency in clinical trials in relation to cell source, dose, delivery route, passage and timing of administration, but probably even more on the local preconditioning and the mechanisms by which they exert their effects. GROWING POINTS: Understanding the origin and the regenerative environment of MSCs, and manipulating their homing properties, proliferative ability and functionality through drug discovery and reprogramming strategies are important for their efficacy in vascular repair for regenerative medicine therapies and tissue engineering approaches. AREAS TIMELY FOR DEVELOPING RESEARCH: Characterization of MSCs' in vivo origins and biological properties in relation to their localization within tissue niches, reprogramming strategies and newer imaging/bioengineering approaches.

Laser doppler imaging - the role of poor burn perfusion in predicting healing time and guiding operative management.

AIM: To identify if the proportion of poor blood flow (blue) within an LDI (Laser doppler Imaging) image of a burn independently correlates with healing time. METHODS: Patient age, gender, burn type, and burn surface area were collected from the IBID (International Burn Injury Database). All LDI images were copied from the MoorLDI2-BI- Laser Doppler (MLDI) Scanner, onto Adobe Photoshop® version 2020 for pixel counting analysis and calculation of % TBSA (Total Body Surface Area) blue. Multiple linear regression analysis determined whether a proportional relationship was present for each parameter (age, gender, % TBSA Blue and comorbidities) with healing time. RESULTS: 110 patients with 197 burns were scanned with MLDI. Median age was 5 years (IQR 1-6). Median burn surface area was 1.5% (IQR 1-2.4). 56.4% of patients were male and patients were scanned an average of 2.68 days (SD±1.37) following burn injury. Number of physical comorbidities and age were found to have a statistically significant relationship with healing time (p = 0.03, p = 0.002). Gender and %TBSA blue did not have a statistically significant relationship with healing time (p = 0.07 and p = 0.058 respectively). We found a statistically significant difference in the mean healing time between burns with and without blue (3.43 weeks vs. 2.80 weeks, p = 0.0001). % TBSA Blue was more than four times higher in the operated group (0.48% vs. 0.11%) and was shown to have a statistically significant relationship with decision to operate (p = 0.027). Positive predictive value for the presence of blue on operative rate was 71.6%. Age, gender and number of comorbidities did not have a statistically significant influence on operative rate (p = 0.07, p = 0.50 and p = 0.49). CONCLUSION: % TBSA blue was not found to be a reliable independent indicator of burn healing time, but the presence of blue within an LDI image, advanced patient age and increased number of comorbidities did have a statistically significant relationship with healing time. This suggests their standardised inclusion into management decisions regarding intermediate depth burns is warranted.

Scarring, stem cells, scaffolds and skin repair.

The treatment of full thickness skin loss, which can be extensive in the case of large burns, continues to represent a challenging clinical entity. This is due to an on-going inability to produce a suitable tissue engineered substrate that can satisfactorily replicate the epidermal and dermal in vivo niches to fulfil both aesthetic and functional demands. The current gold standard treatment of autologous skin grafting is inadequate because of poor textural durability, scarring and associated contracture, and because of a paucity of donor sites in larger burns. Tissue engineering has seen exponential growth in recent years with a number of 'off-the-shelf' dermal and epidermal substitutes now available. Each has its own limitations. In this review, we examine normal wound repair in relation to stem/progenitor cells that are intimately involved in this process within the dermal niche. Endothelial precursors, in particular, are examined closely and their phenotype, morphology and enrichment from multiple sources are described in an attempt to provide some clarity regarding the controversy surrounding their classification and role in vasculogenesis. We also review the role of the next generation of cellularized scaffolds and smart biomaterials that attempt to improve the revascularisation of artificial grafts, the rate of wound healing and the final cosmetic and functional outcome.

Raised serum lactate: a marker of necrotizing fasciitis?

BACKGROUND: Distinguishing necrotizing fasciitis from non-necrotizing soft-tissue infections remains a difficult clinical judgement call, with a paucity of diagnostic aids to the clinician. The aim of this study was to assess raised serum lactate as a point-of-care test to aid in differentiating necrotizing from non-necrotizing soft tissue infections. METHODS: The authors performed a post-hoc analysis of a prospectively compiled database. All patients referred to a single surgeon (A.P.A.) as suspected cases of necrotizing fasciitis at one hospital between September 2000 and September 2010 were included. Serum lactate at presentation was recorded, along with demographic and outcome data. Using histological evidence of tissue necrosis as the 'gold standard', patients were divided into those with or without necrotizing fasciitis, and their serum lactate at presentation compared. RESULTS: Fifty three patients met the inclusion criteria. Twenty eight had histologically proven necrosis, 25 did not. Serum lactate (mean±SD) was 4.1±1.62 mmol/l in the necrotizing fasciitis group and 1.8±0.46 mmol/l in the non-necrotizing fasciitis group (p≤0.0001). A serum lactate level above 2.0 mmol/l had a sensitivity of 1.00 and a specificity of 0.76 for necrotizing fasciitis in this series. CONCLUSIONS: In this series of patients with suspected necrotizing soft tissue infection, serum lactate levels above 2.0 mmol/l at presentation were strongly associated with the presence of tissue necrosis. Although no test can be relied upon in isolation, our results suggest that serum lactate is a promising adjunct to the diagnosis of necrotizing infection, which could help to expedite appropriate management.

The simple transverse intraosseous phalangeal suture for zone 1 flexor digitorum profundus injuries: case series and review of the literature.

BACKGROUND: Zone 1 flexor digitorum profundus injury often precludes the use of a simple core suture as a result of a distal remnant that is too short. The aim of this study was to assess the senior author's (S.I.) simple technique for reinsertion of the flexor digitorum profundus tendon. METHODS: The case series consisted of 12 patients who required a primary flexor digitorum profundus repair in zone 1, with all repairs performed by the senior author. A Bruner incision was extended to the pulp to expose the base of the distal phalanx. A two-strand repair was anchored to the distal phalanx using the author's technique, which involved passing a 3-0 polypropylene suture on a straight needle through a hypodermic needle that had been drilled through the base of the distal phalanx. This provided a stable, intraosseous, internal repair, allowing a standard early active mobilization regimen. RESULTS: Two patients had excellent results and 10 had good results in terms of distal interphalangeal joint range of movement (mean, 57 degrees; range, 51 to 80 degrees) and Quick Disabilities of the Arm, Shoulder and Hand questionnaire scores (mean, 12; range, 0 to 31.8). There were no reported tendon ruptures at the time of writing this article (range, 6 to 37 months after surgery). CONCLUSIONS: The authors present a technique for the repair of zone 1 flexor digitorum profundus injuries that is simple, can be performed quickly, is easily learned, and has results that compare favorably with other techniques in the literature. Furthermore, there is limited morbidity to surrounding fingertip structures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The dual tendon palmaris longus variant causing dynamic median nerve compression in the forearm.

This article describes a variant of palmaris longus muscle resulting in median nerve compression in the mid forearm. Although the palmaris longus has several well-documented anomalies, these seldom lead to nerve compression. The dual tendon, central muscle belly variant observed in this case is the first of its kind to be reported causing compressive neuropathy at this level. This is of both anatomical and clinical interest as it reminds surgeons of the anatomical variations of this unique muscle and presents a new mechanism of nerve compression in the forearm.

An elderly patient presenting with hip pain following a fall: an unusual presentation of necrotising fasciitis.

Necrotising fasciitis (NF) is a rapidly progressive soft tissue infection involving necrosis of subcutaneous tissues. Early surgical intervention reduces mortality, but initial clinical findings are often non-specific and can delay the diagnosis. An 80-year-old patient, presented to our emergency department with pain in her left hip and mild bruising following a fall. An x-ray, requested to investigate a possible hip fracture, in fact demonstrated air in the subcutaneous tissues. She rapidly deteriorated and soon developed blood-filled blisters, crepitus and fixed staining of the skin. She underwent urgent debridement of involved tissues in theatre confirming the diagnosis of NF. The presence of subcutaneous emphysema on plain radiograph as in this case, is extremely specific to the diagnosis of NF. Although other imaging modalities can aid diagnosis these remain as an adjunct rather than a definitive diagnostic tool and should not delay surgical intervention based on clinical findings.

Necrotising fasciitis of the thumb.

Necrotising fasciitis is a rare condition that should be diagnosed early and managed aggressively in order to avoid death. We present a case of necrotising fasciitis of the thumb and discuss the assessment and management of this serious condition. A 44-year-old woman presented with a painful and erythematous right thumb and progressive swelling of her hand following a minor injury to the tip of her thumb 3 days previously. A diagnosis of necrotising fasciitis was made and the patient underwent urgent debridement of non-viable tissue. She required 1 week of supportive therapy in intensive treatment unit and was discharged from hospital after 3 weeks. Necrotising fasciitis is a rapidly progressing life-threatening infection, usually caused by streptococcal organisms. Immediate resuscitation, broad-spectrum intravenous antibiotics and early surgical debridement are necessary in order to avoid significant morbidity and mortality.

Reverse digital artery flap from radial and ulnar borders of palm.

Reconstructing skin defects of the volar aspect of fingers can be a challenging task due to a lack of local expendable tissue. The reverse digital artery flap is a versatile and reliable technique that can be used to manage such disabling injuries. Various authors have used this flap effectively, but most have used the digit itself as the donor site. This limits the size of the flap and also necessitates skin grafting to cover the donor site. Large reverse digital artery flaps can be raised from the radial and ulnar borders of the palm facilitating coverage of significant digital defects and primary closure of the donor site, resulting in minimal donor-site morbidity. We describe 3 illustrative cases to highlight the flaps versatility.

The simple wire interosseous fixation technique (SWIFT) for reattachment of FDP avulsions with a large bony fragment.

Avulsion injuries of the flexor digitorum profundus tendon can be with or without a bony fragment. Types 3, 4, and 5 injuries often have a sizeable bony fragment. In the past, they have been repaired with either a screw, plate, or pull-out wire with a dorsal button, often in combination with a K wire to immobilize the distal interphalangeal joint. We illustrate with 2 cases a simple technique for secure repair of the flexor digitorum profundus avulsions with a bony fragment. In contrast to previously described techniques, our technique involves minimal dissection, has a significantly reduced risk of fracture to the bony fragment, is completely internalized thereby reducing the risk of postoperative infection and allows immediate mobilization.